c-peptide and Obesity

Topics: Adiposity; Blood Glucose; C-Peptide; Diet; Female; Humans; Hyperinsulinism; Infant; Infant, Newborn; Insulin; Obesity; Pregnancy

Concomitant confluent and reticulated papillomatosis (CRP) and acanthosis nigricans (AN) is rare. We present a case of concomitant CRP and obesity-associated AN in a 12-year-old obese Japanese girl. Curiously, oral minocycline therapy, which has been shown to be effective for CRP, was effective against both CRP and AN. Possible mechanisms by which minocycline could have improved skin lesions of CRP and obesity-associated AN are discussed. In addition, reports of concomitant CRP and obesity-associated AN are reviewed. CRP and obesity-associated AN share common clinicopathological features and some reports have described concomitant CRP and obesity-associated AN. Together with the observation that skin lesions of CRP and obesity-associated AN in the present case responded to oral minocycline therapy, these facts suggest a tight relationship or a common pathogenetic pathway between these pathologies.

Topics: Acanthosis Nigricans; Alkaline Phosphatase; Anti-Bacterial Agents; Biopsy; Blood Glucose; C-Peptide; Child; Female; Humans; Insulin Resistance; Minocycline; Obesity; Papilloma; Rare Diseases; Skin; Skin Neoplasms; Syndrome; Treatment Outcome

Insulin stimulates cell proliferation and inhibits apoptosis. While epidemiologic studies have investigated associations between markers of insulin resistance/hyperinsulinemia (i.e., circulating insulin, homeostasis model assessment-insulin resistance (HOMA-IR), C-peptide) and risk of colorectal adenoma (CRA), the effect size has not yet been quantified.. We aimed to summarize the association between hyperinsulinemia/insulin resistance and risk of CRA, including whether the association is independent of adiposity.. Pubmed and Embase were searched through April, 2015 to identify observational studies investigating the associations between insulin, C-peptide and HOMA-IR and CRA risk. Using the highest versus lowest category meta-analysis and dose-response meta-analysis based on a random-effects model, we estimated summary odds ratio (OR) and the corresponding 95% confidence interval (95% CI).. A total of 27 studies (insulin: 16 studies including 14,007 cases; C-peptide: 11 studies including 8639 cases; HOMA-IR: 8 studies including 11,619 cases) were included in this meta-analysis. The summary ORs of CRA comparing the highest with the lowest quantile were 1.33 for insulin (95% CI=1.12-1.58, I(2)=73.9%, Pheterogeneity<0.001), 1.44 for C-peptide (95% CI=1.13-1.83, I(2)=63.5%, Pheterogeneity=0.003), and 1.33 for HOMA-IR (95% CI=1.10-1.60, I(2)=69.1%, Pheterogeneity=0.004). Upon stratification by ethnicity, higher levels of insulin and C-peptide were significantly associated with increased risk of CRA in non-Asian ethnicity (summary OR for insulin=1.67 [95% CI=1.28-2.17], I(2)=34.9%, Pheterogeneity=0.16; summary OR for C-peptide=1.59 [95% CI=1.22-2.08], I(2)=21.5%, Pheterogeneity=0.27) but not in Asians (summary OR for insulin=1.10 [95% CI=0.92-1.33], I(2)=76.6%, Pheterogeneity=0.001; summary OR for C-peptide=1.27 [95% CI=0.84-1.91], I(2)=72.6, Pheterogeneity=0.01). We observed evidence for the existence of publication bias for insulin (P=0.01 by Egger test) and HOMA-IR (P=0.05 by Egger test). The results were confirmed in linear dose-response meta-analysis. These significant positive associations generally persisted even after adjustment for adiposity, although the effect size was substantially attenuated.. Independent of adiposity, higher levels of insulin, C-peptide, and HOMA-IR were significantly associated with increased risk of CRA. The weaker associations and high heterogeneity in Asian studies warrant further research. These results indicate that insulin resistance and hyperinsulinemia may contribute in part to the association between obesity and CRA risk.

Topics: Adenoma; Adiposity; Blood Glucose; C-Peptide; Colorectal Neoplasms; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Obesity; Risk Factors

This review focuses on recent literature on insulin resistance in youth with type 2 diabetes mellitus (T2DM). Insulin resistance is associated with a variety of cardiometabolic problems leading to increased morbidity and mortality across the lifespan.. Functional pancreatic β-cell changes play a role in the transition from obesity to impaired glucose tolerance (IGT). Insulin resistance drives islet cell upregulation, manifested by elevated glucagon and c-peptide levels, early in the transition to IGT. Surrogate measurements of insulin resistance and insulin secretion exist but their accuracy compared to clamp data is imperfect. Recent large longitudinal studies provide detailed information on the progression from normoglycemia to T2DM and on the phenotype of T2DM youth. Defining prediabetes and T2DM remains a challenge in youth. Lifestyle interventions do not appear as effective in children as in adults. Metformin remains the only oral hypoglycemic agent approved for T2DM in youth.. New insights exist regarding the conversion from insulin resistance to T2DM, measurement of insulin resistance and phenotypes of insulin resistance youth, but more information is needed. Surrogate measurements of insulin resistance, additional treatment options for insulin resistance and individualization of treatment options for T2DM adolescents in particular require further investigation.

Topics: Adolescent; Body Mass Index; C-Peptide; Child; Diabetes Mellitus, Type 2; Exercise Tolerance; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Male; Metformin; Obesity; Phenotype; Young Adult

Type 2 diabetes mellitus (T2DM) has dramatically increased throughout the world in many ethnic groups and among people with diverse social and economic backgrounds. This increase has also affected the young such that over the past decade, the increase in the number of children and youth with T2DM has been labeled an 'epidemic'. Before the 1990s, it was rare for most pediatric centers to have significant numbers of patients with T2DM. However, by 1994, T2DM patients represented up to 16% of new cases of diabetes in children in urban areas and by 1999, depending on geographic location, the range of percentage of new cases because of T2DM was 8-45% and disproportionately represented among minority populations. Although the diagnosis was initially regarded with skepticism, T2DM is now a serious diagnostic consideration in all young people who present with signs and symptoms of diabetes in the USA.

Topics: Adolescent; Age of Onset; C-Peptide; Child; Combined Modality Therapy; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diet, Diabetic; Exercise; Humans; Hypoglycemic Agents; Insulin; Obesity; Patient Education as Topic; Sex Factors

Topics: Adolescent; Adult; Aged; C-Peptide; Child; Coronary Disease; Diabetes Complications; Glucose; Humans; Insulin; Insulin Resistance; Leptin; Middle Aged; Obesity; Potassium; Risk Factors; Vascular Resistance

Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Glucoregulatory abnormalities have also been associated with the use of antipsychotic medications themselves. While antipsychotics may increase adiposity, which can decrease insulin sensitivity, disease- and medication-related differences in glucose regulation might also occur independent of differences in adiposity.. Modified oral glucose tolerance tests were performed in schizophrenic patients (n = 48) receiving clozapine, olanzapine, risperidone, or typical antipsychotics, and untreated healthy control subjects (n = 31), excluding subjects with diabetes and matching groups for adiposity and age. Plasma was sampled at 0 (fasting), 15, 45, and 75 minutes after glucose load.. Significant time x treatment group interactions were detected for plasma glucose (F(12,222) = 4.89, P<.001) and insulin (F(12,171) = 2.10, P =.02) levels, with significant effects of treatment group on plasma glucose level at all time points. Olanzapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at all time points, in comparison with patients receiving typical antipsychotics as well as untreated healthy control subjects. Clozapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at fasting and 75 minutes after load, again in comparison with patients receiving typical antipsychotics and untreated control subjects. Risperidone-treated patients had elevations in fasting and postload glucose levels, but only in comparison with untreated healthy control subjects. No differences in mean plasma glucose level were detected when comparing risperidone-treated vs typical antipsychotic-treated patients and when comparing typical antipsychotic-treated patients vs untreated control subjects.. Antipsychotic treatment of nondiabetic patients with schizophrenia can be associated with adverse effects on glucose regulation, which can vary in severity independent of adiposity and potentially increase long-term cardiovascular risk.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Brief Psychiatric Rating Scale; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose; Humans; Hydrocortisone; Insulin; Male; Obesity; Schizophrenia

The hormone insulin remains the cornerstone of diabetic therapy since it is required for almost all cases of Type 1 and many cases of Type 2 diabetes. Since the discovery of insulin in 1921, much has been learned about its chemistry, structure and action as well as its production in the beta cell. Insulin is formed through a series of precursors, beginning with preproinsulin, the protein encoded in the insulin gene. These precursors direct the prohormone into the secretory pathway and ultimately into the secretory granules where it is converted into insulin and C-peptide. These products are stored and secreted together in a highly regulated manner in response to glucose and other stimuli. This review focuses on the recently discovered prohormone convertases, PC2 and PC3 (PC1), the enzymes responsible for the endoproteolytic processing of proinsulin to insulin and C-peptide in the beta cell as well as for the selective processing of proglucagon to glucagon in the alpha cell or GLP1 in intestinal L-cells. PC2 and PC3 are calcium-dependent serine proteases related to the bacterial enzyme subtilisin. They cleave selectively at Lys-Arg or Arg-Arg sites in precursors, generating products with C-terminal basic residues that are then removed by carboxypeptidase E, an exopeptidase. All 3 enzymes are expressed mainly in secretory granules of neuroendocrine cells throughout the body and in the brain. Inherited defects affecting the prohormone-processing enzymes have recently been found in association with unusual syndromes of obesity and other metabolic disorders.

Topics: Animals; Aspartic Acid Endopeptidases; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucagon; Humans; Insulin; Islets of Langerhans; Obesity; Organ Specificity; Proinsulin; Proprotein Convertase 2; Proprotein Convertases; Subtilisins

The effects were investigated of weight loss on the relationship between hyperinsulinemia, body weight and body fat distribution in two groups of women with central-type obesity (CTO) (waist-to-hip ratio WHR greater than 0.85) or peripheral-type obesity (PTO) (WHR less than 0.85). An oral glucose tolerance test was carried out before and after a hypocaloric nutritional treatment lasting 4 months. Both groups were matched for age, body mass index and amount of body fat. At the basal condition, group CTO had fasting and glucose-stimulated insulin levels significantly higher than group PTO; fasting (but not stimulated) C peptide levels were also higher in CTO compared with PTO. Weight and fat loss were significantly higher in CTO than in PTO women. Moreover, unlike PTO, CTO subjects significantly reduced their WHR values. In both groups weight loss led to a significant drop in fasting and glucose-stimulated insulin and C peptide levels. However, PTO women reduced their C peptide levels significantly less than CTO. In conclusion, weight loss only modified body fat distribution in women with CTO, who appeared to be prone to a greater weight loss than the PTO women. Compared to PTO, CTO women were characterized by higher insulin levels and peripheral insulin resistance, which improved during hypocaloric feeding probably due to the combined effect of weight loss and the change in body fat distribution.

Topics: Adipose Tissue; Adult; Body Weight; C-Peptide; Energy Intake; Female; Humans; Insulin; Insulin Secretion; Obesity; Weight Loss

Topics: C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Obesity; Physical Education and Training; Prediabetic State; Radioimmunoassay

Proinsulin is the single chain precursor of insulin. It consists of insulin, plus a peptide which connects the A and B chains of insulin. This peptide is termed C-peptide. C-peptide an insulin are secreted in equimolar amounts from pancreatic beta-cells, Hence, circulating C-peptide levels provide a measure of beta-cell secretory activity. C-peptide measurements are preferable to insulin measurements because of lack of hepatic extraction, slower metabolic clearance rate, and lack of cross reactivity with antibodies to insulin. This article reviews the methods for determination of C-peptide levels in body fluids, and discusses the applications of C-peptide measurement. These include the investigation of hypoglycemia and the assessment of insulin secretory function in insulin-treated and non-insulin-dependent diabetics. The contribution of C-peptide measurement to the understanding of the interrelationships between insulin secretory function and age, sex, obesity, blood lipids, and blood glucose concentrations will also be evaluated.

Topics: Amniotic Fluid; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Islets of Langerhans; Kidney; Liver; Male; Obesity; Pregnancy; Proinsulin; Radioimmunoassay; Reference Values

The large and variable hepatic extraction of insulin is a major obstacle to our ability to quantitate insulin secretion accurately in human subjects. The evidence that C-peptide is secreted from the beta cell in equimolar concentration with insulin, but not extracted by the liver to any significant degree, has provided a firm scientific basis for the use of peripheral C-peptide concentrations as a semiquantitative marker of beta cell secretory activity in a variety of clinical situations. Thus, plasma C-peptide has proved to be extremely valuable in the study of the natural history of type 1 diabetes, to monitor insulin secretion in patients with insulin antibodies, and as an adjunct in the investigation of patients with hypoglycemic disorders. The use of the peripheral C-peptide concentration to accurately quantitate the rate of insulin secretion is more controversial. This is mainly because understanding of the kinetics and metabolism of C-peptide under different conditions is incomplete. Unfortunately, sufficient quantities of human C-peptide are not available to allow the experimental validation of the mathematical formulae that have been proposed for the calculation of insulin secretion from peripheral C-peptide concentrations. Until it is possible to perform such experiments, the accuracy of studies that have derived insulin secretion rates from peripheral C-peptide levels will remain uncertain. The assumption that the peripheral C-peptide:insulin molar ratio can be used as a reflection of hepatic insulin extraction has not been experimentally validated. The marked difference in the plasma half-lives of insulin and C-peptide complicates the interpretation of changes in their ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Animals; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Glucose Tolerance Test; Half-Life; Humans; Insulin; Insulin Secretion; Kidney Diseases; Kinetics; Liver; Male; Metabolic Clearance Rate; Obesity; Tissue Distribution

Nutrition therapy for gestational diabetes mellitus (GDM) has conventionally focused on carbohydrate restriction. In a randomized controlled trial (RCT), we tested the hypothesis that a diet (all meals provided) with liberalized complex carbohydrate (60%) and lower fat (25%) (CHOICE diet) could improve maternal insulin resistance and 24-h glycemia, resulting in reduced newborn adiposity (NB%fat; powered outcome) versus a conventional lower-carbohydrate (40%) and higher-fat (45%) (LC/CONV) diet.. After diagnosis (at ∼28-30 weeks' gestation), 59 women with diet-controlled GDM (mean ± SEM; BMI 32 ± 1 kg/m2) were randomized to a provided LC/CONV or CHOICE diet (BMI-matched calories) through delivery. At 30-31 and 36-37 weeks of gestation, a 2-h, 75-g oral glucose tolerance test (OGTT) was performed and a continuous glucose monitor (CGM) was worn for 72 h. Cord blood samples were collected at delivery. NB%fat was measured by air displacement plethysmography (13.4 ± 0.4 days).. There were 23 women per group (LC/CONV [214 g/day carbohydrate] and CHOICE [316 g/day carbohydrate]). For LC/CONV and CHOICE, respectively (mean ± SEM), NB%fat (10.1 ± 1 vs. 10.5 ± 1), birth weight (3,303 ± 98 vs. 3,293 ± 81 g), and cord C-peptide levels were not different. Weight gain, physical activity, and gestational age at delivery were similar. At 36-37 weeks of gestation, CGM fasting (86 ± 3 vs. 90 ± 3 mg/dL), 1-h postprandial (119 ± 3 vs. 117 ± 3 mg/dL), 2-h postprandial (106 ± 3 vs. 108 ± 3 mg/dL), percent time in range (%TIR; 92 ± 1 vs. 91 ± 1), and 24-h glucose area under the curve values were similar between diets. The %time >120 mg/dL was statistically higher (8%) in CHOICE, as was the nocturnal glucose AUC; however, nocturnal %TIR (63-100 mg/dL) was not different. There were no between-group differences in OGTT glucose and insulin levels at 36-37 weeks of gestation.. A ∼100 g/day difference in carbohydrate intake did not result in between-group differences in NB%fat, cord C-peptide level, maternal 24-h glycemia, %TIR, or insulin resistance indices in diet-controlled GDM.

Topics: Adiposity; Blood Glucose; C-Peptide; Diabetes, Gestational; Diet, Fat-Restricted; Female; Glucose; Humans; Infant, Newborn; Insulin Resistance; Obesity; Pregnancy; Random Allocation

The rate of gastric emptying and glucoregulatory hormones are key determinants of postprandial glycaemia. Intragastric administration of L-tryptophan slows gastric emptying and reduces the glycaemic response to a nutrient drink in lean individuals and those with obesity. We investigated whether tryptophan decreases postprandial glycaemia and slows gastric emptying in type 2 diabetes (T2D).. Twelve men with T2D (age: 63 ± 2 years, HbA1c: 49.7 ± 2.5 mmol/mol, BMI: 30 ± 1 kg/m. Tryptophan alone stimulated C-peptide (P = 0.002) and glucagon (P = 0.04), but did not affect fasting glucose. In response to the drink, Trp-3 lowered plasma glucose from t = 15-30 min and from t = 30-45 min compared with control and Trp-1.5, respectively (both P < 0.05), with no differences in peak glucose between treatments. Gastric emptying tended to be slower after Trp-3, but not Trp-1.5, than control (P = 0.06). Plasma C-peptide, glucagon and 3-OMG increased on all days, with no major differences between treatments.. In people with T2D, intragastric administration of 3 g tryptophan modestly slows gastric emptying, associated with a delayed rise, but not an overall lowering of, postprandial glucose.

Topics: 3-O-Methylglucose; Aged; Beverages; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Routes; Gastric Emptying; Glucagon; Glucose; Humans; Insulin; Intestinal Absorption; Male; Middle Aged; Nutrients; Obesity; Postprandial Period; Tryptophan

Although a single bout of postmeal exercise can lower postprandial glucose (PPG), its optimal timing remains unclear.. This study aimed to investigate the effect of exercise timing using an individualized approach on PPG in overweight or obese young men.. Twenty men [age: 23.0 ± 4.3 y; BMI (kg/m2): 27.4 ± 2.8] each completed three 240-min trials in a randomized order separated by 6-14 d: 1) sitting (SIT), 2) walking initiated at each participant's PPG-peak time (PPGP) (iP), and 3) walking initiated 20 min before the PPGP (20iP). For each participant, PPGP was predetermined using continuous glucose monitoring. Walking was performed at 50% maximal oxygen consumption for 30 min. Venous blood was collected at 15- and 30-min intervals for 0-120 min and 120-240 min, respectively. The primary outcome was plasma PPG. Generalized estimating equations were used for comparison between trials.. Compared with SIT, the 4-h incremental AUCs (iAUCs) for plasma PPG (-0.6 mmol · L-1 · h; P = 0.047) and insulin (-28.7%, P < 0.001) were reduced in 20iP only, and C-peptide concentrations were lower after iP (-14.9%, P = 0.001) and 20iP (-28.7%, P < 0.001). Plasma insulin (-11.1%, P = 0.006) and C-peptide (-8.3%, P = 0.012) were lower due to the 20iP compared with iP treatment. Finally, PPG reductions due to iP and 20iP occurred only in men with a BMI > 27.5 kg/m2 (iP, -11.2%; 20iP, -14.7%; P = 0.047) and higher glucose iAUC values during SIT (iP, -25.5%; 20iP, -25.7%; P < 0.001).. Walking initiated 20 min before PPGP lowered PPG and plasma insulin and C-peptide concentrations in young men with overweight or obesity, in particular in those with high BMI or glucose iAUC values during SIT; it also lowered plasma insulin and C-peptide concentrations more effectively than did exercise initiated at PPGP. This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) as ChiCTR1900023175.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Cross-Over Studies; Exercise; Heart Disease Risk Factors; Humans; Insulin; Male; Obesity; Overweight; Postprandial Period; Time Factors; Walking; Young Adult

Excess body weight and insulin resistance lead to type 2 diabetes and other major health problems. There is an urgent need for dietary interventions to address these conditions.. To measure the effects of a low-fat vegan diet on body weight, insulin resistance, postprandial metabolism, and intramyocellular and hepatocellular lipid levels in overweight adults.. This 16-week randomized clinical trial was conducted between January 2017 and February 2019 in Washington, DC. Of 3115 people who responded to flyers in medical offices and newspaper and radio advertisements, 244 met the participation criteria (age 25 to 75 years; body mass index of 28 to 40) after having been screened by telephone.. Participants were randomized in a 1:1 ratio. The intervention group (n = 122) was asked to follow a low-fat vegan diet and the control group (n = 122) to make no diet changes for 16 weeks.. At weeks 0 and 16, body weight was assessed using a calibrated scale. Body composition and visceral fat were measured by dual x-ray absorptiometry. Insulin resistance was assessed with the homeostasis model assessment index and the predicted insulin sensitivity index (PREDIM). Thermic effect of food was measured by indirect calorimetry over 3 hours after a standard liquid breakfast (720 kcal). In a subset of participants (n = 44), hepatocellular and intramyocellular lipids were quantified by proton magnetic resonance spectroscopy. Repeated measure analysis of variance was used for statistical analysis.. Among the 244 participants in the study, 211 (87%) were female, 117 (48%) were White, and the mean (SD) age was 54.4 (11.6) years. Over the 16 weeks, body weight decreased in the intervention group by 5.9 kg (95% CI, 5.0-6.7 kg; P < .001). Thermic effect of food increased in the intervention group by 14.1% (95% CI, 6.5-20.4; P < .001). The homeostasis model assessment index decreased (-1.3; 95% CI, -2.2 to -0.3; P < .001) and PREDIM increased (0.9; 95% CI, 0.5-1.2; P < .001) in the intervention group. Hepatocellular lipid levels decreased in the intervention group by 34.4%, from a mean (SD) of 3.2% (2.9%) to 2.4% (2.2%) (P = .002), and intramyocellular lipid levels decreased by 10.4%, from a mean (SD) of 1.6 (1.1) to 1.5 (1.0) (P = .03). None of these variables changed significantly in the control group over the 16 weeks. The change in PREDIM correlated negatively with the change in body weight (r = -0.43; P < .001). Changes in hepatocellular and intramyocellular lipid levels correlated with changes in insulin resistance (both r = 0.51; P = .01).. A low-fat plant-based dietary intervention reduces body weight by reducing energy intake and increasing postprandial metabolism. The changes are associated with reductions in hepatocellular and intramyocellular fat and increased insulin sensitivity.. ClinicalTrials.gov Identifier: NCT02939638.

Topics: Absorptiometry, Photon; Adult; Aged; Blood Glucose; Body Composition; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, Fat-Restricted; Diet, Vegan; Energy Intake; Energy Metabolism; Female; Glycated Hemoglobin; Hepatocytes; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Lipid Metabolism; Liver; Male; Middle Aged; Muscle Fibers, Skeletal; Muscle, Skeletal; Obesity; Overweight; Postprandial Period; Proton Magnetic Resonance Spectroscopy; Triglycerides

Augmenting nicotinamide adenine dinucleotide (NAD+) metabolism through dietary provision of NAD+ precursor vitamins translates to improved glucose handling in rodent models of obesity and diabetes. Preclinical evidence suggests that the NAD+/SIRT1 axis may be implicated in modulating important gut-related aspects of glucose regulation. We sought to test whether NAD+ precursor supplementation with nicotinamide riboside (NR) affects β-cell function, α-cell function, and incretin hormone secretion as well as circulating bile acid levels in humans.. A 12-week randomized, double-blind, placebo-controlled, parallel-group trial in 40 males with obesity and insulin resistance allocated to NR at 1000 mg twice daily (n = 20) or placebo (n = 20). Two-hour 75-g oral glucose tolerance tests were performed before and after the intervention, and plasma concentrations of glucose, insulin, C-peptide, glucagon, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were determined. β-Cell function indices were calculated based on glucose, insulin, and C-peptide measurements. Fasting plasma concentrations of bile acids were determined.. NR supplementation during 12 weeks did not affect fasting or postglucose challenge concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, or GIP, and β-cell function did not respond to the intervention. Additionally, no changes in circulating adipsin or bile acids were observed following NR supplementation.. The current study does not provide evidence to support that dietary supplementation with the NAD+ precursor NR serves to impact glucose tolerance, β-cell secretory capacity, α-cell function, and incretin hormone secretion in nondiabetic males with obesity. Moreover, bile acid levels in plasma did not change in response to NR supplementation.

Topics: Blood Glucose; C-Peptide; Double-Blind Method; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Niacinamide; Obesity; Pyridinium Compounds

Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon-like peptide-1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16-week intervention were sustained beyond the intervention period.. One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C-peptide, and lipids comparing 1-year follow-up levels to end of treatment (week 16) and baseline (week 0) levels.. From end of treatment to the 1-year follow-up, body weight had increased in the liraglutide-treated group. However, compared to baseline levels, the placebo-subtracted body weight loss remained significantly reduced (-3.8 kg, 95% CI: -7.3 to -0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C-peptide, and lipids had each returned to baseline levels 1 year after stopping liraglutide.. The body weight reduction during 16 weeks of liraglutide treatment was partially sustained 1 year after the intervention was completed. However, the improvements in other metabolic parameters returned to baseline levels.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Blood Glucose; Body Weight; C-Peptide; Clozapine; Denmark; Fasting; Female; Follow-Up Studies; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Lipid Metabolism; Liraglutide; Male; Middle Aged; Obesity; Olanzapine; Overweight; Placebos; Prediabetic State; Schizophrenia; Young Adult

Topics: Adolescent; Appetite; Blood Glucose; C-Peptide; Child; Cross-Over Studies; Dairy Products; Female; Glucagon-Like Peptide 1; Humans; Insulin; Liver; Male; Obesity; Overweight; Postprandial Period; Snacks

It may be difficult to distinguish between adults with type 1 diabetes and type 2 diabetes by clinical assessment. In patients undergoing bariatric surgery, it is critical to correctly classify diabetes subtype to prevent adverse perioperative outcomes including diabetic ketoacidosis. This study aimed to determine whether testing for C-peptide and islet cell antibodies during preoperative evaluation for bariatric surgery could improve the classification of type 1 versus type 2 diabetes compared to clinical assessment alone.. The participant with type 1 diabetes was similar to the 11 participants with type 2 diabetes in age at diagnosis, adiposity, and glycemic control but had the lowest C-peptide levels. Among insulin-treated participants, fasting and stimulated C-peptide correlated strongly with the C-peptide area-under-the-curve on mixed meal tolerance testing (R = 0.86 and 0.88, respectively). Three participants, including the one with type 1 diabetes, were islet cell antibody positive.. Clinical characteristics did not correctly identify type 1 diabetes in this study. Preoperative C-peptide testing may improve diabetes classification in patients undergoing bariatric surgery; further research is needed to define the optimal C-peptide thresholds.

Topics: Adult; Autoantibodies; Bariatric Surgery; Blood Glucose; C-Peptide; Clinical Laboratory Techniques; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Fasting; Female; Humans; Male; Middle Aged; Obesity; Postoperative Period; Retrospective Studies; Weight Loss

Tryptophan stimulates plasma cholecystokinin and pyloric pressures, both of which slow gastric emptying. Gastric emptying regulates postprandial blood glucose. Tryptophan has been reported to decrease energy intake. We investigated the effects of intragastric tryptophan on the glycaemic response to, and gastric emptying of, a mixed-nutrient drink, and subsequent energy intake. Lean and obese participants (

Topics: Administration, Oral; Adult; Appetite Depressants; Beverages; Biomarkers; Blood Glucose; C-Peptide; Cholecystokinin; Double-Blind Method; Energy Intake; Food, Formulated; Gastric Emptying; Glucagon; Humans; Male; Obesity; Postprandial Period; South Australia; Time Factors; Treatment Outcome; Tryptophan

Sedentary children have greater risk of developing abnormalities in glucose homeostasis. We investigated whether interrupting sedentary behavior (sitting) with very short periods of walking would improve glucose metabolism without affecting dietary intake in children with overweight or obesity. We hypothesized that interrupting sitting with short bouts of moderate-intensity walking would decrease insulin area under the curve (AUC) during an oral glucose tolerance test (OGTT) compared with uninterrupted sitting.. Overweight/obese (BMI ≥85th percentile) children 7-11 years of age underwent two experimental conditions in random order: prolonged sitting (3 h of continuous sitting) and interrupted sitting (3 min of moderate-intensity walking at 80% of ventilatory threshold every 30 min for 3 h). Insulin, C-peptide, and glucose were measured every 30 min for 3 h during an OGTT. Each session was followed by a buffet meal. Primary outcomes were differences in OGTT hormones and substrates and in buffet meal intake by condition.. Among 35 children with complete data, mixed-model results identified lower insulin and C-peptide in the interrupted condition (. Interrupting sitting with brief moderate-intensity walking improved glucose metabolism without significantly increasing energy intake in children with overweight or obesity. Interrupting sedentary behavior may be a promising intervention strategy for reducing metabolic risk in such children.

Topics: Blood Glucose; C-Peptide; Child; Cross-Over Studies; Energy Intake; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Obesity; Overweight; Risk Reduction Behavior; Sedentary Behavior; Sitting Position; Time Factors; Walking

Despite their widespread use in this population, data on the pharmacodynamic (PD) properties of the insulin analogs detemir and glargine in severely obese patients with type 2 diabetes are lacking.. The primary objective of the study was to compare the PD properties of two different doses of the basal insulin analogs detemir and glargine in patients with type 2 diabetes and a BMI > 35 kg/m2. PD data were derived from euglycemic clamp studies over 30 hours and each subject was studied for four times after the subcutaneous injection of a lower (0.8 U/kg body weight) and higher (1.6 U/kg body weight) dose of both detemir and glargine using a single-blind, randomised cross-over design.. Six male and four female patients with type 2 diabetes and a mean BMI of 43.2±5.1 kg/m2 (mean age 55.7±2 years, mean HbA1c 7.2±0.3%) completed the study. The total GIRAUC0-30 (mean difference 1224 mg/kg, 95%CI 810-1637, p = 0.00001), GIRAUC0-24 (mean difference 1040 mg/kg, 95%CI 657-1423; p = 0.00001), GIRAUC24-30 (mean difference 181 mg/kg, 95%CI 64-298; p = 0.004), GIRmax (mean difference 0.93 mg/kg/min, 95%CI 0.22-1.64, p = 0.01) and time to GIRmax (+1.9 hours, 95%CI 0.5-3.2; p = 0.009) were higher after the higher doses of both insulins, without significant differences between detemir and glargine. However, during the last 6 hours of the clamp the GIRAUC24-30 was significantly increased with glargine (mean difference 122 mg/kg, 95%CI 6-237, p = 0.043), reflecting a more pronounced late glucose lowering effect.. A clear dose-response relationship can be demonstrated for both insulin analogs, even at very high doses in severely obese patients with type 2 diabetes. Compared to detemir, glargine has a more pronounced late glucose lowering effect 24-30 h after its injection.. Controlled-Trials.com ISRCTN57547229.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glucose Clamp Technique; Humans; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Obesity

The prevalence of impaired glucose tolerance (IGT) is rising among obese adolescents in parallel with epidemic obesity. In some cases, IGT reverts to normal glucose tolerance (NGT) by the end of puberty. The aims of the present study were to investigate metabolic factors determining changes over time of glucose at 120 min (Glu120) following an oral glucose tolerance test (OGTT), and to verify whether preserved β-cell glucose sensitivity (βCGS) protects against persistent IGT.. We performed a cohort study of 153 severely obese children and adolescents evaluated with a 5-point OGTT at baseline and at follow-up with measurements of glucose, insulin, and C-peptide to estimate several empirical parameters of insulin sensitivity (includ ing oral glucose insulin sensitivity [OGIS] and OGTT-derived glucose effectiveness) and secretion.. At follow-up (range 0.9-4.8 year), 113 (73.9%) patients remained with NGT, 9 (5.9%) had IGT, and 28 (18.3%) had reverted to NGT; 3 NGT patients had developed IGT. In multivariable models, change in loge(βCGS) was inversely associated with time-related change in loge(Glu120), with (model 2) and without (model 1) correction for the change in loge(OGIS). Model 2 was more strongly associated with change in loge(Glu120).. Changes in βCGS and insulin sensitivity were inversely associated with changes in Glu120 at follow-up, contributing a likely explanation for the reversal of IGT to NGT.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Obesity

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is released in response to food intake. It is unclear how meals high in protein (HP) and monounsaturated fat (HMF) affect GLP-1 response.. To examine the effect of a HP versus a HMF meal on GLP-1 response.. Twenty-four overweight/obese participants consumed two meals (HP: 31.9 % energy from protein; HMF: 35.2 % fat and 20.7 % monounsaturated fat) in a random order. Both meals contained the same energy and carbohydrate content. GLP-1, insulin, glucagon, C-peptide, and glucose were assessed from blood drawn in the fasting and postprandial states. The effect of meal condition on hormone and glucose responses and appetite ratings were assessed by repeated measures analysis.. Statistically significant (p < 0.01) time by meal condition effect was observed on active GLP-1, total GLP-1, insulin, C-peptide, and glucagon, but not glucose (p = 0.83). Area under the curve was significantly higher during the HP versus the HMF meal conditions for active GLP-1 (23.7 %; p = 0.0007), total GLP-1 (12.2 %; p < 0.0001), insulin (54.4 %; p < 0.0001), C-peptide (14.8 %; p < 0.0001), and glucagon (40.7 %; p < 0.0001). Blood glucose was not different between the HP versus HMF conditions (-4.8 %; p = 0.11). Insulin sensitivity was higher during the HMF versus HP conditions (Matsuda index mean difference: 16.3 %; p = 0.007). Appetite ratings were not different by meal condition.. GLP-1 and insulin responses were higher during the HP condition. However, no difference was found in blood glucose between conditions, and insulin sensitivity was higher during the HMF condition, indicating that a HMF meal may be optimal at regulating blood glucose in overweight/obese individuals without type 2 diabetes.

Topics: Adolescent; Adult; Aged; Appetite; Blood Glucose; Body Mass Index; C-Peptide; Cross-Over Studies; Exercise; Female; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Male; Meals; Mental Recall; Middle Aged; Obesity; Overweight; Postprandial Period; Young Adult

The purpose of this study is to compare effects of different nations on Roux-en-Y gastric bypass (RYGB) vs. intensive medical management (IMM) in achieving remission of type 2 diabetes mellitus (T2DM).. At baseline, Taiwanese participants had a lower BMI, younger age, and shorter duration of T2DM than American participants. At 24 months, weight loss was greater in the RYGB group in both populations than in the IMM group. No IMM participant of either population had partial or complete remission of T2DM. In the RYGB group, a substantial proportion of the subjects achieved complete or partial remission (57 % in Taiwanese and 27 % in American participants, P = 0.08). Logistic regression revealed stimulated C-peptide (Odds ratio 2.22, P = 0.02) but not nationality as a significant predictor of diabetes remission.. Adding RYGB to lifestyle and medical management was associated with a greater likelihood of remission of T2DM in both Taiwanese and American subjects with mild obesity with type 2 diabetes. Residual beta-cell function at baseline appears to be the major factor predicting remission of T2DM. Trial registry number: clinicaltrials.gov Identifier: NCT00641251.

Topics: Adult; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Humans; Hypoglycemic Agents; Life Style; Male; Middle Aged; Obesity; Remission Induction; Taiwan; Time Factors; Treatment Outcome; United States

Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects (n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 (sem 0·5)×10-3 v. -0·5 (sem 0·5)×10-3 mg/kg per min per pmol, respectively, P=0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT (P=0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Double-Blind Method; Female; Fragaria; Fruit; Glucose Tolerance Test; Humans; Inflammation; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Obesity; Oxidative Stress; Plant Extracts; Polyphenols; Vaccinium macrocarpon

Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and β-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin-(9-39) (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose-tolerant patients were studied after RYGB in a randomized, placebo-controlled, 4-day crossover study with standard mixed-meal tests and concurrent administration of placebo, oral sitagliptin, Ex-9 infusion, or combined Ex-9-sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated β-cell function, and aggravated postprandial hyperglucagonemia compared with placebo, whereas sitagliptin had no effect despite two- to threefold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or β-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4-sensitive glucose-lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB.

Topics: Adult; Blood Glucose; C-Peptide; Cross-Over Studies; Enzyme-Linked Immunosorbent Assay; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Linear Models; Male; Obesity; Peptide Fragments; Postprandial Period; Single-Blind Method; Sitagliptin Phosphate

The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads.. The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water.. Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects.. It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance.. ClinicalTrials.gov NCT01875575.

Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Case-Control Studies; Diabetes Mellitus; Double-Blind Method; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Incretins; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Young Adult

To determine whether interrupting prolonged sitting with brief bouts of light-intensity walking (LW) or simple resistance activities (SRA) improves postprandial cardiometabolic risk markers in adults with type 2 diabetes (T2D).. In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men 62 ± 6 years old) underwent the following 8-h conditions on three separate days (with 6-14 days washout): uninterrupted sitting (control) (SIT), sitting plus 3-min bouts of LW (3.2 km · h(-1)) every 30 min, and sitting plus 3-min bouts of SRA (half-squats, calf raises, gluteal contractions, and knee raises) every 30 min. Standardized meals were consumed during each condition. Incremental areas under the curve (iAUCs) for glucose, insulin, C-peptide, and triglycerides were compared between conditions.. Compared with SIT, both activity-break conditions significantly attenuated iAUCs for glucose (SIT mean 24.2 mmol · h · L(-1) [95% CI 20.4-28.0] vs. LW 14.8 [11.0-18.6] and SRA 14.7 [10.9-18.5]), insulin (SIT 3,293 pmol · h · L(-1) [2,887-3,700] vs. LW 2,104 [1,696-2,511] and SRA 2,066 [1,660-2,473]), and C-peptide (SIT 15,641 pmol · h · L(-1) [14,353-16,929] vs. LW 11,504 [10,209-12,799] and SRA 11,012 [9,723-12,301]) (all P < 0.001). The iAUC for triglycerides was significantly attenuated for SRA (P < 0.001) but not for LW (SIT 4.8 mmol · h · L(-1) [3.6-6.0] vs. LW 4.0 [2.8-5.1] and SRA 2.9 [1.7-4.1]).. Interrupting prolonged sitting with brief bouts of LW or SRA attenuates acute postprandial glucose, insulin, C-peptide, and triglyceride responses in adults with T2D. With poor adherence to structured exercise, this approach is potentially beneficial and practical.

Topics: Aged; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Exercise Therapy; Female; Humans; Insulin; Male; Middle Aged; Obesity; Overweight; Postprandial Period; Posture; Resistance Training; Sedentary Behavior; Triglycerides; Walking

The aim of the article is to determine whether maternal body mass index (BMI) influences the beneficial effects of diabetes treatment in women with gestational diabetes mellitus (GDM).. Secondary analysis of a multicenter randomized treatment trial of women with GDM. Outcomes of interest were elevated umbilical cord c-peptide levels (> 90th percentile 1.77 ng/mL), large for gestational age (LGA) birth weight (> 90th percentile), and neonatal fat mass (g). Women were grouped into five BMI categories adapted from the World Health Organization International Classification of normal, overweight, and obese adults. Outcomes were analyzed according to treatment group assignment.. A total of 958 women were enrolled (485 treated and 473 controls). Maternal BMI at enrollment was not related to umbilical cord c-peptide levels. However, treatment of women in the overweight, Class I, and Class II obese categories was associated with a reduction in both LGA birth weight and neonatal fat mass. Neither measure of excess fetal growth was reduced with treatment in normal weight (BMI < 25 kg/m(2)) or Class III (BMI ≥ 40 kg/m(2)) obese women.. There was a beneficial effect of treatment on fetal growth in women with mild GDM who were overweight or Class I and Class II obese. These effects were not apparent for normal weight and very obese women.

Topics: Adipose Tissue; Adult; Blood Glucose Self-Monitoring; Body Mass Index; C-Peptide; Diabetes, Gestational; Diet Therapy; Female; Fetal Blood; Fetal Macrosomia; Humans; Hypoglycemic Agents; Insulin; Obesity; Overweight; Pregnancy; Pregnancy Complications; Severity of Illness Index; Treatment Outcome; Young Adult

To elucidate whether increased insulin concentration after salsalate treatment (3 g/day for 7 days) is attributable to an increased insulin secretion rate (ISR) or to reduced metabolic clearance of endogenous insulin (MCI) during stepped glucose infusion (SGI). The analysis was performed in obese subjects who participated in a randomized double-blind, parallel, placebo-controlled clinical trial. A total of 27 participants (16 on salsalate, 11 on placebo) completed baseline and follow-up SGI. During SGI in the salsalate group, C-peptide concentrations were reduced by 11%, while plasma insulin concentrations were increased by 30%, corresponding to a 30% reduction in MCI (p < 0.0001). At molar increments of glucose, insulin concentrations were increased by 27% (p = 0.02), but ISR was unchanged. Salsalate did not alter insulin secretion, but lowered MCI, indicating that a reduction in insulin clearance is the principal mechanism for increased insulin levels after salsalate administration.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; C-Peptide; Double-Blind Method; Female; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Obesity; Salicylates; Secretory Rate

Stem cell therapy (SCT) is now the up-coming therapeutic modality for treatment of type 1 diabetes mellitus (T1DM).. Our study was a prospective, open-labeled, two-armed trial for 10 T1DM patients in each arm of allogenic and autologous adipose-derived insulin-secreting mesenchymal stromal cells (IS-AD-MSC)+bone marrow-derived hematopoietic stem cell (BM-HSC) infusion. Group 1 received autologous SCT: nine male patients and one female patient; mean age, 20.2 years, disease duration 8.1 years; group 2 received allogenic SCT: six male patients and four female patients, mean age, 19.7 years and disease duration, 7.9 years. Glycosylated hemoglobin (HbA1c) was 10.99%; serum (S.) C-peptide, 0.22 ng/mL and insulin requirement, 63.9 IU/day in group 1; HbA1c was 11.93%, S.C-peptide, 0.028 ng/mL and insulin requirement, 57.55 IU/day in group 2. SCs were infused into the portal+thymic circulation and subcutaneous tissue under non-myelo-ablative conditioning. Patients were monitored for blood sugar, S.C-peptide, glutamic acid decarboxylase antibodies and HbA1c at 3-month intervals.. Group 1 received mean SCs 103.14 mL with 2.65 ± 0.8 × 10(4) ISCs/kg body wt, CD34+ 0.81% and CD45-/90+/73+, 81.55%. Group 2 received mean SCs 95.33 mL with 2.07 ± 0.67 × 10(4) ISCs/kg body wt, CD34+ 0.32% and CD45-/90+/73+ 54.04%. No untoward effect was observed with sustained improvement in HbA1c and S.C-peptide in both groups with a decrease in glutamic acid decarboxylase antibodies and reduction in mean insulin requirement.. SCT is a safe and viable treatment option for T1DM. Autologous IS-AD-MSC+ BM-HSC co-infusion offers better long-term control of hyperglycemia as compared with allogenic SCT.

Topics: Adipose Tissue; Adult; Blood Glucose; Bone Marrow Cells; C-Peptide; Cell- and Tissue-Based Therapy; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Insulin; Insulin Secretion; Leukocyte Common Antigens; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Obesity; Prospective Studies; Subcutaneous Fat; Young Adult

Improvement in type 2 diabetes after Roux-en-Y gastric bypass (RYGB) has been attributed partly to weight loss, but mechanisms beyond weight loss remain unclear. We performed an ancillary study to the Diabetes Surgery Study to assess changes in incretins, insulin sensitivity, and secretion 1 year after randomization to lifestyle modification and intensive medical management (LS/IMM) alone (n = 34) or in conjunction with RYGB (n = 34). The RYGB group lost more weight and had greater improvement in HbA1c. Fasting glucose was lower after RYGB than after LS/IMM, although the glucose area under the curve decreased comparably for both groups. Insulin sensitivity increased in both groups. Insulin secretion was unchanged after LS/IMM but decreased after RYGB, except for a rapid increase during the first 30 min after meal ingestion. Glucagon-like peptide 1 (GLP-1) was substantially increased after RYGB, while gastric inhibitory polypeptide and glucagon decreased. Lower HbA1c was most strongly correlated with the percentage of weight loss for both groups. At baseline, a greater C-peptide index and 90-min postprandial C-peptide level were predictive of lower HbA1c at 1 year after RYGB. β-Cell glucose sensitivity, which improved only after RYGB, and improved disposition index were associated with lower HbA1c in both groups, independent of weight loss. Weight loss and preserved β-cell function both predominantly determine the greatest glycemic benefit after RYGB.

Topics: Adiponectin; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Treatment Outcome; Weight Loss

Ingestion of probiotics can modify gut microbiota and alter insulin resistance and diabetes development in rodents. We hypothesized that daily intake of Lactobacillus reuteri increases insulin sensitivity by changing cytokine release and insulin secretion via modulation of the release of glucagon-like peptides (GLP)-1 and -2.. A prospective, double-blind, randomized trial was performed in 21 glucose-tolerant humans (11 lean: age 49 ± 7 years, BMI 23.6 ± 1.7 kg/m(2); 10 obese: age 51 ± 7 years, BMI 35.5 ± 4.9 kg/m(2)). Participants ingested 10(10) b.i.d. L. reuteri SD5865 or placebo over 4 weeks. Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess incretin effect and GLP-1 and GLP-2 secretion, and euglycemic-hyperinsulinemic clamps with [6,6-(2)H2]glucose were used to measure peripheral insulin sensitivity and endogenous glucose production. Muscle and hepatic lipid contents were assessed by (1)H-magnetic resonance spectroscopy, and immune status, cytokines, and endotoxin were measured with specific assays.. In glucose-tolerant volunteers, daily administration of L. reuteri SD5865 increased glucose-stimulated GLP-1 and GLP-2 release by 76% (P < 0.01) and 43% (P < 0.01), respectively, compared with placebo, along with 49% higher insulin (P < 0.05) and 55% higher C-peptide secretion (P < 0.05). However, the intervention did not alter peripheral and hepatic insulin sensitivity, body mass, ectopic fat content, or circulating cytokines.. Enrichment of gut microbiota with L. reuteri increases insulin secretion, possibly due to augmented incretin release, but does not directly affect insulin sensitivity or body fat distribution. This suggests that oral ingestion of one specific strain may serve as a novel therapeutic approach to improve glucose-dependent insulin release.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Limosilactobacillus reuteri; Male; Middle Aged; Obesity; Oxidative Stress; Pilot Projects; Probiotics; Prospective Studies; Protein Precursors

The gut microbiota has been implicated in obesity and its progression towards metabolic disease. Dietary interventions that target the gut microbiota have been suggested to improve metabolic health. The aim of the present study was to investigate the effect of interventions with Lactobacillus paracasei F19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity. A total of fifty-eight obese postmenopausal women were randomised to a single-blinded, parallel-group intervention of 6-week duration, with a daily intake of either L. paracasei F19 (9.4 × 1010 colony-forming units), flaxseed mucilage (10 g) or placebo. Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota. Diet-induced changes in metabolic markers were explored using adjusted linear regression models. The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test (P< 0.05) and improved insulin sensitivity measured by Matsuda index (P< 0.05). Comparison of gut microbiota composition at baseline and after 6 weeks of intervention with flaxseed mucilage showed alterations in abundance of thirty-three metagenomic species (P< 0.01), including decreased relative abundance of eight Faecalibacterium species. These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity. The intake of L. paracasei F19 did not modulate metabolic markers compared with placebo. In conclusion, flaxseed mucilage improves insulin sensitivity and alters the gut microbiota; however, the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species.

Topics: Aged; C-Peptide; Diet; Feces; Female; Flax; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Intestines; Lactobacillus; Middle Aged; Obesity; Plant Mucilage; Postmenopause; Prebiotics; Probiotics; Single-Blind Method

The hyperinsulinemia of obesity is a function of both increased pancreatic insulin secretion and decreased insulin clearance, and contributes to cardiovascular risk. Whilst weight loss is known to enhance insulin clearance, there is a paucity of data concerning the underlying mechanisms. This study was conducted to examine the inter-relationships between changes in sympathetic nervous system (SNS) activity, vascular function and insulin clearance during a weight loss program.. Seventeen non-smoking, un-medicated individuals aged 55 ± 1 years (mean ± SEM), body mass index (BMI) 33.9 ± 1.7 kg/m(2), underwent a 4-month hypocaloric diet (HCD), using a modified Dietary Approaches to Stop Hypertension diet, whilst seventeen age- and BMI-matched subjects acted as controls. Insulin sensitivity and insulin clearance were assessed via euglycemic hyperinsulinemic clamp (exogenous insulin clearance); hepatic insulin extraction was calculated as fasting C-peptide to insulin ratio (endogenous insulin clearance); SNS activity was quantified by microneurographic nerve recordings of muscle sympathetic nerve activity (MSNA) and whole-body norepinephrine kinetics; and vascular function by calf venous occlusion plethysmography and finger arterial tonometry.. Weight loss averaged -8.3 ± 0.6% of body weight in the HCD group and was accompanied by increased clamp-derived glucose utilization (by 20 ± 9%, P = 0.04) and exogenous insulin clearance (by 12 ± 5%, P = 0.02). Hepatic insulin extraction increased from 6.3 ± 0.8 to 7.1 ± 0.9 (P = 0.09). Arterial norepinephrine concentration decreased by -12 ± 5%, whole-body norepinephrine spillover rate by -14 ± 8%, and MSNA by -9 ± 5 bursts per 100 heartbeats in the HCD group (P all >0.05 versus control group). Step-wise regression analysis revealed a bidirectional relationship between enhanced exogenous insulin clearance post weight loss and reduction in calf vascular resistance (r = -0.63, P = 0.01) which explained 40% of the variance. Increase in hepatic insulin extraction was predicted by enhanced finger reactive hyperaemic response (P = 0.006) and improvement in oral glucose tolerance (P = 0.002) which together explained 64% of the variance.. Insulin clearance is independently and reciprocally associated with changes in vascular function during weight loss intervention. Trial registration ClinicalTrials.gov: NCT01771042 and NCT00408850.

Topics: Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Caloric Restriction; Female; Fingers; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Kinetics; Liver; Male; Manometry; Middle Aged; Muscle, Skeletal; Norepinephrine; Obesity; Plethysmography; Sympathetic Nervous System; Treatment Outcome; Vascular Resistance; Victoria; Weight Loss

To examine associations of baseline insulin dynamics with changes in body composition and resting energy expenditure (REE) following weight loss.. Twenty-one participants with overweight or obesity achieved 10-15% weight loss and then received 3 weight loss maintenance diets (high-carbohydrate, moderate-carbohydrate, and low-carbohydrate) in random order, each for 4 weeks. Body composition was measured at baseline and after weight loss. Insulin 30 min after glucose consumption (insulin-30; insulin response), C-peptide deconvolution analysis, HOMA, hepatic insulin sensitivity (IS), and REE were assessed at baseline and after each maintenance diet.. Insulin-30, but not maximal insulin secretion, hepatic IS, or HOMA, predicted changes in fat mass (standardized β = 0.385, 1.7 kg difference between 10th and 90th centile of insulin-30, P = 0.04) after weight loss. Insulin-30 (β = -0.341, -312 kcal day(-1) , P = 0.008), maximal insulin secretion (β = -0.216, -95 kcal day(-1) , P = 0.0002), HOMA (β = -0.394, -350 kcal day(-1) , P = 0.002), and hepatic IS (β = 0.217, 225 kcal day(-1) , P = 0.0003) predicted change in REE during weight loss maintenance, independent of changes in body composition. The inverse relationship between insulin-30 and REE was substantially attenuated when the low-carbohydrate diet was consumed first.. These findings distinguish a novel phenotype, characterized by high insulin response, at risk for weight regain, and identify a dietary approach to ameliorate this risk.

Topics: Adult; Body Composition; Body Weight; C-Peptide; Diet, Carbohydrate-Restricted; Diet, Reducing; Energy Metabolism; Female; Humans; Insulin; Insulin Resistance; Male; Obesity; Overweight; Rest; Weight Loss; Young Adult

Obesity is associated with a higher risk of aggressive prostate cancer and alters circulating levels of insulin and adiponectin, two hormones that influence biologic processes implicated in carcinogenesis. Results of some studies showed associations of circulating levels of adiponectin, insulin, and c-peptide (a marker of insulin secretion) with aggressive prostate cancer, but the size of these studies was limited.. A nested case-control study of 272 aggressive prostate cancer cases [Gleason score ≥ 7 (4+3) or T3-T4] and 272 age- and race-matched controls from the Cancer Prevention Study II Nutrition Cohort was conducted to determine the associations of prediagnostic plasma levels of c-peptide and adiponectin with risk of aggressive prostate cancer.. Neither circulating adiponectin nor c-peptide was associated with risk of aggressive prostate cancer. In analyses of the highest-risk aggressive prostate cancer (Gleason score ≥ 8 or T3-T4), the highest quartile of c-peptide, compared with the lowest, was associated with an OR of 1.41 [95% confidence interval (CI), 0.72-2.78].. Our findings provide no support for the hypothesis that adiponectin is associated with risk of aggressive prostate cancer but a possible association of high levels of c-peptide with particularly high-risk prostate cancer cannot be ruled out.. These results indicate that changes in circulating levels of adiponectin and c-peptide do not play an important role in risk of aggressive prostate cancer.

Topics: Adiponectin; Aged; Biomarkers; C-Peptide; Case-Control Studies; Cohort Studies; Follow-Up Studies; Humans; Insulin; Male; Neoplasm Staging; Nutritional Status; Obesity; Prognosis; Prostate; Prostatic Neoplasms; Risk Factors

Plasma calprotectin is a potential biomarker of cardiovascular disease (CVD), insulin resistance (IR), and obesity. We examined the relationship between plasma calprotectin concentrations, CVD manifestations and the metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (T2DM) in order to evaluate plasma calprotectin as a risk assessor of CVD in diabetic patients without known CVD.. An automated immunoassay for determination of plasma calprotectin was developed based on a fecal Calprotectin ELIA, and a reference range was established from 120 healthy adults. Plasma calprotectin concentrations were measured in 305 T2DM patients without known CVD. They were screened for carotid arterial disease, peripheral arterial disease (PAD), and myocardial ischemia (MI) by means of carotid artery ultrasonography, peripheral ankle and toe systolic blood pressure measurements, and myocardial perfusion scintigraphy.. The reference population had a median plasma calprotectin concentration of 2437 ng/mL (2.5-97.5% reference range: 1040-4262 ng/mL). The T2DM patients had significantly higher concentrations (3754 ng/mL, p < 0.0001), and within this group plasma calprotectin was significantly higher in patients with MetS (p < 0.0001) and also in patients with autonomic neuropathy, PAD, and MI compared with patients without (p < 0.001, p = 0.021 and p = 0.043, respectively). Plasma calprotectin was by linear regression analysis found independently associated with BMI, C-reactive protein, and HDL cholesterol. However, plasma calprotectin did not predict autonomic neuropathy, PAD, MI or CVD when these variables entered the multivariable regression analysis as separate outcome variables.. T2DM patients had higher concentrations of plasma calprotectin, which were associated with obesity, MetS status, autonomic neuropathy, PAD, and MI. However, plasma calprotectin was not an independent predictor of CVD, MI, autonomic neuropathy or PAD.. NCT00298844.

Topics: Adult; Aged; Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leukocyte L1 Antigen Complex; Male; Metabolic Syndrome; Middle Aged; Obesity; Reference Values; Young Adult

Postprandial glucagon secretion was shown to be dysregulated in patients with type 2 diabetes. However, the differences in secretory patterns between obese and non-obese patients and their physiological effects on plasma glucose levels are not fully understood. This study population consisted of 21 (10 obese and 11 non-obese) consecutive patients with type 2 diabetes admitted for glycemic control. A 3-hour mixed-meal tolerance test was performed after glycemic control improved. Six non-diabetic subjects were also enrolled in the test. Postprandial glucagon levels increased after 30 min in diabetic patients but not in non-diabetic subjects. The glucagon levels in obese diabetic patients were significantly higher than those in non-obese diabetic patients, while the percent values of postprandial glucagon levels were not different between these groups. In diabetic patients, there were significant positive correlations between the percent value at 30 min and the early postprandial glucose levels at 0, 15 and 30 min and the areas under the curve (AUC0-30 and AUC30-90). Interestingly, the ratio of this percent glucagon value to the C-peptide level at 30 min was significantly associated with the late half of the postprandial glucose levels at 90, 120, 150 and 180 min and the AUC90-180. This is the first report that demonstrates the glucagon secretory patterns and the close correlations in detailed time course between the early postprandial glucagon response and the early and the late half of the postprandial glucose levels in obese and non-obese patients with type 2 diabetes.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Glucagon; Humans; Insulin; Meals; Middle Aged; Obesity; Postprandial Period; Up-Regulation

This study investigated if additional non-starch polysaccharide (NSP) or resistant starch (RS), above that currently recommended, leads to better improvement in insulin sensitivity (IS) than observed with modest weight loss (WL). Obese male volunteers (n = 14) were given an energy-maintenance (M) diet containing 27 g NSP and 5 g RS daily for one week. They then received, in a cross-over design, energy-maintenance intakes of either an NSP-enriched diet (42 g NSP, 2.5 g RS) or an RS-enriched diet (16 g NSP, 25 g RS), each for three weeks. Finally, a high protein (30% calories) WL diet was provided at 8 MJ/day for three weeks. During each dietary intervention, endogenous glucose production (EGP) and IS were assessed. Fasting glycaemia was unaltered by diet, but plasma insulin and C-peptide both decreased with the WL diet (p < 0.001), as did EGP (-11%, p = 0.006). Homeostatis model assessment of insulin resistance improved following both WL (p < 0.001) and RS (p < 0.05) diets. Peripheral tissue IS improved only with WL (57%-83%, p < 0.005). Inclusion of additional RS or NSP above amounts currently recommended resulted in little or no improvement in glycaemic control, whereas moderate WL (approximately 3 kg fat) improved IS.

Topics: Blood Glucose; C-Peptide; Carbohydrate Metabolism; Cross-Over Studies; Diet, Reducing; Dietary Proteins; Energy Intake; Energy Metabolism; Fasting; Homeostasis; Humans; Insulin; Insulin Resistance; Leucine; Male; Metabolic Syndrome; Models, Biological; Obesity; Polysaccharides; Starch; Weight Loss

Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n=15,595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (OR(T3 vs T1)=2.96; 95% CI, 1.21-7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (OR(T3 vs T1)=2.11; 95% CI, 0.69-6.44; P trend=0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.

Topics: Adipokines; Adiponectin; Aged; Aged, 80 and over; Body Mass Index; C-Peptide; Case-Control Studies; Endometrial Neoplasms; Estrogens; Female; Humans; Leptin; Longitudinal Studies; Middle Aged; Obesity; Postmenopause; Prognosis; Risk Factors

Hyperglycemia and elevated free fatty acids (FFA) are implicated in the development of endothelial dysfunction. Infusion of soy-bean oil-based lipid emulsion (Intralipid®) increases FFA levels and results in elevation of blood pressure (BP) and endothelial dysfunction in obese healthy subjects. The effects of combined hyperglycemia and high FFA on BP, endothelial function and carbohydrate metabolism are not known. Twelve obese healthy subjects received four random, 8-h IV infusions of saline, Intralipid 40 mL/h, Dextrose 10% 40 mL/h, or combined Intralipid and dextrose. Plasma levels of FFA increased by 1.03±0.34 mmol/L (p=0.009) after Intralipid, but FFAs remained unchanged during saline, dextrose, and combined Intralipid and dextrose infusion. Plasma glucose and insulin concentrations significantly increased after dextrose and combined Intralipid and dextrose (all, p<0.05) and were not different from baseline during saline and lipid infusion. Intralipid increased systolic BP by 12±9 mmHg (p<0.001) and diastolic BP by 5±6 mmHg (p=0.022),and decreased flow-mediated dilatation (FMD) from baseline by 3.2%±1.4% (p<0.001). Saline and dextrose infusion had neutral effects on BP and FMD. The co-administration of lipid and dextrose decreased FMD by 2.4%±2.1% (p=0.002) from baseline, but did not significantly increase systolic or diastolic BP. Short-term Intralipid infusion significantly increased FFA and BP; in contrast, FFA and BP were unchanged during combined infusion of Intralipid and dextrose. Combined Intralipid and dextrose infusion resulted in endothelial dysfunction similar to Intralipid alone.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Emulsions; Endothelium, Vascular; Fatty Acids, Nonesterified; Female; Glucose; Humans; Infusions, Intravenous; Insulin; Male; Middle Aged; Obesity; Phospholipids; Soybean Oil; Triglycerides

Our aim was to study the potential mechanisms responsible for the improvement in glucose control in Type 2 diabetes (T2D) within days after Roux-en-Y gastric bypass (RYGB). Thirteen obese subjects with T2D and twelve matched subjects with normal glucose tolerance (NGT) were examined during a liquid meal before (Pre), 1 wk, 3 mo, and 1 yr after RYGB. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent-insulinotropic polypeptide (GIP), and glucagon concentrations were measured. Insulin resistance (HOMA-IR), β-cell glucose sensitivity (β-GS), and disposition index (D(β-GS): β-GS × 1/HOMA-IR) were calculated. Within the first week after RYGB, fasting glucose [T2D Pre: 8.8 ± 2.3, 1 wk: 7.0 ± 1.2 (P < 0.001)], and insulin concentrations decreased significantly in both groups. At 129 min, glucose concentrations decreased in T2D [Pre: 11.4 ± 3, 1 wk: 8.2 ± 2 (P = 0.003)] but not in NGT. HOMA-IR decreased by 50% in both groups. β-GS increased in T2D [Pre: 1.03 ± 0.49, 1 wk: 1.70 ± 1.2, (P = 0.012)] but did not change in NGT. The increase in DI(β-GS) was 3-fold in T2D and 1.5-fold in NGT. After RYGB, glucagon secretion was increased in response to the meal. GIP secretion was unchanged, while GLP-1 secretion increased more than 10-fold in both groups. The changes induced by RYGB were sustained or further enhanced 3 mo and 1 yr after surgery. Improvement in glycemic control in T2D after RYGB occurs within days after surgery and is associated with increased insulin sensitivity and improved β-cell function, the latter of which may be explained by dramatic increases in GLP-1 secretion.

Topics: Adult; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Hyperglycemia; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Obesity, Morbid; Postprandial Period; Time Factors

Elevated thyroid-stimulating hormone (TSH) concentrations in association with normal/slightly elevated free triiodothyronine (fT(3)) and/or free thyroxine (fT(4)) have been consistently found in obese children. To examine relationships between adiposity, insulin sensitivity, and TSH, fT(3) and fT(4).. 240 overweight/obese prepubertal children were studied. Fasting TSH, fT(3), fT(4), glucose, insulin, C-peptide, lipids, leptin and adiponectin were evaluated. Insulin sensitivity and resistance were estimated [quantitative insulin check index (QUICKI), insulin sensitivity index (ISI), and hepatic insulin resistance index]. Body fat was measured by dual-energy X-ray absorptiometry. The central obesity index was calculated as the ratio of fat tissue in the trunk region to fat tissue in the leg region.. The multiple regression analysis with age, gender and measures of fatness as covariates showed that QUICKI was the only significant negative predictor of TSH and central obesity index the strongest positive predictor of fT(3), in association with either age or hepatic insulin resistance index, and that the only positive determinant of fT(4) was hepatic insulin resistance index.. Reduced insulin sensitivity is associated with augmented TSH and fT(4), while progressive central fat accumulation is strictly related to a parallel increase in fT(3) levels, independently from total body fat. Further studies are needed to understand mechanisms linking thyroid function to insulin sensitivity and body composition in obese children.

Topics: Adiponectin; Adiposity; Blood Glucose; C-Peptide; Child; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Obesity; Thyroid Function Tests; Thyroxine; Triiodothyronine

Protein intake in early infancy has been suggested to be an important risk factor for later obesity, but information on potential mechanisms is very limited.. This study examined the influence of protein intake in infancy on serum amino acids, insulin, and the insulin-like growth factor I (IGF-I) axis and its possible relation to growth in the first 2 y of life.. In a multicenter European study, 1138 healthy, formula-fed infants were randomly assigned to receive cow-milk-based infant and follow-on formulas with lower protein (LP; 1.77 and 2.2 g protein/100 kcal) or higher protein (HP; 2.9 and 4.4 g protein/100 kcal) contents for the first year. Biochemical variables were measured at age 6 mo in 339 infants receiving LP formula and 333 infants receiving HP formula and in 237 breastfed infants.. Essential amino acids, especially branched-chain amino acids, IGF-I, and urinary C-peptide:creatinine ratio, were significantly (P < 0.001) higher in the HP group than in the LP group, whereas IGF-binding protein (IGF-BP) 2 was lower and IGF-BP3 did not differ significantly. The median IGF-I total serum concentration was 48.4 ng/mL (25th, 75th percentile: 27.2, 81.8 ng/mL) in the HP group and 34.7 ng/mL (17.7, 57.5 ng/mL) in the LP group; the urine C-peptide:creatinine ratios were 140.6 ng/mg (80.0, 203.8 ng/mg) and 107.3 ng/mg (65.2, 194.7 ng/mg), respectively. Most essential amino acids, IGF-I, C-peptide, and urea increased significantly in both the LP and HP groups compared with the breastfed group. Total IGF-I was significantly associated with growth until 6 mo but not thereafter.. HP intake stimulates the IGF-I axis and insulin release in infancy. IGF-I enhances growth during the first 6 mo of life. This trial was registered at clinicaltrials.gov as NCT00338689.

Topics: Amino Acids, Branched-Chain; Animals; Biomarkers; Blood Glucose; Breast Feeding; C-Peptide; Child Development; Creatinine; Double-Blind Method; Endocrine System; Energy Intake; Female; Humans; Infant; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Milk; Milk Proteins; Obesity; Risk Factors; RNA-Binding Proteins; White People

Sleeve gastrectomy is a new bariatric surgery, and many reports have showed that patients who have undergone sleeve gastrectomy have experienced rapid resolution of type 2 diabetes. The mechanisms accounting for the beneficial effects of sleeve gastrectomy on glucose homeostasis are not well understood and remain speculative. This trial assessed prospectively the effect of sleeve gastrectomy on type 2 diabetes and the serial changes of insulin secretion to oral glucose loads.. Prospective study on the response of insulin secretion to oral glucose loads in 20 severe diabetic patients (body mass index [BMI] >25 and <35, HbA1C >7.5%) before and at 1, 4, 12, 26, and 52 weeks after sleeve gastrectomy. The insulin secretion was measured by insulinogenic index and area under the curve (AUC) during a standard oral glucose tolerance test (OGTT). Remission of type 2 diabetes was defined as fasting glucose level <126 mg/dL and HbA1C <6.5% without any glycemic therapy.. Of the 20 patients enrolled, the mean age was 46.3 + or - 8.0 years, mean BMI was 31.0 + or - 2.9 kg/m(2), and mean HbA1C was 10.1 + or - 2.2. The mean BMI and excess body weight loss at 1, 4, 12, 26, and 52 weeks after operation were 28.9 (22.1%), 27.4 (43.0%), 25.7 (55.1%), 24.9 (71.9%), and 24.6 (69.1%), respectively. The mean HbA1C at 1, 4, 12, 26, and 52 weeks after operation were 9.2, 8.4, 7.7, 7.3, and 7.1, respectively. Resolution of type 2 diabetes was achieved in 2 (20%) patients at 4 weeks, 6 (30%) at 12 weeks, 8 (40%) at 26 weeks, and 10 (50%) at 52 weeks after sleeve gastrectomy. Before operation, the mean fasting plasma glucose and insulin levels were 240.1 + 80.9 mg/dL and 16.8 + or - 15.4 uIU/mL, respectively. The OGTT test showed a blunted insulin secretion pattern with an AUC of 3,135 uIU x min/mL. At 1 week after operation, the fasting plasma glucose and insulin levels significantly decreased to 158 + or - 52 mg/dL and 5.6 + or - 3.2 uIU/mL, respectively. The AUC decreased to 2,988.7 uIU x min/mL. The AUC at 4, 12, 26, and 52 weeks after operation was 2,211, 1,584, 3,621, and 3,351 uIU x min/mL, respectively. The diabetes resolution rates for those with pre-operative C-peptide <3, 3-6, and >6 ng/mL were 1/7 (14.3%), 7/11 (63.6%), and 2/2 (100%), respectively (P < .05).. Laparosopic gastric sleeve gastrectomy resulted in remission of poorly controlled nonmorbidly obese T2DM patients up to 50% at 1 year after operation. The effect is related more to the decreasing of insulin resistance because of calorie restriction and weight loss rather than to the increasing of insulin secretion. C-peptide >3 ng/mL is the most important predictor for a successful treatment.

Topics: Adult; Bariatric Surgery; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastrectomy; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Secretion; Laparoscopy; Male; Middle Aged; Obesity; Prospective Studies; Remission Induction; Weight Loss

Glucose-dependent insulinotropic peptide (GIP) contributes to incretin effect of insulin secretion which is impaired in Type 2 diabetes mellitus. The aim of this study was to introduce a simple meal test for evaluation of GIP secretion and action and to examine GIP changes in Type 2 diabetic patients. Seventeen Type 2 diabetic patients, 10 obese non-diabetic and 17 non-obese control persons have been examined before and after 30, 60 and 90 min stimulation by meal test. Serum concentrations of insulin, C-peptide and GIP were estimated during the test. Impaired GIP secretion was found in Type 2 diabetic patients as compared with obese non-diabetic and non-obese control persons. The AUCGIP during 90 min of the meal stimulation was significantly lower in diabetic patients than in other two groups (p<0.03). Insulin concentration at 30 min was lower in diabetic than in non-diabetic persons and the GIP action was delayed. The deltaIRI/deltaGIP ratio increased during the test in diabetic patients, whereas it progressively decreased in obese and non-obese control persons. Simple meal test could demonstrate impaired GIP secretion and delayed insulin secretion in Type 2 diabetic patients as compared to obese non-diabetic and non-obese healthy control individuals.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus, Type 2; Diagnostic Techniques, Endocrine; Dietary Fats; Dietary Proteins; Dietary Sucrose; Gastric Inhibitory Polypeptide; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Middle Aged; Obesity

Prolonged elevation of plasma nonesterified fatty acids (NEFA) induces insulin resistance and impairs pancreatic β-cell adaptation to insulin resistance. Studies in rodents suggest that inflammation may play a role in this "lipotoxicity." We studied the effects of sodium salicylate, an anti-inflammatory agent, on lipid-induced alterations in β-cell function and insulin sensitivity in six overweight and obese nondiabetic men. Each subject underwent four separate studies, 4-6 wk apart, in random order: 1) SAL, 1-wk placebo followed by intravenous (iv) infusion of saline for 48 h; 2) IH, 1-wk placebo followed by iv infusion of intralipid plus heparin for 48 h to raise plasma NEFA approximately twofold; 3) IH + SS, 1-wk sodium salicylate (4.5 g/day) followed by 48-h IH infusion; and 4) SS, 1-wk oral sodium salicylate followed by 48-h saline infusion. After 48-h saline or lipid infusion, insulin secretion and sensitivity were assessed by hyperglycemic clamp and euglycemic hyperinsulinemic clamp, respectively, in sequential order. Insulin sensitivity was reduced by lipid infusion (IH = 67% of SAL) and was not improved by salicylate (IH + SS = 56% of SAL). Lipid infusion also reduced the disposition index (P < 0.05), which was not prevented by sodium salicylate. Salicylate reduced insulin clearance. These data suggest that oral sodium salicylate at this dose impairs insulin clearance but does not ameliorate lipid-induced insulin resistance and β-cell dysfunction in overweight and obese nondiabetic men.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Area Under Curve; C-Peptide; Emulsions; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Heparin; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Overweight; Phospholipids; Sodium Salicylate; Soybean Oil; Triglycerides

A comparison of the plasma glucose and insulin day profiles between two prandial rapid-acting insulin analogues, insulin glulisine (glulisine) and insulin lispro (lispro), in 18 obese subjects with Type 2 diabetes. Subjects (body mass index: males, 36.7 [33.2-43.8] kg/m(2); females, 40.0 [35.7-46.5] kg/m(2)) received subcutaneous glulisine or lispro (0.15 U/kg) at 4-h intervals immediately (within 2 min) before three standard test meals during each of two 12-h, randomised, open-label, crossover studies (7+/-2-day interval between each). Overall, preprandial-subtracted glucose concentrations (area under the curve) were similar on the glulisine and lispro study days. However, the mean of the three maximal preprandial subtracted plasma glucose concentrations (DeltaGLU(max)) were lower with glulisine versus lispro (12%; p<0.01). Mean concentrations of insulin analogue were significantly higher post-meal with glulisine (p<0.01 for all). Post hoc analysis showed a significantly faster absorption rate for glulisine versus lispro in the first 30 min post-meal (estimated difference 0.48 microU/min; p<0.0001). Only two cases of hypoglycaemia were reported; both from one subject during the lispro day. When glulisine is injected immediately before a meal in obese patients with Type 2 diabetes, glulisine achieves significantly lower glucose excursions over lispro. Significantly faster absorption with higher and sustained post-meal levels of insulin analogue was achieved at every meal with glulisine versus lispro.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Male; Middle Aged; Obesity

Obesity and aging increase the risk of type 2 diabetes (T2D). We evaluated whether weight loss therapy improves pancreatic endocrine function and insulin sensitivity in obese older adults.. Twenty-four obese (BMI: 38 +/- 2 kg/m(2)) older (age: 70 +/- 2 years) adults completed a 6-month randomized, controlled trial. Participants were randomized to diet and exercise (treatment group) or no therapy (control group). beta-Cell function (assessed using the C-peptide minimal model), alpha-cell function (assessed by the glucagon response to an oral glucose load), insulin sensitivity (assessed using the glucose minimal model), and insulin clearance rate were evaluated using a 5-h modified oral glucose tolerance test.. Body weight decreased in the treatment group, but did not change in the control group (-9 +/- 1% vs. 0 +/- 1%; P < 0.001). Insulin sensitivity doubled in the treatment group and did not change in the control group (116 +/- 49% vs. -11 +/- 13%; P < 0.05). Even though indices of beta-cell responsivity to glucose did not change (P > 0.05), the disposition index (DI), which adjusts beta-cell insulin response to changes in insulin sensitivity, improved in the treatment group compared with the control group (100 +/- 47% vs. -22 +/- 9%; P < 0.05). The glucagon response decreased in the treatment but not in the control group (-5 +/- 2% vs. 4 +/- 4%; P < 0.05). Insulin secretion rate did not change (P > 0.05), but insulin clearance rate increased (51 +/- 25%; P < 0.05), resulting in lower plasma insulin concentrations.. Weight loss therapy concomitantly improves beta-cell function, lowers plasma glucagon concentrations, and improves insulin action in obese older adults. These metabolic effects are likely to reduce the risk of developing T2D in this population.

Topics: Aged; Aging; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diet, Reducing; Exercise; Female; Glucagon; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Islets of Langerhans; Male; Obesity; Risk Factors; Weight Loss

Children with new onset diabetes (n = 175) were evaluated over 12-months. Patients were presumptively diagnosed with type 2 diabetes mellitus (T2DM) (n = 26) based on obesity, a relative with T2DM, the ability to wean from insulin, and absence of glutamic acid decarboxylase-65 (GAD-65) antibodies. We hypothesized that markers of insulinization at diagnosis, including fasting C-peptide and insulin-like growth factor-binding protein (IGFBP)-1, in addition to initial CO(2) levels and urine ketones, would help in distinguishing type 1 diabetes mellitus (T1DM) from T2DM.. Children with T1DM (84 male, 65 female) had a mean age of 8.7 +/- 4.3 yr and a racial background of 78% white, 19% black, and 3% other. In contrast, children with T2DM (13 female, 13 male) had a mean age of 14.2 +/- 3.1 yr with a racial background of 58% black, 27% white, and 15% other. Fasting C-peptide level was 0.38 +/- 0.37 ng/mL in T1DM vs. 2.66 +/- 2.14 ng/mL in T2DM; a C-peptide of 0.85 ng/mL had 83% sensitivity in distinguishing T1DM from T2DM. Fasting IGFBP-1 level was 38.1 +/- 39.1 ng/mL (T1DM) vs. 3.6 +/- 4.5 ng/mL (T2DM); a value of 3.6 ng/dL could distinguish the two types of diabetes with 93% sensitivity. Urinary ketones were found in 79% of children with T1DM compared with 56% of those with T2DM, and the magnitude was associated with type of diabetes. Initial CO(2) level for T1DM was 17.9 +/- 6.9 mmol/L vs. 22.7 +/- 5.7 mmol/L for T2DM; a value of 21.5 mmol/L could distinguish the two types of diabetes with 83% sensitivity.. In addition to obesity, family history of T2DM, and absence of GAD-65 antibodies, children with new-onset T2DM may be distinguished from those with T1DM by a combination of biochemical parameters (C-peptide, IGFBP-1, CO(2), and urine ketones).

Topics: Adolescent; Biomarkers; C-Peptide; Carbon Dioxide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Ketones; Male; Obesity

Obesity is positively associated with hyperinsulinaemia, and it has been suggested that hyperinsulinaemia may contribute to maintain the obese state in insulin-resistant obese individuals. The aim of the present study was to investigate the effect of inhibition of insulin secretion by diazoxide on weight loss in obese, normoglycaemic (fasting plasma glucose of > or =6.1 mmol/l), hyperinsulinaemic (fasting plasma insulin of > or =100 pmol/l) adults during a 2.5 MJ/day energy-deficient diet.. In an 8-week, double-blind, placebo-controlled parallel design, 35 overweight and obese subjects (age: 23-54 years, body mass index: 27-66 kg/m(2)) were randomized either to 2 mg/kg/day (maximum 200 mg/day) of oral diazoxide or to placebo. Body composition and resting energy expenditure (REE) were measured before and after the intervention. Blood samples, and appetite sensations by visual analogue scales, were collected during fasting, during an oral glucose tolerance test (OGTT) and 4 h postprandially after a test meal. Subsequently, an ad libitum meal was given.. Thirty-one subjects completed the protocol. Eight weeks of diazoxide decreased incremental area under the response curve (iAUC) for insulin (iAUC(insulin)) and for C-peptide (iAUC(C-peptide)) and increased iAUC for glucose (iAUC(glucose)) during the OGTT and the test meal compared with the use of placebo (p < 0.003). No differences in changes between the groups in body weight, body fat, REE or appetite were observed during the 8-week trial.. These findings do not suggest that hyperinsulinaemia per se contributes to maintenance of the obese state, and insulin secretion inhibition seems not a promising drug target.

Topics: Adult; Blood Glucose; C-Peptide; Counseling; Diazoxide; Diet, Reducing; Double-Blind Method; Energy Intake; Female; Humans; Hyperinsulinism; Insulin; Insulin Antagonists; Insulin Secretion; Male; Obesity; Patient Dropouts; Placebos; Vasodilator Agents; Weight Loss

We have previously demonstrated abnormalities in insulin secretion in adolescents with type 2 diabetes mellitus (DM2) in response to the mixed meal test and to glucagon. In order to further assess beta-cell function in DM2, we measured insulin and C-peptide responses to oral glucose in adolescents with DM2 in comparison to non-diabetic obese and lean adolescents. We studied 20 patients with DM2, 25 obese adolescents with matching body mass index (BMI) (33.8 +/- 1.4 vs 34.3 +/- 1.0 kg/m2), and 12 non-obese control adolescents (BMI 22.6 +/- 0.6 kg/m2). Mean age, sex and sexual maturation did not differ between the three groups. All adolescents with DM2 had negative islet cell antibodies (ICA); five patients were on diet and 15 on insulin treatment. Fasting lipid profiles were determined in all participants. Plasma glucose and serum C-peptide and insulin levels were measured at 0, 30, 60, 90, and 120 min after an oral glucose load. The C-peptide increment (deltaCP) was calculated as peak minus fasting C-peptide. Area under the curve (AUC) was estimated using the trapezoid method. Insulin resistance was estimated using the HOMA model (HOMA-IR). The first phase of insulin secretion (PH1) was computed using a previously published formula. Serum triglyceride levels were significantly higher in the patients with DM2 compared to the non-obese controls (1.4 +/- 0.1 vs 0.9 +/- 0.1 mmol/l; p = 0.02). Plasma glucose AUC was greater in the patients with DM2 compared to the obese and non-obese control groups (1,660 +/- 130 vs 717 +/- 17 vs 647 +/- 14 mmol/l x min; p < 0.0001). ACP was lower in adolescents with DM2 than in obese and non-obese adolescents (761 +/- 132 vs 1,721 +/- 165 vs 1,225 +/- 165 pmol/l; p < 0.001). Insulin AUC was lower in the patients with DM2 compared to obese controls (888 +/- 206 vs 1,606 +/- 166 pmol/l x h; p = 0.009), but comparable to that of the non-obese controls (888 +/- 206 vs 852 +/- 222 pmol/l x h; p = 0.9). Insulin AUC was also higher in the obese than in the non-obese group (p = 0.05). PH1 was significantly higher in the obese group compared to the patients with DM2 as well as to the non-obese controls (2,614 +/- 2,47.9 vs 929.6 +/- 403.5 vs 1,946 +/- 300.6 pmol/l, respectively; p = 0.001). PH1 was also higher in the non-obese controls than in the patients with DM2 (p = 0.05). HOMA-IR was three-fold higher in the patients with DM2 than in the BMI-matched obese group, and five-fold higher than in the lean controls (14.3 +/- 1.2 vs 5.4

Topics: Adolescent; Black or African American; Blood Glucose; C-Peptide; Child; Cholesterol; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Humans; Hyperglycemia; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Obesity; Reference Values; Triglycerides

Increased intake of dietary fiber reduces the risk of obesity and type 2 diabetes. We assessed the effects of a fiber-rich diet on body weight, adipokine concentrations, and the metabolism of glucose and lipids in non-obese and obese subjects in Korea, where rice is the main source of dietary carbohydrates.. Eleven healthy, non-obese and 10 obese subjects completed two 4-week phases of individual isoenergetic food intake. During the control diet phase, subjects consumed standard rice; during the modified diet phase, subjects consumed equal proportions of fiber-rich Goami No. 2 rice and standard rice. We used a randomized, controlled, crossover study design with a washout period of 6 weeks between the two phases.. After the modified diet phase, body weight was significantly lower in both the non-obese and obese subjects (non-obese, 57.0 +/- 2.9 vs. 56.1 +/- 2.8 kg, p = 0.001; obese, 67.7 +/- 2.1 vs. 65.7 +/- 2.0 kg, p < 0.001 for before vs. after). The BMI was significantly lower in obese subjects (26.9 +/- 0.5 vs. 26.0 +/- 0.6 kg/m2, p < 0.001). The modified diet was associated with lower serum triacylglycerol (p < 0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.05), and C-peptide (p < 0.05) concentrations in the obese subjects.. These results indicate that fiber-rich Goami No. 2 rice has beneficial effects and may be therapeutically useful for obese subjects.

Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Cross-Over Studies; Dietary Carbohydrates; Dietary Fiber; Female; Glycated Hemoglobin; Humans; Leptin; Lipid Metabolism; Male; Obesity; Oryza; Resistin; Triglycerides

Animal and some human studies have indicated that the consumption of chili-containing meals increases energy expenditure and fat oxidation, which may help to reduce obesity and related disorders. Because habitual diets affect the activity and responsiveness of receptors involved in regulating and transporting nutrients, the effects of regular consumption of chili on metabolic responses to meals require investigation.. The objective was to investigate the metabolic effects of a chili-containing meal after the consumption of a bland diet and a chili-blend (30 g/d; 55% cayenne chili) supplemented diet.. Thirty-six subjects with a mean (+/-SD) age of 46 +/- 12 y and a body mass index (in kg/m2) of 26.3 +/- 4.6 participated in a randomized, crossover, intervention study with 2 dietary periods (chili and bland) of 4 wk each. The postprandial effects of a bland meal after a bland diet (BAB), a chili meal after a bland diet (CAB), and a chili meal after a chili-containing diet (CAC) were evaluated. Serum insulin, C-peptide, and glucose concentrations and energy expenditure (EE) were measured at fasting and up to 120 min postprandially.. Significant heterogeneity was observed between the meals for the maximum increase in insulin and the incremental area under the curve (iAUC) for insulin (P = 0.0002); the highest concentrations were with the BAB meal and the lowest with the CAC meal. When separated at the median BMI (26.3), the subjects with a BMI > or = 26.3 also showed heterogeneity in C-peptide, iAUC C-peptide, and net AUC EE (P < 0.02 for all); the highest values occurred after the BAB meal and the lowest after the CAC meal. Conversely, the C-peptide/insulin quotient (an indicator of hepatic insulin clearance) was highest after the CAC meal (P = 0.002).. Regular consumption of chili may attenuate postprandial hyperinsulinemia.

Topics: Adult; Aged; Area Under Curve; Blood Glucose; Body Mass Index; C-Peptide; Capsicum; Cross-Over Studies; Energy Metabolism; Fasting; Female; Humans; Insulin; Male; Middle Aged; Obesity; Oxidation-Reduction; Postprandial Period

Adolescent obesity is a serious public health concern.. The aim of the study was to determine whether obese adolescents can adapt metabolically to changes in dietary macronutrient intake.. Using a random cross-over design, 13 healthy obese volunteers (six boys and seven girls; age, 14.7 +/- 0.3 yr; body mass index, 34 +/- 1 kg/m2; body fat, 42 +/- 1%) were studied twice after 7 d of isocaloric, isonitrogenous diets with 60% carbohydrate (CHO) and 25% fat (high CHO), or 30% CHO and 55% fat (low CHO).. Glucose metabolism, insulin sensitivity, and first- and second-phase insulin secretory indices were measured by stable isotope techniques and the stable labeled iv glucose tolerance test. The results were compared with those of previously studied lean adolescents.. Obese adolescents increased first- and second-phase insulin secretory indices by 18 (P = 0.05) and 36% (P = 0.05), respectively, to maintain normoglycemia during the high-CHO diet because they failed to increase insulin sensitivity as did the lean adolescents. Regardless of diet, in obese adolescents, insulin sensitivity was half (P < 0.05) and first- and second-phase insulin secretory indices twice (P < 0.01), compared with the the corresponding values in lean subjects. In obese adolescents, gluconeogenesis increased by 32% during the low-CHO (high-fat diet) (P < 0.01).. In obese adolescents, insulin secretory demands were increased regardless of diet. Failure to increase insulin sensitivity while receiving a high-CHO diet required a further increase in insulin secretion, which may lead to earlier beta-cell failure. A low-CHO/high-fat diet resulted in increased gluconeogenesis, which may be a prelude to the increased glucose production and hyperglycemia observed in type 2 diabetics.

Topics: Adolescent; Blood Glucose; C-Peptide; Cross-Over Studies; Dietary Carbohydrates; Dietary Fats; Energy Metabolism; Female; Gluconeogenesis; Glycolysis; Humans; Insulin; Insulin Resistance; Insulin Secretion; Kinetics; Lipids; Male; Obesity; Oxidation-Reduction

To evaluate the safety and effectiveness of rosiglitazone in the treatment of overweight subjects with type 1 diabetes.. A total of 50 adult type 1 diabetic subjects with a baseline BMI > or =27 kg/m(2) were randomly assigned in a double-blind fashion to take insulin and placebo (n = 25) or insulin and rosiglitazone 4 mg twice daily (n = 25) for a period of 8 months. Insulin regimen and dosage were modified in all subjects to achieve near-normal glycemic control.. Both groups experienced a significant reduction in HbA(1c) (A1C) level (rosiglitazone: 7.9 +/- 1.3 to 6.9 +/- 0.7%, P < 0.0001; placebo: 7.7 +/- 0.8 to 7.0 +/- 0.9%, P = 0.002) and a significant increase in weight (rosiglitazone: 97.2 +/- 11.8 to 100.6 +/- 16.0 kg, P = 0.008; placebo: 96.4 +/- 12.2 to 99.1 +/- 15.0, P = 0.016). Baseline measures of BMI (P = 0.001), total daily insulin dose (P = 0.002), total cholesterol (P = 0.005), HDL cholesterol (P = 0.001), and LDL cholesterol (P = 0.02) were predictors of improvement in A1C level only in the group treated with rosiglitazone. Total daily insulin dose increased in subjects taking placebo (74.0 +/- 33.8 to 82.0 +/- 48.9 units, P < 0.05 baseline vs. week 32), but it decreased slightly in subjects taking rosiglitazone (77.5 +/- 28.6 to 75.3 +/- 33.1 units). Both systolic blood pressure (137.4 +/- 15.6 vs. 128.8 +/- 14.8 mmHg, baseline vs. week 32, P < 0.02) and diastolic blood pressure (87.2 +/- 9.4 vs. 79.4 +/- 7.2 mmHg, P < 0.0001) improved in the group treated with rosiglitazone. The total incidence of hypoglycemia did not differ between groups.. Rosiglitazone in combination with insulin resulted in improved glycemic control and blood pressure without an increase in insulin requirements, compared with insulin- and placebo-treated subjects, whose improved glycemic control required an 11% increase in insulin dose. Weight gain and hypoglycemia were similar in both groups at the end of the study. The greatest effect of rosiglitazone occurred in subjects with more pronounced markers of insulin resistance.

Topics: Adult; Blood Glucose; Body Mass Index; Body Size; C-Peptide; Diabetes Mellitus, Type 1; Double-Blind Method; Ethnicity; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Obesity; Placebos; Rosiglitazone; Thiazolidinediones; Weight Gain

Glucocorticoids increase both appetite and leptin secretion; the hyperleptinemic effect might be a counterregulatory response to the orexigenic effect of glucocorticoids. However, the effect of glucocorticoid inhibition on leptin production has not been reported.. We tested the hypothesis that if glucocorticoid-induced hyperleptinemia plays a physiological role, then inhibition of endogenous cortisol biosynthesis should decrease leptin secretion.. A randomized, placebo-controlled, cross-over study design was used.. The study was carried out at a General Clinical Research Center.. Eight obese subjects (four men, four women; mean age, 30.4 +/- 1.56 yr; mean body mass index, 42.0 +/- 1.33 kg/m2) participated in the study.. The subjects were treated with metyrapone (750 mg every 4 h) or placebo for 24 h during two overnight admissions, 2 wk apart. Blood sampling for measurement of cortisol, leptin glucose, insulin, and C-peptide was performed hourly for 6 h and every 2 h for 24 h.. The change in plasma leptin from baseline during metyrapone vs. placebo treatment was measured.. Metyrapone treatment was associated with a significant decrease in plasma cortisol level; the cortisol nadir was 4.84 +/- 1.22 microg/dl during placebo and 2.80 +/- 0.65 microg/dl during metyrapone treatment (P = 0.009). Compared with placebo, metyrapone treatment was associated with a significant reduction in circulating leptin levels and marked attenuation of the nocturnal rise in plasma leptin (+28.45 +/- 11.12% vs. +55.51 +/- 5.42%; P = 0.01).. We conclude that metyrapone-induced inhibition of cortisol biosynthesis results in hypoleptinemia, which indicates that glucocorticoids may play an important role in the physiological regulation of leptin.

Topics: Adult; Antimetabolites; C-Peptide; Circadian Rhythm; Cross-Over Studies; Female; Humans; Hydrocortisone; Leptin; Male; Metyrapone; Obesity

To evaluate the effects of metformin administration on spontaneous LH episodic release in a group of nonobese polycystic ovary (PCOS) patients.. Controlled clinical study.. PCOS patients in a clinical research environment.. Twenty nonobese PCOS patients were enrolled after informed consent.. All patients underwent hormonal evaluations and a pulsatility study (sampling every 10 minutes for 4 hours) before and at the sixth month of therapy (metformin, 500 mg, p.o. b.i.d.). Ultrasound examinations and Ferriman-Gallwey scoring were also performed.. Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17-hydroxy-progesterone (17-OHP), and testosterone (T), glucose, insulin, and C-peptide concentrations.. After 6 months of metformin administration, the plasma LH, 17-OHP, A, and T levels and LH/FSH ratio were significantly reduced. Insulin sensitivity, expressed as the glucose-to-insulin ratio, was significantly improved under glucose load after 6 months of treatment. Spontaneous LH episodic release showed a significant reduction in pulse amplitude with no changes in pulse frequency. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic women. The ovarian volume and Ferriman-Gallwey scores also were significantly reduced.. Metformin administration improves reproductive axis functioning in hyperandrogenic nonobese PCOS patients. By acting on the ovary and restoring normal ovarian activity, metformin positively modulates the reproductive axis (namely GnRH-LH episodic release).

Topics: 17-alpha-Hydroxyprogesterone; Adult; Androstenedione; Area Under Curve; Blood Glucose; C-Peptide; Estradiol; Female; Follicle Stimulating Hormone; Humans; Insulin; Luteinizing Hormone; Menstrual Cycle; Metformin; Obesity; Ovary; Polycystic Ovary Syndrome; Testosterone

A prolonged increase of plasma NEFA impairs acute glucose-stimulated insulin secretion (GSIS) in vitro and in vivo. Our study therefore examined the combined effect of increased plasma NEFA and glucose on GSIS in humans.. We examined GSIS on four occasions in eight obese men during a 10 mmol/l hyperglycaemic clamp and after a 24-h infusion of (i) normal saline, (ii) intralipid and heparin to raise plasma NEFA about two-fold above basal, (iii) 20% dextrose to raise plasma glucose to about 7.5 mmol/l and (iv) intralipid and heparin combined with 20% dextrose to raise plasma NEFA and glucose.. In study (iii) insulin sensitivity was about 20% greater than in study (i) and the disposition index was about 50% higher. Insulin sensitivity tended to be lower in study (ii) whereas the disposition index was lower than in study (i), confirming previous observations. The combination of increased plasma NEFA and glucose (study iv) reduced insulin sensitivity in comparison with study (i) and completely abolished the increase in insulin sensitivity and disposition index seen in study (iii), but did not reduce the latter to a lower value than that in the saline control study (study i).. We showed that a prolonged increase of plasma NEFA completely abolishes the stimulatory effect of moderate hyperglycaemia on insulin sensitivity and beta-cell function in obese humans. This suggests that previous observations, showing that a prolonged increase of plasma NEFA impairs pancreatic beta-cell function, also apply to the hyperglycaemic state.

Topics: Blood Glucose; C-Peptide; Fasting; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Glucose; Glucose Clamp Technique; Heparin; Humans; Infusions, Intravenous; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Obesity; Patient Selection; Triglycerides

We examined the long-term metabolic effects of glipizide gastrointestinal therapeutic system (GITS), a potent sulfonylurea (SU), in impaired glucose-tolerant (IGT), first-degree relatives of African American patients with type 2 diabetes. To this end, we assessed glucose homeostasis, beta-cell function, insulin sensitivity (Si), and glucose effectiveness (Sg) in patients with IGT before and at yearly intervals for 24 months of GITS or an identical placebo in a randomized, double-blind manner. Eighteen IGT patients were randomized to receive either glipizide GITS (GITS, 5 mg/d, n = 9; mean age, 43.3 +/- 8.7 years; mean body mass index [BMI], 32.9 +/- 6.3 kg/m(2)) or identical placebo (PLAC, n = 9; mean age, 41.5 +/- 5.7 years; mean BMI, 39 +/- 4.2 kg/m(2)) for 24 months. Each of the subjects underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT) at baseline and yearly intervals for 2 years. Si and Sg were determined by Bergman's minimal model method. The ability of beta cell to compensate for peripheral insulin resistance was calculated as the disposition index (DI). Chronic administration of glipizide GITS attenuated serum glucose responses to oral glucose challenge at 12 and 24 months when compared to baseline (0 months). In contrast, serum glucose levels at fasting and during OGTT tended to increase in the IGT/PLAC group at 12 and 24 months when compared to baseline. Serum insulin (P <.05 to 0.01) and serum C-peptide levels progressively increased in the GITS group at 12 and 24 months versus 0 months. In contrast, serum insulin and C-peptide responses remained unchanged in the IGT/PLAC group. During FSIGT, chronic GITS was associated with significant improvement in the blunted acute first insulin release in the IGT patients at 12 and 24 months. These parameters remained blunted in the IGT/PLAC group. We found that Si increased in the IGT/GITS group at 12 months (P <.01) and 24 months(P <.05) versus baseline, but deteriorated in the IGT/PLAC group. Similarly, the DIs significantly (P <.01) increased following GITS therapy at 12 and 24 months when compared to baseline. In contrast, DI did not change from baseline values in the IGT/PLAC group throughout the study period. Chronic GITS partially restored the ability of beta cells to compensate for peripheral insulin resistance (as assessed by DIs). GITS was well tolerated without any symptoms suggestive of either hypoglycemia or significant weight gain.

Topics: Adult; Black or African American; Blood Glucose; Body Composition; C-Peptide; Diabetes Mellitus, Type 2; Double-Blind Method; Glipizide; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Middle Aged; Models, Biological; Obesity; Risk Factors

Hyperproinsulinaemia reflects both beta cell dysfunction and insulin resistance in cross-sectional studies, but it is not known whether changes in proinsulin concentrations are related to insulin resistance over time. As trans10cis12 (t10c12)-conjugated linoleic acid (CLA) supplementation induces insulin resistance in obese men, we used this fatty acid to investigate the effects on plasma proinsulin, insulin, C-peptide and adiponectin concentrations, including their associations with change in insulin sensitivity.. We randomised (double-blind) 57 non-diabetic abdominally obese men to receive either 3.4 g t10c12CLA, CLA-isomer mixture or control oil for 12 weeks. Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), intact proinsulin, insulin, the proinsulin : insulin ratio, C-peptide, glucose and adiponectin were assessed before and after supplementation.. Supplementation with t10c12CLA increased proinsulin (p<0.01), the proinsulin : insulin ratio (p<0.05) and C-peptide concentrations (p<0.001) in comparison with control subjects. Adiponectin, however, did not change significantly. The change in proinsulin, but not the proinsulin : insulin ratio, was related to impaired insulin sensitivity (r= -0.58, p<0.0001), independently of changes in insulin, C-peptide, glucose, adiponectin and BMI. Conversely, the correlation between insulin sensitivity and specific insulin (r=-0.46, p<0.001) did not remain significant after adjustment for proinsulin. Induced hyperproinsulinaemia was also correlated to adiponectin concentrations ( r= -0.34, p<0.01).. In obese men, t10c12CLA induces hyperproinsulinaemia that is related to impaired insulin sensitivity, independently of changes in insulin concentrations. These results are of clinical interest, as hyperproinsulinaemia predicts diabetes and cardiovascular disease. The use of weight-loss supplements containing this fatty acid is worrying.

Topics: Abdomen; Adiponectin; Adipose Tissue; Analysis of Variance; Blood Glucose; C-Peptide; Dietary Supplements; Double-Blind Method; Drug Administration Schedule; Humans; Hyperinsulinism; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Linoleic Acids, Conjugated; Male; Obesity; Time Factors

Caffeine ingestion decreases the insulin sensitivity index (ISI) for an oral-glucose-tolerance test (OGTT) and decreases insulin-induced glucose disposal in lean male subjects during a hyperinsulinemic clamp.. We examined the effects of caffeine ingestion on insulin and glucose homeostasis in obese men before and after a nutrition and exercise intervention.. Nine sedentary, obese [body mass index (in kg/m(2)): 34.0 +/- 1.0] men who had refrained from exercise and caffeine ingestion for 48 h underwent 2 oral-glucose-tolerance tests (OGTTs). The subjects randomly received caffeine (5 mg/kg) or placebo 1 h before each OGTT. After a 12-wk nutrition and exercise intervention, during which time the subjects avoided dietary caffeine, the OGTTs were repeated.. The intervention resulted in decreases (P < or = 0.05) in body weight (8.5 +/- 1.5 kg), percentage body fat (2.8 +/- 0.7%), and fasting glucose, insulin, and proinsulin concentrations and increases in the ISI for the placebo OGTT (P < or = 0.05). Caffeine caused a greater (P < or = 0.05) OGTT insulin response and a lower (P < or = 0.05) ISI both before and after weight loss. The proinsulin-insulin ratio indicated that neither weight loss nor caffeine affected the nature of the beta cell secretion of insulin.. A nutrition and exercise intervention improved, whereas caffeine ingestion impaired, insulin-glucose homeostasis in obese men. The results are consistent with previous findings that caffeine ingestion contributes to insulin resistance.

Topics: Administration, Oral; Adult; Area Under Curve; Blood Glucose; C-Peptide; Caffeine; Central Nervous System Stimulants; Diet, Reducing; Double-Blind Method; Exercise; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Lactic Acid; Male; Obesity; Proinsulin; Weight Loss; Xanthines

Obesity is associated with increased hepatic glycogen content. In vivo and in vitro data suggest that plasma free fatty acids (FFA) may cause this increase. In this study we investigated the effect of physiological plasma FFA levels on hepatic glycogen metabolism by studying intrahepatic glucose pathways in lean and obese subjects. Six lean and 6 obese males were studied twice during a 16- to 22-hour fast, once with and once without acipimox, an inhibitor of lipolysis. Intrahepatic glucose fluxes were measured by infusion of [2-(13C1)]glycerol, [1-(2H1)]galactose, and [U-(13C6)]glucose. Acetaminophen was administered as a glucuronate probe. In both lean and obese control studies, plasma FFA levels increased progressively, whereas acipimox completely suppressed plasma FFA levels for the whole study period. In lean males glycogenolysis did not change in the acipimox study, but decreased in the control study (P < .01). In lean males, neither glycogen synthesis, glycogen synthesis retained as glycogen, nor glycogen balance differed between control and acipimox studies. In obese males glycogenolysis did not change in the acipimox study, but decreased in the control study (P < .01). Glycogen synthesis did not change in either study. Glycogen synthesis retained as glycogen did not change in acipimox study, but increased in the control study (P = .03). Glycogen balance did not change in the acipimox study, but increased in the control study (P < .01). This study demonstrates that in obese males physiological levels of FFA contribute to the retention of hepatic glycogen during short-term fasting by inhibiting breakdown of glycogen and increasing glycogen synthesis retained as glycogen, whereas in lean males this effect was absent due to unaltered glycogen synthesis retained as glycogen.

Topics: Adult; C-Peptide; Fasting; Fatty Acids, Nonesterified; Gas Chromatography-Mass Spectrometry; Gluconeogenesis; Glucose; Hormones; Humans; Hypolipidemic Agents; Insulin; Liver Glycogen; Male; Middle Aged; Obesity; Pyrazines; Stimulation, Chemical

We investigated effects of weight loss from diet and exercise regimen in obese subjects with normal fasting plasma glucose or impaired glucose tolerance (IGT) on insulin release capacity and insulin sensitivity. Eight subjects were recruited among visceral obesity patients (4 men, 4 women; age range, 24 to 57 years; body mass index [BMI], 32.8 to 60.3 kg/m(2)). All were admitted to Chiba University Hospital for 2 weeks, were treated with a tapering 5,023 to 2,930 kJ diet, and were given exercise equivalent to 628 kJ/d. For assessments, we used a combination of C-peptide secretion rate determination and minimal model analysis as previously reported. BMI and visceral fat area (V) significantly decreased (BMI on initiation v after intervention, 43.0 +/- 3.2 v 40.3 +/- 3.1 kg/m(2), P <.05; V, 224 +/- 22 v 188 +/- 22 cm(2); P <.05). Fasting immunoreactive insulin (F-IRI) and leptin concentrations decreased significantly. Capacity for insulin release in response to glucose increased in all subjects (first-phase insulin secretion [CS1], 4.66 +/- 4.05 v 6.81 +/- 4.57 ng/mL/5 min, P <.05), but the insulin sensitivity index (S(i)) did not change significantly. These data suggest that weight reduction early in development of type 2 diabetes can oppose progression of diabetes by improving capacity for insulin release.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Exercise Therapy; Female; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Models, Biological; Obesity; Weight Loss

Metformin is recognized as the treatment of chronic obese, insulin-resistant type 2 diabetic patients. Whether it improves insulin sensitivity in obese patients with normal glucose tolerance remains unknown.. Eight obese female patients with normal glucose tolerance were studied during a double blinded, randomized cross-over study including a 2-week administration of metformin and a 2-week administration of placebo. Insulin secretion and insulin sensitivity were assessed after metformin and placebo by means of a 3-hour hyperglycemic clamp.. The plasma insulin and C-peptide concentrations during the hyperglycemic clamp were identical after placebo or metformin (both first and second phases). Insulin-mediated glucose disposal, stimulation of glucose oxidation and suppression of endogenous glucose production were identical after metformin and placebo.. Metformin does not improve insulin sensitivity nor insulin secretion in obese female patients with normal glucose tolerance.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Cross-Over Studies; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Secretion; Metformin; Obesity; Placebos; Reference Values

To assess the postprandial leptin responses to a carbohydrate and a fatty meal in obese subjects and its association with postprandial insulin response.. Eight obese and 11 lean women were given, in a random order, an isocaloric carbohydrate meal (3.43 MJ, 166g of carbohydrates, 38g of proteins) or fat meal (3.35 MJ, 70g of fat, 36g of proteins) or remained fasting. Blood samples were collected hourly during the nine hours after the meal for leptin, insulin, C-peptide and glucose determinations.. In obese subjects, as in lean subjects, postprandial leptin response, calculated as the increment above fasting values, was higher after the carbohydrate meal than after the fatty meal (p < 0.01). However, after the carbohydrate meal, postprandial leptin increment was lower (p < 0.05) in obese subjects than in lean controls. In contrast, there was no difference in postprandial leptin response between lean and obese subjects after the fatty meal. Correlation analyses showed that the area under the postprandial leptin response curve (leptin AUC) was correlated to insulin AUC in lean (r = 0.70, p < 0.01), but not in obese subjects.. These results indicate that postprandial leptin response is lower after a carbohydrate meal in obese women than in lean controls, suggesting an impairment of postprandial leptin regulation in obese women.

Topics: Adult; Blood Glucose; C-Peptide; Dietary Carbohydrates; Dietary Fats; Fasting; Female; Food; Humans; Insulin; Leptin; Obesity

Insulin resistance decreases blood flow and volume in fat tissue. We hypothesised that fat tissue nutritive blood flow and volume, and thereby water content, would increase during weight loss and weight maintenance in obese persons.. Longitudinal clinical intervention with a 9-week very-low-calorie diet (VLCD) followed by one year of weight maintenance.. Obese men (n=13) and women (n=14) with the metabolic syndrome.. Water content of abdominal subcutaneous fat tissue as estimated by a sensor on the skin surface measuring the dielectric constant at 300 MHz. Anthropometric measures of fatness and fat distribution. Biochemical measures related to insulin resistance.. Subjects lost 14.5+/-3.4% of body weight during the VLCD, and generally sustained this weight loss during weight maintenance. Insulin sensitivity as estimated by an index (qualitative insulin sensitivity check index) increased during the VLCD, and remained increased throughout weight maintenance. The dielectric constant increased from 23.3+/-2.3 to 25.0+/-2.1 (P<0.001) during the VLCD, and further to 27.8+/-1.9 (P<0.001) during weight maintenance, indicating an increase in the water content of subcutaneous fat. The increase in subcutaneous fat water content did not correlate with weight loss and other measures of adiposity during the VLCD, but there was an inverse correlation that strengthened in significance from baseline to 6, 9 and 12 mo (r=-0.32 to -0.64, P=0.079-0.002). Increases in subcutaneous fat water content also correlated with improvements in insulin sensitivity at 6, 9 and 12 months of weight maintenance (r=0.34-0.54, P=0.094-0.006).. Water content of abdominal subcutaneous adipose tissue increases with weight loss in obese persons with the metabolic syndrome, and may reflect increased subcutaneous fat tissue nutritive blood flow. The increase in water content correlates with the increase in insulin sensitivity, suggesting that weight loss and consequent improved insulin sensitivity could mediate the increase in abdominal subcutaneous fat hydration.

Topics: Abdomen; Adipose Tissue; Adult; Blood Glucose; Body Composition; Body Water; C-Peptide; Cholesterol, HDL; Double-Blind Method; Energy Intake; Female; Humans; Insulin; Insulin Resistance; Lipoproteins, LDL; Longitudinal Studies; Male; Middle Aged; Obesity; Subcutaneous Tissue; Weight Loss

We studied the effect of a low-grade short- and long-term 20% Intralipid infusion (0.4 mL(-1) x kg(-1) x h(-1)) on insulin secretion and insulin action in 15 elderly obese men; 7 glucose intolerant first-degree relatives of type 2 diabetic patients (impaired glucose tolerance [IGT] relatives) and 8 healthy controls of similar age and body mass index (BMI). Intravenous glucose tolerance test (IVGTT) and a graded glucose infusion (dose-response test [DORE]) were performed to determine first phase insulin response and to explore the dose response relationship between glucose concentration and insulin secretion rates (ISR). ISR were calculated by deconvolution of plasma C-peptide concentrations. Insulin action was determined by performing a 120-minute hyperinsulinemic euglycemic clamp. All tests were performed 3 times, preceded by 0, 2, or 24 hours Intralipid infusion. Disposition indices (DI) were calculated for the IVGTT. Insulin action was reduced 25% after 2 and 24 hours Intralipid infusion in both groups. In IGT relatives, the beta-cell responsiveness to glucose (measured during DORE) decreased after 2 and 24 hours Intralipid infusion (P=.02), whereas first phase insulin response (measured during IVGTT) decreased after 24 hours Intralipid infusion. Insulin secretion measured during DORE and IVGTT was not affected by Intralipid infusion in controls. DI decreased after 2 and 24 hours Intralipid infusion in the total study population. In conclusion, insulin resistance induced by low-grade short- and long-term Intralipid infusion is not balanced by an adequate compensatory increase in insulin secretion in IGT relatives or in matched controls. IGT relatives appear to be more sensitive to the deleterious effects of low-grade fat infusion on insulin secretion than normal glucose tolerant control subjects.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Obesity; Triglycerides

The dynamic of glycemia, insulin, C-peptide, glycosylated hemoglobin, fructosamine, thyroid hormones, parameters of serum lipids, lipid peroxidation and system of antioxidant defense in 81 hospital patients and out-patients with obesity associated with diabetes mellitus type II was studied of influence of hypocaloric diet 9. Universal normalizing influence of hypocaloric diet 9 with vegetation tea was discovered on parameters of carbohydrate, lipid and oxidative metabolism and of patients clinical state of pateni. The additional criteria of evaluation of efficacy of food dietary supplements in complex treatment of patients with obesity associated with diabetes mellitus type II was offered on basis of study of influence vegetation tea on mechanisms of metabolic disorders in these patients.

Topics: Adult; Aged; Beverages; Blood Glucose; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diet Therapy; Female; Fructosamine; Glycated Hemoglobin; Humans; Insulin; Male; Medicine, Chinese Traditional; Middle Aged; Obesity; Plants, Medicinal; Thyroid Gland; Thyroid Hormones; Ultrasonography

Type 2 diabetes is caused by reduced insulin secretion and insulin resistance in skeletal muscle and liver. We tested the combination therapy with insulin aspart, rosiglitazone, and metformin with the purpose of treating all three defects in order to test the hypothesis that this "triple therapy" will normalize glucose metabolism.. Sixteen obese type 2 diabetic outpatients on human NPH or MIX (regular + NPH insulin) insulin twice daily were randomized to either triple therapy, i.e., insulin aspart (a rapid-acting insulin analog) at meals, metformin (which improves hepatic insulin sensitivity), and rosiglitazone (which improves peripheral insulin sensitivity), or to continue their NPH or MIX insulin twice daily for 6 months. Insulin doses were adjusted in both groups based on algorithms. HbA(1c), insulin dose, hypoglycemic episodes, insulin sensitivity (clamp), hepatic glucose production (tracer), and diurnal profiles of plasma glucose and insulin were used in evaluating treatment.. In the triple therapy group, HbA(1c) declined from 8.8 to 6.8% (P < 0.01) without inducing severe hypoglycemic events. Postprandial hyperglycemia was generally avoided, and the diurnal profile of serum insulin showed fast and high peaks without any need to increase insulin dose. In the control group, the insulin dose was increased by 50%, but nevertheless both HbA(1c) and 24-h blood glucose profiles remained unchanged. Insulin sensitivity improved in both skeletal muscle and the liver in the triple therapy group, whereas no change was observed in the control group.. We conclude that treatment of the three major pathophysiological defects in type 2 diabetic subjects by triple therapy significantly improved glucose metabolism in obese type 2 diabetic subjects.

Topics: Aged; Blood Glucose; Blood Pressure; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucose Clamp Technique; Glycated Hemoglobin; Glycolysis; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Male; Metformin; Middle Aged; Obesity; Rosiglitazone; Thiazolidinediones

Acarbose is an oral antidiabetic mainly acting on postprandial blood glucose, inhibiting alphaglucosidase. Through this mechanism, it could improve the peripheral insulin sensitivity and/or increase the insulin secretion. The aim of the present study is to assess the therapeutic efficacy of Acarbose in obese type 2 diabetic patients on both insulin resistance and insulin secretion.. 17 obese non insulin-dependent diabetic patients, well controlled with diet alone were randomized into 2 groups: acarbose (2 x 50 mg) or placebo during 16 weeks. A glucagon test allowed to evaluate insulin secretion before and after treatment as well as a triple test (glucose-insulin-somatostatin) with indirect calorimetry allowed to evaluate insulin sensitivity.. A significant improvement in post-prandial plasma glucose was detected only in the Acarbose group (8.0 +/- 0.5 mmol/l before vs 6.5 0.5 mmol/l after, p<0.05). Basal C-peptide secretion was similar between groups and remained unchanged after treatment. However, stimulated insulin secretion was significantly increased by 30%, p<0.05, in the Acarbose group while no change was detected in the placebo group. Interestingly, the group receiving Acarbose disclosed a 15% reduction in insulin resistance (15.0 +/- 1.8 mmol/l before vs 12.8 +/- 1.4 mmol/l after).. Our results show that a treatment with Acarbose is efficient even in diabetic patients presenting a good glucose control without any other associated treatment. By decreasing post-prandial blood glucose, acarbose improves both insulin sensitivity and secretion.

Topics: Acarbose; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Obesity; Placebos; Research Design

The insulinotropic hormone, glucagon-like peptide-1 (GLP-1), is being examined as a potential new agent for treatment in type 2 diabetic patients. Whereas the insulinotropic properties of this peptide are well established, another property of the hormone, an insulinomimetic effect per se, is controversial. In the normal glucose-tolerant lean state, it is difficult to demonstrate an insulinomimetic effect. The current study was conducted to examine whether GLP-1 has insulinomimetic effect in the obese state. Ten obese volunteers (body mass index, 34.6 +/- 0.8 kg/m(2)), whose ages were 32.5 +/- 3.0 yr, participated in two euglycemic clamp studies (n = 20 clamps) for 120 min. Five of the volunteers were females. The initial clamp was performed with a primed (0-10)-constant (10-60) infusion of GLP-1 at a final rate of 1.5 pmol x kg(-1) x min(-1). At 60 min, the GLP-1 infusion was terminated, and euglycemic was maintained from 60-120 min. After the GLP-1 study, each individual's plasma insulin level was measured. A second study was performed that was identical to the first, with the infusion of regular insulin in place of GLP-1. Insulin infusion rates were regulated in each individual to simulate plasma insulin levels produced during the GLP-1 infusion. The rate of disappearance of glucose was calculated for each subject. Fasting plasma insulin levels were similar between studies. In response to the GLP-1 infusion, with maintenance of plasma glucose level clamped at fasting level, significant increases in plasma insulin occurred in all subjects (P < 0.001). The insulin levels during the insulin infusion study were similar to that induced by GLP-1. The rate of disappearance of glucose (insulin-mediated glucose uptake) progressively increased in response to both the GLP-1 and insulin infusion. However, the rate of disappearance of glucose during the GLP-1 study was significantly higher (P = 0.033) than during the insulin study. We conclude that in insulin-resistant states, GLP-1 has insulinomimetic properties per se.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fatty Acids, Nonesterified; Female; Glucagon; Glucagon-Like Peptide 1; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Obesity; Peptide Fragments; Protein Precursors

This study was designed to compare the efficacy of acute premeal administration of glipizide versus nateglinide in controlling postprandial hyperglycemia in subjects with non-insulin-requiring type 2 diabetes.. A total of 20 subjects (10 female, 10 male) with non-insulin-requiring type 2 diabetes were admitted overnight to the General Clinical Research Center on four occasions. In random order, 10 mg glipizide (30 min premeal), 120 mg nateglinide (15 min premeal), 10 mg glipizide plus nateglinide (30 and 15 min premeal, respectively), or placebo pills (30 and 15 min premeal) were administered in a double-blind fashion before a standardized breakfast. Blood was drawn for analysis of glucose, insulin, and C-peptide at -0.05, 0, 0.5, 1, 2, 3, and 4 h relative to the meal.. The subjects were aged 56 +/- 2 years and were moderately obese (BMI 31 +/- 1 kg/m(2)), with a mean HbA(1c) of 7.4 +/- 0.4%. The peak postprandial glucose excursion above baseline was higher with placebo (6.1 +/- 0.5 mmol/l) than glipizide (4.3 +/- 0.6 mmol/l, P = 0.002), nateglinide (4.2 +/- 0.4 mmol/l, P = 0.001), or glipizide plus nateglinide (4.1 +/- 0.5 mmol/l, P = 0.001). The area under the curve for the glucose excursion above baseline was also higher with placebo (14.1 +/- 1.8 mmol/h. l) compared with glipizide (6.9 +/- 2.4 mmol/h. l, P = 0.002), nateglinide (9.7 +/- 2 mmol/h. l, P = 0.004), or glipizide plus nateglinide (5.6 +/- 2.2 mmol/h. l, P < 0.001). Peak and integrated glucose excursions did not differ significantly between glipizide and nateglinide. However, by 4 h postmeal, plasma glucose levels were significantly higher with nateglinide (9 +/- 0.9 mmol/l) compared with the premeal baseline (7.8 +/- 0.6 mmol/l, P = 0.04) and compared with the 4-h postprandial glucose level after administration of glipizide (7.6 +/- 0.6 mmol/l, P = 0.02). Integrated postprandial insulin levels were higher with glipizide (1,556 +/- 349 pmol/h. l) than nateglinide (1,364 +/- 231 pmol/h. l; P = 0.03). Early insulin secretion, as measured by insulin levels at 30 min postmeal, did not differ between glipizide and nateglinide.. Acute premeal administration of nateglinide or glipizide has equal efficacy in controlling postbreakfast hyperglycemia in type 2 diabetes when each drug is administered at the optimum time before the meal. Glipizide causes a more pronounced and sustained postmeal insulin secretory response compared with nateglinide. Glipizide facilitates the return to near-fasting glucose levels at 4 h postmeal, but with the possible risk of increased frequency of postmeal hypoglycemia in drug-naive patients. The clinical decision to use glipizide versus nateglinide should be based on factors other than the control of postprandial hyperglycemia in type 2 diabetes.

Topics: C-Peptide; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glipizide; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Obesity; Postprandial Period

Our aim was to distinguish beneficial effects of B-cell rest from other effects of correction of hyperglycaemia. For this purpose we used diazoxide which reversibly blocks insulin secretion.. Eight obese (age 53 +/- 1 yr: BMI 33 +/- 2 kg/m2: 4 females) type 2 diabetic patients with poor metabolic control (HbA1c 8.7 +/- 0.9% ref.<5.2%) were studied twice after a randomly ordered treatment period of five days of intensive i.v. insulin treatment alone or i.v. insulin with peroral diazoxide (300 mg/day, divided into 3 doses). The glycaemic control was not altered between the two treatment periods. Insulin secretion was measured in response to i.v. glucose and arginine.. Insulin infusion was used to achieve close to identical degrees of glycaemia during the two treatment periods. Previous treatment with diazoxide was associated with a moderate 1.9 +/- 0.6 fold rise in insulin response to intravenous glucose (p=0.04) and 1.6 +/- 0.4 fold increased glucose potentiation of arginine-induced insulin secretion (GPAIS) (p=0.04). Conversely, after insulin alone there was no response to i.v. glucose and no change in GPAIS.. Short-term diazoxide treatment improved important parameters of B-cell function and these effects could be dissociated from confounding effects of changes in glycaemia. Consequently, the results indicate beneficial effects of B-cell rest.

Topics: Antihypertensive Agents; Blood Glucose; C-Peptide; Cholesterol; Cholesterol, LDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diazoxide; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Secretion; Islets of Langerhans; Middle Aged; Obesity; Proinsulin; Regression Analysis; Triglycerides

To evaluate the effects of long-term acipimox administration on glucose-induced insulin secretion and peripheral insulin sensitivity in polycystic ovarian syndrome (PCOS), 20 PCOS subjects (eight lean and 12 obese) and 14 body mass index-matched controls (seven lean and seven obese) were investigated.. Fasting blood samples were collected for basal hormone and lipoprotein assays, after which patients underwent an oral glucose tolerance test (OGTT). The following day a euglycaemic-hyperinsulinaemic clamp was performed. After 4-6 weeks of treatment with acipimox at a dose of 250 mg given orally three times a day, the patients repeated the study protocol.. No significant differences were found in the glucose, insulin or C-peptide responses to OGTT before and after anti-lipolytic drug administration in any group, nor was there any effect on insulin sensitivity. Concerning the lipid profile, acipimox administration led to a significant decrease of cholesterol and low-density lipoprotein levels in obese PCOS patients as well as in obese and lean controls. Lower triglycerides were found after the drug administration in both obese groups. Post-treatment free fatty acid levels were not significantly different when compared with basal values.. Acipimox does not appear to be an effective insulin-lowering drug in PCOS, even if it can be used in obese women with PCOS as an additional therapeutic agent to ameliorate the atherogenic lipid profile of the syndrome.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Hypolipidemic Agents; Insulin; Obesity; Pilot Projects; Polycystic Ovary Syndrome; Pyrazines; Thinness; Time Factors; Triglycerides

To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG)and beta-cell function.. Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet.. Twelve obese patients (11 women, 1 man), age 45.8 +/- 10.5 years, body weight (BW) 99.7 +/- 13.3 kg, BMI 35.3 +/- 2.8 kg/m(2).. At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning.. The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a19% increase. A significant decrease in both fasting (p = 0.038) and 2 h (p = 0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = - 0.83,p = 0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in S(I) explaining 67% of the variation. First phase insulin response (AIRg)remained unchanged whereas insulin disposition index increased significantly (p = 0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later.. In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Body Composition; C-Peptide; Female; Glucose Tolerance Test; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Placebos; Weight Loss

A weight-reducing effect of metformin has been demonstrated in obese subjects with and without diabetes. The mechanisms of this action are unclear, which may be partly due to the fact that in obese and diabetic patients the substance's effects result from a complex interaction with the distinct endocrine and metabolic disturbances in these patients. To dissociate primary from secondary action of metformin, we examined effects of the substance in normal-weight healthy subjects. Fifteen normal-weight men were treated with metformin (850 mg twice daily) or placebo for a 15-day period in a double-blind, placebo-controlled, cross-over study. Anthropometric, psychologic, cardiovascular, endocrine, and metabolic parameters were assessed before and at the end of the treatment period. Metformin did not affect body weight (P =.838) and body fat mass (P =.916). Yet, serum leptin concentration was distinctly reduced after metformin (P <.001). Also, metformin reduced the concentration of plasma glucose (P =.011), serum insulin (P=.044), and serum insulin-like growth factor -1 (IGF-1) (P=.013), while it increased serum glucagon concentration (P <.001). There were no effects of metformin on feelings of hunger, blood pressure, heart rate, resting energy expenditure, the respiratory quotient, free fatty acids, beta-hydroxybutyrate, glycerol, triglycerides, cholesterol, and uric acid (all P >.1). Data indicate that metformin decreases the serum leptin concentration even without affecting body weight and body composition in normal-weight men.

Topics: Adipose Tissue; Adult; Blood Pressure; Body Weight; C-Peptide; Diabetes Mellitus; Glucagon; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Metformin; Obesity; Reference Values

The aim of this study was to evaluate the effects of sibutramine on plasma leptin levels, body weight and glucose metabolism in non-dieting women. Fourteen healthy, non-diabetic, obese women were studied before treatment, after 1 week of placebo administration, and after a 2-week course of sibutramine (10 mg/day). At each of these stages, we assessed body composition, measured the levels of plasma leptin, C-peptide and various biochemical parameters, and also recorded plasma insulin and glucose levels during oral glucose tolerance tests. After 1 week of placebo treatment, there were no significant changes in any of the parameters. However, two weeks of 10 mg/day sibutramine dropped plasma leptin levels from a mean (+/-SE) of 48.84+/-4.54 to 42.84+/-4.74 ng/ml (p<0.04), reduced BMI from 39.36+/-2.01 to 38.57+/-1.93 kg/m2 (p<0.002), and decreased insulin resistance (IR, as measured using the homeostasis model assessment of insulin resistance) from 5.59+/-0.85 to 3.66+/-0.43 (p<0.02). There was no correlation between the reduction in leptin concentration and the decrease in BMI, fat mass, percent body fat, IR, C-peptide, or the area under curve for glucose or insulin. There was also no correlation between the decrease in leptin levels and the increases that occurred in the insulin sensitivity index or the hepatic sensitivity index. The results showed that treatment with 10 mg/day sibutramine significantly reduces BMI, IR and leptin levels in non-dieting obese women.

Topics: Adult; Appetite Depressants; Blood Glucose; Body Mass Index; C-Peptide; Cyclobutanes; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Liver; Obesity; Placebos

This study was designed to explore whether low doses of recombinant human (rh)GH affect lipid, glucose, or protein metabolism in men with visceral obesity. Four different studies were performed in six, otherwise healthy, obese men (age, 42 +/- 3; body mass index, 33 +/- 1 kg/m(2); waist circumference, 111 +/- 3 cm; mean +/- SEM). Lipid, glucose, and protein kinetics was estimated by infusing stable isotopes (glycerol, glucose, leucine) in the basal state and after 1 wk of treatment with sc bedtime injections of either placebo, 2.5 (GH2.5), or 3.3 (GH3.3) microg rhGH/kg body weight per day. When compared with baseline, placebo had no effect on lipid, glucose, or protein fluxes. In contrast, GH2.5 and GH3.3 increased lipolysis by approximately 25% (P < 0.04) without changing glucose and protein turnover rates. The two rhGH treatments increased within the normal range serum IGF-I (by approximately 30%; P < 0.01), whereas they augmented insulin secretion (P < 0.04) in a dose-dependent manner (GH2.5 by 19%, GH3.3 by 37%). C-peptide secretion was increased (P = 0.01) only by GH3.3 (by 28%). In conclusion, 1 wk of treatment with low doses of rhGH is sufficient to increase lipolysis in visceral obese men, but it does not modify glucose and protein turnover rates. The results of this study provide the rationale to design clinical trials using low doses of rhGH to attempt to reduce fat mass.

Topics: Adult; Blood Glucose; C-Peptide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fatty Acids, Nonesterified; Hormones; Human Growth Hormone; Humans; Keto Acids; Leucine; Lipid Metabolism; Lipolysis; Male; Middle Aged; Obesity; Osmolar Concentration; Recombinant Proteins; Viscera

We studied the significance of BsmI restriction enzyme polymorphism of the vitamin D receptor (VDR) gene and the XbaI and PvuII polymorphisms of the estrogen receptor (ER) gene in patients with type 2 diabetes (n=49), android type obesity with normal carbohydrate metabolism (n=29) and healthy controls (n=138).. The distribution of genotypes in the study groups, as well as their relationship to fasting and 1 h postprandial serum C-peptide levels were analyzed.. Postprandial serum C-peptide levels of BB genotypes were significantly higher in the diabetes and obese groups (6.18+/-5.09 ng/ml) compared with other genotypes (2.71+/-2.45 vs. 1.72+/-1.97 ng/ml, respectively, P=0.05). Among patients with type 2 diabetes and obese subjects, the XX allelic variant of the ER gene was more frequent (P=0.00015). Postprandial C-peptide levels of subjects exhibiting XX genotype were significantly lower compared with those with Xx genotype (1.67+/-2.16 vs. 3.8+/-3.72 ng/ml, P=0.021). The BBXx allelic combination of the VDR/ER receptor genes was less frequent in diabetic patients than in healthy subjects or in obese patients. The BBXx genotype was associated with significantly elevated postprandial C-peptide levels in all subjects compared with other combinations (9.65+/-3.14 vs. 1.35+/-2.82 ng/ml, P=0.003). No difference was found in the distribution of the PvuII polymorphism of the ER gene or in the association with the C-peptide levels among study groups.. Polymorphisms of the VDR/ER receptor genes might play a role in the pathogenesis of type 2 diabetes by influencing the secretory capacity of beta-cells.

Topics: Adult; Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Obesity; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; Vitamin D

To investigate the effect of chromium picolinate (CP) supplementation on body composition, resting metabolic rate (RMR), selected biochemical parameters and iron and zinc status in moderately obese women participating in a 12-week exercise program.. Forty-four women, 27 to 51 years of age, were randomly assigned to two groups based on their body mass index. Subjects received either 400 microg/day of chromium as a CP supplement or a placebo in double-blind fashion and participated in a supervised weight-training and walking program two days per week for 12 weeks. Body composition and RMR were measured at baseline, 6 and 12 weeks. Selected biochemical parameters and iron and zinc status were measured at baseline and 12 weeks.. Body composition and RMR were not significantly changed by CP supplementation. No significant differences in fasting plasma glucose, serum insulin, plasma glucagon, serum C-peptide and serum lipid concentrations or in iron and zinc indices were found between the two groups over time. Serum total cholesterol concentration significantly decreased (p = 0.0016) over time for all subjects combined, probably as a result of the exercise training. Exercise training significantly reduced total iron binding capacity (TIBC) by 3% for all subjects combined (p = 0.001 1).. Twelve weeks of 400 microg/day of chromium as a CP supplement did not significantly affect body composition, RMR, plasma glucose, serum insulin, plasma glucagon, serum C-peptide and serum lipid concentrations or iron and zinc indices in moderately obese women placed on an exercise program. The changes in serum total cholesterol levels and TIBC were a result of the exercise program.

Topics: Adult; Basal Metabolism; Blood Glucose; Blood Proteins; Body Composition; C-Peptide; Cholesterol; Chromium; Diet; Dietary Supplements; Double-Blind Method; Exercise; Fasting; Female; Glucagon; Humans; Insulin; Iron; Lipids; Middle Aged; Obesity; Patient Compliance; Placebos; Zinc

To evaluate the effects of acute lowering of FFAs on glucose-induced insulin secretion and GH response to GHRH in polycystic ovary syndrome (PCOS), 27 PCOS subjects (11 lean and 16 obese) and 17 body mass index-matched controls (8 lean and 9 obese) were investigated. Patients underwent an oral glucose tolerance test and a GHRH test before and after administration of the antilipolytic drug acipimox (250 mg orally 3 h and 1 h before the starting of the tests). Blood samples were collected for 2 h after GHRH bolus and for 4 h after the oral glucose tolerance test. Serum concentrations of GH, insulin, glucose, and c-peptide were assayed in each sample, and the results were expressed as area under the curve (AUC). No significant differences were found as to glucose, insulin, and c-peptide AUC before and after acute FFA plasma reduction in any of the investigated groups. Basally, lower GH-AUC was found in lean PCOS compared with body mass index-matched controls and in obese vs. lean controls; no significant differences were found as to the same variable between the two obese groups. The acipimox induced FFA suppression elicited in the four groups a sustained increase in the GH response to its trophic hormone; indeed, the GH-AUC nearly doubled with respect to basal evaluation in all the studied groups. However, the antilipolytic drug was not able to abolish the differences found between lean groups in basal conditions. In conclusion, the presented data confirm that FFAs have a main role in regulating GH secretion at the pituitary level; however, it does not seem that they could explain the GH as well as insulin dysfunction of PCOS.

Topics: Adult; Area Under Curve; Body Mass Index; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Growth Hormone-Releasing Hormone; Hormones; Human Growth Hormone; Humans; Hypolipidemic Agents; Insulin; Insulin Resistance; Lipids; Obesity; Polycystic Ovary Syndrome; Pyrazines

Insulin secretion rates are greater after oral glucose than after parenteral administration of an equivalent glucose load. This augmented beta-cell secretory response to an oral glucose load results from the release of mainly two gut hormones: gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1, which potentiate glucose-induced insulin secretion. Because of their insulinotropic action, their abnormal secretion may be involved in the pathogenesis of the hyperinsulinemia of childhood obesity. In this study, we used the hyperglycemic clamp with a small oral glucose load to assess the effect of childhood obesity on GIP response in seven prepubertal lean and 11 prepubertal obese children and in 14 lean adolescents and 10 obese adolescents. Plasma glucose was acutely raised to 11 mM by infusing i.v. glucose and kept at this concentration for 180 min. Each subject ingested oral glucose (30 g) at 120 min, and the glucose infusion was adjusted to maintain the plasma glucose plateau. Basal insulin and C-peptide concentrations and insulin secretion rates (calculated by the deconvolution method) were significantly greater in obese children compared with lean children (p < 0.001). Similarly, during the first 120 min of the clamp, insulin secretion rates were higher in obese than lean children. After oral glucose, plasma insulin, C-peptide, and insulin secretion rates further increased in all four groups. This incretin effect was 2-fold greater in obese versus lean adolescents (p < 0.001). Circulating plasma GIP concentrations were similar at baseline in all four groups and remained unchanged during the first 120 min of the clamp. After oral glucose, plasma GIP concentrations rose sharply in all groups (p < 0.002). Of note, the rise in GIP was similar in both lean and obese children. In conclusion, under conditions of stable hyperglycemia, the ingestion of a small amount of glucose elicited equivalent GIP responses in both lean and obese children. However, despite similar GIP responses, insulin secretion was markedly augmented in obese adolescents. Thus, in juvenile obesity, excessive alimentary beta-cell stimulation may be independent of the increased release of GIP.

Topics: Administration, Oral; Adolescent; Area Under Curve; Blood Glucose; C-Peptide; Child; Female; Gastric Inhibitory Polypeptide; Glucose; Glucose Clamp Technique; Humans; Infusions, Intravenous; Insulin; Insulin Secretion; Male; Obesity

To characterize metabolic effects of troglitazone in type 2 diabetic, obese, and lean subjects, and examine the effects of troglitazone 2-3 weeks after discontinuation.. Nine type 2 diabetic, nine obese, and nine lean subjects underwent baseline metabolic studies including an 8-h meal-tolerance test (MTT) and a 5-h glucose clamp. Subjects then received troglitazone (600 mg/day) for 12 weeks and subsequently had repeat metabolic studies. Diabetic subjects remained off hypoglycemic agents for 2-3 weeks and then underwent a 5-h glucose clamp.. In diabetic subjects, fasting plasma glucose was reduced (P<0.05) and insulin-stimulated glucose disposal (Rd) was enhanced by treatment (P<0.02). The area under the MTT 8-h plasma glucose curve declined with therapy (P<0.001), and its change was positively correlated with the improvement in Rd (r = 0.75, P<0.05). There was also a positive correlation between the change in fasting hepatic glucose output (HGO) and the change in fasting plasma glucose with treatment (r = 0.92, P<0.001). Discontinuation of therapy for 2-3 weeks did not significantly affect fasting plasma glucose or insulin-stimulated glucose Rd. In obese subjects, insulin-stimulated glucose Rd improved with therapy (P<0.001), allowing for maintenance of euglycemia by lower plasma insulin concentrations (P<0.05). In lean subjects, an increase in fasting HGO (P<0.001) and glucose clearance (P<0.01) was observed.. Troglitazone lowers fasting and postprandial plasma glucose in type 2 diabetes by affecting both fasting HGO and peripheral insulin sensitivity. Its effects are evident 2-3 weeks after discontinuation. In obese subjects, its insulin sensitizing effects suggest a role for its use in the primary prevention of type 2 diabetes.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Cholesterol; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Thiazoles; Thiazolidinediones; Troglitazone

Unlike other pharmacological therapies used in obese type 2 diabetic patients, metformin has been shown to improve glycemic control with lower insulin levels and not to involve weight gain. We therefore examined the effect of adjunct metformin in 13 severely obese type 2 diabetic patients (BMI 39.3 +/- 3.9 kg/m2) in suboptimal glycemic control pretreated with intensified insulin therapy. Patients were randomly assigned to either metformin or placebo treatment (double-blind) for 10 weeks and after a 2 week washout period received the opposite treatment, respectively, for 10 additional weeks. HbA1c decreased comparably during placebo (from 8.1 +/- 0.4 to 7.6 +/- 0.3%) and metformin (from 8.5 +/- 0.4 to 7.4 +/- 0.3%, p = 0.29 vs. placebo). Changes in fasting glucose levels were also not different between placebo (from 9.3 +/- 0.7 to 9.5 +/- 0.7 mM) and metformin (from 10.3 +/- 0.5 to 9.5 +/- 0.6 mM, p = 0.44 vs. placebo). Total exogenous insulin requirements decreased from 53 +/- 10 to 35 +/- 7 units during metformin treatment (p = 0.02 vs. placebo). Changes in fasting insulin levels during placebo and metformin treatments were not different (p = 0.11). Metformin had no effect on body weight and serum triglycerides but marginally decreased serum cholesterol levels (from 239 +/- 18 to 211 +/- 14 mg/dl, p = 0.005, p = 0.08 vs. placebo). During the oral glucose tolerance test no differences were observed in the areas under the curve for glucose and insulin while that for C-peptide showed a tendency to increase during metformin administration. We conclude that addition of metformin to insulin treatment in severely obese type 2 diabetic patients improves glycemia but not hyperinsulinemia in comparison to intensive insulin therapy alone. With adjunct metformin, approximately 30% less exogenous insulin is required. With respect to glycemia and lipids, adjunct metformin can be a reasonable treatment alternative in selected obese patients with type 2 diabetes already on intensive insulin therapy.

Topics: Body Mass Index; Body Weight; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Lipoproteins; Male; Metformin; Middle Aged; Obesity; Placebos; Triglycerides

The insulin-sensitizing action of troglitazone may be mediated through the activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and the promotion of preadipocyte differentiation in adipose tissue on which troglitazone has depot-specific effects. We investigated the relationship between efficacy of the drug and body fat distribution. Changes in body fat distribution were also investigated by long-term administration of the drug.. Troglitazone was given at a dose of 400 mg/day to 20 patients with type 2 diabetes whose diet and sulfonylurea therapy produced unsatisfactory glycemic control (HbA(1c) >7.8%) and whose insulin secretory capacity was found to be preserved (postprandial C-peptide >3 ng/ml). HbA(1c) values, serum lipid levels, and body weight were measured monthly Body fat distribution was evaluated in subcutaneous (SC) and visceral fat using a computed tomography scan at umbilical levels before and after troglitazone therapy. During the 1-year troglitazone treatment, HbA(1c) was significantly decreased (from 9.2 +/- 0.2 to 7.1 +/- 0.2%, P < 0.01), showing lowest values at 4-6 months, whereas body weight was significantly increased (BMI 24.6 +/- 0.6 to 25.7 +/- 0.6 kg/m2, P < 0.01). Reduction of HbA(1c) (deltaHbA(1c)) from the baseline value during treatment was significantly greater in obese patients (BMI >26 kg/m2) than in nonobese patients (-3.2 +/- 0.4 vs. -2.1 +/- 0.3%, P < 0.05) and was more significant in women than in men (-3.2 +/- 0.2 vs. - 1.4 +/- 0.2%, P < 0.01). The level of deltaHbA(1c) during treatment showed a significant negative correlation with SC fat area (r = -0.742, P < 0.01) but not with visceral fat area. Weight gain during troglitazone treatment resulted in increased accumulation of SC fat without a change in visceral fat area and, consequently. in a significant decrease in the visceral-to-SC fat ratio.. Predominant accumulation of SC fat for the visceral fat tissue was an important predictor of the efficacy of troglitazone therapy in patients with type 2 diabetes. Greater efficacy of troglitazone was observed in women who were characterized by more accumulation of SC adipose tissue than men. Long-term administration of the drug resulted in weight gain with increased accumulation of SC adipose tissue, probably because of the activation of PPAR-gamma in the region.

Topics: Adipose Tissue; Body Mass Index; C-Peptide; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Sex Characteristics; Thiazoles; Thiazolidinediones; Tomography, X-Ray Computed; Troglitazone; Viscera; Weight Gain

To correlate anthropometric, computed tomography and fat cell data from abdominal regions with the levels of serum insulin, C-peptide, leptin, tumor necrosis factor-alpha (TNF-alpha), testosterone, 17beta-estradiol, androstenedione, dehydroepiandrosterone sulphate (DHEA-S) and sex hormone-binding globulin (SHBG).. The sample consisted of 84 obese patients (29 men, 22 premenopausal women and 33 postmenopausal women) who had undergone abdominal surgery. Weight, height, percentage of body fat by skinfolds, waist, hip and thigh circumferences, sagittal and coronal diameters, visceral and subcutaneous area, serum hormones and fat cell data were studied.. Premenopausal women showed the lowest values in most abdominal distribution parameters, although, depending on the waist circumference criteria at the umbilicus level perimeter (W1) or midway between lower rib margin and iliac crest perimeter (W2), the population was classified differently, as gynoid or android. Although there were no differences in fat cell size between genders, gynoid women had smaller and more numerous fat cells than the android type. Perivisceral fat cell size was significantly smaller than subcutaneous fat cell size. In women, central obesity was significantly correlated with an increase in serum insulin, leptin, TNF-alpha, testosterone and androstenedione levels, and a decrease in 17beta-estradiol and DHEA-S, while in men significant correlations were positive with insulin and negative with testosterone and androstenedione. Fat cell size was positively correlated with serum levels of leptin, insulin, DHEA-S, androstenedione and inversely correlated with SHBG. These data indicate that hormones seem to interact not only with body fat distribution but also with fat cell size. This interaction differs between genders and between the different abdominal adipose tissue regions.

Topics: Adipocytes; Adult; Aged; Aging; Androstenedione; C-Peptide; Dehydroepiandrosterone Sulfate; Estradiol; Female; Gonadal Steroid Hormones; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Sex Hormone-Binding Globulin; Testosterone; Tomography, X-Ray Computed; Tumor Necrosis Factor-alpha

Peripheral administration of glucagon-like peptide-1 (GLP-1) for four hours, to normal weight and obese humans, decreases food intake and suppresses appetite.. The aim of this study was to assess the effect of an eight hour infusion of GLP-1 on appetite and energy intake at lunch and dinner in obese subjects.. Randomised, blinded cross-over design with intravenous infusion of GLP-1 (0.75 pmol x kg(-1) min(-1)) or saline.. Eight obese (body mass index, BMI, 45.5 +/- 2.3 kg/m2) male subjects.. Ad libitum energy intake at lunch (12.00 h) and dinner (16.00 h) after an energy fixed breakfast (2.4 MJ) at 08.00 h. Appetite sensations using visual analogue scales, (VAS) immediately before and after meals and hourly in-between. Blood samples for the analysis of glucose, insulin, C-peptide, GLP-1 and peptide YY. Gastric emptying after breakfast and lunch using a paracetamol absorption technique.. Hunger ratings were significantly lower with GLP-1 infusion. The summed ad libitum energy intake at lunch and dinner was reduced by 1.7 +/- 0.5 MJ (21 +/- 6%) by GLP-1 infusion (P = 0.01). Gastric emptying was delayed by GLP-1 infusion, and plasma glucose concentrations decreased (baseline: 6.6 +/- 0.35 mmol/L; nadir: 5.3 +/- 0.15 mmol/L). No nausea was recorded during GLP-1 infusion.. Our results demonstrate that GLP-1 decreases feelings of hunger and reduces energy intake in obese humans. One possible mechanism for this finding might be an increased satiety primarily mediated by gastric vagal afferent signals.

Topics: Adult; Appetite; Blood Glucose; Body Mass Index; C-Peptide; Cross-Over Studies; Double-Blind Method; Eating; Energy Intake; Gastric Emptying; Glucagon; Glucagon-Like Peptide 1; Humans; Hunger; Infusions, Intravenous; Insulin; Male; Obesity; Peptide Fragments; Peptide YY; Protein Precursors

Patients with type 2 diabetes are often obese and require large doses of insulin to achieve glycemic control. Weight gain often accompanies insulin therapy and results in increasing insulin requirements.. To evaluate the efficacy of metformin in combination with insulin in patients with type 2 diabetes poorly controlled with insulin therapy alone.. Randomized, double-blind, placebo-controlled trial.. Outpatient diabetes clinic at a university medical center.. 43 patients with poorly controlled type 2 diabetes who were receiving insulin therapy.. Patients were randomly assigned to receive placebo or metformin in combination with insulin for 24 weeks.. Hemoglobin A1c levels decreased by 2.5 percentage points (95% CI, 1.8 to 3.1 percentage points) in the metformin group, a significantly greater change (P = 0.04) than the decrease of 1.6 percentage points in the placebo group. Average final hemoglobin A1c levels were 6.5% in the metformin group and 7.6% in the placebo group (difference, 11%). For patients who received placebo, the insulin dose increased 22.8 units (CI, 11 to 44 units) or 29% more than did the dose for patients who received metformin (P = 0.002); for these patients, the insulin dose decreased slightly. Patients in the placebo group gained an average of 3.2 kg of body weight (CI, 1.2 to 5.1 kg); patients in the metformin group gained an average of 0.5 kg of body weight (P = 0.07). Total cholesterol and low-density lipoprotein cholesterol levels decreased in both groups. High-density lipoprotein cholesterol and triglyceride levels did not change.. The addition of metformin to insulin therapy resulted in hemoglobin A1c concentrations that were 10% lower than those achieved by insulin therapy alone. This improvement in glycemic control occurred with the use of 29% less insulin and without significant weight gain. Metformin is an effective adjunct to insulin therapy in patients with type 2 diabetes.

Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Energy Intake; Hemoglobin A; Humans; Hypoglycemic Agents; Insulin; Lipids; Metformin; Obesity; Statistics, Nonparametric

This study was initiated to test the hypothesis that metformin treatment leads to enhanced glucose disposal at ambient insulin concentrations.. Nineteen obese patients with impaired glucose tolerance (IGT) were treated with either metformin or placebo in a randomized, double-blind, placebo-controlled, cross-over study. Insulin secretion and insulin resistance were quantified using the homeostasis model assessment (HOMA) and insulin-stimulated glucose disposal were measured by determining the steady-state plasma glucose (SSPG).. The average benefit of metformin was 0.6 mmol/l for glucose (95% confidence interval (CI) 0.2-0.9 P = 0.002), 2.8 pmol/l for insulin (95% CI 0.2-5.4, P = 0.019). Insulin resistance, as quantified by HOMA, was improved by 1.1 (95% CI 0.2-2.0, P = 0.004), without any change in insulin secretion. Basal and insulin-stimulated glucose oxidation were comparable in the placebo and metformin-treated groups at the end of each treatment period, as was the SSPG concentration. However, both systolic and diastolic blood pressures fell significantly following metformin administration as compared to treatment with placebo.. These results indicate that metformin administration to patients with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure. In contrast, neither glucose oxidation nor glucose disposal were increased in association with metformin treatment under conditions of physiological hyperinsulinaemia.

Topics: Blood Glucose; C-Peptide; Double-Blind Method; Female; Fructosamine; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Male; Metformin; Obesity; Placebos

When presenting with diabetic ketoacidosis (DKA), lean and obese patients differ in their subsequent clinical course. Although lean patients tend to remain insulin dependent, most obese patients recover endogenous insulin secretion and discontinue insulin therapy. The aim of this study was to determine whether obese African-American patients with DKA could be determined to have type 1 or type 2 diabetes based on insulin secretion or the presence of immunological and genetic markers.. This was a prospective study that analyzed the clinical characteristics, insulin secretion indices, immunological markers (islet cell, GAD, ICA512, and insulin autoantibodies), and HLA susceptibility genes (DR/DQ) in 131 patients with DKA (77 obese and 54 lean), 51 obese patients with hyperglycemia but no DKA, and 25 nondiabetic subjects. All subjects were African-American. Beta-cell function was evaluated by the C-peptide response to glucagon (1 mg i.v.) within 48 h of resolution of DKA or hyperglycemia.. The acute C-peptide response was lower in obese DKA patients (1.0+/-0.1 ng/ml) than in obese patients with hyperglycemia (1.7+/-0.2 ng/ml, P < 0.01), but was higher than that in lean DKA patients (0.2+/-0.1 ng/ml, both P < 0.01). The overall prevalence of autoantibodies in obese subjects with DKA (17%) and obese subjects with hyperglycemia (16%) was lower than that in lean subjects with DKA (65%, P < 0.01). Obese patients with hyperglycemia and positive autoantibodies had lower rates of insulin secretion than those without antibodies. Regardless of body weight, all DKA patients with GAD autoantibodies carried the DQB1*0201 allele. However, there were no significant differences in HLA distribution between the three patient groups.. Our results indicate that most obese African-American patients with DKA have type 2 diabetes characterized by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA genetic association. In contrast, most lean African-American patients with DKA have metabolic and immunological features of type 1 diabetes. At presentation, assessment of beta-cell function and determination of autoimmune markers allow for correct classification of diabetes in African-Americans with hyperglycemic crises.

Topics: Adult; Alleles; Autoantibodies; Black People; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Genotype; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunogenetics; Insulin; Insulin Secretion; Male; Obesity

We investigated the influence of genetic predisposition to hypertension by studying the relation between insulin sensitivity and left ventricular (LV) mass and function in untreated lean and obese hypertensives. We selected 50 lean hypertensives with normotensive parents (negative family history of hypertension [F-]), 64 lean hypertensives with 1 or both parents hypertensive (positive family history of hypertension [F+]), 40 obese F- hypertensives, and 43 obese F+ hypertensives. The 4 groups were comparable regarding age, gender, 24-hour blood pressure profile, and known duration of hypertension. We measured glucose, insulin, and C-peptide during fasting and during an oral glucose tolerance test; LV morphology and function were assessed by digitized M-mode echocardiography. Glucose (fasting and test) levels were normal in all and similar among the 4 groups. Insulin and C-peptide (fasting and stimulated) levels were higher in obese hypertensives than in lean hypertensives; at similar body mass index, insulin and C-peptide levels were higher in F+ than in F- groups. Compared with lean hypertensives, obese hypertensives had greater LV mass index; LV systolic function was normal in all and similar among the groups. The indices of LV diastolic function were significantly lower in F+ than in F- groups. LV mass index did not correlate with metabolic parameters; the indices of LV diastolic function were inversely correlated with insulin area during test in only the 2 F+ groups. In conclusion, genetic predisposition to hypertension is associated with a reduced insulin sensitivity and affects the response of the myocardium to increased insulin levels, inducing a greater impairment of diastolic function. Insulin sensitivity and genetic predisposition to hypertension seem to have no influence on LV mass.

Topics: Adult; Analysis of Variance; Area Under Curve; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Diastole; Echocardiography; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Heart Ventricles; Humans; Hypertension; Insulin; Male; Middle Aged; Obesity; Regression Analysis; Thinness; Ventricular Function, Left

To determine the effect of benfluorex on glycaemic control in obese insulin-requiring Type 2 diabetes, 76 patients (aged 53.8 +/- 12.8 years) receiving insulin (> or = 0.5 IU/kg) and an appropriate low-calorie diet were evaluated after a 1-month run-in followed by a 3-month double-blind treatment period (3 tablets daily) with benfluorex (B; n = 37) vs placebo (P; n = 39). At inclusion, the B and P groups respectively did not differ in body weight (80.9 +/- 10.3 vs 77.2 +/- 9.1 kg), body mass index (BMI) (30.1 +/- 4.6 vs 29.0 +/- 2.3 kg/m2) or fasting blood glucose (11.22 +/- 4.33 vs 10.35 +/- 4.42 mmol/l). However, daily insulin dose and HbA1c levels were higher in the B group (59.9 +/- 18.6 vs 50.4 +/- 12.8 IU, p = 0.012; and 7.72 +/- 1.60 vs 6.96 +/- 1.27%, p = 0.025, respectively). After 3 months of treatment, the decrease in daily insulin dose was greater in the B group (8.7 +/- 10.1 vs 2.7 +/- 8.1 IU; p = 0.032), with a decrease in HbA1c (-0.73 +/- 1.74%, p = 0.026), vs no change in the P group (+0.01 +/- 1.65%, NS) and a tendency towards a greater decrease in fasting blood glucose (-1.43 +/- 5.41 vs +0.42 +/- 3.78 mmol/l respectively). Body weight and BMI were also lower in the B group (1.77 ñ 2.27 vs 0.21 ñ 2.68 kg, p = 0.013; and 0.64 +/- 0.84 vs 0.07 +/- 1.07 kg/m2, p = 0.019, respectively) in parallel with the decrease in insulin dose. Triglycerides decreased in the B group vs an increase in the P group (-0.54 +/- 2.04 vs +0.21 +/- 0.70 mmol/l p = 0.06). Total cholesterol decreased within the B group (-0.47 +/- 1.01 mmol/l; p = 0.013) and vs the P group (intergroup p = 0.006). Adverse events were reported in 11 patients in the B group vs 5 in the P group (NS), causing dropout in only one case (intercurrent illness, P group). Addition of benfluorex in obese insulin-requiring Type 2 diabetes thus enhances glycaemic control and lowers both daily insulin requirement and body weight. Benfluorex + insulin is a valid alternative for obese patients who remain poorly controlled despite insulin or who require high doses of insulin.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Fenfluramine; Humans; Hypolipidemic Agents; Insulin; Insulin Resistance; Male; Middle Aged; Monitoring, Physiologic; Obesity; Postprandial Period

To determine whether the lipoprotein response to weight loss in obese patients with type 2 diabetes can be improved by modifying the macronutrient composition of the commonly prescribed low-fat, high-carbohydrate (CHO) hypocaloric diet.. Nine obese patients with type 2 diabetes were treated with a monounsaturated fatty acid (MUFA)-enriched weight-reducing formula diet and compared with eight obese patients with type 2 diabetes treated with a low-fat, high-CHO weight-reducing formula diet. Weight loss ensued for 6 weeks, followed by 4 weeks of refeeding using isocaloric formulas enriched with MUFA or CHO, respectively. Fasting blood samples were obtained to measure plasma lipoproteins and LDL susceptibility to oxidation (measured as lag time: time required to induce in vitro formation of conjugated dienes).. At baseline, there were no differences between the groups in plasma lipids, lipoproteins, or LDL susceptibility to oxidation. Weight loss was similar between the groups. Dieting resulted in decreases in total plasma cholesterol, LDL, HDL, triglycerides, and apolipoproteins A and B (P < 0.05), but the MUFA group manifested a greater decrease in total cholesterol, triglycerides, and apolipoprotein B and a smaller decrease in HDL and apolipoprotein A than the CHO group (P < 0.05). Improvements in these parameters were sustained during refeeding. After dieting, lag time was prolonged in the MUFA group (208 +/- 10 min) compared with the CHO group (146 +/- 11 min; P < 0.05). Lag time was prolonged further during refeeding in the MUFA group (221 +/- 13 min, P = 0.10), while the CHO group remained unchanged (152 +/- 9 min, P < 0.05). Lag time correlated strongly with the oleic acid content of LDL after dieting and refeeding (r = 0.74 and r = 0.93, respectively; both P < 0.001).. Macronutrient content is an important determinant of the lipoprotein response to weight loss in obese patients with type 2 diabetes. MUFA-enriched hypocaloric diets potentiate the beneficial effects of weight loss to ameliorate cardiovascular risk factors in obese patients with type 2 diabetes.

Topics: Apolipoproteins; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Dietary Carbohydrates; Dietary Fats, Unsaturated; Energy Intake; Fatty Acids, Monounsaturated; Female; Humans; Insulin; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Regression Analysis; Risk Factors; Triglycerides; Weight Loss

This study tested a simple algorithm for beginning insulin for obese patients with type 2 diabetes after sulfonylurea failure, comparing suppertime 70/30 insulin plus continued glimepiride with insulin alone.. This was a multicenter ambulatory randomized double-masked parallel comparison. There were 208 subjects with secondary failure to sulfonylureas who took glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting plasma glucose (FPG) 180-300 mg/dl (10-16.7 mmol/l) on this treatment were randomized to placebo plus insulin (PI) or glimepiride plus insulin (GI) for 24 weeks. A dosage of 70/30 insulin before supper was titrated, seeking fasting capillary blood glucose (FBG) 120 mg/dl (6.7 mmol/l), equivalent to FPG 140 mg/dl (7.8 mmol/l). Outcome measures included FPG, HbA1c, insulin dosage, weight, serum insulin and lipids, and adverse events.. FPG and HbA1c were equivalent at baseline: 261 vs. 250 mg/dl (14.5 vs. 13.9 mmol/l), and 9.9 vs. 9.7%. At 24 weeks, the FPG target was achieved in both groups (136 vs. 138 mg/dl, 7.6 vs. 7.6 mmol/l), and HbA1c values were equal (7.7 vs. 7.6%). However, with GI, control improved faster and fewer subjects dropped out (3 vs. 15%, P < 0.01), and less insulin was needed (49 vs. 78 U/d, P < 0.001). The outcomes were alike in other respects. No subject had severe hypoglycemia.. Injection of 70/30 insulin before supper safely restored glycemic control of type 2 diabetes not controlled by glimepiride alone. Control was restored more rapidly and with less injected insulin when glimepiride was continued.

Topics: Aged; Blood Glucose; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Patient Dropouts; Sulfonylurea Compounds; Treatment Outcome; Triglycerides

Insulin sensitivity is impaired in overweight subjects with IGT and is accompanied by hyperinsulinemia, a condition, that might promote early B-cell exhaustion. Twelve subjects were recruited for a double-blind trial using either 100 mg of acarbose or placebo for three months. Insulin sensitivity was measured by hyperglycemic clamp and with the minimal model. Baseline characteristics such as body weight, BMI, blood glucose, HB-A1c and serum lipids did not change throughout the study period. The steady state glucose infusion rate (SSGIR) improved significantly following acarbose. The insulin sensitivity as measured by clamp (MI) or minimal model, (SI), however, increased only descriptively (p = 0.08). The fasting proinsulin was raised in all subjects during pretreatment. Following acarbose, the proinsulin dropped from 20.3 +/- 12.9 to 13.6 +/- 7.1 ng/ml, but remained unchanged in the placebo group. Due to the high variability of values and the low number of subjects in this study, differences were only descriptive and did not reach significance (p = 0.08). The proinsulin/insulin ratio, however, significantly decreased after 3 months of acarbose treatment. Acarbose might therefore be considered recommendable for the protection of the B-cell function and for delaying the transition of IGT to overt NIDDM.

Topics: Acarbose; Adult; Analysis of Variance; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Double-Blind Method; Glucose; Glucose Clamp Technique; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Obesity; Proinsulin; Trisaccharides

The gut peptide glucagon-like peptide 1(7-36) amide (GLP-1) is released into the circulation after food intake. GLP-1 has been shown to have an incretin effect and inhibits gastrointestinal motility in humans. In rats, intracerebral administration of GLP-1 results in reduced food intake. Obese humans have been found to have an attenuated plasma GLP-1 response to a mixed meal. To approximate the physiologic state, GLP-1 or saline was administered intravenously and randomly at the beginning of a test meal served on a universal eating monitor to 6 obese subjects to test our hypothesis that GLP-1 influences termination of food intake (and thus food intake during a meal) and feelings of satiety in humans. As a marker for gastric emptying, 1.5 g acetaminophen was given at the start of the meal. Blood samples for analysis of acetaminophen, insulin, glucose, glucagon, and C-peptide were obtained. Hunger, fullness, and food choice were assessed with visual analogue scales and food-choice questionnaires. GLP-1 infusion resulted in a prolonged period of reduced feelings of hunger, desire to eat, and prospective consumption after the meal. The rate of gastric emptying was slower during infusion of GLP-1. Postprandial blood glucose concentrations were reduced during the GLP-1 infusion, but the amount of energy consumed, eating rate, and plasma concentrations of insulin, glucagon, and C-peptide were unchanged. GLP-1 given exogenously at the start of a meal did not seem to affect meal termination or the amount of food eaten. However, postprandial feelings of hunger decreased, suggesting that exogenous GLP-1 may influence feelings of hunger and satiety in humans.

Topics: Adult; Blood Glucose; C-Peptide; Double-Blind Method; Gastric Emptying; Glucagon; Glucagon-Like Peptide 1; Humans; Hunger; Infusions, Intravenous; Insulin; Male; Obesity; Pain Measurement; Peptide Fragments; Postprandial Period; Protein Precursors; Radioimmunoassay; Satiation

Acarbose is an alpha-glucosidase inhibitor which reversibly inhibits oligosaccharidase and disaccharidase at the brush border of the small intestine. The aim of this study was to observe its effectiveness in the treatment of obesity.. Two groups of 25 obese women were put on a 15 kcal/kg/day low-calorie diet for 12 weeks. One group (the study group) received 150 mg/day acarbose for the first 2 weeks and 300 mg/day acarbose for the remaining 10 weeks. The second group (controls) received no additional treatment. Body weight, BMI, skinfold thickness, serum lipids, OGTT, and insulin and C-peptide responses to OGTT were assessed before and after the study.. Body weight, BMI and skinfold thickness decreased significantly in both groups. Basal insulin and triglyceride levels in the study group, total and LDL cholesterol and triglyceride levels in the control group decreased significantly. No difference was found between the two groups when these decrements were compared, but the triglyceride level fell more in the control group.. Additional acarbose therapy is not more beneficial than low-calorie diet therapy alone.

Topics: Acarbose; Adolescent; Adult; Body Mass Index; C-Peptide; Cholesterol, LDL; Combined Modality Therapy; Diet, Reducing; Dose-Response Relationship, Drug; Drug Administration Schedule; Glucose Tolerance Test; Humans; Insulin; Middle Aged; Obesity; Skinfold Thickness; Triglycerides

It is difficult to treat obese non-insulin-dependent diabetic patients (NIDDs) whose glycaemic control remains poor despite maximal oral antidiabetic therapy. We studied the effect of a continuous subcutaneous insulin infusion (CSII) associated with a low-calorie diet and metformin 1,700 mg/day on glycaemic control and basal and stimulated insulin secretion in a series of 82 overweight NIDD before (T1), during CSII (T2), and after CSII withdrawal (T3). Patients were treated for 8 to 23 days with a mean amount of 0.50 +/- 0.02 IU/kg/day. Glycaemic control was very good after 3-5 days of CSII and remained good at T3. At T2, fasting and postprandial plasma C peptide levels decreased significantly. At T3, fasting C peptide was very similar to T1, and postprandial C peptide was significantly higher than at T1. The molar fasting and postprandial plasma C peptide/glycaemia ratios increased significantly at T3. After glucagon injection, the molar delta C peptide/glycaemia ratio was significantly increased at T2 and even higher at T3. At T2, as at T1 and T3, there were significant correlations between fasting and postprandial C peptide levels and between the glucagon-induced C peptide peak and fasting and postprandial C peptide levels. Between T1 and T3 weight changes correlated significantly with the molar fasting C peptide/glycaemia ratio at T1. Twenty-nine of the 30 patients for whom this ratio was > 6.6 x 10(-8) lost weight. The length of CSII treatment did not correlate with weight changes or other biological parameters. This study shows that CSII with moderate amounts of insulin associated with a low-calorie diet and metformin provided rapid glycaemic control, led to weight loss, maintained regulation of insulin secretion and seemed to improve insulin secretion and sensitivity. These results were obtained in only 8 to 10 days.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Infusions, Parenteral; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Secretory Rate; Time Factors

Many newly diagnosed obese African-American patients with history of severe hyperglycemia or diabetic ketoacidosis (DKA) are able to discontinue pharmacological treatment with continued good metabolic control. However, many of these individuals relapse into hyperglycemia within 1 year. In such patients, we compared the effect of low-dose sulfonylurea and dietary therapy in the prevention of recurrence of hyperglycemia.. We conducted an intention-to-treat study in 35 obese newly diagnosed diabetic patients (17 with DKA and 18 with severe hyperglycemia). After discontinuation of insulin, seven of 17 patients with DKA and seven of 18 patients with hyperglycemia were managed with diet and glyburide (1.25-2.5 mg/day), whereas other patients were followed with diet alone. In all patients, pancreatic insulin reserve was documented 1 day after resolution of hyperglycemic crises and within 1 week of discontinuation of insulin. Recurrence of hyperglycemia was defined as fasting blood glucose > 7.8 mmol/l (140 mg/dl) or random blood glucose > 10 mmol/l (180 mg/dl) on two or more consecutive determinations, or HbA1c > 7.5%.. Both treatment groups were comparable in age, sex, duration of diabetes, months of insulin therapy, BMI, glucose, and HbA1c. At presentation, the acute C-peptide response to glucagon in obese DKA patients was lower than in patients with hyperglycemia (P < 0.01), but responses were comparable after discontinuation of insulin. Sulfonylurea treatment significantly reduced recurrence of hyperglycemia in both obese DKA and obese hyperglycemic patients (P = 0.03). With a median follow-up of 16 months, hyperglycemia recurred in six of 10 DKA patients and in five of 11 hyperglycemia patients treated with diet alone, compared with one of seven DKA and one of seven hyperglycemia patients treated with glyburide. Readmission with metabolic decompensation occurred in four patients treated with diet but in none of the patients treated with diet and glyburide.. Low-dose sulfonylurea therapy prevents recurrence of hyperglycemia in newly diagnosed obese African-American patients with a history of hyperglycemic crises.

Topics: Adult; Black or African American; Black People; Blood Glucose; C-Peptide; Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diet, Diabetic; Female; Georgia; Glyburide; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Islets of Langerhans; Male; Middle Aged; Obesity; Recurrence

High intake of trans fatty acids and saturated fatty acids (SFAs) is known to increase the risk of coronary heart disease. We studied the effects of diets enriched in various fatty acids on postprandial insulinemia and fasting serum levels of lipids and lipoproteins in obese patients with NIDDM.. Sixteen obese NIDDM patients were studied in a free-living outpatient regimen. After a run-in period, the patients received three different isocaloric diets for 6 weeks using a randomized crossover design. The patients were instructed to keep the energy intake from carbohydrate and protein constant at 50 and 20 E% (percent of energy intake), respectively, on all three diets. The fat composition of the diets differed: saturated fat (SAT) diet (20 E% SFAs, 5 E% polyunsaturated fatty acids [PUFAs], and 5 E% monounsaturated fatty acids [MUFAs]) versus cis monounsaturated fatty acid (CMUFA) diet (20 E% cis-MUFAs, 5 E% PUFAs, and 5 E% SFAs) versus trans monounsaturated fatty acid (TMUFA) diet (20 E% trans-MUFAs, 5 E% PUFAs, and 5 E% SFAs). Fasting serum levels of lipids and lipoproteins were measured at baseline and in the fasting state before meal tolerance tests at the end of each study period. Insulin secretion was assessed from incremental serum insulin and C-peptide responses during the meal tests.. BMI, waist-to-hip ratio, and glycemic control remained stable throughout the study. After meal stimulation, postprandial glycemic responses were similar on all diets; however, serum insulin and C-peptide responses were greater following the TMUFA and SAT diets than following the baseline or CMUFA diets (P < 0.05). No statistical difference was found in fasting levels of serum lipids (total cholesterol, triglyceride, phospholipid, and nonesterified fatty acids) or lipoproteins of HDL cholesterol, VLDL cholesterol, LDL cholesterol, and apolipoprotein B between diets.. In the presence of unchanged glycemia, both dietary trans fatty acids and SFAs induce an increase in postprandial insulinemia in obese patients with NIDDM.

Topics: Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Fats, Unsaturated; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; Humans; Insulin; Insulin Secretion; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Postmenopause; Random Allocation; Time Factors

This study compared the effect of mild exercise while fasting on plasma glucose concentrations in subjects with NIDDM treated with extended-release glipizide and subjects not taking an oral hypoglycemic agent.. Twenty-five moderately obese subjects with NIDDM were randomized to treatment with extended-release glipizide or placebo. After 9 weeks of treatment, they fasted overnight, took their study drug, omitted breakfast, and exercised on a treadmill for 90 min. Glucose, insulin, and C-peptide concentrations were measured before, during, and after exercise.. On the fasting-exercise day, fasting glucose concentrations were lower (153 vs. 241 mg/dl, P < 0.01) and insulin and C-peptide concentrations higher in the extended-release glipizide group. The decrement of glucose from the fasting baseline was modest and equivalent in the two groups: 17 vs. 21 mg/dl at the end of exercise and 28 vs. 27 mg/dl after 2 h of recovery. No subject had hypoglycemic symptoms.. Chronic use of extended-release glipizide does not enhance the hypoglycemic effect of fasting plus mild exercise for people with NIDDM. Routine lifestyle treatments for NIDDM may be continued during ongoing use of this agent.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Exercise; Exercise Test; Female; Glipizide; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Time Factors

The present study was carried out to evaluate the effect of a low-dose intravenous supplementation of L-arginine on insulin-mediated vasodilatation and insulin sensitivity. The study was performed in healthy subjects (n = 7) and patients with obesity (n = 9) and non-insulin-dependent diabetes mellitus (NIDDM) (n = 9). Insulin-mediated vasodilatation was measured by venous occlusion plethysmography during the insulin suppression test, evaluating insulin sensitivity. Experiments were performed twice in each subject in the presence or absence of a concomitant infusion of L-arginine (0.52 mg kg-1 min-1). L-Arginine restored the imparied insulin-mediated vasodilatation observed in obesity (22.4 +/- 4.1%, P < 0.01 vs. without L-arginine) and NIDDM (20.3 +/- 3.2%, P < 0.01 vs. without L-arginine). In healthy subjects, no effect on insulin mediated-vasodilatation was observed (24.8 +/- 3.1% vs. 21.4 +/- 3.1%). Insulin sensitivity was improved significantly (P < 0.001) in all three groups by infusion of L-arginine. No effect of L-arginine was observed on insulin, insulin-like growth factor I (IGF-I), free fatty acids (FFAs) or C-peptide levels during the insulin suppression test. Our data indicate that defective insulin-mediated vasodilatation in obesity and NIDDM can be normalized by intravenous L-arginine. Furthermore, L-arginine improves insulin sensitivity in obese patients and NIDDM patients as well as in healthy subjects, indicating a possible mechanism that is different from the restoration of insulin-mediated vasodilatation.

Topics: Adult; Arginine; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids; Female; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Male; Middle Aged; Obesity; Vasodilation

We student basal, glucose- and glucagon-induced insulin secretion in non-insulin diabetes mellitus (NIDDM) patients in relation to body mass index (BMI) and fasting serum glucose (FBS) level. A total of 46 NIDDM patients and 22 control subjects with varying degrees of BMI and FBS were given 100 g of oral glucose and 1 mg of intravenous glucagon on separate days. C-peptide response to glucose, but not basal serum C-peptide and C-peptide response to glucagon, was significantly lower in NIDDM than in controls (P < 0.001). FBS was inversely correlated with C-peptide response to glucose in NIDDM patients (r = -0.67, P < 0.001), but not with basal C-peptide level and C-peptide response to glucagon. On the other hand, BMI was positively correlated with basal serum C-peptide level both in NIDDM (r = 0.60, P < 0.001) and in control subjects (r = 0.74, P < 0.001). In 15 poorly controlled NIDDM patients, the tests were repeated after insulin treatment for 10-14 days. C-peptide response to glucose significantly increase, but not to a level in control subjects, after glycemic control. Basal serum C-peptide level and the C-peptide response to glucagon decreased after glycemic control to significantly lower levels than those in the baseline and those in control subjects. These results suggest that beta cell secretory reserve is reduced in moderate to severe NIDDM patients.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Cohort Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Female; Glucagon; Glucose; Glucose Tolerance Test; Humans; Injections, Intravenous; Injections, Subcutaneous; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Reference Values

Recent studies have demonstrated the restoration of a normal 24 h GH profile induced by a reduction of insulinaemia after weight loss, suggesting a reciprocal relationship between plasma insulin and GH concentrations. We aimed to clarify if an opiate-induced reduction in plasma insulin could affect GH secretion in obesity.. We have studied the insulin response to an oral glucose tolerance test (OGTT) and the GH response to GHRH before and after prolonged treatment with Naltrexone (NTX). C-peptide, IGF-I, IGFBP-3 plasma levels and the IGF-I/IGFBP-3 molar ratio were also determined.. Twelve obese women (aged 25-41 y; Body mass index (BMI): 31-39 kg/m2) and six lean normal women (aged 25-38; BMI: 19.8-23.1 kg/m2).. GH was determined by the IRMA method; insulin, C-peptide, IGF-I and IGFBP-3 were assayed by the RIA method. For molar comparison between IGF-I and IGFBP-3 we have considered 30.5 kDa the molar weight of IGFBP-3. Results are expressed as mean +/- s.e.m.. We observed a significant decrease in basal concentration of both insulin (230.1 +/- 34.9 vs 133.2 +/- 16.9 pmol/L; P < 0.005) and C-peptide (3.7 +/- 0.3 vs 2.4 +/- 0.1 micrograms/L; P < 0.02). No modifications in the insulin secretory response to the OGTT were observed. A significant increase of the GHRH-induced GH peak response (7.7 +/- 1.4 vs 19.7 +/- 3.1 micrograms/L; P < 0.01) and GH-AUC (533 +/- 151 vs 1415 +/- 339 micrograms/L/120 min; P < 0.01) was found after NTX treatment. A negative correlation was found between basal insulin and GH peak values, both before (r = -0.641, P = 0.027) and after NTX (r = -0.714, P = 0.013). No modifications were found in IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio. Moreover, NTX affected neither the insulin response to OGTT or IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio in a group of six lean controls. Conversely, NTX significantly reduced the GH response to GHRH, when expressed as both peak and AUC values.. The opiate antagonist significantly reduced basal insulin concentrations and augmented the GH response to GHRH in obese subjects. In the absence of modifications in IGF-I and IGFBP-3 plasma levels and their molar ratio, we propose that insulin may exert a negative feedback on GH secretion.

Topics: Adult; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Naltrexone; Narcotic Antagonists; Obesity

Large interindividual variation is characteristic of the cephalic-phase insulin response (CPIR). Our aim was to examine the largely unknown determinants of CPIR in obese nondiabetic subjects before and after weight reduction. After a 12-hour overnight fast, 20 healthy, obese (body mass index, 31.1 to 41.4 kg/m2) subjects were individually exposed to food without being allowed to eat it. Levels of insulin, glucose, C-peptide, free fatty acids, and salivation, together with assessments of feeling of hunger and desire to eat, were measured during the experiment. Subjects were divided into three groups according to CPIR before the weight reduction: positive (PR), intermediate (IR), and negative (NR) responders. CPIR measurements before and after weight reduction correlated significantly with each other (r = .61, P < . 01,n=18). At the beginning of the study, NR had higher fasting plasma glucose and insulin values, as well as higher postload plasma glucose values, as compared with PR and IR. These differences disappeared after weight reduction. In an intravenous glucose tolerance test (IVGTT) performed 9 to 12 months afterward, first-phase insulin secretion was significantly lower in NR. Thus, the negative CPIR during visual and olfactory exposure to food-related stimuli may be related to the attenuated first-phase insulin secretion and mildly impaired glucose metabolism, possibly related to insulin resistance.

Topics: Adult; Blood Glucose; C-Peptide; Diet, Reducing; Eating; Fatty Acids, Nonesterified; Female; Follow-Up Studies; Food; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Sensory Thresholds

To determine whether high-ketogenic very-low-energy diets (VLEDs) can reduce hepatic glucose output (HGO) and hyperglycemia more effectively than can low-ketogenic VLEDs in obese patients with non-insulin-dependent diabetes mellitus (NIDDM), seven patients were treated with a high-ketogenic VLED for 3 wk and were compared with six patients treated with a low-ketogenic VLED. All patients were then crossed over and treated with the alternate diet for another 3 wk. Basal HGO, fasting ketone bodies, and glycemia, insulin, and C-peptide after fasting and an oral-glucose-tolerance test (OGTT) were measured. Before treatment, prediet weight and fasting, OGTT, and HGO measurements were not different between groups. After dieting, weight loss was not different between the groups. However, fasting and OGTT glycemia were lower during treatment with the high-ketogenic VLED than with the low-ketogenic VLED (treatment effect: P < 0.05, by analysis of variance). Moreover, there was a strong correlation between basal HGO and fasting plasma ketone bodies (r = -0.71 at 3 wk, r = -0.67 at 6 wk; both P < 0.05). In contrast, fasting and OGTT plasma insulin and C-peptide concentrations were not different between treatment groups. These data indicate that in obese patients with NIDDM, high-ketogenic VLEDs have a more clinically favorable effect on glycemia than do low-ketogenic VLEDs.

Topics: Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Metabolism; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Ketone Bodies; Ketosis; Liver; Male; Middle Aged; Obesity

Although moderate weight loss improves glycemic control in obese NIDDM patients, quite often it is not normalized. To determine whether the response to weight loss can be improved by altering the macronutrient composition of hypocaloric diets, 17 obese NIDDM patients were studied at I) baseline, 2) after dieting for 6 weeks on a formula diet enriched in either monounsaturated fatty acids (MUFAs, n = 9) or carbohydrates (CHOs, n = 8) at a 50% caloric deficit, and 3) after 4 weeks of postdiet refeeding on the respective formulas with caloric intake titrated to achieve weight maintenance. Fasting, 24-h, and oral glucose tolerance test (OGTT) blood glucose, plasma insulin, and C-peptide levels were measured. All prediet parameters were similar between groups. After dieting, although weight loss was similar between groups, the fasting glucose level decreased significantly more in the MUFA group (-4.6 +/- 0.7 mmol/l) than in the CHO group (-2.4 +/- 1.0 mmol/l; P < 0.05). Twenty-four-hour glycemia decreased in both groups after dieting, but the MUFA group had a greater decrease than the CHO group (P < 0.05, analysis of variance [ANOVA]). Although decreases in fasting glycemia were maintained in both groups after refeeding, postprandial glycemia deteriorated after refeeding with the CHO- but not the MUFA-enriched formula (P < 0.05). After dieting and refeeding, fasting C-peptide increased 204 +/- 47 pmol/l in the MUFA group, but the CHO group remained at prediet levels (P < 0.05). Twenty-four-hour C-peptide levels were similar between groups after dieting and refeeding, despite the lower glycemia and CHO content of the MUFA formula. However, when equal amounts of CHO were consumed during the OGTT, the MUFA group had significantly higher C-peptide levels after both dieting and refeeding (P < 0.05). Fasting, 24-h, and OGTT insulin levels were similar between groups throughout the study. These results indicate that macronutrient composition is an important determinant of the glycemic response to weight-loss therapy in obese NIDDM patients. Based on the C-peptide response during the OGTT, increased CHO-induced insulin secretion is one possible mechanism by which this occurs.

Topics: Analysis of Variance; Blood Glucose; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Fatty Acids, Monounsaturated; Female; Glucagon; Humans; Insulin; Male; Middle Aged; Obesity; Time Factors; Triglycerides; Weight Loss

The pharmacokinetics and pharmacodynamics of glipizide were evaluated in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). The group consisted of 12 obese subjects (seven women, five men; mean +/- SD age, 53.5 +/- 8.5 years; total body weight (TBW), 95.5 +/- 17.2 kg; percentage > IBW (ideal body weight), 57.8 +/- 31.7%); and eight nonobese subjects (two women, six men; age, 57.8 +/- 11.7 years; TBW, 80.8 +/- 9.9 kg; percentage > IBW, 15.6 +/- 10.3%). After a 2-week antidiabetic drug-free period, patients were started on glipizide therapy for 12 weeks. Glipizide dosages were titrated to achieve specified therapeutic goals or a maximum daily dose of 40 mg. Glipizide pharmacokinetics were assessed by serum concentrations obtained during a 24-h pharmacokinetic evaluation performed after the first 5-mg dose (SD) and after 12 weeks of chronic therapy (CD). Glipizide pharmacodynamics were evaluated with serum glucose, insulin, and C-peptide responses to Sustacal tolerance test done at baseline, after SD, and after CD. No statistically significant differences in the SD pharmacokinetic parameters (Tmax = 3.1 +/- 1.2 vs. 2.8 +/- 1.6 h; Cmax = 332.5 +/- 92.5 vs. 420.8 +/- 142 g/L; area under the curve extrapolated to infinity (AUCI) = 2,598.3 +/- 1,148 vs. 3,138.9 +/- 1,847 g/h/L; oral clearance/bioavailability (CL/F), 2.3 +/- 1.0 vs. 2.0 +/- 1.0 L/h; volume of distribution/bioavailability (V/F), 19.5 +/- 4.4 vs. 17.2 +/- 4.3 L; t1/2 = 5.0 +/- 2.3 vs. 5.2 +/- 2.0 h) were observed between the obese and nonobese groups, respectively. The pharmacokinetic parameters assessed under CD conditions were also closely matched in the two groups. No differences in glucose responses to Sustacal challenge at baseline, SD, and CD (AUC0-->4.glucose:baseline, 52.3 +/- 18.0 vs. 44.9 +/- 9.8; SD, 50.4 +/- 20.9 vs. 36.1 +/- 11.0; CD, 37.8 +/- 10.7 vs. 36.6 +/- 8.5 mM/h) were noted between the obese and nonobese groups, respectively. However, glucose concentrations increased more and decreased to a smaller extent after SD in the obese as compared to nonobese subjects. Mean fasting serum insulin and C-peptide concentrations were not statistically different between the two groups. However, obese subjects exhibited higher fasting insulin (114.0 +/- 69 vs. 68.8 +/- 52 pM) at week 12 evaluation and C-peptide concentrations (0.83 +/- 0.2 vs. 0.63 +/- 0.2 nM) after SD as compared to the nonobese group. A smaller percentage increase in C peptide in response to Sustacal challenge

Topics: Biological Availability; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glipizide; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Retrospective Studies

Most obese patients with noninsulin-dependent diabetes mellitus (NIDDM) are initially treated with diet, then with oral hypoglycemic agents, eventually with insulin. However several reports indicate that in these patients insulin therapy has little chance to control glucose metabolism, promotes weight gain and arterial hypertension, and is likely to aggravate insulin resistance. In this randomized, double-blind trial vs. placebo (P) we evaluated in 29 obese NIDDM patients poorly controlled by insulin (daily insulin doses 48.7 +/- 4.0 U/day, HbA1c 10 +/- 0.27%, mean daily blood glucose levels 12.3 +/- 0.3 mmol/L, fasting C-peptide 1.8 +/- 0.2, C-peptide after 1 mg iv glucagon 3.2 +/- 0.3 ng/mL, means +/- SE), the clinical and metabolic effects of benfluorex (B), a lipid-lowering drug able to improve insulin sensitivity. After a 2-3 week run-in period (1 tablet P at dinner and diet 800 cal/day to lose 5% of the initial body weight (BWi), patients received a 1000 kcal/day diet and were randomized to B, 150 mg/ tablet, or P (3 tablets/day); the time limit was set at a 10% decrease of BWi or at 90 days. At the end of run-in there was a significant reduction of BWi (P < 0.001), fasting (P = 0.002) and mean daily blood glucose levels (P < 0.001), triglycerides (P = 0.02), cholesterol (P < 0.001) and daily insulin doses (P < 0.001). At the end of the double-blind trial, weight-loss was greater (P < 0.05), faster (P = 0.018), and more frequent (P < 0.05) with B than with P, and systolic blood pressure (P < 0.05) decreased only with B. Considering only patients with a 10% decrease of BWi (B = 15, P = 10), HbA1c (P < 0.001) decreased only with B, while fasting insulin levels decreased with both B (P < 0.01) and with P (P < 0.05). Insulin sensitivity was evaluated by means of a double infusion test (LDIGIT, insulin 25 mU/Kg/h plus glucose 4 mg/kg/min, lasting 150 min) at the end of run-in and at the end of the double-blind trial; at the end of the double-blind trial steady state blood glucose (SSBG, P < 0.05), free fatty acids (FFA, P < 0.05) and blood beta-hydroxybutyrate (P < 0.05) decreased only with B, while blood glycerol decreased both with both P (P < 0.05) and B (P < 0.06). At the end of the double-blind trial, C-peptide release was unchanged with either P or B. In conclusion, benfluorex potentiates the effects of hypocaloric diet on weight loss and on glycemic control in obese NIDDM patients treated with insulin, and this effect seems to be the result of an

Topics: 3-Hydroxybutyric Acid; Appetite Depressants; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Nonesterified; Fenfluramine; Glucose; Glycerol; Humans; Hydroxybutyrates; Insulin; Insulin Resistance; Insulin Secretion; Middle Aged; Obesity; Placebos

To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load.. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp.. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2).. Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies.. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects.. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

Topics: Adolescent; Adult; beta-Endorphin; Blood Glucose; C-Peptide; Glucose; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Male; Obesity

To compare results obtained with metformin versus those obtained with DNA-recombinant insulin in obese patients with NIDDM suffering from secondary failure to sulfonylureas.. We conducted an open, prospective, randomized, and comparative study comprising a total of 60 patients selected and placed in two parallel groups. We had previously confirmed that the subjects had secondary failure to high doses of sulfonylureas. The initial metformin dosage was a single 850 mg tablet, and the dosage was increased to two or three tablets depending on the patient's metabolic changes. The initial dosage of DNA-recombinant insulin was 24 U, subcutaneously administered and divided into two portions: two-thirds at around 8:00 A.M., before breakfast, and the remaining third at 8:00 P.M., before dinner. The dosage was adjusted based on the patient's clinical and metabolic response.. The initial average glucose value for the metformin group was 269.1 +/- 32.2 mg/dl, decreasing by the end of the study to 159.7 +/- 30.5 mg/dl. For the insulin group, these figures went from 270.7 +/- 24.0 mg/dl at the beginning of the study to 134.8 +/- 26.7 mg/dl. This decrease correlates with the reduction in glycosylated hemoglobin from 12.8 to 8.9% for the first group and from 12.3 to 8.2% for the second, as well as with the reduction in triglyceride values from 230.3 to 183.1 mg/dl and from 218.4 to 186.3 mg/dl, respectively. The BMI (27.5-26.4), blood pressure (systolic from 145.7-132.1 mmHg, diastolic from 90.3-84.8 mmHg), and total cholesterol levels (235-202 mg/dl) decreased in only the metformin group.. Metformin is an effective, safe, and well-tolerated treatment that improves metabolic control and favorably modifies secondary clinical alterations due to insulin resistance, such as arterial hypertension, overweight, and hyperlipidemia, in obese patients with NIDDM suffering from secondary failure to sulfonylureas.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Lipids; Male; Metformin; Middle Aged; Obesity; Recombinant Proteins; Regression Analysis; Sulfonylurea Compounds; Treatment Failure; Triglycerides

To examine the safety and overall clinical effects of normalizing the fasting plasma glucose (FPG) level with bedtime NPH insulin alone in patients with non-insulin-dependent diabetes mellitus (NIDDM) that is poorly controlled with maximal doses of sulfonylureas.. Twelve obese male NIDDM subjects were treated for 16 weeks with bedtime insulin after a 4-week sulfonylurea washout. The insulin dosage was increased until the FPG level was normalized. The 24-h plasma glucose profiles and lipid and HbA1c levels were measured at the beginning and end of the study, and the incidence and severity of hypoglycemic episodes were closely monitored. In addition, hyperglycemic clamp studies were performed to assess insulin secretion and provide an indirect measurement of insulin sensitivity.. FPG (14.6 +/- 0.9 mmol/l at week 0) was normalized ( < 6.4 mmol/l) within 6 weeks (5.9 +/- 0.6 mmol/l) and remained at target levels until the end of the study (4.0 +/- 0.03 mmol/l at week 16, P < 0.001). The insulin dose was 80 +/- 9 U/day (0.86 +/- 0.10 U/kg). Improved glycemic control was confirmed by a reduction in HbA1c (10.9 +/- 0.05 vs. 7.2 +/- 0.2%, P < 0.001) and mean 24-h glucose (17.2 +/- 0.2 vs. 7.4 +/- 0.2 mmol/l, P < 0.001). The incidence of mild or moderate hypoglycemic episodes was 3.4 +/- 1/patient for the entire 16-week study, and no patient experienced severe hypoglycemia. Bedtime insulin significantly improved total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglyceride levels (P < 0.01). Weight gain was 2.4 +/- 0.7 kg, and blood pressure was unchanged. During the hyperglycemic clamp, there was an improvement in the first phase (P < 0.001) and in the second phase (P < 0.01) of insulin secretion. There also was an increase in the rate of exogenous glucose infused (M) (P < 0.01) and in the M/C-peptide ratio (P < 0.02), suggesting enhanced insulin sensitivity.. NPH insulin given at bedtime in amounts sufficient to achieve a normal FPG level does not cause excessive or severe hypoglycemia and does lead to good glycemic and lipid control in NIDDM. Bedtime insulin therapy also is accompanied by improved insulin secretion and insulin sensitivity. We conclude that a single dose of insulin alone at bedtime merits consideration as a therapeutic strategy in patients with poorly controlled NIDDM.

Topics: Analysis of Variance; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Glucose; Glycated Hemoglobin; Humans; Insulin, Isophane; Liver; Male; Middle Aged; Obesity; Reference Values; Time Factors; Triglycerides

12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) were studied for insulin sensitivity (euglycemic insulin clamp, 40 mU/m2 per min), hepatic glucose production (HGP, [3-3H]glucose infusion), and insulin secretion (oral glucose tolerance test and hyperglycemic [12 mM] clamp, including glucagon administration). Five of the nondiabetic twins had normal and seven had impaired glucose tolerance. 13 matched, healthy subjects without a family history of diabetes were included as control subjects. The NIDDM twins were more obese compared with their non-diabetic co-twins. The nondiabetic twins were insulin resistant and had a delayed insulin and C-peptide response during oral glucose tolerance tests compared with controls. Furthermore, the nondiabetic twins had a decreased first-phase insulin response and a decreased maximal insulin secretion capacity during hyperglycemic clamping and intravenous glucagon administration. Nondiabetic twins and controls had similar rates of HGP. Compared with both nondiabetic twins and controls, the NIDDM twins had an elevated basal rate of HGP, a further decreased insulin sensitivity, and a further impaired insulin secretion pattern as determined by all tests. In conclusion, defects of both in vivo insulin secretion and insulin action are present in non- and possibly prediabetic twins who possess the necessary NIDDM susceptibility genes. However, all defects of both insulin secretion and glucose metabolism are expressed quantitatively more severely in their identical co-twins with overt NIDDM.

Topics: Age of Onset; Aged; Blood Glucose; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucagon; Gluconeogenesis; Glucose Clamp Technique; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Liver; Middle Aged; Obesity; Reference Values; Triglycerides; Tritium; Twins, Monozygotic

In a double-blind, randomized, cross-over study, the metabolic effects of a short treatment with metformin (2 x 850 mg day-1 for 2 days and 850 mg 1 h before evaluation) were compared to those of placebo in 15 obese subjects (BMI: 33.2 +/- 0.9 kg m-2), with abdominal distribution of adipose tissue and impaired glucose tolerance. An intravenous glucose tolerance test (0.3 g glucose kg-1) was performed after each period of treatment. Areas under the curve (AUC0-180 min) were calculated for plasma glucose, insulin, and C-peptide levels. Glucose tolerance was estimated by the coefficient of glucose assimilation (KG). Insulin sensitivity (SI) and glucose effectiveness (SG) indices were calculated using Bergman's minimal model. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide levels and insulin metabolic clearance rate (MCR) was estimated by dividing AUC 1SR by AUC insulin. Fasting plasma insulin levels were reduced after metformin (89.3 +/- 15.9 vs 112.4 +/- 24.3 pmol l-1; p = 0.04). AUC glucose, KG and SG were similar in both tests. However, AUC insulin was reduced (39.7 +/- 6.5 vs 51.8 +/- 10.4 nmol min l-1; p = 0.02), while SI (6.98 +/- 1.14 vs 4.61 +/- 0.42 10(-5) min-1 pmol-1 l; p = 0.03) and insulin MCR (715 +/- 116 vs 617 +/- 94 ml min-1 m-2; p = 0.03) were increased after metformin. The demonstration that metformin rapidly improves insulin sensitivity should encourage further research to evaluate the long-term effects of metformin in android obese subjects with impaired oral glucose tolerance.

Topics: Adult; Blood Glucose; Body Constitution; C-Peptide; Cross-Over Studies; Double-Blind Method; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Obesity

Insulin resistance is a significant pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM). A new class of drugs, the thiazolidinediones, have been shown to lower blood glucose levels without stimulating insulin secretion. We report the metabolic effect of the thiazolidinedione, darglitazone, in obese NIDDM subjects. Nineteen subjects were enrolled in a double-blind placebo-controlled study in which 25 mg of darglitazone was given once a day for 14 days. Nine subjects received the active drug and ten subjects received placebo. Darglitazone-treated subjects showed; 1) a decrease in 24-h plasma glucose area under the curve from 292.8 +/- 31.2 to 235.2 +/- 21.6 mmol.h-1.l-1 p = 0.002; 2) a decrease in 24-h serum insulin area under the curve from 1027.2 +/- 254.4 to 765.6 +/- 170.4 microU.h-1.l-1 p = 0.045; 3) a decrease in 24-h non-esterified fatty acid area under the curve from 1900 +/- 236 to 947 +/- 63 g.h-1.l-1 p = 0.002; 4) a decrease in mean 24-h serum triglyceride by 25.9 +/- 6.2% as compared to -3.9 +/- 4.8% for the placebo-treated group, p = 0.012. Placebo-treated subjects showed no change in their metabolic parameters after treatment. Thus, darglitazone is effective in increasing insulin effectiveness in obese NIDDM subjects. The potential for this and similar drugs to treat or prevent NIDDM as well as the insulin-resistance syndrome needs to be explored.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Nonesterified; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Obesity; Thiazoles; Thiazolidinediones

The aim of this single-blind, placebo-controlled study was to investigate the effects of the new beta-adrenergic compound Ro 40-2148 on resting energy expenditure (REE) at rest and after an oral glucose load in non-diabetic obese women before and after two weeks of treatment. After one week of placebo administration and after an overnight fast and one hour rest, REE and glucose and lipid oxidation rates were measured by indirect calorimetry (hood system) before and for 6 h after a single dose of placebo solution. A 75 g oral glucose tolerance test (OGTT) was performed during this period starting 90 min after the placebo administration. During the following two weeks, using a randomization design, six patients received Ro 40-2148 at a dose of 400 mg diluted in 100 ml water twice a day (i.e. 800 mg per day), while six others continued with the placebo administration. The same tests and measurements were repeated after two weeks, except for the treatment group which received the drug instead of the placebo. The 14-day period of drug administration did not increase REE measured in post-absorptive conditions. Similarly, there was no acute effect on REE of a 400 mg dose of Ro 40-2148. In contrast, glucose-induced thermogenesis was significantly increased after two weeks in the treatment group (means +/- s.e.m.: 3.7 +/- 1.3%, P = 0.047), while no change was observed in the placebo group (-0.8 +/- 0.7%, not significant). Since there was no significant change in the respiratory quotient, the increase in energy expenditure observed in the treatment group was due to stimulation of both lipid and glucose oxidation. The drug induced no variations in heart rate, blood pressure, axillary temperature or in plasma glucose, insulin and free fatty acid levels. In conclusion, this study shows that Ro 40-2148 activates glucose-induced thermogenesis in obese non-diabetic patients.

Topics: Adrenergic beta-Agonists; Adult; Blood Glucose; Body Temperature Regulation; C-Peptide; Calorimetry, Indirect; Energy Metabolism; Female; Glucose; Glucose Tolerance Test; Hemodynamics; Humans; Insulin; Lipid Metabolism; Middle Aged; Obesity; Organic Chemicals; Oxidation-Reduction; Proteins; Single-Blind Method

To determine whether previously reported abnormalities in fibrinolytic activity and plasma lipoprotein (a) levels could reflect obesity rather than diabetes per se, plasma concentrations of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and lipoprotein (a) (Lp (a)) were investigated in sixty-four type 2 diabetic patients (56.1 +/- 9.5 years; body mass index, 24.6 +/- 3.3 kg/m2) and thirty-two control subjects (57.9 +/- 8.9 years; body mass index, 24.6 +/- 3.4 kg/m2). Both the plasma t-PA and PAI-1 antigen levels were similar between the diabetic group (10.6 +/- 3.8 ng/ml; 27.7 +/- 11.6 ng/ml) and the control group (12.2 +/- 3.5 ng/ml; 27.7 +/- 9.6 ng/ml). The PAI-1 levels were evenly distributed from 5.93 to 52.7 ng/ml in diabetic patients. The difference of Lp (a) levels between the two groups was negligible (the diabetic group, median 11 mg/dl (range 0-72 mg/dl); the control group, median 13 mg/dl (range 0-55 mg/dl)). Significant correlations between PAI-1 levels and body mass index (BMI) were observed in both groups. In the diabetic group, PAI-1 levels also correlated with fasting C-peptide levels (r = 0.54, P < 0.01) and serum triglyceride levels (r = 0.28, P < 0.05). However, we could not find a significant association between either t-PA or PAI-1 levels and Lp (a) levels in the diabetic and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fibrinolysis; Glycated Hemoglobin; Humans; Hypertension; Korea; Lipids; Lipoprotein(a); Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator

The metabolic effects of a 3-week dietary supplement of a fish oil concentrate was examined in mildly obese, normotriglyceridemic men with non-insulin-dependent diabetes mellitus (NIDDM) treated with hypoglycemic agents (n = 20). Patients were randomized into two groups, receiving 15 ml per day of fish oil (Martens Oil, Norway) containing 3.1 g of omega-3 fatty acids (FA) (n = 10) or placebo (n = 10). Whereas fish oil led to the expected increase in the ratio of omega-3 to omega-6 FA in serum phospholipids, reflecting the increase in omega-3 FA intake, it did not alter fasting or mixed meal stimulated blood glucose, plasma insulin, and C-peptide concentrations. No changes in insulin action were noted, estimated by the metabolic clearance rates of glucose at plasma insulin levels of approximately 100 microU/ml and 1,400 microU/ml during a hyperinsulinemic, isoglycemic clamp; no changes were seen in insulin binding to erythrocytes. We conclude that during short-term administration, no adverse effects of low dose fish oil on glucose homeostasis were found in mildly obese NIDDM patients treated with oral hypoglycemic agents.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fats, Unsaturated; Fatty Acids, Omega-3; Fish Oils; Glyburide; Humans; Insulin; Kinetics; Male; Middle Aged; Obesity; Triglycerides

To examine the effect of prior meal ingestion on the glucose, insulin, and C-peptide response to a 50-g glucose challenge test in the third trimester of pregnancy.. Ten pregnant women with gestational diabetes mellitus and 12 nondiabetic pregnant control subjects matched for age and weight underwent a 50-g glucose challenge test on three occasions within a 2-wk period, in random order. On one occasion the test was administered in the fasting state (fasting glucose challenge test), on a second occasion the test was administered 1 h after ingestion of a standard mixed meal (1-h postprandial study), and on a third occasion the test was administered 2 h after ingestion of a standard mixed meal (2-h postprandial study).. In the control subjects, the plasma glucose level 1 h after ingestion of 50 g of glucose was higher in the fasting study (7.8 +/- 0.4 mM, 7 of 12 subjects with glucose > or = 7.8 mM) than in the 1-h postprandial study (6.7 +/- 0.3 mM, 3 of 12 subjects with glucose > or = 7.8 mM) and the 2-h postprandial study of (6.3 +/- 0.4 mM, 3 of 12 with glucose > or = 7.8 mM) (P < 0.01). In the postprandial studies of control subjects, insulin and C-peptide levels were higher at the time of ingestion of the 50 g of glucose, but the early (1 h) insulin secretory response was less than in the fasting study. In the diabetic patients, glucose levels 1 h after 50-g glucose ingestion were similar in the fasting study (10.5 +/- 0.4 mM, no subjects with glucose value < 7.8 mM) and the 1-h postprandial study (11.0 +/- 0.6 mM, 1 subject with glucose < 7.8 mM), but was lower in the 2-h postprandial study (9.3 +/- 0.3 mM, 1 subject with glucose < 7.8 mM) (P < 0.03). In contrast to the control subjects, the insulin secretory response to 50 g of oral glucose was greater in the two postprandial studies than in the fasting study.. We have reached the following conclusions. 1) In nondiabetic gravidas, plasma glucose concentrations 1 h after ingestion of a 50-g oral glucose load are higher if administered in the fasting state compared with the postprandial state. 2) During normal pregnancy the Staub-Traugott Effect, i.e., improved glucose disposal after successive glucose load administrations, occurs and appears to be caused by mechanisms other than enhanced insulin secretion with successive glucose loads. 3) The effect of the prandial state on plasma glucose response to the 50-g glucose challenge test used to screen for gestational diabetes mellitus may be of sufficient magnitude to significantly alter the operating characteristics, i.e., sensitivity and specificity, of this test.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes, Gestational; Eating; Female; Glucose Tolerance Test; Humans; Inulin; Obesity; Pregnancy; Pregnancy Trimester, Third; Reference Values

Benfluorex hydrochloride has known lipid- and glucose-lowering effects. We evaluated the change in lipids, fasting glucose, and insulin sensitivity in ten obese type 2 diabetic patients after treatment with benfluorex or a placebo for 2 weeks using a double-blind, cross-over design. Insulin sensitivity was measured using the euglycaemic-hyperinsulinaemic glucose clamp technique at two insulin infusion rates for 2 h each: 0.05 U/kg per h (clamp 1) and 0.10 U/kg per h (clamp 2). Mean fasting glucose decreased from 13.1 +/- 1.1 to 10.2 +/- 0.9 mmol/l after benfluorex (p < 0.001) and rose from 11.9 +/- 0.9 to 13.3 +/- 1.0 mmol/l after the placebo (p = 0.028). Insulin did not change significantly. Glucose uptake (GU) as a parameter for insulin sensitivity was compared for treatment with benfluorex versus the placebo. Total GU during clamp 1 was 643.4 +/- 323.8 mmol after benfluorex and 250.1 +/- 193.3 mmol after the placebo (p = 0.035), and during clamp 2, 2490.7 +/- 490.5 mmol after benfluorex and 1544.3 +/- 693.9 mmol after the placebo (p = 0.018). The dynamic analysis on the last 30 min of clamp 2 showed a significant difference in glucose infusion rate (GIR) profile, with mean levels yielding 5.36 mmol/kg per min after benfluorex and 3.87 mmol/kg per min after the placebo (p = 0.018); there were no differences in plasma insulin concentrations or plasma glucose levels. It is concluded that in this short-term study benfluorex increases insulin sensitivity in obese type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Fenfluramine; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Middle Aged; Obesity

The efficacy and safety of metformin in the treatment of obese, non-insulin-dependent, diabetic subjects poorly controlled by insulin after secondary failure to respond to sulphonylureas has been investigated. Fifty insulin-treated, obese diabetics participated in this prospective, randomised double-blind six-month trial. After a four-week run-in period, during which all patients were given placebo (single-blind), patients were randomly assigned to continue to receive placebo or to active treatment with metformin. At six months, there was a relevant and significant improvement in glycaemic control in diabetics receiving the combined insulin-metformin treatment (decrease in glucose -4.1 mmol.l-1; glycosylated haemoglobin A1 decrease -1.84%). No significant changes were seen in diabetics receiving insulin and placebo. There was a significant decrease in blood lipids (trygliceride and cholesterol), an increase in HDL-cholesterol and a reduction in blood pressure in diabetics taking metformin. These positive findings were most marked in the 14 diabetics who experienced a good response to metformin (glucose profile < 10 mmol.l-1), and were less marked but still significant in the remaining 13 diabetics, whose response to therapy was not so good (glucose profile > 10 mmol.l-1). The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (-21.6 U/day). Metformin was well tolerated by all diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucagon; Glycated Hemoglobin; Homeostasis; Humans; Islets of Langerhans; Lipids; Male; Metformin; Middle Aged; Obesity; Prospective Studies; Risk Factors; Single-Blind Method

To evaluate the change in lipids and insulin sensitivity in 10 obese type II diabetic patients after treatment with benfluorex or placebo for 2 wk.. The study had a double-blind, cross-over design. Insulin sensitivity was measured with the euglycemic hyperinsulinemic glucose clamp technique at two different insulin infusion rates: 0.05 (clamp 1) and 0.10 U.kg-1.h-1 (clamp 2).. Subanalysis of the glucose infusion rate under steady-state conditions in the last 30 min of clamp 2 yielded a glucose infusion rate of 5.36 and 3.87 mmol.kg-1.min-1 after benfluorex and placebo, respectively (P = 0.018).. Benfluorex increases insulin sensitivity in obese type II diabetic patients.

Topics: Apolipoprotein A-I; Apolipoproteins B; Appetite Depressants; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fenfluramine; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lipids; Middle Aged; Multivariate Analysis; Obesity; Placebos; Triglycerides

In a short-term (eight days) double-blind crossover study involving 10 obese patients, the effects of dexfenfluramine on glucose and lipid metabolism were examined. The protocol comprised whole body in vivo measurements (hyperinsulinemic euglycemic clamp in combination with indirect calorimetry) and in vitro studies of isolated adipocytes (lipolysis and glucose transport). All study participants were weight stable during the study period (103.1 +/- 3.2, placebo vs 103.3 +/- 3.1 kg, dexfenfluramine, NS). The following parameters were significantly reduced after dexfenfluramine treatment: fasting levels of plasma glucose (6.2 +/- 0.2 vs 5.7 +/- 0.2 mmol/l, p < 0.01), serum insulin (168.0 +/- 14.5 vs 138.9 +/- 7.9 pmol/l, p < 0.05), serum C-peptide (0.68 +/- 0.03 vs 0.58 +/- 0.02 nmol/l, p < 0.05) and total serum cholesterol (6.07 +/- 0.41 vs 5.48 +/- 0.38 mmol/l, p < 0.01). In the basal state glucose oxidation rate was significantly reduced by 36% (p < 0.001), whereas non-oxidative glucose disposal was significantly increased by 41% (p < 0.01), following dexfenfluramine treatment. Insulin-stimulated (2 mU.kg-1 x min-1) glucose disposal rate tended to be increased (18%, p = 0.10) after dexfenfluramine. In conclusion, dexfenfluramine possesses beneficial regulatory effects on glucose and lipid metabolism in non-diabetic obese patients, independently of weight loss.

Topics: Adipose Tissue; Adult; Biological Transport; Blood Glucose; C-Peptide; Double-Blind Method; Female; Fenfluramine; Glucose; Glucose Clamp Technique; Humans; Insulin; Lipid Metabolism; Lipids; Lipolysis; Male; Obesity; Oxidation-Reduction

Insulin resistance contributes to the metabolic defects in non-insulin-dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. The serotonin-reuptake inhibiting agent fluoxetine has recently been recognized as an anorectic agent. The effect of fluoxetine on insulin action has not yet been determined. In a double blind placebo controlled crossover study, we examined hepatic and peripheral insulin action by the sequential hyperinsulinemic euglycemic clamp technique with infusion of 3-3H-glucose in eight obese NIDDM and in eight obese nondiabetics, matched for age, sex and body mass index. Body weight was kept constant. After 14 days of fluoxetine, 60 mg daily, in NIDDM half-maximal peripheral glucose uptake was achieved at a lower insulin level than after placebo (ED50pgu 180.5 +/- 25.8 vs 225.3 +/- 39.9 mU/l, P less than 0.05), but not in nondiabetics (140 +/- 15.3 vs 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral glucose uptake (Vmaxpgu) did not change significantly. Basal hepatic glucose production (HGP) was reduced after fluoxetine in both NIDDM (9.45 vs 10.37 mumol/kg/min) and in nondiabetics (8.57 vs 9.16 mumol/kg/min), although the difference was only significant in nondiabetics (P less than 0.05). Multivariate analysis disclosed no differences in the effect of fluoxetine between NIDDM and nondiabetics. When nondiabetics and NIDDM were considered together, only the most insulin-resistant individuals demonstrated a decrease in ED50pgu (P less than 0.001). Likewise, only the individuals with the most outspoken hepatic insulin resistance demonstrated a decrease in insulin level, at which hepatic glucose production is completely suppressed (HGP0) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: C-Peptide; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Fluoxetine; Glucose; Humans; Insulin; Insulin Secretion; Liver; Male; Middle Aged; Multivariate Analysis; Obesity

To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas.. A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment.. Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients.. The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight.

Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Eating; Fasting; Glyburide; Glycated Hemoglobin; Humans; Insulin, Isophane; Metformin; Middle Aged; Obesity

Topics: Adaptation, Physiological; Adult; C-Peptide; Female; Fetal Diseases; Fetus; Gestational Age; Growth Hormone; Humans; Infant, Newborn; Insulin; Male; Obesity; Pregnancy; Pregnancy Complications; Risk Factors

Combined insulin and sulfonylurea therapy for type 2 diabetes may improve the effectiveness of a single injection of insulin, thereby postponing the need for multiple injections. This concept was tested in 21 obese subjects imperfectly controlled by 20 mg of glyburide daily in a double masked, placebo-controlled, parallel design, 16-week protocol. Premixed 70% NPH/30% Regular insulin was taken before supper, and the dosage was adjusted weekly by an algorithm seeking nearly normal fasting glycemia. Eleven subjects using insulin plus 10 mg glyburide before breakfast had lower mean fasting glucose at 10-16 weeks than 10 subjects using insulin with placebo (mean +/- SEM; 5.9 +/- 0.3 versus 7.5 +/- 0.7 mmol/L; p less than 0.05), and had a greater decrement of glycosylated hemoglobin from baseline values (1.3 +/- 0.1 versus 0.8 +/- 0.2% A1, p less than 0.05). After 16 weeks the combined therapy group used half as much insulin as the insulin-only group (50 +/- 5 versus 101 +/- 13 units/d; p less than 0.01). Fasting serum free insulin values increased 58% from baseline after insulin therapy in the insulin-only group (p less than 0.05) but did not increase with combined therapy. Weight gain was similar in the two groups. These data support this form of combined therapy as one option for treating obese persons with type 2 diabetes no longer responsive to oral therapy alone.

Topics: Adult; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Glyburide; Glycated Hemoglobin; Humans; Insulin; Lipoproteins; Obesity; Triglycerides

In this study, we investigated the hypothesis that increased opioid activity may be involved in the development of hyperinsulinemia in women with obesity and abdominal body fat distribution. Two groups of nine obese body (body mass index [BMI], 30 to 40 kg/m2) women with abdominal (A-ob) (waist to hip ratio [WHR] greater than 0.85) or gluteo-femoral (F-ob) (WHR greater than or equal to 0.80) fat distribution were examined and compared with eight normal-weight controls. Basal beta-endorphin levels were higher in the A-ob group than in the other groups. Each woman underwent two oral glucose tolerance tests (OGTT, 75 g glucose). A bolus of naloxone (0.8 mg) followed by a constant infusion of naloxone (0.04 mg/kg/h) or saline was also administered during the glucose challenge in random order, and blood samples for glucose, insulin, and C-peptide were collected at regular times after glucose administration. No difference was observed in basal or stimulated glucose concentrations between the three groups, nor between the saline or naloxone study. However, basal and stimulated insulin levels were significantly higher in obese women (particularly in the A-ob group) than in controls. Naloxone administration, however, did not significantly modify insulin and C-peptide glucose-stimulated concentrations in controls and in the F-ob group, whereas it significantly reduced (by approximately 47%) insulin levels in the A-ob group. Partial correlation coefficients showed a significant negative correlation between percent variation of glucose-stimulated insulin incremental areas during the naloxone study and the WHR in all women considered together (r = .544, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Adipose Tissue; Adult; beta-Endorphin; C-Peptide; Endorphins; Female; Humans; Insulin; Naloxone; Obesity

Data on the influence of calcium antagonists on glucose tolerance and insulin release in humans are conflicting. The present double-blind, double-dummy, controlled trial was designed to investigate the effect of a short-term (7 days) treatment with nitrendipine, 20 mg b.i.d.; nitrendipine, 20 mg once daily; or placebo on blood glucose and plasma insulin and C-peptide response to an intravenous glucose load in mildly or transiently hypertensive nondiabetic obese patients. No statistically significant differences were found in fasting glucose, insulin, and C-peptide, or in the glucose disappearance rate and in any of the parameters for insulin and C-peptide response after i.v. glucose, between the three groups of patients. However, a slight decrease in early insulin response to glucose was observed in the nifedipine and the nitrendipine groups. This study confirms that calcium antagonists have no clinically relevant effect on glucose homeostasis even if a slight alteration of insulin release after glucose load cannot be ruled out.

Topics: Adult; Analysis of Variance; Blood Glucose; C-Peptide; Double-Blind Method; Female; Humans; Hypertension; Insulin; Insulin Secretion; Male; Middle Aged; Nifedipine; Nitrendipine; Obesity; Time Factors

To determine whether hyperinsulinaemia of human obesity is dependent on the activity of the parasympathetic nervous system, and whether activation of the parasympathetic nervous system plays a role in glucose-induced thermogenesis, the metabolic effect of a continuous intravenous glucose infusion [44.4 mumol kg-1 body weight (bw) min-1] with or without atropine infusion was assessed in 11 obese patients and 10 lean controls. Compared with lean controls, obese patients had increased basal and glucose-stimulated plasma insulin and C-peptide concentrations and increased plasma glucose concentrations during glucose infusion. Glucose oxidation during i.v. glucose was lower in obese patients than in lean controls. Glucose-induced thermogenesis was similar in obese patients and in lean controls. Atropine infusion did not affect basal plasma glucose, insulin or free fatty acid concentrations nor glucose-stimulated plasma glucose, insulin, C-peptide, glucagon or free fatty acid concentrations in both groups of subjects. Glucose and lipid oxidation rates and glucose-induced thermogenesis were also unaffected by atropine administration. It is concluded that (1) glucose-stimulated hyperinsulinaemia in human obesity is not dependent on a hyperactivity of the parasympathetic nervous system, which indicates that human obesity is different from most animal models of obesity; (2) glucose-induced thermogenesis is similar in obese and lean subjects when a similar load of glucose is administered; (3) inhibition of the parasympathetic nervous system does not affect the thermic effect of i.v. glucose.

Topics: Adult; Atropine; Blood Glucose; Body Temperature Regulation; C-Peptide; Female; Glucose; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Male; Obesity; Parasympathetic Nervous System

In previous studies growth hormone (GH) injections [0.1 mg/kg ideal body wt (IBW) every other day] produced significant increases in plasma insulin-like growth factor I (IGF-I) concentrations and nitrogen retention, which were attenuated when 12 kcal/kg IBW was ingested. The present study was done to determine whether doubling the GH dose would enhance its anabolic effects and facilitate fat loss. Eight women (33-83% over IBW) were fed 12 kcal/kg IBW for 14 wk. They received GH or vehicle injections, each for 5 wk during either weeks 2-6 or 9-13. GH improved nitrogen balance (GH, 3.6 +/- 123.2 mmol/d; vehicle, -132.0 +/- 117.9 mmol/d; means +/- SD; p less than 0.001). Plasma IGF-I increased from 32.1 +/- 9.6 to 79.4 +/- 22.1 nmol/L by day 5 of GH (p less than 0.001) and remained elevated until GH injections were discontinued. No significant effect of GH on mean body fat loss was observed. GH can induce significant anabolic responses even when caloric intake is decreased to 12 kcal/kg IBW. The degree and duration of these anabolic responses are dependent on the GH dose given.

Topics: Adolescent; Adult; Body Composition; C-Peptide; Diet, Reducing; Dietary Carbohydrates; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Female; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Nitrogen; Obesity; Weight Loss

Hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) stimulates peripheral glucose uptake, which tends to compensate for impaired insulin-mediated glucose uptake. The metabolic fate of glucose and suppression of fat oxidation may differ, however, when glucose uptake is stimulated primarily by insulin or hyperglycemia. To address this issue, three hyperinsulinemic glucose-clamp studies were performed in combination with indirect calorimetry in seven nonobese subjects with NIDDM. In the first two experiments, when glucose uptake was matched at approximately 8 mg.kg-1 fat-free mass (FFM).min-1 with primarily hyperinsulinemia (1350 +/- 445 pM) or hyperglycemia (20.8 +/- 1.8 mM), identical rates of glucose oxidation (3.21 +/- 0.29 and 3.10 +/- 0.23 mg.kg-1 FFM.min-1, NS) and nonoxidative glucose metabolism (5.19 +/- 0.75 and 5.46 +/- 0.61 mg.kg-1 FFM.min-1, NS) were achieved. When glucose uptake was increased further to 11.11 +/- 0.36 mg.kg-1 FFM.min-1 with less insulin (625 +/- 70 pM) and hyperglycemia, glucose oxidation (3.85 +/- 0.26 mg.kg-1 FFM.min-1) and nonoxidative glucose metabolism (7.26 +/- 0.51 mg.kg-1 FFM.min-1) rose significantly (both P less than 0.05 from matched studies at lower rates of glucose uptake). During all glucose-clamp studies, free fatty acids were comparably suppressed by 40-46% (all P less than 0.005 vs. basal values), whereas fat oxidation was suppressed by 70-80% (all P less than 0.005 vs. basal values). A strong negative correlation was observed between rates of glucose and fat oxidation (r = -0.88, P less than 0.001) when all studies were combined.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Calorimetry; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucagon; Glucose; Glucose Clamp Technique; Humans; Hyperglycemia; Hyperinsulinism; Insulin; Lipid Metabolism; Male; Middle Aged; Obesity; Oxidation-Reduction

Forty-two obese subjects with non-insulin-dependent diabetes mellitus had their plasma insulin, C peptide, and glucose levels measured after an overnight fast and in response to a 75-g oral glucose loading. Subjects were then prospectively followed up with dietary treatment, and the same measurements were repeated at 1 year. Although insulin values tended to be lower with greater fasting hyperglycemia at baseline, no correlation was observed among three parameters. However, near-normalization of glycemia (measured as the level of hemoglobin A1) was associated with significantly higher fasting and stimulated plasma insulin concentrations. Sixteen subjects were matched to each other for equivalent baseline hyperglycemia (by glycosylated hemoglobin) and divided into group 1 (normalization of the hemoglobin A1 value to 7.0% +/- 0.3% [mean +/- SE]) and group 2 (persistent hyperglycemia) (hemoglobin A1 value, 10.7% +/- 0.7% [mean +/- SE]). Before dietary therapy, the plasma insulin concentrations were twofold to threefold higher in group 1, and despite similar degrees of weight loss, group 2 failed to demonstrate improved glycemia. We concluded that the outcome of diet therapy for non-insulin-dependent diabetes mellitus is dependent on the duration of diabetes and endogenous insulin secretory reserve. There is a subgroup of patients with non-insulin-dependent diabetes mellitus in whom delayed dietary intervention may have a beneficial effect.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Time Factors

Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study. Metformin 0.5 g trice daily or placebo were given for 4 weeks. At the end of each period fasting and day-time postprandial values of plasma glucose, insulin, C-peptide and lactate were determined, and in vivo insulin action was assessed using the euglycemic clamp in combination with [3-3H]glucose tracer technique. Metformin treatment significantly reduced mean day-time plasma glucose levels (10.2 +/- 1.2 vs 11.4 +/- 1.2 mmol/l, P less than 0.01) without enhancing mean day-time plasma insulin (43 +/- 4 vs 50 +/- 7 mU/l, NS) or C-peptide levels (1.26 +/- 0.12 vs 1.38 +/- 0.18 nmol/l, NS). Fasting plasma lactate was unchanged (1.57 +/- 0.16 vs 1.44 +/- 0.11 mmol/l, NS), whereas mean day-time plasma lactate concentrations were slightly increased (1.78 +/- 0.11 vs 1.38 +/- 0.11 mmol/l, P less than 0.01). The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization (370 +/- 38 vs 313 +/- 33 mg.m-2.min-1, P less than 0.01), whereas insulin-mediated suppression of hepatic glucose production was unchanged. Also basal glucose clearance was improved (61.0 +/- 5.8 vs 50.6 +/- 2.8 ml.m-2.min-1, P less than 0.05), whereas basal hepatic glucose production was unchanged (81 +/- 6 vs 77 +/- 4 mg.m-2.min-1, NS).. 1) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Circadian Rhythm; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Double-Blind Method; Fasting; Humans; Insulin; Lactates; Lactic Acid; Liver; Metformin; Middle Aged; Obesity

Considerable disagreement exists regarding the levels of immunoreactive glucose dependent insulinotropic polypeptide in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Glucose dependent insulinotropic polypeptide levels were therefore studied during oral glucose and mixed meal tolerance tests in normal subjects (n = 31) and newly presenting previously untreated patients with Type 2 diabetes mellitus (n = 68). The tests were performed in random order after overnight fasts and blood samples were taken at 30 min intervals for 4 h. During the oral glucose tolerance test plasma glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a fasting value of 20 +/- 3 pmol/l to a peak of 68 +/- 5 pmol/l at 30 min and in the Type 2 diabetic patients from a similar fasting level of 27 +/- 3 pmol/l to a higher peak value of 104 +/- 6 pmol/l at 30 min (p less than 0.001). Glucose dependent insulinotropic polypeptide levels were significantly higher in the diabetic patients compared with the normal subjects from 30-90 min (p less than 0.01-0.001) following oral glucose. During the meal tolerance test glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a pre-prandial value of 22 +/- 4 pmol/l to a peak of 93 +/- 6 pmol/l at 90 min and in the Type 2 diabetic patients from a similar basal level of 25 +/- 2 pmol/l to a higher peak of 133 +/- 7 pmol/l at 60 min. Glucose dependent insulinotropic polypeptide concentrations were significantly higher in Type 2 diabetic patients compared with the normal subjects at 30 min (p less than 0.001), 60 min (p less than 0.01) and from 210-240 min (p less than 0.05) during the meal tolerance test. The groups were subdivided on the basis of degree of obesity and glucose dependent insulinotropic polypeptide concentrations were still higher in the diabetic subgroups compared with the normal subjects matched for weight. Type 2 diabetes mellitus is associated with an exaggerated glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals which is independent of any effect of obesity.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Eating; Female; Gastric Inhibitory Polypeptide; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Obesity; Random Allocation; Reference Values

Insulin requirements, C-peptide levels, and serum lipids have been assessed in 12 obese, insulin-requiring (greater than 60 U/day) patients with type II diabetes mellitus, in a randomized crossover fashion with two treatment regimens: NPH alone and combined NPH and tolazamide, over a period of 3 months each, with maintenance of weight and glycemic control (HgA1, 2hpp and mean 24h glucose profile) at comparable levels. Serum cholesterol improved in both groups compared to their respective baseline values (p less than 0.05). In addition, serum triglyceride was lower (p less than 0.05) in the combined therapy as compared with NPH alone therapy. Insulin requirements were decreased by 23% (p less than 0.002) in the combined therapy group, without significant change in weight, glycemic control, or C-peptide levels. However, C-peptide increments in the combined therapy group were significantly higher than the baseline by 70% (p less than 0.02). NPH plus tolazamide therapy as compared with NPH alone lowers insulin requirement in obese, type II diabetic women without significant alteration in glycemic control, possibly by an increased tissue sensitivity to insulin, and decreases serum triglyceride levels.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Insulin, Isophane; Middle Aged; Obesity; Prospective Studies; Random Allocation; Tolazamide; Triglycerides

An insulin suppression test performed in random order with either biosynthetic human insulin or purified pork insulin was used to compare biological activity of these two insulins in obese patients suffering from varying degrees of glucose intolerance. Blood glucose curve, steady-state blood glucose levels, insulin sensitivity indices and steady-state plasma insulin levels were identical during the two sets of tests. Furthermore endogenous insulin and glucagon secretion were similarly suppressed. The insulin suppression test is a simple and rapid procedure to compare the biological activity of fast-acting insulins. Our results confirm the insulin-resistance in obesity and clearly show that biosynthetic human and porcine insulins have similar biological potency.

Topics: Adult; Aged; Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose; Humans; Insulin; Insulin Resistance; Insulin, Regular, Pork; Male; Middle Aged; Obesity; Recombinant Proteins; Somatostatin; Swine

This study was performed in two randomly defined groups of obese patients with polycystic ovaries to investigate the overall effects of hypocaloric diet combined (group 2) or not combined (group 1) with an antiandrogenic therapy (cyproterone acetate, 50 mg/day, plus ethinyl estradiol, 0.05 mg/day) on sex hormone plasma levels, insulin secretion and resistance, and body weight loss and on their reciprocal interrelationships. All obese patients with polycystic ovaries showed elevated luteinizing hormone and androgen levels, hyperinsulinemia, and marked insulin resistance. After an average period of 3 months both groups showed a similar weight loss and a similar reduction in the insulin-resistant state. During treatment in group 1 three patients had a greater frequency of menstrual bleeding, and in one of them an ovulatory cycle was documented. Whereas, no changes in gonadotropin and sex steroid levels were found in group 1, a significant fall was observed in group 2. No relationships were observed between these changes and those which occurred on insulin levels. We conclude that hyperandrogenism in obese patients with polycystic ovaries does not appear to be a primary factor leading to the insulin-resistant state.

Topics: Adolescent; Adult; Androgen Antagonists; Body Weight; C-Peptide; Energy Intake; Female; Glucose Tolerance Test; Gonadal Steroid Hormones; Humans; Insulin; Insulin Resistance; Male; Obesity; Polycystic Ovary Syndrome

Bay m 1099 is a newly developed inhibitor of intestinal alpha-glucosidase. Its ability to lower postprandial plasma glucose, serum insulin and C-peptide levels in Type II diabetics has been investigated. Fifteen obese Type II diabetic patients with inadequate metabolic control during sulphonylurea treatment received a standardized diet and were treated either with Bay m 1099, b.d. (100 mg before breakfast and dinner) or placebo for 3 days, according to a double-blind cross-over design. The postprandial blood glucose level was significantly lower during Bay m 1099 treatment compared to placebo after breakfast and dinner (AUC after breakfast p less than 0.001). The reduced postprandial hyperglycaemia was associated with a decrease in meal stimulated serum insulin and C-peptide levels. Thus, Bay m 1099 may be a useful addition in the treatment of Type II diabetic patients.

Topics: 1-Deoxynojirimycin; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Eating; Female; Glucosamine; Glycoside Hydrolase Inhibitors; Humans; Imino Pyranoses; Insulin; Male; Middle Aged; Obesity; Pancreatic Hormones

An assessment of the metabolic effect of dietary carbohydrate on daily insulin secretion, reflected by the 24-h urine output of C-peptide, has been made. Urinary C-peptide excretion increased when the carbohydrate intake of 6 normal subjects was increased from 200 to 400 g. A high-fibre diet rich in beans and lentils caused a significant fall in urine C-peptide and a lowering of blood glucose values in both normal and diabetic subjects. This confirms the insulin-sparing effect of leguminous foods. An increase of dietary fibre to 50 g mainly as cereal fibre did not significantly alter urine C-peptide excretion in normal subjects. Urinary C-peptide estimations could be useful for assessing the effect of different diets on daily insulin secretion.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diet; Dietary Carbohydrates; Dietary Fiber; Dose-Response Relationship, Drug; Edible Grain; Fabaceae; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Peptides; Plants, Medicinal

In 18 obese women a very-low-calorie diet (VLCD) has been combined with exercise (three times a week = 1650 kcal/week; 6.9 MJ) and compared with the effects of diet alone. The adherence and tolerance of the diet was quite good. Oxygen uptake decreased significantly only in the exercising group. Sex hormones binding globulin increased while prealbumin and retinol binding protein decreased in both groups. Changes in T4, T3, rT3, TSH, TBG and insulin secretion appeared to be equal in both groups. No significant differences between the two groups have been found with respect to body weight, body fat and lean body mass loss. Glucose tolerance deteriorated in the diet only group but remained unchanged in the group combining diet and exercise. Insulin production after oral glucose load did not change in either of the two groups. A more pronounced decrease in c peptide concentration has been observed in exercising groups. Sex hormones binding globulin and testosterone concentration increased in both groups. No changes have been detected in the concentration of transcortin. It is concluded that during a short period of VLCD exercise did not produce a higher body weight loss nor a protective effect on lean body mass.

Topics: Blood Proteins; Body Composition; C-Peptide; Diet, Reducing; Female; Glucose Tolerance Test; Gonadal Steroid Hormones; Humans; Insulin; Middle Aged; Obesity; Oxygen Consumption; Physical Exertion; Thyroid Hormones; Time Factors

Excessive visceral adipose tissue (VAT) is associated with higher secretion of pro-inflammatory molecules, contributing to systemic inflammation and obesity-related metabolic disturbances.. This prospective analysis includes 117 overweight/obese adults (55-75 years) from the PREDIMED-Plus study. Fourteen inflammatory markers and adipokines are measured using a Bio-Plex assay with multiplex technology: insulin, glucagon, IL-6, visfatin, ghrelin, GLP-1, TNF-α, MCP-1, PAI-1, resistin, C-peptide, leptin, adipsin, and adiponectin. Participants are categorized into tertiles according to changes in VAT after 1-year of follow-up, determined by dual-energy X-Ray absorptiometry. Participants allocate in tertile 3, which represent an increase of VAT content after 1-year of follow-up compared to tertile 1, show significant differences in insulin (T3 vs T1, fully adjusted model: p = 0.037, p for trend 0.042), PAI-1 (fully adjusted model: p = 0.05, p for trend 0.06), c-peptide (fully adjusted model: p = 0.037, p for trend 0.042), and TNF-α (fully adjusted model p = 0.037, p for trend 0.042).. The results evidence that a reduction in VAT is associated with clinical improvements in several inflammatory and adiposity markers, mainly in insulin, c-peptide, and PAI-1 levels, and these improvements may contribute to a reduction in cardiometabolic disturbances observe in obesity.

Topics: Adult; C-Peptide; Humans; Intra-Abdominal Fat; Metabolic Syndrome; Obesity; Plasminogen Activator Inhibitor 1; Tumor Necrosis Factor-alpha

Sleeve gastrectomy (SG) successfully recovers metabolic homeostasis in obese humans and rodents while also resulting in the normalization of insulin sensitivity and insulinemia. Reduced insulin levels have been attributed to lower insulin secretion and increased insulin clearance in individuals submitted to SG. Insulin degradation mainly occurs in the liver in a process controlled, at least in part, by the insulin-degrading enzyme (IDE). However, research has yet to explore whether liver IDE expression or activity is altered after SG surgery. In this study, C57BL/6 mice were fed a chow (CTL) or high-fat diet (HFD) for 10 weeks. Afterward, the HFD mice were randomly assigned to two groups: sham-surgical (HFD-SHAM) and SG-surgical (HFD-SG). Here, we confirmed that SG improves glucose-insulin homeostasis in obese mice. Additionally, SG reduced insulinemia by reducing insulin secretion, assessed by the analysis of plasmatic C-peptide content, and increasing insulin clearance, which was evaluated through the calculation of the plasmatic C-peptide:insulin ratio. Although no changes in hepatic IDE activity were observed, IDE expression was higher in the liver of HFD-SG compared with HFD-SHAM mice. These results indicate that SG may be helpful to counteract obesity-induced hyperinsulinemia by increasing insulin clearance, likely through enhanced liver IDE expression.

Topics: Animals; C-Peptide; Diet, High-Fat; Gastrectomy; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin, Regular, Human; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Weight Loss

Both continuous and accumulated walking lowered post-meal glucose, insulin and C-peptide levels and improved glucose fluctuation.Postprandial glucose was kept lower for a longer time in accumulated than continuous walking.Accumulated post-meal exercise (e.g. three 10-min bouts of walking) could be recommended as a feasible and practical alternative protocol for postprandial glucose control, especially for those who have difficulty performing sufficient exercise in one session.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; C-Peptide; Cross-Over Studies; Exercise; Humans; Male; Obesity; Walking; Young Adult

Both obesity and a poor diet are considered major risk factors for triggering insulin resistance syndrome (IRS) and the development of type 2 diabetes mellitus (T2DM). Owing to the impact of low-carbohydrate diets, such as the keto diet and the Atkins diet, on weight loss in individuals with obesity, these diets have become an effective strategy for a healthy lifestyle. However, the impact of the ketogenic diet on IRS in healthy individuals of a normal weight has been less well researched. This study presents a cross-sectional observational study that aimed to investigate the effect of low carbohydrate intake in healthy individuals of a normal weight with regard to glucose homeostasis, inflammatory, and metabolic parameters.. The study included 120 participants who were healthy, had a normal weight (BMI 25 kg/m. Low carbohydrate intake (<45% of total energy) was found to significantly correlate with dysregulated glucose homeostasis as measured by elevations in HOMA-IR, HOMA-β% assessment, and C-peptide levels. Low carbohydrate intake was also found to be coupled with lower serum bicarbonate and serum albumin levels, with an increased anion gap indicating metabolic acidosis. The elevation in C-peptide under low carbohydrate intake was found to be positively correlated with the secretion of IRS-related inflammatory markers, including FGF2, IP-10, IL-6, IL-17A, and MDC, but negatively correlated with IL-3.. Overall, the findings of the study showed that, for the first time, low-carbohydrate intake in healthy individuals of a normal weight might lead to dysfunctional glucose homeostasis, increased metabolic acidosis, and the possibility of triggering inflammation by C-peptide elevation in plasma.

Topics: Acidosis; Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Humans; Insulin; Insulin Resistance; Metabolic Syndrome; Obesity

Sex-specific differences exist in insulin secretion (ISec) and sensitivity (IS) in humans. However, current fasting indices used to estimate them, such as HOMA and QUICKI, are not sex-specific. We aimed to develop sex-specific models to improve the prediction of ISec and IS by fasting measures in adults with overweight/obesity. A post hoc analysis was conducted on baseline data of two clinical trials completed between 2010 and 2020 (37 men and 61 postmenopausal women, 45-73 years, BMI > 25 kg/m

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin, Regular, Human; Male; Obesity; Overweight

To evaluate the therapeutic effects of two therapeutic strategies based on metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus (T2DM) in obese patients.. In both of the groups, the patients all showed significant reductions of BMI, waist circumference, FBG, postprandial blood glucose and HbA1C (all. Both metformin hydrochloride/vildagliptin and liraglutide have good therapeutic effects on T2DM in obese patients and can achieve good blood glucose and weight control, but liraglutide has a better effect for weight control.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Liraglutide; Metformin; Obesity; Retrospective Studies; Treatment Outcome; Vildagliptin

The prevalence of obesity in general pediatric population increases without sparing children with T1D. We intended to find factors associated with the possibility of preserving endogenous insulin secretion in individuals with long-standing T1D. At onset, higher BMI is associated with higher C-peptide level, which may indicate to be one of the favorable factors involved in preserving residual β-cell function. The study determines the influence of BMI on C-peptide secretion in children newly diagnosed with T1D in two years observation.. We assessed the possible relationship between selected pro- and anti-inflammatory cytokines, body mass at recognition and β-cell function status. 153 pediatric patients with newly diagnosed T1D were divided into quartiles according to BMI-SDS index. We separated a group consisted of patients with BMI-SDS >1. Participants were followed up for two years and examined for changes in body weight, HbA1c, and insulin requirement. C-peptide was assessed at baseline and after two years. We evaluated the patients' levels of selected inflammatory cytokines at baseline.. Subjects with higher BMI-SDS presented higher serum C-peptide levels and lower insulin requirements at diagnosis than children with lower body weight. The two-year follow-up showed that C-peptide levels of obese patients dropped more rapidly than in children with BMI-SDS within normal limits. The group with BMI-SDS >1 showed the greatest decrease in C-peptide level. Despite statistically insignificant differences in HbA1c at diagnosis between the study groups, in the fourth quartile and BMI-SDS >1 groups, HbA1c as well as insulin requirements increased after two years. The levels of cytokines varied the most between BMI-SDS <1 and BMI-SDS >1 groups and were significantly higher within BMI-SDS >1 group.. Higher BMI, associated with enhanced levels of inflammatory cytokines, relates to preservation of C-peptide at T1D recognition in children but is not beneficial in the long term. A decrease in C-peptide levels combined with an increase in insulin requirements and in HbA1c among patients with high BMI occur, which may indicate a negative effect of excessive body weight on the long term preservation of residual β-cell function. The process seems to be mediated by inflammatory cytokines.

Topics: Body Mass Index; Body Weight; C-Peptide; Child; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Insulin; Obesity; Weight Gain

This study sought to examine the impacts of a high dietary fiber cereal meal in comparison to conventional dietary management for diabetes on body weight, distribution of adipose tissue, and cardiovascular risk among individuals diagnosed with type 2 diabetes (T2DM).. A cohort of 120 patients diagnosed with T2DM was enlisted as the study population and divided into two groups using a ratio of 2:1-namely, the W group (n=80) and the U group (n=40). The U group (control) received usual diet, while the W group (intervention) incorporated a high dietary fiber cereal meal in place of their regular staple food in addition to adhering to conventional diabetes dietary recommendations. The high dietary fiber cereal meal was based on whole grains, traditional Chinese medicinal foods, and prebiotics. A subsequent follow-up period of 3 months ensued, during which diverse parameters such as body mass index (BMI),waist-hip ratio (WHR), glycated hemoglobin (HbA1c),fasting blood glucose(FBG),C-peptide levels, blood pressure, blood lipids, high-sensitivity C-reactive protein (hsCRP),10-year cardiovascular disease (CVD) risk, and Lifetime CVD risk were assessed before and after the intervention.. Among the participants, a total of 107 successfully completed the intervention and follow-up, including 72 individuals from the W group and 35 from the U group. Following the intervention, both cohorts exhibited decrease in BMI, WHR, HbA1c, FBG, blood pressure, and blood lipid levels in contrast to their initial measurements. Remarkably, the improvements in BMI, WHR, HbA1c, FBG, total cholesterol (TC), triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C), and the ratio of 2-hour C-peptide (2hCP) to fasting C-peptide (FCP) were more marked within the W group, exhibiting statistically significant disparities (. The intervention centred on a cereal-based dietary approach showcased favourable outcomes with regard to body weight, adipose distribution, and cardiovascular risk in overweight individuals grappling with T2DM.

Topics: Body Weight; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Diabetes Mellitus, Type 2; Dietary Fiber; Edible Grain; Glycated Hemoglobin; Heart Disease Risk Factors; Humans; Lipids; Obesity; Risk Factors; Triglycerides

Oxidative stress and apoptosis are involved in the pathogenesis of obesity-related diseases. This observational study investigates the antioxidant and apoptotic markers response to an oral glucose tolerance test (OGTT) in a population of overweight children and adolescents, with normal (NGT) or impaired glucose tolerance (IGT). Glucose, insulin, and C-peptide concentrations, as well as oxidative stress (SOD, GPx3) and apoptotic markers (Apo1fas, cck18), were determined at T = 0, 30, 60, 90, 120, and 180 min after glucose intake during OGTT. The lipid profile, thyroid function, insulin-like growth factor1, leptin, ghrelin, and adiponectin were also measured at baseline. The 45 participants, with a mean age of 12.15 (±2.3) years old, were divided into two subcategories: those with NGΤ (n = 31) and those with IGT (n = 14). The area under the curve (AUC) of glucose, insulin, and C-peptide was greater in children with IGT; however, only glucose differences were statistically significant. SOD and GPx3 levels were higher at all time points in the IGT children. Apo1fas and cck18 levels were higher in the NGT children at most time points, whereas Adiponectin was lower in the IGT group. Glucose increased during an OGTT accompanied by a simultaneous increase in antioxidant factors, which may reflect a compensatory mechanism against the impending increase in oxidative stress in children with IGT.

Topics: Adiponectin; Adolescent; Antioxidants; Blood Glucose; C-Peptide; Child; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Obesity; Superoxide Dismutase; Weight Gain

The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications.. A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels.. 113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C-peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C-peptide levels.. Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.

Topics: C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Hypertension; Obesity

To examine the associations of trimester-specific maternal prenatal carbohydrate (CHO) intake with offspring adiposity and metabolic health during peripuberty.. Mexico City, Mexico.. 237 mother-child pairs in the Early Life Exposure in Mexico to Environmental Toxicants cohort.. In this study of mother-child pairs in Mexico City, children born to women in the highest quartile of CHO intake during pregnancy had lowest C-peptide and CP-IR during peripuberty. Additional research is warranted to replicate and identify mechanisms.

Topics: Adiposity; Adolescent; Biomarkers; Body Mass Index; C-Peptide; Carbohydrates; Child; Female; Humans; Obesity; Prenatal Exposure Delayed Effects; Prospective Studies

The role of executive functions (EF) is to maintain particular behaviours in order to achieve intended goals. EF are crucial in management of pre-diabetes, diabetes and obesity which are grievous diseases and can lead to severe complications. The aims of our study were to: assess EF in group of obese subject with carbohydrate disorders, evaluate whether biochemical factors and comorbidities related to metabolic disorders have adverse effect on EF in this group of patients.. The study included 185 obese patients (146 women; 39 men) who were divided on three groups: pre-diabetic, diabetic and control subgroup. Patient underwent Wisconsin Card Sorting Test (WCST) to evaluate EF. Assessed biochemical factors included C-peptide, fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c).. Diabetic patients showed the worst WCST scores among the rest of groups. Pre-diabetic individuals did not differ in EF performance from control subgroup. We observed significant correlations between FPG and HbA1c and worse WCST scores in pre-diabetic subgroup. In diabetic patients C-peptide correlated with poorer EF. Depressive symptoms and hypertension significantly correlated with non-perseverative errors in WCST.. The subgroup of diabetic patients were the most obese and had the worst glycemia parameters. They also showed the worst EF in WCST. According to obtained results, hyperglycemia positively correlated with poor EF in pre-diabetes. However, in diabetic subjects cognitive deterioration may results from insulin resistance rather than hyperglycemia. In obese individuals with carbohydrate disorders both hypertension and depressive symptoms significantly contributed to EF dysfunction.

Topics: C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Male; Obesity; Prediabetic State; Prefrontal Cortex

Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known.. The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case-control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH; <1st tertile) and metabolically unhealthy (MU; ≥1st tertile) status among the control participants. These metabolic health definitions were combined with normal weight (NW); body mass index (BMI)<25 kg/m2 or waist circumference (WC)<80 cm or waist-to-hip ratio (WHR)<0.8) and overweight (OW; BMI≥25 kg/m2 or WC≥80 cm or WHR≥0.8) status, generating four phenotype groups for each anthropometric measure: (i) MH/NW, (ii) MH/OW, (iii) MU/NW, and (iv) MU/OW.. In a multivariable-adjusted conditional logistic regression model, compared with MH/NW individuals, endometrial cancer risk was higher among those classified as MU/NW [ORWC, 1.48; 95% confidence interval (CI), 1.05-2.10 and ORWHR, 1.68; 95% CI, 1.21-2.35] and MU/OW (ORBMI, 2.38; 95% CI, 1.73-3.27; ORWC, 2.69; 95% CI, 1.92-3.77 and ORWHR, 1.83; 95% CI, 1.32-2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (ORWC, 1.94; 95% CI, 1.24-3.04).. Women with metabolic dysfunction appear to have higher risk of endometrial cancer regardless of their body size. However, OW status raises endometrial cancer risk even among women with lower insulin levels, suggesting that obesity-related pathways are relevant for the development of this cancer beyond insulin.. Classifying women by metabolic health may be of greater utility in identifying those at higher risk for endometrial cancer than anthropometry per se.

Topics: Body Mass Index; Body Size; C-Peptide; Case-Control Studies; Endometrial Neoplasms; Female; Humans; Obesity; Phenotype; Prospective Studies; Risk Factors

Topics: Adipokines; Adiposity; Bone Density; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Leptin; Obesity; Pregnancy; Prospective Studies; Vascular Endothelial Growth Factor A

The aim: To investigate the relationship between leptin resistance, lipid and carbohydrate metabolism, blood pressure in obese pregnant women.. Materials and methods: Under observation were 65 women (main group) with obesity (I degree -27 women, II degree - 24 women, III degree - 14 women) in the II trimester of pregnancy, who were hospitalized in the Department of Pathology of Pregnancy KNP «Maternity Clinical house №1 "in Lviv during 2017-2020 on preeclampsia of varying severity, which were sent for inpatient treatment by women's clinics. The control group consisted of 30 healthy pregnant women without obesity.. Results: Serum leptin in obese women was directly correlated with BMI (r = 0.66, p<0.001), body weight (r = 0.29, p<0.05), total cholesterol (cholesterol) (r = 0, 37, p<0,009), low density lipoproteins (LDL cholesterol) (r = 0.33, p<0.05) and inversely with high density particles (HDL cholesterol) (r = -0.37, p<0.02 ). Studies of carbohydrate metabolism indicate the following correlation coefficients of BMI with glucose level r = 0.351; p<0,001, BMI with the level of C-peptide r = 0,450; p<0,001, BMI with HOMA index r = 0,1504; p = 0.036. Inverse correlations of C-peptide were detected with the level of P (r = -0.169; p = 0.025).. Conclusions: The discovery of the relationship between leptin resistance, lipid and carbohydrate metabolism, blood pressure indicates the possibility of using signs of leptin resistance to prevent complications during pregnancy in the second trimester.

Topics: Body Mass Index; C-Peptide; Cholesterol; Female; Humans; Insulin Resistance; Leptin; Obesity; Pregnancy; Pregnant Women

To investigate the relationship between thyroid hormone concentrations and β-cell function in euthyroid patients with obesity and type 2 diabetes.. We performed a single-center cross-sectional study of 254 patients with type 2 diabetes mellitus aged ≥40 years. The participants were allocated to an obesity group or non-obesity group on the basis of their body mass index (BMI). Their β-cell function was assessed by measuring C-peptide concentration during a 75-g oral glucose tolerance test (OGTT); and their serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone concentrations were measured.. The serum FT3 concentration and the C-peptide concentrations at five time points of the OGTT were significantly higher in the obesity group than in the non-obesity group. FT3 was positively associated with the β-cell function of the obesity group, but not that of the non-obesity group, in multiple linear regression analysis, after adjustment for potential confounding factors. Serum FT3 concentration was also significantly associated with indices of obesity (BMI, waist circumference, body fat percentage, fat mass, fat mass/height. Obesity-associated high serum FT3 concentrations might affect β-cell function in euthyroid patients with obesity and type 2 diabetes.

Topics: C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Obesity; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes mellitus occurring primarily in tropical countries like Bangladesh and has distinct characteristics. The present study aimed to describe the demographic, clinical and biochemical characteristics of patients with FCPD. This cross-sectional study was conducted at Mymensingh Medical College Hospital, Bangladesh, from January 2019 to December 2021. All patients with FCPD (previously or newly diagnosed) admitted to the inpatient Endocrinology department of the hospital were evaluated. Out of the 15 patients, 73.3% were aged 10-29 years at diagnosis, the male: female ratio was 11:4, rural: urban ratio was 9:6, 20.0% had FCPD in the first-degree family members, 73.3% were underweight, none were overweight/obese or central obese and one of them was hypertensive. Diabetes was uncontrolled in all, with a mean HbA1c of 10.5±1.9%. All but one had low C-peptide and all required insulin to manage diabetes. Although their average (mean or median) lipid parameters were normal, 73.3% of them had dyslipidemia. Among diabetic complications, diabetic nephropathy (66.7%) and neuropathy (66.7%) were more frequent, whereas diabetic retinopathy (6.7%), ischemic heart disease (6.7%) and peripheral vascular disease (6.7%) were less frequently observed; 13.3% had a history of diabetic ketoacidosis. Malnutrition manifested as abnormal skin and hair conditions and anemia was also common in the study subjects. Patients with FCPD are usually young males from rural residences. Microvascular diabetic complications are common, but macrovascular complications and DKA can occur in FCPD.

Topics: Bangladesh; C-Peptide; Cross-Sectional Studies; Demography; Diabetes Complications; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Lipids; Male; Obesity

The pathogenesis of the development of chronic lung diseases assumes the participation of systemic inflammation factors, as well as hormone-like substances produced by adipose tissue. The aim of this study was to evaluate the associations of certain adipokines/cytokines and chronic bronchitis against the background of abdominal obesity in young people. The study included 1415 people aged 25-44. In total, 115 people were selected by the random numbers method, who were divided into two subgroups: those with chronic bronchitis and abdominal obesity and those with chronic bronchitis without abdominal obesity. A control group of patients with comparable gender and age was also selected. In the group of patients with chronic bronchitis, adiponectin, TNFa and GIP levels were 1.4 times higher. The levels of C-peptide, MCP-1 and PP in the group of chronic bronchitis were 1.3 times higher compared to the control. Adipsin, lipocalin-2, IL-6 and resistin were significantly higher in the group with chronic bronchitis. Glucagon, amylin and ghrelin were 2.2, 2.3 and 3.2 times lower, respectively, in the group of patients with chronic bronchitis. Against the background of abdominal obesity, the probability of having chronic bronchitis increased with an increase in the level of lipocalin-2 and GIP and TNFa.

Topics: Adipokines; Adiponectin; Adolescent; Bronchitis, Chronic; C-Peptide; Complement Factor D; Cytokines; Ghrelin; Glucagon; Humans; Interleukin-6; Islet Amyloid Polypeptide; Lipocalin-2; Obesity; Obesity, Abdominal; Resistin

While there is an emerging role of pancreatic fat in the aetiology of type 2 diabetes mellitus (T2DM), its impact on the associated decrease in insulin secretion remains controversial. We aimed to determine whether pancreatic fat negatively affects β-cell function and insulin secretion in women with overweight or obesity but without T2DM.. 20 women, with normo- or dysglycaemia based on fasting plasma glucose levels, and low (< 4.5%) vs high (≥ 4.5%) magnetic resonance (MR) quantified pancreatic fat, completed a 1-hr intravenous glucose tolerance test (ivGTT) which included two consecutive 30-min square-wave steps of hyperglycaemia generated by using 25% dextrose. Plasma glucose, insulin and C-peptide were measured, and insulin secretion rate (ISR) calculated using regularisation deconvolution method from C-peptide kinetics. Repeated measures linear mixed models, adjusted for ethnicity and baseline analyte concentrations, were used to compare changes during the ivGTT between high and low percentage pancreatic fat (PPF) groups.. No ethnic differences in anthropomorphic variables, body composition, visceral adipose tissue (MR-VAT) or PPF were measured and hence data were combined. Nine women (47%) were identified as having high PPF values. PPF was significantly associated with baseline C-peptide (p = 0.04) and ISR (p = 0.04) in all. During the 1-hr ivGTT, plasma glucose (p<0.0001), insulin (p<0.0001) and ISR (p = 0.02) increased significantly from baseline in both high and low PPF groups but did not differ between the two groups at any given time during the test (PPF x time, p > 0.05). Notably, the incremental areas under the curves for both first and second phase ISR were 0.04 units lower in the high than low PPF groups, but this was not significant (p > 0.05).. In women with overweight or obesity but without T2DM, PPF did not modify β-cell function as determined by ivGTT-assessed ISR. However, the salient feature in biphasic insulin secretion in those with ≥4.5% PPF may be of clinical importance, particularly in early stages of dysglycaemia may warrant further investigation.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Obesity; Overweight

To characterise the association between type 2 diabetes mellitus (T2DM) subtypes (new-onset T2DM (NODM) or long-standing T2DM (LSDM)) and pancreatic cancer (PC) risk, to explore the direction of causation through Mendelian randomisation (MR) analysis and to assess the mediation role of body mass index (BMI).. Information about T2DM and related factors was collected from 2018 PC cases and 1540 controls from the PanGenEU (European Study into Digestive Illnesses and Genetics) study. A subset of PC cases and controls had glycated haemoglobin, C-peptide and genotype data. Multivariate logistic regression models were applied to derive ORs and 95% CIs. T2DM and PC-related single nucleotide polymorphism (SNP) were used as instrumental variables (IVs) in bidirectional MR analysis to test for two-way causal associations between PC, NODM and LSDM. Indirect and direct effects of the BMI-T2DM-PC association were further explored using mediation analysis.. Findings of this study do not support a causal effect of LSDM on PC, but suggest that PC causes NODM. The interplay between obesity, PC and T2DM is complex.

Topics: Aged; Body Mass Index; C-Peptide; Case-Control Studies; Causality; Diabetes Mellitus, Type 2; Educational Status; Female; Glycated Hemoglobin; Humans; Male; Mediation Analysis; Middle Aged; Obesity; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; Risk Factors; Sex Factors; Smoking

Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity-endometrial cancer link in postmenopausal women.. We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis.. The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5-<25 kg/m. Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight.. If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.

Topics: Adiponectin; Adiposity; Biomarkers; Body Mass Index; C-Peptide; Case-Control Studies; Causality; Endometrial Neoplasms; Estrogens; Female; Humans; Obesity; Odds Ratio; Postmenopause; Prospective Studies; Risk Factors

Recent studies have suggested C-X-C motif chemokine ligand 14 (CXCL14), secreted from adipose tissue, to play an important role in the pathogenesis of metabolic syndrome. However, the clinical significance of CXCL14 in humans has not been elucidated. This study aimed to assess correlations between serum CXCL14 levels and clinical parameters in patients with type 2 diabetes mellitus.. In total, 176 individuals with type 2 diabetes mellitus were recruited. Serum CXCL14 concentrations were determined by enzyme-linked immunosorbent assay. We examined the associations of serum CXCL14 levels with laboratory values, abdominal computed tomography image information, surrogate markers used for evaluating the pathological states of diabetes, obesity and atherosclerosis.. Serum CXCL14 levels correlated positively with body mass index, waist circumference, subcutaneous and visceral fat areas, and serum alanine transaminase, uric acid, total cholesterol, low-density lipoprotein cholesterol, triglycerides and C-peptide (CPR) levels. In contrast, CXCL14 levels correlated inversely with age, pulse wave velocity and serum adiponectin levels. Multiple linear regression analysis showed serum levels of CPR (β = 0.227, P = 0.038) and the fatty liver index (β = 0.205, P = 0.049) to be the only parameters showing independent statistically significant associations with serum CXCL14 levels.. Serum CXCL14 levels were independently associated with serum CPR and fatty liver index in patients with type 2 diabetes mellitus. In these patients, a high serum CPR concentration might reflect insulin resistance rather than β-cell function, because CXCL14 showed simple correlations with obesity-related parameters. Collectively, these data suggested that serum CXCL14 levels in type 2 diabetes patients might be useful predictors of elevated serum CPR and hepatic steatosis.

Topics: Adiponectin; Age Factors; Aged; Alanine Transaminase; Biomarkers; Body Mass Index; C-Peptide; Chemokines, CXC; Cholesterol; Diabetes Mellitus, Type 2; Fatty Liver; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Linear Models; Lipoproteins, LDL; Liver Function Tests; Male; Middle Aged; Obesity; Pulse Wave Analysis; Triglycerides; Uric Acid; Waist Circumference

The influence of type 2 diabetes mellitus (T2D) duration on cancer incidence remains poorly understood.. We prospectively followed for cancer incidence 113 429 women in the Nurses' Health Study (1978-2014) and 45 604 men in the Health Professionals Follow-up Study (1988-2014) who were free of diabetes and cancer at baseline. Cancer incidences were ascertained by review of medical records.. In the multivariable-adjusted model incident, T2D was associated with higher risk of cancers in the colorectum, lung, pancreas, esophagus, liver, thyroid, breast, and endometrium. The pooled hazard ratios (HRs) ranged from 1.21 (95% confidence interval [CI] = 1.06 to 1.38) for colorectal cancer to 3.39 (95% CI = 2.24 to 5.12) for liver cancer. For both composite cancer outcomes and individual cancers, the elevated risks did not further increase after 8 years of T2D duration. The hazard ratio for total cancer was 1.28 (95% CI = 1.17 to 1.40) for T2D duration of 4.1-6.0 years, 1.37 (95% CI = 1.25 to 1.50) for 6.1-8.0 years, 1.21 (95% CI = 1.09 to 1.35) for 8.1-10.0 years, and 1.04 (95% CI = 0.95 to 1.14) after 15.0 years. In a cross-sectional analysis, a higher level of plasma C-peptide was found among participants with prevalent T2D of up to 8 years than those without T2D, whereas a higher level of HbA1c was found for those with prevalent T2D of up to 15 years.. Incident T2D was associated with higher cancer risk, which peaked at approximately 8 years after diabetes diagnosis. Similar duration-dependent pattern was observed for plasma C-peptide. Our findings support a role of hyperinsulinemia in cancer development.

Topics: Adult; Aged; C-Peptide; Cohort Studies; Confidence Intervals; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Health Surveys; Humans; Incidence; Life Style; Male; Middle Aged; Neoplasms; Obesity; Proportional Hazards Models; Prospective Studies; Risk Factors; Time Factors; United States

24-h average (IC) plasma concentrations of cortisol and growth hormone are lower in obese youth and adults without Type 2 diabetes (T2D) compared to lean subjects. Here we examined IC-cortisol and IC-growth hormone levels in obese youth with and without T2D.. We pooled ½-hourly samples from 20 to 24-hour sampling to create an IC for cortisol, cortisone, C-peptide, insulin, growth hormone and cortisol-binding-globulin in obese African-American youth with (n = 8) and without T2D (N = 9). Analytes were assayed by standard methods.. The groups were similar in age and sex, all participants had BMI% ≥94. T2D patients had slightly lower BMI z-score (2.25 ± 0.36 versus 2.58 ± 0.16, p = 0.0429). IC-cortisol (5.70 ± 1.8 μg/dl vs 4.18 ± 1.07 μg/dl, p = 0.0481) was higher and IC-C-peptide (2.33 ± 0.89 ng/ml vs 4.36 ± 1.12 ng/ml, p = 0.001) lower in T2D. There were no differences in cortisone/cortisol or for other analytes between groups. IC-cortisol was correlated with IC-cortisone (r = 0.46, p = 0.0471) but not with ICs of insulin, C-peptide, cortisol-binding-globulin, or growth hormone.. IC-cortisol levels are higher and IC-C-peptide lower in obese African-American youth with T2D. Higher levels of IC-cortisol in obese youth with T2D may indicate a change in hypothalamic-pituitary-adrenal regulation which may exacerbate hyperglycemia and other metabolic complications of obesity.

Topics: Adolescent; Black or African American; C-Peptide; Cortisone; Diabetes Mellitus, Type 2; Female; Globulins; Growth Hormone; Humans; Hydrocortisone; Insulin; Male; Obesity

One of the therapeutic approaches in the treatment of obesity is the use of histamine H. Histamine ligands were selected based on the preliminary studies which included determination of intrinsic activity and selected pharmacokinetic parameters. Female Wistar rats were fed palatable feed for 28 days and simultaneously the tested compounds were administered intraperitoneally at a dose of 10 mg/kg b.w./day. Rats' weight was evaluated daily and calories intake was evaluated once per week. At the end of experiment insulin and glucose tolerance tests was performed. Plasma levels of cholesterol, triglycerides, leptin, insulin, glucose, C-peptide and CRP were also determined. In order to rule out false-positive results the influence of tested compounds on spontaneous activity of rats was monitored.. Animals fed palatable feed and treated with KSK-61 or KSK-63 compounds showed the slowest weight gain which was comparable to the one observed in control animals. Both compounds with the highest pharmacological activity have also similar pharmacokinetic properties with quite long half-life and high volume of distribution indicating that they can freely cross most biological barriers. Some compounds, especially KSK-63, compensated for metabolic disorders.. The presented study proves that search among the active histamine H

Topics: Adipose Tissue; Animals; Body Weight; C-Peptide; Carrier Proteins; Cholesterol; Energy Intake; Feeding Behavior; Female; Glucose Tolerance Test; Histamine Agonists; Histamine Antagonists; Injections, Intraperitoneal; Insulin; Insulin Resistance; Leptin; Ligands; Metformin; Models, Animal; Obesity; Rats, Wistar; Receptors, Histamine H3; Triglycerides

The quantification of peptide hormones by means of liquid chromatography (LC) coupled to mass spectrometry (MS) or other techniques (e.g. immunoassays) has been a challenging task in modern analytical chemistry. Especially for insulin, its synthetic analogs, and C-peptide, reliable determinations are urgently needed due to their diagnostic value in the management of diabetes and insulin resistance and because of the illicit use of insulin as a performance-enhancing agent in professional sports or as an effective toxin in forensic toxicology. The concomitant measurement of C-peptide and insulin offers an established tool for the diagnostic workup of hypoglycemia (endogenous vs. exogenous hyperinsulinemia), characterizing hepatic insulin clearance, and the assessment of beta-cell function (insulin secretion). Thus, the present approach offers the possibility to determine human insulin and its synthetic analogs (lispro, glulisine, aspart, glargine metabolite, degludec, detemir, porcine, and bovine) and C-peptide simultaneously after sample preparation utilizing protein precipitation and a mixed-mode cation-exchange solid-phase extraction, and subsequent detection by LC-high resolution MS. The method was fully validated regarding the following parameters: specificity, limit of detection (0.2 ng/mL), limit of quantification (0.6 ng/mL), recovery (40-90%), accuracy (78-128%), linearity, precision (< 21%), carry over, robustness, and matrix effects. The proof-of-concept was shown by analyzing authentic plasma samples from adults with class II obesity and prediabetes collected in the course of an oral glucose tolerance test. All sample preparation steps were controlled by two stable isotope-labeled internal standards, namely [[

Topics: C-Peptide; Chromatography, Liquid; Female; Humans; Insulin; Limit of Detection; Male; Obesity; Sensitivity and Specificity; Solid Phase Extraction; Tandem Mass Spectrometry; Young Adult

We aimed to determine the immediacy of exercise intervention on liver-specific metabolic processes in nonalcoholic fatty liver disease.. We undertook a short-term (7-d) exercise training study (60 min·d treadmill walking at 80%-85% of maximal heart rate) in obese adults (N = 13, 58 ± 3 yr, 34.3 ± 1.1 kg·m, >5% hepatic lipid by H-magnetic resonance spectroscopy). Insulin sensitivity index was estimated by oral glucose tolerance test using the Soonthorpun model. Hepatic insulin extraction (HIE) was calculated as the molar difference in area under the curve (AUC) for insulin and C-peptide (HIE = 1 - (AUCInsulin/AUCC-Pep)).. The increases in HIE, V˙O2max, and insulin sensitivity index after the intervention were 9.8%, 9.8%, and 34%, respectively (all, P < 0.05). Basal fat oxidation increased (pre: 47 ± 6 mg·min vs post: 65 ± 6 mg·min, P < 0.05) and carbohydrate oxidation decreased (pre: 160 ± 20 mg·min vs post: 112 ± 15 mg·min, P < 0.05) with exercise training. After the intervention, HIE correlated positively with adiponectin (r = 0.56, P < 0.05) and negatively with TNF-α (r = -0.78, P < 0.001).. By increasing HIE along with peripheral insulin sensitivity, aerobic exercise training rapidly reverses some of the underlying physiological mechanisms associated with nonalcoholic fatty liver disease, in a weight loss-independent manner. This reversal could potentially act through adipokine-related pathways.

Topics: Blood Glucose; C-Peptide; Carbohydrate Metabolism; Exercise; Glucagon-Like Peptide 1; Heart Rate; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Liver; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Oxygen Consumption

Circulating follistatin (Fst) binds activin A and thereby regulates biological functions such as muscle growth and β-cell survival. However, Fst and activin A's implication in metabolic regulation is unclear.. To investigate circulating Fst and activin A in obesity and type 2 diabetes (T2D) and determine their association with metabolic parameters. Further, to examine regulation of Fst and activin A by insulin and the influence of obesity and T2D hereon.. Plasma Fst and activin A levels were analyzed in obese T2D patients (N = 10) closely matched to glucose-tolerant lean (N = 12) and obese (N = 10) individuals in the fasted state and following a 4-h hyperinsulinemic-euglycemic clamp (40 mU·m-2·min-1) combined with indirect calorimetry.. Circulating Fst was ~30% higher in patients with T2D compared with both lean and obese nondiabetic individuals (P < .001), while plasma activin A was unaltered. In the total cohort, fasting plasma Fst correlated positively with fasting plasma glucose, serum insulin and C-peptide levels, homeostasis model assessment of insulin resistance, and hepatic and adipose tissue insulin resistance after adjusting for age, gender and group (all r > 0.47; P < .05). However, in the individual groups these correlations only achieved significance in patients with T2D (not plasma glucose). Acute hyperinsulinemia at euglycemia reduced circulating Fst by ~30% (P < .001) and this response was intact in patients with T2D. Insulin inhibited FST expression in human hepatocytes after 2 h and even further after 48 h.. Elevated circulating Fst, but not activin A, is strongly associated with measures of insulin resistance in patients with T2D. However, the ability of insulin to suppress circulating Fst is preserved in T2D.

Topics: Activins; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Fasting; Female; Follistatin; Hep G2 Cells; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity

The relationship between disturbances in glucose homeostasis and heart failure (HF) progression is bidirectional. However, the mechanisms by which HF intrinsically impairs glucose homeostasis remain unknown. The present study tested the hypothesis that the bioavailability of intact glucagon-like peptide-1 (GLP-1) is affected in HF, possibly contributing to disturbed glucose homeostasis. Serum concentrations of total and intact GLP-1 and insulin were measured after an overnight fast and 15 min after the ingestion of a mixed breakfast meal in 49 non-diabetic patients with severe HF and 40 healthy control subjects. Similarly, fasting and postprandial serum concentrations of these hormones were determined in sham-operated rats, and rats with HF treated with an inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP4), vildagliptin, or vehicle for 4 weeks. We found that HF patients displayed a much lower increase in postprandial intact and total GLP-1 levels than controls. The increase in postprandial intact GLP-1 in HF patients correlated negatively with serum brain natriuretic peptide levels and DPP4 activity and positively with the glomerular filtration rate. Likewise, the postprandial increases in both intact and total GLP-1 were blunted in HF rats and were restored by DPP4 inhibition. Additionally, vehicle-treated HF rats displayed glucose intolerance and hyperinsulinemia, whereas normal glucose homeostasis was observed in vildagliptin-treated HF rats. We conclude that the postprandial increase in GLP-1 is blunted in non-diabetic HF. Impaired GLP-1 bioavailability after meal intake correlates with poor prognostic factors and may contribute to the establishment of a vicious cycle between glucose disturbance and HF development and progression.

Topics: Aged; Animals; Blood Glucose; C-Peptide; Female; Glucagon-Like Peptide 1; Glucose Intolerance; Heart Failure; Humans; Insulin; Male; Middle Aged; Obesity; Peptide Fragments; Postprandial Period; Rats, Wistar

To examine whether proinflammatory and hyperinsulinemic diets are associated with increased risk of type 2 diabetes.. We prospectively followed 74,767 women from the Nurses' Health Study (1984-2016), 90,786 women from the Nurses' Health Study II (1989-2017), and 39,442 men from the Health Professionals Follow-up Study (1986-2016). Using repeated measures of food-frequency questionnaires, we calculated empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores, which are food-based indices that characterize dietary inflammatory or insulinemic potential based on circulating biomarkers of inflammation or C-peptide. Diagnoses of type 2 diabetes were confirmed by validated supplementary questionnaires.. We documented 19,666 incident type 2 diabetes cases over 4.9 million person-years of follow-up. In the pooled multivariable-adjusted analyses, individuals in the highest EDIP or EDIH quintile had 3.11 times (95% CI 2.96-3.27) and 3.40 times (95% CI 3.23-3.58) higher type 2 diabetes risk, respectively, compared with those in the lowest quintile. Additional adjustment for BMI attenuated the associations (hazard ratio 1.95 [95% CI 1.85-2.05] for EDIP and hazard ratio 1.87 [95% CI 1.78-1.98] for EDIH), suggesting adiposity partly mediates the observed associations. Moreover, individuals in both highest EDIP and EDIH quintiles had 2.34 times higher type 2 diabetes risk (95% CI 2.17-2.52), compared with those in both lowest quintiles, after adjustment for BMI.. Higher dietary inflammatory and insulinemic potential were associated with increased type 2 diabetes incidence. Findings suggest that inflammation and hyperinsulinemia are potential mechanisms linking dietary patterns and type 2 diabetes development.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Peptide; Diabetes Mellitus, Type 2; Diet; Female; Follow-Up Studies; Food; Humans; Hyperinsulinism; Incidence; Inflammation; Male; Middle Aged; Nurses; Obesity; Proportional Hazards Models; Prospective Studies; Risk; Self Report; United States

Vitamin D3 (vit. D3) deficiency is considered as one of the main factors involved in the development of type 2 diabetes (T2D). We assessed insulin resistance (IR), β-cell functional activity and metabolic profile according to 25(OH) vit. D3 status in patients with T2D.. The study included 109 patients with T2D, divided in 3 groups: group 1 (N.=11) with normal levels of vit. D3 (>30 ng/mL); group 2 (N.=38) with vit. D3 insufficiency (21-29 ng/mL); and group 3 (N.=60) with vit. D3 deficiency (<20 ng/mL). IR and β-cell functional activity were assessed as change in C-peptide concentration and homeostasis model assessment-estimated (HOMA) β-cell function which was calculated using HOMA2 calculator.. Patients with vit. D3 deficiency presented significantly higher C-peptide concentration compared to other groups. HOMA2 (3.29±1.89 vs. 2.12±0.71; P=0.049) and hemoglobin (H8b)A1c (9.11±1.63 vs. 7.75±1.06; P=0.016) levels changed significantly only in patients with vit. D3 deficiency compared to diabetics with normal vit. D3 levels. Furthermore, in univariate Pearson's correlation analysis, we observed significant association between vit. D3 levels and C-peptide, insulin sensitivity, HOMA2, triglyceride-glucose index, HbA1c and Body Mass Index, only in the vit. D3 deficiency group. In multivariate logistic regression analysis, poor glycemic control, as defined by HbA1c levels, was independent from metformin use while high density lipoprotein-cholesterol levels were associated with vit. D3 deficiency.. Our study demonstrated that vit. D3 deficiency in patients with T2D was associated with more severe IR, poor glycemic control and obesity compared to normal status or vit. D3 insufficiency.

Topics: Adolescent; Adult; Aged; Body Mass Index; C-Peptide; Cholecalciferol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Ergocalciferols; Female; Glycemic Control; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Middle Aged; Obesity; Vitamin D Deficiency; Young Adult

The concept of metabolic obesity phenotypes has been proposed, but its relevance to metabolic features is unclear.. To determine a new definition of metabolic obesity phenotype, investigate the characteristics of expressing clustered normal and abnormal metabolic parameters, and analyze factors associated with metabolic abnormalities.. Characteristics of 600 patients were analyzed. The definition of metabolic obesity phenotype includes elevated blood pressure, glucose, lipid, and uric acid levels and abnormal lipoprotein levels. Independent sample t test and a general linear model with repeated measures were applied to investigate the differences in metabolic parameters.. A total of 108 (18.0%) participants were obese yet metabolically healthy, whereas 492 (82.0%) were obese and metabolically unhealthy. Body weight at baseline was significantly higher in metabolically unhealthy phenotype (P < 0.001). For non-phasic oral glucose tolerance test (OGTT) curve shape, 100% glucose, 100% C-peptide, and 95.8% insulin curves were found in the metabolically unhealthy group. Men had an increased risk for elevated lipid level than women (OR = 1.83, 1.21-2.77). Individuals with class II/III obesity had an increased risk for elevated blood pressure, glucose, and UA levels than did those with class I obesity (OR = 2.22, 1.43-3.44; OR = 1.73, 1.11-2.68; OR = 3.61, 2.29-5.69, respectively).. Approximately one-fifth of individuals with obesity had a metabolically healthy phenotype, and nearly one-third of individuals with class III obesity had this phenotype. Non-phasic OGTT curve shape is a meaningful predictive factor of metabolically unhealthy phenotype before bariatric surgery. Male sex and class II/III obesity are risk factors associated with specific metabolic abnormalities.

Topics: Adolescent; Adult; Aged; Bariatric Surgery; Biomarkers; C-Peptide; Cohort Studies; Cross-Sectional Studies; Female; Humans; Hypertension; Insulin; Linear Models; Lipid Metabolism; Male; Middle Aged; Obesity; Phenotype; Risk Factors; Uric Acid; Young Adult

Newborn adiposity is associated with childhood obesity. Cord blood metabolomics is one approach that can be used to understand early-life contributors to adiposity and insulin resistance.. To determine the association of cord blood metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of newborns.. Cross-sectional, observational study.. Hyperglycemia and Adverse Pregnancy Outcome study.. One thousand six hundred multiethnic mother-newborn pairs.. Cord blood C-peptide, birthweight, and newborn sum of skinfolds.. Meta-analyses across four ancestry groups (Afro-Caribbean, Northern European, Thai, and Mexican American) demonstrated significant associations of cord blood metabolites with cord blood C-peptide, birthweight, and newborn sum of skinfolds. Several metabolites, including branched-chain amino acids (BCAAs), medium- and long-chain acylcarnitines, nonesterified fatty acids, and triglycerides were negatively associated with cord C-peptide but positively associated with birthweight and/or sum of skinfolds. 1,5-Anhydroglucitol, an inverse marker of recent maternal glycemia, was significantly inversely associated with birthweight and sum of skinfolds. Network analyses revealed groups of interrelated amino acid, acylcarnitine, and fatty acid metabolites associated with all three newborn outcomes.. Cord blood metabolites are associated with newborn size and cord blood C-peptide levels after adjustment for maternal body mass index and glucose during pregnancy. Negative associations of metabolites with C-peptide at birth were observed. 1,5-Anhydroglucitol appears to be a marker of adiposity in newborns. BCAAs were individually associated with birthweight and demonstrated possible associations with newborn adiposity in network analyses.

Topics: Adiposity; Adult; Anthropometry; Biomarkers; Birth Weight; C-Peptide; Cross-Sectional Studies; Ethnicity; Female; Fetal Blood; Glucose Tolerance Test; Humans; Hyperglycemia; Hyperinsulinism; Infant, Newborn; Male; Metabolomics; Native Hawaiian or Other Pacific Islander; Obesity; Pregnancy; Pregnancy Outcome; Severity of Illness Index

Adolescence is the most critical phase of human growth that radically alters physiology of the body and wherein any inconsistency can lead to serious health consequences in adulthood. The timing and pace at which various developmental events occur during adolescence is highly diverse and thus results in a drastic change in blood biochemistry. Monitoring the physiological levels of various biochemical measures in ample number of individuals during adolescence can call up for an early intervention in managing metabolic diseases in adulthood. Today, only a couple of studies in different populations have investigated blood biochemistry in a small number of adolescents however, there is no comprehensive biochemical data available worldwide. In view, we performed a cross-sectional study in a sizeable group of 7,618 Indian adolescents (3,333 boys and 4,285 girls) aged between 11-17 years to inspect the distribution of values of common biochemical parameters that generally prevails during adolescence and we observed that various parameters considerably follow the reported values from different populations being 3.56-6.49mmol/L (fasting glucose), 10.60-199.48pmol/L (insulin), 0.21-3.22nmol/L (C-peptide), 3.85-6.25% (HbA1c), 2.49-5.54mmol/L (total cholesterol), 1.16-3.69mmol/L (LDL), 0.78-1.85mmol/L (HDL), 0.33-2.24mmol/L (triglycerides), 3.56-11.45mmol/L (urea), 130.01-440.15μmol/L (uric acid) and 22.99-74.28μmol/L (creatinine). Barring LDL and triglycerides, all parameters differed significantly between boys and girls (p< 0.001). Highest difference was seen for uric acid (p = 1.3 x10-187) followed by C-peptide (p = 6.6 x10-89). Across all ages during adolescence, glycemic and nitrogen metabolites parameters varied markedly with gender. Amongst lipid parameters, only HDL levels were found to be significantly associated with gender following puberty (p< 0.001). All parameters except urea, differed considerably in obese and lean adolescents (p< 0.0001). The present study asserts that age, sex and BMI are the essential contributors to variability in blood biochemistry during adolescence. Our composite data on common blood biochemical measures will benefit future endeavors to define reference intervals in adolescents especially when the global availability is scarce.

Topics: Adolescent; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Child; Cross-Sectional Studies; Fasting; Female; Humans; Insulin; Lipids; Male; Obesity; Sex Factors; Sexual Maturation

Alterations in glucose metabolism that lead to the development of metabolic and cardiovascular disease may begin already in childhood.. This study aims to generate pediatric age and sex-specific reference values for fasting concentrations of glucose, hemoglobin A1c (HbA1c), insulin, C-peptide, and homeostasis model assessment: insulin resistance (HOMA-IR) in Danish/North-European white children and adolescents from a population-based cohort and to compare values from children and adolescents with overweight/obesity with this reference.. The population- and obesity clinic-based cohorts consisted of 2451 and 1935 children and adolescents between 6 and 18 years of age. Anthropometric measurements and blood samples were obtained and percentile curves were calculated.. In the population-based cohort, glucose, insulin, and HOMA-IR values increased before the expected onset of puberty (P < .05). Thereafter, all variables decreased in girls (P < .05) and HbA1c decreased in boys (P < .05). Concentrations of all measured markers of glucose metabolism were higher in the obesity clinic-based cohort than the population-based cohort (both sexes P < .001). Specifically, insulin and HOMA-IR continued to increase to 18 years in the clinic-based cohort, particularly among boys.. Fasting glucose, insulin, and HOMA-IR change during childhood, making pediatric reference values essential for timely identification of derangements in glucose metabolism. Children and adolescents with obesity exhibit increased concentrations of these biomarkers.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Cohort Studies; Female; Humans; Insulin; Male; Obesity; Reference Values

Metabolic procedures provide better outcomes for obese patients with type 2 diabetes mellitus. Our aim was to compare the glycemic regulation in patients that have undergone the laparoscopic ileal interposition with diverted sleeve gastrectomy (II-DSG), laparoscopic transit bipartition with sleeve gastrectomy (TB-SG), and laparoscopic sleeve gastrectomy (LSG) throughout a 12-month follow-up period retrospectively.. This study considered patients with T2DM who underwent metabolic procedures. The postoperative changes in the glucose, C-peptide, HbA1c, HOMA-IR, insulin, cholesterol, body mass index, and total weight loss (TWL) were compared retrospectively. The intended outcome was to reach a long lasting fasting blood glucose (FBG) <126 mg/dl. A multivariate regression analysis was applied to define the predictive markers in glucose regulation.. Our results showed that II-DSG and TB-SG ensured significant regression rates during the follow-up period. Since the TB-SG achieved these outcomes by finite anastomoses and intervening segments, it was considered to be a superior procedure compared to II-DSG and LSG procedures.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastrectomy; Humans; Ileum; Insulin; Laparoscopy; Male; Middle Aged; Obesity; Postoperative Period; Retrospective Studies; Treatment Outcome; Weight Loss

The aim of this prospective, observational study was to investigate the impact of gestational weight gain (GWG) among euglycaemic obese pregnant women on maternal and foetal metabolic parameters and neonatal outcome. Total GWG was recorded for 101 obese, non-diabetic women with a singleton pregnancy. At 28 weeks of gestation, fasting maternal blood samples were analysed for glucose, insulin, c-peptide and lipids. Cord bloods were collected at delivery for analysis of glucose, c-peptide and lipids. GWG (mean ± SD =10.9 ± 5.5 kg) was greatest among those of younger age and lower body mass index and 58% of women exceeded the Institute of Medicine GWG recommendations of 5-9 kg for obese pregnancy. GWG was significantly positively associated with increased risk of birthweight >4 kg, cord c-peptide levels and inversely associated with cord total cholesterol. This study identified that higher GWG in obese pregnancy may increase the risk of macrosomia and neonatal hyperinsulinaemia, within a euglycaemic maternal cohort. Impact statement Excess gestational weight gain (GWG) and maternal obesity frequently co-occur with adverse consequences for maternal and neonatal health; however, little is known of the underlying biological pathways which may be affected to contribute to adverse outcomes. Greater understanding of the biological mechanisms involved may help guide future studies to develop targeted interventions for more effective clinical outcomes. This study identified that higher GWG among obese pregnant women resulted in foetal hyperinsulinaemia even in the absence of maternal hyperglycaemia, potentially representing a biological pathway for larger birthweight babies. These results may highlight the need for more intensive dietary and lifestyle interventions among obese women who would not normally receive additional counselling beyond standard antenatal care if not diagnosed with glucose intolerance in pregnancy.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Fasting; Female; Fetal Blood; Humans; Insulin; Lipids; Obesity; Pregnancy; Pregnancy Complications; Prospective Studies; Weight Gain

The purpose of this study is to investigate placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels in maternal obesity and associations between placental ghrelin expression, cord blood ghrelin levels and maternal and infant variables.. Placental ghrelin and leptin expression were analyzed by RT-PCR in 32 severely obese and 32 matched normal-weight women. Cord blood ghrelin, adiponectin, leptin, and C-peptide concentrations were analyzed by ELISA.. Neither ghrelin nor leptin expression and neither cord blood ghrelin nor adiponectin levels differed between the groups. Placental ghrelin expression was associated with BMI at delivery in the obese women (r = 0.424, p = .016) and in the infants born to normal-weight women with their weight z-scores at six (r = -0.642, p = .010), nine (r = -0.441, p = .015), and 12 months of age (r = -0.402, p = .028).. Placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels do not seem to be altered in severe maternal obesity. Placenta-derived ghrelin may influence the infants' postnatal weight gain, but possibly only when the mother has normal weight.

Topics: Adiponectin; Adult; C-Peptide; Case-Control Studies; Female; Fetal Blood; Ghrelin; Humans; Infant, Newborn; Leptin; Male; Obesity; Placenta; Pregnancy; Pregnancy Complications; Young Adult

Gamma-glutamyltranspeptidase (GGT) levels are an independent risk marker for the development of type 2 diabetes (T2DM). We investigated the relationship between the newly identified serum GGT fractions and glucose metabolism in obese subjects before and after bariatric surgery.. Twenty-nine T2DM subjects, wait-listed for Roux-en-Y gastric bypass (RYGB; n = 21) or laparoscopic sleeve gastrectomy (LSG; n = 8), received a 5-h mixed meal test before (T0), 15 days (T15), and 1 year after surgery (T365). Insulin sensitivity was assessed by the OGIS index and β-cell function by C-peptide analysis; fractional GGT (b-, s-, m-, and f-GGT) analysis was performed by gel-filtration chromatography.. At T15, total GGT activity decreased by 40% after LSG (p = 0.007) but remained unchanged after RYGB. At T365, all patients showed a reduction in total GGT, in particular b-GGT (≥ 60%) and m-GGT (≥ 50%). In patients with biopsy-proven steatohepatitis (n = 10), total, b-, s-, and m-GGT fractions at T0 were significantly higher than in patients with low-grade steatosis (p = 0.016, 0.0003, and 0.005, respectively); at T365, there was a significant fall in total GGT as well as in each fraction in both groups. In a multiple regression model, b-GGT was the only fraction related to insulin sensitivity (p = 0.016; β coeff. = - 14.0) independently of BMI, fasting glucose, and triglycerides.. While GGT activity is generally associated with impaired glucose metabolism, fractional GGT analysis showed that the b-GGT fraction specifically and independently tracks with insulin resistance.

Topics: Adult; Aged; Bariatric Surgery; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Fatty Liver; Female; gamma-Glutamyltransferase; Gastrectomy; Gastric Bypass; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Obesity, Morbid; Triglycerides

There is growing evidence that fruit polyphenols exert beneficial effects on the metabolic syndrome, but the underlying mechanisms remain poorly understood. In the present study, we aimed to analyse the effects of polyphenolic extracts from five types of Arctic berries in a model of diet-induced obesity.. Male C57BL/6 J mice were fed a high-fat/high-sucrose (HFHS) diet and orally treated with extracts of bog blueberry (BBE), cloudberry (CLE), crowberry (CRE), alpine bearberry (ABE), lingonberry (LGE) or vehicle (HFHS) for 8 weeks. An additional group of standard-chow-fed, vehicle-treated mice was included as a reference control for diet-induced obesity. OGTTs and insulin tolerance tests were conducted, and both plasma insulin and C-peptide were assessed throughout the OGTT. Quantitative PCR, western blot analysis and ELISAs were used to assess enterohepatic immunometabolic features. Faecal DNA was extracted and 16S rRNA gene-based analysis was used to profile the gut microbiota.. Treatment with CLE, ABE and LGE, but not with BBE or CRE, prevented both fasting hyperinsulinaemia (mean ± SEM [pmol/l]: chow 67.2 ± 12.3, HFHS 153.9 ± 19.3, BBE 114.4 ± 14.3, CLE 82.5 ± 13.0, CRE 152.3 ± 24.4, ABE 90.6 ± 18.0, LGE 95.4 ± 10.5) and postprandial hyperinsulinaemia (mean ± SEM AUC [pmol/l × min]: chow 14.3 ± 1.4, HFHS 31.4 ± 3.1, BBE 27.2 ± 4.0, CLE 17.7 ± 2.2, CRE 32.6 ± 6.3, ABE 22.7 ± 18.0, LGE 23.9 ± 2.5). None of the berry extracts affected C-peptide levels or body weight gain. Levels of hepatic serine phosphorylated Akt were 1.6-, 1.5- and 1.2-fold higher with CLE, ABE and LGE treatment, respectively, and hepatic carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 tyrosine phosphorylation was 0.6-, 0.7- and 0.9-fold increased in these mice vs vehicle-treated, HFHS-fed mice. These changes were associated with reduced liver triacylglycerol deposition, lower circulating endotoxins, alleviated hepatic and intestinal inflammation, and major gut microbial alterations (e.g. bloom of Akkermansia muciniphila, Turicibacter and Oscillibacter) in CLE-, ABE- and LGE-treated mice.. Our findings reveal novel mechanisms by which polyphenolic extracts from ABE, LGE and especially CLE target the gut-liver axis to protect diet-induced obese mice against metabolic endotoxaemia, insulin resistance and hepatic steatosis, which importantly improves hepatic insulin clearance. These results support the potential benefits of these Arctic berries and their integration into health programmes to help attenuate obesity-related chronic inflammation and metabolic disorders.. All raw sequences have been deposited in the public European Nucleotide Archive server under accession number PRJEB19783 ( https://www.ebi.ac.uk/ena/data/view/PRJEB19783 ).

Topics: Animals; C-Peptide; Diet, High-Fat; Endotoxemia; Fatty Liver; Fruit; Glucose; Homeostasis; Insulin; Insulin Resistance; Intestines; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Plant Extracts; RNA, Ribosomal, 16S; Time Factors

Soda intake is associated with an increased risk of cardiovascular disease. Consumption of diet sodas, often considered healthy alternatives to sodas, could also increase the likelihood of cardiovascular outcomes.. This study aims to evaluate the relation between soda and diet soda and biomarkers of cardiovascular risk.. We conducted a cross-sectional analysis among 825 Mexican women free of diabetes, cardiovascular disease, and cancer, and for whom serum concentrations of C-reactive protein (CRP), C-peptide, adiponectin, and leptin were available. Mean ± SD age was 45.9 ± 6.6 y, the majority of women were premenopausal (60.4%), and the prevalence of obesity was 35%. We estimated the adjusted percentage differences in biomarkers and 95% CIs by performing multiple linear regression models comparing categories of consumption for soda and diet soda adjusting for age, family history of heart disease, menopause, menopausal hormone therapy, socioeconomic status, region, smoking, physical activity, alcohol intake, and dietary patterns.. In the entire study sample we observed a 50% higher serum CRP concentration in women in the highest soda intake quartile (median intake: 202.9 mL/d, IQR: 101.4, 304.3 mL/d) compared to those in the lowest (median intake: 11.8 mL/d, IQR: 0.0, 152.1 mL/d). After stratification by menopausal status, results remained significant only for premenopausal women. Premenopausal women in the highest quartile of soda intake had 56% higher CRP concentration relative to women in the lowest quartile. We observed no significant association with the other biomarkers. After further adjustment for body mass index, a potential mediator, results remained significant only for CRP. Diet soda consumption was not associated with any of the biomarkers.. Consumption of soda was associated with adverse levels in a biomarker of inflammation and cardiovascular risk, serum CRP, in Mexican women. These results add to the accumulating evidence on soda and cardiovascular risk. More research is necessary to understand the potential impact of artificially sweetened sodas.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Peptide; C-Reactive Protein; Carbonated Beverages; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Exercise; Female; Humans; Inflammation; Leptin; Mexico; Middle Aged; Nutritive Sweeteners; Obesity; Risk Factors; Socioeconomic Factors

Obesity is one of the major causes for development of T2DM. Metabolic surgery has been proved to be a successful and cost-effective treatment modality for managing the patients with obesity and T2DM. Many scoring systems and models have been described in literature to predict the outcome of T2DM after metabolic surgery. The aim of this study is to compare the efficacy of Diarem, DRS, and ABCD score in predicting the T2DM remission.. A total number of 102 diabetic patients, who underwent LMGB/LOAGB, were selected for this study. A retrospective analysis of the three scoring systems when applied to these patients and their predictive abilities were analyzed.. At 1 year after surgery, 72 (70.59%) patients achieved remission of T2DM. Though the pairwise comparisons between AUC on ROC analysis of ABCD, Diarem, and DRS scores does not show statistically significant difference between them, Diarem score has the maximum relative area under ROC curves. By multivariate analysis, it was found that factors significantly associated with T2DM remission were duration of T2DM, C-peptide, and Pre-Op HbA1c.. Among the three scoring systems, though DiaRem score has the best sensitivity and specificity and maximum AUC, no statistically significant difference was found in their diabetes remission predicting abilities. A shorter duration of T2DM, a lower HbA1C, and higher levels of C-peptide were significantly associated with a higher chance of T2DM remission.

Topics: Adolescent; Adult; Aged; Bariatric Surgery; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glycated Hemoglobin; Humans; Male; Middle Aged; Obesity; Obesity, Morbid; Prognosis; Protein Precursors; Remission Induction; Retrospective Studies; ROC Curve; Time Factors; Treatment Outcome; Young Adult

The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (>70 %) energy restriction (ER) interspersed with normal eating. Studies to date comparing IER to continuous energy restriction (CER) have predominantly measured fasting indices of cardiometabolic risk. This study aimed to compare the effects of IER and CER on postprandial glucose and lipid metabolism following matched weight loss. In all, twenty-seven (thirteen male) overweight/obese participants (46 (sem 3) years, 30·1 (sem 1·0) kg/m2) who were randomised to either an IER intervention (2638 kJ for 2 d/week with an overall ER of 22 (sem 0·3) %, n 15) or a CER intervention (2510 kJ below requirements with overall ER of 23 (sem 0·8) %) completed the study. Postprandial responses to a test meal (over 360 min) and changes in anthropometry (fat mass, fat-free mass, circumferences) were assessed at baseline and upon attainment of 5 % weight loss, following a 7-d period of weight stabilisation. The study found no statistically significant difference in the time to attain a 5 % weight loss between groups (median 59 d (interquartile range (IQR) 41-80) and 73 d (IQR 48-128), respectively, P=0·246), or in body composition (P≥0·437). For postprandial measures, neither diet significantly altered glycaemia (P=0·266), whereas insulinaemia was reduced comparatively (P=0·903). The reduction in C-peptide tended (P=0·057) to be greater following IER (309 128 (sem23 268) to 247781 (sem20 709) pmol×360 min/l) v. CER (297 204 (sem25 112) to 301 655 (sem32 714) pmol×360 min/l). The relative reduction in TAG responses was greater (P=0·045) following IER (106 (sem30) to 68 (sem 15) mmol×360 min/l) compared with CER (117 (sem 43) to 130 (sem 31) mmol×360 min/l). In conclusion, these preliminary findings highlight underlying differences between IER and CER, including a superiority of IER in reducing postprandial lipaemia, which now warrant targeted mechanistic evaluation within larger study cohorts.

Topics: Adult; Blood Glucose; Body Composition; Body Weight; C-Peptide; Caloric Restriction; Diet, Reducing; Energy Intake; Fasting; Female; Humans; Hyperinsulinism; Insulin Resistance; Lipid Metabolism; Male; Middle Aged; Obesity; Overweight; Postprandial Period; Weight Loss

To test whether cognitive function is impaired in early states of diabetes and to identify possible risk factors for cognitive impairment.. A cross-sectional analysis within the German Diabetes Study included patients with type 1 or type 2 diabetes within the first year after diagnosis or five years after study inclusion and metabolically healthy individuals. Participants underwent comprehensive metabolic phenotyping and testing of different domains of cognitive function. Linear regression models were used to compare cognition test outcomes and to test associations between cognitive function and possible influencing factors within the groups.. In participants with recently diagnosed diabetes, verbal memory was poorer in patients with type 2 diabetes (. Verbal memory is impaired in individuals with recently diagnosed type 2 diabetes and likely associated with higher body mass. This trial is registered with the trial registration number NCT01055093.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Cognition; Cognition Disorders; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Germany; Glycated Hemoglobin; Humans; Intelligence; Male; Memory; Middle Aged; Obesity; Prognosis; Prospective Studies; Risk Factors; Sex Factors; Time Factors; Verbal Behavior

The aim of the study was to evaluate the levels of adipokines such as adiponectin, resistin, leptin as well as C-peptide in overweight and obese pregnant women.. The adipokines and C-peptide concentrations were measured in the group of 38 overweight/obese pregnant women (BMI > 25 kg/m2) and in 42 pregnant women of normal weight (BMI < 25 kg/m2) with ELISA tests between 24th and 34th weeks of gestation.. The overweight/obese women compared to lean ones were characterized by significantly higher concentrations of leptin (43.44 ± 31.41 vs. 21.29 ± 12.67 ng/mL, p = 0.0001) and C-peptide (2.77 ± 1.88 vs. 2.25 ± 1.42 ng/mL, p = 0.034). There were no significant differences between groups in resistin (17.39 ± 7.59 vs. 15.76 ± 6.64 ng/mL, NS) and adiponectin (6.93 ± 3.52 vs. 8.07 ± 6.53 μg/mL, NS) levels. In the overweight/obese patients, no relationships between the adipokines, C-peptide and CRP concentrations were found. BMI was negatively correlated with the resistin levels (R = -0.406, p = 0.011). The significant correlation between leptin and C-peptide concentrations was observed in the study group (R = 0.517, p = 0.012). In the control group, the negative correlation between adiponectin concentrations and BMI was shown (R = -0.446, p = 0.003).. The higher levels of leptin in the overweight and obese pregnant women seem to reflect the leptin resistance condition and the higher levels of C-peptide in this group is suggestive for hyperinsulinemia. The positive correlation between C-peptide and leptin levels but not with resistin and adiponectin might confirm the role of leptin in the hyperinsulinemia development in overweight and obesity during pregnancy.

Topics: Adult; Biomarkers; Body Mass Index; C-Peptide; Case-Control Studies; Female; Humans; Leptin; Obesity; Pregnancy; Pregnancy Complications; Up-Regulation; Young Adult

Sex hormone-binding globulin (SHBG) negatively associates with pre-gestational body mass index (BMI) and gestational weight gain. The link with other cardio-metabolic risk factors in pregnant women is poorly understood. Our aim was to study the association of SHBG levels with common cardio-metabolic risk parameters in pregnant woman. Serum SHBG was quantified in 291 Caucasian pregnant women (142 with normal weight, 42 with pregestational obesity, 50 with gestational obesity and 57 with pregestational plus gestational obesity) with uncomplicated pregnancies and parturition. Cardio-metabolic [C-reactive protein (CRP), blood pressure (BP), glycosylated hemoglobin (HbAc1), glucose, C-peptide, insulin, triglycerides and high molecular weight (HMW) adiponectin], and endocrine [testosterone and estradiol] parameters were also assessed. SHBG was negatively correlated with BMI, but also with CRP, BP, HbAc1, pre and post-load glucose, C-peptide, HOMA-IR, triglycerides; and positively with HMW adiponectin (all p<0.01 to p<0.0001). These associations were more robust in women with pregestational plus gestational obesity, who had lower SHBG, in comparison to normal-weight women (p<0.0001). In multivariate analyses in women with pregestational plus gestational obesity SHBG showed independent associations with CRP (β = -0.352, p = 0.03, R2 = 8.0%), DBP (β = -0.353, p = 0.03, R2 = 7.0%) and SBP (β = -0.333, p = 0.04, R2 = 6.0%) independently of BMI and metabolic and endocrine parameters. SHBG is decreased in pregnant women with pregestational plus gestational obesity in association with common cardio-metabolic parameters. SHBG could represent an integrating biomarker for an adverse cardio-metabolic profile in pregnant women with pregestational plus gestational obesity.

Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; C-Reactive Protein; Cohort Studies; Female; Glycated Hemoglobin; Humans; Infant, Newborn; Obesity; Pregnancy; Pregnancy Complications; Sex Hormone-Binding Globulin; Triglycerides; White People

Proinsulin connecting peptide (C-Peptide) is a marker of the beta-cell function and has been considered a marker of insulin resistance whose evidence suggests were associated with cardiovascular mortality. Our study aims to evaluate the association of C-Peptide with metabolic cardiovascular risk factors among young adults followed since birth in southern Brazil.. In 1982, maternity hospital in Pelotas, a southern Brazilian city, were visited daily and all births were identified. Live births whose family lived in the urban area of the city were identified, their mothers interviewed, and these subjects have been prospectively followed. Casual hyperglycemia patients were excluded from analysis. C-Peptide was assessed at 23 years, when transversely analyzed its association with cardiometabolic and hemodynamic risk factors, and longitudinally 30 years of age.. At age 23, 4297 individuals were evaluated, and C-Peptide was measured in 3.807. In a cross-sectional analysis at 23 years of age, C-Peptide was positively associated with waist circumference, body mass index, glycaemia, triglycerides, and C-reactive protein. The association with HDL cholesterol was negative. In the longitudinal analysis at 30 years, C-Peptide remained associated with BMI, waist circumference, glycated hemoglobin, triglycerides, and C-reactive protein, whereas the association was negative for HDL.. In the Pelotas birth cohort, the C-Peptide was associated with obesity indicators (waist circumference and BMI) cross-sectional (23 years) and longitudinal (30 years). We also observed cross-sectional and longitudinal associations of C-Peptide with cardiometabolic and inflammatory risk factors.

Topics: Adult; Biomarkers; Body Mass Index; Brazil; C-Peptide; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Obesity; Prospective Studies; Risk Factors; Waist Circumference; Young Adult

Obesity and age, key risk factors for aggressive prostate cancer, are associated with insulin resistance. Glucose-related parameters in patients with aggressive prostate cancer were compared with 2 reference groups: men of similar age and body mass index (BMI) without cancer, and healthy young men. Acute changes in these parameters following radiation treatment were also evaluated.. Nine patients with aggressive prostate cancer underwent metabolic assessments prior to treatment (baseline), 7 and 33 weeks post-baseline (post-treatment initiation). Baseline measures were compared with the 2 reference groups. Evaluations included: 1) fasting and oral glucose tolerance test (OGTT) blood samples for glucose, C-peptide, and insulin, 2) fasting blood samples for triglycerides, cholesterols, leptin, adiponectin, IL-6, and TNF-α, 3) body composition, 4) nutrition, and 5) physical activity.. At baseline, patients had normal fasting glucose concentrations (<5.6 mM; 4.9 ± 1.2 mM) but impaired 2-h OGTT glucose concentrations (>7.8 mM; 8.7 ± 2.9 mM). Both reference groups had normal fasting (matched males: 4.2 ± 0.5 mM; young males: 3.7 ± 0.4 mM) and 2-h OGTT glucose concentrations (matched males: 5.6 ± 1.8 mM; young males: 3.1 ± 0.1 mM) that were significantly lower than patient values. During the OGTT, patients had higher insulin (120 min) and C-peptide (45, 60, 90, 120 min) concentrations compared to the matched males. At 7 weeks, 2-h OGTT glucose concentrations in patients improved to healthy ranges without changes in insulin, C-peptide, IGF-1, IGFBP-3 or other metabolic parameters.. At baseline patients with aggressive prostate cancer demonstrated impaired glucose tolerance compared with men of similar age and body size. Following treatment, glucose tolerance improved in the absence of changes in expected modifiers of glucose metabolism. These improvements may be related to treatment.

Topics: Adult; Age Factors; Aged; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Glucose Intolerance; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Obesity; Prostatic Neoplasms; Young Adult

Type 2 diabetes is associated with cardiovascular complications. It is largely unknown which patients have poor treatment response and high complication risk; biomarkers are studied for this purpose. The aim of the study was to investigate the association between clinical factors such as HbA1c, level of biomarkers (C-peptide, copeptin) at diagnosis and changes in HbA1c, blood pressure or body mass index (BMI) after five years.. Clinical data and blood samples from 460 newly diagnosed type 2 diabetes patients from the Skaraborg diabetes register (SDR) at diagnosis and after 5years and were analyzed with linear and logistic regressions.. High BMI at diagnosis and smoking were associated with less reduction of HbA1c i.e. poorer treatment outcome after 5years. A high HbA1c at baseline predicted a greater reduction of HbA1c and need for insulin treatment. High systolic blood pressure and BMI at baseline were associated with greater reduction. The biomarkers were not associated with increase of blood pressure, HbA1c, BMI or need for insulin treatment.. Smokers and patients with high HbA1c at diagnosis respond poorer to treatment over 5years. This highlights the importance of advice for non-smoking and weight reduction and more intensive treatment over time.

Topics: Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Female; Follow-Up Studies; Glycated Hemoglobin; Glycopeptides; Humans; Male; Middle Aged; Obesity; Overweight; Prognosis; Registries; Risk Factors; Sweden; Tobacco Smoking

Experimental bone marrow transplantation (BMT) in mice is commonly used to assess the role of immune cell-specific genes in various pathophysiological settings. The application of BMT in obesity research is hampered by the significant reduction in high-fat diet (HFD)-induced obesity. We set out to characterize metabolic tissues that may be affected by the BMT procedure and impair the HFD-induced response. Male C57BL/6 mice underwent syngeneic BMT using lethal irradiation. After a recovery period of 8 weeks they were fed a low-fat diet (LFD) or HFD for 16 weeks. HFD-induced obesity was reduced in mice after BMT as compared to HFD-fed control mice, characterized by both a reduced fat (-33%; p<0.01) and lean (-11%; p<0.01) mass, while food intake and energy expenditure were unaffected. As compared to control mice, BMT-treated mice had a reduced mature adipocyte volume (approx. -45%; p<0.05) and reduced numbers of preadipocytes (-38%; p<0.05) and macrophages (-62%; p<0.05) in subcutaneous, gonadal and visceral white adipose tissue. In BMT-treated mice, pancreas weight (-46%; p<0.01) was disproportionally decreased. This was associated with reduced plasma insulin (-68%; p<0.05) and C-peptide (-37%; p<0.01) levels and a delayed glucose clearance in BMT-treated mice on HFD as compared to control mice. In conclusion, the reduction in HFD-induced obesity after BMT in mice is at least partly due to alterations in the adipose tissue cell pool composition as well as to a decreased pancreatic secretion of the anabolic hormone insulin. These effects should be considered when interpreting results of experimental BMT in metabolic studies.

Topics: Adipocytes; Adipose Tissue, White; Animals; Bone Marrow Transplantation; C-Peptide; Diet, Fat-Restricted; Diet, High-Fat; Eating; Energy Metabolism; Fatty Acids, Nonesterified; Feces; Glucose Tolerance Test; Insulin; Insulin Secretion; Macrophages; Male; Mice; Mice, Inbred C57BL; Obesity; Pancreas; Triglycerides; Weight Gain

Obesity is associated with dysregulated lipid metabolism and adipokine secretion. Our group has previously reported obesity and adipokines are associated with % total fatty acid (FA) differences in plasma phospholipids. The objective of our current study was to identify in which complex lipid species (i.e., phosphatidylcholine, sphingolipids, etc) these FA differences occur. Plasma lipidomic profiling (n = 126, >95% Caucasian, 48-65 years) was performed using chromatographic separation and high resolution tandem mass spectrometry. The responses used in the statistical analyses were body mass index (BMI), waist circumference (WC), serum adipokines, cytokines, and a glycemic marker. High-dimensional statistical analyses were performed, all models were adjusted for age and smoking, and p-values were adjusted for false discovery. In Bayesian models, the lipidomic profiles (over 1,700 lipids) accounted for >60% of the inter-individual variation of BMI, WC, and leptin in our population. Across statistical analyses, we report 51 individual plasma lipids were significantly associated with obesity. Obesity was inversely associated lysophospholipids and ether linked phosphatidylcholines. In addition, we identify several unreported lipids associated with obesity that are not present in lipid databases. Taken together, these results provide new insights into the underlying biology associated with obesity and reveal new potential pathways for therapeutic targeting.

Topics: Adipokines; Algorithms; Bayes Theorem; Biomarkers; Body Mass Index; C-Peptide; Humans; Male; Middle Aged; Obesity; Phospholipids; Tandem Mass Spectrometry; Waist Circumference

Bariatric surgery can improve glucose metabolism in obese patients with diabetes, but the factors that can predict diabetes remission are still under discussion. The present study aims to examine the impact of preoperative beta cell function on diabetes remission following surgery.. We investigated a cohort of 363 obese diabetic patients who underwent bariatric surgery. The impact of several preoperative beta cell function indexes on diabetes remission was explored through bivariate logistic regression models.. Postoperative diabetes remission was achieved in 39.9 % of patients. Younger patients (p < 0.001) and those with lower HbA1c (p = 0.001) at the baseline evaluation had higher odds of diabetes remission. Use of oral anti-diabetics and insulin therapy did not reach statistical significance when they were adjusted for age and HbA1c. Among the evaluated indexes of beta cell function, higher values of insulinogenix index, Stumvoll first- and second-phase indexes, fasting C-peptide, C-peptide area under the curve (AUC), C-peptide/glucose AUC, ISR (insulin secretion rate) AUC, and ISR/glucose AUC predicted diabetes remission even after adjustment for age and HbA1c. Among them, C-peptide AUC had the higher discriminative power (AUC 0.76; p < 0.001).. Patients' age and preoperative HbA1c can forecast diabetes remission following surgery. Unlike other studies, our group found that the use of oral anti-diabetics and insulin therapy were not independent predictors of postoperative diabetes status. Preoperative beta cell function, mainly C-peptide AUC, is useful in predicting diabetes remission, and it should be assessed in all obese diabetic patients before bariatric or metabolic surgery.

Topics: Adult; Bariatric Surgery; Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Postoperative Period; Preoperative Period; Remission Induction; Retrospective Studies; Weight Loss

Medical treatment fails to provide adequate control for many obese patients with type 2 diabetes mellitus (T2DM). A comparative observational study of bariatric procedures was performed to investigate the time at which patients achieve glycemic control within the first 30 postoperative days following sleeve gastrectomy (SG), mini-gastric bypass (MGB), and diverted sleeve gastrectomy with ileal transposition (DSIT).. During the first postoperative month, glycemic control (<126 mg/dL) was achieved following DSIT and MGB, but not SG. Preoperative BMI and postprandial C-peptide levels were independent predictors of early glycemic control following DSIT.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastrectomy; Gastric Bypass; Humans; Ileum; Male; Middle Aged; Obesity; Postoperative Period; Retrospective Studies; Time Factors; Treatment Outcome; Weight Loss

The duodenal-jejunal bypass sleeve ((DJBS) or EndoBarrier Gastrointestinal Liner) induces weight loss in obese subjects and may improve glucose homeostasis in patients with type 2 diabetes (T2D). To explore the underlying mechanisms, we evaluated postprandial physiology including glucose metabolism, gut hormone secretion, gallbladder emptying, appetite and food intake in patients undergoing DJBS treatment.. A total of 10 normal glucose-tolerant (NGT) obese subjects and 9 age-, body weight- and body mass index-matched metformin-treated T2D patients underwent a liquid mixed meal test and a subsequent ad libitum meal test before implantation with DJBS and 1 week (1w) and 26 weeks (26w) after implantation.. At 26w, both groups had achieved a weight loss of 6 to 7 kg. Postprandial glucagon-like peptide-1 (GLP-1) and peptide YY responses increased at 1w and 26w, but only in T2D subjects. In contrast, glucose-dependent insulinotropic polypeptide responses were reduced only by DJBS in the NGT group. Postprandial glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin responses were unaffected by DJBS in both groups. Satiety and fullness sensations were stronger and food intake was reduced at 1w in NGT subjects; no changes in appetite measures or food intake were observed in the T2D group. No effect of DJBS on postprandial gallbladder emptying was observed, and gastric emptying was not delayed.. DJBS-induced weight loss was associated with only marginal changes in postprandial physiology, which may explain the absence of effect on postprandial glucose metabolism.

Topics: Adult; Appetite; Bariatric Surgery; Blood Glucose; Body Composition; C-Peptide; Case-Control Studies; Cholecystokinin; Comorbidity; Diabetes Mellitus, Type 2; Eating; Female; Gallbladder Emptying; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastrins; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period; Prospective Studies; Satiety Response; Treatment Outcome

The metabolic effects of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in type 2 diabetes (T2D) patients who do not meet National Institutes of Health indications has not been well studied.. To compare the effectiveness of LSG and LRYGB in Chinese T2D patients with body mass index (BMI)<35 kg/m. University hospital, China.. A nonrandomized cohort of patients who underwent LRYGB (n = 64) and LSG (n = 19) were followed up for 3 years and the outcomes (weight loss and remission of diabetes and other metabolic parameters) were compared. Univariate and multivariate analyses were applied to find associated parameters of T2D remission.. In total, 5 patients (6%) were lost to follow-up. No significant differences in mean percentage of excess weight loss and BMI were observed between the 2 groups at 2 years. At 3-year follow-up, the LRYGB group had significantly higher percentage of excess weight loss and lower BMI. The total (complete and partial) remission rate achieved with both bariatric procedures was 75.9% at 1 year and 56.4% at 3 years. Surgical safety, diabetes remission, and remission of other obesity-related co-morbidities were comparable between the 2 groups. Patients who achieved complete or partial remission had lower fasting plasma glucose, lower plasma glucose at 2 hours, lower glycated hemoglobin, and higher fasting C peptide than the other patients at baseline. High recurrence rates of hypertension and hyperuricemia were observed at 3 years postoperation.. Both LSG and LRYGB are safe and effective bariatric procedures for T2D in this Chinese population with diabetes and BMI<35 kg/m

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Epidemiologic Methods; Fasting; Female; Gastrectomy; Gastric Bypass; Glycated Hemoglobin; Humans; Hypertension; Hyperuricemia; Laparoscopy; Male; Obesity; Recurrence; Treatment Outcome; Weight Loss

Irisin is an exercise-responsive myokine that has been proposed to exert anti-obesity benefits; yet its response during exercise in obese women is not described. This study characterized plasma irisin levels during a single bout of afternoon isocaloric-exercise of different intensities (moderate- vs high-intensity) in obese females.. Eleven obese females participated in 3 randomized study days beginning at 1600h: 1) no exercise (NoEx), 2) moderate exercise (ModEx; 55%VO2max) and 3) high intensity interval exercise (IntEx; 4 min (80%VO2max)/3 min (50% VO2max). Frequent blood samples were analyzed for glucose and lactate (whole-blood), and insulin, c-peptide, glucagon, and irisin (plasma) throughout 190 min of testing.. Plasma irisin increased above baseline during ModEx and IntEx (P<0.05), but not NoEx (P>0.05). Peak irisin levels during ModEx and IntEx exercise were 11.9± 3.4% and 12.3 ± 4.1% relative to baseline (P<0.05), respectively, with no differences between exercise intensities (P>0.05). Irisin levels remained elevated above resting for 125 minutes post-exercise during ModEx, whereas levels returned to baseline within 15 minutes post-exercise during IntEx. Similarly, no associations were found between plasma irisin levels and circulating lactate, glucose, insulin, c-peptide, or glucagon among study days (P>0.05). However, there was an inverse association between basal irisin and lean mass (r = -0.70, P = 0.01).. A single bout of moderate and high intensity afternoon exercise induces modest increases in circulating irisin concentrations during exercise; however the regulation post-exercise appears to be dimorphic between exercise intensity in obese females. Future studies are needed to compare morning and afternoon exercise on irisin secretion.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Exercise; Female; Fibronectins; Gene Expression; Glucagon; Humans; Insulin; Lactic Acid; Obesity; Oxygen Consumption; Random Allocation; Time Factors

To investigate whether children with a family history of diabetes (FHD) in second-degree relatives (grandparents, aunts/uncles) are at increased risk of developing obesity and diabetes, and whether the risk differs between maternal or paternal transmission.. In the multiethnic population-based cohort Amsterdam-Born Children and Their Development (ABCD) Study, body mass index (BMI), waist-to-height ratio (WHR), fat percentage (fat%), fasting glucose and C-peptide in 5- or 6-year-old children with no second-degree FHD (n=2226) were compared with children with maternal-only (n=353), paternal-only (n=281) or both maternal and paternal (n=164) second-degree FHD. Children of diabetic mothers or fathers were excluded.. None of the children in any of our FHD categories differed in body composition after adjusting for maternal, paternal and childhood lifestyle covariates. However, children with both maternal and paternal second-degree FHD had increased C-peptide levels (0.03nmol, 95% CI: 0.01-0.05) compared with those in the other three study groups. Results were similar when analyses were restricted to only the Dutch children.. Children with FHD in second-degree relatives on both maternal and paternal sides already have higher C-peptide levels at an early age. This might be the result of a double burden of a shared obesogenic lifestyle, or of more diverse diabetogenic genes compared to children without FHD or with only FHD in one side of the family. In any case, second-degree FHD could be used as a public-health screening tool to identify children at risk of adverse metabolic outcomes and of possible future disease.

Topics: Adult; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Child; Child, Preschool; Female; Humans; Male; Obesity; Risk Factors; Waist Circumference

Obesity and late-night food consumption are associated with impaired glucose tolerance. Late-night carbohydrate consumption may be particularly detrimental during late pregnancy because insulin sensitivity declines as pregnancy progresses. Further, women who were obese (Ob) prior to pregnancy have lower insulin sensitivity than do women of normal weight (NW). The aim of this study is to test the hypothesis that night-time carbohydrate consumption is associated with poorer glucose tolerance in late pregnancy and that this association would be exacerbated among Ob women. Forty non-diabetic African American women were recruited based upon early pregnancy body mass index (NW, <25 kg m(-2) ; Ob, ≥30 kg m(-2) ). Third trimester free-living dietary intake was assessed by food diary, and indices of glucose tolerance and insulin action were assessed during a 75-g oral glucose tolerance test. Women in the Ob group reported greater average 24-h energy intake (3055 kcal vs. 2415 kcal, P < 0.05). Across the whole cohort, night-time, but not day-time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05). Multiple linear regression modelling within each weight group showed that the associations among late-night carbohydrate intake, glucose concentrations and insulin secretion were present only in the Ob group. This is the first study to report an association of night-time carbohydrate intake specifically on glucose tolerance and insulin action during pregnancy. If replicated, these results suggest that late-night carbohydrate intake may be a potential target for intervention to improve metabolic health of Ob women in late pregnancy.

Topics: Adolescent; Adult; Black or African American; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diet; Diet Records; Dietary Carbohydrates; Feeding Behavior; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Linear Models; Metabolic Diseases; Nutrition Assessment; Obesity; Pregnancy; Time Factors; Young Adult

The role of incretins in type 2 diabetes is controversial. This study investigated the association between incretin levels in obese Korean children and adolescents newly diagnosed with type 2 diabetes.. We performed a 2-hr oral glucose tolerance test (OGTT) in obese children and adolescents with type 2 diabetes and with normal glucose tolerance.. Twelve obese children and adolescents with newly diagnosed type 2 diabetes (DM group) and 12 obese age-matched subjects without type 2 diabetes (NDM group) were included.. An OGTT was conducted and insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were measured during the OGTT.. The mean age of the patients was 13·8 ± 2·0 years, and the mean body mass index (BMI) Z-score was 2·1 ± 0·5. The groups were comparable in age, sex, BMI Z-score and waist:hip ratio. The DM group had significantly lower homeostasis model assessment of β and insulinogenic index values (P < 0·001). The homeostasis model assessment of insulin resistance index was not different between the two groups. Insulin and C-peptide secretions were significantly lower in the DM group than in the NDM group (P < 0·001). Total GLP-1 secretion was significantly higher in the DM group while intact GLP-1 and GIP secretion values were not significantly different between the two groups.. Impaired insulin secretion might be important in the pathogenesis of type 2 diabetes in obese Korean children and adolescents, however, which may not be attributed to incretin secretion.

Topics: Adolescent; Analysis of Variance; Asian People; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Child; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin Resistance; Male; Obesity; Republic of Korea

The aim of this study was to investigate the insulin clearance in diet-induced obese (DIO) mice submitted to acute endurance exercise (3h of treadmill exercise at 60-70% VO2max). Glucose-stimulated insulin secretion in isolated islets; ipGTT; ipITT; ipPTT; in vivo insulin clearance; protein expression in liver, skeletal muscle, and adipose tissue (insulin degrading enzyme (IDE), insulin receptor subunitβ(IRβ), phospho-Akt (p-Akt) and phospho-AMPK (p-AMPK)), and the activity of IDE in the liver and skeletal muscle were accessed. In DIO mice, acute exercise reduced fasting glycemia and insulinemia, improved glucose and insulin tolerance, reduced hepatic glucose production, and increased p-Akt protein levels in liver and skeletal muscle and p-AMPK protein levels in skeletal muscle. In addition, insulin secretion was reduced, whereas insulin clearance and the expression of IDE and IRβ were increased in liver and skeletal muscle. Finally, IDE activity was increased only in skeletal muscle. In conclusion, we propose that the increased insulin clearance and IDE expression and activity, primarily, in skeletal muscle, constitute an additional mechanism, whereby physical exercise reduces insulinemia in DIO mice.

Topics: AMP-Activated Protein Kinases; Animals; C-Peptide; Diet, High-Fat; Glucose; Insulin; Insulysin; Liver; Male; Metabolic Clearance Rate; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle, Skeletal; Obesity; Phosphorylation; Physical Conditioning, Animal; Proto-Oncogene Proteins c-akt; Receptor, Insulin

What is the prevalence of reactive hypoglycemia (RH) in polycystic ovary syndrome (PCOS) versus age- and body mass index (BMI)-matched healthy controls.. The prevalence of RH was increased in PCOS versus controls.. Previous studies suggested an increased prevalence of RH in PCOS.. Cross-sectional study of 88 women with PCOS and 34 healthy age- and BMI-matched controls.. Eighty-eight women with PCOS and 34 age- and BMI-matched controls were included. The study was conducted at Odense University Hospital, Denmark. Participants underwent 5 h oral glucose tolerance test (5 h OGTT). Indices of insulin resistance, β-cell function, and area under the curve (AUC) for glucose, insulin and C-peptide were calculated. Insulin clearance was estimated as 5 h AUC C-peptide/insulin. RH was defined as blood glucose ≤3.3 mmol/l during 5 h OGTT.. RH occurred in 15/88 (17%) women with PCOS versus 0/34 controls ( ITALIC! P = 0.01). Nine out of 15 women with RH were obese and 6 were lean ( ITALIC! P = 0.42). Obese patients with RH had significantly higher 5 h AUCs insulin and C-peptide compared with lean patients with RH ( ITALIC! P = 0.02 and 0.04, respectively). Obese patients with RH had significantly lower 5 h AUC C-peptide/insulin versus obese patients without RH ( ITALIC! P = 0.02). In lean patients with RH, 5 h AUCs insulin and C-peptide were similar to lean controls.. The 5 h OGTT was used to diagnose RH and may be a limitation of the study. Although the 5 h OGTT is the most widely accepted method, no gold standard exists in terms of diagnosing RH. The 5 h OGTT was suggested to over-estimate the incidence of RH compared with meal test.. The study supports previous suggestions of increased prevalence of RH in women with PCOS compared with controls.. This study was funded by Jacob Madsen's and Olga Madsen's Foundation, Institute of Clinical Research, Odense University Hospital, Kolding Hospital, AP Møller's Foundation, Bernhard and Marie Kleins Foundation, The Novo Nordisk Foundation, and The Danish Medical Association. The authors declare no conflict of interest.. The trial was registered at www.clinicaltrials.gov (registration numbers NCT00451568 (patients) and NCT01995773 (controls)).

Topics: Adolescent; Adult; Area Under Curve; Blood Glucose; Body Mass Index; C-Peptide; Cross-Sectional Studies; Denmark; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Prevalence

Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans.. This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT. Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulin sensitivity and beta-cell function derived from glucose, insulin and C-peptide concentrations during the OGTT.. Circulating Sfrp5 associated inversely with the insulinogenic index based on C-peptide (rs = -0·244, P = 0·001), but not with the insulinogenic index based on insulin levels (rs = -0·007, P = 0·926) after adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = -0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index.. The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Eye Proteins; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Membrane Proteins; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity

Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.. The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of. These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

Topics: Adiposity; Biomarkers; Body Mass Index; Body Size; C-Peptide; Case-Control Studies; Chi-Square Distribution; Colorectal Neoplasms; Europe; Female; Health Status; Humans; Hyperinsulinism; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; Obesity; Obesity, Metabolically Benign; Odds Ratio; Phenotype; Prospective Studies; Protective Factors; Risk Assessment; Risk Factors; Waist Circumference

The body compensates for early-stage insulin resistance by increasing insulin secretion. A reliable and easy-to-use mathematical assessment of insulin secretion and disposal could be a valuable tool for identifying patients at risk for the development of type 2 diabetes. Because the pathophysiology of insulin resistance is incompletely understood, assessing insulin metabolism with minimal assumptions regarding its metabolic regulation is a major challenge. To assess insulin secretion and indexes of insulin disposal, our marginalized and regularized absorption approach (MRA) was applied to a sparse sampling oral glucose tolerance test (OGTT) protocol measuring the insulin and C-peptide concentrations. Identifiability and potential bias of metabolic parameters were estimated from published data with dense sampling. The MRA was applied to OGTT data from 135 obese adolescents to demonstrate its clinical applicability. Individual prehepatic basal and dynamic insulin secretion and clearance levels were determined with a precision and accuracy greater than 10% of the nominal value. The intersubject variability in these parameters was approximately four times higher than the intrasubject variability, and there was a strong negative correlation between prehepatic secretion and plasma clearance of insulin. MRA-based analysis provides reliable estimates of insulin secretion and clearance, thereby enabling detailed glucose homeostasis characterization based on restricted datasets that are obtainable during routine patient care.

Topics: Adolescent; C-Peptide; Child; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Liver; Obesity; Young Adult

It is widely accepted that lifestyle plays a crucial role on the quality of life in individuals, particularly in western societies where poor diet is correlated to alterations in behavior and the increased possibility of developing type-2 diabetes. While exercising is known to produce improvements to overall health, there is conflicting evidence on how much of an effect exercise has staving off the development of type-2 diabetes or counteracting the effects of diet on anxiety. Thus, this study investigated the effects of voluntary wheel-running access on the progression of diabetes-like symptoms and open field and light-dark box behaviors in C57BL/6J mice fed a high-fat diet. C57BL/6J mice were placed into either running-wheel cages or cages without a running-wheel, given either regular chow or a high-fat diet, and their body mass, food consumption, glucose tolerance, insulin and c-peptide levels were measured. Mice were also exposed to the open field and light-dark box tests for anxiety-like behaviors. Access to a running-wheel partially attenuated the obesity and hyperinsulinemia associated with high-fat diet consumption in these mice, but did not affect glucose tolerance or c-peptide levels. Wheel-running strongly increased anxiety-like and decreased explorative-like behaviors in the open field and light-dark box, while high-fat diet consumption produced smaller increases in anxiety. These results suggest that voluntary wheel-running can assuage some, but not all, of the physiological problems associated with high-fat diet consumption, and can modify anxiety-like behaviors regardless of diet consumed.

Topics: Animals; Anxiety; C-Peptide; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Eating; Exploratory Behavior; Insulin; Male; Mice, Inbred C57BL; Obesity; Running; Volition; Weight Gain

There is increasing evidence that serum betatrophin levels, a hormone derived from adipose tissue and liver, are elevated in type 2 diabetes (T2D).. To investigate the relationships among betatrophin and metabolic control, insulin resistance, and pancreatic β-cell function in obese Chinese patients with T2D who underwent Roux-en-Y gastric bypass (RYGB).. University hospital, China.. This 1-year follow-up study included 34 obese individuals with T2D (18 males, 16 females) who underwent RYGB in our hospital. Anthropometric results, glucose levels, lipid profiles, and serum betatrophin levels were determined before and 1 year after RYGB.. The serum betatrophin level decreased significantly after RYGB (72.0 ng/mL [33.4-180.9] versus 35.7 ng/mL [14.8-103.3]); P<.001]. The change in betatrophin was significantly positively correlated with the changes in hemoglobin A1c and fasting plasma glucose and negatively correlated with the changes in the 2-hour C-peptide/fasting C-peptide and homeostasis model of assessment of β-cell function (P<.05). Multiple stepwise regression analysis indicated that the change in the serum betatrophin level was independently and significantly associated with the changes in fasting plasma glucose (β = .586, P<.001) and 2-hour C-peptide/fasting C-peptide (β = -.309, P = .021).. Circulating betatrophin might be involved in the regulation of glucose control and insulin secretion in obese Chinese with T2D soon after RYGB.

Topics: Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Biomarkers; Blood Glucose; C-Peptide; China; Diabetes Mellitus, Type 2; Fasting; Female; Follow-Up Studies; gamma-Glutamyltransferase; Gastric Bypass; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Lipids; Male; Middle Aged; Obesity; Peptide Hormones; Postoperative Care; Postprandial Period

Overweight and obese women are at a higher risk for gestational diabetes mellitus. The gut microbiome could modulate metabolic health and may affect insulin resistance and lipid metabolism. The aim of this study was to reveal relationships between gut microbiome composition and circulating metabolic hormones in overweight and obese pregnant women at 16 weeks' gestation. Fecal microbiota profiles from overweight (n = 29) and obese (n = 41) pregnant women were assessed by 16S rRNA sequencing. Fasting metabolic hormone (insulin, C-peptide, glucagon, incretin, and adipokine) concentrations were measured using multiplex ELISA. Metabolic hormone levels as well as microbiome profiles differed between overweight and obese women. Furthermore, changes in some metabolic hormone levels were correlated with alterations in the relative abundance of specific microbes. Adipokine levels were strongly correlated with Ruminococcaceae and Lachnospiraceae, which are dominant families in energy metabolism. Insulin was positively correlated with the genus Collinsella. Gastrointestinal polypeptide was positively correlated with the genus Coprococcus but negatively with family Ruminococcaceae This study shows novel relationships between gut microbiome composition and the metabolic hormonal environment in overweight and obese pregnant women at 16 weeks' gestation. These results suggest that manipulation of the gut microbiome composition may influence pregnancy metabolism.

Topics: Adipokines; Adult; Blood Glucose; C-Peptide; Energy Metabolism; Enzyme-Linked Immunosorbent Assay; Female; Gastrointestinal Microbiome; Gestational Age; Humans; Insulin; Obesity; Overweight; Pregnancy; RNA, Ribosomal, 16S; Ruminococcus

The goals of this study were to determine baseline and postbariatric surgical characteristics associated with type 2 diabetes remission and if, after controlling for differences in weight loss, diabetes remission was greater after Roux-en-Y gastric bypass (RYGBP) than laparoscopic gastric banding (LAGB).. An observational cohort of obese participants was studied using generalized linear mixed models to examine the associations of bariatric surgery type and diabetes remission rates for up to 3 years. Of 2,458 obese participants enrolled, 1,868 (76%) had complete data to assess diabetes status at both baseline and at least one follow-up visit. Of these, 627 participants (34%) were classified with diabetes: 466 underwent RYGBP and 140 underwent LAGB.. After 3 years, 68.7% of RYGBP and 30.2% of LAGB participants were in diabetes remission. Baseline factors associated with diabetes remission included a lower weight for LAGB, greater fasting C-peptide, lower leptin-to-fat mass ratio for RYGBP, and a lower hemoglobin A1c without need for insulin for both procedures. After both procedures, greater postsurgical weight loss was associated with remission. However, even after controlling for differences in amount of weight lost, relative diabetes remission rates remained nearly twofold higher after RYGBP than LAGB.. Diabetes remission up to 3 years after RYGBP and LAGB was proportionally higher with increasing postsurgical weight loss. However, the nearly twofold greater weight loss-adjusted likelihood of diabetes remission in subjects undergoing RYGBP than LAGB suggests unique mechanisms contributing to improved glucose metabolism beyond weight loss after RYGBP.

Topics: Adult; Bariatric Surgery; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Gastroplasty; Glycated Hemoglobin; Humans; Laparoscopy; Longitudinal Studies; Male; Middle Aged; Obesity; Remission Induction; Weight Loss

Currently increasing importance is attributed to the inflammatory process as a crucial factor responsible for the progressive damage to vascular walls and progression of atherosclerosis in obese people. We have studied the relationship between clinical and biochemical parameters and C-peptide and anti-inflammatory IL-10, as well as selected markers of inflammation and endothelial dysfunction such as: CCL2, CRP, sICAM-1, sVCAM-1 and E-selectin in obese women with various degree of glucose metabolism disturbance.. The studied group consisted of 61 obese women, and 20 normal weight, healthy volunteers. Obese patients were spited in subgroups based on the degree of glucose metabolism disorder. Serum samples were analyzed using ELISA kits.. Increased concentrations of sICAM-1, sVCAM-1, E-selectin, CCL2 and CRP were found in all obese groups compared to the normal weight subjects. In patients with Type 2 diabetes mellitus (T2DM) parameters characterizing the degree of obesity significantly positively correlated with levels of CRP and CCL2. Significant relationships were found between levels of glucose and sICAM-1and also E-selectin and HOMA-IR. C-peptide levels are positively associated with CCL2, E-selectin, triglycerides levels, and inversely with IL-10 levels in newly diagnosed T2DM group (p<0.05). Concentrations of IL-10 correlated negatively with E-selectin, CCL2, C-peptide levels, and HOMA-IR in T2DM group (p<0.05).. Disturbed lipid and carbohydrate metabolism are manifested by enhanced inflammation and endothelial dysfunction in patients with simply obesity. These disturbances are associates with an increase of adhesion molecules. The results suggest the probable active participation of higher concentrations of C-peptide in the intensification of inflammatory and atherogenic processes in obese patients with type 2 diabetes. In patients with obesity and type 2 diabetes, altered serum concentrations of Il-10 seems to be dependent on the degree of insulin resistance and proinflammatory status.

Topics: Biomarkers; C-Peptide; Chemokine CCL2; Diabetes Mellitus, Type 2; E-Selectin; Enzyme-Linked Immunosorbent Assay; Female; Glucose; Humans; Intercellular Adhesion Molecule-1; Interleukin-10; Obesity; Triglycerides; Vascular Cell Adhesion Molecule-1

Increasing evidence indicates a role of oxytocin in controlling energy metabolism. The aim of his study was to investigate oxytocin effects on obese phenotype in leptin-resistant Zucker fatty rats, focusing on glucose and lipid metabolism. Zucker fatty rats and their lean controls were treated with oxytocin (3.6 μg/100g body weight/day) by osmotic minipumps implanted subcutaneously for 2 weeks. Two-hours intraperitoneal glucose tolerance test was performed in fasting rats. Oxytocin decreased food intake in both phenotypes while body weight gain reduced only in obese animals. In obese rats oxytocin impaired hepatic insulin extraction and enhanced liver triglyceride accumulation. Moreover, in the skeletal muscle of lean rats oxytocin treatment downregulated insulin signal transduction by decreasing of insulin receptor substrate 1 protein level and stimulating of its serine phosphorylation. Concurrently, the gene expression of insulin receptor substrate 1 in the skeletal muscle and adipose tissue was downregulated by oxytocin. In obese rats, oxytocin reduced adipocyte size and normalised mRNA levels of both fatty acid binding protein 4 and fatty acid synthase but attenuated gene expression of glucose transporter 4. The present study in Zucker fatty rats demonstrated ambivalent effects of oxytocin treatment with predominantly negative impact on skeletal muscle insulin pathway in lean animals.

Topics: Adipose Tissue; Animals; C-Peptide; Eating; Fatty Acid Synthase, Type I; Fatty Acid-Binding Proteins; Glucose Tolerance Test; Insulin; Leptin; Liver; Male; Muscle, Skeletal; Obesity; Oxytocin; Rats, Zucker; Receptors, Oxytocin; RNA, Messenger; Triglycerides

The changes in body composition and biomarker levels that occur during the aging process are complex and remain poorly understood. The present study aimed to evaluate changes in serum C-peptide levels and fat mass-to-lean mass ratio (FM/LM ratio) with increasing age, and to explore the associations between serum C-peptide levels and FM/LM ratio.. This was a population-based cross-sectional study that included 3912 participants aged 30-85 years. Body composition was measured using dual-energy X-ray absorptiometry. Analysis of covariance was used to evaluate how the serum C-peptide level and FM/LM ratio change with increasing age, as well as how the FM/LM ratio changes in line with increasing serum C-peptide level. A multiple linear regression analysis was carried out to determine the association between serum C-peptide level and FM/LM ratio.. Analysis of covariance showed that serum C-peptide levels, and most regional FM/LM ratios tended to increase in line with increasing age. Total fat mass, total lean mass, percentage total fat mass and total FM/LM ratio were significantly elevated, and percentage total lean mass decreased significantly with increasing serum C-peptide levels in both men and women. Multiple linear regression analysis showed that serum C-peptide level was strongly associated with the total FM/LM ratio.. The findings showed that both serum C-peptide level and FM/LM ratio increased with increasing age, and the serum C-peptide level was closely associated with changes in the total FM/LM ratio.

Topics: Absorptiometry, Photon; Adult; Aged; Aging; Body Mass Index; Bone Density; C-Peptide; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Obesity

To determine whether modestly severe obesity modifies glucose homeostasis, levels of cardiometabolic markers, and HDL function in African Americans (AAs) and white Americans (WAs) with prediabetes.. We studied 145 subjects with prediabetes (N = 61 WAs, N = 84 AAs, mean age 46.5 ± 11.2 years, mean BMI 37.8 ± 6.3 kg/m(2)). We measured fasting levels of lipids, lipoproteins, and an inflammatory marker (C-reactive protein [CRP]); HDL functionality (i.e., levels of paraoxonase 1 [PON1]); and levels of oxidized LDL, adiponectin, and interleukin-6 (IL-6). We measured serum levels of glucose, insulin, and C-peptide during an oral glucose tolerance test. Values for insulin sensitivity index (Si), glucose effectiveness index (Sg), glucose effectiveness at zero insulin (GEZI), and acute insulin response to glucose (AIRg) were derived using a frequently sampled intravenous glucose tolerance test (using MINMOD software).. Mean levels of fasting and incremental serum glucose, insulin, and C-peptide tended to be higher in WAs versus AAs. The mean Si was not different in WAs versus AAs (2.6 ± 2.3 vs. 2.9 ± 3.0 × 10(-4) × min(-1) [μU/mL](-1)). Mean values for AIRg and disposition index as well as Sg and GEZI were lower in WAs than AAs. WAs had higher serum triglyceride levels than AAs (116.1 ± 55.5 vs. 82.7 ± 44.2 mg/dL, P = 0.0002). Mean levels of apolipoprotein (apo) A1, HDL cholesterol, PON1, oxidized LDL, CRP, adiponectin, and IL-6 were not significantly different in obese AAs versus WAs with prediabetes.. Modestly severe obesity attenuated the ethnic differences in Si, but not in Sg and triglyceride levels in WAs and AAs with prediabetes. Despite the lower Si and PON1 values, AAs preserved paradoxical relationships between the Si and HDL/apoA1/triglyceride ratios. We conclude that modestly severe obesity has differential effects on the pathogenic mechanisms underlying glucose homeostasis and atherogenesis in obese AAs and WAs with prediabetes.

Topics: Adiponectin; Adult; Aged; Black or African American; Blood Glucose; C-Peptide; C-Reactive Protein; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Resistance; Interleukin-6; Lipid Metabolism; Lipoproteins; Lipoproteins, HDL; Male; Middle Aged; Obesity; Prediabetic State; Triglycerides; United States; White People; Young Adult

Obesity is a recognised positive risk factor for colorectal adenoma and colorectal cancer. Obesity is associated with insulin resistance and compensatory hyperinsulinaemia, and circulating insulin and C-peptide, a biomarker of insulin levels, have been positively associated with colorectal cancer risk. However, whether a similar relationship exists for colorectal adenomas, an established colorectal cancer precursor, is unclear.. In a nested case-control study of 273 colorectal adenoma cases and 355 matched controls from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, serum C-peptide levels were measured by a chemiluminescent immunometric assay. Multivariable unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for colorectal adenoma within quartiles of C-peptide. Further, to explore the temporal stability of C-peptide, repeat samples from the incident adenoma cases (n=50) and controls (n=30), over a 5-year period were assayed and the intra-class correlations (ICC) estimated.. In a multivariable model that included established colorectal adenoma risk factors, C-peptide levels were not associated with colorectal adenoma (Q4 vs. Q1, OR 0.83, 95% CI: 0.52-1.31; P-trend 0.32); similar null associations were observed by gender, by adenoma subsite and for advanced adenomas. Among control participants, the ICC value over a 5-year period was 0.66.. Our results suggest that higher C-peptide levels were not associated with colorectal adenoma incidence in this study population. Other biological pathways associated with obesity may be more relevant to the early stages of colorectal tumorigenesis.

Topics: Adenoma; C-Peptide; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Incidence; Male; Middle Aged; Obesity; Prospective Studies; Risk Factors

Obesity is a major risk factor for several cancers, including female cancers. Endogenous hormones and inflammatory factors may mediate the association between anthropometric measures and cancer risk, although these associations have been studied mainly in Caucasians. The aim of the current study was to explore the association of circulating hormones, adipokines, and inflammatory factors with obesity and overweight in premenopausal Mexican women.. We conducted a cross-sectional analysis of 504 premenopausal women from the large Mexican Teachers' Cohort (MTC, ESMaestras) study to determine the association of insulin-like growth factor I (IGF-I), its major circulating binding protein (IGFBP-3), leptin, adiponectin, C-peptide, and C-reactive protein with comprehensive measures of body size. Biomarkers were measured by immunoassays. Multivariate regression analyses were performed to compare geometric mean biomarker concentrations with measured markers of body size and adiposity.. Mean IGF-I and IGFBP-3 concentrations significantly increased with increasing height and leg length. Concentrations of IGF-I, adiponectin, and the IGF-I/IGFBP-3 ratio strongly decreased with increasing BMI, weight, waist and hip circumferences, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), while CRP, leptin, C-peptide concentrations, and the leptin/adiponectin ratio strongly increased. Adiponectin and the leptin/adiponectin ratio remained significantly related to measures of central adiposity (waist circumference, WHpR, and WHtR) after adjustment by body mass index.. The results of our study suggest a strong relation between biomarkers and body size in this study population and suggest that different fat depots may have different metabolic properties.

Topics: Adiposity; Adult; Biomarkers; Body Mass Index; Body Size; Body Weight; C-Peptide; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Female; Humans; Immunoassay; Inflammation; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Mexico; Middle Aged; Multivariate Analysis; Obesity; Overweight; Premenopause; Waist Circumference; Waist-Hip Ratio

Metabolic surgery is a novel therapy for mild obesity (BMI 30-35 Kg/m(2)) in type 2 diabetes mellitus (T2DM) patients. The ABCD score, which comprise age, BMI, C-peptide level, and duration of T2DM (years), was reported as useful in predicting the success of T2DM treatment using metabolic surgery. This study examines gastric bypass and sleeve gastrectomy as a salvage treatment for non-obese (BMI < 30 kg/m(2)) T2DM patients and evaluates the role of ABCD scores.. From January 2007 to July 2013, 512 (71.2%) of 711 T2DM patients enrolled in a metabolic surgical program had at least 1-year follow-up were recruited. Clinical data and outcomes of 80 (15.6%) patients with BMI < 30 Kg/m(2) were compared with those of the other 432 (84.4%) patients with BMI ≥ 30 Kg/m(2). Complete remission was defined as HbA1c ≤ 6%, and partial remission was defined as HbA1c < 6.5%. A binary logistic regression was used to identify predictors of T2DM remission.. Mean age of the 80 non-obese T2DM patients was 47.7 ± 9.1 years, and mean HbA1c and disease duration were 9.1 ± 1.8% and 6.5 ± 5.1 years, respectively. Mean total body weight loss was 17.1 ± 7.4% at 1 year, and mean BMI decreased from 26.9 ± 2.2 to 22.7 ± 2.5 kg/m(2) at 1 year. Complete remission of T2DM was achieved in 25.0% of patients, and partial remission was achieved in 23.8%. The complete remission rate was significantly lower than the 49.5% found in patients with BMI 30-35 and 79.0% of patients with BMI > 35 Kg/m(2). In univariate analysis, non-obese patients who had T2DM remission after surgery were heavier and had a wider waist, higher C-peptide levels, shorter disease duration, more weight loss, and higher ABCD score than those without remission. The ABCD score remained the only independent predictor of success after multivariate logistical regression analyses (P = 0.003).. Metabolic surgery may be useful in achieving glycemic control of selected non-obese T2DM patients. The ABCD score is a simple multidimensional grading system that can predict the success of T2DM treatment.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastrectomy; Gastric Bypass; Humans; Male; Middle Aged; Obesity; Prognosis; Remission Induction; Research Design; Time Factors; Weight Loss

Type 1 diabetes (T1D) TrialNet is a National Institutes of Health-sponsored clinical trial network aimed at altering the disease course of T1D. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic and immunologic characteristics of individuals with recent-onset T1D, to identify cohorts of interest and to aid in planning of future studies.. Eight hundred eighty-three individuals with recent-onset T1D involved in five TrialNet studies were categorized by age as follows: ≥18 years, 12-17 years, 8-12 years and <8 years. Data were compared with healthy age-matched subjects in the National Health and Nutrition Examination Survey.. Only 2.0% of the individuals overall were excluded from trial participation because of insufficient C-peptide values (<0.2 pmol/mL). A disproportionate number of these subjects were <8 years old. Leukopenia was present in 21.2% of individuals and lymphopenia in 11.6%; these frequencies were markedly higher than age-matched healthy National Health and Nutrition Examination Survey population. Of the cohort, 24.5% were overweight or obese. Neither high-risk human leukocyte antigen type DR3 nor DR4 was present in 31% of adults and 21% of children.. The ability of recent-onset T1D patients to meet key entry criteria for TrialNet studies, including C-peptide >0.2 pmol/mL, varies by age. Lower C-peptide level requirements for younger participants and other aspects of heterogeneity of recent-onset T1D patients, such as white blood cell count abnormalities and body mass index should be considered in the design of future clinical studies.

Topics: Adolescent; Adult; Age Factors; Autoantibodies; Biomarkers; Body Mass Index; C-Peptide; Child; Cohort Studies; Diabetes Mellitus, Type 1; Humans; Italy; Leukopenia; Lymphopenia; Middle Aged; North America; Obesity; Overweight; Pediatric Obesity; Young Adult

Circulating levels of the adipokine adipocyte fatty acid-binding protein (AFABP) are increased in obesity. However, the influence of circulating AFABP on insulin sensitivity in vivo remains unclear.. C57BL/6NTac mice (10 weeks) were treated over 8 weeks i.p. with saline (control) or recombinant AFABP (0.5 mg/kg/d). A comprehensive characterization of metabolic parameters, body composition, and energy expenditure was performed. Furthermore, the effect of AFABP on pancreatic β-cell responsiveness, hepatic glycogen content, and peroxisome proliferator-activated receptor (PPAR) γ protein expression was elucidated.. In male mice, AFABP treatment induced insulin resistance with significantly increased fasting insulin, C-peptide, and homeostasis model assessment of insulin resistance. In female animals, a similar trend was observed. In both genders, no difference in body weight, lipid parameters, body composition, or energy expenditure could be detected between AFABP-treated and control mice. Insulin resistance in male AFABP-treated mice was accompanied by decreased PPARγ protein content in perigonadal adipose tissue and diminished circulating adiponectin. AFABP treatment did not affect pancreatic β-cell responsiveness and hepatic glycogen content.. Circulating AFABP induces insulin resistance in male mice. AFABP-mediated degradation of PPARγ in adipose tissue and subsequently decreased expression of insulin-sensitizing adiponectin are potential mechanisms for this effect.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Body Weight; C-Peptide; Fatty Acid-Binding Proteins; Female; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; PPAR gamma

Hyperglycemia represents one of possible mediators for activation of immune system and may contribute to worsening of inflammatory state associated with obesity. The aim of our study was to investigate the effect of a short-term hyperglycemia (HG) on the phenotype and relative content of immune cells in circulation and subcutaneous abdominal adipose tissue (SAAT) in obese women without metabolic complications.. Three hour HG clamp with infusion of octreotide and control investigations with infusion of octreotide or saline were performed in three groups of obese women (Group1: HG, Group 2: Octreotide, Group 3: Saline, n=10 per group). Before and at the end of the interventions, samples of SAAT and blood were obtained. The relative content of immune cells in blood and SAAT was determined by flow cytometry. Gene expression analysis of immunity-related markers in SAAT was performed by quantitative real-time PCR.. In blood, no changes in analysed immune cell population were observed in response to HG. In SAAT, HG induced an increase in the content of CD206 negative monocytes/macrophages (p<0.05) and T lymphocytes (both T helper and T cytotoxic lymphocytes, p<0.01). Further, HG promoted an increase of mRNA levels of immune response markers (CCL2, TLR4, TNFα) and lymphocyte markers (CD3g, CD4, CD8a, TBX21, GATA3, FoxP3) in SAAT (p<0.05 and 0.01). Under both control infusions, none of these changes were observed.. Acute HG significantly increased the content of monocytes and lymphocytes in SAAT of healthy obese women. This result suggests that the short-term HG can modulate an immune status of AT in obese subjects.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; Cell Count; Female; Gene Expression Regulation; Health; Humans; Hyperglycemia; Insulin; Macrophages; Monocytes; Obesity; Octreotide; Phenotype; RNA, Messenger; Subcutaneous Fat, Abdominal; T-Lymphocytes

Individuals with Prader-Willi syndrome (PWS) are commonly restricted to 60-75% of height-appropriate calorie intake because they rapidly become obese on a normal diet. This study measured changes in energy expenditure, glucose and lipid homeostasis, and metabolic flexibility in response to a meal in PWS adults.. 11 adults with PWS were compared with 12 adiposity-matched and 10 lean subjects. Indirect calorimetry was conducted at baseline and 210 min after a standardized 600 kCal breakfast to assess energy expenditure and substrate utilization. Circulating glucose, insulin, C-peptide, glucagon, nonesterified fatty acids, and triglycerides were measured up to 240 min. Insulin sensitivity and insulin secretion rate were assessed by HOMA-IR and C-peptide deconvolution, respectively. Body composition was determined by dual-energy X-ray absorptiometry.. The PWS group had lower lean mass than the obesity control group. Corrected for lean mass, there were no differences between the PWS and obesity groups in resting metabolic rate or metabolic flexibility. Total and abdominal fat mass, insulin sensitivity, and insulin secretion rate were also similar between these groups.. This study did not detect an intrinsic metabolic defect in individuals with PWS. Rather, lower lean mass, combined with lower physical activity, may contribute to weight gain on an apparent weight-maintenance diet.

Topics: Absorptiometry, Photon; Adiposity; Adult; Basal Metabolism; Body Composition; C-Peptide; Energy Metabolism; Female; Glucose; Humans; Insulin; Insulin Resistance; Male; Obesity; Postprandial Period; Prader-Willi Syndrome; Triglycerides

C-peptide has been reported to be a marker of subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, whereas its role in coronary artery disease (CAD) has not been clarified, especially in diabetics with differing body mass indices (BMIs).. This cross-sectional study included 501 patients with T2DM. First, all subjects were divided into the following two groups: CAD and non-CAD. Then, binary logistic regression was used to determine the risk factors for CAD for all patients. To clarify the role of obesity, we re-divided all subjects into two additional groups (obese and non-obese) based on BMI. Finally, binary logistic regression was used to determine the risk factors for CAD for each weight group.. The patients with CAD showed a higher BMI and fasting C-peptide level in addition to an increased prevalence of traditional risk factors for CAD, such as hypertension, insulin resistance, higher cholesterol, cysteine-C (Cys-C) and lower estimated glomerular filtration rate (eGFR). Logistic regression analysis showed that fasting C-peptide (OR=1.513, p=0.005), insulin treatment (OR=1.832, p=0.027) hypertension (OR=1.987, p=0.016) and hyperlipidemia (OR=4.159, p<0.001) significantly increased the risk of clinical CAD in the T2DM patients independent of age, gender, diabetes duration, smoking and alcohol statuses, fasting insulin and glucose, hypoglycemic episodes, UA and eGFR. Additionally, in both of the obese (OR=1.488, p=0.049) and non-obese (OR=1.686, p=0.037) DM groups, C-peptide was associated with an increased risk of CAD after multiple adjustments.. C-peptide is associated with an increased CAD risk in T2DM patients, no matter whether they are obese or not.

Topics: Body Mass Index; C-Peptide; Coronary Artery Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Logistic Models; Obesity; Risk Factors

Third trimester fetal growth is partially regulated by C-peptide and insulin-like growth factor I (IGF-I). Prenatal exposures including maternal obesity and high gestational weight gain as well as high birth weight have been linked to subsequent metabolic disease. We evaluated the associations between newborn regional body composition and cord blood levels of C-peptide and IGF-I.. We prospectively included obese and normal-weight mothers and their newborns; cord blood was collected and frozen. Analyses of C-peptide and IGF-I were performed simultaneously, after recruitment was completed. Newborn regional body composition was assessed with dual-energy X-ray absorptiometry scanning (DXA) within 48 hours of birth.. Three hundred thirty-six term infants were eligible to participate in the study; of whom 174 (52%) infants had cord blood taken. Total, abdominal and arm and leg fat mass were positively associated with C-peptide (p < 0.001). Arm and leg fat mass was associated with IGF-I concentration: 28 g [95% confidence interval: 4, 53] per doubling of IGF-I. There was no association between total or abdominal fat mass and IGF-I. Fat-free mass was positively associated with both C-peptide (p < 0.001) and IGF-I (p = 0.004).. Peripheral fat tissue accumulation was associated with cord blood C-peptide and IGF-I. Total and abdominal fat masses were related to C-peptide but not to IGF-I. Thus, newborn adiposity is partially mediated through C-peptide and early linear growth is associated with IGF-I.

Topics: Abdomen; Absorptiometry, Photon; Adiposity; Arm; Body Composition; Body Mass Index; C-Peptide; Female; Fetal Blood; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Leg; Male; Mothers; Obesity; Pregnancy; Prospective Studies

Stress during pregnancy is a known contributing factor for the development of obesity in the offspring. Since maternal obesity is on the rise, we wanted to identify the effects of prenatal stress in the offspring of diet-induced obese (DIO) rats and compare them with the offspring of dietary-resistant (DR) rats. We hypothesized that prenatal stress would make both DIO and DR offspring susceptible to obesity, but the effect would be more pronounced in DIO rats. Pregnant DIO and DR rats were divided into two groups: nonstressed controls (control) and prenatal stress (subjected to restraint stress, three times/day from days 14 to 21 of gestation). After recording birth weight and weaning weight, male offspring were weaned onto a chow diet for 9 wk and shifted to a high-fat (HF) diet for 1 wk. At the end of the 10th wk the animals were euthanized, and visceral adipose mass, blood glucose, serum insulin, and C-peptide levels were measured. Prenatal stress resulted in hyperinsulinemia and higher C-peptide levels without altering caloric intake, body weight gain, or fat mass in the DIO offspring after 1 wk of HF intake, but not in DR offspring. To determine the mechanism underlying the hyperinsulinemia, we measured the levels of CEACAM1 that are responsible for insulin clearance. CEACAM1 levels in the liver were reduced in prenatally stressed DIO offspring after the HF challenge, suggesting that preexisting genetic predisposition in combination with prenatal stress increases the risk for obesity in adulthood, especially when offspring are fed a HF diet.

Topics: Animals; Blood Glucose; C-Peptide; Carcinoembryonic Antigen; Diet, High-Fat; Female; Genetic Predisposition to Disease; Hyperinsulinism; Insulin; Intra-Abdominal Fat; Obesity; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rats; Restraint, Physical; Stress, Psychological

We investigated whether obese pregnant women negative for gestational diabetes (GDM) still experience dysglycemia, as indicated by high glycated hemoglobin (Hb A1c) at delivery, and whether this impacts offspring and long-term maternal outcomes.. Data of 462 mother-child pairs of our prospective Programming of Enhanced Adiposity Risk in Childhood - Early Screening (PEACHES) cohort study were analyzed. Of 885 obese and normal-weight pregnancies prospectively enrolled after GDM testing according to the International Association of Diabetes and Pregnancy Study Groups criteria, 462 GDM-negative mothers and their offspring were investigated. We assessed associations of maternal Hb A1c at delivery with large-for-gestational-age (LGA) birth weights, cord-blood C-peptide, and biomarkers of glucose metabolism and inflammation in obese mothers followed for 2.9 years (median) postpartum (n = 42).. Cumulative distribution analysis in GDM-negative normal-weight women (n = 155) revealed that 12% had Hb A1c ≥5.7% at delivery (high Hb A1c). Among obese GDM-negative women (n = 307), 31.9% (95% CI, 26.7%-37.4%) equaled or exceeded this cutoff. In obese GDM-negative women with Hb A1c ≥5.7% (n = 98) vs <5.7% (n = 209) at delivery, newborns were more likely to be born LGA [adjusted odds ratio 3.56 (95% CI, 1.64-8.02)], and mean cordblood serum C-peptide was increased by 0.09 ng/mL (95% CI, 0.01-0.17 ng/mL). In the mothers at follow-up, mean postpartum Hb A1c, fasting glucose, high-sensitivity C-reactive protein, and fibrinogen concentrations were higher by 0.3% (95% CI, 0.1%-0.5%), 6.0 mg/dL (95% CI, 2.4-9.5 mg/dL), 6.8 mg/L (95% CI, 1.4-12.3 mg/L), and 74.9 mg/dL (95% CI, 13.6-136.2 mg/dL), respectively.. Increased Hb A1c in obese GDM-negative women at delivery indicates gestational dysglycemia, potentially conferring offspring and long-term maternal health risks. These findings should raise awareness as to careful monitoring of obese pregnancies. Measurement of Hb A1c at delivery could help select women who may need closer postpartum health checks.

Topics: Birth Weight; Blood Glucose; C-Peptide; Child, Preschool; Delivery, Obstetric; Diabetes, Gestational; Female; Fetal Blood; Glycated Hemoglobin; Humans; Infant; Infant, Newborn; Male; Obesity; Postpartum Period; Pregnancy; Pregnancy Complications; Prospective Studies

Betatrophin has been suggested as an inducer of β-cell proliferation in mice in addition to its function in regulating triglyceride. Recent data showed that betatrophin was increased in Type 2 Diabetes (T2D), however, its ability to induce insulin production has been questioned. We hypothesized that the increased betatrophin in T2D is not affecting insulin production from β-cells. To test this hypothesis, we investigated the association between betatrophin and C-peptide level in humans, which acts as a measure of endogenous insulin production from β-cells.. This study was designed to examine the association between plasma betatrophin level and C-peptide in 749 T2D and non-diabetics.. Betatrophin and C-peptide levels were higher in T2D subjects compared with non-diabetics subjects. Betatrophin showed strong correlation with C-peptide in non-diabetics subjects (r = 0.28, p = < 0.0001). No association between betatrophin and C-peptide were observed in T2D subjects (r = 0.07, p = 0.3366). Dividing obese and non-obese subjects into tertiles according to betatrophin level showed significantly higher C-peptide levels at higher tertiles of betatrophin in obese non-diabetics subjects P-trend = 0.0046. On the other hand, C-peptide level was significantly higher in subject with higher betatrophin level in non-diabetics subjects across all age groups but not in T2D subjects. Multiple logistic regression models adjusted for age, BMI, gender, ethnicity as well as C-peptide level showed that subjects in the highest tertiles of betatrophin had higher odds of having T2D [odd ratio (OR) = 7.3, 95% confidence interval (CI) 4.0-13.3].. Increased betatrophin level in obese subjects is correlated with an increase in C-peptide level; which is possibly caused by the increased insulin resistance. On the other hand, no correlation is observed between increased betatrophin level and C-peptide in T2D subjects. In conclusion, the increased betatrophin in T2D subject does not cause any increase in insulin production as indicated by C-peptide level.

Topics: Adult; Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Arabs; Asian People; Biomarkers; C-Peptide; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; India; Insulin Resistance; Kuwait; Male; Middle Aged; Obesity; Pakistan; Peptide Hormones; Up-Regulation

Since insulin resistance is genetically determined and observed in type 1 diabetes, the study was designed to elucidate an involvement of Ala 12 Pro PPARg2 gene polymorphism in residual C-peptide secretion and BMI variation in children with type 1 diabetes.. In 103 patients with type 1 diabetes genetic analysis of PPARg2 polymorphism, C-peptide measurements and evaluation of BMI and clinical parameters were performed. Control group consisted of 109 healthy subjects.. In diabetic patients, only three individuals exhibited Ala 12 Ala genotype (2.9%) and 29 patients were heterozygous Ala 12 Pro (28.2%). Interestingly, Ala12+ variants were associated with higher C-peptide levels in 6 th , 12 th and 24 th months after the onset than Pro 12 Pro genotype (0.39±0.24 pmol/mL vs. 0.22±0.14 pmol/mL, P=0.007 and 0.19±0.09 vs. 0.11±0.07, P=0.01 and 0.13±0.09 vs. 0.07±0.05, P=0.021, respectively). Similarly, C-peptide was also significantly increased in patients with history of type 2 diabetes in the first-degree relatives. The observation was even more evident when Ala12+ variants were taken together with family history of type 2 diabetes. Besides, in 24 th and 36 th months after the onset, Ala12+ variants revealed to be associated with higher BMI normalized by age and sex as compared to Pro 12 Pro (0.557±0.84 vs. -0.119±0.73, P=0.001 and 0.589±0.919 vs. 0.066±0.630, P=0.016, respectively).. Thus, it is likely that PPARg2 gene polymorphism and/or the genetically determined insulin resistance may be associated with residual C-peptide secretion and involve excessive BMI in type 1 diabetes.. Wprowadzenie i cel pracy. Z uwagi na występowanie w cukrzycy typu 1 (T1D) zjawiska insulinooporności oraz możliwość jej genetycznego uwarunkowania celem pracy była ocena wpływu polimorfizmu Ala 12 Pro genu PPARg2 na resztkową insulinosekrecję mierzoną stężeniem peptydu C oraz zmiany wartości indeks BMI u dzieci z cukrzycą typu 1. Materiał i metody. W grupie 103 pacjentów z T1D została przeprowadzona analiza genetyczna polimorfizmu genu PPARg2, pomiary stężenia peptydu C oraz ocena indeksu BMI i parametrów klinicznych. Grupa kontrolna obejmowała 109 zdrowe osoby. Wyniki. U pacjentów z T1D jedynie 3 dzieci posiadało genotyp Ala 12 Ala (2.9%), podczas gdy 29 pacjentów było heterozygotami Ala 12 Pro (28.2%). Interesujące, że warianty Ala12+ były związane z wyższym stężeniem peptydu C w 6, 12 oraz 24 miesiącu trwania choroby w porównaniu z genotypem Pro 12 Pro (0.39±0.24 pmol/mL vs. 0.22±0.14 pmol/mL, P=0.007 i 0.19±0.09 vs. 0.11±0.07, P=0.01 oraz 0.13±0.09 vs. 0.07±0.05, P=0.021, odpowiednio). Podobnie stężenie peptydu C było istotnie wyższe u pacjentów z dodatnim wywiadem w kierunku cukrzycy typu 2 u krewnych pierwszego stopnia. Obserwacja ta była jeszcze bardziej wyraźna, gdy warianty Ala12 + były oceniane łącznie z rodzinnym wywiadem cukrzycy typu 2. Ponadto pacjenci, u których stwierdzono warianty Ala12+ charakteryzowali się w 24 i 36 miesiącu trwania cukrzycy wyższym indeksem BMI znormalizowanym pod względem płci i wieku w porównaniu do nosicieli Pro 12 Pro (0.557±0.84 vs. -0.119±0.73, P=0.001 i 0.589±0.919 vs. 0.066±0.630, P=0.016, odpowiednio). Wnioski. Wydaje się prawdopodobne, że polimorfizm genu PPARg2 i/lub genetycznie uwarunkowana insulinooporność mogą być związane z resztkową insulinosekrecją oraz wzrostem BMI w cukrzycy typu 1 u dzieci.

Topics: Adolescent; Body Mass Index; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Genetic Predisposition to Disease; Humans; Insulin Resistance; Male; Obesity; Poland; Polymorphism, Genetic; PPAR gamma; Risk Factors

The study was undertaken to assess the selected carbohydrate parameters in children exposed to gestational diabetes in utero.. 50 children exposed to gestational diabetes were compared with 46 control subjects. Anthropometric parameters of a newborn were obtained from the medical records. In all participants height, body mass, waist and hip circumferences were measured; BMI, WHR and WHtR were calculated. Values of fasting glucose, insulin, C-peptide and HbA1c were measured and HOMA2-IR, HOMA2-S, HOMA2-B were calculated. In obese children (BMI ≥95th percentile) OGTT was performed.. The prevalence of overweight/obesity in the study group was 38%, in the control group 41% (p=0.19). Higher fasting glucose level (p=0.02) and HbA1c (p=0.00004) were found in the study group comparing to the control. In children exposed to GDM in utero a positive correlation of fasting insulin and WHR (Rs=0.31, p=0.028) as well as significantly lower HOMA2-B (p=0.03) were observed. In the study group higher HOMA2-IR (p=0.0002) and HOMA2-B (p=0.0000039) and also lower HOMA2-S (p=0.0002) were observed among participants with overweight/obesity comparing to children with normal body weight. In the study group a correlation of HOMA2-IR and SD of the birth weight was found (Rs=0.28, p=0.049).. Children exposed to gestational diabetes in utero, in spite of similar prevalence of overweight/obesity comparing to their non-exposed peers, could have higher risk of glucose intolerance and diabetes mellitus in future. Towards observed decreased insulin sensitivity and compensatory increase in insulin secretion, prevention of overweight and obesity in this group seems to be essential.

Topics: Adolescent; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Child; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Obesity; Overweight; Pregnancy; Prenatal Exposure Delayed Effects; Prevalence; Waist-Height Ratio; Waist-Hip Ratio

Metabolically healthy obese (MHO) are relatively insulin sensitive and have a favorable cardio-metabolic risk profile compared with metabolically abnormal obese (MAO). To evaluate whether MAO individuals have a decreased insulin clearance compared with MHO individuals, 49 MHO, 147 MAO, and 172 non-obese individuals were analyzed in this cross-sectional study. Insulin clearance and insulin sensitivity were assessed through euglycemic hyperinsulinemic clamp. MHO subjects exhibited significant lower triglycerides, total cholesterol, 2-h post-challenge glucose, fasting and 2-h post-challenge insulin, steady-state plasma insulin, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase as compared with MAO individuals. Disposition index was higher in MHO subjects as compared with MAO individuals after adjusting for gender and age (P = 0.04). Insulin clearance was significantly lower in MAO individuals as compared with MHO and non-obese individuals. The difference between the two obese subgroups remained significant after adjusting for gender, age, waist circumference, fat mass, and insulin-stimulated glucose disposal (P = 0.03). The hepatic insulin extraction (C-peptide/insulin) in the fasting state was significantly higher in MHO subjects as compared with MAO individuals (P < 0.0001). In univariate analysis adjusted for gender and age, insulin clearance was correlated with hepatic insulin extraction (P = 0.01). In conclusion, insulin clearance differs among obese subjects with different metabolic phenotypes. Impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia observed in MAO individuals.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; C-Peptide; Chi-Square Distribution; Cholesterol; Cross-Sectional Studies; Female; gamma-Glutamyltransferase; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Male; Obesity; Triglycerides; Waist Circumference

Weight gain in breast cancer patients during treatment is prevalent; the metabolic implications of this weight gain are poorly understood. We aimed to characterize glucose metabolism in breast cancer patients near the initiation of chemotherapy.. Stage I-II breast cancer patients (n = 8) were evaluated near the initiation of chemotherapy and compared with a group of age- and body mass index-matched, as well as a group of young healthy, non-malignant females. Fasting blood samples (analyzed for lipids and cytokines) were taken and an oral glucose tolerance test was performed. Body composition, waist circumference, diet, cardiovascular fitness and muscle strength were evaluated.. Breast cancer patients were abdominally obese (mean ± SD: 94.6 ± 14.0 cm), overweight (28.8 ± 6.0 kg/m(2)) and dyslipidemic (triacylglycerides: 1.84 ± 1.17 mM; high-density lipoprotein cholesterol: 1.08 ± 0.23 mM). Compared to non-malignant matched females, fasting glucose and insulin concentrations were similar but fasting c-peptide was greater in patients (2.6 ± 1.2 ng/mL vs. 1.9 ± 0.8 ng/mL, p = 0.005). Glucose was elevated to a greater extent in patients during the oral glucose tolerance test compared with all non-malignant females. During the glucose tolerance test, c-peptide, but not insulin, remained elevated in patients compared with all non-malignant females. No differences in body composition, serum cytokines, nutrition or exercise capacity between patients and matched, non-malignant females emerged.. Breast cancer patients present with unhealthy metabolic features early in the disease trajectory. Future investigations need to examine the underlying mechanisms and the potential longitudinal changes following chemotherapy.

Topics: Adolescent; Adult; Blood Glucose; Body Composition; Body Mass Index; Breast Neoplasms; C-Peptide; Cholesterol, HDL; Cytokines; Diet Records; Dyslipidemias; Energy Intake; Energy Metabolism; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Middle Aged; Motor Activity; Muscle Strength; Obesity; Waist Circumference; Weight Gain; Young Adult

Although elevated serum C-peptide level as an indicator of insulin resistance increases the obesity-associated risk of cardiovascular disease among diabetic patients, evidence indicating that serum C-peptide level is associated with stroke in nondiabetic subjects is limited. The aim of this study is to evaluate the association between serum C-peptide level and ever stroke in nondiabetic subjects and investigated the associations of serum C-peptide level with body fat distribution and stroke events among nondiabetic subjects.. This study was a population-based cross-sectional study that included 7030 participants aged 12-85 years. Body fat distribution was determined by dual-energy X-ray absorptiometry. Serum C-peptide level was measured using the radioimmunoassay method. The association between serum C-peptide level and body fat distribution was evaluated by multiple linear regression models. Logistic regression analysis was performed to calculate the odds ratio (OR) of serum C-peptide level being associated with ever stroke.. A total of 103 nondiabetic subjects reported having a stroke. Logistic regression analysis revealed a high-serum C-peptide level significantly associated with ever stroke among nondiabetic subjects (OR: 3.71, 95% confidence interval: 1.78-7.75). Meanwhile, in multiple linear regression analysis, serum C-peptide level was positively associated with total and regional fat distribution among nondiabetic subjects.. The serum C-peptide level is strongly associated with the ever stroke in nondiabetic subjects and significantly associated with total and regional body fat distribution.

Topics: Absorptiometry, Photon; Adiposity; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; C-Peptide; Child; Cross-Sectional Studies; Female; Humans; Linear Models; Logistic Models; Male; Middle Aged; Nutrition Surveys; Obesity; Odds Ratio; Radioimmunoassay; Risk Factors; Stroke; United States; Up-Regulation; Young Adult

Neonatal body fat is an important indicator of foetal energy supply and growth with potential importance for long-term health. In this study, we wanted to explore seasonal variation of 25-hydroxy-vitamin D (25(OH)D) in maternal and umbilical cord plasma (UCP) to examine whether maternal and foetal 25(OH)D levels were associated with maternal BMI and neonatal fat mass (FM), and to explore the relationship among maternal and neonatal 25(OH)D levels, maternal glucose/insulin levels and UCP C-peptide.. An observational, prospective study of determinants of foetal growth and birth weight in healthy pregnant women. Total body composition in 202 newborns was measured by dual-energy X-ray absorptiometry. Circulating levels of biomarkers were assessed in mothers at gestational weeks 14-16 and 30-32 and UCP.. The mean 25(OH)D concentration in UCP was significantly lower than in maternal circulation (31 vs 45 nmol/l, P<0.001). Maternal and UCP 25(OH)D levels varied significantly with season. No significant association between maternal BMI (weeks 14-16) and UCP 25(OH)D concentration was found. We found a strong positive association between maternal 25(OH)D and UCP 25(OH)D (P<0.001). There was no significant linear association between maternal BMI (weeks 14-16) and maternal 25(OH)D. We found no association between maternal 25(OH)D levels and glucose/insulin levels, nor with maternal or UCP 25(OH)D on UCP C-peptide levels. Finally, neonatal total body FM was positively associated with UCP 25(OH)D, P=0.02.. We demonstrated seasonal variation in maternal and neonatal 25(OH)D levels at northern latitudes. UCP, but not maternal, 25(OH)D was a significant predictor of neonatal total FM. Maternal BMI and metabolic parameters such as glucose, insulin and UCP C-peptide levels were not associated with 25(OH)D in mothers or offspring.

Topics: Absorptiometry, Photon; Adiposity; Adult; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Female; Fetal Blood; Fetal Development; Humans; Infant, Newborn; Insulin; Linear Models; Male; Norway; Obesity; Pregnancy; Prospective Studies; Seasons; Vitamin D; Vitamin D Deficiency

Previously we reported studies of XMetA, an agonist antibody to the insulin receptor (INSR). We have now utilized phage display to identify XMetS, a novel monoclonal antibody to the INSR. Biophysical studies demonstrated that XMetS bound to the human and mouse INSR with picomolar affinity. Unlike monoclonal antibody XMetA, XMetS alone had little or no agonist effect on the INSR. However, XMetS was a strong positive allosteric modulator of the INSR that increased the binding affinity for insulin nearly 20-fold. XMetS potentiated insulin-stimulated INSR signaling ∼15-fold or greater including; autophosphorylation of the INSR, phosphorylation of Akt, a major enzyme in the metabolic pathway, and phosphorylation of Erk, a major enzyme in the growth pathway. The enhanced signaling effects of XMetS were more pronounced with Akt than with Erk. In cultured cells, XMetS also enhanced insulin-stimulated glucose transport. In contrast to its effects on the INSR, XMetS did not potentiate IGF-1 activation of the IGF-1 receptor. We studied the effect of XMetS treatment in two mouse models of insulin resistance and diabetes. The first was the diet induced obesity mouse, a hyperinsulinemic, insulin resistant animal, and the second was the multi-low dose streptozotocin/high-fat diet mouse, an insulinopenic, insulin resistant animal. In both models, XMetS normalized fasting blood glucose levels and glucose tolerance. In concert with its ability to potentiate insulin action at the INSR, XMetS reduced insulin and C-peptide levels in both mouse models. XMetS improved the response to exogenous insulin without causing hypoglycemia. These data indicate that an allosteric monoclonal antibody can be generated that markedly enhances the binding affinity of insulin to the INSR. These data also suggest that an INSR monoclonal antibody with these characteristics may have the potential to both improve glucose metabolism in insulinopenic type 2 diabetes mellitus and correct compensatory hyperinsulinism in insulin resistant conditions.

Topics: Allosteric Site; Animals; Antibodies, Monoclonal; Antigens, CD; C-Peptide; Cell Separation; CHO Cells; Cricetinae; Cricetulus; Diabetes Mellitus, Type 2; Flow Cytometry; Glucose; Humans; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Resistance; Mice; Mice, Inbred C57BL; Obesity; Peptide Library; Phosphorylation; Protein Structure, Tertiary; Receptor, Insulin; Signal Transduction

Proton pump inhibitors as adjunctive therapy would improve diabetes control and could enhance the hypoglycaemic activity of DPP-4 inhibitors. The aim of the study was to investigate the short-term effects of lansoprazole (LPZ), sitagliptin (SITA) and their combination therapy on glucose regulation and gut peptide secretion.. Glucose and gut peptide were determined and compared after short-term administration of LPZ or SITA, or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects (n = 16) in a 75 g oral glucose tolerance test (OGTT) by a crossover design.. In DIO mice, LPZ significantly improve glucose metabolism, increase plasma C-peptide and insulin compared with vehicle treatment. Furthermore, the combination of LPZ and SITA improved glucose tolerance additively, with higher plasma insulin and C-peptide levels compared with SITA-treated mice. Similarly, in human in the OGTT, the combination showed significant improvement in glucose-lowering and insulin increase vs SITA-treated group. However, no significant differences in area under curve (AUC) of insulin, glucose and C-peptide between the LPZ-treated group and baseline, except that mean AUCgastrin was significantly increased by LPZ.. LPZ and SITA combination therapy appears to have complementary mechanisms of action and additive antidiabetic effect.

Topics: Adult; Animals; Area Under Curve; Blood Glucose; C-Peptide; Diet; Drug Synergism; Drug Therapy, Combination; Glucose; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Lansoprazole; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Pyrazines; Sitagliptin Phosphate; Triazoles

To examine the associations between gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines and neonatal adiposity in the five North American field centers of the Hyperglycemia and Adverse Pregnancy Outcome study.. GWG was categorized as less than, within, or greater than 2009 IOM guidelines. Birthweight, body fat percentage, cord serum C-peptide, and sum of neonatal flank, subscapular, and triceps skin fold thicknesses were dichotomized as >90th percentile or ≤90th percentile obtained by quantile regression. Logistic regression analysis was used.. Of the 5297 participants, 11.6% gained less, 31.9% gained within, and 56.5% gained more than the recommendation. With adjustment for glucose tolerance levels, normal and overweight women who gained more than the recommendation had increased odds of delivering infants with sum of skin folds >90th percentile (OR = 1.75 and 4.77, respectively) and percentage body fat >90th percentile (OR = 2.41 and 2.59, respectively), and normal weight and obese women who gained more than the recommendation had increased odds of delivering infants with birthweight >90th percentile (OR = 2.80 and 1.93, respectively) compared to women who gained within the recommendation.. This analysis showed independent associations between exceeding IOM GWG recommendations and neonatal adiposity in normal and overweight women, controlling for glucose tolerance levels.

Topics: Adiposity; Adult; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Female; Gestational Age; Glucose Tolerance Test; Humans; Hyperglycemia; Infant, Newborn; Male; North America; Obesity; Overweight; Pregnancy; Pregnancy Complications; Pregnancy Outcome; United States; Weight Gain

This study aims to investigate if the benefits on glycemic control following Roux-en-Y gastric bypass (RYGB) in morbidly obese type 2 diabetes (T2DM) patients are maintained in the 30-35 kg/m(2) BMI (body mass index) range, comparing results with those in literature.. The study participants were twenty T2DM patients aging 35-70 years, BMI 30.0-34.9 kg/m(2), minimum diabetes duration 3 years, glycosylated haemoglobin (HbA1c) ≥7.5% despite good clinical practice medical therapy, submitted to laparoscopic RYGB, and monitored during 36 months. Twenty-seven matched diabetic patients as controls.. Five females, mean age 57 (42-69) years, weight 96.0 (70-111) kg, BMI 32.9 (30.3-34.9) kg/m(2), waist circumference 112 (100-128) cm, diabetes duration 14 (3-28) years, HbA1c 9.5 (7.5-14.2) %, and C-peptide 3.2 (1,6-9.1) mcg/l. Ten patients were on insulin. There was no mortality, and there were two major late complications. BMI and waist decreased stabilizing around 25 kg/m(2) and 92 cm. Fasting serum glucose and HbA1c reached values around 150 mg/dl and 7%, which subsequently maintained. There was remission in 25% of cases, control 45%, and all the others improved. HOMA-IR and insulin sensitivity index normalized at 1 month, then maintained. AIR and insulinogenic index showed no postoperative changes. Diabetes remission correlated negatively with duration (p < 0.05; r (2) = 0.61), while control positively with C-peptide (p < 0.05; r (2) = 0.19). In the control group, FSG, HbA1c, serum triglyceride, and cholesterol significantly decreased with considerable progressive increase of antidiabetic/antihyperlipemic therapy. All patients had HbA1c >7% at 2-3 years.. Glycemic control obtained by RYGB in this study was less good than that reported by others, apparently due to different patient selection criteria. Our results do not support RYGB weight loss-independent effect on beta-cell function in the T2DM patients with BMI 30-35 kg/m(2).

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glycated Hemoglobin; Humans; Insulin Resistance; Laparoscopy; Male; Middle Aged; Obesity; Patient Selection; Remission Induction; Treatment Outcome; Waist Circumference; Weight Loss

Diverticulosis can lead to diverticulitis, a colon condition involving inflammation and other complications. Diverticulosis can result from biological, behavioral, or genetic causes. However, the etiology of diverticulosis is unknown. Although diet is associated with diverticulosis, recent studies suggest other factors influence risk. We sought to identify anthropometric or serum markers that were associated with the presence of diverticulosis. To determine these associations, 126 asymptomatic men (48-65 yr) were recruited at the time of preventative screening colonoscopy. Anthropometric measures were taken, and blood was collected for serum protein analysis. Data were analyzed by logistic regression and factor analysis. Obese individuals (BMI >30) were 7.8 (CI: 2.3-26.3) times more likely than normal weight (BMI <25) individuals to have diverticulosis. The relationship was similar for waist circumference. Individuals with a waist circumference >45 inches were 8.1 (CI: 2.8-23.8) times more likely to have diverticulosis than those with a waist circumference <38 inches. Leptin was also positively associated with diverticulosis (OR = 5.5, CI: 2.0-14.7). Both low molecular weight adiponectin (LMW, OR = 0.50; CI: 0.3-0.8) and the soluble receptor for advanced glycation end products (sRAGE, OR = 0.4, CI: 0.3-0.7) were inversely related to the presence of diverticulosis. sRAGE levels were not correlated with leptin or C-peptide concentrations. The pattern of high BMI, waist circumference, leptin and C-peptide increased the odds of diverticulosis while the pattern of high levels of sRAGE and LMW adiponectin decreased the odds of diverticulosis. Associations between diverticulosis and anthropometric or serum markers may elucidate the origins of diverticulosis and may enable physicians to identify individuals at risk for diverticulitis.

Topics: Adiponectin; Aged; Anthropometry; Asymptomatic Diseases; Biomarkers; Body Mass Index; C-Peptide; Colonoscopy; Cross-Sectional Studies; Diverticulum; Factor Analysis, Statistical; Humans; Leptin; Logistic Models; Male; Middle Aged; Obesity; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Waist Circumference

A key aspect of research into the prevention and treatment of type 2 diabetes is the availability of reproducible clinical research methodology to assess β-cell function. One commonly used method employs nonglycemic secretagogues like arginine (arg) or glucagon (glgn). This study was designed to quantify the insulin response to arg and glgn and determine test repeatability and tolerability. Obese overnight-fasted subjects with normal glucose tolerance were studied on 4 separate days: twice using arg (5 g iv) and twice with glgn (1 mg iv). Pre- and postinfusion samples for plasma glucose, insulin, and C-peptide were acquired. Arg and glgn challenges were repeated in the last 10 min of a 60-min glucose (900 mg/min) infusion. Insulin and C-peptide secretory responses were estimated under baseline fasting glucose conditions (AIRarg and AIRglgn) and hyperglycemic (AIRargMAX AIRglgnMAX) states. Relative repeatability was estimated by intraclass correlation coefficient (ICC). Twenty-three (12 men and 11 women) subjects were studied (age: 42.4 ± 8.3 yr; BMI: 31.4 ± 2.8 kg/m²). Geometric means (95% CI) for baseline-adjusted values AIRarg and AIRglgn were 84 (75-95) and 102 (90-115) μU/ml, respectively. After the glucose infusion, AIRargMAX and AIRglgnMAX were 395 (335-466) and 483 (355-658) μU/ml, respectively. ICC values were >0.90 for AIRarg andAIRargMAX. Glucagon ICCs were 0.83, 0.34, and 0.36, respectively, although the exclusion of one outlier increased the latter two values (to 0.84 and 0.86). Both glgn and arg induced mild adverse events that were transient. Glucagon, but not arginine, induced moderate adverse events due to nausea. Taken together, arginine is preferred to glucagon for assessment of β-cell function.

Topics: Adult; Aged; Arginine; Blood Glucose; Body Mass Index; C-Peptide; Female; Glucagon; Humans; Hyperglycemia; Infusions, Intravenous; Insulin; Insulin Secretion; Insulin-Secreting Cells; Kinetics; Male; Middle Aged; Mouth Mucosa; Nausea; Obesity; Paresthesia; Reproducibility of Results

A frequent eating pattern may alter glycaemic control and augment postprandial insulin concentrations in some individuals due to the truncation of the previous postprandial period by a subsequent meal. The present study examined glucose, insulin, C-peptide and glucose-dependent insulinotropic peptide (GIP) responses in obese individuals when meals were ingested in a high-frequency pattern (every 2 h, 6M) or in a low-frequency pattern (every 4 h, 3M) over 12 h. It also examined these postprandial responses to high-frequency, high-protein meals (6MHP). In total, thirteen obese subjects completed three 12 h study days during which they consumed 6276 kJ (1500 kcal): (1) 3M - 15 % protein and 65 % carbohydrate; (2) 6M - 15 % protein and 65 % carbohydrate; (3) 6MHP - 45 % protein and 35 % carbohydrate. Blood samples were collected every 10 min and analysed for glucose, insulin, C-peptide and GIP. Insulin total AUC (tAUC) and peak insulin concentrations (P< 0·05) were higher in the 3M condition than in the 6M condition, but there were no differences in glucose tAUC between the conditions. The 6MHP regimen (glucose: 3569 (se 83) mmol/l × min (64·3 (se 1·5) g/dl × min), insulin: 1·577 (se 0·146) pmol/l (22·7 (se 2·1) μIU/dl) for 12 h) lowered glucose and insulin excursions more so over 12 h than either the 3M regimen (glucose: 3913 (se 78) mmol/l × min (70·5 (se 1·4) g/dl × min), insulin: 2·195 (se 0·146) pmol/l × min (31·6 (se 2·1) μIU/dl × min) for 12 h) or the 6M regimen (glucose: 3902 (se 83) mmol/l × min (70·3 (se 1·5) g/dl × min), insulin: 1·861 (se 0·174) pmol/l × min (26·8 (se 2·5) μIU/dl × min) for 12 h; P< 0·01). Insulin secretion, GIP concentrations and the glucose:insulin ratio were not altered by meal frequency or composition. In obese subjects, ingestion of meals in a low-frequency pattern does not alter glucose tAUC, but increases postprandial insulin responses. The substitution of carbohydrates with protein in a frequent meal pattern results in tighter glycaemic control and reduced postprandial insulin responses.

Topics: Adult; Blood Glucose; C-Peptide; Dietary Carbohydrates; Dietary Proteins; Energy Intake; Fasting; Female; Gastric Inhibitory Polypeptide; Humans; Insulin; Kinetics; Male; Meals; Middle Aged; Obesity; Postprandial Period; Time Factors

Obesity is widely acknowledged as a critical risk factor for metabolic complications. Among obese subjects, there is a phenotype of metabolically healthy but obese (MHO) individuals that shows a favorable cardiometabolic risk profile. We aimed to evaluate the potential mechanisms underlying the metabolic profile of this subset, including alpha and beta cell function and entero-insular axis.. One hundred twenty-nine obese and 24 nonobese subjects were studied. Obese participants were defined as MHO or at-risk obese, according to the homeostasis model of assessment-insulin resistance (HOMA-IR) index (MHO: lower tertile of HOMA-IR, n = 43; at-risk: upper tertile of HOMA-IR index, n = 41). Insulin, glucagon, and incretin responses after a 120' oral glucose tolerance test (75-g OGTT) were investigated.. During OGTT, MHO individuals showed in comparison with at-risk subjects: lower fasting and afterloads plasma levels of glucose, insulin, and C-peptide; higher disposition index; lower fasting (P = 0.004) and at 30' (P = 0.01) plasma glucose-dependent insulinotropic polypeptide (GIP) levels; lower area under the curve (AUC) (0-30) for GIP (P = 0.008); higher glucagon-like peptide-1 (GLP-1) plasma levels at 90' (P = 0.02) and 120' (P = 0.02); lower glucagon plasma levels at baseline (P = 0.04) and at 30' (P = 0.03); and appropriate glucagon suppression after the oral glucose load.. MHO subjects show, as well as normal-weight individuals, a lower diabetogenic profile by virtue of higher disposition index and unaffected entero-insular axis. At-risk obese individuals present increased GIP levels that might play a role in determining increased glucagon secretion and inappropriate glucagon responses after glucose load, thus contributing to impaired glucose homeostasis.

Topics: Adult; Area Under Curve; Blood Glucose; C-Peptide; Fasting; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Secreting Cells; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Obesity

Health and nutrition modulate postnatal growth. The availability of amino acids and energy, and insulin and insulin-like growth factor-I (IGF-I) regulates early growth through the mTOR pathway. Amino acids and glucose also stimulate the secretion of IGF-I and insulin. Postnatal growth induces lasting, programming effects on later body size and adiposity in animals and in human observational studies. Rapid weight gain in infancy and the first 2 years was shown to predict increased obesity risk in childhood and adulthood. Breastfeeding leads to lesser high weight gain in infancy and reduces obesity risk in later life by about 20%, presumably partly due to the lower protein supply with human milk than conventional infant formula. In a large randomized clinical trial, we tested the hypothesis that reduced infant formula protein contents lower insulin-releasing amino acid concentrations and thereby decrease circulating insulin and IGF-I levels, resulting in lesser early weight gain and reduced later obesity risk (the 'Early Protein Hypothesis'). The results demonstrate that lowered protein in infant formula induces similar - but not equal - metabolic and endocrine responses and normalizes weight and BMI relative to breastfed controls at the age of 2 years. The results available should lead to enhanced efforts to actively promote, protect and support breastfeeding. For infants that are not breastfed or not fully breastfed, the use of infant formulas with lower protein contents but high protein quality appears preferable. Cows' milk as a drink provides high protein intake and should be avoided in infancy.

Topics: Amino Acids; Amino Acids, Branched-Chain; Animals; Blood Glucose; Body Mass Index; Breast Feeding; C-Peptide; Dietary Proteins; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Milk; Milk, Human; Nutritional Status; Obesity; Risk Factors; RNA-Binding Proteins; Urea; Weight Gain

Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances.. Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group.. The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group.. Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia.

Topics: Adipose Tissue; Body Mass Index; C-Peptide; Case-Control Studies; Cholesterol, HDL; Diabetes Mellitus, Type 2; Female; Gene Expression; Genetic Markers; Humans; Insulin; Insulin Resistance; Macrophages; Male; Obesity; Oligonucleotide Array Sequence Analysis; Triglycerides

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) help regulate postprandial triacylglycerol (TAG) and insulin concentrations, but the effects of acute aerobic exercise on GLP-1 or GIP responses are unclear. The purpose of this study was to determine whether reductions in postprandial TAG and insulin with exercise are associated with GLP-1 and GIP responses.. Thirteen normal-weight (NW) and 13 obese (Ob) individuals participated in two, 4-d trials in random order including an exercise (EX) and a no exercise (NoEX) trial. Diet was controlled during both trials. The EX trial consisted of 1 h of treadmill walking (55%-60% of V˙O2peak) during the evening of day 3 of the trial, 12 h before a 4-h mixed meal test on day 4, during which frequent blood samples were collected to assess postprandial lipemia, glycemia, insulin, C-peptide, GIP, and GLP-1 responses. Insulin secretion was estimated using the insulinogenic index, and insulin clearance was estimated using the ratio of insulin to C-peptide.. Postprandial TAG were 29% lower after EX in Ob individuals (P < 0.05) but were not significantly altered in NW individuals (P > 0.05). The drop in postprandial HDL cholesterol was attenuated with EX in Ob individuals (P < 0.05). Insulin responses were 14% lower after EX in Ob individuals (P < 0.05), and this was associated with reduced insulin secretion (P < 0.05), with no change in insulin clearance (P > 0.05). Glucose, C-peptide, GIP, and GLP-1 were not different between trials.. A 1-h bout of moderate-intensity aerobic exercise the night before a mixed meal attenuates TAG and insulin responses in Ob but not NW individuals, an effect not associated with altered GLP-1 or GIP responses.

Topics: Adult; C-Peptide; Cholesterol, HDL; Exercise Test; Fasting; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Humans; Insulin; Male; Obesity; Oxygen Consumption; Physical Exertion; Postprandial Period; Triglycerides; Walking; Young Adult

To report Type 2 diabetes-related outcomes after the implantation of a duodenal-jejunal bypass liner device and to investigate the role of proximal gut exclusion from food in glucose homeostasis using the model of this device.. Sixteen patients with Type 2 diabetes and BMI <36 kg/m(2) were evaluated before and 1, 12 and 52 weeks after duodenal-jejunal bypass liner implantation and 26 weeks after explantation. Mixed-meal tolerance tests were conducted over a period of 120 min and glucose, insulin and C-peptide levels were measured. The Matsuda index and the homeostatic model of assessment of insulin resistance were used for the estimation of insulin sensitivity and insulin resistance. The insulin secretion rate was calculated using deconvolution of C-peptide levels.. Body weight decreased by 1.3 kg after 1 week and by 2.4 kg after 52 weeks (P < 0.001). One year after duodenal-jejunal bypass liner implantation, the mean (sem) HbA(1c) level decreased from 71.3 (2.4) mmol/mol (8.6[0.2]%) to 58.1 (4.4) mmol/mol (7.5 [0.4]%) and mean (sem) fasting glucose levels decreased from 203.3 (13.5) mg/dl to 155.1 (13.1) mg/dl (both P < 0.001). Insulin sensitivity improved by >50% as early as 1 week after implantation as measured by the Matsuda index and the homeostatic model of assessment of insulin resistance (P < 0.001), but there was a trend towards deterioration in all the above-mentioned variables 26 weeks after explantation. Fasting insulin levels, insulin area under the curve, fasting C-peptide, C-peptide area under the curve, fasting insulin and total insulin secretion rates did not change during the duodenal-jejunal bypass liner implantation period or after explantation.. The duodenal-jejunal bypass liner improves glycaemia in overweight and obese patients with Type 2 diabetes by rapidly improving insulin sensitivity. A reduction in hepatic glucose output is the most likely explanation for this improvement.

Topics: Area Under Curve; Blood Glucose; C-Peptide; Device Removal; Diabetes Mellitus, Type 2; Duodenum; Fasting; Female; Gastric Bypass; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Resistance; Insulin Secretion; Jejunum; Male; Middle Aged; Obesity; Prospective Studies; Treatment Outcome; Weight Loss

Insulin responses to oral and intravenous glucose markedly differ by ethnicity. This study examined whether ethnic differences in pancreatic insulin secretion, hepatic insulin extraction and clearance explain these disparate findings in 35 obese African-American and 41 Latina girls (Tanner Stages: IV-V; ages: 14-18; body mass index percentile: 85.9-99.8%).. Pancreatic insulin secretion, hepatic insulin extraction and clearance were estimated by C-peptide and insulin modeling during an oral glucose tolerance test. Insulin sensitivity (SI), acute insulin response to glucose (AIRG ) and disposition index were derived from a frequently sampled intravenous glucose tolerance test.. Compared to Latinas, obese African-American adolescents had lower pancreatic insulin secretion (21.3%; P < 0.01), glucose incremental area under the curve (IAUC) (41.7%, P = 0.02), C-peptide IAUC (25.1%, P < 0.01) and SI (33.7%; P < 0.01). There were no ethnic differences in hepatic insulin extraction and clearance (P's > 0.05).. Compensatory mechanisms to insulin resistance do not appear to explain the ethnic differences in insulin responses to oral and intravenous glucose in obese African-American and Latina girls.

Topics: Adolescent; Area Under Curve; Black or African American; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Hispanic or Latino; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Obesity; United States

The mechanisms of weight loss after Roux-en-Y gastric bypass (RYGB) surgery are incompletely understood.. Our objective was to investigate changes in metabolic processing of ingested food that may contribute to the weight-reducing effect of RYGB surgery.. This was a cross-sectional case-control study at the Interdisciplinary Obesity Center, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.. Ten formerly obese women (mean ± SEM body mass index [BMI] = 26.6 ± 0.9 kg/m(2)) who had undergone RYGB surgery 41.9 ± 9.7 months before, 8 severely obese women (BMI = 40.8 ± 2.0 kg/m(2)), and 10 lean women (BMI = 20.9 ± 0.6 kg/m(2)).. Intervention was a standardized liquid meal test.. The thermic effect of food (TEF), respiratory quotient, and circulating levels of glucose, insulin, and C-peptide were assessed before and repeatedly during the first 90 minutes after the ingestion of a standardized liquid mixed meal containing 39.2 g carbohydrates, 15.4 g protein, and 2.8 g fat.. TEF area under curve (0-90 minutes) was significantly greater in RYGB patients than in severely obese and lean women (both P < .01). After ingestion of the mixed meal, the respiratory quotient increased to significantly greater values in the RYGB patients than in the severely obese and lean group (P < .001 for ANOVA time × group interaction). Also, the postprandial rise in circulating glucose, insulin, and C-peptide levels was remarkably higher in the RYGB patients than in the other 2 groups (all P < .001 for ANOVA time × group interaction).. Data demonstrate an enhanced TEF after RYGB surgery. Although this observation likely contributes to the weight-reducing effects of the surgery, data also point to an altered metabolic processing of food in RYGB patients characterized by an enhanced glucose absorption and postprandial carbohydrate oxidation.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Calorimetry, Indirect; Case-Control Studies; Cross-Sectional Studies; Energy Metabolism; Female; Food; Gastric Bypass; Heart Rate; Humans; Insulin; Middle Aged; Obesity; Postprandial Period; Thermogenesis

Genome-wide association studies have revealed several gene variants associated with obesity; however, only a few studies have further investigated their association with metabolic syndrome. We performed a study of eleven variants in/near genes TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, and FTO in Czech adolescents and analysed their association with obesity, metabolic syndrome and related traits. Genotyping was performed in 1,443 adolescents aged 13.0-17.9 years. Anthropometric parameters, biochemical parameters and blood pressure were assessed. Metabolic syndrome was defined according to the International Diabetes Federation. The FTO rs9939609 variant was associated with overweight/obesity (OR 1.40, 95% CI 1.21-1.63, P < 0.001). The minor allele of TMEM18 rs7561317 was related to underweight (OR 1.78, 95% CI 1.14-2.79, P = 0.015). BDNF rs925946 and MC4R rs17782313 were associated with metabolic syndrome (OR 1.53, 95% CI 1.14-2.04, P = 0.005; 1.51, 95% CI 1.12-2.04, P = 0.009). The PCSK1 rs6235 variant was negatively related to increased blood glucose (OR 0.69, 95% CI 0.49-0.97, P = 0.040). In conclusion, the FTO variant was associated with overweight/obesity in Czech adolescents. Moreover, MC4R and BDNF variants increased the risk of metabolic syndrome, probably through their effect on abdominal obesity. The PCSK1 variant may have a protective role in the development of type 2 diabetes.

Topics: Adiposity; Adolescent; Anthropometry; Blood Glucose; C-Peptide; Cohort Studies; Czech Republic; Female; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Insulin; Lipids; Male; Metabolic Syndrome; Obesity; Overweight; Thinness

The prevalence of adolescents' obesity and overweight has dramatically elevated in China. Obese children were likely to insulin resistance and dyslipidemia, which are risk factors of cardiovascular diseases. However there was no cut-off point of anthropometric values to predict the risk factors in Chinese adolescents. The present study was to investigate glycolipid metabolism status of adolescents in Shanghai and to explore the correlations between body mass index standard deviation score (BMI-SDS) and metabolic indices, determine the best cut-off value of BMI-SDS to predict dyslipidemia.. Fifteen schools in Shanghai's two districts were chosen by cluster sampling and primary screening was done in children aged 9-15 years old. After screening of bodyweight and height, overweight and obese adolescents and age-matched children with normal body weight were randomly recruited in the study. Anthropometric measurements, biochemical measurements of glycolipid profiles were done. SPSS19.0 was used to analyze the data. Receiver operating characteristic (ROC) curves were made and the best cut-off values of BMI-SDS to predict dyslipidemia were determined while the Youden indices were maximum.. Five hundred and thirty-eight adolescents were enrolled in this research, among which 283 have normal bodyweight, 115 were overweight and 140 were obese. No significant differences of the ages among 3 groups were found. There were significant differences of WC-SDS (p<0.001), triacylglycerol (p<0.05), high and low density lipoprotein cholesterol (p<0.01), fasting insulin (p<0.01) and C-peptide (p<0.001) among 3 groups. Significant difference of fasting glucose was only found between normal weight and overweight group. Significant difference of total cholesterol was found between obese and normal weight group. There was no significant difference of glycated hemoglobin among 3 groups. The same tendency was found in boys but not in girls. Only HDL-C reduced and TG increased while BMI elevated in girls. The best cut-off value of BMI-SDS was 1.22 to predict dyslipidemia in boys. The BMI cut-off was 21.67 in boys.. Overweight and obese youths had reduced insulin sensitivity and high prevalence of dyslipidemia.When BMI-SDS elevated up to 1.22 and BMI was higher than 21.67 in boys, dyslipidemia may happen.

Topics: Adolescent; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Child; China; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Dyslipidemias; Female; Humans; Insulin; Insulin Resistance; Male; Obesity; Prevalence; Prognosis; Risk Factors; ROC Curve; Sex Factors; Triglycerides

The objective of this study was to assess the relationship between fasting proinsulin (PI) and age in general population and to determine whether there are differences regarding this association in obese and non-obese persons.. A random population-based sample (n=656) of Romanians (26-80 years) living in Bucharest, Romania was studied; 432 persons had diabetes and they were not analyzed in this paper. Circulating levels of fasting plasma glucose (FPG), fasting plasma insulin (FPI), fasting plasma proinsulin (FPP), fasting plasma C-peptide, HbA1c, lipid profile, creatinine, urea were measured. The homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-B, and Quicki index were also calculated.. For all participants proinsulin was the highest in the third quartile of the age group (59-67 years), with a median proinsulin of 5.8 pmol/L. Subsequently, proinsulin increased with age, from 2.6 pmol/L for participants aged 20-51 years, to 4.7 pmol/L for participants aged 51-59 years; proinsulin levels decreased in the upper quartile 4.8 pmol/L for those aged over 67 years. In sex-specific analyses, proinsulin increased with age for both men and women, except for those in the upper quartile. The prevalence of the obesity was 30.4% (n=68); obesity prevalence did not increase with age (p=0.26). Fasting proinsulin levels significantly increased with body mass index (BMI) category from lean (n=67, 2.9 pmol/L) to overweight (n=89, 4.5 pmol/L) and obese (n=69, 6.63 pmol/L) (p<0.0001).. Our study has demonstrated a close association between age and elevated proinsulin and proinsulin/insulin ratio in general population.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; C-Peptide; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Proinsulin

With the increasing rates of obesity, many people diet in an attempt to lose weight. As weight loss is seldom maintained in a single effort, weight cycling is a common occurrence. Unfortunately, reports from clinical studies that have attempted to determine the effect of weight cycling on mortality are in disagreement, and to date, no controlled animal study has been performed to assess the impact of weight cycling on longevity. Therefore, our objective was to determine whether weight cycling altered lifespan in mice that experienced repeated weight gain and weight loss throughout their lives.. Male C57BL/6J mice were placed on one of three lifelong diets: a low-fat (LF) diet, a high-fat (HF) diet or a cycled diet in which the mice alternated between 4 weeks on the LF diet and 4 weeks on the HF diet. Body weight, body composition, several blood parameters and lifespan were assessed.. Cycling between the HF and LF diet resulted in large fluctuations in body weight and fat mass. These gains and losses corresponded to significant increases and decreases, respectively, in leptin, resistin, GIP, IGF-1, glucose, insulin and glucose tolerance. Surprisingly, weight cycled mice had no significant difference in lifespan (801±45 days) as compared to LF-fed controls (828±74 days), despite being overweight and eating a HF diet for half of their lives. In contrast, the HF-fed group experienced a significant decrease in lifespan (544±73 days) compared with LF-fed controls and cycled mice.. This is the first controlled mouse study to demonstrate the effect of lifelong weight cycling on longevity. The act of repeatedly gaining and losing weight, in itself, did not decrease lifespan and was more beneficial than remaining obese.

Topics: Animals; C-Peptide; Chemokine CCL2; Diet, Fat-Restricted; Diet, High-Fat; Energy Intake; Gastric Inhibitory Polypeptide; Insulin; Interleukin-6; Leptin; Longevity; Male; Mice; Mice, Inbred C57BL; Obesity; Peptide Fragments; Resistin; Time Factors; Weight Gain; Weight Loss

To compare indices of insulin secretion, insulin sensitivity (IS), and oral disposition index (oDI) during the liquid mixed-meal test in obese youth with clinically diagnosed type 2 diabetes mellitus (T2DM) and negative autoantibodies (Ab(-)) versus those with T2DM and positive autoantibodies (Ab(+)) to examine whether differences in β-cell function can be detected between the 2 groups.. Twenty-seven youth with Ab(-) and 15 youth with Ab(+) clinically diagnosed T2DM underwent a mixed-meal test (Boost; 55% carbohydrate, 25% protein, and 20% fat). Fasting and mixed-meal-derived insulin and C-peptide indices of IS, secretion (30-minute insulinogenic [ΔI(30)/ΔG(30)] and C-peptide [ΔC(30)/ΔG(30)]), and oDI were calculated.. Indices of insulin secretion were ~40%-50% lower in patients with Ab(+) T2DM compared with those with Ab(-) T2DM. After controlling for body mass index, ΔI(30)/ΔG(30), ΔC(30)/ΔG(30), C-peptide area under the curve (AUC)/glucose AUC, and insulin AUC/glucose AUC were significantly (P < .05) lower in the Ab(+) group compared with the Ab(-) group. Sensitivity indices were significantly higher in the Ab(+) group. The oDI, 1/fasting insulin × ΔI(30)/ΔG(30) (0.04 ± 0.02 vs 0.12 ± 0.02 mg/dL(-1); P = .005), and 1/fasting C-peptide × ΔC(30)/ΔG(30) (0.02 ± 0.009 vs 0.05 ± 0.006 mg/dL(-1); P = .018) were lower in the Ab(+) group. Receiver operating characteristic curve analyses revealed that fasting C-peptide <3.2 ng/mL had 87% sensitivity and 74% specificity and ΔC(30)/ΔG(30) <0.075 ng/mL per mg/dL had 93% sensitivity and 80% specificity for identifying youth with Ab(+) T2DM.. During a liquid mixed-meal test, indices of β-cell function were lower and IS was higher in patients with Ab(+) T2DM versus those with Ab(-) T2DM, with high sensitivity and specificity for fasting and stimulated C-peptide as markers of Ab(+) status. Indices of insulin secretion during this standardized mixed-meal test could be used to assess β-cell function in therapeutic trials of β-cell restoration in youth with T2DM.

Topics: Adolescent; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Meals; Obesity

The purpose of this investigation is to determine the role of osteopontin and adiponectin in the formation of arterial hypertension in adolescents with obesity. 67 adolescents with obesity have been examined. Two groups were composed taking into account the state of arterial pressure. The first group included adolescents with obesity and arterial hypertension, the second group - adolescents with obesity and without arterial hypertension. Arterial pressure was measured and serum content of osteopontin, insulin, C-peptid and adiponectin in blood has been determined. The result of the investigation has revealed that in adolescents without arterial pressure the growth of insulin and C-peptid in the serum of blood has been observed; in patients with obesity and arterial hypertension the increase of content of osteopontin and hypoadiponectinemia has been occurred. The revealed changes indicated about the pathogenic role of osteopontin and adiponectin in the formation of arterial hypertension in adolescents with obesity.

Topics: Adiponectin; Adolescent; Arterial Pressure; C-Peptide; Case-Control Studies; Female; Humans; Hypertension; Insulin; Insulin Resistance; Male; Obesity; Osteopontin

Accumulating evidence has implicated insulin and the insulin-like growth factor (IGF) axis in colorectal carcinogenesis. Of interest, adiposity is likely to impose a greater risk on men than on women, which indicates that the association of insulin and the IGF axis with colorectal neoplasia may differ by gender. However, epidemiological evidence for this possible gender difference is limited to date.. We measured plasma concentrations of C-peptide, IGF-I and IGF-binding proteins (IGFBPs) 1 and 3 in 1520 healthy volunteer examinees who underwent total colonoscopy between February 2004 and February 2005, and cross-sectionally investigated the association of these biomarkers with colorectal adenoma by gender. An unconditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for colorectal adenoma after adjustment for potential confounders.. We observed a positive association of C-peptide and IGF-I (P (trend)<0.001 and 0.02, respectively) and an inverse association of IGFBP-1 (P (trend)=0.002) with colorectal adenoma in men. Adjusted ORs of colorectal adenoma for the highest compared with the lowest quartile were also statistically significant for C-peptide (OR: 2.62, 95% CI: 1.71-4.01), IGF-I (OR: 1.63, 95% CI: 1.08-2.46) and IGFBP-1 (OR: 0.49, 95% CI: 0.32-0.75). In contrast, no measurable association was seen in women. Corresponding ORs for C-peptide, IGF-I and IGFBP-1 were 0.98 (95% CI: 0.56-1.71), 0.79 (95% CI: 0.44-1.43) and 1.05 (95% CI: 0.60-1.86), respectively. The gender difference was statistically significant for C-peptide (P (interaction)=0.03) and marginally significant for IGF-I and IGFBP-1 (P (interaction)=0.14 and 0.12, respectively).. Our observations suggest that insulin and the IGF axis act differently by gender in colorectal carcinogenesis, at least in its early stage. The findings of this study further our understanding of the complexities of the gender difference in the association between adiposity and colorectal neoplasia.

Topics: Adenoma; Adult; Aged; Asian People; C-Peptide; Case-Control Studies; Cell Transformation, Neoplastic; Colonoscopy; Colorectal Neoplasms; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Life Style; Logistic Models; Male; Middle Aged; Obesity; Odds Ratio; Risk Factors; Sex Distribution; Sex Factors; Surveys and Questionnaires

It has been reported that beta cell function progressively declines in patients with type 2 diabetes. The objective of this study was to assess the effect of obesity on declining beta cell function after diagnosis of type 2 diabetes. We conducted a cross-sectional study of 689 consecutive subjects with type 2 diabetes who were admitted to our hospital from 2000 to 2007. Fasting and postprandial serum C-peptide immunoreactivity (CPR) and urinary CPR levels had been measured during admission. The subjects were stratified according to BMI and time since diagnosis. CPR index was calculated as CPR (ng/mL) / plasma glucose (mg/dL) x 100. All CPR measurements were significantly higher in the 263 obese (BMI ≥25) subjects compared to the 426 lean subjects (BMI <25). There was a significant negative correlation between CPR indices and duration of diabetes, suggesting a progressive decline in beta cell function after diagnosis of type 2 diabetes. However, this decline was more apparent in obese subjects (postprandial CPR index 0.059/year) compared to lean subjects (0.025/year). The significant difference in serum CPR indices between the lean and obese subjects was lost in subjects more than 10 years after diagnosis. In conclusion, our observations suggest that beta cell function shows a greater progressive decline in obese subjects than in lean subjects with type 2 diabetes. Treatment of obesity may be an important strategy to preserve beta cell function in patients with type 2 diabetes.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Postprandial Period; Retrospective Studies

People with type 2 diabetes mellitus (T2DM) are characterized by reduced incretin effect and inappropriate glucagon levels. We evaluated α and β-cell responses to oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI) in lean and obese persons with T2DM or normal glucose tolerance (NGT) to elucidate the impact of obesity on the incretin effect and incretin hormone and glucagon responses.. Four hour 50-g OGTT and IIGI were performed in (i) Eight obese patients with T2DM [mean body mass index (BMI): 37 (range: 35-41) kg/m(2)]; (ii) Eight obese subjects with NGT [BMI: 33 (35-38) kg/m(2)]; (iii) Eight lean patients with T2DM [BMI: 24 (22-25) kg/m(2)]; and (iv) Eight lean healthy subjects [BMI: 23 (20-25) kg/m(2)].. The incretin effect was significantly (p < 0.05) reduced in patients with T2DM {obese: 7 ± 7% [mean ± standard error of the mean (SEM)]; lean: 29 ± 8%; p = 0.06)} and was lower in obese subjects (41 ± 4%) than in lean subjects with NGT (53 ± 4%; p < 0.05). Obese subjects with NGT were also characterized by elevated fasting plasma glucagon levels, but the inappropriate glucagon responses to OGTT found in the T2DM patients were not evident in these subjects.. Our findings suggest that reduced incretin effect and fasting hyperglucagonaemia constitute very early steps in the pathophysiology of T2DM detectable even in obese people who despite their insulin-resistant state have NGT.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Glucagon; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Obesity

Hyperinsulinemia of nondiabetic overweight and obese subjects is associated with weight-dependent increased insulin secretion and decreased insulin clearance. The present analysis examines whether similar effects can be observed in overweight and obese patients with type 2 diabetes mellitus (DM2). Additionally basal and postprandial insulin secretion and clearance were analyzed in relation to duration of disease. In a random sample of 348 DM2 patients basal plasma insulin concentrations were significantly higher in most BMI groups compared to matched nondiabetic (ND) controls. The weight-dependent increase of basal insulin in DM2 was primarily the result of reduced clearance rather than augmented secretion. Postprandial insulin concentrations were lower in DM2 patients and did not show any BMI-related increase. The weight-dependent reduction of postprandial insulin clearance was absent in DM2. At the time of diagnosis basal insulin concentration was higher and secretion was comparable to ND subjects and this did not change with duration of diabetes. The early postprandial insulin response was still comparable between DM2 and ND subjects at the time of diagnosis but deteriorated with longer duration of disease. The later postprandial response at diagnosis (AUC 90-180) was characterized by significantly greater insulin secretion and concentration while later on the 3-fold higher secretion was paralleled by comparable peripheral plasma concentrations due to a significantly greater postprandial insulin clearance in DM2. In conclusion, the present data indicate that apart from disturbances of insulin secretion substantial changes of insulin clearance contribute to inadequate peripheral insulin concentrations in obese DM2 patients.

Topics: Area Under Curve; Blood Glucose; Body Mass Index; C-Peptide; Demography; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Postprandial Period; Time Factors

Glucose-dependent insulinotropic polypeptide (GIP) secretion in diabetic Europeans with type 1 (T1DM) and type 2 (T2DM) following test meal (TM) has been shown to be normal. In Japanese patients with T2DM, GIP secretion was also normal. We determined whether GIP secretin is influenced by various factors. Plasma glucose (PG), serum insulin (s-IRI), serum C-peptide (s-CPR), and plasma total GIP (p-total GIP) levels were measured at 0, 30, and 60 minutes after TM (560 kcal) in patients with T1DM (n = 15, group 1) and T2DM (n = 29, group 2) treated with various medications. HbA1c was also measured. At baseline, means of age, BMI, HbA1c, PG, s-CPR, SUIT (secretory unit in transplantation) and p-total GIP were significantly lower in group 1 than in group 2. Each mean of postprandial p-total GIP levels after TM in all patients was more dramatically increased than other factors. The area under the curve (AUC) of p-total GIP levels in early-phase (0 to 30 min) was significantly positively correlated with BMI in group 2 but not in group 1, and not with other factors. These results indicate that the GIP secretion after TM in diabetic Japanese patients was dramatically increased, and the AUC of GIP secretion in early-phase was positively correlated with BMI in non-obese and obese patients with T2DM, but not with T1DM. The increase was not influenced by gender, age, glycemic control, duration of disease, micro- or macro-vascular disturbances, or oral drugs.

Topics: Asian People; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Obesity; Postprandial Period

Gut hormones play a role in diabetes remission after a Roux-en-Y gastric bypass (RYGB). Our aim was to investigate differences in gut hormone secretion according to diabetes remission after surgery. Second, we aimed to identify differences in insulin secretion and sensitivity according to diabetes remission after RYGB.. Twenty-two severely obese patients with type 2 diabetes underwent RYGB. A meal tolerance test (MTT) was performed 12 months after RYGB. The secretions of active glucagon-like peptide-1 (active GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY, C-peptide and insulin during the MTT test were calculated using total area under the curve values (AUC). Remission was defined as glycated haemoglobin (A(1C)) of <6.5% and a fasting glucose concentration of <126 mg/dL for 1 year or more without active pharmacological therapy.. Of the 22 patients, 16 (73%) had diabetes remission (remission group). The secretion CURVES of active GLP-1, GIP and peptide YY were not different between the groups. AUC of insulin and C-peptide were also not different. Homeostasis model assessment estimate of insulin resistance was significantly lower (1.26 ± 1.05 versus 2.37 ± 1.08, p = 0.006), and Matsuda index of insulin sensitivity was significantly higher in the remission group (10.5 ± 6.2 versus 5.8 ± 2.1, p = 0.039). The disposition index (functional reserve of beta cells) was significantly higher in the remission group compared with that in the non-remission group (5.34 ± 2.74 versus 1.83 ± 0.70, p < 0.001).. Remission of diabetes after RYGB is not associated with a difference in gut hormone secretion. Patients remaining diabetic had higher insulin resistance and decreased β cell functional reserve.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Prognosis; Prospective Studies; Remission Induction; Young Adult

Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-h blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean (s.d.) age 41 (5) years; BMI 27.4 (2.0) kg/m(2)) completed two 14-day treatments with hypocaloric diet and 8.5- or 5.5-h nighttime sleep opportunity in random order 7 (3) months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free fatty acids (FFA), 24-h blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 (0.3) BMI units) during each treatment. Bedtime restriction reduced sleep by 131 (30) min/day. Recurrent sleep curtailment decreased 24-h serum insulin concentrations (i.e., enhanced 24-h insulin economy) without changes in oral glucose tolerance and 24-h glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA, which suppressed normally following glucose ingestion, and lower total and low-density lipoprotein cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-h insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability.

Topics: Adult; Blood Glucose; C-Peptide; Diet, Reducing; Fasting; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Insulin-Secreting Cells; Lipids; Male; Obesity; Sedentary Behavior; Sleep Deprivation; Weight Loss

Aim of this study was the investigation of feature of hormonal status in patients with metabolic syndrome (MetS). 111 reproductive age women were included in the study. According to diagnostic criteria for MetS of Society of Cardiology of the Russian Federation (2009) they were divided into two groups--study group (n=52) and control group (n=59). It was studied composition of body (fat mass, skeletal mass, lean mass, total, intracellular and extracellular fluid), parameter of lipid and carbohydrate metabolism, parameter of hormonal status. Study of hormonal status in reproductive age women with MetS showed a higher level of fasting and postprandial levels of insulin and C-peptide, hyperleptinemia and a reduced level of sex hormone-binding globulinn (SHBG). We suggest that serum leptin and SHBG levels may be used as an additional diagnostic criteria in these patients.

Topics: Adipose Tissue; Adolescent; Adult; Biomarkers; Blood Chemical Analysis; Body Composition; Body Mass Index; C-Peptide; Female; Gonadal Steroid Hormones; Health Status; Humans; Insulin; Leptin; Lipoproteins, HDL; Lipoproteins, LDL; Metabolic Syndrome; Middle Aged; Obesity; Reproduction; Risk Factors; Sex Hormone-Binding Globulin; Triglycerides; Waist-Hip Ratio

To examine the relationship between BMI and beta-cell function at diagnosis of autoimmune type 1 diabetes (T1D) in a large group of ethnically diverse children.. Cross-sectional analysis of 524 children (60.8% White, 19.5% Hispanic, 14.5% African-American, 5.2% other non-Hispanic; mean age = 9.8 yr [SD = 2.5]) with newly diagnosed autoimmune T1D.. As much as 22.2% of children were overweight or obese. Median random serum C-peptide was 0.40 ng/mL (25th-75th percentiles = 0.3-0.8), with median glycemia of 366 mg/dL (25th-75th percentiles = 271-505). Median C-peptide was 0.3, 0.5, 0.7, and 0.85 ng/mL, respectively, in underweight, normal weight, overweight, and obese children (p < 0.0001, Kruskal-Wallis). In the final model (p < 0.0001), the odds of having preserved C-peptide (≥0.6 ng/mL) were increased by 2.4-fold (95% CI = 1.2-4.9, p < 0.015) and 4.1-fold (1.9-8.5, p < 0.0001), respectively, in overweight and obese compared to lean children; 1.3-fold per each year of age; 2.5-fold in girls compared to boys; 4-fold in children who presented without, compared to with, diabetes ketoacidosis (DKA); and decreased by 21% for each point increase in HbA1c. Tanner stage, race/ethnicity, glycemia, and number of anti-islet antibodies expressed were not independently associated with preserved C-peptide. The association between BMI and C-peptide levels was significant in children with and without preserved C-peptide. Excluding patients who presented with DKA and/or using BMI obtained 5 wk after diagnosis did not alter the results.. Obese and overweight children compared to lean children have greater beta-cell function at the onset of autoimmune T1D. Prospective studies on the relationships among BMI, beta-cell function, and progression to clinical T1D are warranted.

Topics: Autoantibodies; Black or African American; Blood Glucose; Body Mass Index; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Hispanic or Latino; Humans; Insulin-Secreting Cells; Male; Obesity; Overweight; Puberty; White People

The aim of this study was to evaluate the risk factors of mild cognitive impairment (MCI) in middle-aged patients with type 2 diabetes (T2DM).. Montreal Cognitive Assessment (MoCA) was applied as cognition assessment implement. One hundred and fifty-seven middle-aged type 2 diabetic patients were enrolled in this cross-section study (age 40~69, mean age 55 ± 7). There were 93 patients with MCI (MoCA score<26) in MCI group and 64 with normal cognitive function (MoCA score ≥ 26) in control group. Information of history of disease, family history, data of BMI, WHR, HbA1c, FINS, C-Peptide (C-P), SBP, DBP, blood lipid (TG, TC, LDL-C, HDL-C and carotid ultrasound (carotid IMT, carotid resistance index [RI]) was collected.. There were significant differences in the rate of patients with hypertension ([40.63 vs. 58.06%], P=0.026), duration of diabetes mellitus ([3.09 ± 4.04 y vs. 4.80 ± 4.94 y], P=0.024), C-P ([2.79 ± 1.09 ng/ml vs. 2.26 ± 1.00 ng/ml], P=0.008), Max C-IMT ([0.81 ± 0.15 mm vs. 0.91 ± 0.15 mm], P<0.001), Min C-RI (0.71 ± 0.06 vs. 0.68 ± 0.06, P<0.05), and no significant differences in the duration of hypertension and hyperlipidemia, BMI, WHR, HbA1c, SBP, DBP and blood lipid between control group and MCI group. MoCA scores were positively correlated with C-P (r=0.252, P=0.005), and negatively correlated with the history of hypertension (r=-0.244, P=0.002), duration of DM (r=-0.161, P=0.044), Max C-IMT (r=-0.253, P=0.005) and Min C-RI (r=-0.183, P=0.023). Multiple regression analysis showed that history of hypertension (Beta=-0.267, P=0.002), C-P (Beta=0.281, P=0.001) and Min C-RI (Beta=-0.221, P=0.011) were significantly independent determinants for the MoCA scores.. The longer duration of diabetes, history of hypertension, lower serum C-P levels, thickened C-IMT and higher C-RI could be risk factors of MCI in type 2 diabetic patients. This finding could have an important impact on the management of cognitive decline in diabetic patients.

Topics: Aged; Anthropometry; C-Peptide; Carotid Intima-Media Thickness; Carotid Stenosis; China; Cognitive Dysfunction; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Obesity; Psychological Tests; Risk Factors; Severity of Illness Index; Vascular Resistance

Changes in the clinical presentation of diabetes mellitus in childhood and adolescence associated with obesity have resulted in an overlap of the two most common types of diabetes with a greater clinical heterogeneity. In order to characterize the type of diabetes at onset and assess the effect of obesity, 50 children with diabetes were studied. The patients were divided into two groups according to their nutritional status at diagnosis (over-weight/obese vs. normal weight). Insulin reserve was evaluated by measuring basal C-peptide and stimulated C-peptide in response to a mixed meal (MMTT) as well as HLA-DQB1 genotype, antibodies, and family history of risk factors for metabolic disease. Of all 50 patients, 38% was overweight/obese, 84% had a positive family history of metabolic syndrome, 82% had positive antibodies, and 100% were positive for the high-risk HLA-DQB1 genotype. No significant differences were found in fasting C-peptide or glycemic index/C-peptide levels between the two groups. In the overweight/obese group C-peptide response to MMTT showed higher levels at 60 and 120 minutes (p = 0.02 and 0.03) and the area under the curve for C-peptide was also higher (1.77 ng / ml vs. 5.5 ng/ ml, p = 0.0007) than in the normal-weight group. In conclusion, overweight/obese patients with type 1A diabetes had a greater pancreatic reserve, suggesting that nutritional status may accelerate disease onset.

Topics: Adolescent; Autoimmunity; Biomarkers; C-Peptide; Chi-Square Distribution; Child; Diabetes Mellitus, Type 1; Female; Genotype; Glutamate Decarboxylase; HLA-DQ beta-Chains; Humans; Insulin Antibodies; Male; Metabolic Syndrome; Obesity; Prospective Studies; Receptor-Like Protein Tyrosine Phosphatases, Class 8; Risk Factors

Pulses are low in energy density, supporting their inclusion in the diet for the management of risk factors of the metabolic syndrome (MetSyn). The aim of the present study was to describe the effects of frequent consumption (five cups/week over 8 weeks) of pulses (yellow peas, chickpeas, navy beans and lentils), compared with counselling to reduce energy intake by 2093 kJ/d (500 kcal/d), on risk factors of the MetSyn in two groups (nineteen and twenty-one subjects, respectively) of overweight or obese (mean BMI 32·8 kg/m2) adults. Body weight, waist circumference, blood pressure, fasting blood parameters and 24 h food intakes were measured at weeks 1, 4 and 8. Blood glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and ghrelin were measured after a 75 g oral glucose load at weeks 1 and 8. At week 8, both groups reported reductions in energy intake, waist circumference, systolic blood pressure, glycosylated Hb (HbA1c) and glucose AUC and homeostasis model of insulin resistance (HOMA-IR) following the glucose load (P < 0·05). However, HDL, fasting C-peptide and insulin AUC responses were dependent on diet (P < 0·05). HDL and C-peptide increased by 4·5 and 12·3 %, respectively, in the pulse group, but decreased by 0·8 and 7·6 %, respectively, in the energy-restricted group. Insulin AUC decreased in both females and males on the energy-restricted diet by 24·2 and 4·8 %, respectively, but on the pulse diet it decreased by 13·9 % in females and increased by 27·3 % in males (P < 0·05). In conclusion, frequent consumption of pulses in an ad libitum diet reduced risk factors of the MetSyn and these effects were equivalent, and in some instances stronger, than counselling for dietary energy reduction.

Topics: Adult; Blood Glucose; C-Peptide; Caloric Restriction; Counseling; Diet; Fabaceae; Female; Glucagon-Like Peptide 1; Humans; Insulin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Risk Factors; Seeds; Waist Circumference

To evaluate the one year effect of modified Roux-en-Y gastric bypass (RYGP) in the treatment of non-obese type 2 diabetes and to investigate the reasonable indications for surgery.. Totally 72 patients diagnosed as type 2 diabetes underwent RYGP from May 2009 to June 2010. There were 45 male and 27 female patients, with an average age of (47 ± 10) years. Preoperative body mass index (BMI) of the patients was 18.69 to 31.22 kg/m(2), average (26 ± 4) kg/m(2). The follow-up data included fasting plasma glucose (FPG), 2 h plasma glucose after oral glucose challenge (2hPG), weight, BMI and medication usage in 1, 3, 6 and 12 months postoperative; hemoglobin A1c (HbA1c), fasting C-peptide (C-P), fasting serum insulin (Fins) and homeostasis model assessment of insulin resistance index (HOMA-IR) in 6 and 12 months postoperative, respectively.. Compared with the preoperative, FPG, 2hPG, weight and BMI in 1, 3, 6 and 12 months after surgery were improved (t = 7.014 to 10.254, P = 0.000), while HbA1c, C-P and HOMA-IR in 6 and 12 months after surgery were improved (t = 1.782 to 7.789, P = 0.000 to 0.103) and there was no significant difference in Fins (P > 0.05). The rates of complete remission in 1, 3, 6 and 12 months after surgery were gradually improved to 22.2%, 27.8%, 36.1% and 60.6%, respectively, and the rate of remission in 1 year was 94.3%. The complete remission of 1 year after surgery was associated with normal C-P, insulin antibody and oral antidiabetic drugs (χ(2) = 11.730, P = 0.003; χ(2) = 7.131, P = 0.028;χ(2) = 6.149, P = 0.046).. Modified RYGP is safely and effectively in the treatment of no-obese type 2 diabetes patients. The function of islet cells is significantly improved after operation. Especially for the patients of whom C-P is normal, insulin antibody is negative before surgery, the rate of complete remission after 1 year is better.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Bypass; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Weight Loss

It has been suggested that adipokine changes might precede changes in plasma non-esterified fatty acids and other obesity metabolic biomarkers. The aim of the present study was to evaluate changes in fasting and postprandial plasma levels of adiponectin, non-esterified fatty acids, and tumor necrosis factor-alpha in prepubertal obese children and age-matched normal-weight children.. Fifty-four children of prepubertal age (34 obese, comprising 23 males and 11 females, and 20 normal-weight comprising 11 males and 9 females) were studied. A standard 438 kcal breakfast was given to both groups. Baseline measurements included anthropometry and plasma lipids. The following parameters were determined in plasma before and after breakfast: glucose, insulin, and C-peptide at baseline and 2h and non-esterified fatty acids, adiponectin, and tumor necrosis factor-alpha at baseline and 1, 2, and 3h. Fasting plasma non-esterified fatty acid levels were lower in the obese versus normal-weight children (P=0.021). Both at baseline and postprandially, plasma adiponectin levels were lower in the obese versus normal-weight children (P<0.001). A trend was observed (P=0.06) that levels of tumor necrosis factor-alpha were lower in the obese versus normal-weight children. Adiponectin was inversely associated with insulin in the obese children after adjustment for BMI and sex (r=-0.401, P=0.025).. At prepubertal age, obese children show lower fasting and postprandial plasma adiponectin levels in comparison to normal-weight children, whereas non-esterified fatty acids and tumor necrosis factor-alpha were not yet increased. Therefore, adiponectin appears to be a good marker of early metabolic alterations associated with childhood obesity.

Topics: Adiponectin; Anthropometry; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Child; Diet; Fasting; Fatty Acids, Nonesterified; Female; Humans; Insulin; Lipids; Male; Obesity; Postprandial Period; Predictive Value of Tests; Sex Factors; Tumor Necrosis Factor-alpha

The aim of the presented study is to evaluate metabolic features in adolescents with polycystic ovary syndrome (PCOS) in comparison with age- and BMI-matched subjects. Forty-three adolescents with PCOS according to ESHRE criteria were prospectively evaluated and compared with 48 control subjects. Blood sampling was done in the early follicular phase of menstrual cycle, between 1st and 5th day, for plasma glucose, total and high-density lipoprotein (HDL)-cholesterol, triglycerides, insulin and C peptide. The diagnosis of metabolic syndrome was done according to IDF adolescent criteria. Adolescents with PCOS have increased low-density lipoprotein (LDL)-cholesterol (p < 0.002), decreased HDL-cholesterol (p <0.0007) and increased C peptide levels (p < 0.02) in comparison with healthy adolescents. Total cholesterol, triglycerides, fasting blood glucose, fasting insulin, HOMA-IR, waist-to-hip ratio, systolic and diastolic blood pressure did not differ between the groups. There was no difference when we compared the prevalence of adolescents with at least one feature of metabolic syndrome between PCOS (17 from 43) and healthy controls (27 from 48). In conclusion, adolescents with PCOS have less favourable blood lipid profiles with higher LDL-cholesterol and lower levels of HDL-cholesterol and are more insulin resistant than their healthy counterparts having higher fasting C peptide levels.

Topics: Adolescent; Adult; Body Mass Index; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Czech Republic; Female; Follicular Phase; Humans; Hypercholesterolemia; Insulin Resistance; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Prevalence; Prospective Studies; Young Adult

The aim of this analysis was to evaluate glucagon and c-peptide concentrations in two scenarios: euglycemic hyperinsulinemia and hyperglycemic hyperinsulinemia. We postulated that worsening obesity and insulin resistance will be reflected as an up-regulated (less suppressible) islet secretion profile.. Eighty-two [34 obese with normal glucose tolerance (NGT), 30 obese with impaired glucose tolerance (IGT), and 18 nonobese with NGT] subjects underwent a euglycemic-hyperinsulinemic clamp (EHC) and a hyperglycemic clamp. C-peptide and glucagon were evaluated at basal and steady-state (SS) conditions.. Basal glucagon was significantly elevated in obese insulin-resistant and obese IGT subjects as was basal c-peptide. SS glucagon and c-peptide levels during the EHC were lower in the lean and obese insulin-sensitive subjects compared with the obese insulin-resistant subjects with NGT or IGT. Fasting glucagon was the only significant determinant (β = 0.66, P < 0.001) of SS glucagon during the EHC (R(2) = 0.57). In a longitudinal follow-up of a subsample, those who converted from normal to IGT significantly increased their fasting glucagon concentration in comparison with those who remained with NGT.. Islet up-regulation manifesting as basal elevated glucagon and c-peptide secretion that determines the suppressive effects of hyperinsulinemia appears early in the course of deteriorating glucose tolerance.

Topics: Adolescent; Analysis of Variance; Area Under Curve; Blood Glucose; C-Peptide; Glucagon; Glucagon-Secreting Cells; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Obesity; Regression Analysis; Up-Regulation; Young Adult

This study investigated the relationship of obesity, insulin resistance, inflammation and angiogenesis with cancer progression and survival in a colorectal cancer cohort.. Clinical and pathological data, along with anthropometric and follow-up data, were collected from 344 consecutive colorectal cancer patients. Serum samples at diagnosis were analysed by immunoassay for adiponectin, C-reactive protein (CRP), vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang-2), insulin-like growth factor-1 (IGF-1), insulin and C-peptide.. Serum Ang-2 and VEGF-A levels increased with tumour T stage (P=0.007 and P=0.025, respectively) and N stage (P=0.02 and P=0.03, respectively), and correlated with CRP levels (r=0.43, P<0.001 and r=0.23, P<0.001, respectively). Angiopoietin-2 correlated with C-peptide (r=0.14, P=0.007) and VEGF-A with IGF-1 in males (r=0.25, P=0.001). Kaplan-Meier analysis showed that patients with high serum levels of CRP and Ang-2 had significantly reduced survival (both P≤0.001). After adjusting for tumour stage and age, Ang-2 remained a significant predictor of survival. The CRP levels were inversely associated with survival in American Joint Committee on Cancer stage II patients (P=0.038), suggesting that CRP could be used to support treatment decisions in this subgroup. Serum markers and anthropometric measures of obesity correlated with each other, but not with survival.. Our study supports the concept that obesity-related inflammation, rather than obesity itself, is associated with colorectal cancer progression and survival. The study confirms serum Ang-2 as a predictive marker for outcome of colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Angiopoietin-2; Biomarkers; Body Mass Index; C-Peptide; C-Reactive Protein; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Female; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Male; Middle Aged; Obesity; Prospective Studies; Survival Rate; Treatment Outcome; Vascular Endothelial Growth Factor A

Obesity is one of the most important modifiable risk factors for the prevention of type 2 diabetes. The aim of this study was to examine the prevalence of diabetes with increasing severity of obesity and the distribution of HbA1c levels in diabetics participating in the latest National Health and Nutrition Examination Survey (NHANES).. Data from a representative sample of adults with diabetes participating in the NHANES between 1999 and 2006 were reviewed. The prevalence of diabetes and levels of fasting glucose, insulin, c-peptide, and HbA1c were examined across different weight classes with normal weight, overweight, and obesity classes 1, 2, and 3 were defined as body mass index (BMI) of <25.0, 25.0-29.9, 30.0-34.9, 35.0-39.9, and equal to 40.0, respectively. The distribution of HbA1c levels among adults with diabetes was also examined.. There were 2,894 adults with diabetes (13.6%) among the 21,205 surveyed participants. Among the adults with diabetes, the mean age was 59 years, the mean fasting glucose was 155 ± 2 mg/dl, and the mean HbA1c was 7.2%; 80.3% of diabetics were considered overweight (BMI ≥ 25) and 49.1% of diabetics were considered obese (BMI ≥ 30). The prevalence of adults with diabetes increased with increasing weight classes, from 8% for normal weight individuals to 43% for individuals with obesity class 3; the distribution of HbA1c levels were considered as good (<7.0%) in 60%, fair (7.0-8.0%) in 17%, and poor (>8.0%) in 23%. The mean fasting glucose and HbA1c levels were highest for diabetics with BMI <25.0, suggesting a state of higher severity of disease. Mean insulin and c-peptide levels were highest for diabetics with BMI = 35.0, suggesting a state of insulin resistance.. In a nationally representative sample of US adults, the prevalence of diabetes increases with increasing weight classes. Nearly one fourth of adults with diabetes have poor glycemic control and nearly half of adult diabetics are considered obese suggesting that weight loss is an important intervention in an effort to reduce the impact of diabetes on the health care system.

Topics: Adult; Body Mass Index; C-Peptide; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Nutrition Surveys; Obesity; Obesity, Morbid; Severity of Illness Index; United States

To explore whether it is possible to predict a child's eventual diabetes phenotype using characteristics at initial presentation, we reassessed 111 young patients on average 7.8 ± 4.2 (2.2-19.7) [mean ± SD (range)] years after diagnosis.. Medical records at diagnosis for 111 patients, aged 0-17, were compared with their follow-up characteristics including stimulated C-peptide (CP) and islet autoantibodies (AB).. Initially, 18 patients were obese; 9 displayed other type 2 diabetes (T2DM) features (polycystic ovary syndrome, acanthosis, diagnosed T2DM); the remaining 84 had a classic type 1 diabetes (T1DM) presentation. At follow-up, 83 patients (75%) with no measured CP were classified as T1DM; 17 (15%) were CP+ and AB- and thus considered T2DM. Eleven patients with both T1DM and T2DM features were classified as having mixed diabetes phenotype (MDM). One-fifth (22 subjects) changed presumed phenotype at follow-up. In multivariable models, T1DM patients were younger at diagnosis, had higher initial glucose values, were more likely to have experienced ketoacidosis, and less likely to be obese or of African American ethnicity.. Ten percent of subjects had MDM and 15% had T2DM at ∼8 years' duration. Although no onset feature was completely reliable, ketoacidosis and hyperglycemia were more likely to predict T1DM; obesity and African American ethnicity made T2DM more likely. At diagnosis, features of T2DM in addition to obesity were strongly predictive of eventual T2DM phenotype. Given the significant percentage who changed or had mixed phenotype, careful tracking of all young people with diabetes is essential to correctly determine eventual disease type.

Topics: Adolescent; Adult; Autoantibodies; Black or African American; C-Peptide; Chicago; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; Insulin-Secreting Cells; Longitudinal Studies; Male; Obesity; Phenotype

Weight-loss independent mechanisms may play an important role in the improvement of glucose homeostasis after Roux-en-Y gastric bypass (RYGB). The objective of this analysis was to determine whether RYGB causes greater improvement in glucostatic parameters as compared with laparoscopic adjustable gastric banding (LAGB) or low calorie diet (LCD) after equivalent weight loss and independent of enteral nutrient passage. Study 1 recruited participants without type 2 diabetes mellitus (T2DM) who underwent LAGB (n = 8) or RYGB (n = 9). Study 2 recruited subjects with T2DM who underwent LCD (n = 7) or RYGB (n = 7). Insulin-supplemented frequently-sampled intravenous glucose tolerance test (fsIVGTT) was performed before and after equivalent weight reduction. MINMOD analysis of insulin sensitivity (Si), acute insulin response to glucose (AIRg) and C-peptide (ACPRg) response to glucose, and insulin secretion normalized to the degree of insulin resistance (disposition index (DI)) were analyzed. Weight loss was comparable in all groups (7.8 ± 0.4%). In Study 1, significant improvement of Si, ACPRg, and DI were observed only after LAGB. In Study 2, Si, ACPRg, and plasma adiponectin increased significantly in the RYGB-DM group but not in LCD. DI improved in both T2DM groups, but the absolute increase was greater after RYGB (258.2 ± 86.6 vs. 55.9 ± 19.9; P < 0.05). Antidiabetic medications were discontinued after RYGB contrasting with 55% reduction in the number of medications after LCD. No intervention affected fasting glucagon-like peptide (GLP)-1, peptide YY (PYY) or ghrelin levels. In conclusion, RYGB produced greater improvement in Si and DI compared with diet at equivalent weight loss in T2DM subjects. Such a beneficial effect was not observed in nondiabetic subjects at this early time-point.

Topics: Adiponectin; Adult; Blood Glucose; C-Peptide; Caloric Restriction; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Laparoscopy; Male; Middle Aged; Obesity; Peptide YY; Weight Loss

Laparoscopic ileal interposition associated with a sleeve gastrectomy (LII-SG) is a safe and effective operation for the treatment of type 2 diabetic (T2DM) patients with BMI below 35. The aim of this study was to evaluate insulin sensitivity (IS) and β-cell function using the euglycemic hyperinsulinemic clamp (EHC) with the intravenous glucose tolerance test (IVGTT).. This was a prospective study of 24 T2DM patients submitted to a 3-hour EHC-IVGTT before and 1 month after LII-SG. Mean BMI was 29.0, mean age was 54.8 years and mean duration of T2DM was 10.2 years; insulin therapy was used by 62.5% of the patients.. Mean BMI decreased from 29.0 to 25.8 (p < 0.001). Mean fasting plasma glucose and mean postprandial glucose were 202 and 251.3 mg/dl and dropped to 127.7 and 131.8 mg/dl (p < 0.001), respectively. Mean preoperative IS was 1.4 mmol·min(-1)·nmol(-1) and increased to 2.2 mmol· min(-1)·nmol(-1) postoperatively (p < 0.001). Mean C-peptide AUC was 488 pmol·nmol(-1) and increased to 777 pmol· nmol(-1) (p = 0.37). The disposition index increased from 9.4 to 36.4 postoperatively (p = 0.01).. According to the clamp technique, II-SG significantly improved IS and β-cell function as early as 30 days postoperatively in a T2DM population with a BMI of 21.9-33.8.

Topics: Adult; Area Under Curve; Bariatric Surgery; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastrectomy; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Ileum; Insulin; Insulin Resistance; Insulin-Secreting Cells; Laparoscopy; Male; Middle Aged; Obesity; Postoperative Period; Preoperative Period; Prospective Studies; Weight Loss

In preparation for islet transplantation, diabetes was induced using streptozotocin (STZ) in non-human primates ranging from juveniles to adults with diverse body types: we studied the process with respect to the diabetic state and emergence of adverse events (AEs) and their severity, and identified risk factors for clinical and laboratory AEs. Pharmaceutical-grade STZ was given based on body surface area (BSA) (1050-1250 mg/m(2), equivalent to 80-108 mg/kg) or on body weight (BW) (100 mg/kg) to 54 cynomolgus and 24 rhesus macaques. AEs were related to risk factors, i.e. obesity parameters, BW and BSA, age and STZ dose in mg/m(2). Clinical AEs during the first days after infusion prompted euthanasia of three animals. Except for those three animals, diabetes was successfully induced as shown by circulating C-peptide levels, the intravenous glucose tolerance test and/or arginine stimulation test. C-peptide after infusion weakly correlated (P = 0.048) with STZ dose in mg/m(2). Grade ≥3 nephrotoxicity or hepatotoxicity (serum markers >3× baseline or >5 × baseline, respectively) occurred in about 10% of cases and were generally mild and reversible. Grade ≥2 clinical AEs occurred in seven of 78 animals, reversed in four cases and significantly correlated with obesity parameters. Taking girth-to-height ratio (GHtR) as an indicator of obesity, with threshold value 0.92-0.95, the positive predictive value of obesity for AEs was 92% and the specificity 94%. We conclude that diabetes is successfully induced in non-obese animals using a 100 mg/kg pharmaceutical grade STZ dose. Obesity is a significant risk factor, and animals with a higher than normal GHtR should preferably receive a lower dose. The incidence of relevant clinical or laboratory AEs is low. Careful monitoring and supportive medical intervention can result in recovery of AEs.

Topics: Animals; Body Surface Area; Body Weight; C-Peptide; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Glucose Tolerance Test; Macaca fascicularis; Macaca mulatta; Male; Obesity; Risk Factors; Streptozocin

Compare metabolic responses after mixed versus liquid meals of similar caloric/nutritional content in healthy and type 2 diabetes (T2D) subjects.. Ten healthy men and 10 men with T2D received mixed and liquid meals after an overnight fast. Classical (insulinogenic index; insulin/glucose areas under curves, AUC(insulin)/AUC(glucose)) and model-based (beta-cell glucose sensitivity; rate sensitivity; potentiation factor ratio, PFR) beta-cell function estimates were calculated. Between-meal differences in glucose, insulin, C-peptide, triglyceride (TG), beta-cell function and oral glucose insulin sensitivity (OGIS) and between-meal correlations for beta-cell function and OGIS were evaluated.. Among healthy subjects, beta-cell function and OGIS were similar between meals. C-peptide (p=0.03), insulin (p=0.002), AUC(insulin)/AUC(glucose) (p=0.004) and insulin secretion (p=0.04) were higher after the liquid meal. Among T2D subjects, glucose, insulin, C-peptide, beta-cell function, and OGIS were similar. PFR was higher (p=0.004) and TG increased more slowly (p=0.002) after the liquid meal. OGIS and beta-cell function were correlated during both meals in both groups (r=0.66-0.98), except incremental AUC(insulin)/AUC(glucose), rate sensitivity, and, in healthy subjects, PFR.. Metabolic responses after mixed or liquid meals of similar content were highly correlated in T2D and healthy subjects. In T2D, the liquid meal produced beta-cell function estimates generally similar to the mixed meal.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Postprandial Period; Triglycerides

OBJECTIVE Wld(S) (Wallerian degeneration slow), a fusion protein from a spontaneous mutation containing full-length nicotinamide mononucleotide adenylyltransferase 1, has NAD biosynthesis activity and protects axon from degeneration robustly. NAD biosynthesis is also implicated in insulin secretion in β-cells. The aim of this study was to investigate the effect of Wld(S) on β-cells and glucose homeostasis.. Using the Wld(S) mice, we measured the expression of Wld(S) in pancreas and analyzed the effect of Wld(S) on glucose homeostasis. The direct effect of Wld(S) on insulin transcription and secretion and the related mechanisms was measured in isolated islets or β-cell lines. Silent information regulator 1 (SIRT1), an NAD-dependent protein deacetylase, is involved in insulin secretion. Thus, Wld(S) mice with SIRT1 deficiency were generated to study whether the SIRT1-dependent pathway is involved.. Wld(S) is highly expressed in the pancreas and improves glucose homeostasis. Wld(S) mice are resistant to high-fat diet-induced glucose intolerance and streptozotocin (STZ)-induced hyperglycemia. Wld(S) increases insulin transcription dependent on its NAD biosynthesis activity and enhances insulin secretion. SIRT1 is required for the improved insulin transcription, secretion, and resistance to STZ-induced hyperglycemia caused by Wld(S). Moreover, Wld(S) associates with SIRT1 and increases NAD levels in the pancreas, causing the enhanced SIRT1 activity to downregulate uncoupling protein 2 (UCP2) expression and upregulate ATP levels.. Our results demonstrate that Wld(S) combines an insulinotropic effect with protection against β-cell failure and suggest that enhancing NAD biosynthesis in β-cells to increase SIRT1 activity could be a potential therapeutic approach for diabetes.

Topics: Adenosine Triphosphate; Animals; Blotting, Western; C-Peptide; Cell Line, Tumor; Diet, High-Fat; Fluorescent Antibody Technique; Glucose; Immunohistochemistry; Immunoprecipitation; Insulin; Insulin Secretion; Insulin-Secreting Cells; Mice; Mice, Inbred C57BL; NAD; NADP; Nerve Tissue Proteins; Niacin; Obesity; Real-Time Polymerase Chain Reaction; Signal Transduction; Sirtuin 1

Our study was carried out to ascertain the role of valproic acid for inducing metabolic disorders like hyperinsulinemia, insulin resistance and metabolic syndrome. Seventy-nine subjects were enrolled into the study. They were divided in 3 groups: 26 patients with epilepsy on VPA monotherapy and 28 patients with epilepsy on CBZ monotherapy and 25 healthy controls. Blood samples for fasting insulin, glucose, C-peptide, TG and HDL were collected. We compared insulin, C-peptide, C-peptide/insulin ratio, HOMA-IR, BMI, central obesity and metabolic syndrome in patients treated with VPA, patients treated with CBZ and in healthy controls. VPA treatment was associated with insulin resistance (30.8%) in opposite to CBZ treatment (7.1%). Metabolic syndrome existed in 34,6%, 14,3% and 12% among VPA, CBZ and control groups, respectively. There was no difference in C peptide/insulin ratio between study groups. Interestingly lean VPA treated patients showed high frequency of insulin resistance and metabolic syndrome compared to lean CBZ treated patients and controls. Therefore we suppose that obesity should not be an obligatory factor for VPA induced metabolic disturbances. VPA treatment is associated with insulin resistance and metabolic syndrome. This metabolic disorders were not connected with diminished hepatic insulin extraction. Although VPA treated patients showed central obesity predominance, we suggest that VPA can induce such metabolic and endocrine changes without obesity.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Carbamazepine; Cholesterol, HDL; Epilepsy; Female; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Obesity; Triglycerides; Valproic Acid

Transoral gastroplasty (TOGA) recently emerged as a new, feasible and relatively safe technique for the surgical treatment of obesity. However, so far there are no data on the effects on insulin sensitivity in the literature. Our aim is to evaluate the effect of TOGA on insulin sensitivity and secretion.. Nine glucose normo-tolerant obese subjects (age:41+/-6 years; BMI:42.49+/-1.03 kg/m(2)) were studied. Fat-free mass (FM) and fat mass (FM) were assessed by bioelectrical impedance; plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT) before and 3 months after the operation. Insulin sensitivity was calculated using the oral-glucose insulin-sensitivity index, and insulin secretion by C-peptide deconvolution. Three months after surgery, a significant (P=0.008) reduction of BMI to 35.65+/-0.65 kg/m(2), with a decrease of FM and FFM from 57.22+/-2.19 to 41.46+/-3.02 kg (P=0.008) and from 59.52+/-1.36 to 56.67+/-1.10 kg (P=0.048) respectively, was observed. Insulinemia was significantly reduced at fast and at 120 min after OGTT; in contrast, no significant change in glucose concentration was observed. Insulin sensitivity significantly increased (348.45+/-20.08 vs. 421.18+/-20.84 ml/min/m(2), P=0.038) and the incremental area of insulin secretion rate (total ISR) significantly decreased (from 235.05+/-27.50 to 124.77+/-14.50 nmol/min/m(2), P=0.021). Total ISR correlated with weight, BMI and FM (r=0.522, P=0.028; r=0.541, P=0.020; r=0.463, P=0.049, respectively). BMI represented the most powerful predictor of ISR decrease (R(2)=0.541, P=0.020).. Transoral gastroplasty allows a significant weight loss 3 months after the intervention as well as an amelioration of insulin sensitivity with subsequent reduction of the insulin secretion.

Topics: Adiposity; Adult; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Electric Impedance; Energy Intake; Female; Gastroplasty; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Obesity; Treatment Outcome; Weight Loss

To describe the clinical experience and the pharmacokinetics of U-500 regular insulin in severely insulin-resistant obese type 2 diabetic patients.. Patients requiring >200 units of insulin with A1C levels >8.0% were switched to U-500 regular insulin. For the pharmacokinetic study, fasting subjects received 100 units of U-500 regular insulin subcutaneously, and samples drawn before and every 30-60 min for glucose, insulin, and C-peptides until glucose fell below 100 mg/dl.. U-500 regular insulin doses were adjusted using the same approach as for adjusting NPH insulin doses. Mean values at baseline and at minimum A1C levels were, respectively, A1C 9.9 and 7.1%, 3.2 and 3.3 units/kg, and weight 98.6 and 102.8 kg. Pharmacokinetically, insulin concentrations rose briskly by 30 min and remained elevated for at least 7 h.. Uncontrolled severely insulin-resistant obese type 2 diabetic patients can be satisfactorily controlled with U-500 regular insulin.

Topics: Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Obesity

Adiponectin is a peptide hormone secreted from the adipose tissue, affecting the proliferation and insulin sensitivity in different cell types. The levels of adiponectin have been found to be decreased in hyperinsulinemia and insulin resistant states, such as obesity. The previous studies have suggested that plasma adiponectin levels are decreased in patients with endometrial and breast cancer. In our study, the relationship among serum adiponectin levels, demographic features and histopathological variables was evaluated in gastric cancer patients. Forty consecutive patients with gastric cancer who underwent gastrectomy with standard lymph node dissection were included and 43 healthy controls were included in this study. The serum levels of glucose, insulin, C-peptide, HbA1c and adiponectin were measured in both groups. We analyzed the correlation among these parameters and patients' demographic features, such as age, gender, body mass index (BMI) and histopathological variables such as tumor localization, stage, nodal status, histological grade, vascular and lymphatic invasion. The mean age was 60.05+9.72 in patients, while it was 38.6+12.73 in controls. The mean serum adiponectin levels were 12.62+7.9 and 10.07+6.72 ng/ml, respectively, in groups. There was no different in terms of adiponectin, C-peptide, HOMA-R level in both groups. On the other hand, BMI, glucose and insulin levels were significantly different in gastric cancer patients in comparison with the controls. There was no correlation among the levels of adiponectin, BMI, insulin and c-peptide levels in patient group (P>0.05). The adiponectin levels of woman were significantly lower than male patients (P=0.002). No relations were detected among tumor stage, tumor localization, nodal status, lymphatic and vascular invasion, and the levels of serum adiponectin (P>0.05). Interestingly, a positive correlation was found between tumor grade and plasma adiponectin levels (r=0.372; P=0.018). Our results suggest that plasma adiponectin levels were similar in both patients with gastric cancer and the controls. In addition, no correlation was found between adiponectin levels and demographic features and histopathological variables of patients. But, in undifferentiated tumors, plasma adiponectin level was significantly higher than well-differentiated grade tumors.

Topics: Adiponectin; Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Female; Gastrectomy; Gastric Mucosa; Humans; Insulin; Insulin Resistance; Lymph Node Excision; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Obesity; Prognosis; Risk Factors; Stomach Neoplasms; Survival Rate

The metabolic syndrome (MS) has become an epidemiological problem in Western countries. We developed a diet-induced obese rat model that mimics all the symptoms of MS in humans, but whose insulin resistance, hyperphagia and hyperleptinemia are caused by nutrition rather than genetic modifications.. Spontaneously hypertensive rats (SHR) were allowed for 12 weeks to choose between a cafeteria diet (CD, 20.3 kJ/g) and standard rat chow (11.7 kJ/g). Controls received rat chow.. Body weight (BW) exceeded control levels when SHR were fed with CD. The increase in BW was attributed to enhanced energy intake. The abundance of abdominal fat as well as the plasma levels of leptin and triglycerides increased concomitant with glucose, insulin and C-peptide. This prediabetic condition was further confirmed by a markedly increased insulin response following glucose challenge and by impaired glucose utilization after insulin tolerance tests.. Increases in food intake and BW despite hyperleptinemia indicate leptin resistance following CD feeding. CD-fed SHR feature leptin and insulin resistance, hypertension and obesity, thus mimicking the situation of MS patients. As such, our model is more suitable than the genetically modified rat models used to study human MS.

Topics: Abdominal Fat; Animals; Biomarkers; Blood Glucose; Blood Pressure; Body Weight; C-Peptide; Diet; Disease Models, Animal; Energy Intake; Heart Rate; Hyperphagia; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Triglycerides

Incretin secretion and effect on insulin secretion are not fully understood in patients with type 2 diabetes. We investigated incretin and insulin secretion after meal intake in obese and non-obese Japanese patients with type 2 diabetes compared to non-diabetic subjects. Nine patients with type 2 diabetes and 5 non-diabetic subjects were recruited for this study. Five diabetic patients were obese (BMI > or = 25) and 4 patients were non-obese (BMI < 25). In response to a mixed meal test, the levels of immunoreactive insulin during 15-90 min and C-peptide during 0-180 min in non-obese patients were significantly lower than those in obese patients. Total GLP-1 and active GIP levels showed no significant difference between obese and non-obese patients throughout the meal tolerance test. In addition, there were no significant differences between diabetic patients and non-diabetic subjects. In conclusion, incretin secretion does not differ between Japanese obese and non-obese patients with type 2 diabetes and non-diabetic subjects.

Topics: Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Incretins; Insulin; Insulin Secretion; Middle Aged; Obesity

Macrophages are more abundant in adipose tissue from obese individuals than from those of normal weight and may contribute to the metabolic consequences of obesity by producing various circulating factors. One of these factors is plasminogen activator inhibitor-1 (PAI-1), which contributes to both atherosclerosis and insulin resistance. Because nutritional factors appear to regulate PAI-1 expression, we hypothesized that exposure to fatty acids and adipocyte secretory products could stimulate production of PAI-1 by adipose macrophages. Increased free fatty acid (FFA) concentrations in blood for 5 hours in nondiabetic, overweight subjects markedly suppressed insulin-stimulated glucose uptake and raised circulating PAI-1 concentrations, with a concomitant increase in the expression of the PAI-1 gene in adipose tissue. FFAs also rapidly increased PAI-1 gene expression in adipose macrophages and PAI-1 protein immunofluorescence surrounding these cells. By contrast, PAI-1 expression in circulating monocytes was very low and was not affected by raising the concentration of FFAs. Medium from cultured adipocytes stimulated PAI-1 expression in cultured macrophages and potentiated the increase in PAI-1 messenger RNA expression in response to FFAs. Together, our data suggest that adipocyte-derived factors prime adipose macrophages so that they respond to nutritional signals (FFAs) by releasing a key inflammatory adipokine, PAI-1.

Topics: Adipocytes; Adipokines; Animals; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Humans; Insulin; Macrophages; Male; Mice; Obesity; Plasminogen Activator Inhibitor 1

Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, beta-cell dysfunction, or glucose intolerance.. We genotyped 1498 German subjects for SNPs rs6232 and rs6235 within PCSK1. The subjects were metabolically characterized by oral glucose tolerance test with glucose, insulin, proinsulin, and C-peptide measurements. A subgroup of 512 subjects underwent a hyperinsulinemic-euglycemic clamp.. The minor allele frequencies were 25.8% for SNP rs6235 and 6.0% for rs6232. After adjustment for sex and age, we found no association of SNPs rs6235 and rs6232 with BMI or other weight-related traits (all p >or= 0.07). Both minor alleles, adjusted for sex, age, BMI and insulin sensitivity were associated with elevated AUCproinsulin and AUCproinsulin/AUCinsulin (rs6235: p(additive) model or= 0.08). The minor allele of SNP rs6232 was additionally associated with 15% higher OGTT-derived and 19% higher clamp-derived insulin sensitivity (pdom

Topics: Body Composition; C-Peptide; Genotype; Glucose; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Obesity; Polymorphism, Single Nucleotide; Proinsulin; Risk Factors; White People

It is believed that important pathogenic mechanism in polycystic ovary syndrome (PCOS) is hyperinsulinemia. Insulin synthesis is linked to C-peptide release, but the role of C-peptide in PCOS is not well described. THE AIM OF THE STUDY was to evaluate C-peptide serum levels in overweight or obese women with PCOS and assessment of correlation between serum concentrations of C-peptide and androgens and metabolic disturbances in PCOS.. 65 women diagnosed with PCOS were included to the study. I group consisted of 5 overweight PCOS women (27.2 +/- 3.6 years old; BMI 27.3 +/-1.5 kg/m2), and II group included 60 obese PCOS women (26.2 +/- 6.3 years old; BMI 35.0 +/- 4.45 kg/m2). The control group consisted of 10 healthy, ovulatory women with normal weight (aged 28.8 +/- 4.8 years; BMI 21.2 +/- 2.1 kg/m2). Folliculotrophin (FSH), lutrophin (LH), 17beta-estradiol (E2), testosterone (T), dehydroepiandrosterone sulfate (DHEAS) and insulin concentrations were measured in serum. Serum fasting glucose levels and lipid profile was assessed: total cholersterol (Ch), triglycerides (TG), low (LDL) and high density lipoproteins (HDL). C-peptide levels were measured using commercially available test (Human C-Peptide ELISA Kit, Dako).. C-peptide concentrations in PCOS overweight group were 1.39 +/- 0.9, and in PCOS obese group were 1.31 +/- 1.05 nmol/I, whereas among healthy women 1.62 +/- 1.56 nmol/I. Those differences were not statistically significant. C-peptide serum levels did not correlated significantly with FSH, LH, E2, T, DHEAS serum levels within studied groups. Negative correlation between C-peptide and glucose serum levels was found in control group (R = -0.71; p < 0.05). Positive correlation between these values in PCOS overweight group was found (R = 0.90; p < 0.05). In PCOS obese group there was no correlation between these values.. Young obese or overweight women with PCOS are characterized by comparable serum C-peptide levels to serum C-peptide concentration in healthy young women. There is no correlation between serum C-peptide and androgens in obese or overweight patients with PCOS. The link between C-peptide and hyperinsulinemia and other metabolic disturbances in PCOS is very complex and requires further studies.

Topics: Adult; C-Peptide; Female; Humans; Obesity; Overweight; Polycystic Ovary Syndrome; Reference Values

Diabetes, characterized by perturbations in insulin production and signaling, is inversely associated with prostate cancer risk irrespective of stage. Obesity, a diabetes risk factor, is inversely associated with localized disease but positively associated with advanced disease. To understand the complex association between hyperinsulinemia and prostate cancer, we evaluated the association of plasma C-peptide, an insulin secretion marker, with prostate cancer risk in a case-control study nested in a prospective community cohort. Prostate cancer cases (n = 264) and matched controls (n = 264) were identified in the CLUE II cohort between 1989 (baseline) and 2002. C-peptide concentration was measured in baseline plasma by ELISA. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression, adjusting for being overweight or obese and family history. Median C-peptide concentration was lower in cases (1,180 pmol/L) than in controls (1,365 pmol/L; P = 0.03). Men in the highest (versus lowest) fourth of C-peptide had a lower risk for prostate cancer (OR, 0.65; 95% CI, 0.37-1.14; P-trend = 0.08), primarily localized disease (OR, 0.44; 95% CI, 0.19-1.03; P-trend = 0.04). Associations were similar to overall, when excluding cases diagnosed during the first 5 years of follow-up, men with diabetes, or men who had not had a prostate-specific antigen test. C-peptide concentration was inversely associated with subsequent diagnosis of prostate cancer, primarily localized disease, similar to the association for obesity. However, we cannot rule out detection bias that might result if men with higher C-peptide have lower prostate-specific antigen irrespective of whether prostate cancer is present or not.

Topics: Aged; Aged, 80 and over; Body Mass Index; C-Peptide; Case-Control Studies; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Humans; Hyperinsulinism; Incidence; Male; Middle Aged; Neoplasm Staging; Obesity; Prostatic Neoplasms; Risk Factors

Despite existing epidemiologic data concerning the increased incidence of breast cancer in diabetes type 2, the association between insulin resistance and breast carcinogenesis is not yet well defined. In this cross-sectional study, we examined the homeostatic model assessment values of insulin resistance (HOMA-IR) among 82 patients with malignant breast tumor, 48 subjects with benign breast mass, and 838 healthy Iranian women. One hundred and thirty (n = 130) surgical inpatients of Tehran Central Cancer Institute (Tehran, Iran) were evaluated preoperatively. Healthy subjects were nondiabetic, nonhypertensive women aged 20-77 years from four different locations in Tehran. Age and central obesity-adjusted HOMA-IR values were 3.6 [95% confidence interval (CI), 2.8-4.4], 2.3 (1.7-2.9), and 1.7(1.6-1.8) correspondingly in subjects with malignant breast tumor, those with benign breast mass, and healthy subjects. The interaction effect of age on the association between breast mass (malignant/ benign /no breast mass) with HOMA-IR values was significant [F(54) = 10, P < 0.001, partial eta squared = 0.03]. The interaction of central obesity on this association was also significant [F(54) = 37, P < 0.001, partial eta squared = 0.11]. We conclude that the noted linkage between insulin resistance and breast cancer may indicate an underlying pathology of mammary carcinogenesis.

Topics: Adult; Age Factors; Aged; Blood Glucose; Breast Neoplasms; C-Peptide; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Iran; Middle Aged; Obesity; Risk Factors

To assess the influence of alterations in glucose concentrations on androgen levels in patients with polycystic ovary syndrome (PCOS) and in healthy controls.. Prospective, controlled study.. Tertiary care center.. Seven patients with PCOS and 20 healthy controls.. Hyperinsulinemic glucose clamp study with stepwise reduction of the plasma glucose level from hyperglycemia to hypoglycemia.. Concentrations of insulin, C-peptide, cortisol, T, androstenedione, 17-hydroxyprogesterone, DHEA, and DHEAS during hyperglycemia, euglycemia, and hypoglycemia.. Total T levels and the free androgen index were significantly higher in the PCOS group at baseline and throughout the clamp. The levels of T, androstenedione, DHEAS, and 17-hydroxyprogesterone were not influenced by short-term changes of plasma glucose concentrations in both groups. However, hypoglycemia led to a significant increase in DHEA levels in PCOS patients as well as in controls. Cortisol levels were not increased during hypoglycemia in either group.. In contrast to men, androgen levels are not influenced by short-term changes of plasma glucose levels in PCOS patients and in healthy women. However, DHEA concentrations increase with decreasing glucose levels independently from an activation of the hypothalamic-pituitary-adrenal axis. This supports a gender difference regarding the counterregulatory hormone response to hypoglycemia.

Topics: 17-alpha-Hydroxyprogesterone; Adult; Androgens; Androstenedione; Blood Glucose; C-Peptide; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Glucose Clamp Technique; Humans; Hydrocortisone; Insulin; Obesity; Polycystic Ovary Syndrome; Prospective Studies; Reference Values; Testosterone; Waist-Hip Ratio; Young Adult

Minimally invasive methodology, mathematical model, and software for analysis of glucose homeostasis by deconvolution of insulin secretion, hepatic extraction, post-hepatic delivery, and sensitivity from 24-hour standardized meals test have been developed and illustrated by the study of glucose homeostasis of a genetically based leptin-deficient patient before and after leptin replacement treatment. The only genetically leptin-deficient adult man identified in the world was treated for 24 months with recombinant methionyl human leptin. Blood was collected every 7 minutes for 24 hours, with standardized meals consumed during the 4 visits: at baseline, one-week, 18-months, and 24-months after initiation of the treatment. Concentrations of insulin, C-peptide, and plasma glucose were measured. Insulin secretion was obtained by deconvolution of C-peptide data. Hepatic insulin extraction was determined based on our modifications of the insulin kinetics model . Insulin sensitivity for each of the four meals was calculated by using the minimal glucose model approach. Hepatic extraction of insulin was the first element of glucose homeostasis to respond to leptin replacement treatment and increased 2-fold after one week of treatment. Insulin secretion and delivery rates decreased more than 2-fold and insulin sensitivity increased 10-fold after 24 months of treatment. Computer programs for analysis of 24-hour insulin secretion, extraction, delivery, and action are available upon request.

Topics: Adult; C-Peptide; Glucose; Homeostasis; Humans; Insulin; Insulin Secretion; Leptin; Liver; Male; Models, Theoretical; Obesity; Postprandial Period; Recombinant Proteins

Obesity and its associated comorbidities are of major worldwide concern. It is now recognized that there are a number of metabolically distinct pathways of obesity development. The present paper investigates the effect of moderate daily exercise on the underlying mechanisms of one such pathway to obesity, through interrogation of metabolic flexibility. Pregnant Wistar rats were either fed chow ad libitum or undernourished throughout pregnancy, generating control or intrauterine growth restricted (IUGR) offspring, respectively. At 250 d of age, dual-emission x-ray absorptiometry scans and plasma analyses showed that moderate daily exercise, in the form of a measured amount of wheel running (56 m/d), prevented the development of obesity consistently observed in nonexercised IUGR offspring. Increased plasma C-peptide and hepatic atypical protein kinase Czeta levels explained increased glucose uptake and increased hepatic glycogen storage in IUGR offspring. Importantly, whereas circulating levels of retinol binding protein 4 were elevated in obese, nonexercised IUGR offspring, indicative of glucose sparing without exercise, retinol binding protein 4 levels were normalized in the exercised IUGR group. These data suggest that IUGR offspring have increased flexibility of energy storage and use and that moderate daily exercise prevents obesity development through activation of distinct pathways of energy use. Thus, despite a predisposition to develop obesity under sedentary conditions, obesity development was prevented in IUGR offspring when exercise was available. These results emphasize the importance of tailored lifestyle changes that activate distinct pathways of metabolic flexibility for obesity prevention.

Topics: Animal Feed; Animals; Blood Glucose; Body Composition; C-Peptide; Diet, Reducing; Energy Intake; Female; Fetal Growth Retardation; Insulin; Leptin; Lipids; Obesity; Physical Conditioning, Animal; Pregnancy; Rats; Rats, Wistar; Retinol-Binding Proteins, Plasma

Impaired glucose tolerance (IGT) represents a pre-diabetic state. Controversy continues in regards to its pathophysiology. The aim of this study was to investigate the differences in insulin sensitivity (IS) and secretion in obese adolescents with IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes.. A total of 12 obese adolescents with NGT, 19 with IGT, and 17 with type 2 diabetes underwent evaluation of insulin sensitivity (3-h hyperinsulinemic [80 micro/m(2)/min]-euglycemic clamp), first-phase insulin and second-phase insulin secretion (2-h hyperglycemic clamp), body composition, and abdominal adiposity. Glucose disposition index (GDI) was calculated as the product of first-phase insulin x insulin sensitivity.. Insulin-stimulated glucose disposal was significantly lower in subjects with type 2 diabetes compared with subjects with NGT and IGT, with no difference between the latter two. However, compared with youth with NGT, youth with IGT have significantly lower first-phase insulin and C-peptide levels and GDI (P = 0.012), whereas youth with type 2 diabetes have an additional defect in second-phase insulin. Fasting and 2-h glucose correlated with GDI (r = -0.68, P < 0.001 and r = -0.73, P < 0.001, respectively) and first-phase insulin but not with insulin sensitivity.. Compared with youth with NGT, obese adolescents with IGT have evidence of a beta-cell defect manifested in impaired first-phase insulin secretion, with a more profound defect in type 2 diabetes involving both first- and second-phase insulin. GDI shows a significantly declining pattern: it is highest in NGT, intermediate in IGT, and lowest in type 2 diabetes. Such data suggest that measures to prevent progression or conversion from pre-diabetes to type 2 diabetes should target improvement in beta-cell function.

Topics: Abdomen; Adipose Tissue; Adolescent; Black People; Body Mass Index; C-Peptide; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 2; Estradiol; Female; Glucose; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Male; Obesity; Reference Values; Viscera; White People

Obesity is associated with insulin resistance and the resulting hyperinsulinemia has been attributed to an increase of insulin secretion and a reduction of insulin clearance. The present study was intended to further characterize the relative contribution of secretion and clearance especially in the postprandial state. In relation to WHO body weight classes 291 subjects were divided in 5 subgroups Basal insulin concentrations rose stepwise and significantly with increasing BMI. This was paralleled by C-peptide concentrations and insulin secretion, while the reduction of insulin clearance was less stringent in relation to BMI. Basal glucose was unchanged in the BMI25 group and 8% higher in the obese groups (BMI 30, 35, 40) compared to normal weight (NW). Although postprandial insulin concentrations were significantly higher in the overweight and obese groups compared to NW the correlation was not as tight as in the basal state. Furthermore, the present data demonstrate for the first time that insulin secretion only increased in the overweight group without further augmentation in the obese groups. Further hyperinsulinemia of the latter was due to weight-dependent reduction of insulin clearance. The postprandial glucose response was 38-82% higher with increasing weight compared to NW. In summary basal hyperinsulinemia is mainly due to weight related increase of insulin secretion with moderate contribution of reduced insulin clearance. Postprandially, hyperinsulinemia of overweight is predominantly due to secretion while further postprandial hyperinsulinemia of obese subjects is mainly due to reduced clearance. Thus, postprandial insulin secretion cannot respond adequately to the challenge of weight-dependent insulin resistance already in non-diabetic obese subjects.

Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Female; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Male; Obesity

Variants downstream of the melanocortin-4 receptor gene (MC4R) have been reported to associate with obesity. We examined rs17782313, rs17700633, rs12970134, rs477181, rs502933, and rs4450508 near MC4R for association with obesity-related quantitative traits, obesity, and type 2 diabetes in Danish individuals.. The variants were investigated for association with obesity-related quantitative traits in 5,807 population-based sampled individuals, obesity in 14,940 individuals, and type 2 diabetes in 8,821 individuals.. The minor risk alleles of rs17782313, rs17700633, and rs12970134 were associated with BMI (effect per allele 0.25 kg/m2, P = 0.01; 0.23, P = 0.01; and 0.31, P = 7 x 10(-4), respectively), waist circumference (0.67 cm, P = 0.006; 0.53, P = 0.02; and 0.85, P = 3 x 10(-4)), and body weight (1.04 kg, P = 6 x 10(-4); 0.71, P = 0.01; and 1.16, P = 8 x 10(-5)). In case-control studies of obesity defined by BMI, the minor C-allele of rs17782313 was associated with overweight/obesity and obesity (odds ratio [OR] 1.09, P = 0.006 and OR 1.12, P = 0.003, respectively). Similarly, the minor A-allele of rs17700633 was associated with overweight/obesity and obesity (1.12, P = 8 x 10(-5) and 1.16, P = 2 x 10(-5)), and the minor A-allele of rs12970134 was also associated with overweight/obesity and obesity (1.13, P = 2 x 10(-5) and 1.15, P = 6 x 10(-5)). rs477181, rs502933, and rs4450508 were not significantly associated with obesity in the Danish population. The frequency of the minor risk alleles of rs17782313 and rs12970134 was higher among patients with type 2 diabetes than among glucose-tolerant individuals (OR 1.08, P = 0.08 and 1.08, P = 0.06, respectively); however, these borderline associations were abolished after adjustment for BMI.. rs17782313, rs17700633, and rs12970134 near MC4R associate with measures of obesity in Danish individuals.

Topics: Adult; Body Mass Index; C-Peptide; Case-Control Studies; Cholesterol; Denmark; Genetic Variation; Genotype; Humans; Insulin; Middle Aged; Obesity; Quantitative Trait Loci; Receptor, Melanocortin, Type 4; Risk Assessment; Triglycerides; Waist-Hip Ratio

Studies in adipose tissue and skeletal muscle suggest that impaired insulin action is due to defects in the insulin signaling pathway and may play a role in the pathophysiology of insulin resistance associated with gestational diabetes mellitus (GDM) and obesity. The present study tested the hypothesis that endogenous expression levels in the human term placenta of insulin signaling components are altered in placental tissue from GDM women in comparison with normal controls and maternal obesity.. Placental tissue was collected from normal, diet-controlled GDM, and insulin-controlled GDM in both non-obese and obese women (n=6-7 per group). Western blotting and quantitative RT-PCR was performed to determine the level of expression in the insulin signaling pathway.. There was a significant increase in insulin receptor (IR) substrate (IRS)-1 protein expression with a concurrent decrease in IRS-2 protein expression in non-obese women with insulin-controlled GDM compared with diet-controlled GDM and normal controls. Furthermore, a decrease in both protein and mRNA expression of phosphatidyl-inositol-3-kinase (PI3-K) p85alpha and glucose transporter (GLUT)-4 was observed in non-obese and obese women with insulin controlled GDM compared with normal controls. When comparing non-obese to obese patients, significant decreases in mRNA expression of IR-beta, PI3K p85alpha and GLUT-4 was found in obese patients.. Our results suggest that post receptor defects are present in the insulin signaling pathway in placenta of women with pregnancies complicated by diabetes and obesity. In addition, expression studies demonstrate post receptor alterations in insulin signaling possibly under selective maternal regulation and not fetal regulation.

Topics: Adult; Blotting, Western; C-Peptide; Cell Membrane; Cohort Studies; Diabetes, Gestational; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Glucose; Glucose Transporter Type 4; Humans; Immunohistochemistry; Indicators and Reagents; Insulin; Obesity; Phosphatidylinositol 3-Kinases; Placenta; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction

The pubertal transition has been identified as a time of risk for development of type 2 diabetes, particularly among vulnerable groups, such as African Americans (AAs). Documented ethnic differences in insulin secretory dynamics may predispose overweight AA adolescents to risk for type 2 diabetes. The objectives of this longitudinal study were to quantify insulin secretion and clearance in a cohort of 90 AA and European American (EA) children over the pubertal transition and to explore the association of genetic factors and adiposity with repeated measures of insulin secretion and clearance during this critical period. Insulin sensitivity was determined by intravenous glucose tolerance test (IVGTT) and minimal modeling; insulin secretion and clearance by C-peptide modeling; genetic ancestry by admixture analysis. Mixed-model longitudinal analysis indicated that African genetic admixture (AfADM) was independently and positively associated with first-phase insulin secretion within the entire group (P < 0.001), and among lean children (P < 0.01). When examined within pubertal stage, this relationship became significant at Tanner stage 3. Total body fat was a significant determinant of first-phase insulin secretion overall and among obese children (P < 0.001). Total body fat, but not AfADM, was associated with insulin clearance (P < 0.001). In conclusion, genetic factors, as reflected in AfADM, may explain greater first-phase insulin secretion among peripubertal AA vs. EA; however, the influence of genetic factors is superseded by adiposity. The pubertal transition may affect the development of the beta-cell response to glucose in a manner that differs with ethnic/genetic background.

Topics: Adipose Tissue; Adiposity; Adolescent; Black or African American; Blood Glucose; C-Peptide; Child; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Linear Models; Longitudinal Studies; Male; Obesity; Puberty; Risk Factors; White People

To determine whether deuterium enrichment on carbons 5 and 3 (C5/C3) in plasma glucose is influenced by processes other than gluconeogenesis and, if so, whether these processes are altered by type 2 diabetes.. In this study, 10 obese diabetic and 10 obese nondiabetic subjects were infused intravenously with [3,5-(2)H(2)] galactose enriched at a C5-to-C3 ratio of 1.0 as well as the enrichment of deuterium on C5 and C3 of plasma glucose, measured with nuclear magnetic resonance using the acetaminophen glucuronide method.. The ratio of deuterium enrichment on C5 and C3 of glucose was <1 (P < 0.001) in all of the diabetic and nondiabetic subjects, resulting in a means +/- SE C5-to-C3 ratio that did not differ between groups (0.81 +/- 0.01 vs. 0.79 +/- 0.01, respectively).. That the C5-to-C3 glucose ratio is <1 indicates that transaldolase exchange, selective retention of deuterium at the level of the triose-isomerase reaction, or both occur in humans. This also indicates that the net effect of these processes on the C5-to-C3 ratio is the same in people with and without type 2 diabetes. The possible effects of transaldolase exchange or selective retention of deuterium (or tritium) at the level of the triose-isomerase reaction on tracee labeling and tracer metabolism should be considered when the deuterated water method is used to measure gluconeogenesis or [3-(3)H] glucose is used to measure glucose turnover in humans.

Topics: Aged; Blood Glucose; Body Mass Index; C-Peptide; Deuterium; Diabetes Mellitus, Type 2; Galactose; Glucagon; Gluconeogenesis; Humans; Insulin; Isotope Labeling; Middle Aged; Obesity; Reference Values; Transaldolase; Triose-Phosphate Isomerase

Severe obesity is associated with type 2 diabetes mellitus, and both resolve with weight loss after bariatric operations. Intestinal hormones have been identified which are stimulated by rapid nutrient delivery to the lower small bowel after certain weight-loss operations. These incretins stimulate secretion and hypertrophy of the pancreatic beta cells. Surgical procedures are now being performed to treat diabetes in adults of lesser weight, and the importance of ruling out latent autoimmune diabetes in the adult (a variety of type 1) is suggested, before experimenting with these procedures.

Topics: Adult; Bariatric Surgery; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Obesity; Weight Loss

Recent epidemiologic studies have identified obesity as a risk factor for benign prostatic hyperplasia (BPH). We examined whether adiponectin, leptin, and C-peptide were associated with incident, symptomatic BPH and whether these factors mediate the relationship between obesity and BPH risk.. Data are from Prostate Cancer Prevention Trial placebo arm participants who were free of BPH at baseline. Incident BPH (n = 698) was defined as treatment, two International Prostate Symptom Score (IPSS) values > 14, or an increase of >or=5 in IPSS from baseline documented on at least two occasions plus at least one score >or=12. Controls (n = 709) were selected from men reporting no BPH treatment or IPSS > 7 during the 7-year trial. Baseline serum was analyzed for adiponectin, C-peptide, and leptin concentrations.. Neither C-peptide nor leptin was associated with BPH risk. The odds ratio [95% CI] contrasting highest to lowest quartiles of adiponectin was 0.65[0.47, 0.87] P(trend) = 0.004. Findings differed between levels of physical activity: there was a strong inverse association between adiponectin and BPH among moderately/very active men OR = 0.43 [0.29, 0.63], and no association among sedentary/minimally active men OR = 0.92 [0.65, 1.30] P(interaction) = 0.005. Adiponectin concentrations explained only a moderate amount of the relationship between obesity and BPH risk.. High adiponectin concentrations were associated with reduced risk of incident, symptomatic BPH. This association was limited to moderately/very active men; suggesting the relationship between obesity and BPH involves a complex interaction between factors affecting glucose uptake and insulin sensitivity. However, adiponectin is likely not the only mechanism through which obesity affects BPH risk.

Topics: Adiponectin; Aged; C-Peptide; Case-Control Studies; Disease Progression; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Prostatic Hyperplasia; Prostatic Neoplasms; Risk Factors; Washington

Type 2 diabetes is characterized by hyperglycemia resulting from insulin resistance in the setting of inadequate beta-cell compensation. Recent studies indicate that for attaining a well-functioning ss-cell mass, parathyroid hormone-related protein (PTHrP) is a very promising candidate among several insulinotropic peptides. In order to elucidate its role, we determine the levels of PTHrP, insulin and c-peptide in type 2 diabetics and in normal subjects in the fasting state. We enrolled 28 patients (16 men and 12 postmenopausal women) with type 2 diabetes and twenty eight aged-matched healthy individuals as control subjects (15 men and 13 women). PTHrP was statistically significant correlated with glucose in type 2 diabetes and in normal subjects in the fasting state. Additionally, PTHrP serum levels exhibited a significant increase in type 2 diabetes compared to control subjects. Interestingly, PTHrP showed a positive correlation with insulin levels only among healthy individuals presumably due to defective glucose stimulated insulin secretion known to occur in type 2 diabetics. In conclusion, the strong positive relation of PTHrP with glucose in the fasting state in patients with type 2 diabetes mellitus raises several questions for further experimentation concerning its exact role and physiological significance.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Insulin; Male; Middle Aged; Obesity; Parathyroid Hormone-Related Protein; Sex Characteristics; Statistics, Nonparametric

Type 1 diabetes mellitus (T1DM) is characterized by a selective destruction of pancreatic beta cells. Recent data suggest a role of insulin resistance (IR) along with the deficient insulin reserve.. Fifty-eight consecutive patients of T1DM, with low C-peptide levels were included. Patients with an obvious secondary cause like steroid therapy, fibrocalculous pancreatic disease, chronic infections or comorbid illness were excluded. A clinical assessment for the presence of obesity was made based on anthropometric data. Clinical markers of IR and the insulin dose required to achieve a stable glycemic control calculated in terms of body weight were also studied.. There were 30 males and 28 females with a mean age of 16.5 +/- 2.3 (5-39) years. The mean body mass index (BMI) was 19.21 +/- 3.7 and the waist circumference was 67 +/- 5.2 cms. Nineteen ( 32.75%) and six (10.34%) patients were overweight (BMI > 23) and obese (BMI > 27) respectively while 16 (27.58%) had abdominal obesity. The body fat percentage was high (> 25%) in 34 (58.62%), mean 28.33 +/- 11.4%. Acanthosis nigricans was found in 14 (24.13%) cases, hypertension in two (3.4%) but none of the girls had clinical polycystic ovarian syndrome (PCOS). The insulin dose required was 1.11 +/- 0.41 u/kg (0.3-2.9) at an glycated haemoglobin A1C (A1C) of 7.56 +/- 1.04% (4.9-9.3), it was more than 0.6 u/kg/day in 38 (65.51%) patients.. The study concludes that IR is present in a large number of Indian T1DM patients along with a high body fat percentage.

Topics: Adolescent; Adult; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; India; Insulin; Insulin Resistance; Male; Obesity; Overweight; Waist Circumference; Young Adult

There is virtually no information on the metabolic impact of dietary fructose intake in adolescents despite their high fructose consumption, particularly via sweetened beverages.. To determine the short-term metabolic effects of dietary fructose intake in obese adolescents.. Six volunteers (3 M/3 F; 15.2 +/- 0.5 yr; 35 +/- 2 kg/m2; 39 +/- 2% body fat) were studied twice following 7 d of isocaloric, isonitrogenous high carbohydrate (60% CHO; 25% fat) diets with fructose accounting for 6% and 24% of total energy intake, respectively (random order). Insulin sensitivity and secretion were analyzed by the stable labeled intravenous glucose tolerance test and glucose and lipid kinetics using GCMS.. A fourfold increase in dietary fructose intake did not affect insulin sensitivity or secretion, glucose kinetics, lipolysis or glucose, insulin, C-peptide, triglycerides, HDL- and LDL-cholesterol concentrations.. In the short term, when energy intake is constant, dietary fructose per se is not a contributor to insulin resistance and hypersecretion in obese adolescents.

Topics: Adolescent; Blood Glucose; C-Peptide; Dietary Carbohydrates; Energy Intake; Female; Fructose; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Lipid Metabolism; Male; Obesity

Obesity represents a risk factor for insulin resistance, type 2 diabetes mellitus, and atherosclerosis. In addition, for any given amount of total body fat, an excess of visceral fat or fat accumulation in the liver and skeletal muscle augments the risk. Conversely, even in obesity, a metabolically benign fat distribution phenotype may exist.. In 314 subjects, we measured total body, visceral, and subcutaneous fat with magnetic resonance (MR) tomography and fat in the liver and skeletal muscle with proton MR spectroscopy. Insulin sensitivity was estimated from oral glucose tolerance test results. Subjects were divided into 4 groups: normal weight (body mass index [BMI] [calculated as weight in kilograms divided by height in meters squared], < 25.0), overweight (BMI, 25.0-29.9), obese-insulin sensitive (IS) (BMI, > or = 30.0 and placement in the upper quartile of insulin sensitivity), and obese-insulin resistant (IR) (BMI, > or = 30.0 and placement in the lower 3 quartiles of insulin sensitivity).. Total body and visceral fat were higher in the overweight and obese groups compared with the normal-weight group (P < .05); however, no differences were observed between the obese groups. In contrast, ectopic fat in skeletal muscle (P < .001) and particularly the liver (4.3% +/- 0.6% vs 9.5% +/- 0.8%) and the intima-media thickness of the common carotid artery (0.54 +/- 0.02 vs 0.59 +/- 0.01 mm) were lower and insulin sensitivity was higher (17.4 +/- 0.9 vs 7.3 +/- 0.3 arbitrary units) in the obese-IS vs the obese-IR group (P < .05). Unexpectedly, the obese-IS group had almost identical insulin sensitivity and the intima-media thickness was not statistically different compared with the normal-weight group (18.2 +/- 0.9 AU and 0.51 +/- 0.02 mm, respectively).. A metabolically benign obesity that is not accompanied by insulin resistance and early atherosclerosis exists in humans. Furthermore, ectopic fat in the liver may be more important than visceral fat in the determination of such a beneficial phenotype in obesity.

Topics: Adiponectin; Adipose Tissue; Adolescent; Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Carotid Artery, Common; Fatty Acids, Nonesterified; Fatty Liver; Female; Humans; Insulin; Insulin Resistance; Liver; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Obesity; Tunica Intima; Tunica Media; Ultrasonography

We examined the reproducibility of the oral glucose tolerance test (OGTT) in overweight children and evaluated distinguishing characteristics between those with concordant vs. discordant results.. Sixty overweight youth (8-17 yr old) completed two OGTTs (interval between tests 1-25 d). Insulin sensitivity was assessed by the surrogate measures of fasting glucose to insulin ratio, whole-body insulin sensitivity index, and homeostasis model assessment of insulin resistance, and insulin secretion by the insulinogenic index with calculation of the glucose disposition index (GDI).. Of the 10 subjects with impaired glucose tolerance (IGT) during the first OGTT only three (30%) had IGT during the second OGTT. The percent positive agreement between the first and second OGTT was low for both impaired fasting glucose and IGT (22.2 and 27.3%, respectively). Fasting blood glucose had higher reproducibility, compared with the 2-h glucose. Youth with discordant OGTTs, compared with those with concordant results, were more insulin resistant (glucose/insulin 2.7+/-1.4 vs. 4.1+/-1.8, P=0.006, whole-body insulin sensitivity index of 1.3+/-0.6 vs. 2.2+/-1.1, P=0.003, and homeostasis model assessment of insulin resistance 10.6+/-8.1 vs. 5.7+/-2.8, P=0.001), had a lower GDI (0.45+/-0.58 vs. 1.02+/-1.0, P=0.03), and had higher low-density lipoprotein cholesterol (117.7+/-36.6 vs. 89.9+/-20.1, P=0.0005) without differences in physical characteristics.. Our results show poor reproducibility of the OGTT in obese youth, in particular for the 2-h plasma glucose. Obese youth who have discordant OGTT results are more insulin resistant with higher risk of developing type 2 diabetes mellitus, as evidenced by a lower GDI. The implications of this remain to be determined in clinical and research settings.

Topics: Administration, Oral; Adolescent; Blood Glucose; Body Mass Index; C-Peptide; Child; Fasting; Female; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Obesity; Overweight; Puberty; Reproducibility of Results

Here, we examined the association of genetic variants of FOXA2, an upstream activator of the beta-cell transcription factor network, with type 2 diabetes and related phenotypes in North India. We genotyped three SNPs (rs1212275, rs1055080, rs6048205) and the (TCC)( n ) repeat polymorphism in 1,656 participants comprising 1,031 patients with type 2 diabetes and 625 controls. SNPs rs1212275 and rs6048205 were uncommon (MAF < 5%) with similar distribution among patients and controls. We found a strong association of (TCC)( n ) common allele A5 with type 2 diabetes [OR = 1.66 (95% CI 1.36-2.04, p = 5.9 x 10(-7)) for A5 homozygotes]. Obese individuals with A5A5 genotype had enhanced risk when segregated from normal-weight subjects [OR = 1.92 (95% CI 1.47-2.51), p = 1.6 x 10(-6)]. A5 was also nominally associated with higher fasting glucose (p = 0.02) and lower fasting insulin (p = 0.0028) and C-peptide (p = 0.036) levels among controls. At the rs1055080 locus, GG was found to provide reduced risk among normal-weight subjects [OR = 0.59 (95% CI 0.40-0.88), p = 0.011]. Combination of protective GG and non-risk genotypes of (TCC)( n ) showed reduced risk of type 2 diabetes both among normal-weight [OR = 0.43 (95% CI 0.29-0.65), p = 1.2 x 10(-6)] and obese individuals [0.47 (95% CI 0.34-0.64), p = 4.3 x 10(-5)]. For the first time we demonstrated that FOXA2 variants may affect risk of type 2 diabetes and metabolic traits in North India, however replication analyses in other cohorts are required to confirm the findings.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Genotype; Hepatocyte Nuclear Factor 3-beta; Humans; India; Insulin; Male; Middle Aged; Obesity; Polymerase Chain Reaction; Polymorphism, Genetic; Risk Factors

Excess body-mass index (BMI) has been associated with adverse outcomes in prostate cancer, and hyperinsulinaemia is a candidate mediator, but prospective data are sparse. We assessed the effect of prediagnostic BMI and plasma C-peptide concentration (reflecting insulin secretion) on prostate cancer-specific mortality after diagnosis.. This study involved men diagnosed with prostate cancer during the 24 years of follow-up in the Physicians' Health Study. BMI measurements were available at baseline in 1982 and eight years later in 1990 for 2546 men who developed prostate cancer. Baseline C-peptide concentration was available in 827 men. We used Cox proportional hazards regression models controlling for age, smoking, time between BMI measurement and prostate cancer diagnosis, and competing causes of death to assess the risk of prostate cancer-specific mortality according to BMI and C-peptide concentration.. Of the 2546 men diagnosed with prostate cancer during the follow-up period, 989 (38.8%) were overweight (BMI 25.0-29.9 kg/m(2)) and 87 (3.4%) were obese (BMI >/=30 kg/m(2)). 281 men (11%) died from prostate cancer during this follow-up period. Compared with men of a healthy weight (BMI <25 kg/m(2)) at baseline, overweight men and obese men had a significantly higher risk of prostate cancer mortality (proportional hazard ratio [HR] 1.47 [95% CI 1.16-1.88] for overweight men and 2.66 [1.62-4.39] for obese men; p(trend)<0.0001). The trend remained significant after controlling for clinical stage and Gleason grade and was stronger for prostate cancer diagnosed during the PSA screening era (1991-2007) compared with during the pre-PSA screening era (1982-1990) or when using BMI measurements obtained in 1990 compared with those obtained in 1982. Of the 827 men with data available for baseline C-peptide concentration, 117 (14%) died from prostate cancer. Men with C-peptide concentrations in the highest quartile (high) versus the lowest quartile (low) had a higher risk of prostate cancer mortality (HR 2.38 [95% CI 1.31-4.30]; p(trend)=0.008). Compared with men with a BMI less than 25 kg/m(2) and low C-peptide concentrations, those with a BMI of 25 kg/m(2) or more and high C-peptide concentrations had a four-times higher risk of mortality (4.12 [1.97-8.61]; p(interaction)=0.001) independent of clinical predictors.. Excess bodyweight and a high plasma concentration of C-peptide both predispose men with a subsequent diagnosis of prostate cancer to an increased likelihood of dying of their disease. Patients with both factors have the worst outcome. Further studies are now needed to confirm these findings.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; C-Peptide; Case-Control Studies; Follow-Up Studies; Humans; Hyperinsulinism; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Obesity; Physicians; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; United States

Although patients with type 2 diabetes show no bone mineral density (BMD) reduction, fracture risks are known to increase. It is unclear why the patients have an increased risk of fracture despite sufficient BMD. We investigated the relationships of body mass index (BMI), HbA(1c), and urinary C-peptide (uC-peptide) versus BMD, bone metabolic markers, serum adiponectin, and prevalent vertebral fracture (VF). A total of 163 Japanese type 2 diabetic men were consecutively recruited, and radiographic and biochemical data were collected. BMI was positively correlated with BMD at the whole body, lumbar spine, and femoral neck (P < 0.05) and negatively correlated with osteocalcin and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX) (P < 0.01). HbA(1c) was negatively correlated with osteocalcin (P < 0.01) but not BMD at any site. Subjects were classified into four groups based on BMI and HbA(1c) (group LL BMI < 24 and HbA(1c) < 9, group LH BMI < 24 and HbA(1c) > or = 9, group HL BMI > or = 24 and HbA(1c) < 9, group HH BMI > or = 24 and HbA(1c) > or = 9). Serum adiponectin, osteocalcin, and uNTX were lower and the incidence of VF was higher despite sufficient BMD in the HH group. Multivariate logistic regression analysis adjusted for age, duration of diabetes, uC-peptide, and estimated glomerular filtration rate showed that the HH group was associated with the presence of a VF and multiple VFs (odds ratio [OR] = 3.056, 95% confidence interval [CI] 1.031-9.056, P = 0.0439, and OR = 5.415, 95% CI 1.126-26.040, P = 0.0350, respectively). Combination of obesity with hyperglycemia was a risk factor for VF despite sufficient BMD in diabetic men.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Bone Density; C-Peptide; Collagen Type I; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Logistic Models; Male; Middle Aged; Obesity; Osteocalcin; Peptides; Radiography; Risk Factors; Spinal Fractures

Topics: C-Peptide; Humans; Hyperinsulinism; Life Style; Male; Obesity; Prostatic Neoplasms

The aim of present study was to identify the visceral adipose tissue genes differentially expressed in a well-characterized rat model of high-fat diet (HFD)-induced obesity. Male Sprague-Dawley rats were fed either the HFD (17 g lard + 3 g corn oil/100 g) or the normal diet (5 g corn oil/100 g) for 9 weeks. The HFD rats weighed 55% more and accumulated 85% to 133% greater visceral fats than did the normal-diet rats (P < .05). Animals given the HFD for 9 weeks acquired dyslipidemia, fatty liver, insulin resistance, and hyperleptinemia along with the overexpression of several obesity-related genes, such as leptin, tumor necrosis factor alpha, resistin, peroxisome proliferator-activated receptor gamma2, CCAAT/enhancer-binding protein alpha, and sterol regulatory element-binding protein-1c, in the epididymal adipose tissue. The differential gene expression profile obtained from the cDNA microarray analysis followed by the real-time polymerase chain reaction confirmation led to a recruitment of several uncharacterized adipose tissue genes responding to the HFD. We report herein, for the first time, that a series of genes which might be implicated in the insulin-stimulated glucose transporter 4 translocation, such as protein phosphatase 2 (formerly 2A), cell division cycle 42-interacting protein 4, syntaxin 6, linker of T-cell receptor pathways 10, as well as the genes which might be involved in cancer development, such as heat shock 10-kd protein 1, and ras-related C3 botulinum toxin substrate 1, were differentially expressed in the epididymal adipose tissue of rats rendered obese by an HFD.

Topics: Animals; Body Weight; C-Peptide; Dietary Fats; Epididymis; Gene Expression Profiling; Gene Expression Regulation; Glucose; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipids; Liver; Male; Obesity; Oligonucleotide Array Sequence Analysis; Rats; Rats, Sprague-Dawley

To examine the relation of well-known factors of the metabolic syndrome (MetS) as well as related circulating factors, with risk of colorectal cancer.. We performed a case control study of 306 colorectal cancer cases and 595 matched controls nested in the Northern Sweden Health and Disease Cohort. Levels of C-peptide, glycated haemoglobin (HbA1c), leptin and adiponectin were measured in cryopreserved samples. Body mass index (BMI), systolic and diastolic blood pressure and fasting and post-load plasma glucose, had been measured in a subcohort. Conditional logistic regression was used to calculate odds ratios (OR) of disease, including risk assessments for the MetS factors: obesity (BMI>30 kg m(-2)), hypertension (blood pressure > or =140/90 mmHg or use of anti-hypertensive drugs) and hyperglycaemia (fasting glucose > or =6.1 mmol l(-1) or post-load glucose in capillary plasma > or =8.9 mmol l(-1)).. None of the studied variables were significantly associated with risk across quartiles. Presence of obesity, hypertension and hyperglycaemia significantly increased the risk of colorectal cancer; OR for three vs null factors was 2.57 (95% Confidence Interval [CI] 1.20-5.52; P (trend)=0.0021), as compared to a 30 to 70% increased risk for the factors in single. Similarly, top decile levels of C-peptide, HbA1c and leptin/adiponectin ratio were associated with an increased risk; ORs for top vs deciles 1-9 were 1.56 (95% CI 0.93-2.62; P=0.090), 1.83 (95% CI 1.00-3.36; P=0.051) and 1.50 (95% CI 0.83-2.71; P=0.18), respectively.. Our study support the view that components of the MetS increase risk of colorectal cancer, and further suggests that only very high levels of metabolic factors confer an increased risk.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Colorectal Neoplasms; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Sweden

Metabolic syndrome (MetS) is known to increase the risk of cardiovascular disease. C-reactive protein (CRP) has been reported to be elevated in subjects with MetS. However, which component of MetS contributes mostly to the elevation has not been studied in detail.. We studied 628 apparently healthy Japanese subjects (men 262, women 366, age 19-85 years). Body mass index, waist circumference (WC), blood pressure, lipids, glucose, insulin and CRP were measured. MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III report.. In partial correlation analysis, WC showed the strongest correlation with CRP among the variables related to MetS. CRP increased as the number of MetS components increased. The mean CRP value adjusted for demographic variables was higher in subjects with MetS than those without MetS, and further adjustments with variables related to MetS revealed that the significant difference between the two groups disappeared only when further adjustment was made for WC. In multiple linear regression analysis, the independent variable that most strongly explained the CRP level was WC, which was followed by HDL-cholesterol. Finally, comparison of the CRP levels in groups stratified by abdominal obesity and the number of MetS components revealed that those with abdominal obesity tended to show higher CRP levels compared with those without abdominal obesity regardless of the number of MetS components other than WC.. Subjects with MetS showed higher levels of CRP and the main determinant of the CRP elevation was WC.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Exercise; Female; Humans; Hyperglycemia; Hypertension; Insulin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Patient Selection; Waist-Hip Ratio

To explore whether an imbalance between the visceral and subcutaneous fat depots and a corresponding dysregulation of the adipokine milieu is associated with excessive accumulation of fat in the liver and muscle and ultimately with insulin resistance and the metabolic syndrome.. We stratified our multi-ethnic cohort of 118 obese adolescents into tertiles based on the proportion of abdominal fat in the visceral depot. Abdominal and liver fat were measured by magnetic resonance imaging and muscle lipid (intramyocellular lipid) by proton magnetic resonance spectroscopy.. There were no differences in age, BMI Z score, or fat-free mass across tertiles. However, as the proportion of visceral fat increased across tertiles, BMI and percentage of fat and subcutaneous fat decreased, while hepatic fat increased. In addition, there was an increase in 2-h glucose, insulin, c-peptide, triglyceride levels, and insulin resistance. Notably, both leptin and total adiponectin were significantly lower in tertile 3 than 1, while C-reactive protein and interleukin-6 were not different across tertiles. There was a significant increase in the odds ratio for the metabolic syndrome, with subjects in tertile 3 5.2 times more likely to have the metabolic syndrome than those in tertile 1.. Obese adolescents with a high proportion of visceral fat and relatively low abdominal subcutaneous fat have a phenotype reminiscent of partial lipodystrophy. These adolescents are not necessarily the most severely obese, yet they suffer from severe metabolic complications and are at a high risk of having the metabolic syndrome.

Topics: Abdomen; Adipokines; Adipose Tissue; Adolescent; Blood Glucose; Body Mass Index; C-Peptide; Cohort Studies; Cross-Sectional Studies; Ethnicity; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Liver; Magnetic Resonance Imaging; Male; Obesity; Predictive Value of Tests; Presenilins; Viscera

Mononuclear cells (MNCs) are the primary cell type involved in the pro-inflammatory state of obesity-linked insulin-resistance, and atherosclerosis. Increased serum levels of MMP-9 are reported in insulin-resistant type 2 diabetic patients. Here we demonstrate insulin facilitating human monocytic THP-1 cell chemotaxis via prolonged Erk1/2-dependent induction of MMP-9. In vivo, significantly increased serum levels of MMP-9 were found in obesity-induced hyperinsulinemic C57BL/J6 mice, which were diminished by treatment with the anti-diabetic PPARgamma-ligand pioglitazone. In line with this, pioglitazone inhibited Erk1/2-phosphorylation and subsequent insulin-dependent MMP-9 synthesis in THP-1 cells. Thus, insulin increases MMP-9 gelatinolytic activity in monocytic cells, which results in accelerated chemotaxis. Hyperinsulinemia is associated with enhanced MMP-9 serum levels, potentially facilitating monocyte migration to and infiltration of adipose tissue and the arterial wall, thereby contributing to the increased cardiovascular risk in obese, hyperinsulinemic patients.

Topics: Animals; C-Peptide; Cell Line; Cell Movement; Chemotaxis, Leukocyte; Diet; Dietary Fats; Endothelium, Vascular; Humans; Hyperinsulinism; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Leukocytes, Mononuclear; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Monocytes; Muscle, Smooth, Vascular; Obesity; Pioglitazone; Thiazolidinediones

Exercise improves glucose tolerance in obese rodent models and humans; however, effects with respect to mechanisms of beta-cell compensation remain unexplained. We examined exercise's effects during the progression of hyperglycemia in male Zucker diabetic fatty (ZDF) rats until 19 wk of age. At 6 wk old, rats were assigned to 1) basal--euthanized for baseline values; 2) exercise--swam individually for 1 h/day, 5 days/wk; and 3) controls (n = 8-10/group). Exercise (13 wk) resulted in maintenance of fasted hyperinsulinemia and prevented increases in fed and fasted glucose (P < 0.05) compared with sham-exercised and sedentary controls (P < 0.05). Beta-cell function calculations indicate prolonged beta-cell adaptation in exercised animals alone. During an intraperitoneal glucose tolerance test (IPGTT), exercised rats had lower 2-h glucose (P < 0.05) vs. controls. Area-under-the-curve analyses from baseline for IPGTT glucose and insulin indicate improved glucose tolerance with exercise was associated with increased insulin production and/or secretion. Beta-cell mass increased in exercised vs. basal animals; however, mass expansion was absent at 19 wk in controls (P < 0.05). Hypertrophy and replication contributed to expansion of beta-cell mass; exercised animals had increased beta-cell size and bromodeoxyuridine incorporation rates vs. controls (P < 0.05). The relative area of GLUT2 and protein kinase B was significantly elevated in exercised vs. sedentary controls (P < 0.05). Last, we show formation of ubiquitinated protein aggregates, a response to cellular/oxidative stress, occurred in nonexercised 19 wk-old ZDF rats but not in lean, 6 wk-old basal, or exercised rats. In conclusion, improved beta-cell compensation through increased beta-cell function and mass occurs in exercised but not sedentary ZDF rats and may be in part responsible for improved glucoregulation.

Topics: Animals; Blood Glucose; Body Weight; C-Peptide; Cell Count; Cell Proliferation; Eating; Fluorescent Antibody Technique; Glucose Tolerance Test; Glucose Transporter Type 2; Hyperglycemia; Image Processing, Computer-Assisted; In Situ Nick-End Labeling; Insulin; Insulin-Secreting Cells; Male; Obesity; Oncogene Protein v-akt; Physical Conditioning, Animal; Postprandial Period; Proto-Oncogene Proteins c-akt; Rats; Rats, Zucker; Swimming

To quantitate insulin sensitivity in lean and obese nondiabetic baboons and examine the underlying cellular/molecular mechanisms responsible for impaired insulin action to characterize a baboon model of insulin resistance.. Twenty baboons received a hyperinsulinemic-euglycemic clamp with skeletal muscle and visceral adipose tissue biopsies at baseline and at 30 and 120 min after insulin. Genes and protein expression of key molecules involved in the insulin signaling cascade (insulin receptor, insulin receptor substrate-1, p85, phosphatidylinositol 3-kinase, Akt, and AS160) were sequenced, and insulin-mediated changes were analyzed.. Overall, baboons show a wide range of insulin sensitivity (6.2 +/- 4.8 mg x kg(-1) x min(-1)), and there is a strong inverse correlation between indexes of adiposity and insulin sensitivity (r = -0.946, P < 0.001 for % body fat; r = -0.72, P < 0.001 for waist circumference). The genes and protein sequences analyzed were found to have approximately 98% identity to those of man. Insulin-mediated changes in key signaling molecules were impaired both in muscle and adipose tissue in obese insulin-resistant compared with lean insulin-sensitive baboons.. The obese baboon is a pertinent nonhuman primate model to examine the underlying cellular/molecular mechanisms responsible for insulin resistance and eventual development of type 2 diabetes.

Topics: Animals; Biopsy; Blood Glucose; C-Peptide; Cloning, Molecular; Disease Models, Animal; Female; Glucose Clamp Technique; Hyperinsulinism; Insulin; Insulin-Secreting Cells; Male; Muscle, Skeletal; Obesity; Papio; Thinness

The aim of this study was to define the metabolic abnormalities underlying the prediabetic status of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT in obese youth.. We used state-of-the-art techniques (hyperinsulinemic-euglycemic and hyperglycemic clamps), applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration, in 40 normal glucose tolerance (NGT), 17 IFG, 23 IGT, and 11 IFG/IGT obese adolescents. Percent fat (by dual-energy x-ray absorptiometry), age, gender and ethnicity were comparable among groups.. Peripheral insulin sensitivity was similar between the IFG and NGT groups. In contrast, the IGT and IFG/IGT groups showed marked reductions in peripheral insulin sensitivity (P < 0.002). Basal hepatic insulin resistance index (basal hepatic glucose production x fasting plasma insulin) was significantly increased in IFG, IGT, and IFG/IGT (P < 0.009) compared with NGT. Glucose sensitivity of first-phase insulin secretion was progressively lower in IFG, IGT, and IFG/IGT compared with NGT. Glucose sensitivity of second-phase secretion showed a statistically significant defect only in the IFG/IGT group. In a multivariate regression analysis, glucose sensitivity of first-phase secretion and basal insulin secretion rate were significant independent predictors of FPG (total r(2) = 25.9%).. IFG, in obese adolescents, is linked primarily to alterations in glucose sensitivity of first-phase insulin secretion and liver insulin sensitivity. The IGT group is affected by a more severe degree of peripheral insulin resistance and reduction in first-phase secretion. IFG/IGT is hallmarked by a profound insulin resistance and by a new additional defect in second-phase insulin secretion.

Topics: Adolescent; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Obesity; Phenotype

The present study aimed to reveal racial differences in the metabolic pattern of C-peptide and non-esterified fatty acids (NEFA), and in their associations with cardiovascular measures in healthy urban African (102) and Caucasian women (115) from South Africa. An oral glucose tolerance test was performed with measurements before and at 30, 60, 90 and 120min. Various cardiovascular parameters and blood lipids were assessed. Statistical analyses were done in a sub-sample of pre-menopausal women. Fasting C-peptide and hepatic insulin extraction were significantly higher in lean African women compared to their Caucasian counterparts, with no racial differences between women with abdominal obesity. Postchallenge C-peptide response and hepatic insulin extraction were significantly higher in Caucasians with abdominal obesity. There were no racial differences in insulin sensitivity and resistance. Despite different associations of C-peptide and NEFA with cardiovascular measures between the ethnicities both showed significant positive correlations with triglycerides. Increased fasting C-peptide levels and unfavorable associations of C-peptide and NEFA with triglycerides and cardiovascular measures implicate a higher cardiovascular risk in lean African women only. This may be of importance for the development of hypertension in this population group.

Topics: Abdominal Fat; Adult; Black People; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin; Obesity; Premenopause; South Africa; White People

Obesity and type 2 diabetes are worldwide health issues. The present paper investigates prenatal and postnatal pathways to obesity, identifying different metabolic outcomes with different effects on insulin sensitivity and different underlying mechanisms involving key components of insulin receptor signaling pathways. Pregnant Wistar rats either were fed chow ad libitum or were undernourished throughout pregnancy, generating either control or intrauterine growth restricted (IUGR) offspring. Male offspring were fed either standard chow or a high-fat diet from weaning. At 260 d of age, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and other metabolic parameters were measured. As expected, high-fat feeding caused diet-induced obesity (DIO) and insulin resistance. Importantly, the insulin sensitivity of IUGR offspring was similar to that of control offspring, despite fasting insulin hypersecretion and increased adiposity, irrespective of postnatal nutrition. Real-time PCR and Western blot analyses of key markers of insulin sensitivity and metabolic regulation showed that IUGR offspring had increased hepatic levels of atypical protein kinase C zeta (PKC zeta) and increased expression of fatty acid synthase mRNA. In contrast, DIO led to decreased expression of fatty acid synthase mRNA and hepatic steatosis. The decrease in hepatic PKC zeta with DIO may explain, at least in part, the insulin resistance. Our data suggest that the mechanisms of obesity induced by prenatal events are fundamentally different from those of obesity induced by postnatal high-fat nutrition. The origin of insulin hypersecretion in IUGR offspring may be independent of the mechanistic events that trigger the insulin resistance commonly observed in DIO.

Topics: Animal Feed; Animals; Blood Glucose; C-Peptide; Caloric Restriction; Diabetes, Gestational; Dietary Fats; Female; Fetal Growth Retardation; Fetal Nutrition Disorders; Glucose Clamp Technique; Glycogen; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Lipid Metabolism; Liver; Male; Muscle, Skeletal; Obesity; Phosphoenolpyruvate Carboxykinase (GTP); Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar

Anthropometric markers of obesity are simple means that may be used as markers of cardiovascular risk and insulin resistance. We compare body mass index, waist circumference and waist hip ratio as tools to screen for insulin resistance in 81 overweight Indigenous Australians using ROC curve analysis. Body mass index and waist circumference emerged as better predictors of insulin resistance compared with waist hip ratio.

Topics: Adult; Aged; Aged, 80 and over; Anthropometry; Australia; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Middle Aged; Obesity; Predictive Value of Tests; Risk Factors; ROC Curve; Waist-Hip Ratio

Impaired pancreatic beta cell function and insulin sensitivity are fundamental factors in the pathogenesis of type 2 diabetes; however, the predominant defect appears differ among ethnic groups. We conducted a cross-sectional study to evaluate the contribution of impaired beta cell function and insulin sensitivity at different stages of the deterioration of glucose tolerance in Thais. The study involved 420 urban Thais of both sexes, 43-84 years old. A 75-g oral glucose tolerance test was performed on all of the subjects. Indices of insulin resistance and beta cell function were calculated with the use of a homeostasis model assessment. The subjects were classified as having normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG and IGT, or type 2 diabetes mellitus according to the American Diabetes Association (ADA) criteria. There were no differences between groups with regard to gender and age. The percentage of obesity was significantly greatest in the diabetic group. Fasting serum insulin and C-peptide levels progressively increased from the NGT to the diabetic subjects. Serum C-peptide was more strongly associated with newly diagnosed diabetes than insulin, and was an independent factor associated with newly diagnosed diabetic subjects. The insulin resistance index progressively increased when the glucose tolerance stage changed from NGT through diabetic subjects. Beta cell function did not change significantly in any other group compared to the NGT group. An increase in fasting serum C-peptide may be a risk factor for type 2 diabetes. Obesity and insulin resistance are the predominant features in the deterioration of glucose tolerance in Thais.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Prediabetic State; Thailand

The loss of early-phase insulin secretion is a characteristic feature of type 2 diabetes mellitus. The aim of this study is to examine when impairment of early-phase insulin secretion occurs and whether it can be related to increase in insulin resistance caused by obesity. We developed an analytical method to qualify the early-phase insulin secretion; that is, we measured C-peptide immunoreactivity (CPR) response to a selective increase in blood glucose level in portal vein during oral glucose load under a euglycemic hyperinsulinemic clamp (clamp-OGL). Glucose infusion rate, hepatic glucose uptake, and CPR response during clamp-OGL were measured in 30 subjects with diabetes who were divided into 3 groups based on body mass index, 13 obese subjects with normal glucose tolerance (O-NGT), 10 obese subjects with impaired glucose tolerance (O-IGT), and 15 healthy subjects. Significant increase in CPR levels at 10 minutes in clamp-OGL compared with those at steady state was observed in healthy subjects and in O-NGT; however, those were small or absent in diabetic patients and in O-IGT. The incremental ratio of CPR was not correlated to the makers of insulin resistance. The early-phase insulin secretion is well maintained in O-NGT; however, early-phase insulin secretion has already been disturbed in obese subjects with glucose intolerance.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity

Circulating insulin-like growth factor binding protein 1 (IGFBP-1), leptin, and insulin are 3 proteins modified by obesity and have been associated with cancer at several sites in past studies. We conducted a cross-sectional study to describe the correlation of these proteins with gender, race/ethnicity, anthropometric indexes, and dietary and lifestyle factors. We measured fasting plasma levels of IGFBP-1, leptin, and C-peptide, used here as a stable measure of insulin secretion, in a random sample of 450 male and 352 postmenopausal female Hawaii and Los Angeles Multiethnic Cohort Study (MEC) participants (age range 47-82 yr at blood draw). Through a series of multiple linear regressions, we found that the most parsimonious model for plasma IGFBP-1 included inverse associations with age, body mass index (BMI), and regular soda intake. A term for interaction between age and BMI was positively associated with plasma IGFBP-1. Adjusted mean plasma leptins were highest among Whites and African Americans and lowest among Hawaiians and Japanese Leptin was also inversely associated with age and positively associated with the interaction between age and race/ethnicity, female gender, and BMI. A model with only race/ethnicity and BMI (positive association) was best for plasma C-peptide. Adjusted means for C-peptide were highest for Japanese and Whites and lowest for African Americans. The overall percent of variance in protein levels explained by these models was low for IGFBP-1(R2=0.17) and C-peptide (R(3)=0.11) and higher for leptin (R(2)=0.57). We saw no clear correlation between racial/ethnic trends in protein levels with those of colorectal, breast, or prostate cancer incidence rates in the MEC. Research to clarify factors associated with determination of these proteins and their relationship with cancer etiology is warranted.

Topics: Age Factors; Aged; Aged, 80 and over; Asian; Black or African American; Body Mass Index; C-Peptide; Carbonated Beverages; Cohort Studies; Cross-Sectional Studies; Diet; Ethnicity; Female; Humans; Insulin; Insulin Secretion; Insulin-Like Growth Factor Binding Protein 1; Leptin; Life Style; Male; Middle Aged; Neoplasms; Obesity; White People

The worldwide trend towards obesity in childhood is also observed in the Netherlands and one of the consequences may be type 2 diabetes. In this study, we assessed the number of children with type 2 diabetes, diagnosed by paediatricians, in the Netherlands.. In 2003 and 2004 the Dutch Paediatric Surveillance Unit, a nationwide paediatric register, was used to assess new cases of diabetes mellitus. Data on socio-demographic and clinical characteristics were collected by means of a questionnaire. A second questionnaire was sent to the reporting paediatrician if the diagnosis was inconclusive or if the diagnosis was type 1 diabetes in combination with overweight or obesity, according to international criteria.. During the 24 months of registration, the paediatricians reported 1142 new cases of diabetes, 943 of which were eligible for analysis. Initially, 14 patients (1.5%) were reported with type 2 diabetes. Only seven of these patients were classified as type 2 diabetes according to the ADA criteria, as information on C-peptides or antibodies was often missing. Based on clinical characteristics, the other seven patients were very likely to have type 2 diabetes. After the second questionnaire, six more patients met the ADA criteria and two were very likely to have type 2 diabetes. Most of the patients were female (95%), 14% were of Turkish and 18% of Moroccan origin.. This study shows a discrepancy between the number of patients with type 2 diabetes diagnosed by paediatricians in daily practice and diagnosed according to the ADA criteria. Moreover, a considerable amount of reported patients were misclassified. Finally, 2.4% patients were classified as (very likely) type 2 diabetes. The development of programmes and protocols for prevention, diagnosis and classification applicable in daily practice is warranted.

Topics: Adolescent; Body Mass Index; Body Weight; C-Peptide; Child; Child, Preschool; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Infant; Infant, Newborn; Male; Morocco; Netherlands; Obesity; Population Surveillance; Sex Factors; Surveys and Questionnaires; Turkey

[corrected] Oxidative stress plays a critical role in the pathogenesis of various diseases. Recent reports indicate that obesity may induce systemic oxidative stress. The aim of the study was to potentiate oxidative stress as a factor which may aggravate peripheral insulin sensitivity and insulinsecretory response in obesity in this way to potentiate development of diabetes. The aim of the study was also to establish whether insulin-secretory response after glucagonstimulated insulin secretion is susceptible to prooxidant/antioxidant homeostasis status, as well as to determine the extent of these changes.. A mathematical model of glucose/insulin interactions and C-peptide was used to indicate the degree of insulin resistance and to assess their possible relationship with altered antioxidant/prooxidant homeostasis. The study included 24 obese healthy and 16 obese newly diagnozed non-insulin dependent diabetic patients (NIDDM) as well as 20 control healthy subjects, matched in age.. Total plasma antioxidative capacity, erythrocyte and plasma reduced glutathione level were significantly decreased in obese diabetic patients, but also in obese healthy subjects, compared to the values in controls. The plasma lipid peroxidation products and protein carbonyl groups were significantly higher in obese diabetics, more than in obese healthy subjects, compared to the control healthy subjects. The increase of erythrocyte lipid peroxidation at basal state was shown to be more pronounced in obese daibetics, but the apparent difference was obtained in both the obese healthy subjects and obese diabetics, compared to the control values, after exposing of erythrocytes to oxidative stress induced by H2O2. Positive correlation was found between the malondialdehyde (MDA) level and index of insulin sensitivity (FIRI).. Increased oxidative stress together with the decreased antioxidative defence seems to contribute to decreased insulin sensitivity and impaired insulin secretory response in obese diabetics, and may be hypothesized to favour the development of diabetes during obesity.

Topics: Adult; Antioxidants; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Insulin; Insulin Resistance; Insulin Secretion; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Obesity; Oxidative Stress

An important mechanism in the pathogenesis of type 2 diabetes in obese individuals is elevation of plasma free fatty acids (FFAs), which induce insulin resistance and chronically decrease beta-cell function and mass. Our objective was to investigate the role of oxidative stress in FFA-induced decrease in beta-cell function.. We used an in vivo model of 48-h intravenous oleate infusion in Wistar rats followed by hyperglycemic clamps or islet secretion studies ex vivo and in vitro models of 48-h exposure to oleate in islets and MIN6 cells.. Forty-eight-hour infusion of oleate decreased the insulin and C-peptide responses to a hyperglycemic clamp (P < 0.01), an effect prevented by coinfusion of the antioxidants N-acetylcysteine (NAC) and taurine. Similar to the findings in vivo, 48-h infusion of oleate decreased glucose-stimulated insulin secretion ex vivo (P < 0.01) and induced oxidative stress (P < 0.001) in isolated islets, effects prevented by coinfusion of the antioxidants NAC, taurine, or tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl). Forty-eight-hour infusion of olive oil induced oxidative stress (P < 0.001) and decreased the insulin response of isolated islets similar to oleate (P < 0.01). Islets exposed to oleate or palmitate and MIN6 cells exposed to oleate showed a decreased insulin response to high glucose and increased levels of oxidative stress (both P < 0.001), effects prevented by taurine. Real-time RT-PCR showed increased mRNA levels of antioxidant genes in MIN6 cells after oleate exposure, an effect partially prevented by taurine.. Our data are the first demonstration that oxidative stress plays a role in the decrease in beta-cell secretory function induced by prolonged exposure to FFAs in vitro and in vivo.

Topics: Acetylcysteine; Animals; Antioxidants; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose; Infusions, Intravenous; Insulin; Insulin Secretion; Obesity; Oleic Acid; Oxidative Stress; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Taurine

Hyperinsulinemic hypoglycemia is newly recognized as a rare but important complication after Roux-en-Y gastric bypass (GB). The etiology of the syndrome and metabolic characteristics remain incompletely understood. Recent studies suggest that levels of incretin hormones are increased after GB and may promote excessive beta-cell function and/or growth.. We performed a cross-sectional analysis of metabolic variables, in both the fasting state and after a liquid mixed-meal challenge, in four subject groups: 1) with clinically significant hypoglycemia [neuroglycopenia (NG)] after GB surgery, 2) with no symptoms of hypoglycemia at similar duration after GB surgery, 3) without GB similar to preoperative body mass index of the surgical cohorts, and 4) without GB similar to current body mass index of the surgical cohorts.. Insulin and C-peptide after the liquid mixed meal were both higher relative to the glucose level achieved in persons after GB with NG compared with asymptomatic individuals. Glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide levels were higher in both post-GB surgical groups compared with both overweight and morbidly obese persons, and glucagon-like peptide 1 was markedly higher in the group with NG. Insulin resistance, assessed by homeostasis model assessment of insulin resistance, the composite insulin sensitivity index, or adiponectin, was similar in both post-GB groups. Dumping score was also higher in both GB groups but did not discriminate between asymptomatic and symptomatic patients. Notably, the frequency of asymptomatic hypoglycemia after a liquid mixed meal was high in post-GB patients.. A robust insulin secretory response was associated with postprandial hypoglycemia in patients after GB presenting with NG. Increased incretin levels may contribute to the increased insulin secretory response.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Eating; Female; Food; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Incretins; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Obesity, Morbid; Postoperative Complications

Increased C-reactive protein (CRP) concentration and insulin resistance (IR) are associated with increased rates of adverse cardiovascular events. We sought to examine the relationship of CRP with surrogate measures of IR among nondiabetic adults in the US.. We conducted analyses using data from the National Health and Nutrition Examination Survey 1999-2002. We analyzed a nationally representative sample of 2514 men and nonpregnant women age > or = 20 years who were non-Hispanic white, non-Hispanic black, or Mexican American.. After adjustment for age, sex, race/ethnicity, smoking status, systolic blood pressure, and serum concentrations of HDL cholesterol, LDL cholesterol, and triglyceride, CRP was significantly associated with 10 IR measures (all P values <0.01). The strength of the association attenuated after further adjustment for waist circumference (change in adjusted regression coefficients ranging from 60.0% to 75.1%). The association of CRP with each IR surrogate was similar (standardized regression coefficient ranges from 0.06 to 0.09). The association of CRP (>3 vs <1 mg/L) with the homeostasis model for assessment of IR (> or = 75th vs <75th percentile) was statistically significant among people with a body mass index > or = 30 kg/m(2) (odds ratio, 2.6; 95% CI, 1.3-5.1) or with a body mass index <25 kg/m(2) (odds ratio, 2.5; 95% CI, 1.5-4.2).. CRP was significantly associated with the surrogate measures of IR among nondiabetic adults. Obesity may play an important role in the association of CRP with IR in this nationally representative sample.

Topics: Adult; Black People; Blood Glucose; Body Mass Index; C-Peptide; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Fasting; Female; Health Surveys; Homeostasis; Humans; Insulin; Insulin Resistance; Logistic Models; Male; Mexican Americans; Middle Aged; Obesity; Smoking; Triglycerides; United States; White People

People with obesity and/or the metabolic syndrome have an increased risk for developing diabetes and cardiovascular disease and may have low adiponectin levels. The obesity associated with Prader-Willi syndrome (PWS) would be expected to have similar complications. However, it was recently reported that, despite their adiposity, people with PWS have reduced visceral fat and are less likely to develop diabetes mellitus or the metabolic syndrome compared with people with simple obesity.. To determine if plasma adiponectin levels and other variables relevant to diabetes and cardiovascular risk are different in a cohort of PWS subjects with known genetic subtypes compared with age-, sex- and weight-matched control subjects.. Fasting plasma glucose, C-peptide, triglycerides, leptin and cholesterol levels were similar in PWS and obese subjects. Our 20 PWS subjects (mean age = 27.7 years) had higher percent body fat (54.1 vs 48.5%) determined by DEXA measurements and lower percent lean mass (45.9 vs 51.5%) compared with 14 obese controls (mean age = 26.9 year). Plasma adiponectin levels were significantly higher in PWS (15.5 +/- 8.2 microg/ml) than in obese controls (7.5 +/- 2.7 microg/ml). A significant positive correlation was found with insulin sensitivity in PWS subjects (r = 0.75, P = 0.0003) but not in obese controls (r = 0.36, P = 0.20).. Our study confirmed an earlier observation of higher adiponectin levels in PWS subjects and less insulin resistance proportionate to their obesity status than found in subjects with simple obesity. Furthermore, no differences were seen in PWS subjects with the chromosome 15 deletion or maternal disomy 15. The reported excessive visceral adiposity in subjects with simple obesity compared with PWS may be associated with decreased production and lower circulating levels of adiponectin.

Topics: Adiponectin; Adolescent; Adult; Biomarkers; Blood Glucose; Body Composition; Body Fat Distribution; C-Peptide; Humans; Insulin; Insulin Resistance; Leptin; Obesity; Prader-Willi Syndrome; Statistics, Nonparametric; Triglycerides

Women of Asian and South Asian descent are at increased risk of developing gestational diabetes mellitus compared with Caucasians, despite lower body mass index (BMI). Nevertheless, there has been limited study of insulin action during pregnancy in these ethnic groups.. The objective of the study was to compare insulin sensitivity in pregnancy in Asian, South Asian, and Caucasian subjects and to determine whether the impact of obesity on insulin action is modified by ethnicity.. A cross-sectional study was performed in outpatients undergoing oral glucose tolerance testing in late pregnancy. Participants were stratified into three groups: 1) Caucasian (n = 116); 2) South Asian (n = 31); and 3) Asian (n = 28).. Insulin sensitivity was measured using the oral glucose tolerance test (IS(OGTT)) index of M. Matsuda and R. DeFronzo, previously validated in pregnancy.. There were no significant ethnic differences in insulin sensitivity despite variation in prepregnancy BMI (Caucasians, 25.2 kg/m(2); South Asians, 23.3 kg/m(2); Asians, 21.4 kg/m(2); overall P = 0.0001). On multiple linear regression analysis, the strongest independent determinants of IS(OGTT) were gestational diabetes mellitus (t = -5.71; P < 0.0001) and BMI (t = -5.43; P < 0.0001). Importantly, both Asian (t = -2.87; P = 0.0047) and South Asian (t = -2.46; P = 0.015) ethnicity also emerged as negative, independent determinants of IS(OGTT). Furthermore, Asian ethnicity significantly modified the association of prepregnancy BMI with IS(OGTT) (interaction term, t = -2.29; P = 0.0231).. Asian and South Asian ethnicity are both independently associated with increased insulin resistance in late pregnancy. Prepregnancy BMI has a much greater effect on insulin resistance in pregnancy in Asian women than in Caucasians. Ethnicity thus emerges as a factor that modulates the effect of obesity on insulin resistance in pregnancy.

Topics: Adult; Asia, Southeastern; Asian; Biomarkers; Body Mass Index; C-Peptide; Cross-Sectional Studies; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Liver; Obesity; Pregnancy; Pregnancy Complications; Proinsulin; United States; White People

Type 2 diabetes mellitus (T2DM) is estimated to account for 10-45% of incident pediatric diabetes cases.. Our objective was to characterize the metabolic defects underlying T2DM in adolescents and young adults.. We conducted a cross-sectional study of islet function and insulin sensitivity in 16 adolescents with T2DM and 13 obese (OB) and 13 lean (LN) age-matched nondiabetic subjects at a University Medical Center.. We provided oral and iv glucose tolerance tests.. We measured insulin and glucagon levels, insulin sensitivity, acute insulin responses to iv glucose, and the ratio of proinsulin to immunoreactive insulin.. The diabetic subjects had elevated fasting insulin levels and significantly reduced insulin sensitivity (P < 0.05). The acute insulin response to iv glucose was comparable in the T2DM and LN groups (P < 0.05 for the OB vs. LN and T2DM), but insulin secretion adjusted for insulin resistance, the disposition index, was severely impaired in the diabetic subjects (P < 0.05 for the T2DM vs. LN and OB). The ratio of proinsulin to immunoreactive insulin did not differ among the three groups in the basal or stimulated state. Plasma glucagon levels were comparable before and after ingestion of glucose.. These findings demonstrate that diabetic adolescents have significant insulin resistance, even compared with subjects of similar obesity and body fatness, and impaired insulin secretion relative to their degree of insulin resistance. However, the adolescent diabetic subjects retained a first-phase insulin response to glucose that was comparable to lean controls and did not have hyperproinsulinemia or hyperglucagonemia.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Complications; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Obesity; Pancreatic Function Tests

Circulating adiponectin (ADP) level in diabetic patients was mainly studied from a viewpoint of insulin action, with little being known about the regulation by pancreatic beta-cell function. We thus investigated the relationship between the serum ADP concentration and pancreatic beta-cell function in non-obese [body mass index (BMI) <30 kg/m(2)] diabetic patients. Serum ADP was measured in 239 type 2 diabetic patients, 61 type 1 diabetic patients and 159 non-obese and non-diabetic subjects with enzyme-linked immunosorbent assay. Serum ADP was analyzed separately by gender. In both males and females, the ADP level increased in conjugation with beta-cell dysfunction, estimated by fasting serum C-peptide, and showed marked increase in type 1 diabetic patients. Multivariate analysis in type 2 diabetic patients showed that the fasting serum C-peptide was extracted as an independent and significantly negative modulator for serum ADP in addition to BMI. The ADP level was not associated with the daily dose of injected insulin in the multivariate analysis using insulin treated patients with types 1 and 2 diabetes. These results indicate that pancreatic beta-cell function is one of a significant negative modulator for the circulating ADP level in non-obese diabetic patients and support the presence of an adipoinsular axis.

Topics: Adiponectin; Adiposity; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Obesity; Regression Analysis; Sex Characteristics; Statistics as Topic

Circulating levels of adiponectin are negatively associated with multiple indices of insulin resistance, and the concentration is reduced in humans with insulin resistance and type 2 diabetes. However, the mechanisms by which adiponectin improves insulin sensitivity remain unclear.. Combining euglycaemic-hyperinsulinaemic clamp studies with indirect calorimetry and skeletal muscle biopsies, we examined the relationship between plasma adiponectin and parameters of whole-body glucose and lipid metabolism, and muscle glycogen synthase (GS) activity in 51 Caucasians (ten lean, 21 obese and 20 with type 2 diabetes).. Plasma adiponectin was significantly reduced in type 2 diabetic compared with obese and lean subjects. In lean and obese subjects, insulin significantly reduced plasma adiponectin, but this response was blunted in patients with type 2 diabetes. Plasma adiponectin was positively associated with insulin-stimulated glucose disposal (r = 0.48), glucose oxidation (r = 0.54), respiratory quotient (r = 0.58) and non-oxidative glucose metabolism (r = 0.38), and negatively associated with lipid oxidation during insulin stimulation (r = -0.60) after adjustment for body fat (all p < 0.01). Most notably, we found a positive association between plasma adiponectin and insulin stimulation of GS activity in skeletal muscle (r = 0.44, p < 0.01).. Our results indicate that plasma adiponectin may enhance insulin sensitivity by improving the capacity to switch from lipid to glucose oxidation and to store glucose as glycogen in response to insulin, and that low adiponectin may contribute to impaired insulin activation of GS in skeletal muscle of patients with type 2 diabetes.

Topics: Adiponectin; Biopsy; C-Peptide; Diabetes Mellitus, Type 2; Enzyme Activation; Female; Glucose Clamp Technique; Glycogen Synthase; Humans; Insulin; Lipids; Male; Middle Aged; Muscle, Skeletal; Obesity; Reference Values

Our purpose was to investigate the effects of electroacupuncture (EA) therapy on body weight and on levels of serum insulin, c-peptide and glucose in obese women. 52 healthy women were included in this study and were allocated into three groups: 1) Placebo EA group (n = 15; mean age = 41.8 +/- 4.6 and mean body mass index {BMI} = 33.2 +/- 3.5); 2) EA group (n = 20; mean age = 42.1 +/- 4.4 and BMI = 35.9 +/- 3.6) and 3) Diet restriction group (n = 20; mean age = 42.9 +/- 4.3 and BMI = 34.7 +/- 2.7). EA was applied to the ear points Hunger and Shen Men on alternating days and to the body points LI 4, LI 11, St 36 and St 44 once a day for 30 minutes over 20 days. Diet restriction that entailed a 1450 kilocalorie (kcal) diet program was applied to the three groups for 20 days. An increase in weight loss was observed when weight loss in the EA group (p < 0.000) was compared to that in the diet restricted and placebo EA groups using the Tukey HSD test. There were increases in the serum insulin (p < 0.001) and c-peptide levels (p < 0.000) in the women treated with EA compared to those in the women treated with the placebo EA and diet restriction groups. A decrease was observed in the glucose levels (p < 0.01) in both the EA and diet restriction groups compared to those in the placebo EA group. Our results suggest that EA therapy is an effective method in treating obesity. EA therapy also helps serum glucose levels to decrease through the increase of serum insulin and c-peptide levels.

Topics: Blood Glucose; C-Peptide; Case-Control Studies; Electroacupuncture; Female; Humans; Insulin; Obesity; Placebos; Weight Loss

Valproate (VPA) treatment has been reported to be associated with obesity and high fasting serum insulin concentrations in parallel with an unfavorable serum lipid profile and hyperandrogenism and polycystic ovaries in women. The pathogenetic mechanism underlying these changes has remained unknown, although several mechanisms have been implicated.. Fifty-one patients receiving monotherapy (31 male and 20 female patients) were included in this study, with 45 (23 male and 22 female) healthy control subjects. These participants were interviewed, clinically examined, and blood samples for fasting plasma glucose, serum insulin, proinsulin, and C-peptide concentrations were taken after an overnight fast.. The valproate-treated patients had fasting hyperinsulinemia (11.30 +/- 6.23 pM vs. 6.28 +/- 4.66 pM in the control subjects; p < 0.001), although the fasting serum proinsulin and C-peptide concentrations were not significantly higher in the patients than in the control subjects. In addition, proinsulin/insulin (0.30 +/- 0.14) and C-peptide/insulin ratios (35.48 +/- 24.09) were lower (p < 0.001) in the VPA-treated patients when compared with the control subjects (0.53 +/- 0.36 and 94.27 +/- 61.85, respectively), and they also had lower fasting plasma glucose concentrations (4.72 +/- 0.35 mM) than the control subjects (5.12 +/- 0.58 mM; p < 0.01).. This study suggests that valproate does not induce insulin secretion but might interfere with the insulin metabolism in the liver, resulting in higher insulin concentrations in the peripheral circulation. These changes are seen irrespective of concomitant weight gain, suggesting that increased insulin concentrations induce weight gain and not vice versa.

Topics: Adult; Anticonvulsants; Blood Glucose; C-Peptide; Epilepsy; Fasting; Female; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Liver; Male; Obesity; Proinsulin; Secretory Rate; Valproic Acid; Weight Gain

Insulin-stimulated glucose transport in muscle is impaired in obesity and type 2 diabetes, but alterations in levels of relevant signalling factors, i.e. atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt), are still uncertain. Clamp studies using maximal insulin concentrations have revealed defects in activation of aPKC, but not PKB, in both obese non-diabetic and obese diabetic subjects. In contrast, clamp studies using submaximal insulin concentrations revealed defects in PKB activation/phosphorylation in obese non-diabetic and diabetic subjects, but changes in aPKC were not reported. The aim of this study was to test the hypothesis that dose-related effects of insulin may account for the reported differences in insulin signalling to PKB in diabetic muscle.. We compared enzymatic activation of aPKC and PKB, and PKB phosphorylation (threonine-308 and serine-473) during hyperinsulinaemic-euglycaemic clamp studies using both submaximal (400-500 pmol/l) and maximal (1400 pmol/l) insulin levels in non-diabetic control and obese diabetic subjects.. In lean control subjects, the submaximal insulin concentration increased aPKC activity and glucose disposal to approximately 50% of the maximal level and PKBbeta activity to 25% of the maximal level, but PKBalpha activity was not increased. In these subjects, phosphorylation of PKBalpha and PKBbeta was increased to near-maximal levels at submaximal insulin concentrations. In obese diabetic subjects, whereas aPKC activation was defective at submaximal and maximal insulin concentrations, PKBbeta activation and the phosphorylation of PKBbeta and PKBalpha were defective at submaximal, but not maximal, insulin concentrations.. Defective PKBbeta activation/phosphorylation, seen on submaximal insulin stimulation in diabetic muscle, may largely reflect impaired activation of insulin signalling factors present in concentrations greater than those needed for full PKB activation/phosphorylation. Defective aPKC activation, seen at all insulin levels, appears to reflect, at least partly, an impaired action of distal factors needed for aPKC activation, or poor aPKC responsiveness.

Topics: Biopsy; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Muscle, Skeletal; Obesity; Protein Kinase C; Proto-Oncogene Proteins c-akt; Triglycerides

Metabolic syndrome (MetS) defines cardiovascular disease (CVD) risks. Despite higher rates of obesity, type 2 diabetes, and hypertension, African Americans have lower rates of MetS when compared to Caucasians, which is paradoxical, since African Americans are more insulin resistant and have higher rates of cardiovascular morbidity and mortality when compared to White Americans. We hypothesized that genetic inheritance predisposes African Americans to the greater cardiovascular risk and the associated morbidity and mortality. Therefore, we investigated the prevalence of components of MetS in obese, glucose-tolerant, first degree relatives of African American patients with type 2 diabetes.. We examined the clinical and metabolic characteristics of 201 first-degree relatives (159 females and 42 males, mean age 41 +/- 8 years, and mean body mass index (BMI) of 32 +/- 8 (kg/m2). The subjects were categorized with MetS according to the Adult Treatment Panel (ATP) III criteria. Insulin sensitivity (Bergman minimal model method) and insulin resistance (homeostasis model assessment [HOMA]) were determined. We compared the clinical and metabolic characteristics in the relatives with and without MetS. Where appropriate, we compared the prevalence of the components of MetS in our African American sample with those of African American data in the National Health and Nutrition Evaluation Survey (NHANES) III.. Comparing the MetS group (n=65) vs control subjects (n=136), the mean age, BMI, and percent body fat were greater in the MetS group. Mean fasting serum glucose, insulin and C-peptide levels were also greater in the MetS group. Insulin resistance index (HOMA-IR) was higher in the MetS group (HOMA-IR: 3.7 +/- 2.7 vs 2.2 +/- 1.7, P=.0002). Mean insulin sensitivity tended to be lower in the MetS group (2.16 +/- 2.64 vs 2.82 +/- 2.31, P=.08). In addition, despite the moderately severe insulin resistance, the MetS group had very low serum triglyceride levels and was the parameter least likely to meet the ATP criteria. The metabolic cutoff points for ATP III criteria were much lower in African American first-degree relatives with MetS. Of the five components of the ATP III criteria, waist circumference was the single most common parameter to likely meet the MetS criteria. We found that the prevalence of MetS was 29% in women and 40% in men when compared with 20.9% in African American women and 13.9% for African American men in the NHANES III.. We found that: 1) the prevalence of MetS is higher in a subgroup of African Americans who were first-degree relatives of patients with type 2 diabetes than that of African Americans in the NHANES III; and 2) waist circumference rather than metabolic parameters was the single most important parameter and was more likely to meet the MetS criteria in African American relatives.

Topics: Adult; Biomarkers; Black or African American; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Family; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Nutrition Surveys; Obesity; Ohio; Pedigree; Prevalence; Research Design; Severity of Illness Index; Sex Factors; Triglycerides; Waist-Hip Ratio

Normal glucose tolerance is expressed over a wide range of glucose concentrations. Whether there is a continuum of risk for developing type 2 diabetes mellitus even when the 2-h plasma glucose is still within this normal range is uncertain. Oral glucose tolerance tests were performed in 407 obese normal glucose tolerance youth (4-20 yr) to examine the relationship between variations in 2-h plasma glucose levels and beta-cell responsiveness. Individuals were grouped by 2-h plasma glucose levels as follows: 1) less than 100 mg/dl, 2) 100-119 mg/dl, and 3) 120-139 mg/dl. Subsequent analysis stratified each 2-h plasma level by insulin sensitivity index. Increased 2-h glucose level was associated with a progressive increase in glucose between 0 and 30 min (P < 0.05). The Delta (0-30 min) insulin did not vary significantly across levels, thus resulting in a decreased insulinogenic index (P < 0.02). This pattern was observed at every level of insulin sensitivity (P < 0.02). These data translated to an unfavorable (leftward) shift in the insulin feedback system for increasing 2-h glucose level (P < 0.005). Increased 2-h plasma glucose within the range of normal glucose tolerance in obese youth is associated with a specific impairment of beta-cell responsiveness distinct from the deterioration of insulin sensitivity.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; C-Peptide; Child; Child, Preschool; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Kinetics; Obesity

Weight gain is a commonly observed adverse effect of atypical antipsychotic medications, but associated changes in energy balance and body composition are not well defined. The authors report here the effect of olanzapine on body weight, body composition, resting energy expenditure, and substrate oxidation as well as leptin, insulin, glucose, and lipid levels in a group of outpatient volunteers with first-episode psychosis.. Nine adults (six men and three women) experiencing their first psychotic episode who had no previous history of antipsychotic drug therapy began a regimen of olanzapine and were studied within 7 weeks and approximately 12 weeks after olanzapine initiation.. After approximately 12 weeks of olanzapine therapy, the median increase in body weight was 4.7 kg, a significant increase of 7.3% from first observation. Body fat, measured by dual-energy x-ray absorptiometry, increased significantly, with a propensity for central fat deposition. Lean body mass and bone mineral content did not change. Resting energy expenditure, measured by indirect calorimetry, did not change. Respiratory quotient significantly increased 0.12 with olanzapine and was greatest in those who gained >5% of their initial weight. Fasting insulin, C-peptide, and triglyceride levels significantly increased, but there were no changes in glucose levels; total, high density lipoprotein, or low density lipoprotein cholesterol levels; or leptin levels.. Olanzapine appears to have induced an increase in central body fat deposition, insulin, and triglyceride levels, suggesting the possible development of insulin resistance. The decrease in fat oxidation may be secondary or predispose patients to olanzapine-induced weight gain.

Topics: Adipose Tissue; Adult; Antipsychotic Agents; Benzodiazepines; Body Composition; Body Weight; C-Peptide; Energy Metabolism; Female; Humans; Insulin; Male; Obesity; Olanzapine; Oxidation-Reduction; Psychotic Disorders; Respiratory Physiological Phenomena; Schizophrenia; Triglycerides

The aim of this study was to investigate the influence of changes in insulin resistance and early insulin secretion on the insulin secretagogic effects of nateglinide.. Oral glucose tolerance testing (OGTT, 75 g) was performed in obese patients before and after weight loss on 2 consecutive days (first day OGTT without nateglinide, second day OGTT with nateglinide), to compare any weight loss associated changes in the nateglinide-induced insulin response to glucose loading.. Reductions in visceral fat, liver fat, skeletal muscle fat and homeostasis model assessment (HOMA)-R due to weight loss were associated with increased Delta insulin 30 min/Delta glucose 30 min (DeltaI30/DeltaG30), and reduced area under the curve (AUC) for plasma glucose as seen in OGTT results. Results from OGTT showed that nateglinide administration was associated with reductions in plasma glucose AUC, both before and after weight loss. Before weight loss, although there was a significant elevation of DeltaI30/DeltaG30 associated with nateglinide treatment, no major change in the insulin-secreting dynamics after glucose loading was observed. After weight loss, nateglinide administration produced a significant increase in DeltaI30/DeltaG30, with insulin secretion peaking more quickly.. Insulin response to nateglinide after glucose loading varied greatly in conjunction with weight loss. This may be accounted for not only by the enhancement of early insulin response to nateglinide associated with the improvement of early insulin response with weight loss but also by the reduced visceral fat, which in turn led to reduced levels of free fatty acids in portal blood and hepatic triglycerides, as well as increased hepatic insulin clearance.

Topics: Adipose Tissue; Administration, Oral; Blood Glucose; C-Peptide; Cyclohexanes; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Homeostasis; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Liver; Male; Middle Aged; Muscle, Skeletal; Nateglinide; Obesity; Phenylalanine; Weight Loss

We prospectively examined the relationship between leptin and markers of insulin resistance and secretion and future visceral adipose tissue accumulation. In this study, 518 nondiabetic Japanese-American men and women underwent the following measurements at baseline and at 5- and 10-year follow-ups: plasma glucose and insulin measured after an overnight fast and during a 75-g oral glucose tolerance test, insulin secretion ratio (ISR) [(30-min insulin - fasting insulin)/30-min glucose], fasting C-peptide levels, plasma leptin (baseline only), and fat areas (intra-abdominal and subcutaneous) measured by computed tomography. Predictors of future intra-abdominal fat (IAF) were determined using multiple linear regression. Fasting insulin and C-peptide levels at baseline were significantly associated with IAF area at 5 years (coefficient = 0.041, P = 0.001 and coefficient = 1.283, P < 0.001, respectively) and 10 years (coefficient = 0.031, P = 0.020 and coefficient = 0.221, P = 0.035, respectively). ISR was not significantly associated with IAF at 5 or 10 years. Leptin level at baseline was positively associated with IAF at 5 years (coefficient = 0.055, P = 0.002) and 10 years (coefficient = 0.059, P = 0.003). In conclusion, higher levels of fasting insulin, C-peptide, and circulating leptin level predicted visceral fat accumulation independent from subcutaneous fat accumulation in nondiabetic Japanese-American men and women in both short-term (5 years) and long-term (10 years) follow-up.

Topics: Abdomen; Adipose Tissue; Asian; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Time Factors

The profile of insulin secretion and the role of proinsulin processing across the spectrum of glucose tolerance in obese youth have not been studied. The aims of this study were to define the role of insulin secretion and proinsulin processing in glucose regulation in obese youth. We performed hyperglycemic clamps to assess insulin secretion, applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration data. Thirty obese youth with normal glucose tolerance (NGT), 22 with impaired glucose tolerance (IGT), and 10 with type 2 diabetes were studied. The three groups had comparable anthropometric measures and insulin sensitivity. The glucose sensitivity of first-phase secretion showed a significant stepwise decline from NGT to IGT and from IGT to type 2 diabetes. The glucose sensitivity of second-phase secretion was similar in NGT and IGT subjects yet was significantly lower in subjects with type 2 diabetes. Proinsulin-to-insulin ratios were comparable during first- and second-phase secretion between subjects with NGT and IGT and were significantly increased in type 2 diabetes. Obese youth with IGT have a significant defect in first-phase insulin secretion, while a defect in second-phase secretion and proinsulin processing is specific for type 2 diabetes in this age-group.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Male; Obesity; Proinsulin

The levels of the liporegulatory hormone leptin are increased in obesity, which contributes to the metabolic syndrome; the latter is associated with elevated cardiovascular risk and morbidity. Leptin may play a role in the metabolic syndrome since correlations have been observed between serum leptin levels and several components of the metabolic syndrome. The association of leptinemia and hypertension or diabetes is inconsistent. Leptin levels are higher in females versus males and obese versus lean individuals. We investigated if correlations exist between leptin levels and several indices of the metabolic syndrome in obese and lean Moroccan subjects with (63 males, 129 females) and without (123 males, 234 females) diabetes and/or hypertension. Plasma glucose and insulin and systolic and diastolic blood pressures were higher in obese versus lean individuals. Obesity had no effect on lipid profile, plasma IGF-1, or C-peptide levels. Leptin levels were higher in females versus males and in obese versus lean individuals. The levels correlated significantly with body mass index. Serum leptin concentration did not correlate with either systolic or diastolic blood pressure, although there was a trend for higher blood pressure with increased leptin levels in females. There was no significant difference in leptin levels between NIDDM patients and healthy controls. However, in hypertensive patients, leptin levels were significantly higher in both lean males and females with diabetes as compared to those without diabetes. Similarly, the higher leptin levels paralleled elevated insulin levels in obese nondiabetic males and females, and in male and female diabetics with hypertension. Correlations were observed between leptin levels and C-peptide (an estimate of endogenous insulin secretion), but not with serum IGF-1. The calculated values of HOMA-IR, a marker of insulin resistance, were somewhat higher, parallel with elevated leptin levels, in obese male and female individuals compared to their lean counterparts. There was no relationship between leptin levels and serum lipids. There was a trend for increased serum uric acid levels with higher leptin concentrations. Thus, leptinemia is related to some components of metabolic syndrome, and in turn, it may contribute to the syndrome. This study is novel in that relationships were determined between leptin levels and various indices of metaboli syndrome in a large population of the same ethnic/regional background.

Topics: Aged; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Morocco; Obesity; Sex Characteristics; Uric Acid

Compensatory hyperinsulinemia permitting insulin-resistant individuals to maintain normal glucose tolerance is associated with a left shift in the glucose-stimulated insulin secretion rate (GS-ISR) dose-response curve and decrease in the insulin metabolic clearance rate (I-MCR). To see whether these changes would reverse with improvement in insulin sensitivity, 14 nondiabetic insulin-resistant subjects received rosiglitazone for 12 weeks (4 mg daily for 4 weeks and then 8 mg daily for 8 weeks). Insulin-mediated glucose uptake was quantified by measuring the steady-state plasma glucose concentration during the insulin suppression test. GS-ISR and I-MCR were determined during a 240-min graded intravenous glucose infusion. I-MCR was also calculated during the insulin suppression test. After rosiglitazone treatment, insulin sensitivity improved with significant fall in steady-state plasma glucose (means +/- SE from 13.5 +/- 0.62 to 9.8 +/- 1.02 mmol/l, P < 0.001). In response, the integrated GS-ISR decreased by 21% (P < 0.001), with a right shift in the dose-response curve. Calculated I-MCR increased by 34% (P = 0.008) during the insulin suppression test and by 21% (P = 0.03) during the graded glucose infusion. In conclusion, enhanced insulin sensitivity in rosiglitazone-treated nondiabetic insulin-resistant individuals was associated with a shift to the right in the GS-ISR dose-response curve and an increase in I-MCR.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Female; Glucose; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Male; Metabolic Clearance Rate; Middle Aged; Obesity; Rosiglitazone; Thiazolidinediones

Trans-fatty acids have been implicated as a risk factor for cardiovascular disease and diabetes. In addition, a polymorphism at codon 54 (Ala54Thr) in the fatty acid-binding protein 2 (FABP2) gene has been suggested to modify an interaction between dietary fat and insulin sensitivity. We examined the postprandial metabolic profiles after meals enriched with C18:1trans- relative to a similar meal with C18:1cis-fatty acid in individuals who were either FABP2 Ala54 homozygotes or Thr54 carriers. Moderately overweight men and women ate 2 breakfast test meals, separated by 1 week, each providing 40% of their daily energy requirement and containing 50% of energy as fat. In one meal, 10% of energy was from C18:1trans, and in the other meal, the C18:1trans was replaced with C18:1cis. Metabolic parameters were assessed during an 8-hour period. Insulin and C-peptide levels increased more after the C18:1trans meal, and this was associated with a greater fall in free fatty acids. Postprandial glucose levels and oxidation of fatty acids and carbohydrate were not different between the 2 test meals. The Thr54 allele for FABP2 increased the rise in postprandial glucose but not triacylglycerols. Fractional triacylglycerol synthetic rates were higher after consumption of the C18:1trans meal relative to the C18:1cis meal only in Thr54 carriers. These data show that a single meal enriched with C18:1trans-fatty acids can significantly increase insulin resistance, and that in the presence of the FABP2 Thr54 allele, may contribute to increased partitioning of glucose to triacylglycerols and insulin resistance.

Topics: Adult; Blood Glucose; C-Peptide; Dietary Fats; Fatty Acid-Binding Proteins; Fatty Acids, Nonesterified; Female; Genotype; Humans; Insulin; Lipids; Male; Middle Aged; Obesity; Postprandial Period; Triglycerides

Obese and physically inactive breast cancer patients may have poorer survival compared with lighter weight and more active women. Several obesity-related and physical activity-related hormones and peptides may explain this association, including insulin, leptin, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Few studies have examined the associations between obesity, physical activity, and these hormones/peptides among breast cancer survivors.. To determine whether obesity and physical activity are associated with insulin, IGFs, and leptin levels in a population-based sample of 710 women diagnosed with in situ to stage IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study.. We collected a blood sample and information on physical activity among women diagnosed 2 to 3 years earlier using an interview-administered questionnaire. Trained staff measured weight. C-peptide, leptin, and IGFs were assayed by RIA. Mean hormone levels within body mass index and physical activity categories were adjusted for confounders using analysis of covariance methods.. We observed higher C-peptide (P for trend = 0.0001) and leptin (P for trend = 0.0001) levels and lower IGF-I levels (P for trend = 0.0001) with higher levels of body mass index. We observed lower C-peptide (P for trend = 0.001) and leptin (P for trend = 0.001) levels and higher IGF-I (P for trend = 0.0037) and IGF-binding protein-3 (P for trend = 0.055) levels with higher levels of physical activity.. Increasing physical activity and decreasing body fat may be a reasonable intervention approach toward changing insulin and leptin, thereby potentially influencing breast cancer prognosis.

Topics: Adult; Analysis of Variance; Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; C-Peptide; Chi-Square Distribution; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Leptin; Middle Aged; Motor Activity; Obesity; Prospective Studies; Survivors

Recent reports indicate an increasing prevalence of type 2 diabetes mellitus (TD2M) in children and adolescents around the world in all ethnicities, possibly due to increasing prevalence of obesity. Therefore, it is essential that clinicians are aware of the clinical features of T2DM in these age groups.. All published cases of T2DM in children and adolescents were evaluated and the different clinical presentations of T2DM in minorities and Caucasian described.. Manifestation of T2DM is usually at mid-to-late puberty with few symptoms such as mild-polyuria or polydipsia. Most of the children and adolescents are extremely obese. The great majority of children and adolescents with T2DM have relatives with T2DM, and show other clinical features of the insulin resistance syndrome such as hypertension, dyslipidemia, polycystic ovarian syndrome (PCOS) or acanthosis nigricans. One-third of the minority children with T2DM and the majority of the Caucasian children with T2DM were detected by screening in the absence of symptoms.. It is becoming increasingly clear that overweight children above the age of 10 y with (1) clinical signs of insulin resistance (acanthosis nigricans, dyslipidemia, hypertension, PCOS), or (2) relatives with T2DM, or (3) of particular ethnic populations (Asian, Indians, Africa-Americans, Hispanics), or (4) extremely obese children should be screened for T2DM.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 2; Diagnosis, Differential; Ethnicity; Female; Humans; Insulin; Lipids; Male; Obesity; Triglycerides

To characterize the features of type 2 diabetes mellitus among children and adolescents in Al-Ain, the records of every child with diabetes attending a teaching hospital in the city from January 1990 to December 2001 were retrospectively examined. Of 96 young people newly diagnosed with diabetes mellitus, 11 were identified as type 2. The clinical characteristics were: pubertal onset, female preponderance, obesity, strong family history of type 2 diabetes mellitus, high plasma glucose at presentation, adequate beta cell reserve and serum pancreatic islet cell antibody negativity. This case series adds to the evidence that type 2 diabetes mellitus is emerging among children in our region.

Topics: Adolescent; Age of Onset; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 2; Epidemiologic Studies; Fasting; Female; Hospitals, Teaching; Hospitals, Urban; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Male; Obesity; Pedigree; Puberty; Retrospective Studies; Risk Factors; Sex Distribution; United Arab Emirates

Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte-derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case-control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C-peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n = 235) or rectum (n = 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3-fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI = 1.44-5.12) for top vs. bottom quartile (p(trend) = 0.008). The corresponding OR for C-peptide was 1.81 (95% CI = 0.67-4.86; p(trend) = 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC = 0.82) but lower for C-peptide (ICC = 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity-induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.

Topics: Adult; C-Peptide; Case-Control Studies; Colonic Neoplasms; Colorectal Neoplasms; Cryopreservation; Humans; Insulin; Leptin; Logistic Models; Male; Middle Aged; Obesity; Odds Ratio; Registries; Time Factors

Chinese Type 2 diabetic subjects are generally less obese than their Caucasian counterparts. We hypothesized that lean and obese Chinese Type 2 diabetic subjects have different metabolic and insulin secretory profiles. We compared the clinical features, C peptide and metabolic status between lean/normal weight and obese diabetic subjects.. We conducted a cross-sectional study on 521 consecutive diabetic subjects newly referred to a Diabetes Clinic in 1996. The subjects were categorized into underweight (< 18.5 kg/m(2)), normal weight (18.5-23 kg/m(2)) and overweight (>/= 23 kg/m(2)) according to the re-defined WHO criterion for obesity in Asia Pacific Region. Metabolic and anthropometric parameters were compared between groups with different levels of obesity.. In this cohort, 5.8, 30.6 and 63.7% of subjects were underweight, normal weight and overweight, respectively, using the 'Asian' criteria. Of these 521 subjects, 20% had fasting C-peptide less than 0.2 nmol/l, suggesting insulin deficiency. Fasting C-peptide showed linear increasing trend (P < 0.001) while HbA(1c) showed decreasing trend (P = 0.001) with BMI after adjustment for duration of disease. There were more subjects in the underweight group who were treated with insulin (41.3% vs. 13.9 and 8.2%, P < 0.001). Although homeostasis model assessment was similar amongst the three groups, systolic (P = 0.006) and diastolic blood pressure (P < 0.001) and triglyceride (P < 0.001) showed increasing, while HDL-C (P < 0.001) showed decreasing, trends across different BMI groups. The underweight patients had the lowest C-peptide and highest HbA(1c) while overweight patients had the highest C-peptide, blood pressure, triglyceride but lowest HbA(1c) levels.. In Chinese Type 2 diabetic patients, lean subjects had predominant insulin deficiency and obese subjects had features of metabolic syndrome. Clinicians should have low threshold to initiate insulin therapy in lean Type 2 diabetic patients with suboptimal glycaemic control. In obese diabetic patients, aggressive control of multiple cardiovascular risks is of particular importance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; C-Peptide; Cholesterol; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Hong Kong; Humans; Insulin; Male; Middle Aged; Obesity; Patient Education as Topic

Offspring of diabetic or hypertensive patients are insulin resistant at a prediabetic/prehypertensive stage. We tested the hypothesis that insulin action may be impaired in the offspring of obese nondiabetic parents.. Twenty-one lean offspring of nonobese subjects [(OL) 22 +/- 3 years of age] were matched to 23 lean offspring of obese subjects (OOb) by gender distribution, age, BMI, and waist circumference. Anthropometry, oral glucose tolerance, in vivo insulin sensitivity [by a euglycemic insulin clamp (6 pmol/min per kilogram(FFM); where FFM represents fat-free mass)], and thermogenesis (by indirect calorimetry) were measured in each subject. The study subjects were from a population of 267 nuclear families (one offspring and both his/her parents) in which there was statistically significant (chi2 = 30.2, p = 0.001) concordance of BMI between parents and offspring.. In comparing OOb with OL, no statistically significant difference or trend toward a difference was detected in fasting plasma glucose and insulin concentrations, glucose and insulin responses to oral glucose, insulin sensitivity [metabolism value = 45 +/- 12 (OOb) vs. 47 +/- 17 micro mol/min per kilogram(FFM) (OL)], insulin-induced inhibition of protein and lipid oxidation, stimulation of glucose oxidation and nonoxidative glucose disposal, respiratory quotient, resting energy expenditure, and glucose-induced thermogenesis.. The metabolic similarity between lean offspring of obese parents and those of nonobese parents suggests that insulin resistance and its correlates are not co-inherited with the predisposition to develop obesity.

Topics: Adult; Blood Glucose; Body Composition; Body Constitution; Body Mass Index; C-Peptide; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Obesity; Parents

Subclinical inflammation has been implicated in the initiation and/or progression of atherosclerosis. Diabetes mellitus and obesity are risk factors for atherosclerosis, and asymptomatic low grade inflammation occurs prior to overt vascular lesions in these patients. In contrast to adults, little information exists concerning low grade inflammation in young type 1 diabetes and juvenile obesity.. To investigate low grade inflammation and immune activation in juvenile diabetes mellitus and obesity.. hs-CRP, soluble interleukin-2 receptor (sIL-2R), C-peptide, insulin, cortisol, vitamin B12, folic acid, leptin, and homocysteine were determined in 148 patients with juvenile type 1 diabetes, 86 obese children and 142 normal weighted age-matched healthy controls. Intima-media thickness (IMT) and lumen diameter of both common carotid arteries (CCA) was measured by ultrasonography in 52 healthy pediatric controls, 10 diabetics, and 34 obese juveniles.. Serum hs-CRP was significantly elevated in patients with type 1 diabetes (p < 0.0001), and obese children (p < 0.0001) as compared to the control group. The obese juveniles (p < 0.0001) and the diabetics (p < 0.0001) showed significantly increased values for IMT of CAAs. Levels of homocysteine, sIL-2R, insulin, cortisol, vitamin B12, and folic acid did not differ from the controls. The elevation of hs-CRP was more pronounced in obesity as compared to type 1 diabetes (p < 0.0001), and the hs-CRP values correlated significantly with body mass index standard deviation score (BMI-SDS) values. Furthermore, the IMT and the luminal diameter of CCAs showed significant correlations with BMI-SDS values.. A low grade inflammation as determined by serum hs-CRP is significantly increased in children with type 1 diabetes, and even more pronounced in apparently healthy juveniles with obesity. The increased IMT of CCAs strongly argues for an association between this low grade inflammation and early atherosclerotic vessel injury.

Topics: Adolescent; Arteriosclerosis; Body Mass Index; C-Peptide; C-Reactive Protein; Carotid Artery, Common; Child; Diabetes Mellitus, Type 1; Female; Folic Acid; Homocysteine; Humans; Inflammation; Leptin; Male; Obesity; Receptors, Interleukin-2; Tunica Intima; Vitamin B 12

The strong relation between type 2 diabetes mellitus and obesity with acanthosis nigricans is widely concerned. This study investigated the pancreatic beta-cell function in obese children with acanthosis nigricans, so as to find out the role of insulin secretion and insulin resistance in obese children with acanthosis nigricans.. Thirty-five obese children with acanthosis nigricans (19 males and 16 females with mean age 12.8 +/- 1.5 years) were enrolled in this study. Thirty-eight obese children (21 boys and 17 girls with mean age 11.9 +/- 2.6 years) and 39 normal children (20 boys and 19 girls with mean age 11.2 +/- 2.2 years) were recruited as obese and normal control groups. The levels of serum fasting insulin, C-peptide, proinsulin and true insulin were measured in all the subjects. The ratios of proinsulin/insulin and proinsulin/C-peptide were calculated. Homeostasis model assessment was applied to assess the status of insulin resistance and basic function of pancreatic beta-cell.. The levels of fasting insulin, C-peptide proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index of obese children with acanthosis nigricans, obese control children and normal control children were: 18.5 (5.0-60.5) pmol/L, 12.4 (6.1-35.8) pmol/L and 5.1 (2.0-32.8) pmol/L; 3.9 (1.3-14.0) microg/L, 2.4 (1.1-4.0) microg/L and 1.1 (1.0-4.2) microg/L; 28.8 (9.9-64.2) pmol/L, 9.5 (2.2-34.5) pmol/L and 4.2 (2.0-16.0) pmol/L; 33.0 (6.2-66.0) pmol/L, 10.6 (4.8-29.4) pmol/L and 4.5 (1.3-30.1) pmol/L; 1.2 (0.4-8.9), 0.9 (0.2-1.9) and 0.8 (0.4-2.0); 6.9 (2.5-36.6), 4.7 (1.2-12.3) and 3.6 (1.2-9.6); 5.0 (0.8-14.1), 2.6 (1.3-8.1) and 1.2(0.4-6.9); 303.3 (52.2-1,163.8), 213.6 (84.6-572.0) and 51.1 (19.1-561.4). The levels of fasting insulin, C-peptide, proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index in obese children with acanthosis nigricans were significantly higher than those in obese children (P < 0.001) and normal children (P < 0.001).. Obese children with acanthosis nigricans had higher insulin resistance and pancreatic beta-cell dysfunction; acanthosis nigricans may be a skin sign of high risk of type 2 diabetes mellitus.

Topics: Acanthosis Nigricans; Adolescent; C-Peptide; Child; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Male; Obesity; Proinsulin

The continuing increase in the incidence of type 2 diabetes mellitus (DM2) and obesity in children and adolescents is attributable to excessive caloric intake. Abnormal lipid metabolism in the postprandial state leads to long exposure of the vasculature to hyperlipidemia. Most children and adolescents with DM2 are obese, and many have fasting hypertriglyceridemia. Clustering of hyperlipidemia, DM2 and obesity increases the risk for cardiovascular disease. We therefore studied lipids, insulin, C-peptide, and glucose in response to an oral fat load simulating the fat content of a high-fat, fast-food meal in 12 type 2 diabetic obese, 15 non-diabetic obese, and 12 non-diabetic non-obese (control) adolescents (aged 10-19 yr; 87% African-Americans). All three groups were age-, sex-, and sexual maturation-matched. Mean body mass indices were similar in the diabetes and obese groups (32.7 +/- 1.1 vs 35.8 +/- 1.6 kg/m2). All patients with DM2 had fasting C-peptide > 0.2 nmol/l (0.7 ng/ml) and negative diabetes-associated autoantibodies. Serum total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, insulin, C-peptide, and plasma glucose levels were measured at 0, 2, 4, and 6 h after the fat load. The area under the curve (AUC) was calculated by trapezoidal estimation. Triglyceride AUC was significantly greater in the diabetes group than in the other two groups (15.7 +/- 2.9 vs 9.2 +/- 0.7 and 7.5 +/- 0.7 mmol x h/l [1389 +/- 258 vs 819 +/- 60 and 663 +/- 62 mg x h/dl]; p < 0.02 and <0.004, respectively), as were insulin, C-peptide, and glucose AUCs. Incremental triglyceride response (delta triglyceride = peak - fasting) in the diabetes group was significantly higher than that in the control group (2.1 +/- 0.7 vs 0.8 +/- 0.1 mmol/l 189.7 +/- 58.4 vs 71.2 +/- 11.1 mg/dl]; p < 0.04). Insulin resistance was estimated using the homeostasis model assessment (HOMA), which was greater in the diabetes group than in the obese and control groups (14.4 +/- 2.8 vs 5.2 +/- 0.8 and 3.2 +/- 0.4; p < 0.001 and < 0.0001, respectively). The diabetes group was divided into subgroups of high and normal fasting triglycerides on the basis of triglyceride levels above and below the 95th percentile. The delta triglyceride in the subgroup with high fasting triglycerides was substantially greater than in the subgroup with normal fasting triglycerides (3.4 +/- 1.1 vs 0.8 +/- 0.2 mmol/l [305.2 +/- 96.8 vs 74.2 +/- 18.0 mg/dl]; p < 0.001). Total cholesterol and triglycer

Topics: Adolescent; Asian People; Black or African American; C-Peptide; Case-Control Studies; Child; Diabetes Mellitus, Type 2; Fasting; Fats; Female; Hispanic or Latino; Humans; Hyperlipidemias; Hypertriglyceridemia; Insulin; Lipids; Male; Obesity; Postprandial Period; Triglycerides

Topics: Body Composition; C-Peptide; Humans; Insulin Receptor Substrate Proteins; Intracellular Signaling Peptides and Proteins; Islets of Langerhans; Obesity; Phenotype; Phosphoproteins; Polymorphism, Genetic

The fasting serum lipid profile [triglycerides (TGs), total cholesterol (TC), and LDL- and HDL-cholesterol (LDL-C and HDL-C)] is used to calculate lipid ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) that allow identification of individuals at increased risk for cardiovascular disease. Because these individuals are also frequently insulin resistant, this study analyzed the relationships between lipid ratios and insulin sensitivity.. In 132 obese [mean (SE) body mass index, 37.5 (0.6) kg/m(2)] outpatients without known diabetes mellitus, fasting serum lipid profiles and 75-g oral glucose tolerance tests were performed. Insulin sensitivity was assessed from surrogate estimates for fasting (QUICKI) and dynamic (OGIS) conditions.. After exclusion of other endocrine diseases (n = 35), the remaining patients were classified as glucose tolerant (n = 56), glucose intolerant (n = 22), or as having type 2 diabetes (n = 19). QUICKI and OGIS indicated severe insulin resistance in all individuals with type 2 diabetes and impaired glucose tolerance compared with glucose-tolerant individuals: QUICKI, glucose tolerant, 0.302 (0.002); glucose intolerant, 0.290 (0.002); type 2 diabetes, 0.281 (0.005); P <0.001; OGIS (mL . m(-2) . min(-1)), glucose tolerant, 343 (7), glucose intolerant, 293 (9); type 2 diabetes, 256 (12); P <0.001. Serum TG (P <0.005) and TG/HDL-C ratios (P <0.05) were increased in individuals with impaired glucose tolerance. TG/HDL-C ratios negatively correlated with QUICKI (r = -0.370; P < 0.001) and OGIS (r = -0.333; P < 0.005) in nondiabetic individuals (glucose tolerant plus glucose intolerant), but not in patients with type 2 diabetes (not significant).. This study demonstrates that the TG/HDL-C ratio positively correlates with insulin resistance in severely obese nondiabetic individuals.

Topics: Adult; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Lipoproteins; Male; Middle Aged; Obesity; Triglycerides

It is well known that sometimes it is difficult to distinguish between type 1 and 2 diabetes mellitus using clinical criteria, in subjects with disease onset relatively early in adult life. The measurement of C peptide level and of immunological markers may represent important additional tools for establishing the correct diagnosis. The aim of the study is to assess the trend of basal C peptide in patients with clinical diagnosis of type 2 diabetes and to relate it to the type of treatment, the body weight and the positivity for pancreatic autoantibodies.. we studied a group of 268 patients with type 2 diabetes, aged between 30 and 50 years, with a diabetes duration of less than 5 years. In all patients, we measured basal C peptide, islet cell autoantibodies and antibodies against glutamic acid decarboxylase, computed the body mass index and recorded the current antidiabetic treatment.. Based on basal C peptide value, diabetic subjects fell under 3 categories: a) low C peptide (<0.58 ng/ml): 7.5%, b) normal C peptide (0.58-2.70 ng/ml): 57.8%, and c) high C peptide (>2.70 ng/ml): 34.7%. Patients with low C peptide were treated more often with insulin, while those in high C peptide group received more often biguanides. A direct correlation between C peptide and body weight was established. Mean C peptide was lower in patients positive for at least one pancreatic autoantibody, compared to those who were negative for antibodies. Low basal C peptide can be considered criterion for transferring the patients, initially diagnosed as type 2 diabetes, in the type 1 diabetes group.

Topics: Adult; Autoantibodies; Biguanides; Biomarkers; Body Mass Index; Body Weight; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Pancreas; Predictive Value of Tests; Treatment Outcome

Circadian rhythms in glucose metabolism are well documented. Most studies, however, evaluated such variations under conditions of continuous glucose supply, either via food intake or glucose infusion. Here we assessed in 30 subjects circadian variations in concentrations of plasma glucose, serum insulin, and C-peptide during a 72-hour fasting period to evaluate rhythms independent from glucose supply. Furthermore we assessed differences in these parameters between normal-weight (n = 20) and overweight (n = 10) subjects. Blood was sampled every 4 hours. During fasting, plasma glucose, serum insulin, and C-peptide levels gradually decreased (all P < .001). While there was no circadian variation in plasma glucose levels after the first day of fasting, serum levels of insulin were constantly higher in the morning (8.00 h) than at night (0.00 h) (P < .001), although the extent of this morning-associated rise in insulin levels decreased with the time spent fasting (P = .001). Also, morning C-peptide concentrations were higher compared to the preceding night (P < .001). The C-peptide/insulin ratio (CIR) decreased during prolonged fasting (P = .030), suggesting a decrease in hepatic insulin clearance. Moreover, CIR was significantly lower in the morning than at the night of day 1 and day 2 of fasting (P = .010 and P = .004, respectively). Compared to normal-weight subjects, overweight subjects had higher plasma glucose, as well as serum insulin and C-peptide levels (all P < .03). Data indicate preserved circadian rhythms in insulin concentrations in the presence of substantially decreased glucose levels in normal-weight and overweight subjects. This finding suggests a central nervous system contribution to the regulation of insulin secretion independent of plasma glucose levels.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Circadian Rhythm; Fasting; Female; Humans; Insulin; Male; Middle Aged; Obesity; Sex Factors; Time Factors

To assess the effects of acute dietary saturated fat intake on glucose-induced insulin secretion rate (ISR), measured by the C-peptide deconvolution method, and on insulin clearance and sensitivity, five obese and five normal-weight women (controls) were studied after either a 100 g oral butter load or a 100 ml water load. At 120 min after the oral load a hyperglycaemic clamp was performed over 180 min. A dramatic increase of ISR occurred after butter compared with the water challenge in the controls (1305.6 (SE 124.1) v. 616.1 (SE 52.5) pmol/min; P<0.01) and to a lesser degree in the obese subjects (1975.0 (SE 44.1) v. 1417.5 (se 56.0) pmol/min; P<0.05). Insulin sensitivity was impaired after butter (0.60 x 10(-2) (SE 0.11 x 10(-2)) v. 2.26 x 10(-2) (SE 0.32 x 10(-2)) ml/min per kg FFM per (pmol/l); P<0.01) in the controls but not in the obese group. Insulin clearance during the clamp was reduced after butter compared with after the water load only in the controls (0.89 (SE 0.22) v. 1.70 (SE 0.15) litres/min; P<0.01). The data are consistent with the hypothesis that acute excess lipid availability may lead to a compensatory elevation in glucose-induced insulin secretion as a result of the decline in insulin sensitivity and a reduced insulin clearance.

Topics: Administration, Oral; Adult; Blood Glucose; Butter; C-Peptide; Dietary Fats; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin Secretion; Obesity; Time Factors; Triglycerides

Obesity and insulin resistance are common features of Type 2 Diabetes. A new protein called resistin has been shown to be secreted by adipocytes in mice and to influence insulin sensitivity. The goal of the present study was to investigate the associations between one polymorphism (g-420C>G) of the human resistin gene and phenotypes related to adiposity and glucose metabolism. We genotyped 725 (including 42 diabetics) adult subjects participating in the Quebec Family Study (QFS) by a minisequencing method. Forty-two were diabetic subjects. Phenotypes measured were: body mass index (BMI) and waist circumference (WC), % body fat (PFAT) and fat mass (FM) assessed by under water weighing, abdominal total, subcutaneous and visceral fat assessed by computed tomography and fasting plasma glucose, insulin and C-peptide and their responses to an oral glucose tolerance test (OGTT). Comparisons between genotypes were performed in non-diabetic men (no.=280) and women (no.=403) separately by analyses of covariance (ANCOVA). Among men, g-420 G homozygotes had less visceral fat (p < 0.05), lower levels of acute insulin responses to an OGTT and lower levels of C-peptide in a fasting state and in responses to an OGTT than carriers of the C allele (p < 0.01). These associations were independent of age and adiposity but were not observed in women. These results suggest that in men, the human resistin gene is associated with reduced amount of visceral obesity and lower insulin secretory responses to a glucose load.

Topics: Abdomen; Adipose Tissue; Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Composition; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 2; Female; Genotype; Glucose Tolerance Test; Hormones, Ectopic; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Pedigree; Phenotype; Polymorphism, Genetic; Quebec; Resistin

We tested the effects of acute perturbations of elevated fatty acids (FA) on insulin secretion in type 2 diabetes. Twenty-one type 2 diabetes subjects with hypertriglyceridemia (triacylglycerol >2.2 mmol/l) and 10 age-matched nondiabetic subjects participated. Glucose-stimulated insulin secretion was monitored during hyperglycemic clamps for 120 min. An infusion of Intralipid and heparin was added during minutes 60-120. In one of two tests, the subjects ingested 250 mg of Acipimox 60 min before the hyperglycemic clamp. A third test (also with Acipimox) was performed in 17 of the diabetic subjects after 3 days of a low-fat diet. Acipimox lowered FA levels and enhanced insulin sensitivity in nondiabetic and diabetic subjects alike. Acipimox administration failed to affect insulin secretion rates in nondiabetic subjects and in the group of diabetic subjects as a whole. However, in the diabetic subjects, Acipimox increased integrated insulin secretion rates during minutes 60-120 in the 50% having the lowest levels of hemoglobin A(1c) (379 +/- 34 vs. 326 +/- 30 pmol x kg(-1) x min(-1) without Acipimox, P < 0.05). A 3-day dietary intervention diminished energy from fat from 39 to 23% without affecting FA levels and without improving the insulin response during clamps. Elevated FA levels may tonically inhibit stimulated insulin secretion in a subset of type 2 diabetic subjects.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Fat-Restricted; Dietary Proteins; Energy Intake; Exercise; Fasting; Fatty Acids; Female; Glucagon; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertriglyceridemia; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Proinsulin; Pyrazines

To compare serum leptin levels of diabetic and non-diabetic female subjects and also assess the relationship of hyperglycemia with serum insulin, C-peptide and leptin levels.. It is a case control study.. The study was conducted at Medicare Hospital, Family Care Clinic and Baqai Institute of Diabetes and Endocrinology between December 1997 to September 1999.. One hundred and forty female subjects with different body mass indices and fasting blood sugar levels were selected from three different diabetic centers. A venous sample was drawn after an overnight fast (12 hours) for determination of blood parameters in all groups. Glycosylated hemoglobin, hexosamine, fructosamine, insulin and C-peptide were determined only in diabetic patients. Blood glucose, triacylglycerol (TAG), total cholesterol, HDL cholesterol, HbA1C, hexosamine and fructosamine were determined enzymatically. Serum leptin, C-peptide and insulin were measured using enzyme-linked immunoassay.. Serum leptin levels of obese diabetic and non-diabetic subjects were significantly higher as compared with lean diabetic patients and non-diabetic subjects (P< 0.05). Leptin levels were positively correlated with serum insulin and C-peptide levels. Serum leptin increased with increase in body mass index and waist hip ratio was strongly related with insulin resistance in NIDDM.. Leptin levels are increased in obesity and may play a role in development of insulin resistance and NIDDM.

Topics: Adult; Biomarkers; Body Mass Index; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Middle Aged; Obesity; Probability; Reference Values; Sensitivity and Specificity; Severity of Illness Index

Mutations in the peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma 2) gene may cause obesity and insulin resistance. Therefore we investigated whether known variants in the PPAR-gamma 2 gene are associated with obesity and extreme insulin resistance in obese patients with impaired glucose tolerance (IGT). The Pro115 Gln, Pro12Ala, Pro467Leu, Val290Met and a silent polymorphism C478 T were examined in 48 subjects with IGT and insulin resistance (IR), characterized by euglycemic hyperinsulinemic clamps, and in 52 healthy insulin sensitive (IS) controls. We found one proband in the IR group with the Pro115 Gln variant. This subject showed a lower whole body glucose uptake (18 micromol/kg per min) compared to the entire IR group (29 micromol/kg per min). The body weight of the proband (BMI 28.5 kg/m2) was within the average of the IR group (30.3 +/- 0.8 kg/m2). The Pro12Ala variant was not associated with differences in BMI, in the degree of insulin resistance between the IR and IS group. The Pro467Leu, Val290Met mutations and the silent polymorphism CAC478CAT were not detected in any group. In conclusion, the Pro115 Gln variant, but not the Pro12Ala mutation in the PPAR-gamma 2 gene, could be a rare cause of severe insulin resistance.

Topics: Adult; Aged; Amino Acid Substitution; Blood Glucose; C-Peptide; DNA; Female; Genetic Variation; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Mutation, Missense; Obesity; Receptors, Cytoplasmic and Nuclear; Transcription Factors

We report two black adolescent subjects who presented with diabetic ketoacidosis, but who lacked autoimmune markers and demonstrated clinical and biochemical characteristics more typical of Type 2 diabetes, including obesity, acanthosis nigricans, positive family history for Type 2 diabetes, and Type 2 diabetic dyslipidaemia. Subsequent to acute presentation, insulin was discontinued in both subjects and excellent glycaemic control was achieved with metformin therapy alone. Four months following acute presentation, both had adequate C-peptide responses to intravenous glucagon. Type 2 diabetes can present as diabetic ketoacidosis in obese adolescent subjects.

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Metformin; Obesity

Androgens are suggested to interact with leptin production and with insulin sensitivity in both polycystic ovary syndrome (PCOS) and obesity. The aim of the study was to follow these interactions along with two forms of antiandrogen treatment. Twenty women with PCOS were treated with ethinylestradiol and high dose of cyproteroneacetate (EE-CA) and 8 with the gonadotrophin-releasing hormone (GnRH) analogue goserelin for 6 months. The patients were divided into a low and a high body weight group and compared with a group of overweight women without PCOS. Both treatments resulted in a significant reduction of free testosterone but the concentration of leptin remained unchanged. EECA treatment resulted in deterioration and GnRH in improvement of insulin sensitivity. Serum leptin correlated only with body weight and body fat. It is concluded that leptin levels do not adequately reflect changes in insulin sensitivity or androgen levels after short-term antiandrogen or antigonadotropin treatment.

Topics: Adipose Tissue; Adult; Androgen Antagonists; Apolipoproteins A; Apolipoproteins B; Blood Glucose; Body Composition; Body Constitution; Body Mass Index; Body Weight; C-Peptide; Cyproterone Acetate; Dehydroepiandrosterone Sulfate; Ethinyl Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin; Insulin Resistance; Leptin; Lipoprotein(a); Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Triglycerides

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones secreted in response to meal ingestion, thereby enhancing postprandial insulin secretion. Therefore, an attenuated incretin response could contribute to the impaired insulin responses in patients with diabetes mellitus. The aim of the present investigation was to investigate incretin secretion, in obesity and type 1 and type 2 diabetes mellitus, and its dependence on the magnitude of the meal stimulus. Plasma concentrations of incretin hormones (total, reflecting secretion and intact, reflecting potential action) were measured during two meal tests (260 kcal and 520 kcal) in eight type 1 diabetic patients, eight lean healthy subjects, eight obese type 2 diabetic patients, and eight obese healthy subjects. Both in diabetic patients and in healthy subjects, significant increases in GLP-1 and GIP concentrations were seen after ingestion of both meals. The incretin responses were significantly higher in all groups after the large meal, compared with the small meal, with correspondingly higher C-peptide responses. Both type 1 and type 2 diabetic patients had normal GIP responses, compared with healthy subjects, whereas decreased GLP-1 responses were seen in type 2 diabetic patients, compared with matched obese healthy subjects. Incremental GLP-1 responses were normal in type 1 diabetic patients. Increased fasting concentrations of GIP and an early enhanced postprandial GIP response were seen in obese, compared with lean healthy subjects, whereas GLP-1 responses were the same in the two groups. beta-cell sensitivity to glucose, evaluated as the slope of insulin secretion rates vs. plasma glucose concentration, tended to increase in both type 2 diabetic patients (29%, P = 0.19) and obese healthy subjects (22% P = 0.04) during the large meal, compared with the small meal, perhaps reflecting the increased incretin response. We conclude: 1) that a decreased GLP-1 secretion may contribute to impaired insulin secretion in type 2 diabetes mellitus, whereas GIP and GLP-1 secretion is normal in type 1 diabetic patients; and 2) that it is possible to modulate the beta-cell sensitivity to glucose in obese healthy subjects, and possibly also in type 2 diabetic patients, by giving them a large meal, compared with a small meal.

Topics: Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Case-Control Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Feeding Behavior; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Obesity; Peptide Fragments; Protein Precursors; Random Allocation

Little research has explored associations of drinking patterns with glycemic control, especially among women. Our objective was to determine the relationship of patterns of alcohol consumption-including average daily consumption, weekly frequency of consumption, drinking with meals, and beverage type-with biologic markers of insulin resistance in young women.. This study was cross-sectional in design. The subjects consisted of a stratified random subpopulation of 459 U.S. normal-weight and overweight female nurses, 33-50 years of age, drawn from the Nurses' Health Study II and sampled for distinct drinking patterns. Women provided blood samples and detailed information on dietary and lifestyle factors between 1995 and 1999. The main outcome measures were fasting insulin, C-peptide, and HbA(1c).. Adjusting for age, smoking, physical activity, television watching, BMI, and several dietary factors, average alcohol intake was inversely associated with HbA(1c) (units in percentage of HbA(1c)): 0 g/day (reference = 5.36%), 0.1 to <5.0 g/day (-0.04%), 5.0 to <15.0 g/day (-0.09%), 15.0 to <25.0 g/day (-0.10%), and > or =25.0 g/day (-0.17%) (P value, test for trend <0.001). We found an inverse association of alcohol intake and insulin, but only for women with a BMI > or =25 kg/m(2). Specifically, insulin levels were lowest for episodic drinkers consuming > or =2 drinks per day on 0-3 days per week. Consumption with meals and type of alcoholic beverage did not further influence these results.. Moderate alcohol consumption of 1-2 drinks per day on a few to several days of the week may have a beneficial glycemic effect, particularly among overweight women.

Topics: Adult; Alcohol Drinking; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Cross-Sectional Studies; Diet; Female; Humans; Middle Aged; Multivariate Analysis; Obesity; Regression Analysis; Temperance

This study investigated the relationship between physical activity and the obesity-related inflammatory markers C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptors (sTNF-Rs) 1 and 2. Furthermore, we examined the relationship between physical activity and insulin sensitivity (insulin, C-peptide, and hemoglobin A(1c) levels) and whether inflammatory markers mediate this association.. Biomarkers were measured in 405 healthy men and 454 healthy women from two large ongoing prospective studies. Information about physical activity and other variables was assessed by questionnaires.. After adjustment for other predictors of inflammation, physical activity was inversely associated with plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein (p = 0.07, p = 0.004, p = 0.04, and p = 0.009). After further adjustment for BMI and leptin, as a surrogate for fat mass, most of these associations were no longer significant. Physical activity was also inversely related to insulin and C-peptide levels (p = 0.008 and p < 0.001); however, in contrast to BMI and leptin, levels of inflammatory markers explained only very little of this inverse relationship.. These results suggest that frequent physical activity is associated with lower systemic inflammation and improved insulin sensitivity. These associations can partially be explained by a lower degree of obesity in physically active subjects. Although inflammatory markers may mediate obesity-dependent effects of physical activity on inflammatory related diseases such as type 2 diabetes or coronary heart disease, our study suggests that they do not directly account for the beneficial effects of physical activity on insulin resistance.

Topics: Adult; Biomarkers; Body Mass Index; C-Peptide; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Exercise; Female; Glycated Hemoglobin; Humans; Insulin; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Receptors, Tumor Necrosis Factor

In order to perform euglycaemic clamp studies in Type 2 diabetic patients, plasma glucose must be reduced to normal levels. This can be done either (i) acutely during the clamp study using high-dose insulin infusion, or (ii) slowly overnight preceding the clamp study using a low-dose insulin infusion. We assessed whether the choice of either of these methods to obtain euglycaemia biases subsequent assessment of glucose metabolism and insulin action.. We studied seven obese Type 2 diabetic patients twice: once with (+ ON) and once without (- ON) prior overnight insulin infusion. Glucose turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF).. Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10.7 +/- 2.9 mmol/l in the + ON and - ON studies, respectively, and were clamped at -5.5 mmol/l. Basal rates of glucose production (GP) were similar in the + ON and - ON studies, 83 +/- 13 vs. 85 +/- 14 mg m-2 min-1 (NS), whereas basal rates of glucose disappearance (Rd) were lower in the + ON than in the - ON study, 84 +/- 8 vs. 91 +/- 11 mg m-2 min-1 (P = 0.02). During insulin infusion in the clamp period, rates of GP, 23 +/- 11 vs. 25 +/- 10 mg m-2 min-1, as well as rates of Rd, 133 +/- 32 vs. 139 +/- 37 mg m-2 min-1, were similar in the + ON and - ON studies, respectively (NS).. Apart from basal rates of Rd, assessment of glucose turnover rates in euglycaemic clamp studies of Type 2 diabetic patients is not dependent on the method by which plasma glucose levels are lowered.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucagon; Glucose Clamp Technique; Humans; Insulin; Insulin Infusion Systems; Male; Obesity; Predictive Value of Tests; Statistics, Nonparametric

The aim of this study was to establish the effect of polycystic ovary syndrome (PCOS) adjusted for adiposity on proinsulin concentrations.. Ninety-one women with PCOS and 72 normal cycling (NC) women were recruited. A 2 h, 75 g oral glucose tolerance test was performed. Glucose and insulin were measured in each sample. Proinsulin and C-peptide were determined at 0 and 30 min and the fasting proinsulin/insulin ratio (PI/I) was calculated. Insulin sensitivity was estimated by insulin sensitivity index (ISI) composite, and beta-cell function was estimated by insulinogenic index.. Insulin, proinsulin and C-peptide concentrations were higher in women with PCOS than in NC women (P < 0.05). PI/I and insulinogenic index were similar in both groups. Proinsulin concentrations increased with body mass index (P < 0.05) only in women with PCOS; therefore, proinsulin concentrations were higher in obese PCOS patients compared with obese control women (P < 0.05). Moreover, a positive association between proinsulin concentrations and waist diameter adjusted for C-peptide (P < 0.05) and a negative association between proinsulin concentrations and ISI composite values were observed in PCOS patients (P < 0.05).. Data suggest that in PCOS patients an elevated proinsulin concentration could reflect insulin resistance more than beta-cell dysfunction. However, the elevated concentration of proinsulin in these patients could also result from impaired beta-cell function resulting from intra-abdominal obesity independently of insulin resistance.

Topics: Adolescent; Adult; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Obesity; Polycystic Ovary Syndrome; Proinsulin

Glucagon-like-peptide-1 (GLP-1) is strongly insulinotropic in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas glucose-dependent insulinotropic polypeptide (GIP) is less effective. Our investigation evaluated "early" (protocol 1) - and "late phase" (protocol 2) insulin and C-peptide responses to GLP-1 and GIP stimulation in patients with Type II diabetes.. Protocol 1: eight Type II diabetic patients and eight matched healthy subjects received i.v. bolus injections of GLP-1(2.5 nmol) or GIP(7.5 nmol) concomitant with an increase of plasma glucose to 15 mmol/l. Protocol 2: eight Type II diabetic patients underwent a hyperglycaemic clamp (15 mmol/l) with infusion (per kg body weight/min) of either: 1 pmol GLP-1 (7-36) amide (n=8), 4 pmol GIP (n=8), 16 pmol GIP (n=4) or no incretin hormone (n=5). For comparison, six matched healthy subjects were examined.. Protocol 1: Type II diabetic patients were characterised by a decreased "early phase" response to both stimuli, but their relative response to GIP versus GLP-1 stimulation was exactly the same as in healthy subjects [insulin (C-peptide): patients 59+/-9% (74+/-6%) and healthy subjects 62+/-5% (71+/-9%)]. Protocol 2, "Early phase" (0-20 min) insulin response to glucose was delayed and reduced in the patients, but enhanced slightly and similarly by GIP and GLP-1. GLP-1 augmented the "late phase" (20-120 min) insulin secretion to levels similar to those observed in healthy subjects. In contrast, the "late phase" responses to both doses of GIP were not different from those obtained with glucose alone. Accordingly, glucose infusion rates required to maintain the hyperglycaemic clamp in the "late phase" period (20-120 min) were similar with glucose alone and glucose plus GIP, whereas a doubling of the infusion rate was required during GLP-1 stimulation.. Lack of GIP amplification of the late phase insulin response to glucose, which contrasts markedly to the normalising effect of GLP-1, could be a key defect in insulin secretion in Type II diabetic patients.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Synergism; Female; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Hypoglycemic Agents; Injections, Intravenous; Insulin; Male; Middle Aged; Obesity; Peptide Fragments; Protein Precursors; Reference Values; Time Factors

To validate fasting indices of insulin sensitivity and secretion in a diverse pediatric population against gold standard estimates from euglycemic and hyperglycemic clamps.. A total of 31 children (mean BMI 25.1 +/- 4.9 kg/m(2), mean age 8.7 +/- 1.4 years, 15 girls and 16 boys, 12 black and 19 white) underwent euglycemic and hyperglycemic clamps 2-6 weeks apart to derive insulin sensitivity indices (SI (Eug clamp) and SI (Hyper clamp)). Fasting samples were used to derive the homeostasis model assessment of insulin resistance index (HOMA-IR), HOMA of percent beta-cell function (HOMA-B%), quantitative insulin sensitivity check index (QUICKI), insulinogenic index, antilipolytic insulin sensitivity index (ISI-FFA), and C-peptide-to-insulin ratio.. The QUICKI correlated best with SI (Eug clamp) (r = 0.69, P < 0.05) and had greater correlations to SI (Eug clamp) than did either SI (Hyper clamp) (r = 0.45, P < 0.05) or the HOMA-IR (r = -0.51, P < 0.05). Both fasting insulin and the insulinogenic index correlated well with first- and steady-phase insulin secretion (r's from 0.79 to 0.86, P < 0.05). HOMA-B% was not as highly correlated (r = 0.69-0.72, P < 0.05). Fasting C-peptide-to-insulin ratio was not significantly correlated with clamp-derived metabolic clearance rate of insulin. ISI-FFA was not correlated with the degree of free fatty acid suppression obtained from the clamps.. The QUICKI, fasting insulin, and the insulinogenic index all closely correlate with corresponding clamp-derived indices of insulin sensitivity and secretion in this diverse pediatric cohort. These results, if replicated in similarly diverse populations, suggest that estimates based on fasting samples can be used to rank order insulin secretion and sensitivity in pediatric cohorts.

Topics: Black or African American; Blood Glucose; Body Mass Index; C-Peptide; Child; Copper; District of Columbia; Fasting; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Maryland; Obesity; Puberty; Reference Values; Regression Analysis; Reproducibility of Results; Software; White People

The subject was a 26-year-old Japanese woman of 148 cm height, 96.2 kg of body weight (BW) (body mass index (BMI) of 43.8 kg/m(2)). She was referred to our hospital on May 1, 2000 for the evaluation of marked hyperglycemia with clinical symptom of general malaise, polydipsia, and ketonuria (3+). She did not smoke, or drink alcohol. But, she tended to eat lots of sweet food every day before the onset of this symptom. Her father was diagnosed type 2 diabetes mellitus. Her fasting plasma glucose and HbA(1c), and serum C-peptide were 398 mg/dl, 7.8% and less than 0.05 ng/ml [normal range: 0.94-2.8], respectively. She tested negative for anti-glutamic acid decarboxylase (GAD) antibodies and islet-cell antibodies. C-peptide level in her urine was as low as 3.4 microg/day. We immediately started insulin treatment under the diagnosis of abrupt onset of diabetes mellitus with diabetic ketoacidosis on the day of her admission, and the insulin treatment was continued after her being discharged. She showed continuous BW reduction until her BW reached approximately 60 kg, followed by her BW being plateau. During the period, intra-abdominal visceral fat (VF) and subcutaneous fat (SF) volume assessed by helical computerized tomography (CT) showed a substantial reduction [3.9-0.5 l for VF, 19-3.2 l for SF volume]. Pre-heparin plasma lipoprotein lipase (LPL) mass showed a considerably lower value when she had continuous BW reduction than did it when her BW reduction discontinued. These findings suggest that in this subject, continuous BW reduction after the abrupt onset of diabetes is closely associated with intra-abdominal fat mass reduction, which may be related to decreased production of LPL.

Topics: Adipose Tissue; Adult; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Insulin; Japan; Leptin; Lipids; Obesity; Regression Analysis; Tomography, X-Ray Computed

The aim of the present study was to investigate the association between the serum lipid profile and components of the metabolic syndrome, such as central obesity (anthropometric, computed tomography and fat cell data), insulin, sex-hormone-binding-globulin (SHBG) and different hormones influencing this important syndrome, e.g. sex steroids, leptin and tumor necrosis factor-alpha (TNF-alpha). The sample consisted of 85 obese patients (30 men and 55 women) who had undergone abdominal surgery. Fasting serum lipids were analysed, as well as anthropometric and computed tomography data, perivisceral and subcutaneous fat cell size and serum glucose and hormones. Abdominal fat revealed itself as an important correlator of the adverse changes in plasma lipoprotein levels, the waist-to-hip-ratio and waist-to-thigh-ratio being the best morphological correlators in men and women, respectively. Intra-abdominal fat (VA) correlated significantly and positively to perivisceral fat cell size in women, while no correlation was found between subcutaneous fat accumulation (SA) and adipocyte size in both genders. Perivisceral fat cell size showed the greatest number of correlations with the adverse plasma lipid profile compared to that in the subcutaneous depot. SHBG and sex steroids showed a negative correlation with serum lipids considered a cardiovascular risk. In contrast, TNF-alpha and C-peptide were inversely correlated with potential protector lipids. In conclusion, abdominal obesity, adipocyte hypertrophy from visceral fat, serum TNF-alpha and C-peptide seem to be the best correlators of the lipoprotein disturbance characteristic of the metabolic syndrome, whereas SHBG and sex steroids could play a protective role regarding the lipid profile associated to this syndrome.

Topics: Adipocytes; Adipose Tissue; Adult; Aged; Body Constitution; Body Mass Index; C-Peptide; Cell Size; Female; Hormones; Humans; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Postmenopause; Risk Factors; Sex Factors; Sex Hormone-Binding Globulin; Steroids; Tumor Necrosis Factor-alpha; Viscera

When compared with values recorded in 14 control subjects, the 15 overweight patients with type 2 diabetes displayed significantly increased activities of serum alanineaminotransferase (172% of mean values in controls), gamma-glutamyltransferase (253%) and cholinesterase (139%). A much wider dispersion of individual values for the two firstly mentioned enzymes was however noted so that their correlation with serum triglycerides levels were weaker (r = 0.373; p < 0.05 and r = 0.451; p < 0.05 respectively) than the same correlation obtained for serum cholinesterase (r = 0.760; p < 0.001). In two other studies including 28 controls and 30 diabetic patients serum cholinesterase was found to be significantly correlated with serum levels of insulin (r = 0.622; p < 0.001), C-peptide (r = 0.652; p < 0.001) and free fatty acid (r = 0.821; p < 0.001). Circumstantial evidence is provided that insulin resistance and an increased flux of free fatty acids from adipose tissue to the liver would stimulate the hepatic synthesis of serum cholinesterase.

Topics: Adult; C-Peptide; Cholinesterases; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity

Childhood obesity, epidemic in the United States, has been accompanied by an increase in the prevalence of type 2 diabetes among children and adolescents. We determined the prevalence of impaired glucose tolerance in a multiethnic cohort of 167 obese children and adolescents.. All subjects underwent a two-hour oral glucose-tolerance test (1.75 g [DOSAGE ERROR CORRECTED] of glucose per kilogram of body weight), and glucose, insulin, and C-peptide levels were measured. Fasting levels of proinsulin were obtained, and the ratio of proinsulin to insulin was calculated. Insulin resistance was estimated by homeostatic model assessment, and beta-cell function was estimated by calculating the ratio between the changes in the insulin level and the glucose level during the first 30 minutes after the ingestion of glucose.. Impaired glucose tolerance was detected in 25 percent of the 55 obese children (4 to 10 years of age) and 21 percent of the 112 obese adolescents (11 to 18 years of age); silent type 2 diabetes was identified in 4 percent of the obese adolescents. Insulin and C-peptide levels were markedly elevated after the glucose-tolerance test in subjects with impaired glucose tolerance but not in adolescents with diabetes, who had a reduced ratio of the 30-minute change in the insulin level to the 30-minute change in the glucose level. After the body-mass index had been controlled for, insulin resistance was greater in the affected cohort and was the best predictor of impaired glucose tolerance.. Impaired glucose tolerance is highly prevalent among children and adolescents with severe obesity, irrespective of ethnic group. Impaired oral glucose tolerance was associated with insulin resistance while beta-cell function was still relatively preserved. Overt type 2 diabetes was linked to beta-cell failure.

Topics: Adolescent; Black People; Blood Glucose; C-Peptide; Child; Child, Preschool; Cross-Sectional Studies; Diabetes Mellitus; Female; Glucose; Glucose Tolerance Test; Hispanic or Latino; Humans; Insulin; Insulin Secretion; Male; Obesity; Prevalence; Proinsulin; Risk Factors; White People

Healthy human volunteers occasionally elect to undergo surgical removal of the distal half of their pancreas for donation to a relative with type 1 diabetes. This provides the unusual opportunity to study segments of the same pancreas in two markedly different environments, i.e., the normal one of the donor and the unusual one of the ectopically transplanted recipient who is receiving immunosuppressant drugs that can diminish insulin secretion and cause insulin resistance.. We studied eight donor/recipient pairs 9 to 18 years after the original surgery to assess the hypothesis that beta-cell mass is the primary determinant of glucose homeostasis. We measured levels of fasting glucose and hemoglobin A1c, intravenous glucose disappearance rates, acute insulin and C-peptide responses, and beta-cell secretory reserve.. Comparisons of the mean data between the two groups revealed no significant differences in fasting plasma glucose, hemoglobin A1c, fasting insulin or C-peptide, acute insulin or C-peptide responses to arginine and to glucose, or beta-cell secretory reserve. Eight patients were obese; this subgroup contained all patients who developed mild diabetes (four donors and two recipients).. The within-pairs metabolic outcomes support the primacy of pancreatic mass in determining glucose homeostasis, but the discordancy within pairs for developing postoperative diabetes implicates variables, especially obesity, as important secondary determinants in the risk of developing diabetes in donors and recipients. Our data suggest that obesity should be a contraindication to donation of pancreatic segments and that donors should assiduously avoid becoming obese.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Obesity; Pancreas Transplantation; Pancreatectomy; Time Factors; Tissue Donors

In a cross-sectional study, we examined the association between hyperinsulinemia and hypertension, independent of body mass, among White non-Hispanic, Black non-Hispanic, and Mexican-American adults without diabetes.. Data are from 8,004 adults, aged > or = 20 years from the Third National Health and Nutrition Examination Survey, 1988-1994. Univariate differences in C-peptide levels (fasting) were examined in normotensives and hypertensives by racial or ethnic group. Multivariate logistic regression models were used to estimate the likelihood of hypertension across race-specific tertiles of C-peptide levels. Adjustments were made for age, sex, education, body mass index, and waist-to-hip ratio.. The prevalence of hypertension was 21.1% among non-Hispanic Whites, 24.6% among non-Hispanic Blacks, and 10.9% among Mexican Americans. The prevalence of hypertension increased significantly with C-peptide level for each racial or ethnic group. Mexican Americans with a C-peptide level in the upper tertile were 3.3 times (95% confidence interval [CI]=2.2-4.8) more likely to have hypertension than those with a C-peptide level in the lower tertile, after adjustment for age, sex, education, and BMI. Further adjustment for WHR resulted in a slightly lower odds ratio (OR=3.1; 95% CI=2.0-4.6). Among non-Hispanic Whites and Blacks, respectively, persons with a C-peptide level in the upper tertile were 1.6 times (95% CI=1.2-2.2) and 1.7 times (95% CI=1.1-2.6) more likely to have hypertension than those with a C-peptide level in the lower tertile, after multivariate (including WHR) adjustment.. These data suggest that high C-peptide levels, reflecting endogenous insulin secretion, are associated with hypertension, independent of body mass index and diabetes. This association was strongest among Mexican Americans. Our results also suggest that adjustment for waist-to-hip ratio as a confounding factor may be important in evaluation of the relationship between C-peptide level and hypertension.

Topics: Black or African American; C-Peptide; Comorbidity; Confidence Intervals; Cross-Sectional Studies; Female; Humans; Hyperinsulinism; Hypertension; Male; Mexican Americans; Obesity; Odds Ratio; White People

We hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT).. Three groups of 6 subjects were studied: normal weight with normal glucose tolerance (control subjects); obese with normal glucose tolerance (Obese-NGT); and obese with IGT (Obese-IGT). All subjects had a graded glucose infusion protocol to increase (step-up) and then decrease (step-down) plasma glucose. We obtained average insulin-secretion rates (ISR) over the glucose range common to all three groups during step-up and step-down phases, minimal model indices of beta-cell function (f(b), f(d), f(s), T(up), T(down) ), and insulin sensitivity (Si).. ISR differed significantly between step-up and -down phases only in Obese-IGT individuals. Basal (f(b)) and stimulated (f(d), f(s)) beta-cell sensitivity to glucose were similar in the three groups. Delays between glucose stimulus and beta-cell response during both step-up (T(up)) and -down (T(down)) phases were higher in Obese-IGT compared to Controls and Obese-NGT individuals. The product ISR x Si (10(-5.)min(-2) x l) was lower in Obese-IGT compared to Controls, both during step-up (919 +/- 851 vs 3192 +/- 1185, p < 0.05) and step-down (1455 +/- 1203 vs 3625 +/- 691, p < 0.05) phases. Consistently, the product f(s) x Si (10(-14.)min(-2). pmol(-1) x l) was lower in Obese-IGT than in control subjects (27.6 +/- 25.4 vs 103.1 +/- 20.2, p < 0.05).. Subjects with IGT are not able to secrete insulin to compensate adequately for insulin resistance. They also show delays in the timing of the beta-cell response to glucose when glucose levels are either rising or falling.

Topics: Adult; Area Under Curve; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Female; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Secretion; Male; Obesity

First-degree relatives of Type II (non-insulin-dependent) diabetic patients in cross-sectional studies have increased insulin resistance, associated cardiovascular risk factors and abnormalities of fibrinolysis and coagulation. To minimise between-family genetic and environmental confounders, we investigated within-family relationships between early hyperglycaemia and risk factors.. Thirteen age and gender matched sibling pairs of Type II (non-insulin-dependent) diabetic patients, one hyperglycaemic, one normoglycaemic (fasting plasma glucose at screening 6.0-7.7 mmol.l(-1) and < 6.0 mmol.l(-1), respectively) were assessed for plasminogen activator inhibitor antigen (PAI-1), tissue plasminogen activator antigen (t-PA), fibrinogen, Factor VII and Factor VIII/von Willebrand factor antigen. Fasting lipid profiles, blood pressure and HOMA insulin sensitivity (%S) were also measured in siblings and in matched subjects without family history of diabetes.. Hyperglycaemic and normoglycaemic siblings (7 female, 6 male) were aged, mean (SD) 56.8 (8.7) and 55.8 (8.4) years. Hyperglycaemic siblings had increased PAI-1 antigen, geometric mean (i.q.r.): 26.3 (15.1-45.6) vs 11.1 (2.1-23.3) ng/ml, p=0.0002, similar t-PA antigen, mean (SD) 9.5 (4.3) vs 7.4 (2.5) ng/ml, p=0.2 and fibrinogen 2.2 (0.3) vs 2.3 (0.6) g/l, p=0.5, and reduced %S 66.3 (30.5) vs 82.9 (25), p=0.04. PAI-1 correlated negatively with %S ( r=-0.55, p=0.005). No significant differences were found in blood pressure or fasting lipids.. A minor increase in plasma glucose in non-diabetic sibling pairs of Type II (non-insulin-dependent) diabetic patients was associated with reduced insulin sensitivity, increased central adiposity and a doubling of PAI-1 antigen concentration, suggesting impaired fibrinolysis. It is possible that this could contribute to increased cardiovascular risk in these subjects.

Topics: Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Insulin; Insulin Resistance; Islets of Langerhans; Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Proinsulin; Reference Values; Siblings; Smoking

The negative-feedback control exerted by plasma insulin on beta-cell insulin release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-hour fast during the procedure. We elected to elucidate the role of physiologic hyperinsulinemia per se in the insulin negative autofeedback in obese men. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body mass index [BMI], 41 +/- 1.15 kg/m2) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m2) underwent 2 studies in random order: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusion rate of 1 mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05). Exogenous insulin infusion significantly suppressed serum C-peptide at steady state ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 vbaseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-peptide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, and 1.96 +/- 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not superior to a 2.5-hour fast for the suppression of beta-cell activity, suggesting an impairment of the insulin negative autofeedback in this clinical condition.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Fasting; Fatty Acids, Nonesterified; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Male; Obesity

Topics: Blood Glucose; C-Peptide; Case-Control Studies; Circadian Rhythm; Female; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Models, Biological; Models, Theoretical; Obesity

There is a higher prevalence of ischemic heart disease (IHD) in South African white than black women. The objective of this study was to determine biochemical explanations for this prevalence. The study group contained 15 obese black women (OBW) and 14 obese white women (OWW), all premenopausal, who were examined after an overnight fast. Anthropometric measurements and blood concentrations of glucose, non-esterified fatty acids (NEFAs), catecholamines, plasminogen activator inhibitor-1, C-peptide, proinsulin, lipograms, cortisol, growth hormone, and post-heparin lipoprotein lipase activity were measured during an oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis, and subcutaneous and visceral fat mass were assessed with CT-scans. Visceral fat area was higher in OWW (139.7 +/- 10.7 cm(2)) than in OBW (72.3 +/- 3.9 cm(2)) (P < 0.01), as were fasting and 3 h triglyceride concentrations (P < 0.05 for all). OWW also had higher NEFA levels than OBW at 3 and 4 h compared with OBW (P < 0.05 for both). Fasting cortisol (266 +/- 24 vs. 197 +/- 19 nmol/l; P < 0.05) was higher in OWW than in OBW. These data demonstrate that OWW have higher visceral fat mass than OBW, which may lead to a more atherogenic fasting and postprandial lipid profile. The higher cortisol levels of the OWW may promote visceral fat deposition.

Topics: Adult; Area Under Curve; Black People; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Lipid Metabolism; Lipids; Middle Aged; Myocardial Ischemia; Obesity; South Africa; Tomography, X-Ray Computed; White People

Defects in hepatic insulin action in type 2 diabetes and its possible underlying mechanisms were assessed in euglycemic-hyperinsulinemic clamp studies, using improved tracer methods (constant specific activity technique). Ten obese diabetic patients (age 54 years, BMI 29 +/- 0.5 kg/m(2)) and ten matched control subjects were studied at baseline (after an overnight fast) and during insulin infusions of 20- and 40-mU. m(-2). min(-1). In the diabetic patients, plasma glucose levels were normalized overnight before the studies by low-dose insulin infusion. Hepatic sinusoidal insulin levels were estimated, and plasma levels of free fatty acids (FFAs) and glucagon were determined to assess the direct and indirect effects of insulin on hepatic glucose production (HGP) in type 2 diabetes. Baseline rates of HGP (86 +/- 3 vs. 76 +/- 3 mg. m(-2). min(-1), P < 0.05) were slightly elevated in the diabetic patients compared with control subjects, despite much higher hepatic sinusoidal insulin levels (26 +/- 3 vs. 12 +/- 2 mU/l, P < 0.001). Consequently, a marked defect in the direct (hepatic) effect of insulin on HGP appeared to be present at low insulin levels. However, in response to a small increase in baseline hepatic sinusoidal insulin levels of 11 mU/l (26 +/- 3 to 37 +/- 3 mU/l, P < 0.05) in the 20-mU clamp, a marked suppression of HGP was observed in the diabetic patients (86 +/- 3 to 32 +/- 5 mg. m(-2). min(-1), P < 0.001), despite only minimal changes in FFAs (0.33 +/- 0.05 to 0.25 +/- 0.05 mmol/l, NS) and glucagon (14 +/- 1 to 11 +/- 2 pmol/l, P < 0.05) levels, suggesting that the impairment in the direct effect of insulin can be overcome by a small increase in insulin levels. Compared with control subjects, suppression of HGP in the diabetic patients was slightly impaired in the 20-mU clamp (32 +/- 5 vs. 22 +/- 4 mg. m(-2). min(-1), P < 0.05) but not in the 40-mU clamp (25 +/- 2 vs. 21 +/- 3 mg. m(-2). min(-1), NS). In the 20-mU clamp, hepatic sinusoidal insulin levels in the diabetic patients were comparable with control subjects (37 +/- 3 vs. 36 +/- 3 mU/l, NS), whereas both FFA and glucagon levels were higher (i.e., less suppressed) and correlated with the rates of HGP (R = 0.71, P < 0.02; and R = 0.69, P < 0.05, respectively). Thus, at this insulin level impaired indirect (extrahepatic) effects of insulin seemed to prevail. In conclusion, hepatic insulin resistance is present in obese type 2 diabetic patients but is of quantitative significance only at

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucagon; Glucose; Glucose Tolerance Test; Humans; Insulin; Liver; Middle Aged; Obesity

Abnormalities observed in intermediary metabolism may be related to the pathogenesis of obesity-related diseases such as type 2 diabetes. Glycerol and lactate production was estimated in the sc adipose tissue of two anatomical regions of 10 lean (LW), 10 obese (OW), and 10 matched diabetic (DW) black urban women. This was done with the sc microdialysis technique and combined with adipose tissue blood flow (ATBF) rates calculated from (133)Xe clearance. Biochemical measurements were made in the postabsorptive and postprandial state. Bioimpedance and computed tomography scans were used to define body composition. DW present with more visceral fat (DW, 138 +/- 5.0; OW, 66.6 +/- 5.0 cm; P < 0.01). This was associated with elevated free testosterone levels (DW, 1.21 +/- 0.1; OW, 0.75 +/- 0.1 nmol/L; P < 0.05). The fasting FFA, glycerol, and lactate levels increased across the three groups (LW < OW < DW). During the oral glucose tolerance test, glucose levels were elevated in DW, with higher insulin levels [0 h: DW, 207 +/- 8.6; OW, 100 +/- 7.2 pmol/L (P < 0.01); 1 h: DW, 410 +/- 15.2; OW, 320 +/- 10.9 pmol/L (P < 0.05)], but with a flat Cpeptide response (1 h: DW, 932 +/- 40; OW, 1764 +/- 40 pmol/L; P < 0.05). Plasma lactate levels increased significantly in LW and OW at 1 h (P < 0.001), but remained lower in LW vs. OW for all time points. ATBF was highest in LW [abdominal, 0 h: DW, 4.5 +/- 0.2; OW, 1.7 mL/100 g.min (P < 0.01); femoral, 0 h: DW, 3.4 +/- 0.2; OW, 1.8 +/- 0.3 mL/100 g.min (P < 0.01)]. ATBF did not increase in DW during the oral glucose tolerance test. Glycerol release (GR) was used to assess the lipolytic rate and was highest in LW in the abdominal area [0 h: LW, 1.7 +/- 0.2; OW, 1.1 +/- 0.2 micromol/kg.min (P < 0.05); DW, 0.78 +/- 0.05 micromol/kg.min (P < 0.05 vs. OW)]. By contrast, GR was higher in the femoral area of OW (0 h: OW, 1.6 +/- 0.2; LW, 1.15 +/- 0.1 micromol/kg.min; P < 0.05). Regional differences were observed for GR in both OW and DW (femoral > abdominal). Lactate release (LR) was low in DW [abdominal, 0 h: DW, 3.5 +/- 0.4; OW, 7.8 +/- 1.0 micromol/kg.min (P < 0.001); femoral, 0 h: DW, 3.1 +/- 0.3; OW, 9.0 +/- 0.9 micromol/kg.min (P < 0.001)]. LR was appropriately low for body fat mass in LW, with a brisk increase between 0 and 1.5 h. A negative correlation exists between GR (abdominal area) and insulin levels in the postabsorptive state (P < 0.0001). In conclusion, 1) the fasting lipolytic rate is associated with insulin levels;

Topics: Adipose Tissue; Adult; Black People; Body Composition; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Food; Glucose Tolerance Test; Glycerol; Humans; Lactic Acid; Obesity; South Africa; Testosterone; Urban Population

Plasma homocysteine levels have been shown to be associated with indexes of obesity and insulin resistance in obese children and adolescents. We, therefore, investigated the contribution of changes in body composition, markers of insulin resistance, folate, and vitamin B(12) to changes in homocysteine during a weight reduction program in obese children and adolescents. Thirty-seven obese white girls (mean SD; age, 12 +/- 1.8 years, body mass index [BMI], 26.9 +/- 5.25) and 19 obese white boys (age, 11.9 +/- 1.7 years; BMI, 26.2 +/- 5.2) were investigated for body composition, fasting total plasma homocysteine (tHcy), insulin, C-peptide, folate, and vitamin B(12) before and after a 3-week weight reduction program including physical activities. During weight reduction BMI, fat mass (FM), percentage fat mass, insulin, and C-peptide decreased significantly, whereas homocysteine and vitamin B(12) showed a significant increase. Folate and lean body mass (LBM) remained unchanged. tHcy concentration before weight reduction was a function of age, folate, and C-peptide, whereas tHcy concentration after weight reduction was a function of folate and baseline LBM. Changes in tHcy during weight reduction correlated significantly with baseline LBM and were related inversely to changes in LBM during weight reduction. Children who increased LBM showed lower increases in tHcy compared with children who lost LBM. In multiple linear regression analysis, only baseline LBM contributed independently and significantly to changes in tHcy. Our study suggests that LBM has a significant impact on tHcy metabolism during weight reduction.

Topics: Adolescent; Age Factors; Body Composition; Body Mass Index; C-Peptide; Child; Folic Acid; Homocysteine; Humans; Methionine; Obesity; Regression Analysis; Time Factors; Weight Loss

To directly evaluate prehepatic secretion of pancreatic hormones during a 3-h oral glucose tolerance test (OGTT), we measured insulin and C-peptide in six healthy control, six obese, and six type 2 diabetic subjects in the femoral artery and hepatic vein by means of the hepatic catheterization technique. Hypersecretion in obesity was confirmed (309 +/- 66 nmol in obese vs. 117 +/- 22 in control and 79 +/- 13 in diabetic subjects, P 0.3, r(2) = 0.93), whereas estimation of hepatic insulin extraction and insulin clearance needs further investigation for improvement.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Hepatic Artery; Hepatic Veins; Humans; Insulin; Insulin Secretion; Kinetics; Male; Middle Aged; Models, Biological; Obesity; Sensitivity and Specificity

We have shown previously that the increase of plasma non-esterified fatty acids for 48 h results in decreased glucose-stimulated insulin secretion in lean and non-diabetic obese subjects. It is currently not known if a prolonged increase in non-esterified fatty acids also impairs the insulin secretory response to non-glucose secretagogues.. Heparin and intralipid (to increase plasma non-esterified fatty acid concentrations by about two- to fourfold) or normal saline was infused intravenously for 48 h in 14 non-diabetic obese subjects. On the third day in both studies, insulin, C-peptide, proinsulin, and insulin secretion rate were assessed in response to an intravenous arginine infusion at fasting glucose concentration and a second arginine infusion after a 60-min 11 mmol/l hyperglycaemic clamp.. There were no significant differences detected in acute (5 min) or total (90 min) arginine-stimulated C-peptide or insulin secretion response in the heparin-intralipid study compared with the control group at fasting glucose or during hyperglycaemia.. We have shown that a prolonged increase in plasma NEFA does not blunt arginine-stimulated insulin secretion or plasma insulin concentrations in non-diabetic obese subjects. These findings suggest that the previously demonstrated NEFA-induced impairment in insulin secretory response to glucose cannot be generalized for non-glucose secretagogues.

Topics: Adult; Arginine; Blood Glucose; C-Peptide; Fasting; Fatty Acids, Nonesterified; Female; Heparin; Humans; Infusions, Intravenous; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Proinsulin; Thinness; Time Factors

In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.

Topics: Adrenal Glands; Adult; Antipsychotic Agents; beta-Endorphin; Blood Glucose; C-Peptide; Endocrine System; Female; Gonadal Steroid Hormones; Humans; Hypogonadism; Insulin; Insulin Resistance; Leptin; Lipids; Multivariate Analysis; Obesity; Prolactin; Sex Hormone-Binding Globulin; Thyroid Hormones

Cyclo (His-Pro) (CHP) is a gut-brain peptide whose plasma levels in humans are increased after glucose ingestion and preferentially altered by oral glucose ingestion compared to intravenous administration in rats, suggesting a role in the enteroinsular response to nutrient ingestion. We were interested in examining levels of CHP in women of differing weights and comparing these levels to various parameters of insulin secretion. Plasma from 26 fasting, nondiabetic women ranging from 21 to 70 years of age and weighing 43 to 114 kg was assayed for CHP. Insulin and C-peptide levels were measured in 17 of the 26. Fasting CHP levels were elevated in obese compared to nonobese women (2075+/-144 vs. 905+/-187 pg/ml; p < 0.001) and were related by regression analysis to weight (r = 0.668, p < 0.001) and body mass index (r = 0.636, p = 0.001). The fasting C peptide/insulin molar ratio, which may be used as an estimate of hepatic insulin clearance (HIC), was inversely related to CHP levels (r = -0.568, p = 0.017). We conclude CHP levels are increased in obese women and inversely related to their C-peptide/insulin molar ratio. The elevation of CHP in those with a decrease in this estimate of HIC (obese) is interesting as the greater insulin response seen in normal persons after oral glucose compared to intravenous glucose has been postulated to be due to a decrease in HIC by some gut factor. The presence of such a factor in excess in the obese might explain part of their hyperinsulinemia.

Topics: Adult; Aged; Body Constitution; Body Mass Index; Body Weight; C-Peptide; Female; Humans; Insulin; Liver; Middle Aged; Obesity; Peptides, Cyclic; Piperazines; Regression Analysis

The objective of the study reported here was to induce obesity in the female Göttingen minipig to establish a model of the human metabolic syndrome. Nine- to ten-month-old female Göttingen minipigs received a high-fat high-energy (HFE) diet or a low-fat, low-energy (LFE) diet. The energy contents derived from fat were 55 and 13 %, respectively. After 5 weeks, animals were subjected to dual energy x-ray absorptiometry (DEXA) scanning, intravenous glucose tolerance testing (IVGTT), and 6-h growth hormone profile recording. After treatment, mean body weight of pigs of the LFE group was 21.0 +/- 0.4 kg, and was 26.8 +/- 0.2 kg in pigs of the HFE group (P < 0.0001). The DEXA scanning indicated that the fat content of the LFE group was 10.0 +/- 1.2 % versus 15.2 +/- 0.7 % in the HFE group (P < 0.003). Triglycerides concentration was significantly (P < 0.05) increased in pigs of the HFE group (0.24 +/- 0.03 mM), compared with that in pigs of the LFE group (0.13 +/- 0.04 mM). Preprandial plasma glucose and insulin concentrations were not affected, but insulin area under the curve during IVGTT was significantly high in the obese animals. Growth hormone (GH) secretion was low in both groups of pigs. The obese minipig shares some of the metabolic impairments seen in obese humans, and may thus serve as a model of the metabolic syndrome.

Topics: Absorptiometry, Photon; Animals; Area Under Curve; Blood Glucose; C-Peptide; Diet, Fat-Restricted; Dietary Fats; Disease Models, Animal; Fasting; Female; Fructosamine; Glucose Tolerance Test; Growth Hormone; Humans; Hypercholesterolemia; Hypertriglyceridemia; Insulin; Insulin Secretion; Insulin-Like Growth Factor I; Lipids; Metabolic Syndrome; Obesity; Pituitary Gland, Anterior; Species Specificity; Swine, Miniature

Plasma glucose, insulin, and C-peptide concentrations were determined in response to graded infusions of glucose, and insulin secretion rates were calculated over each sampling period. Measurements were also made of insulin clearance, resistance to insulin-mediated glucose, uptake, and the plasma glucose, insulin, and C-peptide concentrations at hourly intervals from 8:00 AM to 4:00 PM in response to breakfast and lunch. Plasma glucose, insulin, and C-peptide concentrations were significantly (P < 0.01) higher in obese women in response to the graded intravenous glucose infusion, associated with a 40% (P < 0.005) greater insulin secretory response. Degree of insulin resistance correlated positively (P < 0.05) with the increase in insulin secretion rate in both nonobese (r = 0.52) and obese (r = 0.58) groups and inversely (P < 0.05) with the decrease in insulin clearance in obese (r = -0.46) and nonobese (r = -0.39) individuals. Weight loss was associated with significantly lower plasma glucose, insulin, and C-peptide concentrations in response to graded glucose infusions and in day-long insulin concentrations. Neither insulin resistance nor the insulin secretory response changed after weight loss, whereas there was a significant increase in the rate of insulin clearance during the glucose infusion. It is concluded that 1) obesity is associated with a shift to the left in the glucose-stimulated insulin secretory dose-response curve as well as a decrease in insulin clearance and 2) changes in insulin secretion and insulin clearance in obese women are more a function of insulin resistance than obesity.

Topics: C-Peptide; Female; Glucose; Humans; Infusions, Intravenous; Insulin; Insulin Resistance; Insulin Secretion; Middle Aged; Obesity; Osmolar Concentration; Weight Loss

Aging appears to decrease delta6-desaturase activity in males, but in females it is uncertain. delta6- and delta5-desaturase functions were investigated in pre- and post-menopausal women who were normoglycemic or had type 2 diabetes (2 x 2 factorial, n = 37). Subjects were compared for indicators of diabetic control, estrogen levels, fatty acid profiles and indices of delta6- and delta5-desaturase activity. Diet intakes that were compared to determine whether results were a function of dietary factors known to influence desaturase activity revealed no differences (P>0.05). Post-menopausal women with type 2 diabetes had more 18:2 n6 in serum phospholipids (P<0.05) than did the pre- and post-menopausal control subjects. Fatty acid ratios of 18:3 n6/18:2 n6 indicated greater delta6-desaturase activity for women with type 2 diabetes, but differences were not found between pre- and post-menopausal groups. Significant correlation (P < 0.05) indicates an association between diabetic status and desaturase function, but function did not appear to be affected by menopausal status. In contrast to reports using male subjects, we found no evidence that desaturase function decreased in aging females, as reported for males, or increased as hypothesized in this study.

Topics: Adult; Aged; Aging; Blood Platelets; C-Peptide; Cholesterol Esters; Delta-5 Fatty Acid Desaturase; Diabetes Mellitus, Type 2; Diet; Fatty Acid Desaturases; Fatty Acids; Female; Humans; Insulin; Linoleoyl-CoA Desaturase; Middle Aged; Obesity; Phospholipids; Postmenopause

Alcohol intake can have hypoglycemic or hyperglycemic effects in patients with type 2 diabetes mellitus. The present study was designed to investigate the glycemic control of male patients with diabetes mellitus from the aspect of the genetic status of alcohol metabolism.. One hundred sixty-three men with type 2 diabetes mellitus were enrolled in the present study. They were all outpatients at the Diabetes Center of Saiseikai Central Hospital. The genotype of the aldehyde dehydrogenase 2 (ALDH2) gene of each patient was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the patients were divided into those with active or inactive ALDH2 phenotype. We compared the amount of habitual alcohol intake and clinical data that included physical findings and blood chemistry of the patients in the active and inactive ALDH2 groups. The glycemic control of each patient was evaluated by the serum level of HbAlc.. Of the 163 patients with type 2 diabetes mellitus, 90 patients had the active ALDH2 phenotype and 73 patients had the inactive ALDH2 phenotype. The mean HbA1c level of the active ALDH2 group was nearly the same as that of the inactive ALDH2 group. However, the HbA1c level of the light-to-moderate drinkers (1-400 g/week) in the inactive ALDH2 group was highest and was significantly higher than the HbA1c level of the light-to-moderate drinkers of the active ALDH2 group. The HbA1c of the patients with diabetic complications was higher than the HbAlc of those without diabetic complications in both the active and inactive ALDH2 groups. However, the HbA1c level of the light-to-moderate drinkers without diabetic complications in the inactive ALDH2 group was significantly higher and the incidence of 24 hr urinary C-peptide was higher than the respective level of the light-to-moderate drinkers without diabetic complications in the active ALDH2 group.. Habitual light-to-moderate alcohol intake worsens glycemic control in diabetic patients who have the inactive ALDH2 phenotype. The data on 24 hr urinary C-peptide level suggested that increased acetaldehyde after light-to-moderate drinking by inactive ALDH2 diabetic patients may increase the HbA1c value by the insulin-resistant condition that resulted in hyperinsulinemia.

Topics: Adult; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Ethanol; Genotype; Glycated Hemoglobin; Humans; Male; Middle Aged; Obesity; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length

To examine the association between baseline testosterone levels and changes in visceral adiposity in Japanese-American men.. Prospective observational study.. Second-generation Japanese-American males enrolled in a community-based population study.. At baseline, 110 men received a 75g oral glucose tolerance test (OGTT), and an assessment of body mass index (BMI); visceral adiposity measured as intra-abdominal fat area (IAF) using computed tomography (CT); fasting insulin and C-peptide levels; and total testosterone levels. IAF was re-measured after 7.5 y. Subcutaneous fat areas were also measured by CT in the abdomen, thorax and thigh. The total fat (TF) was calculated as the sum of IAF and total subcutaneous fat areas (SCF).. After 7.5y, IAF increased by a mean of 8.0 cm2 (95% CI: 0.8, 15.3). Baseline total testosterone was significantly correlated with change in IAF (r= -0.26, P= 0.006), but not to any appreciable degree with change in BMI, TF, or SCF. In a linear regression model with change in IAF as the dependent variable, baseline testosterone was significantly related to this outcome while adjusting for baseline IAF, SCF, BMI, age, diabetes mellitus status (OGTT by the WHO diagnostic criteria) and fasting C-peptide (regression coefficient for baseline testosterone [nmol/l] = -107.13, P = 0.003).. In this Japanese-American male cohort, lower baseline total testosterone independently predicts an increase in IAF. This would suggest that by predisposing to an increase in visceral adiposity, low levels of testosterone may increase the risk of type 2 diabetes mellitus.

Topics: Abdomen; Adipose Tissue; Aged; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Cohort Studies; Humans; Insulin; Japan; Linear Models; Male; Middle Aged; Obesity; Predictive Value of Tests; Prospective Studies; Testosterone; Tomography, X-Ray Computed; Washington

To investigate the independent and combined effects of the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3AR) gene and the (-3826) A-->G polymorphism of the uncoupling protein 1 (UCP1) gene on body weight change in type 2 diabetic and non-diabetic control subjects during a 10y follow-up study.. Controlled 10y follow-up study with baseline, 5 and 10y examinations.. 70 newly diagnosed, middle-aged type 2 diabetic patients and 123 non-diabetic control subjects from eastern Finland.. Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and HbA1c. Genotypes by polymerase chain reaction followed by enzymatic digestion.. No significant differences were found in the frequencies of the two polymorphisms between diabetic and control subjects. The polymorphisms were not cross-sectionally or longitudinally associated with body weight or BMI in diabetic or control subjects. When the diabetic and control subjects were analysed together, the change in the mean body weight was significantly greater among the subjects with both polymorphisms (n = 11) than among those with no polymorphisms (n = 103; change in weight 6.5 +/- 2.5% vs -0.2 +/- 0.8%, P=0.036, and change in Body Mass Index 8.5 +/- 2.6% vs 2.0 +/- 0.8%, P= 0.060, mean +/- s.e.m.).. The simultaneous existence of the two polymorphisms was associated with a tendency to gain weight suggesting a synergistic effect of these polymorphisms on body weight gain.

Topics: Anthropometry; C-Peptide; Carrier Proteins; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Genotype; Glycated Hemoglobin; Humans; Insulin; Ion Channels; Male; Membrane Proteins; Middle Aged; Mitochondrial Proteins; Obesity; Polymerase Chain Reaction; Polymorphism, Genetic; Receptors, Adrenergic, beta; Receptors, Adrenergic, beta-3; Uncoupling Protein 1; Weight Gain

Standard glucose-tolerance test (SGTT) was carried out in 73 patients with endometrial tumors. Elevated concentrations of plasma insulin and C-peptide were established in endometrial carcinoma patients (irrespective of age and reproductive status) after night fast and 120 min after SGTT start, as compared to healthy subjects and breast cancer patients. Obese (BMI index 28 kg/m2) reproductive endometrial carcinoma patients showed pronounced hyperinsulinemia and resistance to insulin. Menopausal patients with endometrial tumors (BMI index < = 28) were characterized by a much faster metabolic clearance of insulin, as compared with all other patients. Therefore, degree of insulin resistance in endometrial carcinoma is determined by both enhanced secretion of insulin and lowered metabolic clearance of this hormone which in turn is associated with obesity.

Topics: Adipose Tissue; Adult; Aged; Blood Glucose; Body Constitution; Body Mass Index; Breast Neoplasms; C-Peptide; Endometrial Neoplasms; Female; Humans; Insulin; Insulin Resistance; Menopause; Middle Aged; Obesity

Sex hormone-binding globulin (SHBG) is a plasma glycoprotein with high binding affinity for testosterone and dihydrotestosterone and lower affinity for estradiol. SHBG is synthesized in the liver, and its plasma level is important in the regulation of plasma free and albumin-bound androgens and estrogens. Obesity and particularly excess visceral fat, known risk factors for cardiovascular and metabolic diseases, are associated with decreased testosterone levels in males and SHBG levels in both sexes. SHBG is usually positively correlated with high-density lipoprotein cholesterol and negatively correlated with triglyceride and insulin concentrations. A positive association between SHBG and various measures of insulin sensitivity has been demonstrated in both sexes, suggesting that decreased SHBG levels may be one of the components of the metabolic syndrome. We have examined pituitary-adrenocortical function, glucose tolerance, and lipoprotein and hormone levels in a large cohort of Finnish males. Abdominal obesity appears to be associated with slight hypocortisolemia and increased sensitivity to exogenous adrenocorticotropin stimulation, which may contribute to the hyperinsulinemia and related metabolic changes including decreased SHBG levels in males.

Topics: Adrenal Glands; Adult; Blood Glucose; Blood Pressure; Body Constitution; Body Mass Index; C-Peptide; Cholesterol, HDL; Finland; Homeostasis; Humans; Insulin; Insulin Resistance; Liver; Male; Middle Aged; Obesity; Pituitary Gland; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone; Triglycerides

When models are used to measure or predict physiological variables and parameters in a given individual, the experiments needed are often complex and costly. A valuable solution for improving their cost effectiveness is represented by population models. A widely used population model in insulin secretion studies is the one proposed by Van Cauter et al. (Diabetes 41:368-377, 1992), which determines the parameters of the two compartment model of C-peptide kinetics in a given individual from the knowledge of his/her age, sex, body surface area, and health condition (i.e., normal, obese, diabetic). This population model was identified from the data of a large training set (more than 200 subjects) via a deterministic approach. This approach, while sound in terms of providing a point estimate of C-peptide kinetic parameters in a given individual, does not provide a measure of their precision. In this paper, by employing the same training set of Van Cauter et al., we show that the identification of the population model into a Bayesian framework (by using Markov chain Monte Carlo) allows, at the individual level, the estimation of point values of the C-peptide kinetic parameters together with their precision. A successful application of the methodology is illustrated in the estimation of C-peptide kinetic parameters of seven subjects (not belonging to the training set used for the identification of the population model) for which reference values were available thanks to an independent identification experiment.

Topics: Adult; Bayes Theorem; Bias; Body Height; Body Surface Area; Body Weight; C-Peptide; Case-Control Studies; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Humans; Linear Models; Male; Markov Chains; Monte Carlo Method; Obesity; Predictive Value of Tests; Tissue Distribution

The insulin receptor substrate-2 (IRS-2) is a major insulin signalling molecule. IRS-2 inactivation in mice induces a form of diabetes characterized by peripheral insulin resistance and reduced beta cell mass. We tested the hypothesis that a common non-conservative amino acid substitution of IRS-2 (G1057D) might interact with overweight in the pathogenesis of type 2 diabetes. The variant was genotyped in 193 Italian patients with type 2 diabetes and 206 control subjects. In the absence of overweight, the risk of type 2 diabetes decreased according to the dosage of the D1057 allele (odds ratio for GD genotype 0.46 [95% CI 0.25-0.86]; DD genotype 0.18 [0.04-0.68]; P for trend = 0.0012). Conversely, the interaction between overweight and genotype increased the risk of type 2 diabetes according to the dosage of the D1057 allele (odds ratio for GD genotype 2.50 [1.11-5.65]; DD genotype 5.74 [1.11-29. 78]; P for trend = 0.0047). Among controls, fasting C-peptide levels, after adjustment for plasma glucose, were inversely related to the dosage of the D1057 allele (P = 0.020). This finding suggested that carriers of the D1057 allele may have higher insulin sensitivity and supported the protective effect of this allele. Conversely, among overweight patients there was a parallel increase in fasting plasma glucose (P for trend = 0.037) and fasting C-peptide according to the dosage of the D1057 allele, suggesting that higher insulin resistance and relative beta cell failure contributed to the increased risk of type 2 diabetes in overweight carriers of this allele. These data provide evidence for a strong association between type 2 diabetes and the G1057D common genetic variant of IRS-2, which appears to be protective against type 2 diabetes in a codominant fashion. Overweight appears to modify the effect of this polymorphism toward a higher risk of type 2 diabetes. Carriers of this polymorphism may represent an elective target for prevention of type 2 diabetes through preventing or treating excessive weight.

Topics: Adult; Aged; Alleles; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Gene Dosage; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Insulin Receptor Substrate Proteins; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Obesity; Odds Ratio; Phosphoproteins; Polymorphism, Genetic; Regression Analysis

Leptin, an adipocyte-derived protein product of the obesity (ob) gene, is a multifunctional polypeptide associated with the development of obesity-related disorders in humans. There is considerable inter-individual variation in plasma leptin even among subjects with comparable obesity levels, which suggests that factors other than adipose mass may be involved in the regulation of leptin expression and/or production. The purpose of this study was to evaluate the potential role of glycemic status and adipose-derived cytokines in regulating plasma leptin levels among normal and overweight men.. Cross-sectional study.. We measured plasma leptin, insulin, c-peptide and plasma soluble tumor necrosis factor receptor (sTNF-R) concentrations in 178 men. The subjects were selected from the Health Professionals Follow-up Study (HPFS), and aged 47-64 y in 1994, were free of cardiovascular disease, diabetes mellitus, malignant neoplasms, and had provided a fasting blood sample and a detailed lifestyle questionnaire.. Men in the highest quintile of plasma leptin (mean = 12.7 ng/ml) weighed more, were less physically active and had higher circulating insulin, c-peptide, sTNF-R1 and sTNF-R2 concentrations than men in the lowest quintile (mean = 2.8 ng/ml). We found a significant correlation between plasma insulin, c-peptide, glycosylated hemoglobin (HbA1c), and sTNF-R1 on leptin concentrations (with Spearman correlation coefficients ranging from 0.17 to 0.48 and all P < 0.05). Only HbA1c and sTNF-R1 were independently and positively associated with plasma leptin after further adjusting for body mass index and other metabolic parameters of interest. Interestingly, these observed associations were limited to men with a BMI > or = 25 kg/m2.. Our results suggest that glucose homeostasis and the activity of the TNF system may modulate leptin secretion and production among overweight men. Glucose homeostasis and TNF-alpha is important in metabolic disorders related to hyperleptinemia.

Topics: Antigens, CD; Body Mass Index; C-Peptide; Case-Control Studies; Cross-Sectional Studies; Glycated Hemoglobin; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II

To investigate the prevalence and potential risk factors of obesity after therapy for childhood acute lymphoblastic leukemia (ALL).. 39 ALL patients (age 10.7-20.5 years) who were in first remission for 3.4-14.6 years after standardized treatment with chemotherapy plus cranial irradiation (n = 25) or with chemotherapy alone (n = 14) were examined. After fasting overnight, the following parameters were investigated: body mass index (BMI) of patients and their parents; patients' BMI before ALL therapy; serum free thyroxin, growth hormone-dependent factors, estradiol, testosterone, cortisol, leptin and c-peptide; fat-free mass (bioelectrical impedance); resting metabolic rate (RMR, indirect calorimetry); caloric intake (24-hour recall); and physical activity (questionnaire). RMR data were applied to the fat-free mass and compared with 83 controls.. The prevalence of obesity (criterion: BMI > 2 SDS) was significantly (p < 0.05) higher after ALL therapy (38%; irradiated patients 48%, non-irradiated patients 21%) than before therapy (3%). Compared to non-irradiated patients, irradiated patients had significantly lower RMRs (-1.07 +/- 0.24 vs. -0.32 +/- 0.21 SDS; p < 0.05), reduced physical activity levels (1.41 +/- 0.03 vs. 1.52 +/- 0.03; p < 0.05), and lower concentrations of insulin-like growth factor-binding protein-3 (-0.65 +/- 0.17 vs. 0.25 +/- 0.33 SDS; p < 0.05) and of free thyroxin (1.17 +/- 0.06 vs. 1.38 +/- 0.08 ng/dl; p < 0.05). Caloric intake was adequate.. After ALL during childhood, patients face a higher risk of obesity. In the cranially irradiated patients, the likely causes are low physical activity, RMRs and hormonal insufficiency.

Topics: Adolescent; Adult; Basal Metabolism; Body Composition; Body Mass Index; C-Peptide; Child; Energy Intake; Energy Metabolism; Estradiol; Female; Humans; Hydrocortisone; Leptin; Male; Obesity; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Testosterone; Thyroxine

To compare serum leptin levels in type 1 diabetic and obese children.. We studied serum leptin levels in 35 type 1 diabetic, 32 obese, and 35 healthy children. Seven of 35 were new-onset diabetics with ketoacidosis. C-peptide (CPE) levels were used for estimating insulin secretion.. Serum leptin levels were lower in diabetics than in controls (p<0.001). Obese children had higher leptin and CPE levels than diabetics and controls. In new-onset diabetics, 1 month insulin treatment did not cause any change in leptin levels (p>0.05). Leptin was correlated positively with body mass index and CPE (p<0.001) and inversely with glucose (p = 0.001) and HbA1c (p<0.05) in the combined group. HbA1c and gender were the independent predictors of leptin in diabetic children (p<0.01).. Low serum leptin levels in type 1 diabetic children may be due to chronic insulin deficiency related with their metabolic control. Leptin and insulin may have complementary roles in maintaining a stable body weight.

Topics: Adolescent; Body Mass Index; Body Weight; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Leptin; Male; Matched-Pair Analysis; Obesity; Statistics as Topic

The rate of glucose disposal was determined in 10 black and 10 white obese nondiabetic urban women from South Africa to assess insulin resistance.. Euglycemic hyperinsulinemic clamp and body composition analysis.. Age, body mass index (BMI), anthropometric measurements and body composition were similar in both groups of women. A five-level computed tomography (CT) scan showed a similar mean subcutaneous fat mass in both groups of women (black obese women 555 +/- 9.0 vs white obese women 532 +/- 6.0 cm2), but less visceral fat in black obese women (90 +/- 3.0 vs 121 +/- 3.1 cm2; P< 0.05). Black obese women had higher fasting free fatty acid (997 +/- 69 vs 678 +/- 93 micromol/l; P < 0.05) and lactate concentrations (1,462 +/- 94 vs 1,038 +/- 39 micromol/l; P < 0.05), but lower fasting insulin levels (87 +/- 12 vs 155 +/- 9 pmol/l; P < 0.001). Black obese women also had a more favorable HDL: total cholesterol ratio (30.5% vs 23.0%; P< 0.04). The mean glucose disposal rate (M) and disposal expressed as glucose sensitivity index (M/I) were reduced in the black obese women vs white obese women (M: 7.1 +/- 0.8 vs 13.7 +/- 1.0 mmol/kg min(-1) x 100; P< 0.01, and M/I: 0.12 +/- 0.01 vs 0.24 +/- 0.02 mmol/kg x min(-1)/pmol/1 x 1,000; P < 0.01). Only black obese women showed a significant decrease in C-peptide levels during the clamp (2.9 +/- 0.22 vs 1.2 +/- 0.12 nmol/l; P<0.001). During the euglycemic period, the black obese women had higher lactate levels at all time points, but only the white obese women had increased lactate levels (918 +/- 66 to 1,300 +/- 53 micromol/l; P< 0.05).. Black obese women demonstrate a higher degree of insulin resistance, despite less visceral fat and a higher HDL: total-cholesterol ratio. In addition, endogenous beta-cell secretory function in black obese women appears to be more sensitive to the suppressive effect of exogenous insulin administration. The significant increase in lactate levels in white obese women confirms that they are more insulin sensitive.

Topics: Adult; Black or African American; Black People; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Lactates; Lipids; Obesity; Prevalence; South Africa; White People

Type 2 diabetes mellitus has never previously been described in UK children, although an increasing incidence in childhood is recognized in international studies. The prevalence of obesity in UK children is increasing and is a recognized risk factor for the development of diabetes. The aim of this study was to identify and characterize children with Type 2 diabetes in the West Midlands and Leicester.. Children were identified by contacting paediatricians responsible for diabetes in five hospitals. Details were collected on demographics, mode of presentation, investigations and treatment on a standard proforma.. Eight girls were identified with Type 2 diabetes, aged 9-16 years and who were of Pakistani, Indian or Arabic origin. They were all overweight (percentage weight for height 141-209%) and had a family history of diabetes in at least two generations. They presented insidiously with hyperglycaemia and glycosuria without ketosis and five were asymptomatic. Islet cell antibodies measured in seven patients were negative. Four had acanthosis nigricans which is a cutaneous marker of insulin resistance and the other four had high plasma levels of insulin and/or C peptide. These patients are distinct from those with maturity-onset diabetes of the young (MODY). All were initially managed with dietary measures, seven have been treated with oral anti-diabetic agents of whom two have subsequently required insulin.. These are the first UK case reports of Type 2 diabetes in children. Paediatricians need to be aware of the risk of Type 2 diabetes developing in childhood in high-risk ethnic groups, particularly in association with obesity and a positive family history.

Topics: Acanthosis Nigricans; Adolescent; Body Mass Index; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Glycosuria; Humans; Hyperglycemia; Hypoglycemic Agents; India; Insulin; Insulin Resistance; Obesity; Pakistan; Saudi Arabia; United Kingdom

We evaluated the effect of troglitazone (given orally 400 mg/day) on glucose intolerance and on the plasma levels of tumour necrosis factor-alpha (TNF-alpha) in 12 obese patients with type 2 diabetes for 12 weeks. Troglitazone significantly decreased fasting plasma glucose, serum C-peptide, serum insulin and HbA1c levels. Plasma levels of TNF-alpha were significantly reduced by troglitazone administered for 8 and 12 weeks. Troglitazone administration significantly improved insulin resistance, but did not affect pancreatic beta-cell function as evaluated by the homeostasis model assessment (HOMA). In the present study, we reported for the first time that troglitazone administration significantly reduces plasma levels of TNF-alpha in obese patients with type 2 diabetes.

Topics: Blood Glucose; C-Peptide; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Obesity; Thiazoles; Thiazolidinediones; Troglitazone; Tumor Necrosis Factor-alpha

The principal metabolic effect of metformin-an oral antihyperglycaemic agent-is the improvement in the sensitivity of peripheral tissues and liver to insulin. This study examined the effect of metformin monotherapy on antioxidative defence system activity in erythrocytes and plasma in diabetic patients. We studied the effect of metformin treatment on the activities of Cu, Zn-superoxide dismutase (EC 1. 15. 1. 1.), catalase (EC 1. 11. 1. 6.) and glutathione peroxidase (EC 1. 11. 1. 9.) in relation to lipid peroxidation products and reduced glutathione level in plasma and erythrocytes. In this study we also examined erythrocytes' susceptibility to H2O2-induced oxidative stress during metformin therapy. Although metformin monotherapy ameliorated the imbalance between free radical-induced increase in lipid peroxidation (by reducing the MDA level in both erythrocytes and plasma) and decreased plasma and cellular antioxidant defences (by increasing the erythrocyte activities of Cu, Zn, SOD, catalase and GSH level) and decreased erythrocyte susceptibility to oxidative stress, it had negligible effect to scavenge Fe ion-induced free radical generation in a phospholipid-liposome system.

Topics: Blood Glucose; C-Peptide; Catalase; Diabetes Mellitus; Diabetes Mellitus, Type 2; Erythrocytes; Fructosamine; Glutathione; Glutathione Peroxidase; Humans; Hydrogen Peroxide; Hypoglycemic Agents; In Vitro Techniques; Lipid Peroxidation; Metformin; Middle Aged; Obesity; Oxidative Stress; Reference Values; Superoxide Dismutase

Syndrome X is used to describe a constellation of factors that lead to coronary heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance, and an abnormality in lipid metabolism. We investigated the relationship between serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in 256 patients with type-2 diabetes mellitus. The serum level of CPR was measured by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index (BMI) and the serum level of triglycerides were significantly higher in the high CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence of hypertension was significantly higher in the high CPR group than in the other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the number of patients receiving insulin therapy was greater in the low CPR group than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The serum CPR level was significantly lower in patients with than without proliferative retinopathy or macroalbuminuria. Our conclusion is that the present data suggest that an increased serum level of CPR is associated with obesity, elevated serum triglycerides, and hypertension in patients with type-2 diabetes mellitus. A low CPR level leading to hyperglycemia is associated with the progression of diabetic microangiopathies, such as retinopathy and nephropathy.

Topics: Albuminuria; Body Mass Index; C-Peptide; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypertriglyceridemia; Insulin; Male; Middle Aged; Obesity; Risk Factors

Type 2 diabetes is a heterogeneous disease in which both beta-cell dysfunction and insulin resistance are pathogenetic factors. Disproportionate hyperproinsulinemia (elevated proinsulin/insulin) is another abnormality in type 2 diabetes whose mechanism is unknown. Increased demand due to obesity and/or insulin resistance may result in secretion of immature beta-cell granules with a higher content of intact proinsulin.. We investigated the impact of obesity on beta-cell secretion in normal subjects and in type 2 diabetic patients by measuring intact proinsulin, total proinsulin immunoreactivity (PIM), intact insulin, and C-peptide (by radioimmunoassay) by specific enzyme-linked immunosorbent assays in the fasting state and during a 120-min glucagon (1 mg i.v.) stimulation test. Lean (BMI 23.5 +/- 0.3 kg/m2) (LD) and obese (30.1 +/- 0.4 kg/m2) (OD) type 2 diabetic patients matched for fasting glucose (10.2 +/- 0.6 vs. 10.3 +/- 0.4 mmol/l) were compared with age- and BMI-matched lean (22.4 +/- 0.6 kg/m2) (LC) and obese (30.8 +/- 0.9 kg/m2) (OC) normal control subjects.. Diabetic patients (LD vs. LC and OD vs. OC) had elevated fasting levels of intact proinsulin 6.6 +/- 1.0 vs. 1.6 +/- 0.3 pmol/l and 7.7 +/- 2.0 vs. 1.2 +/- 0.2 pmol/l; PIM: 19.9 +/- 2.5 vs. 5.4 +/- 1.0 pmol/l and 29.6 +/- 6.1 vs. 6.1 +/- 0.9 pmol/l; and total PIM/intact insulin: 39 +/- 4 vs. 15 +/- 2% and 35 +/- 5 vs. 13 +/- 2%, all P < 0.01. After glucagon stimulation, PIM levels were disproportionately elevated (PIM/intact insulin based on area under the curve analysis) in diabetic patients (LD vs. LC and OD vs. OC): 32.6 +/- 6.7 vs. 9.2 +/- 1.1% and 22.7 +/- 5.2 vs. 9.1 +/- 1.1%, both P < 0.05. Intact insulin and C-peptide net responses were significantly reduced in type 2 diabetic patients, most pronounced in the lean group. The ratio of intact proinsulin to PIM was higher in diabetic patients after stimulation in both LD versus LC: 32 +/- 3 vs. 23 +/- 2%, and OD versus OC: 28 +/- 4 vs. 16 +/- 2%, both P < 0.01. In obese normal subjects, intact proinsulin/PIM was lower both in the fasting state and after glucagon stimulation: OC versus LC: 22 +/- 3 vs. 33 +/- 3% (fasting) and 16 +/- 2 vs. 23 +/- 2% (stimulated), both P < 0.05.. Increased secretory demand from obesity-associated insulin resistance cannot explain elevated intact proinsulin and disproportionate hyperproinsulinemia in type 2 diabetes. This abnormality may be an integrated part of pancreatic beta-cell dysfunction in this disease.

Topics: Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Obesity; Proinsulin; Radioimmunoassay

The aim of the study was to analyse the role of tumour necrosis factor-alpha (TNF-alpha) in insulin resistance and endothelial dysfunction in patients with different types of obesity.. Fasting serum TNF-alpha immunoreactive concentration (enzyme-linked immunosorbent assay, ELISA) and bioactivity (L929 cell cytotoxicity assay), endothelin-1 and C-peptide levels (radioimmunoassay, RIA) were measured in 15 patients with android- and 13 patients with gynoid-type obesity and 15 lean healthy controls with normal glucose tolerance and blood pressure.. Significantly (P<0.01) higher TNF-alpha concentration (8.92 +/- 0.44 pg/ml) and bioactivity (3.12 +/- 0.48 U/ml) were found in patients with android obesity as compared to patients with gynoid obesity (7.01 +/- 0.30 pg/ml, 0.97 +/- 0.11 U/ml) and to the lean controls (6.88 +/- 0.26 pg/ml, 0.88 +/- 0.08 U/ml). Serum endothelin-1 (5.38 +/- 0.30 pg/ml) and C-peptide levels (4.82 +/- 0.71 ng/ml) were also significantly higher (P < 0.01) in patients with android-type obesity than in controls (3.89 +/- 0.43 pg/ml, 1.46 +/- 0.25 ng/ml, respectively). In patients with gynoid-type obesity, only the C-peptide levels proved to be significantly higher (2.84 +/- 0.29 ng/ ml). Endothelin-1 levels, although were found to be slightly higher, did not differ statistically from in controls (4.56 +/- 0.31 pg/ml). There were significant positive linear correlations only in patients with android-type obesity between TNF-alpha, body mass index (BMI), serum endothelin-1 and C-peptide levels.. TNF-alpha may be one of the factors contributing to insulin resistance and vascular dysfunction in patients with android obesity.

Topics: Adult; Body Mass Index; C-Peptide; Case-Control Studies; Endothelin-1; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Humans; Insulin Resistance; Linear Models; Obesity; Tumor Necrosis Factor-alpha

Obesity is a rapidly increasing health problem among US youth. Hyperinsulinemia is associated with obesity and has been found to be a contributory factor for the development of cardiovascular disease in the obese. It has been suggested that hyperinsulinemia of obesity is a result of increased insulin secretion caused by insulin resistance. However, it has been shown in adults that decreased hepatic insulin clearance (HIC) is the primary cause of hyperinsulinemia in this population.. We studied 15 obese children and adolescents (11 F, 4 M; 8.6 to 18.1 years) before and 10 weeks after their enrollment in a multidisciplinary weight reduction program, which included a protein-sparing modified fast, a moderate intensity progressive exercise program, and a behavior-modification intervention.. All patients lost weight (P < 0.05). Measurements of immunoreactive insulin (IRI) and C-peptide reactivity (CPR) were performed before the program and at 10 weeks. IRI levels dropped significantly, whereas CPR levels did not change. CPR/IRI molar ratios, considered an indirect estimation of HIC, rose significantly after weight loss.. Our data suggest that hyperinsulinemia seen in obese children and adolescents is caused by decreased HIC. The cause for this decrease remains unknown, but it is reversible upon weight loss.

Topics: Adolescent; Behavior Therapy; C-Peptide; Child; Diet, Reducing; Exercise; Female; Humans; Insulin; Liver; Male; Obesity; Weight Loss

Plasma leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. Thyroid hormones are permissive for adrenergic activation, which in turn has been shown to decrease leptin expression. This study was therefore designed to test the hypothesis that hyperthyroidism results in lower leptin concentrations, whereas hypothyroidism leads to higher plasma leptin concentrations. In addition, the effects of normalization of thyroid function on plasma leptin were investigated.. Fasting plasma leptin concentrations and body fat mass (total body electrical conductivity) were measured in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Plasma leptin, glucose, insulin and free fatty acid concentrations were monitored during an oral glucose tolerance test (OGTT 75 g).. Fasting plasma leptin concentrations were similar in lean patients, independently of their thyroid function (hyperthyroid 12.5 +/- 2 ng mL-1, hypothyroid 10.2 +/- ng mL-1, euthyroid 12.7 +/- 3 ng mL-1). In obese hypothyroid patients, plasma leptin was threefold higher (P < 0.0005) than in lean hypothyroid patients, twofold higher (P < 0.005) than in obese hyperthyroid patients matched for fat mass and 30% increased (P < 0.01) compared with obese euthyroid subjects. There were no differences between fasting and post-prandial (OGTT) leptin concentrations in any group. Normalization of thyroid function did not affect plasma leptin, which remained elevated (P < 0.005) in formerly obese hypothyroid patients. Plasma leptin was not associated with serum thyroid hormones but highly correlated with body mass index and body fat mass in all patients (r = 0.85, P < 0.001). Plasma leptin correlated with plasma insulin concentration only in hyperthyroid patients (P < 0.01, r = 0.64), who presented with blunted stimulation of insulin release and higher plasma glucose (P < 0.05) than hypothyroid subjects.. The results indicate that (a) the correlation of leptin with body fat mass is preserved in thyroid dysfunction, (b) plasma leptin is markedly increased in obese hypothyroid hyperinsulinaemic patients and (c) plasma leptin is not affected by oral glucose loading.

Topics: Adult; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Hyperinsulinism; Hyperthyroidism; Hypothyroidism; Insulin; Leptin; Male; Middle Aged; Obesity; Proteins

In a detailed evaluation of the data accumulated for 493 type 2 diabetics who participated in the KID Study, pre- and postprandial C-peptide was correlated with blood glucose level, HbA1, body mass index (BMI), duration of disease and age. As described earlier the KID-Study examined a younger cohort of type 2 diabetics predominately practising a profession. Our investigations demonstrate a significant increase of pre- as well as postprandial C-peptide levels with increasing obesity. However, delta C-peptide, as an indicator at the reaction capacity of pancreatic secretion, decreases significantly and continuously. Pre- as well as postprandial C-peptide levels decrease significantly with up to 15-20 years duration of disease. The preprandial pancreatic secretion is usually even at a high normal level at such a late stage whereas the secretory reserve of normal or mildly overweight as well as of obese type 2 diabetics is more impaired. In contrast to patients with a BMI < 30, obese patients with a BMI > 30 will also develop impairment of basal insulin secretion over decades. The patient's age did not influence the pre- or postprandial insulin secretion. The quality of metabolic control as measured by the HbA1 has nearly exclusive impact on the secretory reserve capacity. Correlation with increasing HbA1 concentrations, the postprandial but not the preprandial C-peptide levels decreased significantly and continuously. Predictive factors for a deterioration in pancreatic function are in order of importance: the extent of obesity, the quality of metabolic control and only last the duration of diabetes. Fortunately, consistent diabetic care can have an impact on the first two.

Topics: Age of Onset; Blood Glucose; Body Mass Index; C-Peptide; Chromatography, High Pressure Liquid; Cohort Studies; Diabetes Mellitus, Type 2; Employment; Female; Glycated Hemoglobin; Humans; Longitudinal Studies; Male; Middle Aged; Obesity; Postprandial Period; Predictive Value of Tests; Prevalence; Prospective Studies; Radioimmunoassay

To investigate the relationship between leptin concentrations, various metabolic indices and body composition in six different groups.. Anthropometric measurements, fasting plasma glucose, serum insulin, C-peptide, FFA and leptin levels were performed. In the obese and diabetic subjects, body composition was analysed with bio-impedance equipment and as a 5 level CT scan.. Five lipoatrophic diabetes mellitus (LDM) patients, five normal subjects (N), nine white and nine black obese women (WW, BW), and nine white and nine black diabetic women (DWW, DBW) were investigated after an overnight fast.. In both ethnic groups there was a positive correlation between leptin and BMI (black group: r=0.8; P<0.0001, white group: r=0.7, P<0.002) and leptin and SC fat mass (black group: r=0.6; P<0.005, white group: r=0.6; P<0.004).. Across the groups, there were positive linear correlations between leptin concentrations, BMI, SC fat mass and FFA levels. Leptin and FFA concentrations are higher and insulin levels lower in both groups of black women compared to the two groups of white women, despite a similar BMI and body fat mass. In the DBW the large increase in visceral fat mass may be indicative of a more complex relationship between compensatory insulin resistance, elevated FFA levels and leptin secretion.

Topics: Adult; Anthropometry; Black People; Blood Glucose; Body Composition; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Humans; Insulin; Insulin Resistance; Leptin; Obesity; South Africa; White People

Topics: Adult; C-Peptide; Fatty Liver; Female; Hepatitis; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Lipids; Liver; Male; Obesity; Reference Values

Postmenopausal overweight women have an increased risk of breast cancer. The link between obesity and breast cancer could be mediated through hyperinsulinemia. Insulin and insulin-like growth factor-1 (IGF-1) stimulate mammary cell proliferation in vitro, and cell proliferation is directly linked to the risk of breast cancer. Our objective was to investigate the relationship between breast cancer and body composition, IGF-1, proinsulin, C-peptide, and fasting insulin. A case-control study was conducted of 438 community-dwelling women aged 53-90 years in 1992-1994 who had no history of cancer at the baseline visit in 1972-1974. Women were excluded who were using estrogen replacement therapy (ERT) or tamoxifen at the 1992-1994 visit, when IGF-1, proinsulin, fasting insulin, and C-peptide levels were measured. Prior ERT, alcohol and tobacco use, exercise, and reproductive history were recorded. Weight, height, and waist/hip ratio were measured. The 45 women with breast cancer had similar baseline body mass indices to the 393 women without breast cancer but had gained significantly more weight between the baseline visit in 1972-1974 and 1992-1994, (age-adjusted relative risk [RR] 1.05/kg, 95% confidence interval [CI] 1.01-1.09, p = 0.016). Proinsulin, fasting insulin, and C-peptide were each significantly positively correlated with both current weight and weight gain. However, levels of these hormones and IGF-1 did not differ significantly between women with and without breast cancer (all 95% CI within 0.996-1.004). Past ERT was significantly more common among women with breast cancer (p = 0.015), and duration of use was significantly longer (age-adjusted RR 1.13 per year of use, 95% CI 1.08-1.18, p = 0.000). The risk of breast cancer was significantly increased in women who had gained weight or used ERT. This increased risk was not associated with circulating levels of IGF-1, fasting insulin, proinsulin, or C-peptide.

Topics: Aged; Aged, 80 and over; Body Weight Changes; Breast Neoplasms; C-Peptide; Case-Control Studies; Estrogen Replacement Therapy; Female; Follow-Up Studies; Humans; Insulin; Insulin-Like Growth Factor I; Life Style; Middle Aged; Obesity; Proinsulin; Risk Factors

The correlation between hypertension and related risk factors has been studied in 733 type 2 diabetic patients. Hypertension was more frequent in women (65.35%) than in men (50.35%) (p < 0.0001).. Hypertensive patients showed older age (p < 0.0001) and greater Body Mass Index (BMI) (p < 0.03) than normotensive. In the diabetic group on diet only basal insulinaemia was higher (p < 0.05) in hypertensive than in normotensive diabetic men, but not in women. Such a difference, was not seen in patients of both sexes treated with oral hypoglycaemic agents; besides there was no difference in fasting C-peptide levels between hypertensive and normotensive insulin treated patients. In both sexes hypertension was independently correlated with age, BMI, increased urinary albumin excretion, triglycerides. The strongest correlation was with the family history of hypertension. On the contrary there was no correlation between hypertension and waisthip ratio.. In conclusion, the association between hypertension and type 2 diabetes depends on various risk factors, but a relationship with insulin levels is not surely demonstrable.

Topics: Administration, Oral; Adult; Age Factors; Aged; Albuminuria; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Comorbidity; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Hyperinsulinism; Hypertension; Hypertriglyceridemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Italy; Male; Middle Aged; Obesity; Prevalence; Risk Factors

In order to identify the mutual interaction between GH and leptin, we studied the effect of GH on fatty Zucker rats. GH administration at a high dose (5.0 IU/kg) reduced % body fat after 7 days. The leptin mRNA level in subcutaneous fat tissue was not changed but that in epididymal fat tissue was decreased by an even lower dose of GH (1.5 IU/kg). IGF-I treatment (200 microg/kg/day) did not change the % body fat or leptin mRNA level. These observations suggest that GH directly interacts with visceral fat and reduces fat mass and leptin expression. We also measured serum leptin levels in patients. The levels in patients with acromegaly were significantly lower than those in normal subjects with the same amount of body fat, but serum IGF-I and urinary C peptide excretion rates were higher in the acromegalic. These observations also suggests that GH directly interacts with adipose tissue and reduces leptin expression. Next we investigated the direct action of leptin on GH release from the pituitary. Leptin pretreatment of pituitary cells in culture or rats in a fasted or fed condition did not change GRH induced GH secretion. As indicated also by other recent studies, leptin may increase GRH or decrease somatostatin secretion by the hypothalamus. Thus GH interacts with fat tissues and leptin may be a good marker of the interaction.

Topics: Acromegaly; Adipose Tissue; Animals; Body Composition; C-Peptide; Female; Gene Expression Regulation; Growth Hormone; Humans; Insulin-Like Growth Factor I; Leptin; Male; Obesity; Rats; Rats, Wistar; Rats, Zucker; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Insulin secretion in response to an oral glucose tolerance test (OGTT) and sex hormone levels (free testosterone, androstenedione, dehydroepiandrosterone sulfate [DHEAS], estradiol, and sex hormone-binding globulin [SHBG]) were evaluated in 49 healthy obese premenopausal women (body mass index [BMI], 30 to 50.6 kg/m2) and 21 control subjects (BMI, 17.8 to 24.0 kg/m2) with normal glucose tolerance and without signs of hyperandrogenism. Obese women were divided into two groups according to waist to hip ratio (WHR): 27 subjects with upper-body obesity (WHR > 0.85) and 22 subjects with lower-body obesity (WHR < 0.8). Both fasting and glucose-induced insulin levels were higher in women with upper-body obesity than in controls (P < .001) and those with lower-body obesity (P < .001). Hyperandrogenism was observed in women with upper-body obesity, as evident by significantly elevated free testosterone (P < .05 v controls and subjects with lower-body obesity) and decreased SHBG (P < .001 v controls). The most important independent determinants of fasting insulin levels were BMI (P < .01) and the ratio of DHEAS to free testosterone (P < .01). The most important determinants of cumulative insulin response were WHR (P < .0005), duration of obesity (P < .01), and androstenedione levels (P < .01). In conclusion, in healthy obese premenopausal women without clinical signs of hyperandrogenism, a high BMI and more pronounced upper-body fat localization resulted in hyperinsulinemia and hyperandrogenism. The duration of obesity exaggerated the glucose-induced insulin level and cumulative insulin response independently of the degree of obesity and obesity type. The ratio of DHEAS to free testosterone was an independent determinant of fasting insulin concentration. Furthermore, the ratio of DHEAS to free testosterone rather than either of these androgens alone may be important in the regulation of insulin action in women.

Topics: Adult; Androstenedione; Body Weight; C-Peptide; Dehydroepiandrosterone; Estradiol; Fasting; Female; Glucose; Glucose Tolerance Test; Gonadal Steroid Hormones; Humans; Hyperandrogenism; Hyperinsulinism; Insulin; Obesity; Premenopause; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone

To evaluate the frequency of autoimmune markers (islet cell antibodies (ICA] and glutamic acid decarboxylase antibodies [GADA]) and clinical features in newly diagnosed people with diabetes aged 40-75 years.. Two hundred fifty-nine consecutive patients (aged 40-75 years) with newly suspected diabetes diagnosed during a 2-year period were studied. The diagnosis of newly discovered diabetes was confirmed in 203 patients. Gender, BMI, HbA1c, fasting C-peptide, ICA, and GADA were evaluated. The frequency of obesity was estimated using two different sets of criteria: 1) National Diabetes Data Group (NDDG) criteria, and 2) criteria based on a Swedish reference population.. The annual incidence of diabetes was 106 per 100,000 people. The incidence of diabetes in those patients who were 40-54 years old was significantly higher in men than in women (odds ratio: 2.16; P = 0.001). ICA were detected in 16 of 203 patients (8%), whereas 17 of 203 patients (8%) were GADA+; 10 of 203 (5%) patients were positive for both ICA and GADA. Among the 203 diabetic patients, 19 (9.4%) were classified as having IDDM, giving an IDDM incidence of 10 per 100,000 people aged 40-75 years. The frequency of obesity in NIDDM was high but varied with its definition; the frequency of obesity was highest (P < 0.001) when NDDG criteria, and not Swedish reference values, were used (57 of 75 [76%] vs. 40 of 75 [53%] for women and 66 of 109 [61%] vs. 45 of 109 [41%] for men).. A striking male preponderance was found among incident cases of diabetes in people aged 40-54 years. Autoimmune markers were detected in 10% of incident cases of diabetes in people aged 40-75 years. Using a conservative estimation, as many as 10 of 100,000 middle-aged and elderly subjects developed IDDM. The frequency of obesity in NIDDM was high but this was also the case in the reference population.

Topics: Adult; Aged; Autoantibodies; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Islets of Langerhans; Male; Middle Aged; Obesity; Sex Factors; Sweden

Immunoreactive serum leptin was analysed in 49 women with polycystic ovary syndrome (PCOS) distributed on a wide range of body mass index (BMI; kg/m2) and in 32 normally menstruating women with comparable age, BMI, physical activity and dietary habits. All women with PCOS had increased androgen concentrations and obese women with PCOS (BMI > or = 25, n=24) also showed decreased insulin sensitivity and a preferential accumulation of truncal-abdominal body fat. Anthropometric and hormonal variables, insulin sensitivity, and pancreatic beta-cell activity were investigated in all women. Percentage body fat was calculated using gender-specific regression equations based on skinfold measurements. Serum leptin concentrations were higher in obese than in non-obese women (P < 0.001), but did not differ between the women with PCOS and controls, nor did they differ between glucose intolerant and glucose tolerant, or hirsute and non-hirsute women with PCOS. Both groups showed strong correlations between serum leptin concentrations and percentage body fat, BMI, body fat distribution, fasting plasma insulin and C-peptide, early insulin secretion, the free androgen index (FAI), and the degree of insulin resistance. After correcting for percentage body fat, only the FAI in the women with PCOS remained significant (P < 0.05). However, in a multiple regression analysis with both percentage body fat and the FAI as independent variables, the FAI increased only minimally (2%) the explained variation in leptin concentrations. Thus, serum leptin concentrations are almost exclusively determined by the total amount of body fat, independent of its location, and do not confirm the hypothesis that leptin is involved in the development of the hormonal and metabolic abnormalities in the PCOS.

Topics: Adolescent; Adult; Androgens; Body Composition; Body Constitution; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome; Proteins; Skinfold Thickness

Impaired stimulation of glucose metabolism and reduced suppression of lipolytic activity have both been suggested as important defects related to the insulin resistance of adolescent obesity. To further explore the relationship between these abnormalities, we studied seven obese [body mass index (BMI) 35 +/- 2 kg/m2] and seven lean (BMI 21 +/- 1 kg/m2) adolescents aged 13-15 yr and compared them with nine lean adults (aged 21-27 yr, BMI 23 +/- 1 kg/m2) during a two-step euglycemic-hyperinsulinemic clamp in combination with 1) a constant [2H5]glycerol (1.2 mg.m-2.min-1) infusion to quantify glycerol turnover and 2) indirect calorimetry to estimate glucose and net lipid oxidation rates. In absolute terms, basal glycerol turnover was increased and suppression by insulin was impaired in obese adolescents compared with both groups of lean subjects (P < 0.01). However, when the rates of glycerol turnover were adjusted for differences in body fat mass, the rates were similar in all three groups. Basal plasma free fatty acid (FFA) concentrations were significantly elevated, and the suppression by physiological increments in plasma insulin was impaired in obese adolescents compared with lean adults (P < 0.05). In parallel with the high circulating FFA levels, net lipid oxidation in the basal state and during the clamp was also elevated in the obese group compared with lean adults. Net lipid oxidation was inversely correlated with glucose oxidation (r = -0.50, P < 0.01). In conclusion, these data suggest that lipolysis is increased in obese adolescents (vs. lean adolescents and adults) as a consequence of an enlarged adipose mass rather than altered sensitivity of adipocytes to the suppressing action of insulin.

Topics: Adolescent; Adult; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose; Glycerol; Humans; Insulin; Kinetics; Male; Obesity; Osmolar Concentration

Abdominal obesity is associated with insulin resistance and cardiovascular risk factors, but there has been little information published to advance the use of abdominal anthropometry in the care of diabetic patients.. A cross-sectional survey of municipal hospital outpatients recently diagnosed with type 2 diabetes (73 men and 142 women of whom 89% were African Americans). Age-adjusted linear regression was used to compare the supine sagittal abdominal diameter (SAD), supine waist circumference, four anthropometric ratios, and the body mass index (kg/m2) for their ability to predict serum fasting C-peptide and lipid levels.. The best predictor of log-transformed C-peptide was SAD/height (p<0.0001 for men; p=0.0003 for women). SAD/thigh circumference was the best predictor of log-transformed triglycerides for men (p=0.002) and of total cholesterol/HDL cholesterol for women (p=0.043). The body mass index was less able to predict C-peptide, HDL cholesterol and total cholesterol/HDL cholesterol than was SAD/height or SAD/thigh circumference or waist circumference/height.. Anthropometric indices of abdominal obesity appear to be correlated with insulin production and lipid risk factors among municipal-hospital, type 2 diabetic patients much as they are in other studied populations. Since anthropometric data are inexpensively obtained and immediately available to the practitioner, their utility for preliminary clinical assessment deserves to be tested in prospective outcome studies.

Topics: Abdomen; Adult; Anthropometry; Black People; Body Constitution; Body Mass Index; C-Peptide; Cholesterol, HDL; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Linear Models; Lipids; Male; Middle Aged; Obesity; Supine Position; Triglycerides; United States

Topics: Age Factors; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Reference Values; Sex Characteristics; Tumor Necrosis Factor-alpha

Children with simple obesity (SO) show increased linear growth with normal or high serum insulin-like growth factor-I (IGF-I) levels during prepubertal period, despite low GH secretion. We measured IGF-I, IGFBP-1, GHBP and other factors to clarify the hormonal relation between the nutrition and the linear growth in SO and compared these factors with children with normal short stature (NS). Subjects were 23 SO and 19 NS children, and their height standard deviation (SD) scores were 0.7 +/- 0.2 SD and -3.4 +/- 0.3 SD (mean +/- SEM) (P < 0.01), respectively. Oral glucose tolerance test (OGTT) was performed in all the subjects and GH-releasing factor (GRF) test was also performed in 13 of SO and 17 of NS. The peak levels of GH in the GRF test were significantly lower in SO than in NS (12.8 +/- 1.7 vs. 39.8 +/- 6.9 ng/ml) and showed a significantly positive correlation with sigma IGFBP-1 (r = 0.63, P < 0.01). Serum GHBP level and IGF-I level were significantly higher in SO than in NS on pubertal stage matching. There was a positive correlation between GHBP and sigma insulin during OGTT (r = 0.75, P < 0.01). When the sum of the values during OGTT was expressed as sigma, sigma insulin, sigma C-peptide and sigma glucose were significantly higher in SO than in NS on pubertal stage matching. Basal and sigma IGFBP-1 were significantly lower in SO than in NS, but IGFBP-3 levels showed no significant difference between the two groups either in prepuberty or midpuberty. In conclusion, it can be hypothesized that the overnutrition causes hyperinsulinemia which increases GH receptor and IGF-I secretion despite low GH secretion. Hyperinsulinemia also may increase free IGF-I by lowering IGFBP-1. These two mechanism are supposed to be the nutrition related hormonal changes in SO and can explain the growth of SO. In addition, the increased free IGF-I may contribute the decreased GH secretion due to negative feedback in SO.

Topics: Adolescent; Adult; Blood Glucose; Body Height; C-Peptide; Carrier Proteins; Child; Child, Preschool; Female; Glucose Tolerance Test; Growth; Growth Hormone-Releasing Hormone; Hormones; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Kinetics; Nutritional Physiological Phenomena; Obesity; Puberty

To assess the prevalence of markers of autoimmune destruction of pancreatic beta-cells in patients with non-insulin dependent diabetes mellitus (NIDDM).. 127 hospitalized NIDDM patients subdivided to the following subgroups: non-obese with C-peptide < 0.3 nmol/l (NIDDM-(-)), non-obese with C-peptide > 0.3 nmol/l (NIDDM-(+)), obese with C-peptide < 0.3 nmol/l (NIDDM+(-)) and obese with C-peptide > 0.3 nmol/l (NIDDM2+). METHODS AND MEASURED PARAMETERS: Age, BMI, C-peptide, autoantibodies to glutamic acid decarboxylase (antiGAD-Ab), autoantibodies to islet cells (ICA), markers of specific cellular immunity CD4, CD8, CD19, CD4/CD8, CD4/CD45/RA+, CD4/CD45/RA-, NK (CD16+56), CD3/HLADR, organ specific/non-specific autoantibodies.. AntiGAD-Ab were positive in 5/15 (33.3%) NIDDM-(-), 1/32 (3.1%) NIDDM-(+), 2/9 (22.2%) NIDDM+(-) and in 3/71 (4.2%) NIDDM2+. The positivity of antiGAD-Ab in NIDDM-(-) and NIDDM+(-) was significantly higher (p < 0.05) than in NIDDM-(+) and NIDDM2+.. Some patients with manifestation of diabetes in older age initially classified and treated as having NIDDM may have in fact slowly evolving autoimmune insulin-dependent diabetes mellitus (LADA). These patients can be identified by measurement of antiGAD-Ab or other markers (ICA, IA-2) of autoimmune destruction of pancreatic beta-cells (AID). Moreover, in some patients both AID and insulin resistance may coexist in parallel.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Biomarkers; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; Islets of Langerhans; Male; Middle Aged; Obesity

In the fasted rat, efficient glucose-stimulated insulin secretion (GSIS) is absolutely dependent on an elevated level of circulating free fatty acids (FFAs). To determine if this is also true in humans, nonobese volunteers were fasted for 24 h (n = 5) or 48 h (n = 5), after which they received an infusion of either saline or nicotinic acid (NA) to deplete their plasma FFA pool, followed by an intravenous bolus of glucose. NA treatment resulted in a fall in basal insulin concentrations of 35 and 45% and in the area under the insulin response curve (area under the curve [AUC]) to glucose of 47 and 42% in the 24- and 48-h fasted individuals, respectively. The 48-h fasted subjects underwent the same procedure with the addition of a coinfusion of Intralipid plus heparin (together with NA) to maintain a high concentration of plasma FFAs throughout the study. The basal level and AUC for insulin were now completely normalized (C-peptide profiles paralleled those for insulin). To assess the effect of an overnight fast, nonobese (n = 6) and obese (n = 6) subjects received an infusion of either saline or NA, followed by a hyperglycemic clamp (200 mg/dl). The insulin AUC in response to glucose was unaffected by lowering of the FFA level in nonobese subjects, but fell by 29% in the obese group. The data clearly demonstrate that in humans, the rise in circulating FFA levels after 24 and 48 h of food deprivation is critically important for pancreatic beta-cell function both basally and during subsequent glucose loading. They also suggest that the enhancement of GSIS by FFAs in obese individuals is more prominent than that seen in their nonobese counterparts.

Topics: Adult; Blood Glucose; C-Peptide; Fasting; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Heparin; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Niacin; Obesity

To evaluate the influence of family history of hypertension on insulin sensitivity in obese normotensive adults, comparing them with lean subjects.. 136 normotensives (N)(mean 24 h blood pressure < 130/80 mmHg; age range 35-45 y): 32 lean (body mass index, BMI < or = 25 kg/m2) N with normotensive parents (F-), 37 lean N with one or two parents hypertensive (F+), 32 obese (BMI > or = 30 kg/m2) NF- and, 35 obese NF+.. 24 h ambulatory blood pressure monitoring; glucose, insulin and C-peptide before and 30, 60, 90 and 120 min after an oral glucose load; index of insulin peripheral activity (Ia: 10(4)/insulin x glucose values at glucose peak); fasting insulin/C-peptide ratio (I/Cp).. The four groups were comparable for age, gender and blood pressure values throughout the 24 h. Glucose, fasting and during test, and I/Cp were similar among the four groups; insulin and C-peptide, fasting and stimulated, were significantly higher and Ia lower in obese N than in lean N; at similar BMI, insulin and C-peptide were significantly higher and Ia lower, in F+ than in F-. The correlation between insulin and BMI was significantly closer in F- than in F+.. Family history of hypertension appears to be significantly associated with insulin sensitivity in both lean and obese normotensive adults; moreover, overweight and a genetic predisposition to hypertension may have additive adverse effects on insulin sensitivity in normotensive adult subjects.

Topics: Adult; Blood Glucose; Blood Pressure Monitoring, Ambulatory; Body Constitution; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Insulin Resistance; Male; Middle Aged; Obesity

The main purpose of this work was to study the possible differences in insulin secretion in a large group of type 2 diabetic patients in relation to diabetes duration, obesity, and the presence of secondary failure after treatment with oral hypoglycemic agents.. There were 147 nonobese and 215 obese type 2 diabetic subjects, aged 35-80 years, investigated in a cross-sectional descriptive study Subjects were grouped according to whether glycemic control was good (mean blood glucose <8.5 mmol/l) or poor. Beta-cell function was assessed by measuring meal-stimulated insulin and C-peptide concentrations, as the mean of the three postprandial increments above the premeal value.. Basal C-peptide concentrations were significantly higher in obese than nonobese patients of both groups. The mean of meal-stimulated C-peptide concentrations was also significantly higher in obese than nonobese patients with good glycemic control, but not in the secondary failure groups. In nonobese and obese patients considered separately, a significant negative correlation between the mean of daily blood glucose and meal-stimulated C-peptide was observed (r=-0.705 and r=-0.679, respectively, P < 0.001) and the residual beta-cell function was significantly correlated with the known duration of diabetes and metabolic control, but not with BMI, in both groups.. On average, obese diabetic subjects showed higher meal-stimulated C-peptide than nonobese subjects only in well-controlled groups. In both obese and nonobese patients, an inverse association between meal-stimulated insulin secretion and duration of diabetes was observed. In obese patients, as in nonobese patients, the lower beta-cell function seems likely to be the major pathogenetic factor in the appearance of secondary failure, while being overweight plays only a minor role, thus showing that type 2 diabetes is the same disease in obese and nonobese patients.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Blood Glucose; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Obesity; Postprandial Period

Topics: Adult; C-Peptide; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Humans; Male; Obesity; Postprandial Period; Radioimmunoassay; Reference Values; Tumor Necrosis Factor-alpha

The glucoregulatory and hormonal responses to moderate-intensity exercise (50% VO2max for 45 min) were examined in subjects with type 2 diabetes and mild hyperglycemia. We studied seven obese subjects with type 2 diabetes and seven lean and seven obese control subjects (fasting plasma glucose levels, 7.5 +/- 0.5, 4.8 +/- 0.1, and 5.2 +/- 0.1 mmol/l, respectively). Glucose production, utilization, and cycling (flux between glucose and glucose-6-phosphate [G-6-P]) were measured with [6-(3)H]glucose and [2-(3)H]glucose using the constant specific-activity method. Insulin levels decreased normally during exercise in diabetic subjects. Plasma glucose levels decreased in diabetic subjects, but remained constant in control subjects. Basal glucose production was not different among groups and increased similarly during exercise. The decrease in plasma glucose in diabetic subjects was due to greater glucose utilization (867 +/- 83 vs. 726 +/- 143 micromol x m(-2) x min(-1); P < 0.05). This was a consequence of the mass effect of hyperglycemia, since glucose metabolic clearance increased similarly in all groups. Glucose cycling, expressed as a percentage of total glucose output (i.e., flux through G-6-P) was elevated at rest (P < 0.01), but decreased during exercise (P < 0.01). The catecholamine response to exercise was blunted in diabetic subjects, presumably indicating autonomic dysfunction. In conclusion, during moderate-intensity exercise in obese diabetic subjects with mild hyperglycemia, 1) insulin secretory responses were normally regulated; 2) glucose homeostasis was different from that in nondiabetic subjects because glucose levels decreased during exercise; 3) the decrease in plasma glucose was due to greater-than-normal rates of glucose utilization, which were sustained by hyperglycemia; and 4) elevated basal rates of glucose cycling decreased during exercise, presumably because exercise simultaneously lowered plasma glucose, was associated with a blunted catecholamine response, and accentuated an underlying defect in hepatic glucokinase activity in type 2 diabetes.

Topics: Adult; Alanine; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Exercise; Female; Glucose; Glucose-6-Phosphate; Homeostasis; Humans; Hyperglycemia; Insulin; Lactic Acid; Male; Obesity; Oxidation-Reduction; Oxygen Consumption; Tritium

Obesity is characterized by variable degrees of hyperinsulinaemia, which has been attributed to either beta-cell hypersecretion or reduced hepatic insulin extraction, or both. To investigate this controversial issue, a 4-h frequently sampled i.v. glucose tolerance test (glucose dose 12.8 g m(-2)) was performed in 13 normotolerant, grossly obese adolescents (10 F/3 M; 13+/-1 y; body mass index 32+/-0.9; pubertal stage 4-5; obesity duration 7.8+/-3 y) and in a comparable group of 8 healthy, normal-weight subjects. Glucose, insulin and C-peptide time-course were analysed by the minimal model technique, which estimates beta-cell secretion, insulin sensitivity (Si), glucose effectiveness (SG) and hepatic insulin extraction (HE). Despite similar fasting and after load glucose patterns (SG similar in the two groups), obese adolescents showed sustained peripheral hyperinsulinaemia (total insulin area under the concentration curve 67.2+/-10.8 vs 19.1+/-1.2 pmol l(-1) in 240 min; p <0.002) and a 71% reduction in Si (2.02+/-0.33 vs 6.95+/-1.03 x 10(4) min(-1) (microU ml(-1)); p < 0.001). Compared with control subjects, the total amounts of prehepatic insulin secretion and posthepatic insulin delivery were also increased significantly in obese adolescents by 30% and 46%, respectively; HE was reduced by 15% during the first 30 min of the test, but recovered within the normal range during the rest of the test. In conclusion, severely obese adolescents are insulin resistant and their hyperinsulinaemia is primarily caused by beta-cell hypersecretion, whereas the reduction in insulin hepatic extraction is a transient metabolic phenomenon.

Topics: Adolescent; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Liver; Male; Obesity

Thyrotropin-releasing hormone (TRH) has been found in the gastrointestinal tract, where it mainly exerts an inhibitory action. We used oral TRH, a stable and powerful formulation, to explore the glucoregulatory response of oral glucose tolerance test (OGTT) on obese patients with impaired glucose tolerance (IGT). Seven obese patients with IGT and eight controls were investigated. Three tests were performed on three separate days. On day 1, An oral TRH test: a 40 mg TRH tablet, was given. Blood samples for blood glucose (BG), proinsulin (PI), insulin (INS), C-peptide (CP), thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) were collected every 30 minutes for 3 hours. On day 2, an OGTT with 75 g glucose was performed. On day 3, an oral TRH test was administered 30 minutes before the OGTT, and blood was collected every 30 minutes for 3 hours. Oral-TRH had no effect on basal BG and on pancreatic hormone secretion. Oral TRH, coupled with OGTT in both controls and obese patients, led to a significant inhibition of BG (p < 0.01), of CP (p < 0.001), and of INS (p < 0.001) during the first hour of administration, and afterward, there was only a very slight increase, compared with levels after only OGTT treatment. After OGTT, PI peaked at 90 minutes (9.4+/-3 ng/mL) in controls and at 60 minutes (12.7+/-2.5 ng/mL) in obese patients. TRH application prior to OGTT inhibited PI secretion for 90 minutes in controls, whereas in obese patients PI levels were decreased, not inhibited, during the OGTT. The mechanism of the inhibitory TRH action on OGTT-induced increase of BG and pancreatic hormone secretion is not clear. It could be due to inhibition of gastric motility, and on a paracrine effect that enhances secretion of somatostatin that then suppresses INS, CP, and possibly PI levels. The partial escape of PI from the TRH blockade in obese patients with IGT might indicate a diminished functioning capability of beta-cells and that TRH cannot affect the INS processing within the beta-cells in these patients.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Kinetics; Middle Aged; Obesity; Proinsulin; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

The authors have previously demonstrated abnormalities in glucose and insulin metabolism in nondiabetic black American (BA) adults versus white American (WA) adults. Whether similar glucoregulatory alterations extend to BA adolescents remain unknown. In addition, obesity, a known risk factor for insulin resistance and hyperinsulinemia, occurs in a greater proportion of BA adults and children when compared to WA. The objective of the present study was to examine the differential effects of obesity on glucose homeostasis in BA and WA adolescents.. We examined glucose homeostasis in BA and WA adolescents using oral glucose tolerance test (OGTT), intravenous glucose tolerance test (IVGTT), and [6,6-2H2]-glucose infusion. The study consisted of four age-, sex-, and pubertal stage-matched groups: 15 lean BA, 29 lean WA, 7 obese BA, and 9 obese WA.. Both obese groups had significantly increased insulin and C-peptide area under the curve (AUC) during OGTT and IVGTT when compared to their same-race lean counterparts. During OGTT, obese BA demonstrated greater insulin and C-peptide when compared to obese WA. During IVGTT, first- and second-phase insulin were significantly greater in obese BA versus obese WA.. In summary, BA adolescents demonstrated insulin resistance which is markedly exaggerated in the face of obesity when compared to WA adolescents, implying a differential impact for obesity on glucose homeostasis that is unique to the obese BA adolescent group. In conclusion, there is a need for early aggressive weight management in obese BA adolescents.

Topics: Adolescent; Black People; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Liver; Male; Obesity; White People

In obese children, both spontaneous and stimulated growth hormone (GH) secretion are impaired but a normal or increased height velocity is usually observed. This study was undertaken to explain the discrepancy between impaired GH secretion and normal height velocity. We evaluated the GH bioactivity (GH-BIO), GH serum level by immunofluorimetric assay (GH-IFMA), insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in 21 prepubertal obese children (13 boys and eight girls) aged 5.7 to 9.4 years affected by simple obesity and in 32 (22 boys and 10 girls) age- and sex-matched normal-weight controls. The results were as follows (obese versus [v] controls): GH-IFMA, 4.84 +/- 3.54 v 23.7 +/- 2.04 microg/L (P < .001); GH-BIO, 0.60 +/- 0.45 v 1.84 +/- 0.15 U/mL (P < .001); IGF-I, 173.8 +/- 57.2 v 188.6 +/- 132.6 ng/mL (nonsignificant); IGF-II, 596.1 +/- 139.7 v 439.3 +/- 127.4 ng/mL (P < .001); IGFBP-1, 23.25 +/- 14.25 v 107 +/- 165.7 ng/mL (P < .05); IGFBP-2, 44.37 +/- 62.18 v 385.93 +/- 227.81 ng/mL (P < .001); IGFBP-3, 3.31 +/- 0.82 v 2.6 +/- 0.94 microg/mL (P < .05); and IGFs/IGFBPs, 1.32 +/- 0.32 v 1.07 +/- 0.34 (P < .05). In conclusion, in prepubertal obese children, not only immunoreactive but also bioactive GH concentrations were low. In these subjects, therefore, nutritional factors and insulin may contribute to sustain normal growth also by modulating several components of the IGF-IGFBP system.

Topics: C-Peptide; Child; Child, Preschool; Female; Growth; Growth Hormone; Humans; Immunoassay; Insulin; Insulin-Like Growth Factor Binding Proteins; Male; Obesity; Somatomedins

The role of tumor necrosis factor-alpha in insulin resistance has been studied in 59 patients with Type 2 diabetes, 28 with android type obesity and 35 healthy lean controls. Immunoreactive concentrations and bioactivity of serum tumor necrosis factor-alpha have repeatedly been determined in 8 weeks intervals for 12 months, five times per patients, by using ELISA and L929 cell cytotoxicity bioassay. Significantly higher immunoreactive tumor necrosis factor-alpha concentrations and bioactivity have been found in both, the Type 2 diabetic and obese groups as compared to the healthy persons. Tumor necrosis factor-alpha concentrations and bioactivity have showed a significant positive linear correlation with the elevated basal serum C-peptide levels and body mass indexes in both groups of patients. According to these data the cytokine might play a role in insulin resistance in obesity as well in Type 2 diabetes.

Topics: Adipose Tissue; Aged; Biomarkers; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Male; Middle Aged; Obesity; Reference Values; Tumor Necrosis Factor-alpha

We examined the importance of ethnicity in terms of beta-cell secretion and hepatic insulin extraction (HIE) and insulin clearance (IC) to peripheral insulin levels before and after stimulation in three populations of West African ancestry, namely African-Americans, Ghanaian immigrants, and native Ghanaians living in diverse environments, and white Americans. Following 10 to 12 hours of overnight fasting, each subject ingested a 75-g oral glucose load. Blood samples for determination of serum glucose, insulin, and C-peptide were obtained at baseline and after the oral glucose load at 30-minute intervals for 240 minutes. Basal HIE and IC were calculated as the molar ratios of C-peptide and insulin concentrations at basal steady state, and postprandial values as molar ratios of the incremental integrated C-peptide and insulin areas. Clinical characteristics of the patients were not significantly different among the four groups. During the fasting and postprandial state, serum glucose levels were not significantly different among the four groups. Surprisingly, the mean fasting insulin concentration was significantly greater in native Ghanaians (21.19 +/- 0.93 microU/mL, P < .05) than in African-Americans (11.90 +/- 1.02,microU/ML), Ghanaian immigrants (8.14 +/- 0.96 microU/mL), and white Americans (7.03 +/- 0.78 microU/mL). Following the oral glucose load, the mean serum peak and incremental integrated areas of insulin were significantly (P < .05) greater in native Ghanaians, African-Americans, and Ghanaian immigrants compared with white Americans. In contrast, there were no significant differences in postprandial serum insulin responses among the three groups of West African ancestry, irrespective of country of origin or residence. Despite the higher insulin concentrations in blacks of West African ancestry compared with whites, the corresponding basal and postprandial serum C-peptide levels were not significantly different among the four groups. Mean basal and postprandial HIE and IC were significantly (P < .05 to .01) reduced (25% to 52%) in the three populations of West African ancestry compared with the white Americans, but these values were not significantly different among the West African descendants. When comparing metabolic responses in obese (body mass index [BMI] > 27 kg/m2) and non-obese (BMI < 27 kg/m2) native Ghanaians, we found no significant differences in fasting insulin, C-peptide, and basal HIE or IC. Also, there were no significant relat

Topics: Adult; Aging; Black People; Body Height; Body Mass Index; Body Weight; C-Peptide; Female; Ghana; Glucose; Humans; Insulin; Liver; Male; Obesity; United States; White People

In obesity, a central pattern of fat distribution is mostly associated with hyperinsulinemia, insulin resistance, and hyperlipemia, thus promoting the development of non-insulin-dependent diabetes mellitus and cardiovascular disease. In addition, in obesity, changes in energy expenditure are hypothesized to be involved in the development or maintenance of excessive body fat storage. In this study, abdominal fat distribution by computed tomographic (CT) scan was used to study the relation between the visceral fat depot, insulin secretion, and insulin sensitivity in a group of obese subjects with normal glucose tolerance (n = 26; body mass index [BMI], 39 +/- 1 kg/m2) and a group of normal-weight control subjects (n = 9; BMI, 23 +/- 1 kg/m2). The minimal model method was used to assess insulin sensitivity, S(I), and first-phase (phi1) and second-phase (phi2) beta-cell sensitivity from plasma glucose, insulin, and C-peptide concentrations measured during an intravenous glucose tolerance test ([IVGTT] 0.33 g/kg body weight). Moreover, we evaluated the relationships between these parameters and the resting metabolic rate (RMR) and glucose-induced thermogenesis (GIT) measured by indirect calorimetry. The data show the following: (1) in obese subjects, phi1 is greater but not statistically different from the value in control subjects (252 +/- 41 v 157 +/- 25 dimensionless 10(9)); (2) phi2 is significantly higher in obese subjects (27 +/- 4 v 14 +/- 2 min(-1) x 10(9), P < .05), with a positive correlation between the amount of visceral adipose tissue (VAT) and phi2 (r = .49, P < .05); (3) S(I) is decreased in the obese group (2.8 +/- 0.3 v 9.7 +/- 1.6 10(-4) x min(-1)/microU x mL(-1)), P < .0001), with a negative correlation of S(I) with the adiposity index BMI (r = -.67, P < .0001) and VAT (r = .56, P < .05); (4) RMR, expressed in absolute terms, was significantly increased in obese versus lean subjects (5.9 +/- 0.2 v 4.6 +/- 0.3 kJ/min, P < .01), whereas when RMR was adjusted for fat-free mass (FFM), the difference between the two groups disappeared (0.09 +/- 0.003 v 0.09 +/- 0.002 kJ/min x kg FFM). We did not observe any difference in GIT between lean and obese subjects. Moreover, GIT was significantly correlated with FFM (r = .69, P < .005), but not with BMI. The amount of VAT did not correlate with RMR or GIT. In conclusion, these results suggest that in obese subjects with normal glucose tolerance, insulin sensitivity is impaired and the beta-cell hyperresp

Topics: Abdomen; Adipose Tissue; Adult; Body Composition; C-Peptide; Diabetes Mellitus; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Obesity; Sensitivity and Specificity

Some patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) are positive for antibodies to glutamic acid decarboxylase (anti-GAD), which have been shown to be a useful marker for the diagnosis and prediction of insulin-dependent (Type 1) diabetes mellitus (IDDM). Anti-GAD positive NIDDM patients tend to develop insulin deficiency. We investigated the prevalence of anti-GAD in 200 NIDDM with secondary failure of oral hypoglycaemic therapy (SF) and 200 NIDDM well controlled by diet and/or sulphonylurea agents (NSF). Twenty-two of 200 (11%, p < 0.05) SF patients and 6 of 200 (3%) NSF patients were anti-GAD positive. The positive. The positive rate for anti-GAD was as high as 23.8% in the non-obese and insulin deficient SF patients. The SF patients with anti-GAD tended to be non-obese and to have an impaired release of endogenous insulin. The internal before development of secondary failure was not associated with the presence of anti-GAD in this study. In conclusion we found that anti-GAD was positive in as many as 11% of the SF patients, suggesting that autoimmune mechanisms may play an important role in the pathogenesis of secondary failure or sulphonylurea therapy.

Topics: Analysis of Variance; Antibodies; Autoantibodies; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Glutamate Decarboxylase; Humans; Hypoglycemia; Insulin; Japan; Male; Middle Aged; Obesity; Time Factors; Treatment Failure; Urine

Topics: Adult; C-Peptide; Cross-Over Studies; Fatty Acids, Nonesterified; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Obesity; Proteins; Radioimmunoassay

To determine the prevalence of past and current obesity among patients with non-insulin-dependent diabetes mellitus (NIDDM) and to define the clinical characteristics of non-obese NIDDM patients in South Korea, we studied a cross-section of 749 NIDDM patients and a group of age- and sex-matched control subjects. Current height, weight and waist-to-hip ratio (WHR), the history of weight changes and the family history of diabetes were recorded. Obesity was defined as body mass index (BMI) > 25 kg/m2. The maximum lifetime BMI of diabetic patients was significantly higher than that of control subjects (P < 0.001). Compared with control subjects, current BMI was higher in diabetic women (P < 0.001) but not in diabetic men. In contrast, WHR of both diabetic men and women were significantly higher than those of controls (P < 0.05). BMI and WHR correlated significantly with fasting C-peptide levels and log-triglyceride levels in NIDDM patients. As a whole, 72% of the South Korean NIDDM patients had a history of past obesity as assessed by their maximum weight, while only 38% of them were currently obese. Compared with obese patients, non-obese patients were characterized by lower fasting serum C-peptide levels (P < 0.001), a higher percentage of insulin treatment (P < 0.05), lower maximum BMI (P < 0.001) and more pronounced weight loss from the time at their maximum weight (P < 0.001). In summary, increased upper body adiposity and a history of past obesity were associated with NIDDM in South Korea. Although most South Korean NIDDM patients were previously obese, many of them were currently not obese. Lower maximum BMI, lower serum C-peptide levels and a higher percentage of insulin treatment in non-obese NIDDM patients suggest that the capacity to increase insulin secretion in response to increasing weight gain is rather limited in these patients.

Topics: Adipose Tissue; Adult; Aged; Blood Pressure; Body Constitution; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Korea; Male; Middle Aged; Multivariate Analysis; Obesity; Sex Factors; Time Factors

The pathogenetic mechanisms behind insulin resistance in polycystic ovary syndrome (PCOS) are far from fully elucidated. Aberrant counterregulatory responses to hypoglycaemia have been reported in patients with insulin resistance, and recent reports suggest that plasma glucose may be regulated at lower levels in women with PCOS. In this study we investigated the complete hormonal counterregulatory response to hypoglycaemia in women with PCOS.. Prospective cross-sectional study.. Eight obese (BMI > or = 25) and 10 non-obese (BMI < 25) women with PCOS, diagnosed by means of ultrasonography and clinical signs of chronic anovulation. Eight obese and 9 non-obese controls.. Hypoglycaemia was induced by an intravenous bolus of soluble insulin (0.15 IU/kg body weight). The counterregulatory responses of cortisol, GH, catecholamines, glucagon, chromogranin A (CGA), and neuropeptide Y (NPY) were studied together with symptoms of hypoglycaemia.. The obese women with PCOS had a more pronounced truncal-abdominal body fat distribution (waist hip ratio, WHR) and were hyperinsulinaemic, compared with the obese controls. All the women exhibited blood glucose levels (< 2 mmol/l) well below the threshold for the hormonal counterregulatory response and for the appearance of clinical symptoms. The non-obese women with PCOS showed a greater increase in serum concentrations of GH than the lean controls. The obese women with PCOS exhibited blunted responses of noradrenaline and NPY, but similar increases of adrenaline and CGA, compared with the obese controls. They also showed a lower symptom score during hypoglycaemia. The response of noradrenaline to hypoglycaemia correlated inversely with fasting insulin levels in the women with PCOS. Among all the obese women (PCOS and controls pooled) basal levels of noradrenaline correlated inversely with the WHR.. All the women with PCOS, independent of BMI, body fat distribution and insulin levels, showed preserved counterregulatory responses to hypoglycaemia. The reduced plasma levels of noradrenaline and the lower perception of hypoglycaemic symptoms in the obese women with PCOS could both reflect a lower activation of the sympathetic nervous system. This aberration seems related to truncal-abdominal obesity and hyperinsulinaemia. The finding of an increased response of GH in the lean women with PCOS could support previous suggestions of an altered activity of the GH/IGF-I system in these women.

Topics: Adult; Body Mass Index; C-Peptide; Chromogranin A; Chromogranins; Cross-Sectional Studies; Female; Growth Hormone; Humans; Hypoglycemia; Insulin; Neuropeptide Y; Norepinephrine; Obesity; Polycystic Ovary Syndrome; Prospective Studies

Insulin mediators (inositol phosphoglycans) have been shown to mimic insulin action in vitro and in intact mammals, but it is not known which mediator is involved in insulin action under physiological conditions, nor is it known whether insulin resistance alters the mediator profile under such conditions. We therefore investigated the effects of glucose ingestion on changes in the bioactivity of serum inositol phosphoglycan-like substances (IPG) in healthy men and insulin resistant (obese, non-insulin-dependent diabetic) men. Two classes of mediators were partially purified from serum before and after glucose ingestion. The first was eluted from an anion exchange resin with HCl pH 2.0, and bioactivity was determined by activation of pyruvate dehydrogenase in vitro. The second was eluted with HCl pH 1.3, and bioactivity was determined by inhibition of cyclic AMP-dependent protein kinase. In healthy men, the bioactivity of the pH 1.3 IPG was not altered by glucose ingestion, whereas bioactivity of the pH 2.0 IPG increased to approximately 120% of the pre-glucose ingestion value at 60-240 min post-glucose ingestion (p < 0.05 vs pre-glucose). There was no change in either IPG after glucose ingestion in the insulin-resistant group. These data suggest that the pH 2.0 IPG plays an important role in mediating insulin's effect on peripheral glucose utilization in man under physiological conditions. The data further show, for the first time, a defective change in the bioactivity of an insulin mediator isolated from insulin-resistant humans after hyperinsulinaemia, suggesting that inadequate generation/release of IPGs is associated with insulin resistance.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Glucose; Humans; Inositol Phosphates; Insulin; Insulin Antagonists; Insulin Resistance; Kinetics; Male; Middle Aged; Myocardium; Obesity; Polysaccharides; Pyruvate Dehydrogenase Complex; Reference Values; Swine; Time Factors

To investigate the impact of predominantly upper body fat localisation on the hormonal and metabolic profile in obese, infertile women.. Prospective observational study of premenopausal women with obesity, infertility and menstrual dysfunction.. Department of Endocrinology and Reproduction of the University Hospital of Obstetrics and Gynaecology of Heidelberg.. Eighteen women with android type obesity (waist-hip-ratio = WHR > 0.85, group 1) and 22 women with gynoid type obesity (WHR < or = 0.85, group 2) in a group of 58 premenopausal obese women (median age 28 y) with infertility. Twenty-nine women took part in a weight reducing program lasting 32 +/- 14 (mean +/- s.d.) weeks.. BMI, WHR and blood pressure. Plasma lipids and liver enzymes. Blood glucose, insulin, C-peptide and different steroid and pituitary hormones during oral glucose loading.. In the total group of 58 obese women, WHR was directly correlated to plasma triglycerides, AST, ALT and cholesterol/HDL-cholesterol-ratio. WHR correlated inversely with HDL-cholesterol. Insulin resistance was greater with increasing WHR. Systolic blood pressure, glucose, insulin, C-peptide, triglycerides, cholesterol/HDL-cholesterol-ratio, aspartate (AST) and alanine aminotransferase (ALT) were significantly greater in group 1. Group 2 had greater HDL-cholesterol levels. One subject in group 1, five women in group 2 conceived spontaneously after weight reduction.. Determination of the WHR is a simple measurement to identify obese patients who are at a greater risk of developing the metabolic syndrome. WHR is important in preventive medicine, as typical metabolic profiles are already present in young women before clinical manifestation. Women with android obesity seem to be more prone to develop menstrual irregularity and infertility. The hyperinsulinaemia may be the pathway.

Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Blood Glucose; Blood Pressure; Body Constitution; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Female; Hormones; Humans; Infertility, Female; Insulin; Menstruation Disturbances; Obesity; Pregnancy; Premenopause; Prospective Studies; Triglycerides

To investigate whether fasting hyperinsulinemia is associated with a clustering of cardiovascular disease (CVD) risk factors, manifesting as the insulin resistance syndrome (IRS), in a population of native Hawaiians.. A total of 574 native Hawaiians > or = 30 years of age were examined for blood pressure, waist-to-hip ratio (WHR), BMI, oral glucose tolerance, and fasting lipid, insulin, and C-peptide concentrations. All statistical analyses (n = 384) excluded 190 individuals who had NIDDM or who were taking hypertension medication. Using logistic regression analysis, fasting insulin and C-peptide levels were compared with CVD risk factors (glucose intolerance, hypertension, central adiposity, elevated triglyceride levels, and low HDL cholesterol levels) after adjusting for age and obesity.. Sixty-six percent of native Hawaiians were overweight or obese, and 70% were found to have central adiposity. Fasting insulin concentrations were correlated with BMI, WHR, blood pressure, and triglyceride, HDL cholesterol, and glucose concentrations. Fasting insulin was also significantly associated with an increasing number of CVD risk factors in each participant (P < 0.001). Fasting insulin and C-peptide concentrations were independently associated with glucose intolerance, high triglyceride levels, and low HDL cholesterol levels. However, only fasting C-peptide concentrations were independently associated with hypertension and central adiposity. Apparent differences in the correlates of fasting insulin and C-peptide may be related to multiple factors and warrant further evaluation.. This study provides cross-sectional data confirming the existence of the IRS in native Hawaiians. However, further longitudinal studies are needed to examine the relationship of insulin resistance and/or surrogate markers to increased rates of NIDDM and CVD mortality in native Hawaiians.

Topics: Adult; Asian; Body Constitution; C-Peptide; Cardiovascular Diseases; Cross-Sectional Studies; Fasting; Female; Hawaii; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Logistic Models; Male; Middle Aged; Obesity; Odds Ratio; Prevalence; Risk Factors; Sex Characteristics; Syndrome

Elevated insulin levels may explain part of the increased risk of endometrial cancer observed in obese postmenopausal women. Circulating sex hormones and fasting C-peptide levels were measured in sera obtained from 165 postmenopausal endometrial cancer cases accrued between June 1, 1987, and May 15, 1990, from hospitals in Chicago, Illinois; Hershey, Pennsylvania; Irvine and Long Beach, California; Minneapolis, Minnesota; and Winston-Salem, North Carolina, and 180 community and hysterectomy controls. Women with a personal history of diabetes were excluded. Among controls, C-peptide was positively correlated with body mass index (BMI) ((r = 0.44), waist-to-thigh circumference ratio ((r = 0.24), estrone ((r = 0.18), and estradiol ((r = 0.28) (albumin-bound (r = 0.45), and free (r = 0.37)) and negatively correlated with sex hormone-binding globulin (r = -0.48). In age-adjusted analyses, the odds ratios and 95% confidence intervals for tertiles of C-peptide and endometrial cancer were, from lowest to highest: 1.0 (reference), 0.78 (95% confidence interval (CI) 0.43-1.4), and 2.2 (95% CI 1.3-3.7). Further adjustment for BMI substantially attenuated the odds ratios for the highest tertile of C-peptide (odds ratio = 1.2, 95% CI 0.63-2.1), and adjustment for body mass index and other risk factors for endometrial cancer eliminated the association (odds ratio = 1.0, 95% CI 0.55-2.0). In contrast, adjustment for C-peptide had little influence on the magnitude of the positive associations between body mass index (odds ratio for highest vs. lowest tertile, without and with adjustment for C-peptide = 4.1 (95% CI 2.3-7.5) and 3.7 (95% CI 1.9-7.1), respectively) or several steroid hormones and endometrial cancer. These data are not consistent with the hypothesis that the effect of obesity on endometrial cancer risk is mediated through high insulin levels.

Topics: Adult; Age Factors; Aged; Body Constitution; Body Mass Index; C-Peptide; Cholesterol; Contraceptives, Oral, Hormonal; Endometrial Neoplasms; Estrogen Replacement Therapy; Female; Gonadal Steroid Hormones; Humans; Menarche; Middle Aged; Obesity; Odds Ratio; Parity; Risk Factors

Topics: Adult; Alkaline Phosphatase; Analysis of Variance; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Intestines; Isoenzymes; Obesity

To examine the impact of gestational diabetes mellitus(GDM) on perinatal outcome in a setting where influences of maternal age and obesity would be minimal.. A case-control study was done to compare the outcome of pregnancy in 65 women with GDM and 153 women with normal carbohydrate metabolism matched for age, height, and prepregnancy weight.. The frequencies of preeclampsia and primary cesarean sections were higher and delivery was earlier in pregnancies complicated by GDM. Birth weight, symmetry index, and chest circumference were greater, and macrosomia and need for phototherapy were more common in offspring of mothers with GDM. Cord-serum C-peptide and insulin concentrations were higher in the infants of mothers with GDM and were strongly correlated with birth weight and symmetry index. However, maternal age, prepregnancy weight, and prepregnancy BMI were not correlated with birth weight. Postprandial glucose levels during the first 2 weeks after diagnosis of GDM had associations with the infants' birth weight, symmetry index, and cord insulin concentration in the diet-treated patients with GDM.. Antepartum maternal glucose metabolism was significantly associated with fetal hyperinsulinemia and excessive fetal growth in relatively nonobese Korean women. These findings support a direct role for metabolic factors in the adverse outcomes in pregnancies complicated by GDM.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Case-Control Studies; Cesarean Section; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Gestational Age; Humans; Infant, Newborn; Jaundice, Neonatal; Korea; Maternal Age; Morbidity; Obesity; Parity; Phototherapy; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Regression Analysis

Recently, a gene encoding a novel human uncoupling protein, designated UCP2, was discovered. The murine UCP2 was mapped to a region on mouse chromosome 7 which in several models has been shown to be linked to obesity and hyperinsulinaemia. Single strand conformation polymorphism (SSCP) analysis and direct sequencing of the coding region of the UCP2 gene in 35 obese Caucasian NIDDM patients of Danish ancestry revealed one nucleotide substitution, replacing an alanine with a valine at codon 55. The amino acid polymorphism was present in 24 of the 35 (69%) examined subjects. The allelic frequency of the A/V55 variant was 48.3% (95% CI: 42.5-54.1%) among 144 subjects with juvenile onset obesity, 45.6% (40.5-50.7%) among 182 subjects randomly selected at the draft board examination, and 45.5% (37.1-53.9%) among lean control subjects selected from the same study cohort. Within these cohorts there were no differences in BMI values at different ages among wild-type carriers and A/V55 carriers. In a population-based sample of 369 young healthy Caucasians the variant showed no association with alterations in BMI, waist-to-hip ratio, fat mass or weight gain during childhood or adolescence. The A/V55 polymorphism was not related to alterations in fasting values of serum insulin and C-peptide or to an impaired insulin sensitivity index. We conclude that genetic variability in the human UCP2 gene is not a common factor contributing to NIDDM in obese Danish Caucasian subjects and the common A/V55 amino acid polymorphism of the gene is not implicated in the pathogenesis of juvenile or maturity onset obesity or insulin resistance in Caucasians.

Topics: Adult; Age of Onset; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Genotype; Humans; Insulin; Insulin Resistance; Ion Channels; Male; Membrane Transport Proteins; Middle Aged; Mitochondrial Proteins; Mutation; Obesity; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Proteins; Uncoupling Protein 2; White People

We evaluated the influence of family history of hypertension on insulin sensitivity in lean and obese hypertensive subjects (H): 40 lean [body mass index (BMI) < or = 25 kg m-2] H with normotensive parents (F-), 50 lean H with one or two parents hypertensive (F+), 30 obese HF- (BMI > or = 30 kg m-2) and 35 obese HF+. The four groups were comparable in terms of age, sex and ambulatory blood pressure values. We evaluated glucose, insulin and C-peptide before and 30, 60, 90 and 120 min after an oral glucose load, insulin sensitivity index (ISI, fasting glucose/insulin ratio), fasting insulin/C-peptide ratio (I/Cp). Glucose, fasting and during test, and I/Cp were similar among the four groups; insulin and C-peptide, fasting and stimulated, were significantly higher and ISI lower in obese H than in lean H; at similar BMI, insulin and C-peptide were significantly higher in F+ than in F-. Insulin directly correlated with night-time blood pressure only in lean HF-. The correlation between insulin and BMI was significantly closer in F-than in F+. In conclusion, family history of hypertension appears to play a relevant role in insulin sensitivity in hypertensive subjects also in the presence of obesity.

Topics: Adult; Aging; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Female; Humans; Hypertension; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Regression Analysis; Sex Characteristics

The aim of this study was to evaluate the impact of reduced peripheral insulin sensitivity, beta cell hypersecretion and reduced hepatic insulin clearance in the hyper-insulinaemia of lean and obese PCOS patients. A total of 35 women with polycystic ovary syndrome (PCOS) and 10 lean normo-ovulatory controls underwent an oral glucose tolerance test and an euglycaemic-hyper-insulinaemic clamp study. PCOS patients were classified into four groups according to their BMI and insulin secretion (normo-lean; normo-obese; hyper-lean; hyper-obese), and results were compared between groups and with the controls. All the PCOS groups showed significantly higher insulin secretion than controls; there were no differences in insulin response to glucose load between lean and obese normo- and hyper-insulinaemic patients. Secretion of c-peptide was greater in PCOS groups than controls. All the hyper-insulinaemic PCOS patients had lower values of hepatic insulin clearance, independent of BMI, when compared either with controls (P < 0.001) or with PCOS normo-insulinaemic women (P < 0.01). Normo- and hyper-insulinaemic obese patients had similar total body glucose utilization (M value), which was lower than in lean PCOS subjects and controls. Our results suggest that evaluation of insulin resistance alone does not fully characterize the PCOS population; differences in liver metabolism of insulin are present in obese insulin resistant subjects and in lean patients with normal insulin sensitivity when divided into normo- and hyper-insulinaemic subgroups. Insulin resistance and hyper-insulinaemia may represent two distinct features of the insulin disorder in PCOS: the former appear to reflect the presence of obesity, while the latter may be a primary feature of PCOS.

Topics: Adolescent; Adult; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Liver; Obesity; Polycystic Ovary Syndrome

Studies of GH secretion in patients with non-insulin dependent diabetes mellitus (NIDDM) have produced conflicting results. We aimed to differentiate the effects of obesity and metabolic control on pulsatile GH secretion in patients with NIDDM.. Blood sampling every 15 min from 22.00 hours to 08.00 hours after a fasting period of at least 3 h.. 13 male NIDDM patients, 9 healthy control subjects matched for age and BMI, and 6 lean subjects matched for age.. Measurement of GH by a novel ultrasensitive chemiluminescence assay. Analysis of concentration vs time profiles by a multiparameter deconvolution technique.. GH burst frequency was increased in the NIDDM (0.82 +/- 0.28 h-1) compared with both control groups (lean: 0.6 +/- 0.11; obese: 0.56 +/- 0.19). GH burst mass was decreased in patients (1.57 +/- 0.98 micrograms/l.min) and in obese controls (1.46 +/- 1.44) compared to lean controls (3.71 +/- 3.88). These differences resulted in a significantly higher nocturnal pulsatile GH secretion rate in the lean compared to the obese controls, whereas in the patient group enhanced GH burst frequency compensated for reduced burst mass. The characteristics of GH secretion were not related to nocturnal or early morning blood glucose concentrations. However, GH secretion rate was correlated positively with HbA1c (r = 0.57; P = 0.04), and negatively with plasma C peptide concentrations.. The specific increase in GH burst frequency previously described in insulin-dependent diabetes mellitus is also present in NIDDM. However, GH hypersecretion does not occur because GH burst mass is reduced in proportion to the degree of obesity. The effect of diabetes on the hypothalamic control of GH release appears to be determined by the quality of long-term glycaemic control.

Topics: Analysis of Variance; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Growth Hormone; Humans; Male; Middle Aged; Obesity; Secretory Rate; Statistics, Nonparametric

The majority (> 80%) of patients with non insulin dependent diabetes mellitus (NIDDM) present in Europe and America are obese. In developing countries like India, most NIDDM (> 60%) are non-obese and many are actually lean with a body mass index (BMI) of < 18.5 and are referred to as 'lean NIDDM'. This paper compares the clinical profile of a cohort of 347 lean NIDDM, with a group of 6274 NIDDM of ideal body weight (IBW) and 3252 obese NIDDM attending a diabetes centre at Madras in South India. The lean NIDDM who constituted 3.5% of all NIDDM patients seen at our centre, had more severe diabetes and an increased prevalence of retinopathy (both background and proliferative), nephropathy and neuropathy. Although a larger percentage of the lean NIDDM patients were treated with insulin, 47% of the males and 53% of the females were still on oral hypoglycaemic agents even after a mean duration of diabetes of 9.2 +/- 8.1 years. Studies of GAD antibodies, islet cell antibodies (ICA) and fasting and stimulated C-peptide estimations done in a small subgroup of the lean NIDDM showed that they were distinct from IDDM patients. More studies are needed on metabolic, hormonal and immunological profile of lean NIDDM seen in developing countries like India.

Topics: Adult; Autoantibodies; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Cohort Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diastole; Dose-Response Relationship, Drug; Fasting; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Hypoglycemic Agents; India; Insulin; Islets of Langerhans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Obesity; Postprandial Period; Smoking; Systole; Triglycerides

To examine the relationships between pituitary-adrenal cortical (PA) function, abdominal obesity, hyperinsulinaemia, and dyslipidaemia.. A prospective study.. Helsinki University Central Hospital, Finland.. Seventy-one healthy males aged 30-55 years.. Insulin sensitivity was assessed by the oral glucose tolerance test (OGTT). Basal PA activity was examined by measuring urinary and serum concentrations of hormones, followed by dexamethasone suppression and corticotrophin (ACTH) stimulation tests to determine functional PA activity.. The means of waist-to-hip ratio (WHR), body-mass index (BMI), HDL-cholesterol and triglyceride levels, and insulin and C-peptide measurements during the OGTT were significantly different across the tertiles for insulin:glucose ratio. The ratio of 12-h urinary cortisol excretion to BMI, preceding the OGTT, and the mean basal cortisol level during the OGTT were decreased, while the net increments of cortisol and 17-hydroxyprogesterone (17-OHP) from 0 to 60 min, as well as the ratio of net 17-OHP to 11-deoxycortisol increments, after ACTH, were elevated in the upper compared with the lower tertile. The mean cortisol during the OGTT, and the ratio of urinary cortisol to BMI were negatively related, while absolute DHEA and cortisol responses to ACTH were positively related to fasting and mean insulin levels. Hormonal variables, WHR, insulin, and triglycerides were successfully integrated into a tentative mathematical model by the use of covariance structure (path) analyses.. Several alterations in the PA function, suggestive of decreased 21-hydroxylase activity, mild cortisol deficiency and slight adrenal hyperplasia, are associated with abdominal obesity which, in turn, appears to be an important prelude to insulin resistance and dyslipidaemia.

Topics: 17-alpha-Hydroxyprogesterone; Abdomen; Adrenal Cortex; Adult; Body Constitution; Body Mass Index; C-Peptide; Cholesterol, HDL; Dehydroepiandrosterone; Glucose Tolerance Test; Humans; Hydrocortisone; Hyperinsulinism; Hyperlipidemias; Insulin; Life Style; Male; Middle Aged; Obesity; Pituitary-Adrenal System; Prospective Studies; Risk Factors; Triglycerides

The involvement of the opioid system in human obesity has been demonstrated, but whether the abnormalities in the endorphinergic system play a primary role in overfeeding and weight gain or represent a simple biochemical feature is still unclear. The objectives of this study were to investigate the effects of both physiological and pharmacological plasma beta-endorphin levels on some metabolic and hormonal parameters in a normal weight, but prone to obesity, young population consisting of first degree relatives of obese subjects and in body mass index-, sex, and age- matched control subjects without a family history of obesity. Each subject underwent a 1-h infusion of synthetic human beta-endorphin at a constant rate of 4.5 ng/kg.min (low rate), then after a 1-week interval, at a rate of 500 micrograms/h (high rate). Under basal conditions, there was no significant difference in plasma glucose and pancreatic hormones (insulin, C peptide, and glucagon) between the two groups, except for plasma beta-endorphin levels, which were significantly (P < 0.01) higher in relatives of obese individuals. The low rate of beta-endorphin infusion induced physiological elevations of plasma opioid levels in both groups; no significant change in plasma glucose and pancreatic products in control subjects; and a significant (at least P < 0.05) rise in plasma insulin, C peptide, and glucagon concentrations in relatives of the obese. The high rate of beta-endorphin infusion produced pharmacological elevations of opioid plasma levels in both groups; significant (at least P < 0.05) increments in plasma glucose and glucagon levels and no appreciable modification of plasma insulin and C peptide levels in the control group; and a significant (at least P < 0.05) positive response of plasma glucose, insulin, C peptide, and glucagon levels in relatives of obese subjects. These findings suggest that 1) opioid peptides at least in part play a primary, rather than secondary, role in some metabolic events of obesity; and 2) both physiological and pharmacological plasma levels of beta-endorphin are able to provoke marked islet hormone release in the early phase of human obesity.

Topics: Adult; beta-Endorphin; Blood Glucose; C-Peptide; Female; Glucagon; Humans; Insulin; Kinetics; Male; Obesity; Opioid Peptides

A model describing beta-cell secretion during an oral glucose tolerance test (OGTT) is introduced. The aim was to quantify beta-cell activity in different pathologies by analyzing peripheral concentration data of insulin, C-peptide, and islet amyloid polypeptide (IAPP). Insulin appearance in periphery is given by the fraction of C-peptide secretion, CPS(t), which accounts for liver degradation. A novelty of this study is the inclusion of IAPP delivery assumed proportional to CPS(t). Although IAPP fractional clearance is estimated in every subject, the clearances of insulin and C-peptide are assigned from a wide set of previous independent studies. Sensitivity analysis was performed to quantify the "error" in the estimated variables due to these assignments. All parameters relating to beta-cell secretion increased in the glucose-intolerant states [integrated CPS(t)=56 +/- 8 nmol/l in 180 min vs. 32 +/- 3 of controls, P<0.05; total IAPP delivery= 83 +/- 21 pmol/l in 180 min vs. 41 +/- 6, P<0.05]. Elevated plasma IAPP concentration of the patients was due to augmented secretion since IAPP clearance was found to be even slightly greater than in controls, (0.053 +/- 0.011 vs. 0.034 +/- 0.004 min-1) and markedly lower than that of insulin (0.14 +/- 0.02, P<0.01). In conclusion, the model introduced here allows the characterization of beta-cell secretory parameters during a simple test such as OGTT.

Topics: Amyloid; Blood Glucose; C-Peptide; Dexamethasone; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypertension; Insulin; Insulin Secretion; Islet Amyloid Polypeptide; Islets of Langerhans; Kinetics; Liver; Mathematics; Models, Biological; Obesity; Reference Values; Regression Analysis; Sensitivity and Specificity; Time Factors

Increased resting energy expenditure (REE) and a blunted thermic effect of glucose (TEF) have been reported in obese subjects with non-insulin-dependent diabetes mellitus (NIDDM). I questioned whether the abnormal REE and TEF would be corrected by normalizing glycemia with insulin or a very-low-energy diet (VLED). Three male and four female obese subjects with NIDDM [weighing 108 +/- 6 kg and with body mass index (in kg/m2) of 39 +/- 2] received a weight-maintaing formula diet containing 95 g protein/d for 15 d then a 1.7-MJ, 93-g-protein VLED for 27 d. Insulin was given from days 1 to 8 in doses sufficient to normalize glycemia. REE was measured weekly and TEF was measured on days 8 and 15 of isoenergetic feeding and 28 d after the VLED by using a ventilated-hood indirect calorimeter. Weight decreased 9.8 +/- 1 kg during the VLED. REE was 3% lower with insulin treatment than during hyperglycemia (7878 +/- 364 compared with 8125 +/- 381 kJ/d, P = 0.002). REE decreased by 20% to 6494 +/- 280 kJ/d by week 4 of the VLED. After 112 g oral glucose, increments in energy expenditure were significantly greater during isoenergetic feeding with insulin than without (7.5 +/- 1.3% compared with 4.3 +/- 0.9% above REE) and after the VLED (10.5 +/- 1.0% above REE, P < 0.05). Plasma glucose excursions were greatest without exogenous insulin (peak 21.5 +/- 1.8 mmol/L at 120 min, 16.3 +/- 1.9 mmol/L at 225 min). Plasma fatty acid excursions were the lowest with insulin treatment. The integrated plasma glucose and fatty acid responses above baseline did not differ among studies; the integrated insulin and C-peptide responses were greater after the VLED. Cumulative nonoxidative glucose disposal (stored glucose) was higher with insulin therapy than without (52 +/- 6 compared with 35 +/- 7 g/210 min, P < 0.05) and increased significantly to 66 +/- 6 g after the VLED (compared with the isoenergetic diet without insulin). TEF correlated significantly with integrated C-peptide and insulin responses. The percentage increase in TEF with euglycemia (with insulin and VLED) correlated with the percentage increase in stored glucose (P < 0.05). The greater TEF was associated with a greater insulin response, which was probably responsible for the greater stored glucose.

Topics: Adult; Basal Metabolism; Blood Glucose; Body Temperature Regulation; C-Peptide; Calorimetry, Indirect; Diabetes Mellitus; Diabetes Mellitus, Type 2; Energy Intake; Energy Metabolism; Female; Glucose Tolerance Test; Humans; Insulin; Kinetics; Male; Middle Aged; Obesity

To study the effects of a very low calorie diet (VLCD) on glucose and lipid metabolism in obese subjects, in particular, the effects on insulin sensitivity and the activities of the key enzymes of glucose disposal, glycogen synthase (GS) and the pyruvate dehydrogenase complex (PDHC).. Clinical dietary intervention study (1.67 MJ (400 kcal)/day) until weight loss of > 10%.. 11 (seven male, four female) non-diabetic, obese subjects (age: 27-62 y; BMI: 40.5 +/- 1.4 kg/m2).. Whole body glucose disposal (by euglycemic hyperinsulinemic clamp), respiratory quotient (RQ), resting energy expenditure (REE), glucose and lipid oxidation (by indirect calorimetry), insulin-stimulated PDHC and GS activity (in muscle biopsies) both before and immediately after VLCD (i.e. while still in a hypocaloric state), serum hormone and metabolite levels throughout the dietary period.. Weight loss was accompanied by reduced insulin and elevated NEFA levels, improved insulin sensitivity due to increased nonoxidative glycolysis with no increase in PDHC or GS activities. The rate of weight loss was inversely related to the initial RQ. PDHCa was strongly age-related.. A low RQ may be used as a predictor of the efficacy of VLCD treatment and that while VLCD improves nonoxidative glycolytic flux, changes in oxidative glucose disposal and muscle glucose storage are prevented by high NEFA availability during this catabolic phase of dietary intervention.

Topics: Adult; Anthropometry; Blood Glucose; Blood Pressure; C-Peptide; Diet, Reducing; Energy Intake; Energy Metabolism; Fasting; Fatty Acids, Nonesterified; Female; Glycogen Synthase; Humans; Insulin; Lipids; Male; Middle Aged; Muscles; Obesity; Pyruvate Dehydrogenase Complex; Weight Loss

Insulin resistance and hyperinsulinemia occur more frequently in subjects with greater visceral adiposity, but it is not known whether these metabolic abnormalities precede or follow visceral fat accumulation. We prospectively studied the development of visceral adiposity in relation to fasting and stimulated insulin and C-peptide levels. We followed 137 nondiabetic, second-generation Japanese-American men for changes in visceral adiposity over 5 years. Intra-abdominal fat (IAF) area (square centimeters) was measured at the umbilicus by computed tomography at baseline and after 5 years. Plasma insulin and C-peptide levels were measured after an overnight fast and during an oral glucose tolerance test. Beta-cell function was measured by the insulin secretion ratio (30-0 min plasma insulin difference)/(30-0 min plasma glucose difference). After adjustment for baseline IAF in multiple linear regression models, baseline fasting insulin (coefficient = 0.241, P = 0.048) and C-peptide (coefficient = 38.538, P < 0.001) levels were positively correlated, while the baseline insulin secretion ratio was negatively correlated with IAF change (coefficient = -0.099, P = 0.027). With IAF difference coded as a dichotomous variable (> 0 cm2 vs. < or = 0 cm2), the highest versus lowest tertile of baseline fasting insulin (odds ratio [OR] = 3.0, 95% CI 1.0-9.7) and fasting C-peptide (OR = 8.1, 95% CI 2.4-26.8) levels and the lowest versus highest tertile of the insulin secretion ratio (OR = 3.3, 95% CI 1.0-10.0) were associated with higher odds of IAF gain. Greater insulin resistance and reduced insulin secretion precede visceral fat accumulation in nondiabetic Japanese-American men.

Topics: Abdomen; Adipose Tissue; C-Peptide; Fasting; Follow-Up Studies; Humans; Insulin; Insulin Secretion; Japan; Male; Middle Aged; Obesity; Prospective Studies; Regression Analysis

Recently, a missense mutation replacing tryptophan with arginine at codon 64 of the beta 3-adrenergic receptor gene was shown to be associated with insulin resistance in nondiabetic subjects and to an earlier onset of NIDDM in Pima Indians. We studied whether the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene in a cohort of young healthy Danes was associated with high birth weight, accelerated weight gain during childhood and adolescence, present obesity, or impaired insulin sensitivity. The protocol included 380 unrelated white subjects in whom insulin sensitivity and secretion were measured during a combined intravenous glucose and tolbutamide tolerance test. A number of biochemical and anthropometric characteristics were determined for each subject. The subjects were genotyped for the codon 64 polymorphism by applying polymerase chain reaction restriction fragment-length polymorphism screening with the use of endonuclease BstN1. The allelic frequency of the mutated allele was 7% (95% CI: 5-10%), and it was similar in obese and nonobese subjects. The beta 3-adrenergic receptor gene variant was not related to birth weight or weight gain during childhood or adolescence. In its heterozygous form, the gene variant was not associated with an altered insulin sensitivity index (SI) or other features of the insulin resistance syndrome (BMI, blood pressure, fasting serum lipid levels, or fasting serum fibrinolytic variables). Three homozygous carriers of the polymorphism were identified, and each had a significantly higher BMI (27.4 +/- 1.3 vs. 23.5 +/- 3.7 kg/m2 [mean +/- SD]; P = 0.032), lower SI [4.9 +/- 2.9 vs. 15.4 +/- 9.0 10(-5) x (min x pmol/l)-1; P = 0.013], and higher fasting serum C-peptide (730 +/- 155 vs. 471 +/- 158 pmol/l; P = 0.016) than the wild-type carriers. The homozygous carriers also had significantly higher levels of fasting serum triglyceride (P = 0.042) and serum LDL cholesterol (P = 0.013). When adjustments were made for age, sex, BMI, and VO2max in a multiple regression analysis, a significantly negative association was found between homozygosity for the codon 64 variant and the SI (P = 0.009). We conclude that in young healthy Danes, the homozygous form but not the heterozygous form of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor may be associated with obesity and, independent of BMI, with a low SI. Since only three homozygous carriers were identified among 380 subjects, the results mu

Topics: Adult; Birth Weight; Body Weight; C-Peptide; Denmark; Female; Gene Frequency; Glucose; Heterozygote; Homozygote; Humans; Insulin; Insulin Resistance; Male; Obesity; Point Mutation; Polymorphism, Genetic; Receptors, Adrenergic, beta

The purpose of the present study was to characterize secondary failure (SF) to oral hypoglycaemic agents by assessment of threshold insulin-secretion values in relation to diabetes duration. One hundred and forty-seven nonobese diabetic patients, 35 to 80 years of age, with disease duration ranging from 1 to 36 years, were studied. Beta-cell function was assessed by meal-stimulated (delta CP) and glucagon-stimulated (delta aCP) C-peptide concentrations. The quality of glycaemic control was considered good if mean daily blood glucose was less than 8.5 mmol/l. One group with good (NOb-GC) and another with poor control (NOb-SF) were established. Mean daily glycaemia was negatively correlated with delta CP or delta aCP (r = -0.703 vs r = -0.696; p < 0.001) more than with basal C-peptide (r = -0.453; p < 0.001). A close positive correlation between meal-stimulated (delta CP) and glucagon-stimulated (delta aCP) C-peptide concentrations was observed (r = 0.869; p < 0.001). Residual beta-cell function (delta CP and delta aCP) was significantly correlated with known disease duration in both groups (GC: r = -0.693 and SF: r = -0.680; p < 0.001). Nonobese patients with SF showed early impaired secretion during the first years of disease, meal-stimulated delta CP being below 0.350 mmol/l. The most useful result in this study was the incremental value of C-peptide (delta CP), which showed minimal overlapping between the two groups. Basal, postprandial or postglucagon absolute values were less discriminating. The daily profile allowed measurement of both glycaemic control and insulin production after a regular meal. The validity of this measurement was confirmed by the strong correlation between meal-stimulated and glucagon-stimulated delta C-peptide concentrations. This parameter is a useful physiological marker of secondary failure.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Disease Progression; Female; Food; Glucagon; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Islets of Langerhans; Linear Models; Male; Middle Aged; Obesity; Stimulation, Chemical; Treatment Outcome

To determine the secretion of insulin, C-peptide, and proinsulin after oral glucose loading in healthy elderly subjects compared with middle-aged subjects with and without obesity and with NIDDM.. Subjects fell into four groups: nonobese middle-aged normal control subjects (CNT group; n = 38, 40-64 years old); obese normal subjects (OB group; n = 18, 40-64 years old); nonobese NIDDM subjects (NIDDM group; n = 28, 40-64 years old); and nonobese elderly subjects (OL group; n = 17, 65-92 years old). Insulin, C-peptide, and proinsulin were determined by radioimmunoassay in plasma samples taken at 0, 30, 60, and 120 min during a 75-g oral glucose tolerance test (OGTT).. There were no differences in plasma glucose during the OGTT among the three nondiabetic groups. Hyperinsulinemia was significant in the OB and NIDDM groups but not in the OL group. On the other hand, absolute hyperproinsulinemia was significant in the OL and NIDDM groups compared with the CNT group. Increased proinsulin was rather dominant in the OL group, especially late after glucose loading. Molar ratios of proinsulin to insulin or C-peptide thus were significantly higher in the OL and NIDDM groups.. Alteration of pancreatic beta-cell function independent of that seen with NIDDM occurred in relation to aging. This may be a predisposing factor to the development of impaired glucose tolerance or NIDDM in elderly subjects, that is, independent of obesity.

Topics: Adult; Aged; Aged, 80 and over; Aging; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Middle Aged; Obesity; Proinsulin; Reference Values

Topics: Adolescent; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Coma; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Insulin; Japan; Male; Obesity

To test the hypothesis that hyperinsulinemia and glucose intolerance are present at an early age in australian aborigines and can be used to predict the eventual development of NIDDM.. Baseline anthropometric, pubertal stage, and blood pressure data were collected for 100 Australian aboriginal children and adolescents in 1989. Plasma concentrations of glucose, insulin, C-peptide, triglycerides, and LDL, HDL, and total cholesterol were measured before and during an oral glucose tolerance test. All measurements were repeated in 74 individuals from the original study population in 1994. Results were compared among hyperinsulinemic and normoinsulinemic subjects, and subjects with normal or abnormal glucose tolerance.. The percentage of subjects who were overweight increased from 2.7% at baseline to 17.6% 5 years later. At a mean age of 18.5 years, 8.1% of the population had impaired glucose tolerance (IGT), 2.7% had diabetes, and 21.6% had elevated cholesterol concentrations in plasma. Dyslipidemia was particularly prevalent among male subjects in the population: 34.4% had elevated plasma cholesterol and 21.9% had elevated LDL cholesterol values. Of the eight subjects who had diabetes or IGT in 1994, four were classified as hyperinsulinemic in 1989 and four were not.. The major finding of this study is the high prevalence of risk factors for NIDDM and cardiovascular disease in this population of aboriginal children and adolescents. Abnormalities of carbohydrate and lipid metabolism were well established by late in the second decade of life. Although many subjects had high insulin levels and there was evidence of insulin resistance in the population, hyperinsulinemia did not predict the development of abnormal glucose tolerance 5 years later.

Topics: Adolescent; Anthropometry; Australia; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Child; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; Hyperlipidemias; Insulin; Male; Native Hawaiian or Other Pacific Islander; Obesity; Risk Factors; Sex Characteristics; Sex Factors; Time Factors; Triglycerides

Normal insulin secretion includes oscillations with a period length of 80-150 min which are tightly coupled to glucose oscillations of similar period. To determine whether normal aging is associated with alterations in these ultradian oscillations, eight, modestly overweight, older men (65 +/- 5 years) and eight weight-matched young control subjects (25 +/- 4 years) were studied during 53 h of constant glucose infusion. Blood samples were collected every 20 min and insulin secretion rates were calculated by deconvolution. Ultradian oscillations of glucose and insulin secretion were evident in both groups. Pulse frequency was similar for glucose and insulin secretion, and was not affected by age. The absolute amplitude of the glucose oscillations was similar in both groups but their relative amplitude was slightly dampened in the older adults. Both the absolute and the relative amplitudes of insulin secretory oscillations were markedly reduced in the older subjects. The normal linear increase in the amplitude of insulin oscillations occurring with increasing amplitudes of glucose oscillations was still present in the older adults but analysis of covariance indicated that the slope was significantly lower than in the young control subjects (p < 0.0005), reflecting a decreased responsiveness of the beta cell to glucose changes. The temporal concordance between insulin and glucose oscillations, as estimated by pulse concomitancy and cross-correlation, was also lower in older subjects. The similarities between the alterations in the ultradian oscillations of insulin secretion and glucose in older healthy adults and those occurring in diabetic patients suggest that an impairment of beta-cell function may play a primary role in the deterioration of glucose tolerance in aging.

Topics: Activity Cycles; Adult; Aged; Aging; Blood Glucose; C-Peptide; Humans; Insulin; Insulin Secretion; Male; Obesity; Oscillometry; Reference Values; Regression Analysis

The purpose of this work was to investigate the relationship of gonadotropin levels to body weight and insulin levels in woman with polycystic ovary syndrome (PCOS). Specifically, we wished to test the hypothesis that circulating luteinizing hormone (LH) and insulin levels are different in obese and normal weight patients with PCOS. The basal plasma levels of gonadotropins, estrogens, androgens and sex hormone-binding globulin, the gonadotropin responses to gonadotropin releasing hormone (GnRH) and the insulin and C-peptide responses to a 3-hour oral glucose tolerance test (OGTT) were measured in 19 obese and 19 normal weight patients with PCOS and 7 obese and 8 normal weight ovulatory controls. Data of the patients were evaluated according to body weight (obese vs normal weight) and basal LH (high vs normal). There was no significant difference in basal LH and androgen levels and in the insulin response to oral glucose between obese and normal weight patients with PCOS. Compared to the weight matched controls, both obese and non obese patients showed significantly higher LH responses to GnRH and C-peptide responses to OGTT. When the high LH patients (no = 18) were compared those with normal LH (no = 20), the high LH subjects exhibited significantly higher androstenedione levels. Both obese (no = 10) and normal weight (no = 8) patients with high LH showed significantly greater C-peptide responses to OGTT than obese (no = 9) and non obese (no = 11) patients with normal LH. However, as compared with the weight matched controls, both the high LH and normal LH patients had significantly greater C-peptide responses to OGTT. We conclude that obese and non obese patients with PCOS do not seem to differ in the prevalence of elevated LH levels or in the LH secretory pattern. Insulin resistance, expressed by an enhanced pancreatic sensitivity to oral glucose, is present in both the high LH and the normal LH subjects, even though the PCOS patients with elevated LH tend to be more insulin resistant and hyperandrogenic than the normal LH patients.

Topics: Adult; Androgens; Body Mass Index; Body Weight; C-Peptide; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Humans; Insulin; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin

With the increase of obese children, harmfulness of obesity to their health was studied to lay a basis for formulating corresponding intervention measures. Blood sugar, intelligent quotient (IQ), thyroid function, cardiac and pulmonary function, and index of gonad development were determined in 150 obese children and 150 normal healthy children. Results showed baseline secretion of insulin and C-polypeptide in obese children were significantly higher than that in controls, and thyroid function, total IQ, speech IQ and operation IQ all were relatively lower, cardiac and pulmonary function was significantly lower, and gonad development and maturity took place earlier in the former than in those in the latter. It indicated that there were a lot of risk factors harmful to their health in obese children.

Topics: Adolescent; C-Peptide; Child; Female; Health Status; Humans; Insulin; Male; Obesity; Sampling Studies; Sexual Maturation; Wechsler Scales

To evaluate the prevalence in obese patients of an increased urinary albumin excretion rate (UAER) and the factors involved in this parameter.. Two hundred and seven nondiabetic obese patients with BMI = 34.7 +/- 5.7 (SD) kg/m2. None had proteinuria or a history of nephropathy or uropathy. Fifty-two had moderate hypertension. A control group of 22 lean healthy subjects was also studied.. The UAER was determined from 24-h urine samples by means of immunonephelemetry laser method. Creatinine clearance was calculated. Glycemia and plasma C peptide at fasting and 120 mine after glucose oral administration, HbA1c, serum fructosamine, plasma total cholesterol and triglycerides, HDL and LDL cholesterol were measured. Food intakes were determined by dietary history.. Compared with the control group, the UAER was significantly higher in the obese patients (18.0 +/- 20.1 mg/24 h vs 3.2 +/- 2.8 mg/24 h, P < 0.0001). It was elevated (> 30 mg/24 h) in 25 obese patients (12.1%) and in particular, in 19.2% of the obese patients with hypertension. It was significantly higher in the patients with android or mixed (both android and gynoid) obesity than in those with gynoid obesity (p = 0.050). Log UAER correlated negatively with the duration of hypertension (p = 0.038) and was higher in the patients with familial hypertension than in those without (p = 0.002). Log UAER correlated strongly with log creatinine clearance (p < 0.0001) and fractional albumin clearance (p < 0.0001). It correlated significantly with fasting and 120 min after glucose plasma C peptide concentrations (p = 0.018 and p = 0.046, respectively). Creatinine clearance was significantly higher in the patients with android or mixed obesity than in those with gynoid obesity (p = 0.001). Log creatinine clearance correlated negatively with age (p = 0.046), and log LDL cholesterol (p = 0.025) and positively with log lipid caloric intake (p = 0.014).. These results show the high prevalence of microalbuminuria in nondiabetic obese patients and suggest the involvement of renal hyperfiltration. Microalbuminuria may be an indicator of familial hypertension in obese subjects. Insulin resistance may be involved in the increase in the UAER. Nutritional factors, particularly lipid intake, may contribute to this increase in the UAER via an increase in glomerular hyperfiltration.

Topics: Adult; Albuminuria; Blood Pressure; C-Peptide; Cholesterol; Creatinine; Female; Fructosamine; Glomerular Filtration Rate; Glucose Tolerance Test; Glycated Hemoglobin; Hexosamines; Humans; Hypertension; Linear Models; Male; Middle Aged; Obesity; Prevalence; Time Factors; Triglycerides

To characterize differences in metabolic indices as well as body composition in two ethnic groups.. Eight black and eight white obese urban women were studied.. Eight black and eight white obse (BMI > 34) urban women (BW, WW) were matched for age, BMI, WHR, diet and physical activity and investigated before and after 12 weeks of Dexfenfluramine treatment.. Anthropometric measurements; Post 75 g OGTT, plasma glucose, insulin and C-peptide levels were done. FFA and lactate levels were done at onset. Skinfold thickness with Harpenden calipers, bio-impedance for analyses of body composition and CT scan for assessment of regional adiposity (at onset and after 3 months).. In the postabsorptive state the WW had significantly higher plasma total cholesterol and triglyceride levels and an unfavourable HDL : total cholesterol ratio. Their FFA levels were significantly lower (324 +/- 51 vs 985 +/- 84 mumol/l; p < 0.0001) and their lactate levels were significantly higher (3045 +/- 245 vs 1938 +/- 358 mumol/l; p < 0.001) as compared with the BW. During a 75 g OGTT the BW had significantly higher glucose levels at 1 h (8.6 +/- 0.8 vs 5.1 +/- 0.4 mmol/l; p < 0.005) and 2 h (7.6 +/- 0.6 vs 4.4 +/- 0.3 mmol/l) but not at fasting. In contrast the BW had lower insulin concentrations (fasting: 77 +/- 9 vs 139 +/- 19 pmol/l; p < 0.04 and 1 h 318 +/- 56 vs 624 +/- 75 pmol/l; p < 0.005), and C-peptide concentrations (fasting: 400 +/- 99 vs 1600 +/- 99 pmol/l; p < 0.000 04, 1 h 1400 +/- 433 vs 5966 +/- 333 pmol/l; p < 0.0007 and 2 h 1266 +/- 333 vs 4066 +/- 366 pmol/l; p < 0.0005). CT scan measurements showed that the WW had significantly more visceral fat than the BW (148.5 +/- 2.0 vs 115.5 +/- 6.9 cm2; p < 0.05) but lost less weight during Dexfenfluramine treatment (-4 kg vs -9 kg). Despite this, the WW lost more visceral fat than the BW (-27.3 cm2/-18.5%; p < 0.03 vs -15.5 cm2/-13.2%; p < 0.04). In contrast the BW had a larger reduction in subcutaneous (SC) fat (-13.9% vs -1.7%; p < 0.01), with the greatest reduction in the SC gluteofemoral adipose tissue (widest hip circumference -20.8% vs -0.2%; p < 0.001) and mid-femur region (-13.1% vs -0.7%; p < 0.08).. Weight loss in obese black women is associated with a major reduction in SC fat mass with the most active mobilization of fat tissue occurring in the gluteofemoral area. In contrast the WW had more visceral fat that was more readily mobilized. The difference in adipose tissue distribution and pattern of mobilization was associated with lower plasma insulin, C-peptide and triglyceride concentrations in the BW despite increased FFA and glucose levels. These data suggest that plasma insulin concentrations are important in regulating differences in regional adipose tissue metabolism as well as the serum lipid profile.

Topics: Adipose Tissue; Adult; Anthropometry; Appetite Depressants; Black or African American; Black People; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Cholesterol; Fatty Acids, Nonesterified; Female; Fenfluramine; Humans; Insulin; Lactates; Obesity; Skinfold Thickness; South Africa; Tomography, X-Ray Computed; Triglycerides; Weight Loss; White People

To investigate the rheological properties of RBC in obese subjects and the factors associated with their changes.. Two consecutive studies of non diabetic obese subjects.. Filtration index of RBC using the Hanss hemorheometer, RBC filterability using a cell transit time analyser and RBC aggregation measured on the Myrenne aggregometer.. In both studies an increase in the filtration index of RBC, namely a reduction in their deformability, was found. In the first study the filtration index correlated negatively with hematocrit and positively with plasma C peptide levels. In the second study RBC filterability was also studied by the cell transit time analyzer in which there is no aggregate formation. The RBC transit time was not found to be different in the obese patients and in the controls, but RBC aggregation was increased and correlated significantly with body weight and BMI. RBC aggregation worsened after four days of hypocaloric diet.. (1) obesity, independently of the other cardiovascular risk factors, is associated with significant changes in RBC rheology; (2) these changes are probably related for the most part to plasma factors, possibly via hyperinsulinemia, even if changes in the chemical composition of the RBC membrane are not excluded, (3) RBC aggregation worsens during the first days of a hypocaloric diet; (4) rheological changes in RBC seem to be another component of the insulin resistance syndrome.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Creatinine; Erythrocyte Deformability; Female; Hemorheology; Humans; Hyperinsulinism; Male; Obesity; Uric Acid

Disproportionate hyperproinsulinaemia is a manifestation of the beta-cell dysfunction observed in NIDDM. However, it is unclear when this abnormality develops and whether it predicts the development of the disease. To examine whether changes in proinsulin levels predict the development of NIDDM, baseline measurements of proinsulin and immunoreactive insulin levels were made in 87 second-generation Japanese-American men, a population at high risk for the subsequent development of NIDDM. Subjects were categorized at baseline using WHO criteria as having normal glucose tolerance (NGT; n = 49) or impaired glucose tolerance (IGT; n = 38). After a 5-year follow-up period, subjects were recategorized as having NGT, IGT or NIDDM using the same criteria. During follow-up, 16 subjects developed NIDDM while 71 were NGT or IGT. At baseline, individuals who subsequently developed NIDDM were more obese as measured by intra-abdominal fat area on computed tomography (p = 0.046), had higher fasting glucose (p = 0.0042), 2-h glucose (p = 0.0002), fasting C-peptide (p = 0.0011), fasting proinsulin levels (p = 0.0033), and had disproportionate hyperproinsulinaemia (p = 0.056) when compared to those who remained NGT or IGT after 5 years of follow-up. These findings suggest that alterations in proinsulin levels may also predict the subsequent development of NIDDM.

Topics: Asian; Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Japan; Male; Middle Aged; Obesity; Predictive Value of Tests; Proinsulin; Reference Values; Washington

Earlier we found elevated insulin levels in obese children and adolescents. The present study examines whether alterations in insulin secretion and/or clearance contribute to hyperinsulinemia in obese adolescents.. Fasting circulating insulin and C-peptide concentrations were examined in 1157 adolescents, aged 11-18 y, from a biracial (black/white) community. In this epidemiologic study, plasma C-peptide was used as a noninvasive measure of insulin secretion by beta cells, C-peptide to insulin ratio as an indicator of hepatic insulin extraction, and insulin to glucose ratio as a measure of insulin sensitivity. Body mass index (BMI) was used as an index of obesity, since it is strongly associated with insulin levels and the C-peptide to insulin ratio more so than with measures of skinfolds and percent body fatness.. Obese individuals (BMI > 90th P) had higher levels of plasma insulin (23.7 mu/ml vs 11.7 mu/ml), C-peptide (2.7 ng/ml vs 1.7 ng/ml), and insulin to glucose ratio (0.29 vs 0.15), and lower C-peptide to insulin ratio (0.13 vs 0.16) than non-obese adolescents (all P < 0.001). Elevated C-peptide and decreased C-peptide to insulin ratio were noted in subjects with both obesity and hyperinsulinemia (insulin > 90th P) versus those without these conditions (P < 0.001). Individuals with obesity and low insulin clearance (C-peptide/insulin < 10th P) had 18-fold higher prevalence of hyperinsulinemia versus those without these conditions. Although black adolescents, despite their lower percent body fat, had higher insulin and lower C-peptide and C-peptide to insulin ratio than their white counterparts, BMI related positively to insulin and C-peptide, and inversely with C-peptide to insulin ratio in both races.. These data suggest that both increased insulin secretion and decreased insulin clearance contribute to hyperinsulinema in obese adolescents.

Topics: Adolescent; Black People; Blood Glucose; Body Mass Index; C-Peptide; Child; Female; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Louisiana; Male; Metabolic Clearance Rate; Obesity; White People

In order to study the relationships between obesity, serum uric acid, insulin secretion and insulin resistance in female subjects, we evaluated serum C-peptide and glucose-induced insulin utilization (euglycemic hyperinsulinemic clamp) in 16 obese (8 nonhyperuricemic and 8 hyperuricemic) and 10 nonobese control subjects. Baseline C-peptide levels were significantly higher in hyperuricemic compared to both nonhyperuricemic obese subjects and controls (P < 0.001). M values, a measure of glucose disposal and insulin sensitivity, were significantly lower in hyperuricemic obese compared to nonhyperuricemic obese subjects and controls (P < 0.001) and, for all subjects were inversely correlated with the serum uric acid values (r = -0.821, P < 0.001). In conclusion, in this group of subjects the serum uric acid values were directly related to insulin resistance independently of age, sex, excess body weight, fat distribution and blood pressure.

Topics: Adult; C-Peptide; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Insulin Secretion; Obesity; Uric Acid

To determine the time course of changes in insulin action and secretion that occur early during the development of obesity, we studied children before the onset of puberty. The reason for choosing the prepubertal stage of development is that it is metabolically characterized by both a high sensitivity to insulin and low glucose stimulated insulin responses. Fifteen obese preadolescents (8 male/7 female, age 10 +/- 0.4 years, body mass index (BMI) 31 +/- 1.2 kg/m2 Tanner Stage I) with a duration of obesity of less than 5 years and 10 non-obese preadolescents (6 male/4 female, age 10 +/- 0.4 years, BMI 18 +/- 0.9 kg/m2) matched for gender were studied. In a cross-sectional analysis, we compared responses in obese preadolescents, with those in obese adolescents and obese adults with a longer duration of obesity. The euglycaemic hyperinsulinaemic clamp with 1-13C-glucose (Hot Ginf) and indirect calorimetry were used to quantitate insulin action and the hyperglycaemic clamp used to assess beta-cell function. Insulin-stimulated glucose uptake measured at two physiological levels of hyperinsulinaemia (approximately 180 and 480 pmol) was reduced by 20 and 45% in all three groups of obese compared to non-obese subjects (p < 0.01). Defects in oxidative and non-oxidative glucose metabolism were observed in all three groups of obese subjects at the higher insulin infusion rate. The ability of insulin to inhibit lipid oxidation was impaired in all three obese groups at both levels of hyperinsulinaemia. Increases in basal and glucose-stimulated insulin levels during the hyperglycaemic clamp mirrored the reductions in glucose uptake during the insulin clamp in all obese groups. These results indicate that insulin resistance and hyperinsulinaemia co-exist in preadolescent children with moderate to severe obesity.

Topics: Adolescent; Adult; C-Peptide; Calorimetry, Indirect; Child; Cohort Studies; Cross-Sectional Studies; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Lipid Metabolism; Male; Obesity; Oxidation-Reduction; Time Factors

Topics: Adult; Age of Onset; Body Mass Index; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Insulin; Male; Obesity

The C-peptide suppression test employing the euglycemic hyperinsulinemic clamp technique has been proposed as a useful diagnostic measure for insulinoma. To examine the specificity of the C-peptide suppression, we applied this test to subjects with symptoms suggesting reactive hypoglycemia. Five subjects studied had never experienced fasting hypoglycemia, and were negative in ultrasound, CT and MRI of the pancreas. Plasma C-peptide was not suppressed by physiological (50-100 microU/ml) and supraphysiological (200-500 microU/ml) hyperinsulinemia (% of baseline: 97.3 +/- 8.6% and 90.6 +/- 10.4%, +/- SEM, respectively, both NS). Three subjects were re-examined one year later, when their hypoglycemic episodes were noticeably attenuated. No significant suppression was found. Significant suppression was observed when plasma glucose was clamped at 50-60 mg/dl in four of five subjects (61.7 +/- 11.5%, P < 0.05), but one subject responded to neither higher plasma insulin nor low-normal glucose. In contrast, normal glucose tolerance (n = 13), IGT (n = 12) and obese NIDDM (n = 31) subjects showed highly significant suppression during euglycemic and physiological hyperinsulinemia (37.1 +/- 3.8%, 46.3 +/- 5.6%, 39.9 +/- 2.6%, respectively, all P < 0.001). In conclusion, the results of the present study indicate that a failure of hyperinsulinemic suppression of C-peptide in euglycemia is not specific for insulinoma, and that suppression of C-peptide by insulin at lower plasma glucose levels (50-60 mg/dl) would be a better diagnostic test.

Topics: Adolescent; Adult; Aged; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Male; Middle Aged; Obesity

Inasmuch as previous studies have obtained conflicting results on the contribution of obesity to insulin resistance in noninsulin-dependent diabetes mellitus (NIDDM), we studied 10 nonobese and 10 obese NIDDM patients with the isoglycemic-(approximately 10 mmol/L)-hyperinsulinemic clamp (two insulin infusions of 4 and 40 mU/m-2 min-1), combined with [3-3H]glucose infusion and indirect calorimetry. As compared with nonobese patients, obese NIDDM patients had higher baseline peripheral and estimated portal plasma insulin concentrations (113 +/- 18 vs. 46 +/- 3 pmol/L and 288 +/- 53 vs. 98 +/- 6 pmol/L, respectively; P < 0.05) and less suppressed endogenous insulin production during clamp. Hepatic glucose production was greater in obese than in nonobese patients (basal, 16 +/- 1.1 vs. 12 +/- 0.5 mumol/kg-1 fat-free mass (FFM) min-1; clamp, 5.7 +/- 0.5 vs. 2.8 +/- 0.2 mumol/kg-1 FFM min-1, P < 0.05). Glucose utilization increased to a lesser extent in obese than in nonobese patients (49 +/- 5 vs. 73 +/- 7 mumol/kg-1 FFM min-1, P < 0.05) during clamp because of a lower increase in nonoxidative glucose metabolism (30 +/- 5 vs. 50 +/- 7 mumol/kg-1 FFM min-1, P < 0.05). Plasma free fatty acid concentrations and rates of lipid oxidation were greater in obese (P < 0.05) patients and correlated with hepatic glucose production (r = 0.79 and 0.50, P < 0.05). In conclusion, obesity exaggerates hepatic as well as extra-hepatic insulin resistance in NIDDM. The impaired inhibition of pancreatic beta-cell function by exogenous insulin contributes to exaggerated hyperinsulinemia in obese NIDDM.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Glycolysis; Humans; Infusions, Intravenous; Insulin; Insulin Resistance; Liver; Male; Middle Aged; Obesity; Portal System; Regression Analysis

To evaluate the early metabolic alterations induced by obesity, we studied glucose turnover and lipid levels in obese children with fasting normoinsulinaemia. Two experimental protocols were carried out. Protocol I consisted of a euglycaemic glucose clamp at two rates of insulin infusion. Protocol II was similar to protocol I except for a variable lipid infusion used to maintain basal non-esterified fatty acid (NEFA) levels. During protocol I, the glucose disappearance rates were lower in obese children, while no differences were found in hepatic glucose release. NEFA response to insulin was not substantially altered in obese children either at low or high insulin infusion. During protocol II, the NEFA clamp induced a 25% reduction in peripheral insulin sensitivity in control children whereas no changes were observed in obese children. Interestingly, lipid infusion in control children was not sufficient to reproduce the same degree of insulin resistance observed in obese children, suggesting that NEFA are only one of the determinants of insulin resistance at this stage of obesity. In conclusion, the present study provides a portrait of glucose metabolism and lipid levels in normoinsulinaemic obese children. Our results document that peripheral insulin resistance is the first alteration at this stage of obesity, whereas an increase in insulin secretion and a defect in the inhibition of hepatic glucose release by insulin may develop at a later stage. In addition, primarily receptor and post-receptor defects and some alterations of NEFA metabolism are likely to coexist in the induction of insulin resistance at this stage of obesity.

Topics: 3-Hydroxybutyric Acid; Analysis of Variance; Blood Glucose; Body Mass Index; C-Peptide; Child; Fatty Acids, Nonesterified; Female; Glucagon; Glucose; Glucose Clamp Technique; Glycerol; Humans; Hydroxybutyrates; Infusions, Intravenous; Insulin; Kinetics; Liver; Male; Obesity; Reference Values; Triglycerides

1. We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable-isotope gas chromatography-mass spectrometry method in six obese subjects [three males, three females, age 41.5 +/- 3.4 years (mean +/- SEM), weight 105.0 +/- 4.8 kg, plasma total cholesterol concentration 6.2 +/- 0.4 mmol/l, triacylglycerol 2.8 +/- 0.8 mmol/l, high-density lipoprotein cholesterol 1.0 +/- 0.2 mmol/l] and six lean control subjects (three males, three females, age 41.8 +/- 3.7 years, weight 68.2 +/- 4.9 kg, total cholesterol concentration 4.5 +/- 0.3 mmol/l, triacylglycerol 0.8 +/- 0.2 mmol/l, high-density lipoprotein cholesterol 1.3 +/- 0.1 mmol/l). 2. Plasma total cholesterol, triacylglycerol and mevalonic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the obese subjects than in control subjects (P = 0.02, P = 0.03, P = 0.04, respectively). VLDL apoB pool size and absolute secretion rate were significantly higher in the obese subjects than in control subjects (323.4 +/- 99.8 mg versus 53.6 +/- 17.1 mg, P = 0.004; and 42.3 +/- 13.8 mg kg fat-free mass-1 day-1 versus 10.7 +/- 0.4 mg kg fat-free mass-1 day-1, P = 0.01), but there was no significant difference in the fractional catabolic rate of VLDL apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Apolipoprotein B-100; Apolipoproteins B; C-Peptide; Cholesterol; Female; Gas Chromatography-Mass Spectrometry; Humans; Insulin; Liver; Male; Mevalonic Acid; Middle Aged; Obesity; Triglycerides

We have examined the impact of hypertension and blood glucose control on insulin sensitivity in obese Type 2 (non-insulin-dependent) diabetic patients. Glucose metabolism in the basal state and in response to insulin was examined using the euglycaemic, hyperinsulinaemic (2 mU kg-1 min-1) clamp technique in combination with 3-[3H]-glucose infusion and indirect calorimetry in 60 obese Type 2 diabetic patients (30 normotensive patients and 30 hypertensive patients on antihypertensive treatment) and 10 obese normotensive control subjects. In the basal state and during hyperinsulinaemia, glucose disposal rates (total, oxidative, and nonoxidative) were similar in Type 2 diabetic patients with or without hypertension (230 +/- 83 vs 270 +/- 114 mg m-2 min-1 (NS), 83 +/- 28 vs 95 +/- 7 mg m-2 min-1 (NS), 148 +/- 70 vs 180 +/- 89 mg m-2 min-1 (NS), treated hypertensive vs normotensive subjects, respectively). However, compared to obese control subjects (403 +/- 65 mg m-2 min-1) both groups of diabetic patients had significantly decreased insulin-stimulated glucose disposal rates (p < 0.005). Even in a subset of Type 2 diabetic patients with long-term (> 6 months) near normal blood glucose control (HbA1c < 6.1%) significant defects were detectable in whole-body glucose and lipid metabolism when compared to control subjects. These results indicate that treated hypertension does not significantly aggravate the insulin insensitivity that is already present in Type 2 diabetes mellitus. Furthermore, Type 2 diabetic patients with long-term good metabolic control continue to demonstrate insulin insensitivity in peripheral tissues.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Calorimetry; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Humans; Insulin; Lipid Metabolism; Liver; Male; Middle Aged; Obesity; Oxidation-Reduction; Patient Compliance; Reference Values

In overweight women with polycystic ovary syndrome (PCOS), increased insulin resistance has been observed. Since abdominal obesity is associated with impaired fibrinolytic capacity and elevated levels of plasminogen activator inhibitor (PAI-1) and since PAI-1 seems to be related to insulin resistance, we investigated the possible effects of dietary intervention on lipids, fibrinolysis, coagulation, and insulin sensitivity in obese PCOS women. Nine women aged 22 to 39 years (median weight, 97 kg) ate a protein-rich very-low-calorie diet (VLCD) (Nutrilett, Nycomed Pharma, Oslo, Norway; 421 kcal/d) for 4 weeks (part 1). After significant reductions of body fat (13%, P < .01), two of nine women achieved regular menstruation and became pregnant. Six of the remaining women continued on a conventional low-calorie diet (1,000 to 1,500 kcal/d) for the next 20 weeks (part 2), during which time they were generally able to preserve the body fat loss obtained in part 1 of the study. During part 1, significant reductions of total serum cholesterol (29%, P = .001) and fasting triglyceride ([TG] 31%, P < .05) levels were observed, as well as significant reductions of fasting glucose (6%, P < .05) and insulin (20%, P < .05). Insulin sensitivity (glucose disposal rate [GDR]) was increased by 93% (P < .05). After finishing part 2, insulin sensitivity was still significantly increased (86%, P < .05) and PAI-1 activity was significantly reduced (54%, P < .05). Moreover, overall fibrinolytic activity was significantly improved (serum D-dimer concentration increased by 75%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adult; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diet, Reducing; Factor VII; Female; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Insulin; Insulin Resistance; Lipids; Obesity; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Time Factors; Tissue Plasminogen Activator

Our preliminary data indicate that 15% of African-American patients presenting with diabetic ketoacidosis (DKA) are obese. To determine underlying mechanisms, we analyzed the clinical characteristics and indexes of insulin secretion and insulin sensitivity in 35 obese patients with DKA, 22 obese patients with hyperglycemia, 10 lean patients with DKA, and 10 obese nondiabetic subjects. Studies were performed 1 day after resolution of DKA and after 12 weeks of follow-up. At presentation, both obese DKA and obese hyperglycemic patients had no detectable insulin response to intravenous glucose, but they did respond to glucagon administration. The acute insulin response (AIR) to glucagon in obese DKA patients (0.9 +/- 0.1 ng/ml, P < 0.01), but significantly greater than in lean patients with DKA (0.1 +/- 0.1 ng/ml, P < 0.01). After 12 weeks of follow-up, the AIR to glucose improved in both groups of obese diabetic patients but remained significantly lower than in nondiabetic control subjects (both P < 0.01). In contrast, the AIR to glucagon was not significantly different from that in obese control subjects. Insulin sensitivity was decreased in both groups of obese diabetic patients at presentation and improved after follow-up to levels similar to those in obese nondiabetic control subjects. Reactivity with islet cell antibodies was not detected in any of the patients. During follow-up, 25 of 35 obese DKA and 16 of 22 hyperglycemic patients were able to discontinue insulin therapy, with continued good metabolic control. Our results indicate that in African-Americans, obese patients with DKA represent a subset of type II diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Georgia; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Reference Values; Thinness

The relationship between plasma C-peptide and the 6-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Individuals with younger-onset (n = 548) and older-onset (n = 459) diabetes were included. C-peptide was measured by radioimmunoassay with Heding's M1230 antiserum. Retinopathy was determined from stereoscopic fundus photographs. Younger- and older-onset insulin-using individuals with undetectable or low plasma C-peptide (< 0.3 nmol/l) at baseline had the highest incidence and rates of progression of retinopathy, whereas older-onset individuals with C-peptides > 0.3 nmol/l had the lowest incidence and rates of progression of retinopathy. However, within each group (younger-onset using insulin, older-onset using insulin, and older-onset not using insulin), after we controlled for other characteristics associated with retinopathy, there was no relationship between higher levels of C-peptide at baseline and lower 6-year incidence or progression of retinopathy. These data suggest that glycemic control, and not C-peptide, is related to the incidence and progression of diabetic retinopathy.

Topics: Adult; Age of Onset; Biomarkers; Blood Pressure; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Female; Glycated Hemoglobin; Humans; Incidence; Insulin; Male; Obesity; Proteinuria; Wisconsin

To study the relationships between blood pressure, insulin secretion and insulin resistance in obese female subjects.. Evaluation of insulin-secretion and resistance respectively by blood C-peptide determination and glucose clamp technique in nonhypertensive and hypertensive obese female subjects.. Outpatient clinic of University Hospital.. 12 female obese subjects, six of whom were nonhypertensive, and six hypertensive; and nine nonobese nonhypertensive subjects as control.. Baseline and during OGTT blood C-peptide as insulin secretion index; M, MCR and M/I ratio evaluated by euglycemic hyperinsulinemic clamp as expression of insulin resistance.. No difference is shown in C-peptide levels, between the two groups of obese subjects; the M, MCR and M/I values are significantly lower in hypertensive obese vs nonhypertensive obese subjects and controls (P < 0.001). Considering all the subjects, the same parameters are significantly inversely correlated with mean blood pressure values (P < 0.001).. In the groups of considered obese subjects, homogeneous for age, sex, body weight excess, fat distribution and glucose tolerance, blood pressure values are directly related to insulin resistance but not to insulin secretion.

Topics: Adult; Blood Glucose; Blood Pressure; Body Constitution; Body Weight; C-Peptide; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hypertension; Insulin; Insulin Resistance; Middle Aged; Obesity

To examine the contribution of obesity to insulin resistance and abnormalities of intracellular glucose and fat metabolism in NIDDM.. Glucose turnover measurements and indirect calorimetry were performed in 10 obese non-insulin-dependent diabetes mellitus (NIDDM) and 10 lean NIDDM subjects (body mass index 35.3 +/- 1.0 vs. 24.1 +/- 0.5 kg/m2, P < or = 0.001) in the basal state and during hyperinsulinemic (720 pmol.m-2.min-1) euglycemic (5.0-5.5 mmol/l) clamps.. Obese and lean NIDDM subjects demonstrated similar basal rates of glucose uptake (GU) (1.15 +/- 0.08 vs. 1.26 +/- 0.08 mmol/min, NS) as well as oxidative (0.49 +/- 0.07 vs. 0.53 +/- 0.05 mmol/min, NS) and nonoxidative (0.67 +/- 0.10 vs. 0.73 +/- 0.12 mmol/min, NS) glucose metabolism. During hyperinsulinemic glucose clamp studies, rates of GU were lower in obese NIDDM subjects (34.1 +/- 2.3 vs. 55.2 +/- 3.8 mumol.kg fat-free mass [FFM]-1.min-1, P < or = 0.001) as were rates of oxidative (14.1 +/- 1.3 vs. 22.1 +/- 2.1 mumol.kg FFM-1.min-1, P < or = 0.005) and nonoxidative (20.0 +/- 2.3 vs. 33.1 +/- 3.6 mumol.kg FFM-1. min-1, P < or = 0.01) glucose metabolism. Although absolute rates of insulin-stimulated GU were decreased in the obese group, the relative distribution into glucose oxidation (GOX) and nonoxidative glucose metabolism (NOX) was comparable in both groups (GOX 42% in obese and 41% in lean subjects; NOX 58% in obese and 59% in lean subjects). The NIDDM groups had similar basal free fatty acid levels that were suppressed equally during hyperinsulinemic clamps. However, basal fat oxidation (Fox) was greater in the obese NIDDM group (103 +/- 11 vs. 73 +/- 8 mumol/min, P < or = 0.05) and was less suppressed to insulin (74 +/- 13 vs. 16 +/- 3 mumol/min, P < or = 0.001).. These results indicate that when obesity is present in NIDDM subjects with this degree of hyperglycemia, insulin-stimulated GU is lower by 35-40%. Reduced GU in obese NIDDM subjects leads to decreased intracellular substrate availability and lower rates of oxidative and nonoxidative glucose metabolism. Insulin suppression of Fox is also impaired when obesity is present and may contribute to decreased insulin-mediated GU in NIDDM. We conclude that obesity increases insulin resistance in NIDDM primarily by effects on GU rather than the intracellular pathways of glucose metabolism.

Topics: Adipose Tissue; Blood Glucose; C-Peptide; Calorimetry; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucose; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Insulin; Lactates; Liver; Male; Middle Aged; Obesity; Oxidation-Reduction; Proteins; Thinness

Topics: Age Factors; Aged; Analysis of Variance; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Follow-Up Studies; Glucagon; Humans; Insulin; Insulin Secretion; Male; Morbidity; Myocardial Ischemia; Obesity; Risk Factors; Sex Factors

To determine whether fatty liver impairs insulin clearance and contributes to insulin resistance in obese and lean healthy non-diabetic men and women.. Cross-sectional, descriptive.. Medical outpatient clinic; university hospital.. Twenty-seven (14 men) non-diabetic obese (Body fat % = 31.5 +/- 9.3; mean +/- s.d.) and 19 (13 men) non-diabetic non-obese (body fat % = 19.0 +/- 6.8; P < 0.01 vs obese) healthy subjects aged 31-64 without liver disease.. Liver density relative to the spleen on CT scan (LFS), glucose infusion rate (GIR) and metabolic insulin clearance rate (MIC) during euglycemic hyperinsulinemic clamp; anthropometric (waist-hip ratio: WHR) and CT-determined (visceral fat area: VFA) measures of fat distribution.. Fatty liver was inversely related to MIC (r = -0.39; P < 0.01) with a positive correlation with fasting p-insulin (r = 0.39; P < 0.01). There were no statistically significant correlations between BMI, body fat % or WHR and MIC. GIR was inversely related to body fat % (r = -0.49; P < 0.01), VFA (r = -0.56; P < 0.01) and WHR (r = -0.36; P < 0.01) in all subjects, with an inverse relationship to fatty liver in men (r = -0.43; P < 0.05).. Increased steatosis of the liver is associated with reduced insulin clearance, contributing to insulin resistance in non-diabetic Japanese men and women.

Topics: Adipose Tissue; Adult; Anthropometry; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Cross-Sectional Studies; Fatty Acids, Nonesterified; Fatty Liver; Female; Glucose Clamp Technique; Humans; Hyperglycemia; Insulin; Insulin Resistance; Japan; Male; Metabolic Clearance Rate; Middle Aged; Obesity; Tomography, X-Ray Computed; Triglycerides

In the present series of 204 patients with NIDDM, 37 were lean and 35 obese. Mean FBG and HbA1C were significantly higher (P<0.02 and <0.01) in the former. Serum lipids such as total cholesterol (Tc) and triglycerides (Tg) were lower (P<0.05) in the lean while HDLc values were similar. Eight lean patients and 6 obese (Mean BMI : 15.7 vs.27.4) having similar age (48.0 vs 47.7 years) and mean duration of diabetes (4.6 vs 4.2 years) were subjected to the study of insulin and C-peptide status as well as beta cell reserve. The mean basal serum insulin (IRI) level was lower in the lean (15.3 vs. 28.9 mu u/ml ; P<0.05) while there was no statistical difference in the basal C-peptide values. Serum samples analysed 2 hours after 75 G of oral glucose and 1 mg I.V. glucagon (Novo) on two consecutive occasions for IRI and C-peptide responses revealed remarkable differences. The rise in IRI was significantly lower (p<0.01) in the lean after oral glucose and glucagon as compared to the obese. But the C-peptide values did not reveal significant difference suggesting similar reserve in beta cell function in both these groups of patients with NIDDM. The disparity between IRI and C-peptide levels observed was most likely due to excess extraction of insulin by the liver in lean-NIDDM, leading to lower peripheral levels. This phenomenon accounts for the occurrence of severe hyperglycemia inspite of good beta cell function in lean NIDDM.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Energy Metabolism; Female; Glycated Hemoglobin; Humans; India; Insulin; Islets of Langerhans; Lipids; Male; Middle Aged; Obesity; Pilot Projects; Thinness

Diabetes mellitus is a chronic state of excessive blood glucose levels (hyperglycaemia), which may result from many environmental and genetic factors, often acting jointly. The major regulator of glucose concentration in the blood is insulin. It is known that about 50% of the insulin is taken up by the liver on passing through it after secretion from the pancreas. The precise value of this fractional uptake is not known, so the prehepatic insulin secretion rates cannot be readily estimated from the plasma insulin concentration levels. By utilizing the equimolar secretion of insulin and connecting peptide (C-peptide) from the pancreas, a noninvasive method has been formulated. This was based on a compartmental model which involved the pancreas, liver, and plasma. The resulting differential equation yielded a gamma variate solution which could be readily linearized. The model was then tested on 56 normal (51 nonobese and 5 obese) subjects, and three groups of subjects with diabetes who could be labelled as mild, moderate, and severe (based on the fasting plasma glucose concentration) with 83, 88, and 64 subjects respectively. We have focused on the human patient environment of the clinician to produce a distinct model which gave a consistent pattern within all four groups with good fits between observed and theoretical values of the plasma insulin levels. The consequent rates for insulin secretion were consistent across the groups and were clinically meaningful.

Topics: C-Peptide; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Secretion; Liver; Mathematics; Models, Biological; Obesity; Pancreas

1. Both increased and decreased sensitivity to insulin has been proposed to precede the development of obesity. Therefore, insulin sensitivity was measured during a 2 h hyperinsulinaemia (100 m-units min-1 m-2) euglycaemic (4.5 mmol/l) glucose clamp combined with indirect calorimetry in nine weight-stable post-obese women and in nine matched control women preceded by 12 h fasting after 48 h on a standardized diet. 2. Both glucose disposal rate (post-obese women, 9.5 +/- 2.2 mg min-1 kg-1, control women, 11.2 +/- 1.4 mg min-1 kg-1, not significant) and glucose oxidation (3.6 +/- 0.5 mg min-1 kg-1 versus 4.0 +/- 0.7 mg min-1 kg-1, not significant) were similar in the two groups during the last 30 min of the clamp. Lipid oxidation also decreased similarly during the clamp in the post-obese women (from 30.4 +/- 12 to 2.0 +/- 7 J min-1 kg-1) and in the control women (from 33.6 +/- 11 to 5.4 +/- 8 J min-1 kg-1, not significant). Basal plasma concentrations of free fatty acids were similar, but at the end of the clamp free fatty acids were lower in the post-obese women than in the control women (139 +/- 19 and 276 +/- 48 mumol/l, P = 0.02). 3. We conclude that the insulin sensitivity of glucose metabolism is unaltered in the post-obese state. The study, however, points to an increased antilipolytic insulin action in post-obese subjects, which may favour fat storage and lower lipid oxidation rate postprandially.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Energy Metabolism; Female; Glucose; Glucose Clamp Technique; Humans; Insulin; Obesity; Oxidation-Reduction

The association between psychological coronary risk factors and serum insulin, and C-peptide and blood glucose concentrations, [the latter measured while fasting and during the oral glucose tolerance test (OGTT)], was examined in healthy middle-aged men (n = 64). The results indicate that among the evaluated psychological risk factors, high levels of hostile paranoia and vital exhaustion were most consistently associated with an enhanced insulin/glucose ratio, and enhanced insulin, C-peptide and glucose responses during OGTT. The associations persisted after controlling for age, smoking, alcohol consumption and visceral fat distribution. Thus, in addition to age, life-style factors and obesity, psychological factors may have an effect on insulin and glucose metabolism.

Topics: Adult; Anger; Blood Glucose; C-Peptide; Coronary Disease; Glucose Tolerance Test; Hostility; Humans; Insulin; Life Style; Male; Middle Aged; Obesity; Paranoid Disorders; Psychiatric Status Rating Scales; Risk Factors; Type A Personality

To clarify the utility of islet cell antibodies (ICA) to correctly classify and predict insulin treatment in newly diagnosed diabetic subjects, ICA, body mass index (BMI), glycated hemoglobin (HbA1c), and fasting plasma C-peptide values were evaluated at and 3 years after diagnosis in 233 new, consecutively diagnosed, adult diabetic patients classified as obese or nonobese (National Diabetes Data Group, NDDG criteria). Among the 233 patients, 31 were nonobese ICA-positive (mean age at diagnosis 43 +/- 3 years), 55 nonobese ICA-negative (mean age at diagnosis 58 +/- 2 years), 7 obese ICA-positive (mean age at diagnosis 57 +/- 5 years), and 139 obese ICA-negative (mean age at diagnosis 58 +/- 1 years). Fasting C-peptide decreased (P < 0.05) in nonobese ICA-positive patients who after 3 years showed lower BMI (22.6 +/- 0.6 versus 24.5 +/- 0.4; P < 0.05), lower fasting C-peptide (0.14 +/- 0.06 nmol/l versus 0.71 +/- 0.07 nmol/l; P < 0.001), and higher frequency of insulin treatment [28/31 (90%) versus 6/45 (13%); P < 0.001] than nonobese ICA-negative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 2; Disease Progression; Female; Glycated Hemoglobin; Humans; Islets of Langerhans; Male; Middle Aged; Obesity; Prospective Studies

The aim of this work was to evaluate the prevalence of microalbuminuria in an obese population and to study the relation between albumin excretion rate (AER), various clinical (body mass index, adipose tissue distribution) nutritional (macronutrient intake) and metabolic parameters. A cross-sectional study was carried out, and AER was evaluated in 182 obese subjects (BMI > 27) with no medication, no intercurrent disease, no cardiac, pulmonary or endocrinological disorders (including diabetes and hypertension) and also in 31 control subjects at the outpatient clinic of the department of Nutrition, Hôtel Dieu, Paris, France. The following were measured: BMI, waist/hip ratio (WHR), urinary AER, blood glucose, insulin and C peptide levels, cholesterol (CT), triglycerides, HDL cholesterol (HDL-CT), apoprotein A1 and B. In the obese population, 18 subjects (9.9%) were found to have an increased AER: 13 subjects (7.1%) with microalbuminuria (AER between 30 to 300 mg/24 h) and five with AER over 300 mg/24 h. AER was normal in all control subjects but one, who was found to have microalbuminuria. Log AER was positively correlated to WHR (P < 0.001), blood pressure (P < 0.05), cholesterol (P < 0.05), Apo B levels (P < 0.01) and with fasting Insulin levels and protein intake (P < 0.001). Positive association between log AER and protein intake, insulin levels, Apo B and blood pressure were found independently of BMI and WHR. It is suggested that abdominal obesity may be associated with incipient nephropathy in some obese subjects without diabetes and hypertension. Microalbuminuria may be included among metabolic abnormalities connected with abdominal-type excess weight distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adult; Albuminuria; Apolipoproteins A; Apolipoproteins B; Blood Glucose; Blood Pressure; Body Composition; Body Constitution; Body Mass Index; C-Peptide; Cholesterol; Cross-Sectional Studies; Dietary Proteins; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Prevalence

1. Adults with growth hormone deficiency have an abnormal body composition. Alterations in body composition are closely related to substrate concentrations and insulin action. The lack of growth hormone has been associated with increased insulin sensitivity. 2. We investigated the correlations of body composition with fasting insulin levels and substrate concentrations in 24 adults with growth hormone deficiency over a wide range of adiposity (body mass index 18.8-42.3 kg/m2). 3. Lean body mass was measured by total body potassium, computer tomography of the thigh and urinary creatinine excretion. Muscle fibre distribution was evaluated from vastus lateralis biopsies. Fat mass was assessed by skinfold thickness measurements, computer tomography of the thigh, and waist and hip girth. 4. Fasting plasma insulin level increased with fat mass (r = 0.67, P = 0.0004) and with waist girth (r = 0.76, P = 0.0001). Fasting plasma insulin level increased with fasting plasma glucose level (r = 0.53, P = 0.01). Fasting plasma glucose level in turn was positively correlated with lean body mass (r = 0.49, P = 0.01) and with total thigh muscle area (r = 0.54, P = 0.01). There was no correlation between lean body mass and fat mass (r = 0.17, not significant) nor between muscle fibre types and fat mass or fat distribution. Fasting plasma insulin level showed no correlation with any measurement of lean body mass or muscle fibre type.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Anthropometry; Blood Glucose; Body Composition; C-Peptide; Fasting; Female; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Male; Middle Aged; Muscles; Obesity; Thigh; Time Factors

Insulin resistance is associated with hypertriglyceridemia and elevated free fatty acid (FFA) concentrations in obese and diabetic individuals, but it is unclear to what extent this relationship is independent of obesity and is present in healthy individuals. We studied 92 healthy middle-aged males selected from the top, middle, and lowest quintiles of the insulin sensitivity index (Si) determined in a group of 182 men using the minimal model of glucose disappearance. Plasma FFA, triglyceride, glucose, insulin, and C-peptide concentrations were measured during a 3-hour intravenous glucose tolerance test (IVGTT). The low-Si (most insulin-resistant) group had more central body fat distribution (subscapular/triceps skinfold thickness) and a higher median body mass index (BMI) of 26.8 (range, 21.1 to 41.1) kg.m-2 compared with the middle- and high-Si groups with BMIs of 24.9 (19.1 to 31.5) and 23.7 (18.8 to 33.2) kg.m-2 (P < .05). Relatively minor glucose intolerance in the low-Si group was no longer significant when central adiposity was accounted for. Glucose tolerance was maintained by increased insulin secretion, leading to IVGTT insulin responses twofold and fourfold higher in the middle- and low-Si groups, respectively, compared with the high-Si group (P < .01). Fasting FFA and triglyceride concentrations were increased in the low-Si group relative to the other groups independent of BMI or central adiposity (P < .01). During the IVGTT, FFA decreased to similar minimum concentrations in all three groups. Triglyceride concentrations during the IVGTT increased above their minimum levels, particularly in the low-Si group (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; C-Peptide; Fatty Acids, Nonesterified; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Triglycerides

Our purpose was to investigate whether maternal obesity, or more specifically body fat distribution, is associated with alterations in carbohydrate metabolism during pregnancy.. A longitudinal study of oral glucose tolerance tests, insulin, C peptide, and glucagon levels during each trimester and post partum was undertaken in nine lean and 14 obese women. Obese women were divided into lower body obese (n = 6, waist/hip ratio < 0.9) and upper body obese (n = 8, waist/hip ratio > or = 0.9).. Fasting blood glucose levels declined with advancing gestation only in lean subjects. Upper body obese women demonstrated maximal glucose response and insulin area under the curve by the second trimester, whereas lean and lower body obese women did not until the third trimester. Insulin areas were significantly elevated in upper body obese compared with lower body obese women (second trimester, p < 0.01; third trimester, p < 0.03; post partum p < 0.05). In contrast, C peptide levels were similar in obese subgroups and were significantly elevated only when compared with those of lean women. C peptide/insulin molar ratios were lower in upper body obese women during the second trimester (4.3 +/- 0.8) and third trimester (4.2 +/- 0.7) compared with lean (6.5 +/- 1.3, 6.7 +/- 0.5) and lower body obese women (7.9 +/- 1.4, 6.5 +/- 1.4) (p < 0.01). A significant relationship between waist/hip ratio and glucose level (r = 0.70, p < 0.004) and insulin areas (r = 0.76, p < 0.001) was present in late pregnancy in obese subjects.. Relative hyperinsulinemia and earlier maximal glucose response in upper body obese women suggests that body fat distribution may explain the metabolic heterogeneity present in obese women during pregnancy. Body fat topography may serve as a potential marker for the early development of carbohydrate intolerance during pregnancy.

Topics: Adipose Tissue; Adult; Analysis of Variance; Body Constitution; C-Peptide; Female; Glucagon; Glucose; Glucose Tolerance Test; Humans; Insulin; Longitudinal Studies; Obesity; Pregnancy; Pregnancy Complications; Regression Analysis

To define the chronobiology of glucose tolerance and insulin secretion in obesity, nine obese men and nine lean men were studied during constant glucose infusion for 53 h, including 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples were collected at 20-min intervals to assay glucose, insulin, C-peptide, cortisol, and GH. Sleep was polygraphically monitored. Abnormal temporal profiles of glucose regulation were observed during wakefulness and sleep in obese subjects. During daytime hours, the normal profile of glucose tolerance was reversed, as an improvement, rather than a deterioration, was observed from morning to late evening. This reversal of the daytime pattern appeared to be caused by a dual defect in glucose regulation during the previous night. Indeed, during early sleep, GH secretion was markedly reduced, and the nocturnal rises of glucose and insulin secretion were dampened. During late sleep, obese subjects failed to suppress insulin secretion and plasma glucose, resulting in high morning levels. Comparisons of metabolic and hormonal patterns during nocturnal and daytime sleep suggest that the failure to suppress insulin secretion in late sleep may reflect a relative insensitivity of the beta-cell to acute inhibitory effects of cortisol in addition to insulin resistance.

Topics: Adult; Blood Glucose; C-Peptide; Circadian Rhythm; Glucose Tolerance Test; Growth Hormone; Humans; Hydrocortisone; Insulin; Insulin Secretion; Kinetics; Male; Obesity; Sleep; Wakefulness

Subjects with overt non-insulin-dependent diabetes mellitus (NIDDM) were studied in comparison to obese nondiabetic control subjects and patients with subclinical diabetes. Pancreatic insulin secretion rates were measured by deconvolution of peripheral C-peptide over a 24-h period while subjects consumed an isocaloric mixed diet. Subjects were then placed on caloric restriction for at least 6 weeks, during which time body weight fell by at least 10%. Refeeding with solid mixed meals was then resumed for at least 2 weeks until isocaloric intake was attained, and then the meal profiles were repeated. Before weight loss, insulin, C-peptide, and insulin secretion rates were significantly higher in subjects with subclinical diabetes than in the other two groups. Proinsulin concentrations were significantly greater in the two diabetic groups than in control subjects, but, when expressed as a percentage of the total insulin immunoreactivity, the differences were significant only in the group with overt diabetes. Weight loss because of hypocaloric feeding resulted in a significant increase in the rate of clearance of endogenously secreted insulin but did not affect the clearance of C-peptide. In obese subjects and those with subclinical diabetes, weight loss was associated with a reduction in insulin secretion rates, presumably as a result of improvements in insulin sensitivity. In patients with overt diabetes and hyperglycemia, weight loss improved beta-cell responsiveness to glucose and was associated with an increase in insulin clearance and a reduction in proinsulin immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Humans; Insulin; Metabolic Clearance Rate; Middle Aged; Obesity; Proinsulin; Reference Values; Weight Loss

The effects of two low-energy diets on serum insulin concentrations and weight loss in obese hyperinsulinemic females were compared during a 12-wk period. The first diet (n = 15) was designed to evoke a low insulin response (ID), and the second (n = 15) was a conventionally balanced diet (ND). After a 12-wk washout period, seven and nine subjects who had been on the ID and ND, respectively, changed to the alternative diet for 12 wk. Variables studied were basal and 30- and 120-min concentrations of blood glucose, insulin, and C-peptide after an oral glucose load; body weight; and energy intake. Mean (+/- SD) weight was significantly reduced after ID and ND (9.35 +/- 2.49 and 7.41 +/- 4.23, respectively). The mean weight loss was more after ID. Fasting insulin concentrations decreased more after ID compared with ND (91.3 +/- 61.8 vs 21.0 +/- 71.5 pmol/L; P < 0.05). We conclude that ID significantly reduces serum insulin concentrations and weight in obese hyperinsulinemic females.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Complications; Diabetes Mellitus; Diet, Diabetic; Energy Intake; Fasting; Female; Humans; Hyperinsulinism; Insulin; Obesity; Weight Loss

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Retrospective Studies

Very Low Calorie Diet (VLCD) is known to induce not only weight loss, but also an improvement of metabolic control, in obese type II diabetics. In order to evaluate the therapeutical efficacy of cycles of VLCD shorter than those previously described, 29 obese type II diabetics and 31 obese nondiabetic subjects were entered as inpatients and prescribed a 450 kcal/day diet for 15 days. Metabolic results obtained were similar to those achieved with longer cycles of VLCD, showing that 15 days are sufficient to induce a BMI decrease in diabetic (BMI from 35.3 +/- 4.8 to 33.3 +/- 4.6 after VLCD) and nondiabetic patients (BMI from 40.5 +/- 7.4 to 38.1 +/- 7.2 after VLCD), a desired fall of blood glucose levels and the decrease of daily insulin needs in insulin-treated patients. Glucagon tests were performed before and after VLCD in order to study possible modifications of insulin secretion. Although we did not observe any significant increase of C-peptide basal or peak levels (nM/ml) either in diabetic (basal levels before VLDC: 1.2 +/- 0.4 and peak levels 2.4 +/- 0.7; basal after VLCD 1.23 +/- 0.6 and peak 2.6 +/- 0.7) and nondiabetic patients (basal levels before VLDC 1.0 +/- 0.3 and peak levels 2.5 +/- 0.4; basal after VLCD 0.9 +/- 0.3 and peak 2.4 +/- 0.6). The rise of the C-peptide/glycemia ratio is an index of an improvement of insulin biological activity, which could be partly responsible for the therapeutical effects of VLCD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Female; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Receptor, Insulin; Weight Loss

Interrelationship between the body mass index (BMI), the waist-hip ratio (WHR) and serum concentration of immunoreactive insulin (IRI), C-peptide and sex hormone binding globulin (SHBG) was investigated in adolescents with obesity. Significant positive correlations were found between BMI and IRI, between BMI and C-peptide and there was a negative correlation between BMI and SHBG. WHR did not correlate with IRI, C-peptide and SHBG. IRI, C-peptide and SHBG in the group of central and gluteal obesity differentiated by WHR did not differ significantly. These results suggest that use of WHR to differentiate central and gluteal obesity does not help in adolescent period, possibly because of somatic changes of puberty.

Topics: Adolescent; Body Mass Index; C-Peptide; Female; Humans; Insulin; Male; Obesity; Puberty; Sex Hormone-Binding Globulin

For many years a series of studies has been carried out to evaluate the role of endogenous opioid peptides on glucose metabolism. In this work we studied the influence of endogenous opioid peptides on insulin response to OGTT and glucose-induced thermogenesis before and after a prolonged oral treatment with Naltrexone (50 mg/daily for 6 days), an opioid receptor antagonist, in a group of 9 obese subjects. Moreover in obese patients we evaluated the effect of this anti-opioid drug on insulin secretion and insulin sensitivity during an IVGTT using the minimal model approach. We compared the pre-treatment results with data coming from a group of 5 normal-weight subjects. We measured blood glucose, plasma insulin and C-peptide concentrations and evaluated the following parameters: first (phi 1) and second (phi 2) phase of beta-cell sensitivity, insulin sensitivity and glucose effectiveness. Obese subjects displayed an increased insulin response to oral and i.v. glucose load, due to an increased first phase of insulin secretion (phi 1), a reduced insulin sensitivity (Si) and glucose effectiveness (Sg) in respect to normal-weight subjects. They showed no difference in glucose and insulin area during oral load and in their profiles during i.v. glucose load after naltrexone treatment. Similarly no significant variation in insulin sensitivity and glucose effectiveness was observed. The glucose-induced thermogenesis, measured by indirect calorimetry, was not modified by naltrexone. Therefore our study demonstrates that endogenous opioids do not play any role in the impairment of peripheral insulin sensitivity and energy expenditure in human obesity.

Topics: Adult; Blood Glucose; Body Composition; Body Temperature Regulation; C-Peptide; Energy Metabolism; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Models, Biological; Naltrexone; Obesity; Oxidation-Reduction

We examined the effects of an oral glucose load on plasma insulin, androgens, and beta-endorphin (beta EP) concentrations in patients carefully selected as having polycystic ovary syndrome (PCOS) and normal glucose tolerance. Our aim was to verify whether insulin resistance is a common feature of PCOS and to differentiate the metabolic abnormalities related to PCOS from those associated with obesity. Plasma immunoreactive insulin (IRI), C-peptide (C-PR), testosterone, androstenedione, dehydroepiandrosterone sulfate, ACTH, and beta EP responses to a 3-h oral glucose tolerance test (OGTT) were evaluated in 10 obese (OB-PCOS) and 10 nonobese (NO-PCOS) patients with PCOS and in 7 obese and 7 nonobese ovulatory controls. OB-PCOS and NO-PCOS did not differ significantly from weight-matched controls in the IRI response, but had a significantly higher C-PR response in terms of mean postglucose load levels and mean incremental areas. During OGTT, mean plasma levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate declined in both PCOS groups as well as in controls, and no significant correlation between the plasma androgen and IRI or C-PR responses was found. The ACTH response in OB-PCOS and NO-PCOS was similar to that in controls, with a progressive decrease until 180 min. A similar decline in plasma beta EP was found in controls, whereas no change in plasma beta EP was observed in OB-PCOS and NO-PCOS. These findings indicate that independently of the presence of obesity, PCOS patients have enhanced insulin secretion in response to OGTT and show a peculiar pattern of changes in plasma beta EP.

Topics: Administration, Oral; Adult; Androgens; Androstenedione; beta-Endorphin; C-Peptide; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Radioimmunoassay; Testosterone

Thirty-six women aged 18 to 52 years with body mass indexes (BMIs) between 27 and 52 were studied. Visceral and subcutaneous fat areas and body fat were evaluated by computerized tomography with a single scan at the IV-V lumbar vertebra level. Glucose, insulin, and C-peptide levels were measured before and after a glucose load. Total and free serum testosterone and 24-hour urinary cortisol excretion were measured. A stepwise multiple regression equation showed the visceral to subcutaneous fat area ratio to be the most powerful predictor for glucose alterations both during fasting and after a glucose load, and showed BMI to be the most powerful predictor for insulin and C-peptide levels. Total serum testosterone, after matching for age and BMI, demonstrates a significant negative correlation with visceral fat area. We conclude that in obese women, as in men, intraabdominal fat negatively correlates with serum testosterone levels.

Topics: Abdomen; Adipose Tissue; Adolescent; Adult; Body Mass Index; C-Peptide; Female; Glucose; Humans; Hydrocortisone; Insulin; Middle Aged; Obesity; Testosterone; Tomography, X-Ray Computed

Although it is generally accepted that islet amyloid polypeptide is cosecreted with insulin, relatively few data on its kinetics are available. We therefore studied the dynamics of islet amyloid polypeptide release following oral and frequently sampled intravenous glucose tolerance tests in comparison to insulin and C-peptide using mathematical model techniques in 14 control subjects, 10 obese and 11 hypertensive patients. The fractional clearance rate of islet amyloid polypeptide (0.034 +/- 0.004 min-1 in control subjects, 0.058 +/- 0.008 in the obese and 0.050 +/- 0.008 in the hypertensive patients) was significantly different (p < 0.01) in each group compared with that of insulin (0.14 +/- 0.03 min-1) and similar to that of C-peptide (0.061 +/- 0.007 min-1), at least in the insulin-resistant subjects. Based on the insulin sensitivity index derived from the minimal model analysis of intravenous glucose tolerance test data, both the hypertensive (2.4 +/- 0.4 min-1/(microU/ml); p < 0.0005) and the obese (2.7 +/- 0.5; p < 0.001) patients demonstrated severe insulin resistance compared to control subjects (8.1 +/- 1.3). Marked insulin hypersecretion was found in the hypertensive (57.6 +/- 5.2 nmol.l-1 in 180 min; p < 0.001) and obese (60.8 +/- 10.1; p < 0.003) patients in comparison with control subjects (32.4 +/- 3.2). The release of islet amyloid polypeptide was significantly higher in the hypertensive (83.1 +/- 16.6 pmol/l in 180 min; p < 0.02) and obese (78.6 +/- 13.1; p < 0.005) patients than in control subjects (40.5 +/- 6.4). No correlation was found between islet amyloid polypeptide release and the insulin sensitivity index in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amyloid; Blood Glucose; C-Peptide; Glucose Tolerance Test; Humans; Hypertension; Insulin; Insulin Resistance; Insulin Secretion; Islet Amyloid Polypeptide; Kinetics; Models, Biological; Obesity; Reference Values; Time Factors

The development of hyperinsulinemia and insulin resistance, both common in adults with established obesity, was studied in 16 children, weighing 169 +/- 8% ideal body weight who were 12.7 +/- 0.4 years of age with obesity duration of 0.5-8.5 years and continuous weight gain in excess of normal, and compared with 11 age-matched normal children. Early in the evolution of obesity, insulin and C-peptide responses to a normal meal were increased by 76 and 80%. The first insulin peak was higher (613 +/- 53 pmol/ml) than normal (413 +/- 59 pmol/ml, P < 0.02) and occurred only 50 +/- 7 min after onset of lunch versus 33 +/- 11 min in normal children (P < 0.0005). Obese patients had a total of 3.0 +/- 0.2 large insulin peaks within the 6-h period after the lunch versus only 1.5 +/- 0.2 peaks in normal children (P < 0.0005). In contrast, fasting plasma insulin and C-peptide levels remained normal during the initial years of obesity, then increased progressively with duration (r = 0.73, P < 0.001) and degree (r = 0.59, P < 0.02) of obesity. Insulin sensitivity evaluated as the rate of glucose uptake during a three-step hyperinsulinemic euglycemic clamp was comparable in the obese (20 +/- 1.5 mmol.m-2.min-1) and the normal (21.7 +/- 1.5 mmol.m-2.min-1) children. Initially higher than normal in obese children, the maximal rate of glucose uptake decreased with both obesity duration (r = -0.67, P < 0.005) and children's age (r = -0.66, P < 0.005), indicating the progressive development of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Analysis of Variance; Blood Glucose; Body Weight; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Eating; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Secretion; Male; Obesity; Prediabetic State; Reference Values; Time Factors

Accelerated atherosclerosis is the leading cause of death in patients with non-insulin-dependent diabetes mellitus (NIDDM). Impaired endogenous fibrinolytic activity may accelerate atherosclerosis by exposing vascular luminal wall surfaces to persistent and recurrent thrombi and clot-associated mitogens. This study was conducted to further characterize endogenous fibrinolysis in lean and obese nondiabetic subjects and in NIDDM patients and to identify mechanisms responsible for the alterations identified. Obese and diabetic subjects had threefold elevations of plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1) compared with values in lean control subjects. Despite the lack of significant differences in plasma concentrations of tissue-type plasminogen activator in the obese and diabetic subjects, both basal and stimulated endogenous fibrinolytic activities were decreased. The decreases were associated with increased activity of PAI-1 in plasma, in turn correlated with increased concentrations of immunoreactive insulin and C-peptide. These results are consistent with our previous observations demonstrating direct stimulatory effects of insulin and its precursors on cellular expression of PAI-1 in vitro and observations by others demonstrating decreased basal fibrinolytic activity in NIDDM patients. Impaired endogenous fibrinolytic activity could lead to prolonged or recurrent exposure of luminal surfaces of vessel walls to microthrombi and clot-associated mitogens that may accelerate atherosclerosis in hyperinsulinemic subjects.

Topics: Adult; Analysis of Variance; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolysis; Humans; Insulin; Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Reference Values; Tissue Plasminogen Activator

The hypothesis that spontaneous obesity in rhesus monkeys is associated with abnormalities in energy expenditure was tested. Obese (n=7) and non-obese (n=5) monkeys were described in terms of body size and composition, food intake, and physical activity. Additionally, the relationships among fasting and stimulated insulin levels in serum, C-peptide levels in serum and urine, and urinary catecholamines were examined. Obese animals had primarily abdominal deposition of excess body fat, as indicated by markedly elevated abdominal circumferences and skin-fold thicknesses. Food intake did not differ between groups. Physical activity was much lower in the obese group. Obese monkeys had markedly higher serum insulin and C-peptide levels in the fasted state and in response to an intravenous glucose challenge. Urinary excretion of C-peptide and catecholamines was measured during successive 2-day periods of ad libitum feeding, food deprivation, and refeeding in order to examine potential differences between groups in sympathoadrenal activity and their relationship to insulin secretion. C-peptide excretion was greater for obese and decreased for both groups during food deprivation. Urinary dopamine (DA), norepinephrine (NE), and epinephrine (E) levels were significantly greater for obese animals in all conditions. DA excretion was lowest during deprivation and E excretion was lowest during refeeding, whereas NE excretion was relatively unaffected by feeding condition. The overall patterns of C-peptide and catecholamine excretion were qualitatively similar for both groups, and there were no reliable differences between obese and non-obese in their responses to the feeding manipulation. The results suggest that hyperinsulinemia associated with obesity in rhesus monkeys is linked to increased catecholamine secretion and a resistance to catecholaminergic action.

Topics: Adrenal Glands; Animals; Body Weight; C-Peptide; Catecholamines; Chromatography, High Pressure Liquid; Dopamine; Eating; Epinephrine; Feeding Behavior; Female; Glucose Tolerance Test; Insulin; Lipid Metabolism; Macaca mulatta; Male; Motor Activity; Norepinephrine; Obesity; Physical Conditioning, Animal; Time Factors

Many obese middle-aged rhesus monkeys (Macaca mulatta) spontaneously develop noninsulin dependent diabetes mellitus (NIDDM). Basal hyperinsulinemia and increased stimulated plasma insulin levels are associated with this obesity and precede the onset of overt diabetes. The present studies sought to determine the relative contributions of enhanced insulin secretion and of reduced insulin clearance to this early obesity-associated hyperinsulinemia. Direct simultaneous measurement of portal and jugular vein insulin levels in two normal monkeys showed a constant rate of hepatic insulin extraction of 56+/-3% over the range of peripheral insulin levels from 351+/-113 to 625+/-118 pmol/L. In 33 additional monkeys ranging from normal to diabetic, basal C-peptide levels were examined as an indicator of beta-cell secretion and the molar ratio of plasma C-peptide to insulin (C/I ratio) under basal steady state conditions calculated as an index of hepatic insulin extraction. Well in advance of overt diabetes, there was a progressive decline of 67% in the apparent hepatic insulin extraction rate in association with increased obesity and plasma insulin levels. Basal insulin levels and hepatic insulin extraction returned toward normal in monkeys with impaired glucose tolerance and in those with overt diabetes. We conclude that reduced insulin disposal, probably due to reduced hepatic extraction of insulin, in addition to increased beta-cell activity, contributes to the development of basal hyperinsulinemia in obese rhesus monkeys progressing toward NIDDM. In addition, in overt diabetes, normal hepatic insulin extraction in the presence of limited beta-cell secretion may exacerbate the hypoinsulinemic state.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Disease Models, Animal; Female; Glucose Tolerance Test; Hyperinsulinism; Insulin; Insulin-Secreting Cells; Jugular Veins; Liver; Macaca mulatta; Male; Metabolic Diseases; Obesity; Portal Vein; Receptor, Insulin; Time Factors

Although it is known that circulating levels of the insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBPs) fluctuate in response to changes in nutritional status, there is little information regarding either relative contributions from different dietary components or regulation by insulin in nondiabetic subjects. To define dietary contributions to IGF regulation, the authors examined the effects of fasting and hypocaloric diets of differing nutritional composition on serum IGF-1 and a IGFBP-1 in 16 healthy, obese adult women. Subjects received an isocaloric diet for 6 days, followed by 14 days of calorie restriction (fasting or a hypocaloric diet enriched in either protein, fat, or carbohydrate), and by 4 days refeeding. All diets produced 6-8% weight loss over 14 days with little difference between groups. The "protein-sparing" diet sustained nitrogen balance (+1.2 g/d, versus -4.5 g/d for the other three groups; p < 0.05). Serum IGF-1 levels decreased during calorie restriction with fasting or with diets high in fat or carbohydrates (CHO; combined mean 40 +/- 7%) but showed little change with the high protein regimen (3 +/- 16%; p < 0.05 compared to the other diets). In contrast, IGFBP-1 increased during calorie restriction in all four groups but significantly less with the high CHO diet (43 +/- 17% above baseline) than with the other diets (168 +/- 31%; p < 0.05). Levels of IGF-1 were correlated with nitrogen balance (r = 0.51; p < 0.05) but levels of IGFBP-1 were not. Although IGFBP-1 levels inversely correlated with measures of insulin secretion, IGF-1 levels did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Body Weight; C-Peptide; Carrier Proteins; Diet; Fasting; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Nitrogen; Obesity; Prealbumin; Transferrin

In order to investigate the relationships between glucose metabolism, insulin secretion and endogenous opioids in obese patients, we have studied the effects of a naloxone infusion on insulin and C-peptide release after a normal meal (800 kcal) eaten at 12.00 hr in 16 obese women, aged 20-61 yr, with a BMI ranging from 25 to 37.2 kg/m2, with normal glucose tolerance (Group 1) and with NIDDM (Group 2). Naloxone was administered in a bolus of 1.6 mg i.v., followed by a continuous infusion of 4 mg in 2 hr starting immediately after feeding. In Group 1 naloxone infusion significantly increased the glucose levels, but insulin secretion was unaffected. In Group 2, naloxone infusion failed to modify significantly the postprandial levels of glucose, insulin and C-peptide. Therefore, in our study naloxone infusion seems to have beta-endorphin-like effects in non-diabetic obese subjects by increasing their glycemic levels, with no evidence of expected insulin decrease. In diabetic obese patients we observed a trend towards decrease in glycemic values during naloxone infusion, as expected, due to insulin plasma levels increase. By these data we can hypothesise a complex regulatory role of opioids in metabolic balance in obesity. In diabetic patients, naloxone can improve the surviving insulin secretion with better glucose tolerance. In non-diabetic subjects naloxone exerts its effects, probably, on peripheral organs.

Topics: Adult; Analysis of Variance; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Infusions, Intravenous; Insulin; Middle Aged; Naloxone; Obesity

To investigate the effectiveness of exercise on the regulation of insulin sensitivity.. Eleven premenopausal women, with body fat mass from the normal range to moderate obesity, were examined with glucose clamp at 10 mmol/L glucose concentration to determine insulin-dependent and non-insulin-dependent (after somatostatin inhibition of endogenous insulin production) glucose uptake (= IDGU and NIDGU respectively) before and 24 hrs after a glycogen-decreasing exercise.. IDGU, but not NIDGU, increased after exercise. The degree of increase of IDGU after exercise showed negative correlations with body mass index (borderline, significance), the waist to hip circumference ratio, fasting free testosterone and free fatty acid concentrations, as well as diastolic blood pressure (borderline significance), and a positive relationship to sex hormone binding globulin concentration and IDGU before exercise.. It is concluded that only IDGU contributes to the augmentation of insulin sensitivity after a glycogen-decreasing exercise in women. Additionally, the increase of IDGU is less in abdominal obesity, and negatively dependent on free fatty acid concentrations, hyperandrogenism and hyperinsulinaemia, all putative pathogenetic factors for insulin resistance.

Topics: Adult; Blood Glucose; C-Peptide; Exercise; Fatty Acids, Nonesterified; Female; Humans; Insulin; Insulin Resistance; Middle Aged; Obesity; Premenopause; Somatostatin

We investigated the feedback inhibition of insulin and glucagon secretion during euglycemic-hyperinsulinemic clamp at about 350 pmol/l in 16 patients with abdominal obesity [8 with normal glucose tolerance (oNGT), 8 with impaired glucose tolerance (oIGT)] and 8 normal-weight subjects matched for age, sex and blood pressure. In oNGT and oIGT, fasting plasma C-peptide levels were twice those in the controls (962 +/- 51 and 915 +/- 85 vs 439 +/- 28 pmol/l, P < 0.001) and their suppression was lower than in the controls, both in absolute terms (155 +/- 19 and 185 +/- 17 vs 274 +/- 18 pmol/l, P < 0.001) and as a percentage decline from basal levels (16 +/- 2% and 21 +/- 2% vs 63 +/- 2%, P < 0.001). Fasting plasma glucagon levels were similar in the patients and in the controls, but were less suppressed during clamp in oNGT and oIGT, both in absolute terms (7.0 +/- 0.9 and 5.6 +/- 0.6 vs 13.2 +/- 1.2 pmol/l, P < 0.001) and as a percentage change from basal levels (23 +/- 3% and 19 +/- 2% vs 44 +/- 4%, P < 0.001). These results suggest that the insulin feedback on B and A cells is impaired in abdominal obesity, and that this defect is of similar degree in oNGT and oIGT. These alterations could be implicated in the pathogenesis of hyperinsulinemia in obesity.

Topics: Adult; Blood Glucose; C-Peptide; Feedback; Female; Glucagon; Glucose Clamp Technique; Glucose Intolerance; Humans; Insulin; Insulin Secretion; Male; Obesity; Reference Values

We have studied the pharmacokinetics and pharmacodynamics of glyburide during long-term therapy in 20 patients with type II diabetes mellitus. The patients were divided according to body mass index (BMI) into an obese group [n = 12, age 55(13) y, BMI 36.2(9.2) kg.m-2, total body weight (TBW) 100(23) kg], and a non-obese group [n = 8, age 61(13) y, BMI 24.5(2.1) kg.m-2, TBW 73(7) kg]. The dosages of glyburide were titrated to achieve specified therapeutic goals based upon serum glucose concentrations or to a maximum dosage of 20 mg per day. The pharmacokinetics of glyburide were determined at week 12 of treatment. On the study day, the patients took a 2.5 mg liquid test dose of glyburide with a Sustacal meal challenge. The elimination rate constant (lambda z), clearance (CL), and apparent volume of distribution (Vz) were 0.08 h-1, 3.3 l.h-1, and 47.0 l in the obese group, and 0.07 h-1, 3.1 l.h-1, and 56.8 l in the non-obese group. These values were not statistically significantly different. However, there were differences between the groups when the volume and clearance were corrected by TBW or BMI but not by ideal body weight (IBW) or fat-free mass (FFM). Regression analysis between the pharmacokinetic variables and body weight status revealed statistically significant correlations between volume or clearance and body weight. However, due to large inter-patient variability, these relations were relatively weak and were considered to be non-predictive.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glyburide; Humans; Insulin; Male; Middle Aged; Obesity; Time Factors

Aim of this study was to verify the existence of a correlation between the insular hormones and the atrial natriuretic factor (ANF). We studied 70 subjects (20 control, 20 obese, 20 non insulin-dependent diabetic obese, 10 insulin-dependent diabetic subjects) submitted to a glucagon test (1 mg i.v.). Blood samples were collected at -15, 0, 3, 6, 12, 15, 30, 60, 120, 150 minutes to assay insulin, C-peptide, serum electrolytes and ANF levels. The results to point out are: the ANF basal values are significantly higher (p < 0.01) in non insulin-dependent obese patients than in controls; the obese subjects also present a significant difference (p < 0.05). After glucagon injection no variations have been found in the ANF values until the 15th minute; then the controls, the obese and, above all, the non insulin-dependent diabetic obese subjects showed a significant increase of the ANF values between 60' and 90' (basal values 38 +/- 4 ng/ml; 90' values 85 +/- 7 ng ml). As these high values appear only after the induction of hyperinsulinism in our experiment and are not present in the type-1 diabetic subjects, it's probable that insulin, rather than glucagon, stimulates, directly or indirectly, the ANF secretion. If this hypothesis is confirmed, the correlation between insulin and ANF should deserve attention from a therapeutic point of view in subjects with glycometabolic imbalance.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Obesity; Potassium; Secretory Rate; Sodium

To investigate the relationship between the pituitary-adrenocortical function, abdominal obesity, and insulin resistance syndrome.. A prospective study.. Helsinki University Hospital, Finland.. Sixty-six healthy males aged 30-55 years.. Insulin, C-peptide, cortisol and ACTH responses during the oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone suppression and intravenous adrenocorticotrophic hormone (ACTH) stimulation.. The subjects in the highest tertile of the waist-to-hip ratio (WHR) had lower high-density lipoprotein cholesterol (HDLC) (P < 0.05), but higher triglyceride (TG), insulin, and C-peptide levels, ACTH response to glucose at 2 h, and cortisol response to ACTH (P < 0.01) than those in the lowest tertile. The cortisol response to ACTH correlated positively, but cortisol levels during the OGTT correlated negatively with WHR. The ratio of these cortisol determinations correlated positively with the body-mass index (BMI) (r = 0.554; P < 0.001), WHR (r = 0.536; P < 0.001), TG (r = 0.397; P = 0.001), fasting insulin (r = 0.534; P < 0.001) and C-peptide (r = 0.458; P < 0.001), and negatively with HDLC (r = 0.353; P = 0.004). In multiple regression analyses, BMI and the 2-h ACTH response to glucose were significant predictors of WHR and, in addition, the cortisol ratio, WHR, and BMI of insulin.. Abdominal obesity may be associated with subtle central adrenal insufficiency, which might also affect insulin and lipoprotein metabolism.

Topics: Abdomen; Adrenocorticotropic Hormone; Adult; Blood Glucose; Body Mass Index; C-Peptide; Humans; Hydrocortisone; Insulin; Insulin Resistance; Linear Models; Lipids; Male; Middle Aged; Obesity; Syndrome

Peripheral hyperinsulinism is said to be associated and perhaps implicated in the pathogenesis of hypertension. There is however some inconsistency in the evidence of the relationship between insulin and blood pressure. We prospectively investigated glucose metabolism, insulin and C-peptide values and serum lipids in a large sample of hypertensive as compared with age and body habitus-matched normotensive subjects. As a group, the 145 hypertensives (blood pressure: 160/99 +/- 8.5/6.5 mmHg, mean +/- SD) had significantly elevated fasting plasma insulin (p < 0.02), total and LDL-cholesterol (p < 0.01) than 132 normotensive control subjects. The fasting HbA1c (glycated hemoglobin A1c)/insulin ratio, an estimate of insulin sensitivity, was significantly lower (5.15 +/- 1.45) in the hypertensives than normotensives (5.8 +/- 1.5, p < 0.001). Hypertensives had normal fasting C-peptide levels and lower C-peptide/insulin molar ratios, indicating low hepatic insulin extraction. There was no correlation between mean blood pressure (1/3 systolic + 2/3 diastolic) and fasting serum C-peptide (p = 0.14), insulin (p = 0.11), HbA1c/insulin ratio (p = 0.6), C-peptide/insulin ratio (p = 0.22) and HbA1c (p = 0.19), even after adjusting for age, BMI and family history of diabetes. The differences between hypertensives and normotensives persisted after dividing the subjects according to the presence/absence of either obesity or impaired glucose tolerance, but the significance was lost due to the smaller samples of the subgroups. The obese hypertensives with impaired glucose tolerance had the lowest values of insulin sensitivity and clearance in the fasting state.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypertension; Insulin; Insulin Secretion; Lipids; Male; Metabolic Clearance Rate; Middle Aged; Obesity; Prospective Studies

To determine whether improved metabolic control with long term glyburide treatment alters intracellular glucose metabolism independent of effects on glucose uptake (GU), we studied eight obese patients with noninsulin-dependent diabetes mellitus before and 7 months after glyburide therapy. Indirect calorimetry and skeletal muscle biopsies were performed in the basal state and during 300 pmol/m2.min insulin infusions, with glucose turnover rates determined by [3-3H]glucose turnover. During the glucose clamps, rates of GU were matched before and after treatment using equivalent hyperinsulinemia and variable levels of hyperglycemia. After glyburide treatment, rates of GU were decreased in the basal state [4.16 +/- 0.57 vs. 3.29 +/- 0.37 mg/kg fat free mass (FFM)/min; P < 0.05], but similar during glucose clamps (11.53 +/- 1.42 vs. 11.93 +/- 1.32 mg/kg FFM.min; P = NS) according to study design. In both the basal state and during glucose clamps after glyburide therapy, rates of glucose oxidative metabolism (Gox) increased by 68-78% [1.21 +/- 0.16 vs. 2.03 +/- 0.31 mg/kg FFM.min (P < 0.05) and 3.13 +/- 0.51 vs. 5.58 +/- 0.55 mg/kg FFM.min (P < 0.05), respectively], and rates of nonoxidative glucose metabolism decreased [2.96 +/- 0.68 vs. 1.25 +/- 0.21 mg/kg FFM.min (P < 0.05) and 8.40 +/- 1.50 to 6.30 +/- 1.40 mg/kg FFM.min (P < 0.01), respectively]. Circulating plasma FFA levels and rates of fat oxidation (Fox) remained unchanged in both the basal state and during clamp studies. Skeletal muscle glycogen synthase (GS) activity, expressed as fractional velocity, was unchanged by glyburide therapy (2.2 +/- 0.8 vs. 2.7 +/- 0.3% in the basal state and 7.3 +/- 1.8 vs. 6.1 +/- 0.9% during clamps; both P = NS). In summary, at both matched (during clamp studies) and unmatched (during basal studies) rates of GU, improved metabolic control with glyburide therapy resulted in marked improvement of Gox independent of the effects on GU. The improvement in Gox was not associated with changes in Fox, circulating FFA, or muscle GS activity. These data indicate that long term metabolic control achieved by glyburide therapy markedly improves Gox, but not skeletal muscle GS activity, in noninsulin-dependent diabetes mellitus independent of GU and Fox.

Topics: Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Calorimetry, Indirect; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucagon; Glucose; Glucose Clamp Technique; Glyburide; Glycogen Synthase; Humans; Insulin; Male; Middle Aged; Muscles; Obesity; Oxidation-Reduction; Pyruvate Dehydrogenase Complex

To examine the cause of hyperinsulinemia in obesity, we determined plasma glucose, insulin, and C peptide responses to glucose (75g), arginine (0.5 g/kg body weight), and glucagon (1mg) in seven normal subjects and 20 obese subjects before and after weight loss by very low calorie diet therapy (Optifast, 240 kcal/day for 8 to 12 weeks). Integrated insulin and C peptide secretion in response to three different stimuli were markedly increased before weight loss and were significantly decreased following weight loss in response to glucose (mean +/- s.e. 36.6 +/- 6.4 vs. 18.4 +/- 2.6; 148.2 +/- 12.0 vs. 113.1 +/- 8.7 pmol/ml/h; P < 0.01), arginine (13.8 +/- 2.2 vs. 8.2 +/- 2.1; 94.8 +/- 11.2 vs. 66.0 +/- 6.1 pmol/ml/h; P < 0.01), and glucagon (16.5 +/- 2.7 vs. 10.7 +/- 1.5; 89.0 +/- 6.0 vs. 68.7 +/- 4.8 pmol/m/h; P < 0.01). The molar ratio of integrated C peptide to integrated insulin in response to all three stimuli was markedly decreased before, and this ratio significantly increased following weight loss (mean +/- s.e., 5.01 +/- 0.41 vs. 7.45 +/- 0.65; P < 0.01), and to arginine (7.78 +/- 0.61 vs. 10.97 +/- 1.28; P < 0.05), but not to glucagon (6.72 +/- 0.60 vs. 7.47 +/- 0.66). These findings suggest that both increased insulin secretion and decreased insulin clearance contribute to hyperinsulinemia in obese subjects. Improvement in these abnormalities to all three stimuli after weight loss also suggests that hyperinsulinemia in obesity is a consequence of the obesity itself rather than a pre-existing disorder.

Topics: Adolescent; Adult; Arginine; Blood Glucose; Body Mass Index; C-Peptide; Energy Intake; Glucagon; Glucose; Humans; Insulin; Insulin Secretion; Kinetics; Male; Obesity; Weight Loss

Female hyperandrogenism is often associated with hyperinsulinaemia and insulin resistance. We evaluated the hormone responses in an oral glucose tolerance test to investigate the interactions of gonadotrophins, insulin, C-peptide and androgens in women with polycystic ovarian disease (PCOD). In 28 patients with ultrasonographically diagnosed PCOD, hyperinsulinaemia and insulin resistance were mainly associated with obesity. Both basal and cumulative sum of insulin to C-peptide ratios were high in obese subjects, suggesting decreasing hepatic removal of insulin caused by obesity. Nevertheless, in some lean PCOD women, despite normal fasting insulin concentrations, insulin hypersecretion existed. The mean concentration of testosterone decreased significantly during the oral glucose tolerance test both in PCOD and control women, and of androstenedione in the PCOD patients only. However, an increase in androgen responses was found in a subgroup of PCOD patients, who had both elevated luteinizing hormone (LH) concentrations and hyperinsulinaemic response to oral glucose. In the remaining PCOD patients an inverse correlation between LH and insulin was found. The patients with hyperinsulinaemia together with LH hypersecretion may represent a subgroup of PCOD with deranged regulation of androgen secretion.

Topics: Adolescent; Adult; Androgens; Androstenedione; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Testosterone; Ultrasonography

Conventional immunoassays to quantify insulin concentration do not differentiate between insulin and proinsulin. Thus, previous conclusions as to the relationship between the development of hyperglycemia in patients with noninsulin-dependent diabetes mellitus (NIDDM) and pancreatic insulin secretory function may have been confounded by not being able to determine the contribution made by plasma proinsulin to the putative measurements of plasma insulin concentration in these patients. The current study was initiated to address this issue by making specific measurements of plasma insulin, proinsulin, and C-peptide concentrations in 42 individuals: 14 with normal glucose tolerance, 12 with impaired glucose tolerance (IGT), and 16 with NIDDM. The study population was further subdivided into a nonobese (body mass index, < 30 kg/m2) and an obese (body mass index, > 30 kg/m2) group. Mixed meals were given at 0800, 1200, and 1800 h, and blood was removed at 0800 h (before the meal) and at hourly intervals from then until 1600 h. Plasma glucose concentrations throughout the sampling period were slightly, but significantly (P < 0.01), greater in patients with IGT than in normal individuals. Patients with NIDDM had markedly elevated glycemic excursions, greater than either of the other two groups (P < 0.002). Both plasma immunoreactive insulin and C-peptide concentrations from 0800-1600 h were higher (P < 0.002-0.001) in patients with either IGT or NIDDM than in the group with normal glucose tolerance. Although day-long plasma immunoreactive insulin and C-peptide concentrations were higher, on the average, in patients with IGT compared to those with NIDDM, the difference was not statistically significant. Plasma proinsulin concentrations were highest in patients with NIDDM (P < 0.002), lower in those with normal glucose tolerance (P < 0.002), and intermediate in patients with IGT. When the calculated "true" insulin concentration was determined by taking the proinsulin content into consideration, patients with IGT had the highest day-long levels, with the lowest values found in the control population (P < 0.002). Although absolute values varied as a function of obesity, the generalizations outlined above were found in both weight groups. These results show that ambient plasma proinsulin concentrations increase as glucose tolerance declines. However, true plasma insulin concentrations in response to mixed meals remain highest in patients with IGT, lowest in normal ind

Topics: Blood Glucose; C-Peptide; Circadian Rhythm; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Obesity; Proinsulin; Reference Values

Hyperandrogenism in patients with polycystic ovary syndrome has been shown to correlate with hyperinsulinaemia of insulin resistance. We have investigated if basal levels of insulin and the response to the intravenous administration of glucagon can reveal insulin resistance in patients with polycystic ovary syndrome.. Nine obese (BMI > 25 kg/m2) and nine non-obese (BMI 19-25 kg/m2) women with PCOS, chosen from a population of 91 women attending the infertility clinic, and 19 normally cycling women (seven obese, 12 non-obese) were studied. Oligo or amenorrhoea, hirsutism, and 12 or more follicles in a given ovary were selection criteria.. Glucagon, 1 mg, was given intravenously to 18 of the 91 women and to the control subjects. Blood was taken at -5, 0, 5, 10 and 15 minutes for measurements of integrated areas under the response curve for insulin, C-peptide and glucose, respectively. Basal blood samples were drawn for fasting insulin, C-peptide, glucose, testosterone, sex hormone-binding globulin (SHBG), free fatty acids and IGF-I measurements. The free androgen index was calculated according to the formula FAI = testosterone x 100/SHBG.. There were no significant differences in maximal increment and area under the response curve for glucose, C-peptide and insulin. FAI was significantly higher in all patients with features of polycystic ovary syndrome. However, fasting insulin levels were significantly higher only in obese patients when compared with obese control subjects and lean patients.. The administration of 1 mg glucagon i.v. did not distinguish patients with polycystic ovary syndrome from control subjects. The mild insulin resistance of polycystic ovary syndrome is related only to obesity and is therefore unlikely to play an important role in the hyperandrogenism associated with the syndrome.

Topics: Adult; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Female; Glucagon; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Islets of Langerhans; Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone

The association of blood pressure with clinical and biochemical measures was studied in 185 newly diagnosed Type 2 diabetic patients, 74 impaired-glucose-tolerant (IGT) and 128 non-diabetic control subjects. Hyperglycaemic subjects were older than control subjects (controls 40 (24-59) years, IGT 48 (29-64) years, diabetic 43 (29-60) years, median (5th-95th centile) both p < 0.05). They were also more obese (body mass index (BMI) controls 23.5 kg m-2 (17.2-29.9), IGT 26.0 kg m-2 (19.8-33.9), diabetic 24.2 kg m-2 (19.3-32.2)) and with a greater waist-hip ratio (controls 0.83 (0.70-0.98), IGT 0.88 (0.75-0.98), diabetic 0.89 (0.75-1.00)). Blood pressure was significantly higher in both IGT (systolic 127 mmHg (108-162), diastolic 84 mmHg (66-99)) and diabetic patients (systolic 130 mmHg (104-160), diastolic 84 mmHg (66-102)) compared to non-diabetic controls (systolic 120 mmHg (100-151), diastolic 80 mmHg (60-94)). Univariate analysis showed that in diabetic patients systolic blood pressure was related to age (r = 0.17, p < 0.05), BMI (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting and post glucose, r = approximately 0.25, p < 0.01) but not to C-peptide concentrations; diastolic blood pressure to BMI (r = 0.35, p < 0.001), waist-hip ratio (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting r = 0.30, p < 0.001, post glucose r = approximately 0.20, p < 0.05) but not to C-peptide concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diastole; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Obesity; Systole

Acetate is a short-chain fatty acid derived from colonic fermentation of carbohydrate and dietary fiber, and from endogenous glucose and fatty acid metabolism in the liver. An impaired acetate metabolism has been reported in diabetic subjects. The aim of the study was to evaluate plasma acetate levels in a group of obese diabetic subjects, compared with obese normoglycemic subjects and normal control subjects. Eleven noninsulin-dependent diabetic patients taking oral antidiabetic drugs, eight obese normoglycemic subjects, and seven control subjects were studied. Liver, kidney, and gut functions were normal in all subjects. Blood acetate, glucose, insulin, and C-peptide were evaluated in all subjects. Acetate levels were significantly higher in the diabetic subjects than in obese normoglycemic and normal subjects. Significant correlations between HbA1c, glucose, and acetate levels, but not between acetate and C-peptide or insulin, were also observed.

Topics: Acetates; Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Lipids; Middle Aged; Obesity

The existence of insulin feedback inhibition is a controversial issue. The present study adopted a novel approach to determine whether insulin feedback inhibition exists in vivo during physiologic hyperinsulinemia and if it could contribute to enhanced insulin secretion in obesity. Serial plasma insulin and C-peptide levels were determined during a basal state and a hyperinsulinemic clamp (287 pmol/min/m2) and following discontinuation of the insulin infusion under euglycemic conditions. Insulin secretion rates were derived from plasma C-peptide levels and individual C-peptide kinetics using a two-compartment model. Eight non-obese and nine obese men were recruited for the studies, which were performed in random order. Men with significant variations in glucose levels during hyperinsulinemia were excluded from the analysis. Plasma glucose levels were similar between the non-obese and obese groups during all phases of the study, and similar plasma insulin levels were achieved in both groups during euglycemic hyperinsulinemia. In obese men, C-peptide levels were significantly greater compared with non-obese men during euglycemic hyperinsulinemia (P < .05). However, neither the non-obese nor the obese group demonstrated significant suppression of insulin secretion rates during euglycemic hyperinsulinemia. Expressing the data in absolute terms or as a percent of basal did not alter the results. Moreover, there was no significant change between the non-obese and the obese group during the rapid onset and cessation of hyperinsulinemia. Under euglycemic conditions, physiologic hyperinsulinemia does not induce suppression of endogenous insulin secretion in non-obese or obese men.

Topics: Adult; Analysis of Variance; Blood Glucose; C-Peptide; Feedback; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin; Male; Obesity

Hypertensive obese subjects with glucose intolerance have hyperinsulinaemia, insulin resistance and intracellular cation imbalance resulting in increased sodium content. The aim of our study was to assess in these patients plasma levels of endogenous digoxin-like factor (EDLF), an inhibitor of the sodium-pump mechanism. We studied 14 hypertensive and 12 normotensive subjects with obesity and glucose intolerance for fasting blood glucose, and plasma insulin, C-peptide and EDLF levels: the two groups were matched for age and BMI and were studied after a 2-week wash-out period from hypotensive drugs. Compared with normotensives, hypertensive subjects had higher plasma insulin levels, a greater immunoreactive insulin/C-peptide ratio, a lower glucose/insulin ratio and higher plasma EDLF levels. Our results confirm that among obese people with glucose intolerance, hypertensives are more hyperinsulinaemic and insulin-resistant than normotensives and indicate that the intracellular cation imbalance in these patients may be attributable, at least in part, to EDLF.

Topics: Blood Glucose; Blood Proteins; C-Peptide; Cardenolides; Digoxin; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Hypertension; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Saponins; Sodium-Potassium-Exchanging ATPase

Glucagon-like peptide-1 (7-36) amide (glucagon-like insulinotropic peptide, or GLIP) is a gastrointestinal peptide that potentiates the release of insulin in physiologic concentrations. Its effects in patients with diabetes mellitus are not known.. We compared the effect of an infusion of GLIP that raised plasma concentrations of GLIP twofold with the effect of an infusion of saline, on the meal-related release of insulin, glucagon, and somatostatin in eight normal subjects, nine obese patients with non-insulin-dependent diabetes mellitus (NIDDM), and eight patients with insulin-dependent diabetes mellitus (IDDM). The blood glucose concentrations in the patients with diabetes were controlled by a closed-loop insulin-infusion system (artificial pancreas) during the infusion of each agent, allowing measurement of the meal-related requirement for exogenous insulin. In the patients with IDDM, normoglycemic-clamp studies were performed during the infusions of GLIP and saline to determine the effect of GLIP on insulin sensitivity.. In the normal subjects, the infusion of GLIP significantly lowered the meal-related increases in the blood glucose concentration (P less than 0.01) and the plasma concentrations of insulin and glucagon (P less than 0.05 for both comparisons). The insulinogenic index (the ratio of insulin to glucose) increased almost 10-fold, indicating that GLIP had an insulinotropic effect. In the patients with NIDDM, the infusion of GLIP reduced the mean (+/- SE) calculated isoglycemic meal-related requirement for insulin from 17.4 +/- 2.8 to 2.0 +/- 0.5 U (P less than 0.001), so that the integrated area under the curve for plasma free insulin was decreased (P less than 0.05) in spite of the stimulation of insulin release. In the patients with IDDM, the GLIP infusion decreased the calculated isoglycemic meal-related insulin requirement from 9.4 +/- 1.5 to 4.7 +/- 1.4 U. The peptide decreased glucagon and somatostatin release in both groups of patients. In the normoglycemic-clamp studies in the patients with IDDM, the GLIP infusion significantly increased glucose utilization (saline vs. GLIP, 7.2 +/- 0.5 vs. 8.6 +/- 0.4 mg per kilogram of body weight per minute; P less than 0.01).. GLIP has an antidiabetogenic effect, and it may therefore be useful in the treatment of patients with NIDDM:

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Eating; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Insulin; Insulin Infusion Systems; Insulin Secretion; Male; Middle Aged; Obesity; Peptide Fragments; Peptides; Somatostatin

Serum sex hormone binding globulin (SHBG) concentration of children with obesity was measured and relationships between SHBG level and body mass index (BMI), waist hip ration (WHR), serum insulin, C-peptide, thyroid hormones (thyroxine--T4, triiodothyronine--T3/ sexual hormones (testosterone--T, oestradiol--E2) were investigated. Significant negative correlations were found between SHBG concentration and BMI, serum insulin, C-peptide concentration; significant positive concentrations were found between BMI and serum insulin, C-peptide concentration. Thyroid hormone and sexual hormones did not associate with SHBG levels. These results suggest that insulin hypersecretion has an important role in determining the reduction of SHBG production in obesity.

Topics: Adolescent; Body Mass Index; C-Peptide; Child; Female; Gonadal Steroid Hormones; Humans; Insulin; Male; Obesity; Sex Hormone-Binding Globulin; Thyroid Hormones

Serum C-peptide immunoreactivity (CPR)/immunoreactive insulin (IRI) molar ratio was determined in 136 subjects without renal, hepatic and thyroid disorders, at fasting, and during the initial period of 75 g-oral glucose tolerance test. The subjects were divided into 4 groups based on their body weight and age; Group A, young (< 55 years) and normal body weight (body mass index [BMI, kg/m2] < or = 25) subjects; Group B, young and overweight (BMI > 25) subjects; Group C, aged (> or = 55 years) and normal body weight (BMI < or = 25) subjects; Group D, aged and overweight subjects. Fasting CPR/IRI ratio and absolute CPR level negatively correlated in Groups B and D but not in A and C. After oral glucose load with elevation of insulin, CPR/IRI ratio invariably declined in all groups and significant negative correlation between CPR/IRI and CPR was found in Groups A, B and D but not in C. Slope of the regression lines obtained for correlation between CPR/IRI ratio and CPR were significantly steeper at fasting compared to the post-stimulation phase. CPR/IRI ratio is affected by hyperinsulinemia and oral glucose load but not by obesity alone. Assuming that CPR/IRI ratio reflects hepatic extraction of insulin, the insulin clearance at fasting is progressively reduced with increasing insulin secretion in overweight subjects: failure to detect such phenomenon in normal body weight subjects may be due to a narrower CPR range in this population. Insulin metabolism at fasting and during glucose stimulation is likely to be regulated by distinct factors.

Topics: Aged; Blood Glucose; Body Weight; C-Peptide; Female; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Obesity

Several studies have demonstrated that patients with hypertension have greater plasma insulin levels than normotensive subjects. The aim of the present study was to clarify if hyperinsulinemia in hypertension is a consequence of either increased pancreatic secretion or decreased hepatic clearance, and to determine whether abnormalities of glucose metabolism are equally present in essential and secondary hypertension. In an observational cross-sectional study, fasting blood glucose, plasma insulin, and plasma C-peptide levels were measured in five patient groups: 34 lean normotensive, 19 overweight normotensive, 25 lean essential hypertensive, 27 overweight essential hypertensive, and 20 secondary hypertensive subjects. The blood glucose/plasma insulin and plasma insulin/plasma C-peptide ratios were calculated as indexes of insulin sensitivity and hepatic insulin clearance, respectively. Subjects with essential hypertension and, to a greater extent, those who were overweight, exhibited significantly higher fasting insulin and C-peptide levels and significantly lower glucose/insulin ratios as compared with lean normotensive subjects. In contrast, no differences were observed between secondary hypertensive and control subjects. Mean blood pressure was significantly and independently correlated to body mass index, plasma insulin and plasma C-peptide levels, and the glucose/insulin ratio. In lean essential hypertensive and secondary hypertensive subjects, the insulin/C-peptide ratios were comparable to controls, indicating normal hepatic insulin clearance. In both overweight groups, a trend to increased insulin/C-peptide ratios was observed. This study shows that in essential hypertensive subjects, hyperinsulinemia is caused by insulin hypersecretion, whereas in overweight subjects, both increased insulin secretion and decreased hepatic insulin clearance might be involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Fasting; Female; Humans; Hyperinsulinism; Hypertension; Male; Middle Aged; Obesity

Obesity is characterized by peripheral hyperinsulinemia, for which either beta-cell hypersecretion, diminished hepatic insulin extraction, or both may be responsible. To clarify this issue, we investigated insulin secretion and hormone hepatic extraction in 18 nondiabetic obese patients (body mass index [BMI], 39 +/- 1.3 kg/m2) and 18 healthy, lean control subjects (BMI, 21.3 +/- 0.7 kg/m2). Body fat distribution was calculated by measuring the waist to hip ratio (WHR). A highly reduced tissue insulin sensitivity (2.4 +/- 0.5 v 9.5 +/- 1.5 10(4).min-1/[microU/mL], P > .0005) and glucose effectiveness, ie, glucose's ability to stimulate its own disappearance at basal insulin (16 +/- 2 v 30 +/- 3 10(3).min-1, P > .005), were found in the overweight subjects compared with the controls. The basal (76 +/- 14 v 37 +/- 4 pmol/L/min) and total (377,848 +/- 5,562 v 16,864 +/- 1,850 pmol/L) prehepatic insulin secretion and the basal (15 +/- 2 v 7 +/- 0.7 pmol/L/min) and total (8,286 +/- 2,009 v 2,840 +/- 210 pmol/L) posthepatic insulin delivery were significantly higher in the overweight subjects compared with the controls (P < .005), whereas the mean hepatic insulin extraction did not differ (77.8% +/- 2.6% v 79.5% +/- 2.6%). A significant inverse correlation was found between the hepatic insulin extraction and the WHR (r = .5, P > .04), signifying the importance of fat distribution in insulin metabolism. The obese patients were subdivided into two subgroups according to their glucose tolerance; eight patients exhibited a normal tolerance and the remaining 10 were intolerant.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Adult; Blood Pressure; C-Peptide; Cholesterol; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Hip; Humans; Hyperinsulinism; Insulin; Islets of Langerhans; Liver; Male; Models, Biological; Obesity; Time Factors; Triglycerides

It is known that calcium-antagonist drugs can modify the insulin response to various secretagogues. In order to clarify whether calcium-antagonist effect was directed at the level of pancreatic insulin secretion or hepatic insulin extraction and further investigate the pathogenesis of hyperinsulinemia in obesity, an oral glucose tolerance test (OGTT) was performed in basal conditions and during a Verapamil infusion (VE, 5 mg/h x 3.5 h) in 12 normal subjects and 14 obese patients with normal glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Insulin Secretion; Kinetics; Obesity; Reference Values; Time Factors; Verapamil

Raised insulin levels are now recognized as a characteristic feature of women with polycystic ovaries (PCO), and hyperinsulinism has been shown to stimulate androgen production in such women. We have, however, recently shown that hyperinsulinaemia is present only in the obese subjects with PCO in whom insulin concentrations correlate with those of luteinizing hormone. We therefore studied 24-hour blood profiles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in obese and non-obese women with PCO, for comparison with their levels of insulin, C-peptide and other hormones, such as androgens which are known to be disturbed in PCO. Mean 24-hour GH levels were higher overall in PCO than in control subjects, although the difference was not significant. When, however, a separate analysis was made in obese as compared with non-obese PCO patients, GH concentrations were significantly higher in the non-obese group than in the obese (p = 0.0005). There was a significant negative correlation between body mass index and mean 24-hour GH concentrations (r = -0.641; p = 0.0006). IGF-I concentrations were however similar in the PCO group overall and in controls, as well as in the obese and non-obese PCO patients. The 24-hour blood glucose profile pattern was significantly different in PCO women from controls (p = 0.009), with absence of post-prandial peaks in blood glucose concentrations. These changes were most marked in the non-obese PCO group, who also had significantly lower blood glucose levels than either controls or obese PCO subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; Body Mass Index; C-Peptide; Circadian Rhythm; Female; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Obesity; Polycystic Ovary Syndrome

The effect of the intravenous infusion of peptide p-Glu-His-Ala-OH, analog of the postulated anorexigenic peptide, on the insulinaemic response to an intravenous bolus of 20 g glucose was studied in 6 obese patients (body mass index 43.12 +/- 5.77 kg/m2). The infusion of the peptide reduced the insulinaemic response (p < 0.05) without modifying either the C-peptide or the glucose response. This decreased insulinaemic response is associated with a greater hepatic extraction of insulin (86.45 +/- 1.1% vs 82.1 +/- 1.2%; p 0.05), determined in terms of the molar ratio of the C-peptide to insulin) but not with a smaller pancreatic secretion (determined as C-peptide levels). Our results confirm that the infusion of the peptide increases the hepatic insulin extraction without its effect being mediated by any intestinal factor. Its therapeutic application remains to be determined.

Topics: Adult; Amino Acid Sequence; Appetite Depressants; Blood Glucose; C-Peptide; Female; Glucose; Humans; Infusions, Intravenous; Injections, Intravenous; Insulin; Insulin Secretion; Middle Aged; Molecular Sequence Data; Obesity; Oligopeptides; Pyrrolidonecarboxylic Acid

Insulin resistant glucose metabolism is a key element in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus. Insulin resistance may be of both primary (genetic) and secondary (metabolic) origin. Before and after diet-induced improvement of glycaemic control seven obese patients with newly-diagnosed Type 2 diabetes were studied with the euglycaemic clamp technique in combination with indirect calorimetry and forearm glucose balance. Muscle biopsies were obtained in the basal state and again after 3 h of hyperinsulinaemia (200 mU/l) for studies of insulin receptor and glycogen synthase activities. Similar studies were performed in seven matched control subjects. Insulin-stimulated glucose utilization improved from 110 +/- 11 to 183 +/- 23 mg.m-2.min-1 (p less than 0.03); control subjects: 219 +/- 23 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetes). Non-oxidative glucose disposal increased from 74 +/- 17 to 138 +/- 19 mg.m-2.min-1 (p less than 0.03), control subjects: 159 +/- 22 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetic patients). Forearm blood glucose uptake during hyperinsulinaemia increased from 1.58 +/- 0.54 to 3.35 +/- 0.23 mumol.l-1.min-1 (p less than 0.05), control subjects: 2.99 +/- 0.86 mumol.l-1.min-1 (p = NS, vs post-diet Type 2 diabetes). After diet therapy the increase in insulin sensitivity correlated with reductions in fasting plasma glucose levels (r = 0.97, p less than 0.001), reductions in serum fructosamine (r = 0.77, p less than 0.05), and weight loss (r = 0.78, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Calorimetry; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Fatty Acids, Nonesterified; Female; Fructosamine; Glycogen Synthase; Hexosamines; Humans; Insulin; Male; Muscles; Obesity; Receptor, Insulin; Reference Values

Twenty-four-hour energy expenditure and substrate use were measured by indirect calorimetry in respiration chambers on a fixed physical program and related to body composition and plasma concentrations of various substrates and thermogenic hormones. Fifty premenopausal women with a wide range of body weight were examined in the follicular menstrual phase under weight stable conditions. Most of the variance in the sleeping energy expenditure (82%) was accounted for by two covariates, lean body mass (75%, P less than 0.0001), and fat mass (7%, P less than 0.0001). An additional 6% of the variance in sleeping energy expenditure was accounted for by plasma androstenedione concentration (4%, P = 0.0005) and by free T3 index (2%, P = 0.03). Thus physiological variation among individuals in plasma androstenedione concentration may result in a difference in energy expenditure of 908 kJ/day and the corresponding variation in free T3 index may result in a difference between individuals of 594 kJ/day. Fifty four percent of the variation in carbohydrate oxidation rates was accounted for by 24-h energy balance, and by plasma concentrations of insulin, nonesterified fatty acids, and estradiol. Waist circumference, plasma nonesterified fatty acids, and estradiol concentrations explained 49% of the variance in 24-h lipid oxidation. An obese subgroup of women (n = 27) had significantly higher 24-h energy expenditure, lipid, and carbohydrate oxidation rates than an age-matched normal weight group (n = 16), but the entire group difference in energy expenditure was explained by differences in body composition. We conclude that physiological variations in plasma androstenedione and T3 concentrations contribute to the interindividual variance in energy expenditure of women, and their role is not different in obese women. A positive energy balance and increased insulin action may be mediators of the higher carbohydrate oxidation in obesity, whereas an increased substrate availability seems to bring about the increased lipid oxidation.

Topics: Adolescent; Adult; Blood Glucose; Body Composition; C-Peptide; Calorimetry; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Energy Metabolism; Epinephrine; Estradiol; Female; Growth Hormone; Hormones; Humans; Hydrocortisone; Insulin; Menopause; Middle Aged; Norepinephrine; Obesity; Reference Values; Sex Hormone-Binding Globulin; Testosterone; Thyroxine; Triiodothyronine

Islet amyloid polypeptide (IAPP/Amylin) is a novel peptide which was extracted from islet amyloid deposits in patients with non-insulin-dependent diabetes mellitus (NIDDM). However, its pattern of secretions and plasma concentrations under various conditions has not yet been made clear enough. In this study, we examined IAPP secretion from islet beta-cells in vitro using cultured islet cells of neonatal rat pancreas and plasma IAPP responses under various conditions in vivo in normal control subjects and patients with glucose intolerance. Our data revealed that (1) IAPP is co-secreted with insulin from islet cells of the rat pancreas by glucose and non-glucose stimuli; (2) fasting plasma IAPP levels in normal control subjects are 24.9 +/- 2.0 pg/ml and the molar ratio of IAPP/insulin is approximately 1/7; (3) fasting IAPP levels are high in obese patients and low in insulin-dependent diabetic patients, and the molar ratio of IAPP/C-peptide in NIDDM patients is lower than that in normal control subjects, suggesting the basal hyposecretion of IAPP relative to insulin in NIDDM; and (4) the obese patients who had a hyperresponsiveness of insulin relative to C-peptide had the hyperresponsiveness of IAPP relative to C-peptide during an oral glucose load, suggesting that IAPP may have some physiological effect in glucose metabolism.

Topics: Adult; Amyloid; Animals; Animals, Newborn; Blood Glucose; C-Peptide; Cells, Cultured; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Islet Amyloid Polypeptide; Islets of Langerhans; Middle Aged; Obesity; Rats; Reference Values

To evaluate insulin receptor binding characteristics of urbanized South African black women with normal glucose tolerance and of patients with newly diagnosed untreated non-insulin-dependent diabetes mellitus (NIDDM).. Four groups of 10 subjects each were selected by the following criteria: group A, young (20-39 yr) nonobese (body mass index [BMI] 19.0-24.9 kg/m2) nondiabetic women; group B, middle-aged (40-60 yr) nonobese nondiabetic women; group C, middle-aged obese (BMI greater than 30.0 kg/m2) nondiabetic women; and group D, middle-aged obese newly diagnosed but untreated female patients with NIDDM. Insulin binding to monocyte receptors was determined by radioreceptor assay. Fasting plasma samples were analyzed for glucose, insulin, C-peptide, and nonesterified fatty acids.. In the four groups studied, maximum specific binding and receptor concentration were highest in group A, with a progressive and significant decrease in values through groups B and C to group D. Significant inverse correlations were obtained between maximum specific binding, 50% inhibition dose, and total receptor concentration on the one hand and glucose, insulin, and NEFA on the other.. Our study of urban South African black women showed decreasing insulin-receptor activity with obesity and glucose intolerance. In patients with NIDDM, hyperglycemia and beta-cell dysfunction were associated with a reduction in receptor concentration. In this regard, our findings in South African blacks are consistent with results of similar studies of NIDDM in other communities.

Topics: Adult; Age Factors; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Humans; Insulin; Middle Aged; Monocytes; Obesity; Receptor, Insulin; Reference Values; South Africa; Urban Population

Insulin secretion rates can be accurately estimated from plasma C-peptide levels with a two-compartment model for C-peptide distribution and degradation. In previous studies, the kinetic parameters of C-peptide clearance were derived in each subject from the decay curve observed after bolus intravenous injection of biosynthetic human C-peptide. To determine whether standard parameters for C-peptide clearance could be defined and used to calculate insulin secretion without obtaining a decay curve in each subject, we analyzed 200 decay curves of biosynthetic human C-peptide obtained in normal, obese, and non-insulin-dependent diabetes mellitus subjects studied in our laboratory. This analysis showed that the volume of distribution and kinetic parameters of C-peptide distribution and metabolism vary by less than 30% in a population highly heterogeneous in terms of age, sex, degree of obesity, and degree of glucose tolerance. The volume of distribution correlated with the degree of obesity as quantified by body surface area (BSA). This dependence of C-peptide distribution volume on BSA was more marked in men than in women. The long half-life was slightly longer in elderly subjects than in younger adults. When effects of BSA, sex, and age were taken into account, the parameters of C-peptide kinetics were very similar in normal, obese, and diabetic subjects. Based on these findings, a simple procedure to derive standard parameters for C-peptide clearance taking into account degree of obesity, sex, and age was defined. These standard parameters resulted in estimations of mean insulin secretion rates, which differed in each subject by only 10-12% from those obtained with individual parameters. The approach of using standard rather than individual parameters did not systematically underestimate or overestimate insulin secretion so that group values for the fasting secretion rate, the mean 24-h secretion rate, and the number and the amplitude of secretory pulses obtained with standard parameters differed by only 1-2% from the values obtained with individual parameters. Furthermore, the accuracy of measurements based on standard parameters was not different from that associated with replicate determinations of the parameters of C-peptide clearance in the same subject. We conclude that it is possible to estimate insulin secretion rates from plasma C-peptide levels with standard parameters for C-peptide clearance rather than individually derived parameters without sig

Topics: Adult; Body Mass Index; Body Surface Area; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Secretion; Kinetics; Male; Mathematics; Metabolic Clearance Rate; Models, Biological; Obesity; Reference Values

We measured the degree of association between obesity, blood pressure, insulin resistance, and insulin secretion in 72 male and female obese hypertensive, obese nonhypertensive, and normal weight control subjects. Baseline weight, body mass index, percent body fat, waist/hip ratio, and systolic and diastolic blood pressures were obtained. Insulin sensitivity was assessed according to Bergman's minimal model. Twelve-hour urinary c-peptide was measured after a standard liquid meal. Insulin action was inversely associated with blood pressure status, obesity status, and age. Meal-stimulated c-peptide excretion significantly correlated with systolic blood pressure and percent fat but not with body mass index or age. Multivariate regression analysis indicated that, of the measures of body composition, percent fat and waist/hip ratio had the strongest correlation with insulin action either alone or in combination with c-peptide excretion. Obese hypertensive patients had an index of insulin action (10(-4).min-1/[microunits/ml]) of 1.34 +/- 0.19, which was significantly (p less than 0.003) lower than in the obese nonhypertensive patients (index, 2.26 +/- 0.10) or the nonobese subjects (index, 5.41 +/- 0.26, p less than 0.001). Meal-stimulated c-peptide excretion (nmol/kg lean body mass) was increased only in the obese hypertensive group (0.32 +/- 0.01) and was significantly higher (p less than 0.001) than in the obese nonhypertensive (0.16 +/- 0.01) or the nonobese subjects (0.14 +/- 0.01). These results support the hypothesis that abnormalities in blood pressure regulation, insulin-stimulated glucose uptake, and insulin secretion coexist.

Topics: Adult; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cluster Analysis; Diastole; Eating; Female; Humans; Hypertension; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Obesity; Systole

The time course of plasma glucose, insulin, and C-peptide after intravenous glucose (300 mg/kg body wt) injection was analyzed with minimal model approach in nine normal females and seven obese females. Glucose tolerance, estimated by glucose assimilation coefficient (KG), was positively correlated with glucose effectiveness (SG), but not correlated with peripheral insulin sensitivity (SI) in obese females as well as normal females. These factors were estimated before and after weight loss with 1.8-MJ (420-kcal) very-low-calorie diets (VLCDs) or with 2.5-3.3-MJ (600-800-kcal) low-calorie diets in two obese subjects. KG and glucose effectiveness decreased after acute weight loss with VLCD, although insulin sensitivity increased. Weight loss with low calorie diets resulted in improvement of KG and glucose effectiveness. These results suggest that a significant amount of glucose is taken up through insulin-independent mechanisms during the intravenous glucose tolerance test (ivGTT) in these subjects. This insulin-independent glucose uptake may be an important determinant of the fate of glucose in obese females as well as normal females.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Diet, Reducing; Energy Intake; Female; Glucose Tolerance Test; Humans; Insulin; Obesity; Pancreas

To investigate the temporal organization of insulin secretion and glucose concentration during fasting in Type 2 (non-insulin-dependent) diabetes mellitus, we studied seven patients with Type 2 diabetes, eight obese non-diabetic control subjects and eight normal weight non-diabetic subjects. Blood sampling for glucose, insulin and C-peptide was performed at 15-min intervals during a 24-h period of fasting for the diabetic and the obese control subjects and during an 8-h fasting period for the normal subjects. Insulin secretion rates were calculated from the peripheral C-peptide concentration profiles. Ultradian oscillations of glucose levels and insulin secretion rates were evident during fasting in all subjects. An additional study with blood sampling at 2-min intervals for 8 h further indicated that this ultradian periodicity is expressed independently of rapid 10-15 min insulin oscillations. There were no differences between diabetic and non-diabetic subjects in the frequency of the ultradian oscillations of insulin secretion (which averaged 12-15 oscillations per 24 h) and in the rate of concomitancy of oscillations of insulin secretion with oscillations in glucose levels, which averaged 63-65%. The relative amplitudes of both the insulin and glucose oscillations were also similar in diabetic and nondiabetic subjects. The major abnormality in patients with Type 2 diabetes was evidenced by spectral analysis, and confirmed by calculations of the distributions of inter-pulse intervals. It consisted of a slowing of the glucose oscillations, without a similar slowing of the oscillations in insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Activity Cycles; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Reference Values

Women with upper body obesity are at increased risk for cardiovascular disease (CVD). Several studies have demonstrated a reduced fibrinolytic activity in these patients, mainly due to an enhanced activity of plasminogen activator inhibitor-1 (PAI-1). Since an increase of androgenic activity is a feature of central obesity in women, the present study was aimed at evaluating the possibility of a relationship between androgens and PAI-1 (antigen and activity) in 20 premenopausal women, 10 with upper body obesity and 10 controls. In obese women, PAI-1 antigen showed a positive Pearson correlation with free testosterone (FT), insulin, c-peptide, triglycerides (TG), and waist to hip ratio (WHR) (P less than .01), whereas PAI-1 activity correlated positively only with insulin and WHR (P less than .01). In control women, PAI-1 antigen and activity were positively related only to TG (P less than .01). When we applied the multiple regression model with stepwise backward method to our data, both PAI-1 antigen and activity did not maintain any significant association. However, when the data from both the groups were pooled (n = 20), and PAI-1 antigen was considered as the dependent variable, body weight (Sig T = 0.0001), TG (Sig T = 0.0053), FT (Sig T = 0.013), and luteinizing hormone (LH) (Sig T = 0.0474) met the stepwise criteria, suggesting an independent effect of each of these parameters on PAI-1 antigen. On the other hand, when PAI-1 activity was tested as the dependent variable, only body weight maintained a significant relationship with this parameter (Sig T = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: C-Peptide; Female; Follicle Stimulating Hormone; Humans; Insulin; Luteinizing Hormone; Menopause; Menstruation; Middle Aged; Obesity; Plasminogen Inactivators; Reference Values; Sex Hormone-Binding Globulin; Testosterone

The present study was undertaken to evaluate the metabolic and hormonal responses to physiologic elevations of plasma beta-endorphin concentrations in both normal-weight and obese healthy subjects. The infusion of synthetic human beta-endorphin (4.5 ng/kg/min) produced the following: (1) in normal-weight subjects, no significant change of plasma glucose and pancreatic hormones (insulin, C-peptide, and glucagon), a significant plasma free fatty acids (FFA) increase, and a suppression of glycerol plasma levels; (2) in obese subjects, significant increases of glucose, insulin, C-peptide, and glucagon, a progressive decline of circulating FFA, and no change in glycerol plasma levels. In obese subjects, the intravenous administration of naloxone, given as a bolus (5 mg injected in 5 minutes) before the start of beta-endorphin infusion, reduced the plasma glucose response to the opioid by approximately half, annulled the pancreatic hormonal responses, and also reduced the FFA, but not glycerol, response. In normal-weight subjects, naloxone pretreatment did not induce any change of the flat glucose and hormonal responses to beta-endorphin, but reversed its effects on circulating FFA and glycerol. These data suggest that physiological elevations of plasma beta-endorphin concentrations produce metabolic and hormonal effects in obese subjects significantly different from those occurring in normal-weight subjects; these effects are partially naloxone-sensitive, suggesting the mediation of endogenous opioid receptors.

Topics: Adult; beta-Endorphin; Blood Glucose; Body Weight; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Kinetics; Male; Obesity; Reference Values

In order to assess hepatic glycogen stores in patients with noninsulin dependent diabetes mellitus (NIDDM) after a 3-day fast, the incremental glucose response to 1.0 mg iv glucagon (glucose area under the curve, glucoseAUC) was assessed in 19 obese diabetic subjects after an overnight (14 h) fast and again after a 3-day (64 h) fast. Results were compared to those of lean (n = 6) and obese (n = 15) nondiabetic subjects. During the fast, plasma glucose fell significantly in the lean (4.9 +/- 0.2 to 3.9 +/- 0.2 mmol/L), obese (5.1 +/- 0.1 to 4.2 +/- 0.2 mmol/L), and diabetic (14.7 +/- 0.7 to 10.3 +/- 1.0 mmol/L) subjects. However, in contrast to the fall in glucoseAUC observed in the lean (92.4 +/- 15.4 to 39.9 +/- 8.1 mmol min-1 L-1, P less than 0.02) and obese (64.4 +/- 11.1 to 48.4 +/- 9.4 mmol min-1 L-1) subjects, the glucoseAUC increased in diabetic subjects from 81.6 +/- 8.6 to 103.9 +/- 8.8 mmol min-1 L-1 during the fast, and was significantly greater than that of either the lean (P less than 0.001) or obese (P less than 0.001) nondiabetic subjects after the 64-h fast. Evidence that the glucose response to glucagon after a 64-h fast represents glycogenolysis and not gluconeogenesis was provided by studies in 10 additional subjects (5 obese nondiabetic subjects and 5 patients with NIDDM). Overall hepatic glucose output calculated from glucose kinetic data [( 3-3H]glucose) increased in diabetic and nondiabetic subjects during the first 30 min after glucagon administration and fell progressively thereafter. However, no increase in alanine gluconeogenesis (14C-alanine incorporation into glucose) was observed after glucagon administration in either subject group. The paradoxical accumulation of glycogen in the patients with NIDDM during the fast occurred despite basal rates of hepatic glucose output on the third day of the fast which were greater than those of obese nondiabetic subjects (9.0 +/- 1.2 vs. 5.6 +/- 0.5 mumol kg-1 min-1, P less than 0.05). A glycogen sparing action of increased gluconeogenesis is proposed as the explanation for the preservation of liver glycogen in patients with NIDDM.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Female; Glucagon; Glucose; Humans; Insulin; Insulin Secretion; Liver Glycogen; Male; Obesity; Reference Values

1. The purpose of the present study was to examine the ability of insulin to inhibit its own secretion in type 2 diabetes independently of the prevailing plasma glucose concentration. 2. The responses of the plasma C-peptide concentration to sustained hyperinsulinaemia were assessed during a 200 min isoglycaemic clamp study in 14 patients with type 2 diabetes and seven age- and weight-matched control subjects. The arterialized venous plasma glucose concentration was clamped at approximately 0.3 mmol/l below each subject's own basal level and was not permitted to rise above the basal level. 3. In the fasting state, the plasma C-peptide concentration was slightly, but not significantly, higher in the diabetic patients than in the control subjects (667 versus 413 pmol/l, respectively, P = 0.07), but it remained significantly higher in the diabetic patients during the clamp studies in absolute terms (minimum plasma C-peptide concentration 400 pmol/l in diabetic patients versus 151 pmol/l in control subjects, P less than 0.05) and was suppressed to a lesser extent when expressed as a percentage change from basal (35.8% in diabetic patients versus 59.4% in control subjects, P less than 0.01). 4. In order to investigate whether a high plasma glucose concentration was maintaining the plasma C-peptide concentration in the diabetic patients, six of these patients underwent a second clamp study at euglycaemia (plasma glucose concentration 5.2 mmol/l). Under these conditions, the plasma C-peptide concentration was suppressed to the same extent as in the control subjects (from 623 to 195 pmol/l, a change of 62.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Feedback; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity

The published literature on the influence of obesity on intermediary metabolite concentrations does not adequately address the potential confounding effects of the increased prevalence of impaired glucose tolerance in obese subjects. In order to remove this, we studied 109 subjects with proven normal glucose tolerance ranging from underweight to grossly obese (range 15.3-80.9 body mass index). All had blood intermediary metabolites, plasma insulin and C-peptide measured after an overnight fast. Thirty-six (18 from each end of the range of body mass index) received a 3-hour oral glucose tolerance test for metabolites and insulin. Fasting plasma insulin was highly significantly associated with body mass index (r = 0.72; P less than 0.001). Concentrations of lipid intermediaries were better associated with body mass index than with fasting plasma insulin: non-esterified fatty acids (r = 0.36; P less than 0.001), glycerol (r = 0.47; P less than 0.001) and ketone bodies (r = 0.45; P less than 0.001). Fasting concentrations of carbohydrate intermediaries were, however, better correlated with fasting plasma insulin: lactate (r = 0.29; P less than 0.01), pyruvate (r = 0.24; P less than 0.01) and alanine (r = 0.36; P less than 0.001). Glucose concentrations were associated with both to a similar degree (r = 0.33, r = 0.32, respectively; P less than 0.001). After oral glucose, exaggerated rises in plasma insulin and blood glucose were observed in obese subjects but a lesser rise was seen for lactate. Non-esterified fatty acids and ketones, although having higher fasting concentrations in obese subjects, fell to similar concentrations in the two groups after glucose whereas blood glycerol did not fall so far in the obese subjects. The results suggest, even if those subjects with impaired glucose tolerance are excluded, insensitivity to insulin in several aspects of intermediary metabolism in obesity the degree of which may vary in different metabolic pathways or tissues.

Topics: Adult; Alanine; Blood Glucose; Body Mass Index; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Glycerol; Humans; Insulin; Ketone Bodies; Lactates; Male; Middle Aged; Obesity; Obesity, Morbid; Pyruvates; Pyruvic Acid; Regression Analysis

In 10 obese, newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (group A) continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia over a period of 14 days. Fasting blood glucose was 4.61 +/- 0.22 mmol/l and mean daily blood glucose 5.83 +/- 0.27 mmol/l at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 h. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 56 +/- 0.35 to 24 +/- 0.76 micrograms/24 h. Thus, physiological insulin replacement induced normoglycemia in NIDDM, indicating that insulin resistance is not clinically important. Gliclazide was given to group A following CSII and to 5 obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A and induced in group B excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to iv glucose and by significant increases in the mean daily insulin to mean daily blood glucose ratio and in the 24-h urinary C-peptide to glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on sensitivity to endogenous insulin (slope of disappearance of blood glucose as function of insulin response to glucose infusion). During the 6 months of gliclazide treatment, excellent glycemic control was obtained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose as well as mean by 48-h insulin to glucose and urinary C-peptide to glucose ratios. Again, sensitivity to endogenous insulin was not augmented. We conclude that gliclazide has a beta-cell-stimulating action which is maintained quantitatively unchanged for at least 6 months. The therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on gliclazide action.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Follow-Up Studies; Gliclazide; Glucose Clamp Technique; Humans; Insulin; Insulin Infusion Systems; Insulin Secretion; Middle Aged; Obesity

Topics: Adult; Autonomic Nervous System; Blood Glucose; C-Peptide; Female; Humans; Insulin; Insulin Secretion; Obesity; Pancreas; Periodicity; Pulsatile Flow

Much research has demonstrated that in late pregnancy glucose administration causes a marked increase of peripheral insulin levels. To ascertain whether this particular increase is due to increased insulin secretion and/or to reduced hepatic insulin removal, we measured blood glucose, plasma C-peptide and plasma insulin during OGTT in 7 nonpregnant women and in 20 nondiabetic women at third trimester of gestation and 60-90 days after delivery. The C-peptide/insulin molar ratio was calculated for all subjects. Data obtained showed that both plasma insulin and C-peptide response to oral glucose is considerably higher in women at third trimester of pregnancy as compared with that observed in the same subjects after delivery and in nonpregnant women. The basal (overnight fasting) C-peptide/insulin molar ratio did not differ significantly between pregnant and nonpregnant women. After the oral glucose load the molar ratio was sharply reduced in all groups of subjects, but the overall decrease in the pregnant women in the three hours following oral glucose was considerably greater than in postpartum and in nonpregnant women. The increased plasma C-peptide response clearly indicates that in pregnancy oral glucose-induced hyperinsulinism is caused by increased insulin release from pancreatic B-cells. Moreover, the marked overall decrease of the C-peptide/insulin molar ratio suggests, even if it does not definitely prove, that hyperinsulinism after glucose in late pregnancy may be a consequence not only of increased insulin secretion, but also of decreased hepatic extraction of insulin.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Liver; Obesity; Pancreas; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third

To investigate the relative contribution of insulin and sex hormones in determining the abdominal pattern of fat distribution in premenopausal women, five groups of age-matched subjects were examined: Group 1 consisted of 14 normal weight eumenorrheic women (NO); Group 2 of 9 obese eumenorrheic women (OB); Group 3 of 14 normal weight hyperandrogenic women with polycystic ovary syndrome (NO-HA); Group 4 of 10 obese hyperandrogenic women with polycystic ovary syndrome (OB-HA) and, finally, Group 5 of 10 obese hyperandrogenic women with polycystic ovary syndrome and acanthosis nigricans (OB-HA-AN). Both the two normal weight groups and the three obese groups were matched for body mass index values. Sex hormone pattern showed significantly higher LH and testosterone levels in hyperandrogenic women with respect to NO and OB women but obese hyperandrogenic groups (OB-HA and OB-HA-AN) presented significantly lower LH concentrations than NO-HA. Fasting and glucose-stimulated insulin levels were significantly higher in OB than NO, in OB-HA and OB-HA-AN than in OB and NO-HA, and in OB-HA-AN than in OB-HA, without any significant difference between OB and NO-HA. Body fat distribution, expressed by the waist to hip ratio (WHR), showed progressively higher values (p less than 0.01) from NO to OB, NO-HA, OB-HA and, particularly, OB-HA-AN women. Determination coefficients r2 obtained from simple regression analysis showed that the sum of insulin values during the glucose tolerance test and testosterone levels had a more significant power in determining WHR variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Acanthosis Nigricans; Adipose Tissue; Adult; Androgens; Blood Glucose; Body Mass Index; C-Peptide; Fasting; Female; Glucose; Gonadal Steroid Hormones; Gonadotropins; Humans; Insulin; Male; Obesity; Polycystic Ovary Syndrome; Regression Analysis

Dehydroepiandrosterone (DHEA) has an anti-obesity effect in rodents and reduces body fat in normal men. Therefore, the plasma levels of DHEA were evaluated in nine premenopausal healthy women and in 13 menstrually active nondiabetic obese women, including patients (n = 6) with body mass index (BMI) over 40. In the obese group, a significant inverse correlation between DHEA levels and BMI was found. These results suggest that patients with severe obesity are unable to increase the DHEA adrenal production rate in order to parallel the increase in the hormone metabolic clearance rate (due to enlargement of body fat mass per se). The deficiency of this mechanism might itself contribute to the progressive fat accumulation in severe obesity.

Topics: Abdomen; Adipose Tissue; Adult; Body Mass Index; C-Peptide; Dehydroepiandrosterone; Female; Glucose Tolerance Test; Hip; Humans; Insulin; Menopause; Middle Aged; Obesity; Reference Values; Sex Hormone-Binding Globulin; Testosterone; Triglycerides

To determine whether Impaired Glucose Tolerance gives rise to additional defects in insulin action in lipid and ketone metabolism, thirty-two obese subjects were studied by low-dose incremental insulin infusion. Sixteen had Impaired Glucose Tolerance and 16 had normal glucose tolerance. Body mass index was 36.9-80.9 kg m-2 and was similar in each group. In patients with Impaired Glucose Tolerance, plasma insulin was higher in the fasted state (logarithmic mean 14.5 (9.8-21.6) (-SD(-)+SD) vs 9.6 (6.4-14.5) mU l-1, p less than 0.01) and during the infusion (p less than 0.001). The metabolic clearance rate for insulin at the highest infusion rate was lower (14.2 +/- 0.8 (+/- SE) vs 18.9 +/- 2.1 ml kg-1 min-1, p less than 0.05) in these subjects. Basal hepatic glucose production was higher in subjects with Impaired Glucose Tolerance (6.3 +/- 0.4 vs 4.5 +/- 0.6 mol kg-1 min-1, p less than 0.02) and remained elevated during infusion (p less than 0.01). Glucose disposal per unit circulating insulin at the maximal infusion rate was approximately half in subjects with Impaired Glucose Tolerance (0.022 +/- 0.010 vs 0.047 +/- 0.017 ml kg-1 min-1 mU-1 l, p less than 0.01). When simultaneous insulin and metabolite concentrations during the infusion are plotted as dose-response relationships, a difference in relative sensitivity to insulin in Impaired Glucose Tolerance over subjects with normal glucose tolerance is suggested for non-esterified fatty acids 0.72 (95% CI 0.62-0.84) and glycerol 1.85 (1.37-2.49).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; C-Peptide; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Infusion Systems; Insulin Resistance; Ketone Bodies; Male; Middle Aged; Obesity

Several clinical and epidemiological evidences support the increased risk of cardiovascular disease (CVD) in pathological conditions as obesity, hypertension, non-insulin-dependent diabetes mellitus, which have hyperinsulinemia as a common feature. In this study, we assessed basal plasma insulin (IRI) and C-peptide (CPR) concentrations in 297 volunteers who participated in a survey concerning risk factors of CVD. We found a stepwise increase in fasting insulin and C-peptide levels in normal subjects (IRI 9.10 +/- 0.41 microU/ml; CPR 1.79 +/- 0.08 ng/ml), in obese subjects (IRI 11.31 +/- 0.38 microU/ml; CPR 2.54 +/- 0.07 ng/ml) in obese hypertensive subjects (IRI 14.17 +/- 0.72 microU/ml; CPR 2.64 +/- 0.09 ng/ml), in obese hypertensive diabetic subjects (IRI 22.57 +/- 2.62 microU/ml; CPR 3.33 +/- 0.27 ng/ml). Thus, we found increasing levels of IRI and CPR as normal conditions changed towards progressively more severe pathological conditions. Although several other factors contribute to determine CVD, we conclude that increasing levels of insulin and C-peptide could play an important role in causing CVD.

Topics: Adult; Biomarkers; Blood Pressure; C-Peptide; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hypertension; Insulin; Male; Medical History Taking; Middle Aged; Obesity; Risk Factors; Surveys and Questionnaires

To assess the total insulin secretion in children in different nutritional states we have analysed the 24 h urinary C-peptide excretion in 32 obese children (16 boys and 16 girls) 8-15 years of age as well as in 7 girls with anorexia nervosa 11-16 years of age. Obese children had a median urinary C-peptide excretion rate of 0.27 nmol/kg/24 h, which was not different from that of a group of normal-weight children. In the group of anorectic girls, on the other hand, the median value 0.47 nmol/kg/24 h was significantly (p less than 0.05) higher than for normal-weight girls of the same age (median = 0.26 nmol/kg/24 h). These results indicate that in obese children insulin secretion, measured as the 24 h urinary C-peptide excretion per kg body weight, is the same as in normal-weight children. Total insulin secretion is consequently increased. In anorexia nervosa, on the other hand, the higher C-peptide excretion per kg body weight compared with normal-weight children, indicates that insulin secretion is increased in relation to body weight.

Topics: Adolescent; Anorexia Nervosa; Body Weight; C-Peptide; Child; Circadian Rhythm; Female; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Obesity

We have examined the relationships between obesity indices and various metabolic parameters in seven obese (body mass index (BMI) mean +/- s.e.m. 42 +/- 2.5 kg/m2), ten nonobese (BMI 25.3 +/- 1.2 kg/m2) nondiabetic female relatives of black patients with NIDDM and eight healthy controls (BMI 24.5 +/- 1.1 kg/m2). Despite the greater BMI in the obese relatives, percent body fat was not different from that of the nonobese relatives (38 +/- 2 vs 34 +/- 3 percent). Both values were, however, significantly (P less than 0.05) greater than that of the healthy controls (25 +/- 3 percent). Mean waist-to-hip circumference ratio (WHR) was greatest in obese relatives (0.89 +/- 0.01), intermediate in nonobese relatives (0.83 +/- 0.01) and least in the healthy controls (0.77 +/- 0.04). Mean sum of skinfold thickness from biceps, triceps and subscapular (SS) region was also greatest in obese relatives, intermediate in nonobese relatives and least in controls. Centrality index was not, however, different among the groups. Mean fasting serum glucose levels were slightly higher but not significantly different in the relatives compared to controls (obese 82 +/- 3; nonobese 81 +/- 4; controls 75 +/- 3 mg/dl). Following oral glucose ingestion, serum glucose rose to significantly (P less than 0.05) greater levels at 30, 60 and 90 min in the relative subgroups vs controls. Mean fasting and post-prandial peak serum insulin concentrations were significantly (P less than 0.05-0.01) greater in both relative subgroups vs controls. While mean serum glucose profiles and glucose disappearance decay (KG) following intravenous glucose load were identical in the relatives and controls, serum insulin responses were significantly greater in the relatives. The mean basal and post-stimulation serum C-peptide concentrations were similar in all the three groups, irrespective of the stimulus; thus suggesting a reduced hepatic insulin extraction in the relatives. Fasting serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) as well as FFA levels were not different between the relatives and controls despite the hyperinsulinemia in the former group. WHR correlated with basal insulin in the relatives (r = 0.416, P less than 0.05) and controls (r = 0.68, P less than 0.01) but not with stimulated insulin, lipids and lipoproteins in any of the groups. In contrast, both percent BFM and SS thickness correlated significantly (P less than

Topics: Adipose Tissue; Administration, Oral; Adult; Anthropometry; Black People; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose; Humans; Infusions, Intravenous; Insulin; Lactates; Lactic Acid; Lipoproteins; Liver; Obesity; Skinfold Thickness

Twenty-five newly presenting, untreated, white, non-insulin-dependent diabetic (NIDDM) subjects were studied within 72 hours of diagnosis. They were allocated to three groups according to their body mass index [BMI] (lean BMI less than 25.0, n = 9; overweight BMI 25.0 to 30.0, n = 6; obese BMI greater than .30.0 kg/m2, n = 10). All three groups exhibited equivalent hyperglycemia. Eleven normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, before and during a 240-minute insulin infusion (100 mU/kg/h). Fractional GS activity did not increase in the lean (change, -0.9 +/- 3.3%), the overweight (-1.9 +/- 2.7%), or the obese (+2.2 +/- 1.6%) NIDDM subjects during the insulin infusion and was markedly decreased compared with the control subjects (change, +14.6 +/- 2.4%, all P less than .001). Glucose requirement was also significantly decreased in all three NIDDM groups (103 +/- 23 v 81 +/- 14 v 53 +/- 14 mg/m2/min, respectively) compared with the control subjects (319 +/- 18 mg/m2/min, all P less than .001). There was a significant negative correlation with BMI (r = -.51, P less than .01), but the difference in glucose requirement between the lean and obese NIDDM groups was not significant. Muscle GS activity at the end of the euglycemic clamp correlated with glucose requirement (r = .53, P less than .001), and a similar correlation was observed between the insulin-induced change in muscle GS activity from basal and glucose requirement (r = .47, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3-Hydroxybutyric Acid; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Glycerol; Glycogen Synthase; Humans; Hydroxybutyrates; Infusions, Intravenous; Insulin; Male; Muscles; Obesity

Over the last four years, we have done a prospective study of insulin requiring diabetes (IRD). We offered 59 patients insulin therapy during 10 to 14 days by means of continuous subcutaneous insulin injection with the help of a pump in order to maintain the patient under oral hypoglycemic agents (OHA). We divided our population into two characteristic groups and isolated parameters that were predictive of post-insulin therapy evolution by means of C peptide assays. In one group, in 50% of cases, endogenous insulin production appeared impaired and could not be restored by insulin therapy. The patients in this group suffered a renewed drug failure within 3 months. In the other group, 50% of cases, endogenous insulin production was preserved and the CP/blood glucose level ratio improved. On insulin treatment interruption, we observed a significantly improved fasting blood glucose level and we observed decreased insulin needs. The patients, who were probably insulin resistant, suffered only late failures or went into remission, often for longer than one year. The data bring us to the logical conclusion of IRD heterogeneity. Only some of these patients can benefit from temporary insulin therapy and the remission attempt should be limited to them.

Topics: Biomarkers; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin Infusion Systems; Male; Middle Aged; Obesity; Prognosis; Prospective Studies; Treatment Outcome

The responses of plasma glucose, insulin, C-peptide and glucagon to an infusion of human beta-endorphin (0.5 mg/h) were studied in 10 formerly obese subjects who had lost 35 kg by dieting (body mass index less than 25) and compared with those of 10 normal-weight control (body mass index less than 25) and 10 obese (body mass index greater than 30) subjects. The fasting plasma concentrations of beta-endorphin were significantly higher in both the obese and the post-obese group than in the control group. In both obese and post-obese subjects, the infusion of beta-endorphin caused significant increases in peripheral plasma glucose, insulin, C-peptide and glucagon concentrations. In the control group, matched for age, sex and weight with the formerly obese group, there was no appreciable change in plasma insulin and C-peptide concentrations during the infusion of beta-endorphin, but the rise in plasma glucose was more sustained. Thus, 1. the increased plasma beta-endorphin concentrations found in human obesity are not corrected by normalization of body weight; and 2. formerly obese, normal-weight subjects behave as obese subjects in their metabolic and hormonal responses to beta-endorphin infusion. The alteration of the opioid system in human obesity may play some role in the predisposition to weight gain.

Topics: Adult; beta-Endorphin; Blood Glucose; Body Weight; C-Peptide; Female; Glucagon; Humans; Insulin; Kinetics; Male; Obesity

Fasting hyperglycemia in Type II (non-insulin-dependent) diabetes has been suggested to be due to hepatic overproduction of glucose and reduced glucose clearance. We studied 22 patients (10 lean and 12 obese) with newly diagnosed mild diabetes mellitus (fasting plasma glucose less than 15 mmol/l, urine ketone bodies less than 1 mmol/l), and two age- and weight-matched groups of non-diabetic control subjects. Glucose turnover rates and sensitivity to insulin were determined using adjusted primed-continuous [3-3H]glucose infusion and the hyperinsulinemic euglycemic clamp technique. Insulin-stimulated glucose utilization was reduced in both diabetic groups (lean patients: 313 +/- 35 vs 531 +/- 22 mg.m-2.min-1, p less than 0.01; obese patients: 311 +/- 28 vs 453 +/- 26 mg.m-2.min-1, p less than 0.01). Basal plasma glucose concentrations decreased 0.43 +/- 0.05 mmol/l per h (p less than 0.01). Glucose production rates were smaller than glucose utilization rates (lean patients: 87 +/- 3 vs 94 +/- 3 mg.m-2.min-1, p less than 0.01; obese patients: 79 +/- 5 vs 88 +/- 5 mg.m-2.min-1, p less than 0.01), were not correlated to basal glucose or insulin concentrations, and were not different from normal (lean controls: 87 +/- 4 mg.m-2.min-1; obese controls: 80 +/- 5 mg.m-2.min-1). These results suggest that the basal state in the diabetic patients is a compensated condition where glucose turnover rates are maintained near normal despite defects in insulin sensitivity.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Kinetics; Male; Middle Aged; Obesity

Aim of the present study was to evaluate whether the inhibitory effect of somatostatin on pancreatic B-cell secretion is normal in nondiabetic obese subjects. For this purpose plasma C-peptide concentrations were measured in 10 nondiabetic obese subjects and 10 nonobese healthy controls during a 4-h hyperglycemic (11 mmol/l) glucose clamp. Somatostatin was infused (2.5 nmol/min) during the third hour of the study period in order to inhibit glucose-stimulated B-cell secretion. Fasting C-peptide averaged 0.46 +/- 0.04 nmol/l (mean +/- SEM) in nonobese subjects, and 0.85 +/- 0.08 nmol/l in obese patients (P less than 0.001). In the period 0-120 min the area under the plasma C-peptide curve was significantly higher in obese than in nonobese subjects (292 +/- 23 vs. 230 +/- 17 nmol/l x 120 min, P less than 0.05), however, in the last 20 min of the glucose infusion period without somatostatin (100-120 min) plasma C-peptide was not significantly different in the two groups (2.94 +/- 0.32 nmol/l in nonobese subjects and 3.21 +/- 0.19 nmol/l in obese patients, p = NS). During somatostatin infusion while maintaining hyperglycemia, plasma C-peptide decreased in both groups, and in the period 160-180 min it averaged 0.89 +/- 0.12 nmol/l in control subjects and 0.93 +/- 0.08 nmol/l in obese patients (P = NS), with a percent reduction similar in the two groups (70 +/- 2% in controls and 71 +/- 2% in obese patients). After discontinuing somatostatin infusion, plasma C-peptide increased to concentrations which were higher in obese than in nonobese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Clamp Technique; Humans; Islets of Langerhans; Male; Obesity; Somatostatin

In 26 type 2 diabetic patients with failure to diet and sulphonylureas (fasting blood glucose levels greater than 8.0 mmol/l) the effects of insulin therapy on blood glucose control, islet B-cell function and plasma lipids were studied. Age was 58 +/- 11 (SD) yr, median duration of diabetes 6.5, range 1-24 yr, and body mass index 24.5, range 18.9-36.3 kg/m2. Six patients were obese. Therapy comprised twice daily injections of intermediate-acting insulin with additional fast-acting insulin when necessary. After six months, insulin dose was 39 +/- 10 U in the non-obese patients. Their fasting (14.0 +/- 2.7 mmol/l) and post-prandial blood glucose (17.9 +/- 4.5 mmol/l) and glycosylated haemoglobin (HbA1, 13.0 +/- 2.0%) declined to 7.7 +/- 1.6 mmol/l, 10.6 +/- 2.6 mmol/l and 9.5 +/- 1.0%, respectively (p less than 0.001). Median body weight increased by 3.7 kg (p less than 0.001). The changes in body weight correlated well with the changes in fasting blood glucose (r = -0.75, p less than 0.01) and HbA1 (r = -0.73, p less than 0.01). Fasting plasma insulin increased (p less than 0.01), whereas fasting plasma C-peptide and C-peptide release after glucagon did not change. Free fatty acids, LDL-cholesterol, total and VLDL-triglycerides showed a significant (p less than 0.05) decrease during insulin treatment. In the six obese patients insulin dose after six months was 44 +/- 18 U. Fasting blood glucose fell from 11.3 +/- 2.2 to 8.8 +/- 2.7 mmol/l (p less than 0.01), and HbA1 decreased from 10.7 +/- 1.1% to 9.8 +/- 1.3% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; Body Weight; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Lipoproteins; Male; Middle Aged; Obesity; Sulfonylurea Compounds; Triglycerides

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during oral glucose tolerance testing (OGTT) were evaluated in 10 non obese women with polycystic ovarian disease (NOB-PCOD) and 10 obese women with polycystic ovarian disease (OB-PCOD). Mean plasma glucose response at 120 minutes in OB-PCOD showed impaired glucose tolerance. Also in this group, 1 patient had frank diabetes mellitus, whilst 3 other patients had impaired glucose tolerance 1 NOB-PCOD patient had impaired glucose tolerance. Mean plasma glucose levels and mean incremental glucose areas were higher in the OB-PCOD at all time intervals and reached statistical significance at 60 and 90 minutes. Mean plasma IRI levels were also higher in OB-PCOD at all time intervals, and reached statistically significant higher levels at 0, 60 and 90 minutes. Mean serum C-peptide valves were also higher at all time intervals in OB-PCOD. The relationship between acanthosis nigricans, obesity and PCOD was also analysed. It is evident from this study that obesity has a significant negative impact on the overall carbohydrate status in women with PCOD.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Kinetics; Obesity; Polycystic Ovary Syndrome

A reduced thermic response and an impaired activation of the sympathetic nervous system (SNS) has been reported after oral glucose in human obesity. It is, however, not known whether the reduced SNS activity returns to normal along with weight reduction. The thermic effect of glucose was lower in eight obese patients than in matched control subjects (1.7% vs 9.2%, p less than 0.002). The increase in arterial norepinephrine after glucose was also blunted in the obese patients. After a 30-kg weight loss their glucose and lipid profiles were markedly improved but the thermic effect of glucose was still lower than that of the control subjects (4.2%, p less than 0.001). The glucose-induced arterial norepinephrine response remained diminished in the reduced obese patients whereas the changes in plasma epinephrine were similar in all three groups. The results suggest that a defective SNS may be a cause in the development of obesity.

Topics: Adult; Blood Glucose; Body Temperature Regulation; C-Peptide; Energy Metabolism; Epinephrine; Female; Glucagon; Glucose; Humans; Insulin; Male; Middle Aged; Norepinephrine; Obesity; Sympathetic Nervous System; Weight Loss

To determine the effects of short-term fasting on carbohydrate tolerance, 10 obese women with noninsulin-dependent diabetes mellitus (NIDDM) were studied with meal tolerance tests before and after 3 days of fasting. After 3 days' fast, basal serum glucose declined from 15.2 +/- 0.9 to 7.5 +/- 0.7 mmol/L (273 +/- 17 to 135 +/- 13 mg/dL) (mean +/- SEM, p less than 0.001) and the glycemic response to the test meal (area under the glucose curve) improved by 31%. There were no changes in basal or postprandial insulin levels but a slight increase in serum c-peptide. Resting metabolic rate and the thermic effect of food were unchanged. There was a slight but insignificant change in basal and postprandial free fatty acid levels and a significant elevation of basal beta-hydroxybutyrate levels. Blood lactate rose significantly (from 0.9 to 2.0 mM) during the initial meal tolerance test, but no rise in lactate was seen in the meal tolerance test after fasting. Two subgroups of patients were identified based on the degree of glycemic improvement after short-term fasting. Those with lesser improvement in serum glucose showed overnight rises in serum glucose during the period of fasting (the dawn phenomenon), while those patients who normalized serum glucose showed a steady fall in serum glucose. This finding may help to predict the glycemic response to long-term calorie restriction. Carbohydrate tolerance improves in obese diabetic (NIDDM) women after 3 days of fasting, in contrast to the impairment of glucose tolerance seen in lean or obese nondiabetic subjects after fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Energy Metabolism; Fasting; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Humans; Hydroxybutyrates; Insulin; Lactates; Middle Aged; Obesity; Research Design; Time Factors

Impairment in pancreatic production of insulin, a cardinal feature of noninsulin dependent diabetes mellitus (NIDDM), was quantified and the kinetics of insulin secretion characterized in six obese individuals with NIDDM before and after weight loss (18.0 +/- 3.0 kg, mean +/- SEM) using a validated mathematical model that employs C-peptide as a marker of the in vivo rate of insulin secretion. The metabolic clearance of C-peptide, assessed by decay analysis after bolus injection of biosynthetic human C-peptide, was not changed by weight loss (0.143 +/- 0.009 L/min.m2 vs. 0.137 +/- 0.010 L/min.m2). Kinetic parameters from each individual's decay curve before and after weight loss were used to derive accurate rates of secretion during the basal (postabsorptive) state, an oral glucose tolerance test and two hyperglycemic clamps. Basal rates of insulin secretion declined 20 +/- 5 pmol/min.m2 (96 +/- 15 to 76 +/- 15 pmol/min.m2, P less than 0.05) concomitant with decreases of 6.9 +/- 0.9 mmol/L in fasting serum glucose (13.7 +/- 1.0 to 6.8 +/- 0.7 mmol/L, P less than 0.05), 60 +/- 14 pmol/L in serum insulin (134 +/- 30 to 74 +/- 15 pmol/L, P less than 0.05), and 0.15 +/- 0.03 pmol/ml in plasma C-peptide (0.67 +/- 0.11 to 0.52 +/- 0.08 pmol/ml, P less than 0.05) concentrations. As expected, weight loss resulted in improved glucose tolerance as measured by the glycemic profiles during the oral glucose tolerance test (P less than 0.05 analysis of variance). The insulin secretory response before weight loss showed a markedly reduced ability to respond appropriately to an increase in the ambient serum glucose. After weight loss, the pancreatic response was more dynamic (P less than 0.05, analysis of variance) and parralleled the moment-to-moment changes in glycemia. Insulin production above basal doubled (11.2 +/- 3.2 to 24.5 +/- 5.8 nmol/6h.m2, P less than 0.05) and peak rates of insulin secretion above basal tripled (55 +/- 16 to 157 +/- 32 pmol/min/m2, P less than 0.05). To assess the beta-cell response to glucose per se and the changes associated with weight reduction, two hyperglycemic clamps were performed at steady state glucose levels in the range characteristic of individuals with severe NIDDM. At a fixed glycemia of 20 mmol/L, average rates of insulin secretion increased almost 2-fold with treatment (161 +/- 41 to 277 +/- 60 pmol/min.m2, P less than 0.05). At an increment of 6 mmol/L glucose above prevailing fasting glucose levels, the average rate of insu

Topics: Analysis of Variance; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Models, Theoretical; Obesity; Weight Loss

The kinetics of in vivo insulin-mediated glucose uptake in human obesity have not been previously studied. To examine this, we used the glucose-clamp technique to measure whole-body and leg muscle glucose uptake in seven lean and six obese men during hyperinsulinemia (approximately 2000 pM) at four glucose levels (approximately 4.5, approximately 8.3, approximately 13.5, and approximately 23.5 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference x blood flow). With this approach, we found that rates of whole-body and leg glucose uptake were significantly lower in obese than in lean subjects at each glucose plateau. Leg blood flow rates increased from 4.3 +/- 0.4 to 6.5 +/- 0.8 dl/min over the range of glucose in lean subjects (P less than 0.05) but remained unchanged in obese subjects. The apparent maximal capacity (Vmax), based on whole-body and leg glucose uptake, was reduced in obese compared with lean subjects, but the apparent Km was similar in the lean and obese subjects (6-9 mM, NS). To assess the affinity of muscle for glucose extraction independent of changes in muscle plasma flow, we determined the mean half-maximal effective glucose concentration (EG50) and found it was similar in the lean and obese subjects (6.0 +/- 0.3 vs. 6.0 +/- 0.8 mM, NS). We conclude that 1) the kinetics of in vivo insulin-mediated glucose uptake in skeletal muscle in human obesity are characterized by reduced Vmax but normal Km; 2) the EG50 for insulin-mediated glucose extraction in skeletal muscle was 6 mM in both lean and obese subjects, consistent with a Km characteristic of the glucose-transport system; 3) obese subjects were unable to generate increases in blood flow in response to hyperglycemia under hyperinsulinemic conditions, and this contributed significantly to lower rates of leg and whole-body glucose uptake.

Topics: Adult; Blood Glucose; C-Peptide; Glucose; Glucose Tolerance Test; Humans; Insulin; Leg; Male; Muscles; Obesity; Time Factors

To determine whether a decreased sensitivity to insulin is involved in the pathogenesis of essential hypertension, fasting blood glucose, serum insulin, serum C peptide, the glucose:insulin ratio and the insulin:C-peptide ratio were measured in 14 lean normotensives, 17 overweight normotensives, 17 lean hypertensives and 20 overweight hypertensives. Compared with the lean normotensives, the patients who were overweight, those with hypertension and those who were both overweight and hypertensive showed increased fasting serum insulin and C-peptide levels, and a lower glucose:insulin ratio. No significant difference between the normotensive and the hypertensive subjects was found in the insulin:C-peptide ratio. Diastolic blood pressure was directly correlated with serum insulin (P less than 0.01) and with C-peptide levels (P less than 0.01), and inversely correlated with the glucose:insulin ratio (P less than 0.02). We conclude that insulin resistance is present in both essential hypertensive and overweight subjects. Since the present study showed that hepatic insulin clearance was normal in hypertensives, the hyperinsulinaemia in essential hypertension appears to be due to beta-cell hypersecretion in response to a defective peripheral action of the hormone.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Female; Humans; Hypertension; Insulin; Insulin Resistance; Islets of Langerhans; Male; Middle Aged; Obesity

Serum C-peptide and Immunoreactive Insulin (IRI) level was measured during per os glucose tolerance test as well as fasting specific insulin binding percentage and capacity of erythrocytes in hypothalamic obesity and in obese children due to hypercalorization, and was compared with ideal-weight controls. Integral values of curves (sigma) and sigma C-peptide/sigma IRI ratios were calculated. In 4 cases fasting C-peptide content was substantially increased as compared to the other groups. The data suggest that hyperinsulinism in diencephalic obesity is primary. The ratio of the two peptides was normal or increased: insulin binding % of erythrocytes corresponded to that of the control group, which explains in these cases normal or favourable glucose metabolism. It is thought that in obese children high fasting C-peptide levels with an adequate clinical picture can indicate the functional examination of the hypothalamic-pituitary system. Sigma C-peptide/sigma IRI ratio differing from normal indirectly shows the changes of receptor function.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Child, Preschool; Erythrocytes; Female; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Insulin; Male; Obesity

The effect of fasting during the holy month of Ramadan on the metabolic control of 39 patients with overweight and non-insulin-dependent diabetes (NIDD) was studied. There were 29 females and 10 males with a mean age of 51.5 +/- 1.65 years and body mass index of 31.5 +/- 0.98 kg/m2. All were treated with diet and oral hypoglycaemic agents (OHA). There was no change in body weight, fasting plasma glucose, glycosylated haemoglobin (HbA1), C-peptide and insulin blood levels at the end of fasting. Total blood cholesterol concentration rose significantly (p 0.05) but not triglycerides at the end of Ramadan. There were no acute metabolic complications (e.g. hypoglycaemia) in the present study. We conclude that fasting during Ramadan is generally safe in NIDD. However, patients should be advised to make use of this opportunity to combine the spiritual benefit with improvement in the metabolic control of the diabetes mainly through weight reduction.

Topics: Adult; Aged; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Islam; Male; Middle Aged; Obesity; Patient Compliance; Prospective Studies; Triglycerides

In high degree obesity there a significantly smaller area under the curve of C-peptide after stimulation with Tolbutamide and significantly lower insulin sensitivity measured in vivo by euglycemic hyperinsulinemic clamp-technique (Biostator) than in moderate obesity. This allows the conclusion that high degree obesity is a risk factor for the development of diabetes mellitus.

Topics: Adolescent; Adult; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Obesity; Risk Factors; Tolbutamide

The insulin receptor binding ability was studied in 26 persons with above normal body mass (15 women and 11 men), mean age 44.15 +/- 10.1 years without family history of diabetes mellitus. According to the degree of obesity they were classified into 3 groups. In the persons with I-II degree of obesity parallel with the strongly reduced number of insulin receptors (total and the high affinity) an increase of the receptors affinity appears as a compensatory mechanism which ensures appropriate insulin receptor binding. In the persons with III-IV degree of obesity the number of insulin receptors is strongly reduced but the receptor affinity does not differ from that of the controls with normal body mass. The receptor changes in the persons with excessive obesity are similar to those found by the authors in patients with newly discovered non-insulin dependent diabetes mellitus. This allows the suggestion that these persons are in a potential risk of developing diabetes mellitus.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Female; Humans; Insulin; Iodine Radioisotopes; Male; Middle Aged; Obesity; Receptor, Insulin

Diabetes mellitus is a major health problem in Saudi Arabia. The evaluation of endogenous insulin secretion at diagnosis has not yet been studied in this population. We have therefore studied fasting and post-glucagon stimulation levels of glucose, insulin and C-peptide in 216 newly diagnosed untreated diabetic patients. The mean +/- SD fasting insulin and C-peptide levels were 14.0 +/- 1.8 microU/ml and 1.8 +/- 0.4 ng/ml, while post-glucagon stimulation levels were 21.1 +/- 3 microU/ml and 2.4 +/- 0.4 ng/ml. There were significant post-stimulatory increment levels for insulin, from 4.9 to 13.7 microU/ml, and C-peptide from 0.2 to 1.3 ng/ml (P less than 0.001). Such increments did not affect specified age distribution. We found a significant correlation between the fasting levels and post-stimulation levels of C-peptide and insulin. Obesity correlated with higher basal and post-stimulation levels of both hormones (r = 0.67, P less than 0.001). The mean +/- SD fasting insulin and C-peptide levels were 18.5 +/- 9.1 microU/ml and 2.4 +/- 0.8 ng/ml for obese patients and 11.5 +/- 5.1 microU/ml and 1.9 +/- 1.1 ng/ml for non-obese patients. The type of diabetes among the Saudi adult diabetic patients studied is characterized by high basal C-peptide and insulin levels which increase significantly with stimulation, suggesting diminished but present endogenous B-cell function.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Fasting; Female; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Saudi Arabia

Basal insulin supplementation has been used as a therapy for patients with non-insulin-dependent diabetes mellitus (NIDDM) who require insulin. To determine whether basal insulin supplementation in addition to lowering postabsorptive plasma glucose concentration also improves the postprandial pattern of glucose disposition, glucose metabolism after ingestion of a solid mixed meal was assessed in obese patients with NIDDM before and after treatment with ultralente and compared with glucose metabolism observed in nondiabetic subjects. Splanchnic uptake of ingested glucose clearance was assessed by including [2-3H]glucose (a tracer that only minimally cycles through glycogen) in a solid mixed meal. Postprandial gluconeogenesis was estimated by measuring the rate of incorporation of carbon dioxide into glucose. Net glucose and lipid oxidation were measured by indirect calorimetry. Both splanchnic uptake of ingested glucose (27 +/- 1 vs. 14 +/- 2 g) and postprandial hepatic glucose release (51 +/- 5 vs. 24 +/- 3 g) were greater (P less than .001) in diabetic than in nondiabetic subjects. Although the percentage of postprandial hepatic glucose release accounted for by glucose synthesis from bicarbonate was similar in the two groups (25 +/- 2 vs. 35 +/- 5%), the absolute rate was greater in the diabetic patients (13 +/- 1 vs. 8 +/- 1 g; P less than .05). Postprandial glucose oxidation and glucose disposal (measured either isotopically or by the forearm-catheterization technique) were similar in both groups. However, total lipid oxidation was increased in the diabetic patients. (P less than .05). Two weeks of basal insulin supplementation lowered fasting glucose concentrations (from 219 +/- 22 to 144 +/- 21 mg/dl; P less than .01) and integrated postprandial glycemic response (from 814 +/- 68 to 621 +/- 72 min.mg.ml-1) but not to normal. Although circulating insulin concentrations were two- to threefold greater (P less than .02) after 3 mo of basal insulin supplementation, the postprandial pattern of glucose metabolism remained essentially the same. Basal insulin supplementation decreased (P less than .05) both splanchnic uptake of ingested glucose and hepatic glucose release. The addition of a preprandial injection of soluble insulin to basal insulin supplementation further suppressed (P less than .05) postprandial hepatic glucose release, thereby further improving postprandial glucose tolerance. These studies indicate that initial splanchnic glucose clearance,

Topics: Blood Glucose; C-Peptide; Carbon Dioxide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Eating; Female; Glucagon; Glucose; Humans; Insulin; Insulin, Long-Acting; Lipid Metabolism; Liver; Male; Middle Aged; Obesity

We studied a group of obese hyperandrogenic amenorrheic women to determine the effects of weight loss on anthropometry, hormonal status, menstrual cycles, ovulation, and fertility. Fourteen women had polycystic ovaries, two the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome, one hirsutism of adrenal origin, and three idiopathic chronic anovulation. The duration of amenorrhea before the study ranged from 3-17 months [mean, 8.6 +/- 4.5 (+/- SD)]. All women ate a hypocaloric diet for a period of 8.0 +/- 2.4 months. Weight loss ranged from 4.8 to 15.2 kg (mean, 9.7 +/- 3.1 kg; 1.35 +/- 0.56 kg/month) and the waist to hip ratio, which was used as a measurement of body fat distribution, decreased from 0.86 +/- 0.1 to 0.81 +/- 0.06 (P less than 0.0001). The women's mean plasma testosterone and LH concentrations decreased significantly (P less than 0.001 and P less than 0.005, respectively). A significant positive correlation was found between the decreases in plasma testosterone levels and the decreases in glucose-stimulated insulin levels. Moreover, the decreases in the waist to hip ratio correlated positively with the decreases in glucose-stimulated insulin levels and inversely with the decreases in plasma 17 beta-estradiol. No relationships were found between weight loss and the changes in plasma insulin, steroid, and gonadotropin concentrations. The responsiveness to the weight reduction program was evaluated by comparing the number of menstrual cycles during the study period with the number reported before it. Eight women had significantly improved menstrual cyclicity (responders), while 12 did not (nonresponders). The clinical characteristics and hormone values were similar in responder and nonresponder women. In the group as a whole, 33% of the menstrual cycles during the study were ovulatory, and 4 pregnancies occurred. Hirsutism improved significantly in more than half of the women, as did acanthosis nigricans when present. We conclude that weight loss is beneficial in all obese hyperandrogenic women regardless of the presence of polycystic ovaries, the degree of hyperandrogenism, and the degree and distribution of obesity.

Topics: Adult; Amenorrhea; Androgens; Blood Glucose; C-Peptide; Female; Hormones; Humans; Insulin; Menstrual Cycle; Obesity; Ovulation; Weight Loss

Computed tomography (CT) was used to study the association between adipose tissue localization and glucose tolerance in a sample of 52 premenopausal obese women aged 35.7 +/- 5.5 yr (mean +/- SD) and with a body fat of 45.9 +/- 5.5%. Body-fat mass and the body mass index (BMI) were significantly correlated with plasma glucose, insulin, and connecting peptide (C-peptide) areas after glucose (75 g) ingestion (.40 less than or equal to r less than or equal to .51, P less than .01). Trunk-fat accumulation and the size of fat cells in the abdomen displayed highly significant correlations with postglucose insulin levels. The C-peptide area was also positively correlated with abdominal fat cell size (r = .76, P less than .01) and was more closely associated with the sum of trunk skin folds (r = .59, P less than .001) than with the extremity skin folds (r = .29, P less than .05). Subcutaneous and deep-abdominal-fat areas measured by CT displayed comparable associations with the plasma insulin area (r = .44 and .49, respectively; P less than .001) but marked differences in the associations with glucose tolerance. Indeed, subcutaneous abdominal fat was not significantly correlated with the glucose area, whereas deep abdominal fat showed a significant correlation (r = .57, P less than .001) with the glucose area. Midthigh fat deposition measured by CT was not, however, correlated with plasma glucose, insulin, or C-peptide areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Adipose Tissue; Adult; Blood Glucose; Body Weight; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Obesity; Radiography

We compared estimates of in vivo insulin action derived from insulin tolerance tests (ITT) and euglycemic and hyperglycemic glucose clamp studies in 17 normal subjects and 19 patients with various diseases characterized by insulin resistance. Fifteen subjects underwent an ITT and a euglycemic clamp study, 17 subjects underwent an ITT and a hyperglycemic clamp study, and 4 subjects underwent all 3 tests. The ITT consisted of a bolus iv injection of regular insulin (0.1 U/kg BW). The plasma glucose disappearance rate during the 3- to 15-min period following the insulin injection was taken as a measure of insulin action. In both euglycemic and hyperglycemic clamp studies, which were carried out with standard techniques, the ratio between the amount of glucose infused to maintain glycemia at the desired level and the mean plasma insulin concentration from 60-120 min (M) (euglycemic clamp studies) or 20-120 min (I) (hyperglycemic clamp studies) was used as a measure of insulin action. A close correlation was found between plasma glucose disappearance rate and the M/I ratio during either the euglycemic (r = 0.811; P less than 0.001) or the hyperglycemic (r = 0.826; P less than 0.001) clamp studies. These results suggest that the 15-min ITT is suitable as a simple and rapid estimation of in vivo insulin action when glucose clamp studies are not feasible, as in large series of subjects or serial studies.

Topics: Adult; Blood Glucose; C-Peptide; Epinephrine; Female; Glucagon; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Infusion Systems; Insulin Resistance; Male; Norepinephrine; Obesity

Obesity and fat topography are risk factors for hyperinsulinemia, insulin resistance, and diabetes mellitus. The relative contribution of obesity and body fat distribution indices to fasting and oral glucose-stimulated C peptide, insulin, and glucose concentrations were determined in 33 healthy premenopausal women. Obesity level was assessed by hydrostatic weighing and fat topography by computerized tomography-derived intraabdominal fat area, waist to hip ratio, subscapular skinfold thickness and the ratio of subscapular to triceps skinfold thickness. Both fat mass and regional fat distribution indices were associated closely with changes in insulin secretion. Fat topography indices were more closely correlated (p less than 0.001) to insulin response than were fat mass indices (p less than 0.01). The subscapular skinfold thickness had the greatest integrity for reflecting fat mass and fat distribution as they relate to the metabolic profile. The subscapular skinfold thickness may help identify individuals at risk for noninsulin dependent diabetes mellitus.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Composition; Body Weight; C-Peptide; Female; Glucose; Homeostasis; Humans; Insulin; Male; Menopause; Obesity; Scapula; Skinfold Thickness; Tomography, X-Ray Computed

The effect of weight reduction on fasting serum lipids and lipoproteins and adipose tissue lipoprotein lipase responsiveness to insulin was assessed immediately after and 3 mo subsequent to a mean 11.7% weight reduction in 14 women. Whereas reduction in fasting serum triglycerides persisted after 3 mo, reductions in serum cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein (HDL) cholesterol were not found at 3 mo. In fact, at 3 mo, levels of HDL cholesterol were higher than before weight reduction. Maintenance of the reduced-obese state also increased the HDL2-to-HDL3 cholesterol ratio (P less than 0.01), an effect strongly associated with the change in the responsiveness of adipose tissue lipoprotein lipase to insulin (r = 0.821, P less than 0.001). Moreover, after maintenance of the reduced-obese state, the HDL2-to-HDL3 cholesterol ratio also increased after the ingestion of corn oil and a 6-h insulin-glucose infusion, a response not present before weight reduction. Thus the effect of weight reduction on serum lipids and lipoproteins was not only time dependent, but for HDL, was strongly associated with changes in adipose tissue metabolism.

Topics: Adipose Tissue; Adult; Basal Metabolism; Blood Glucose; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Insulin; Lipoproteins, HDL; Obesity; Triglycerides; Weight Loss

Eighty-five randomly selected women, all born in 1948, were studied. All were nonobese (body mass index [BMI], 23.3 +/- 0.3 (means +/- SD]). The relationships between three indicators of fat distribution (waist-hip, waist-thigh, and subscapular-triceps ratios) and hormonal and metabolic variables were studied. Increased androgenic activity (ratio of free testosterone [T] to total testosterone [free-total T ratio]) and degree of obesity (BMI) were independently related to increased waist-hip ratio. Waist-hip and waist-thigh ratios showed higher correlations with all metabolic variables than did the triceps-subscapular skinfold thickness ratio except for diastolic blood pressure. After adjustment for BMI and free-total T ratio, the waist-hip ratio was still significantly positively related to total cholesterol and C peptide and negatively to the HDL-total cholesterol ratio. In such multiple regression, BMI was independently related to insulin, C peptide, and diastolic blood pressure. The free-total T ratio was independently related to triglycerides. BMI and waist-hip ratio gave important complementary information about risk factors for diseases such as cardiovascular disease and diabetes mellitus.

Topics: Adipose Tissue; Adult; Androgens; Anthropometry; Blood Pressure; C-Peptide; Female; Humans; Insulin; Lipids; Obesity

24-h urinary C-peptide excretion was studied in 119 women with gestational diabetes before and after treatment with diet or diet and insulin. The 24-h urinary C-peptide excretion in normal-weight gestational diabetic women at diagnosis was also compared to that of a healthy reference group. There was a wide variation in urinary C-peptide values which tended to be higher in normal-weight women with gestational diabetes at diagnosis compared to the reference group, but it did not reach statistical significance. Post partum gestational diabetic women had significantly higher urinary C-peptide excretion (p less than 0.002) than the reference group, indicating insulin resistance in women with gestational diabetes at this time. In 29 overweight women with gestational diabetes 24-h urinary C-peptide excretion did not significantly differ from that in normal-weight women with gestational diabetes. In 32 women with a more marked deviation in glucose tolerance (area greater than or equal to 46 mmol/l) 24-h urinary C-peptide values were significantly (p less than 0.05) higher than in 58 women with gestational diabetes with an area between 42 and 45.9 mmol/l. Both treatment alternatives, diet and diet plus insulin, significantly reduced postprandial blood glucose values (p less than 0.05) and urinary C-peptide excretion was significantly decreased (p less than 0.05).

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diet, Diabetic; Female; Humans; Insulin; Obesity; Pregnancy; Pregnancy in Diabetics; Reference Values

Topics: Adult; Blood Pressure; Body Weight; C-Peptide; Diet, Reducing; Energy Intake; Female; Humans; Hypertension; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Obesity

Authors performed 0.5 g/kg intravenous and 1.75 g/kg p.os glucose tolerance tests in 25 alimentary obese children. C-peptide and Immunoreactive Insulin determinations were performed in every case. The average ratio of the two peptide during i.v. loads was calculated, too. Results were compared with the data of 6 children with ideal body weight respectively, whose results were obtained in similar circumstances. They find that i.v. glucose load produces different degrees in detected by C-peptide insulin secretion in normal as well as in obese children and the secretion rate is practically permanent till the end of the test in both groups. The low C-peptide/insulin ratio during i.v. glucose tolerance test in obese children indicates insulin resistance and explains decreased glucose tolerance. The "early-phase insulin release" detected in insulin curves of i.v. glucose load is resulted not only by the insulin reservoir capacity of beta-cells, but also by the insulin excretion capacity of the liver and the receptor activity of target cells. There is no connection between maximum glucose level responses to i.v. load and maximum C-peptide and insulin responses, whereas increases in maximum C-peptide response are parallel with those of in weight. C-peptide responses, being different in degree and experienced during the two types of tolerance test, support the "incretin" phenomenon. This mechanism may be important in the development of beta-cell hyperfunction which has been proved in obesity.

Topics: Administration, Oral; C-Peptide; Child; Glucose; Glucose Tolerance Test; Humans; Injections, Intravenous; Insulin; Obesity

The fasting hyperinsulinaemia characteristic of obesity is due to pancreatic hypersecretion and is accompanied by a corresponding increase in plasma C-peptide concentrations. The exaggerated plasma insulin and C-peptide responses to oral glucose in obese subjects which is greater for insulin than C-peptide suggests that the stimulated hyperinsulinaemia is due to both pancreatic hypersecretion and decreased fractional hepatic extraction of insulin. In obese subjects fasting and stimulated insulin concentrations, but not those of C-peptide, are lower after 3 weeks of energy restriction than before it. This reduction in fasting and stimulated insulin levels is, therefore, due to an increase in the fractional extraction of insulin by the liver rather than to a reduction in pancreatic secretion as had previously been supposed.

Topics: Adult; Blood Glucose; C-Peptide; Diet, Reducing; Female; Glucose; Humans; Insulin; Islets of Langerhans; Liver; Male; Obesity

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Female; Humans; Insulin; Male; Middle Aged; Obesity

Topics: Abdomen; Adipose Tissue; C-Peptide; Diet, Reducing; Energy Intake; Female; Humans; Insulin; Liver; Obesity; Weight Loss

Sixty-one patients with non-insulin-dependent diabetes mellitus and fasting blood glucose of 12.0 +/- 0.6 mmol/l were studied before and after dietary treatment in an outpatient setting. At the start of the study 33 patients were obese (body mass index greater than 27.0 kg/m2). Twenty patients were newly diagnosed, median known duration of diabetes in the others was 5 years. Beta-cell function was measured by the release of C-peptide after i.v. injection of 1 mg glucagon (area under the curve of C-peptide = AUC-cp), as well as calculated according to the formulae of Matthews. Insulin action was estimated by measurement of fasting blood glucose, insulin and free fatty acids (FFA) concentrations. Non-obese patients showed more severe beta-cell deficiency than the obese ones (AUC-cp 2586 +/- 158 vs. 3294 +/- 277 pmol/l per 15 min), and did not improve in metabolic control during treatment. In the obese patients three response patterns to treatment were observed: weight loss and improvement in metabolic control accompanied primarily with increased beta-cell function or increased insulin action, or worsening of metabolic control. Those with less impaired beta-cell function and shorter known duration of diabetes showed the most favourable response.. non-obese type 2 diabetes patients with fasting glucose levels above 10 mmol/l do not improve on dietary treatment alone; in obese type 2 diabetics weight reduction is essential and results in metabolic improvement, irrespective of the preceding fasting blood glucose concentrations. Improved beta-cell function as well as increased insulin action are responsible for this improvement.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Weight Loss

Catecholamines and endogenous opioid peptides are released in response to stress. Exogenous infusions of epinephrine and beta-endorphin (both in doses of 15, 50, and 80 ng/kg.min sequentially, each dose lasting 30 min) were used to mimic short term stress in both normal weight (body mass index, less than 25 kg/m2) and obese (body mass index, greater than 30 kg/m2) subjects. Fasting plasma insulin, C-peptide, and beta-endorphin concentrations were significantly higher in the obese than in the normal subjects (P less than 0.01-0.005). In lean subjects epinephrine produced significant increases in plasma glucose levels, but no appreciable changes in plasma insulin, C-peptide, or glucagon. Infusion of beta-endorphin in the same subjects caused plasma glucose and glucagon to rise, but insulin and C-peptide levels did not change. The simultaneous infusion of epinephrine and beta-endorphin produced a glycemic response which, although greater, was not significantly different than the sum of the responses to the individual hormone infusions. However, the two hormones had a synergistic interaction on plasma glucagon levels [total glucagon response, 2275 +/- 370 pg/min.mL (ng/min.L); sum of single effects, 750 +/- 152 (+/- SE) pg/min.mL (ng/min.L); P less than 0.01]. The plasma epinephrine [207 +/- 21, 607 +/- 70, and 1205 +/- 134 pg/mL (1130 +/- 115, 3640 +/- 382, and 6577 +/- 691 pmol/L] and beta-endorphin [875 +/- 88, 1250 +/- 137, and 1562 +/- 165 pg/mL (250 +/- 25, 358 +/- 39, and 447 +/- 47 pmol/L] concentrations attained during the infusions of each single hormone were not different from those recorded during the combined hormonal infusion. In obese subjects epinephrine raised plasma glucose levels and caused dose-related increments of plasma glucagon concentrations. Plasma insulin and C-peptide concentrations remained low and rebounded at the end of the infusions. In the same subjects, beta-endorphin produced elevations of plasma glucose, insulin, C-peptide, and glucagon. When the combined hormonal infusion was given to obese subjects, the plasma epinephrine and beta-endorphin concentrations rose to values not significantly different from those in normal weight subjects. However, there was a dramatic increase in plasma glucose exceeding 200 mg/dL (11.1 mmol/L), which remained elevated 30 min after the infusion. The glucagon response was not greater than the sum of the single effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; beta-Endorphin; Blood Glucose; C-Peptide; Epinephrine; Female; Glucagon; Humans; Infusions, Intravenous; Insulin; Male; Obesity

The influence of combined therapy using insulin and oral hypoglycaemic agents on blood glucose control and on insulin secretion in Type 2 diabetic patients with secondary failure to oral hypoglycaemic agents was evaluated. Type 2 diabetic patients (n = 180) (98 normal-weight, 82 over-weight), at least 3 years from diagnosis, and having poor blood glucose control on oral hypoglycaemic agents for at least 3 months (fasting plasma glucose greater than 10.0 mmol l-1) despite intensive efforts at improvement, were included in the study. A single daily insulin injection (human ultralente), at a dose of 0.22 +/- 0.07 U kg-1 d-1 in normal-weight and 0.33 +/- 0.10 U kg-1 d-1 in over-weight patients, was added to the previous dietary and drug treatment for 6 months. A progressive and significant (2p less than 0.001) reduction of the mean daily blood glucose was observed during the first 3 months of combined therapy (from 13.2 +/- 3.2 to 8.1 +/- 2.1 mmol l-1 in normal-weight and from 13.4 +/- 3.1 to 8.8 +/- 2.3 mmol l-1 in over-weight patients), with no further significant changes thereafter. A significant increase (2p less than 0.001) in the mean daily C-peptide concentration (from 0.50 +/- 0.30 to 0.71 +/- 0.29 nmol l-1 in normal-weight and from 0.78 +/- 0.36 to 1.00 +/- 0.41 nmol l-1 in over-weight patients) took place during combined therapy. No changes of body weight (+ 1.5 +/- 1.2 kg in normal-weight and + 1.0 +/- 1.0 kg in over-weight patients) were observed.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Eating; Fasting; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin, Long-Acting; Obesity; Recombinant Proteins

This study was proposed to clarify the impairment of first-phase insulin response to glucose in subjects with glucose intolerance by analysis of C-peptide secretion rate after glucose or glucagon injection. The rate was calculated from kinetic analysis of peripheral C-peptide behavior. The rate reached the peak two minutes after glucose injection and then rapidly declined (first-phase secretion) in control subjects. In nonobese subjects with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM), the rate promptly increased in response to glucose and was followed by a second phase increase. The time course of the rate in the subjects was slightly different from that in control subjects. There was a progressively greater deficit in the first-phase increase with increasing severity of glucose intolerance. The time course of the rate in the obese subjects with NIDDM was different from that in control subjects. The first-phase increase was reduced in the obese subjects with NIDDM. The glucose disappearance rate was correlated with the first-phase increase. Since the time course of the rate after glucagon injection in all subjects did correspond well with that in the control subjects, variation of metabolic clearance rate of endogenous C-peptide among the subjects may be negligible for this study. This study provides the precise time course of first- and second-phase insulin response to glucose injection in nonobese and obese subjects with IGT or NIDDM as well as convincing evidence of the progressive reduction of first-phase insulin response with increasing severity of glucose intolerance. First-phase insulin response to glucose might be slightly delayed in some obese subjects with NIDDM.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Glucagon; Glucose; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Obesity

To elucidate if the presence of fatty liver in obesity influences hepatic insulin extraction under basal conditions, serum immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) were measured in 20 obese patients with normal glucose tolerance and in 8 normal subjects. The obese patients were subdivided into two groups matched for age and body weight according to the presence or absence of fatty liver: 8 obese patients without fatty liver (OBN) and 14 with fatty liver (OBF). Basal levels of IRI and CPR were significantly greater in the obese patients than in the normals, but were similar in the two obese groups. In the OBF group, the CPR/IRI molar ratios, a relative measure of hepatic insulin uptake, were significantly lower than in the other two groups, while the ratios of the normal and OBN groups were similar. The CPR/IRI molar ratios in all obese patients correlated well with the degree of fatty liver (r = 0.785, p less than 0.001). These results suggest that hepatic insulin extraction in a subgroup of obese patients is either reduced or indistinguishable from that of non-obese subjects, and that basal CPR/IRI molar ratio may serve as a useful indicator of the presence of fatty liver in simple obesity.

Topics: Adult; Blood Glucose; C-Peptide; Fatty Liver; Humans; Insulin; Obesity; Random Allocation

To study the relationship between childhood obesity, weight loss, hyperinsulinaemia and the erythrocyte insulin receptor, we measured the plasma concentrations of immunoreactive insulin (IRI) and C-peptide and the binding of 125I-insulin to erythrocytes in 12 obese children with a mean age +/- SD of 11.4 +/- 2.5 years and a mean relative weight score +/- SD of 4.8 +/- 1.4 and 12 age-matched normal-weight children. Eight obese children were re-evaluated after 1 year's participation in a weight reduction programme. The obese children had higher fasting plasma concentrations of IRI (P less than 0.01) and C-peptide (P less than 0.05) and a lower C-peptide to IRI molar ratio (P less than 0.01) than the normal-weight children. The obese children had in addition a reduced erythrocyte insulin binding (P less than 0.05 or less) over the physiological range of circulating insulin concentration. There was a negative correlation (r = -0.60; P less than 0.01) between the insulin tracer binding and the relative weight. The weight reduction programme resulted in a decrease of 1.0 SD (P less than 0.05) in the mean relative weight score. At the end of the therapy the obese children had lower fasting blood glucose levels (P less than 0.05) and lower plasma IRI concentrations at 90 min (P less than 0.05) after an oral glucose load than at the onset of therapy. There were no significant differences between the insulin binding characteristics at the commencement and at the end of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Child; Erythrocytes; Female; Humans; Insulin; Male; Obesity; Receptor, Insulin; Weight Loss

We evaluated insulin secretion, insulin sensitivity and blood pressure changes after oral administration of glucose in hypertensive and normotensive elderly subjects. The hypertensive group consisted of 12 subjects (aged 72.5 +/- 1.9 years, mean +/- s.e.m.) who had a history of hypertension lasting 10-25 years and were not more than 20% above ideal body weight. The normotensive group consisted of 12 subjects matched to the hypertensive group for age, sex and weight. All subjects underwent an oral glucose tolerance test (75 g glucose dissolved in 300 ml water), an intravenous glucose tolerance test (0.33 g/kg of a 50% glucose solution) and a euglycaemic, moderately hyperinsulinaemic glucose clamp. In both groups, oral glucose tolerance was normal according to the criteria of the National Diabetes Data Group; the hypertensive group showed significantly higher plasma glucose and insulin responses to oral glucose than the normotensive group, suggesting insulin resistance. The results of the euglycaemic clamp confirmed the state of reduced insulin sensitivity. Our data demonstrate that oral but not intravenous glucose produces a fall in blood pressure in hypertensive but not in normotensive patients, probably because activation of the sympathetic nervous system is impaired in hypertensive subjects; moreover, hypertension in the elderly seems associated with a state of reduced sensitivity to insulin.

Topics: Administration, Oral; Aged; Blood Pressure; C-Peptide; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hypertension; Injections, Intravenous; Insulin; Insulin Resistance; Insulin Secretion; Obesity

Topics: C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Islets of Langerhans; Male; Obesity

Previous studies demonstrated that administration of insulin and oral hypoglycemic agents tends to produce weight gain in type II diabetic patients. The goal of this study was to determine the potential contribution of changes in metabolic rate and urinary glucose excretion to changes in energy balance associated with treatment with glyburide and insulin. Six obese type II diabetic patients (52-61 yr old; 123-214% of ideal weight) were fed a weight-maintaining diet of fixed composition and caloric content in a Clinical Research Center. The mean fasting plasma glucose concentrations were 10.7 +/- 1.3 (+/- SE) mmol/L before treatment, 7.9 +/- 1.4 mmol/L at the end of 2 weeks of glyburide treatment, and 5.2 +/- 0.3 mmol/L at the end of 2 weeks of insulin treatment. Urinary glucose excretion decreased from 48 +/- 19 g/day before treatment to 20 +/- 9 g/day at the end of glyburide treatment and 2 +/- 1 g/day at the end of insulin treatment. Neither treatment affected mean postabsorptive resting metabolic rate (untreated 4.86 +/- 0.50 kJ/min; glyburide-treated, 4.63 +/- 0.45 kJ/min; insulin-treated, 4.70 +/- 0.46 kJ/min) or postprandial resting metabolic rate (untreated, 5.71 +/- 0.55 kJ/min; glyburide-treated, 5.60 +/- 0.39 kJ/min; insulin-treated, 5.70 +/- 0.51 kJ/min). However, the two patients with the largest decreases in urinary glucose excretion also had decreases in energy expenditure. These data indicate that many obese type II diabetic patients could have significant weight gain from reduced energy losses alone.

Topics: Blood Glucose; Blood Urea Nitrogen; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Energy Metabolism; Epinephrine; Female; Glucagon; Glyburide; Glycosuria; Humans; Insulin; Male; Middle Aged; Norepinephrine; Obesity

In order to evaluate whether the hypoglycaemic action of glibenclamide during chronic treatment of obese subjects with NIDDM is primarily due to changes in the daytime insulin level, in insulin secretion or to changes in tissue sensitivity to insulin, we studied eight NIDD's (age 43 +/- 3 years, body mass index 31.4 +/- 2.6 kg/m2) inappropriately controlled by dietary treatment alone. Before and after three months of glibenclamide treatment, plasma glucose, insulin and C-peptide were measured hourly (0800 to 1600 hours) and in vivo insulin sensitivity was evaluated using the sequential euglycaemic clamp (insulin infusion: 0, 0.8, 3.2 mU/kg/min) in combination with 3-3H-glucose tracer technique. During glibenclamide treatment the mean daytime glucose level was reduced (11.2 +/- 0.5 versus 7.1 +/- 0.4 mmol/l, p less than 0.001) but not to normal (5.2 +/- 0.2 mmol/l, p less than 0.001). Before treatment the mean daytime insulin level was higher than normal (38 +/- 58 versus 24 +/- 2 microU/ml, p less than 0.05) and was increased by 79% (67 +/- 8 microU/ml, p less than 0.001) after three months of treatment. In contrast the mean C-peptide level was unchanged (1.40 +/- 0.13 versus 1.30 +/- 0.17 nmol/l, p = NS), although it was higher than normal on both occasions (0.84 +/- 0.09 nmol/l, p less than 0.05). The basal hepatic glucose production rate was normal before treatment (86 +/- 4 versus 82 +/- 3 mg.m-2.min-1 in normals, p = NS), and unchanged after glibenclamide treatment (80 +/- 3 mg.m-2.min-1, p = NS versus pretreatment level).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glyburide; Humans; Insulin; Male; Obesity; Reference Values

The secretion and hepatic extraction of insulin were compared in 14 normal volunteers and 15 obese subjects using a previously validated mathematical model of insulin secretion and rate constants for C-peptide derived from analysis of individual decay curves after intravenous bolus injections of biosynthetic human C-peptide. Insulin secretion rates were substantially higher than normal in the obese subjects after an overnight fast (86.7 +/- 7.1 vs. 50.9 +/- 4.8 pmol/m2 per min, P less than 0.001, mean +/- SEM), over a 24-h period on a mixed diet (279.6 +/- 24.2 vs. 145.8 +/- 8.8 nmol/m2 per 24 h, P less than 0.001), and during a hyperglycemic intravenous glucose infusion (102.2 +/- 10.8 vs. 57.2 +/- 2.8 nmol/m2 per 180 min, P less than 0.001). Linear regression analysis revealed a highly significant relationship between insulin secretion and body mass index. Basal hepatic insulin extraction was not significantly different in the normal and obese subjects (53.1 +/- 3.8 vs. 51.6 +/- 4.0%). In the normal subjects, fasting insulin did not correlate with basal hepatic insulin extraction, but a significant negative correlation between fasting insulin and hepatic insulin extraction was seen in obesity (r = -0.63, P less than 0.02). This finding reflected a higher extraction in the six obese subjects with fasting insulin levels within the range of the normal subjects than in the nine subjects with elevated fasting insulin concentrations (61 +/- 3 vs. 45 +/- 6%, P less than 0.05). During the hyperglycemic clamp, the insulin secretion rate increased to an average maximum of 6.2-fold over baseline in the normal subjects and 5.8-fold in the obese subjects. Over the same time, the peripheral insulin concentration increased 14.1-fold over baseline in the normals and 16.6-fold over baseline in the obese, indicating a reduction in the clearance of endogenously secreted insulin. Although the fall in insulin clearance tended to be greater in the obese subjects, the differences between the two groups were not statistically significant. Thus, under basal, fasting conditions and during ingestion of a mixed diet, the hyperinsulinemia of obesity results predominantly from increased insulin secretion. In patients with more marked basal hyperinsulinemia and during intense stimulation of insulin secretion, a reduction in insulin clearance may contribute to the greater increase in peripheral insulin concentrations that are characteristic of the obese state.+

Topics: Blood Glucose; C-Peptide; Humans; Hyperglycemia; Insulin; Insulin Secretion; Liver; Metabolic Clearance Rate; Obesity

The pattern of endogenous insulin secretion over a 24-h period, which included three mixed meals, was evaluated in 14 normal volunteers and 15 obese subjects. Insulin secretory rates were calculated from plasma C-peptide levels using individually derived C-peptide kinetic parameters and a validated open two-compartment model of peripheral C-peptide kinetics. Insulin secretion rates were consistently elevated in the obese subjects under basal conditions (11.6 +/- 1.2 vs. 5.4 +/- 0.5 nmol/h) and in the 4 h after breakfast (139 +/- 15 vs. 63 +/- 5 nmol/4 h, P less than 0.001), lunch (152 +/- 16 vs. 67 +/- 5 nmol/4 h, P less than 0.001), and dinner (145 +/- 18 vs. 65 +/- 6 nmol/4 h, P less than 0.001). In the normal subjects, basal insulin secretion represented 50 +/- 2.1% of total 24-h insulin production, insulin secretion returned to baseline between meals, and equal quantities of insulin were secreted in the 4 h after breakfast, lunch, and dinner, despite the fact that subjects consumed half the number of calories at breakfast compared to lunch and dinner. Overall glucose responses were also similar after the three meals. In contrast, the pattern of insulin secretion in obese subjects was largely normal, albeit set at a higher level. However, the insulin secretion rate after meals did not return to baseline, and the secretion rate immediately before lunch (350.5 +/- 81.9 pmol/min) and dinner (373.6 +/- 64.8 pmol/min) was considerably higher than the secretion rate immediately before breakfast (175.5 +/- 18.5 pmol/min). In these overweight subjects, the glucose response after lunch was lower than after dinner. Analysis of individual 24-h insulin secretory profiles in the normal subjects revealed that insulin secretion was pulsatile. On average 11.1 +/- 0.5 pulses were produced in each 24-h period. The most prevalent temporal distribution of postmeal secretory pulses was two pulses after breakfast and three pulses after both lunch and dinner. Insulin secretion was also pulsatile during the period without meal stimuli: 3.9 +/- 0.3 pulses occurred during the period of overnight sampling and in the 3-h period before ingestion of the breakfast meal. In the obese subjects, the number and timing of secretory pulses was similar to those of normal volunteers, although the amplitude of the pulses was significantly greater. In both groups of subjects, greater than 80% of insulin pulses were concomitant with a pulse in glucose concentration in the postmeal period. The

Topics: Blood Glucose; C-Peptide; Circadian Rhythm; Eating; Humans; Insulin; Insulin Secretion; Obesity; Periodicity

The relationship between adipose tissue distribution, androgen levels, and metabolic complications of obesity was studied in 20 hirsute and 20 nonhirsute obese premenopausal women. The group of hirsute women showed preferentially an upper body type of obesity as assessed by the waist-to-hip ratio (0.902 + 0.017 v 0.778 +/- 0.015, P less than .01). They had higher serum concentrations of total testosterone (100.4 + 11.7 v 48.8 +/- 4.5 ng/dL, P less than .01) and lower levels of serum sex-hormone-binding globulin (28.1 +/- 3.6 v 44.0 + 4.2 nmol/L, P less than .05) exhibiting an increased androgenic activity as compared to the nonhirsute women. Serum glucose and insulin levels after an oral glucose load were significantly higher in the hirsute women. In addition, the group of hirsute females has significantly higher fasting concentrations of total cholesterol (5.82 +/- 0.28 v 4.75 +/- 0.14 mmol/L, P less than .05) and triglycerides (2.51 +/- 0.38 v 1.14 +/- 0.10 mmol/L, P less than .01). The hirsute group also showed higher systolic (166.7 +/- 5.1 v 142.1 +/- 4.5 mm Hg, P less than .01) and diastolic (100.9 +/- 3.6 v 85.2 +/- 2.5 mm Hg, P less than .01) blood pressure values than the nonhirsute women. Analysis of correlation revealed that an increasing waist-to-hip ratio was accompanied by increasing testosterone levels (r = .39, P less than .05) and by decreasing sex-hormone-binding globulin levels (r = .37, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adult; Blood Pressure; C-Peptide; Cholesterol; Female; Hirsutism; Hormones; Humans; Hydrocortisone; Insulin; Obesity; Testosterone

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Glucose Tolerance Test; Humans; Hypertension; Insulin; Islets of Langerhans; Middle Aged; Obesity

We assessed the effects of weight loss on pancreatic secretion and hepatic extraction of insulin in 11 obese subjects with noninsulin-dependent diabetes mellitus. Weight loss of 15.4 +/- 2.0 kg (mean +/- SE) resulted in decreased fasting insulin [20.2 +/- 2.5 to 9.8 +/- 2.5 microU/mL (145 +/- 18 to 70 +/- 18 pmol/L); P less than 0.02] and C-peptide (850 +/- 80 to 630 +/- 110 pmol/L; P less than 0.05) levels. The plasma glucose response to oral glucose and iv glucagon was improved with unchanged peripheral insulin levels. When plasma glucose levels were matched to those before weight loss, peripheral serum insulin and plasma C-peptide responses to iv glucagon were increased and similar to those in obese nondiabetic subjects studied at euglycemia. The total insulin response (area under the curve) to iv glucagon was reduced 30% (P less than 0.005), while the total C-peptide response area did not change after weight loss. At matched hyperglycemia, the total response area was enhanced 72% for insulin (P less than 0.002) and 64% for C-peptide (P less than 0.001). Incremental (above basal) response areas after weight loss did not change for insulin, but increased 66% for C-peptide (P less than 0.05). The incremental areas were augmented nearly 2-fold (196%) for insulin (P less than 0.01) and 1.7-fold (173%) for C-peptide (P less than 0.01) when assessed at matched hyperglycemia. Both basal (7.3 +/- 0.5 to 14.1 +/- 1.8; P less than 0.01) and total stimulated (6.1 +/- 0.4 to 8.8 +/- 1.4; P less than 0.05) C-peptide to insulin molar ratios increased after weight loss. We conclude that after weight loss in noninsulin-dependent diabetes mellitus, 1) insulin secretion is decreased in the basal state but increased after stimulation; 2) changes in insulin secretion are reflected by peripheral levels of C-peptide but not insulin, due in part to enhanced hepatic insulin extraction; and 3) at matched levels of hyperglycemia insulin secretion is markedly increased and similar to that in obese nondiabetic subjects studied at euglycemia.

Topics: Basal Metabolism; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Fasting; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Liver; Male; Middle Aged; Obesity; Pancreas

To assess the contribution of gastric inhibitory polypeptide (GIP) to the postprandial hyperinsulinemia of obesity, secretion rates of GIP (generated from kinetic analyses from infusions of porcine GIP) and insulin (from C-peptide applied to a validated kinetic model) to meals of 3 sizes were determined in 10 obese (5 male and 5 female) and 10 lean, sex- and age-matched healthy subjects. Although the postprandial secretion rates of GIP were greater in obese subjects (P = 0.03), postprandial concentrations of GIP were not. The latter may be explained by the greater volume of distribution of GIP in obese subjects (P = 0.036). Secretion rates and volume of distribution of GIP were correlated (r = 0.652, P less than 0.01). Despite excessive integrated postprandial (P = 0.010) insulin concentrations, insulin secretion was not significantly different between obese and lean subjects. We conclude that 1) although postprandial plasma GIP concentrations are normal, GIP secretion is increased in obesity, 2) the postprandial hyperinsulinemia of obesity is not due to excessive insulin secretion but is likely secondary to altered insulin clearance, and 3) GIP cannot account for the hyperinsulinemia of obesity through its insulinotropic action.

Topics: Adult; Blood Glucose; C-Peptide; Female; Food; Gastric Inhibitory Polypeptide; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Kinetics; Male; Obesity; Sex Factors

Glucose cycling (GC; G in equilibrium G6P) equals 14% of glucose production in postabsorptive man. Our aim was to determine glucose cycling in six lean and six overweight mild type II diabetics (fasting glycemia: 139 +/- 10 and 152 +/- 7 mg/dl), in postabsorptive state (PA) and during glucose infusion (2 mg/kg per min). 14 control subjects were weight and age matched. GC is a function of the enzyme that catalyzes the reaction opposite the net flux and is the difference between hepatic total glucose output (HTGO) (2-[3H]glucose) and hepatic glucose production (HGP) (6-[3H]-glucose). Postabsorptively, GC is a function of glucokinase. With glucose infusion the flux is reversed (net glucose uptake), and GC is a function of glucose 6-phosphatase. In PA, GC was increased by 100% in lean (from 0.25 +/- 0.07 to 0.43 +/- .08 mg/kg per min) and obese (from 0.22 +/- 0.05 to 0.50 +/- 0.07) diabetics. HGP and HTGO increased in lean and obese diabetics by 41 and 33%. Glucose infusion suppressed apparent phosphatase activity and gluconeogenesis much less in diabetics than controls, resulting in marked enhancement (400%) in HTGO and HGP, GC remained increased by 100%. Although the absolute responses of C-peptide and insulin were comparable to those of control subjects, they were inappropriate for hyperglycemia. Peripheral insulin resistance relates to decreased metabolic glucose clearance (MCR) and inadequate increase of uptake during glucose infusion. We conclude that increases in HGP and HTGO and a decrease of MCR are characteristic features of mild type II diabetes and are more pronounced during glucose infusion. There is also an increase in hepatic GC, a stopgap that controls changes from glucose production to uptake. Postabsorptively, this limits the increase of HGP and glycemia. In contrast, during glucose infusion, increased GC decreases hepatic glucose uptake and thus contributes to hyperglycemia. Obesity per se did not affect GC. An increase in glucose cycling and turnover indicate hepatic insulin resistance that is observed in addition to peripheral resistance. It is hypothesized that in pathogenesis of type II diabetes, augmented activity of glucose-6-phosphatase and kinase may be of importance.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose; Humans; Infusions, Intravenous; Insulin; Liver; Male; Middle Aged; Obesity

The aim of the study was to evaluate the reliability of urinary excretion rate of C-peptide as a marker of B-cell function during fasting. Ten obese subjects of both sexes fasted for 5 days. Diurnal serum C-peptide was collected before and on the 5th day; morning serum samples (for glucose, insulin and C-peptide) and 12-h urine samples (7.00 to 19.00 h) were collected daily. Body weight decreased from 138.7 +/- 15.9 to 132.9 +/- 15.6 kg. Morning glucose, insulin (-40%) and C-peptide (-50%) fell significantly throughout the study. Mean diurnal C-peptide values were 2.19 +/- 0.69 nmol/l before and 0.60 +/- 0.19 nmol/l after fasting (P less than 0.0001) and its secretion rate was 909.4 +/- 297.9 and 244.4 +/- 83.9 nmol/12 h (P less than 0.005), respectively. Excretion rate of C-peptide fell progressively from basal (11.2 +/- 4.2 nmol/12 h) to a nadir value of 1.3 +/- 0.8 nmol/12 h (P less than 0.0005); similarly, the C-peptide to creatinine clearance ratio fell from 0.062 +/- 0.035 to 0.028 +/- 0.015 (P less than 0.05). These results indicate that fasting modifies renal metabolism of C-peptide thus creating several complications in the quantitative interpretation of urinary levels as an index of its secretion rate from the B-cell.

Topics: Adult; Blood Glucose; C-Peptide; Creatinine; Eating; Fasting; Female; Humans; Insulin; Male; Middle Aged; Obesity

It is generally assumed that diet therapy can ameliorate the metabolic derangements experienced by obese type 2 diabetic patients, thereby leading to discontinuation of insulin or oral sulfonylurea drug therapy. We decided to retrospectively investigate which clinical and biochemical parameters affect therapeutic responses.. Sixty-four poorly controlled obese diabetic patients were hospitalized and placed on a precisely defined, hypocaloric diet. Known duration of diabetes, type of pharmacologic therapy, body weight, weight loss, fasting plasma glucose concentrations, C-peptide levels, hemoglobin A1C, and plasma lipid levels were assessed, as were nitrogen and electrolyte balances.. Average weight loss was 13 pounds in a mean of 23 days. During hospitalization, the mean fasting plasma glucose value for the group fell from 221 +/- 10 to 122 +/- 5 mg/dl. In 45 patients (73 percent), the final fasting plasma glucose level was less than 125 mg/dl (mean: 102 +/- 2 mg/dl). Oral glucose tolerance even in those patients in whom fasting plasma glucose levels normalized was still grossly diabetic at the end of the hospital stay, deteriorating further after three days of liberalized caloric intake. In part this may have been due to decreased insulin secretory reserve as reflected by blunted plasma C-peptide response. Forty of 42 patients who entered the study taking insulin were able to discontinue the drug within one to seven days of hospitalization. After a mean follow-up period of 19 months, only 10 of 50 patients continued to maintain fasting euglycemia; five were on diet alone, and five were receiving oral hypoglycemic agents. Thirteen patients were receiving insulin therapy.. Diet therapy in these patients resulted in short-term improvement of glycemic control and, in the majority, normalization of fasting plasma glucose levels. However, long-term outpatient follow-up revealed that relapse occurred in most patients.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Lipids; Male; Middle Aged; Obesity; Retrospective Studies; Time Factors

We evaluated the safety and efficacy of a highly supplemented controlled low-energy (1764 kJ [420 kcal]) diet in the treatment of non-insulin-dependent diabetes and obesity. Six obese, diabetic women ranging from 143% to 297% of ideal body weight were studied in a metabolic ward for 48 days. The subjects ingested a weight-maintenance diet during an eight-day control period followed by 40 days of an experimental diet containing 1764 kJ (420 kcal) of a mixture of protein (43% of energy intake), carbohydrates (51%), and fat (6%), supplemented with minerals, trace elements, and vitamins. The subjects were monitored for balances of nitrogen and minerals, as well as for the appearance of cardiac arrhythmias by 24-hour electrocardiographic recordings. Weight loss was rapid and sustained and averaged 10.1% +/- 0.8% over 40 days. Fasting plasma glucose levels declined from 16.2 +/- 1.9 mmol/L (293 +/- 36 mg/dL) to 6.9 +/- 0.8 mmol/L (126 +/- 16 mg/dL) by day 35. Similarly, hemoglobin A1c levels fell from 0.11 +/- 0.009 (11.2% +/- 0.9%) to 0.8 +/- 0.001 (8.2% +/- 1.1%). Urinary C-peptide levels declined from 62.2 +/- 15.6 nmol/48 h to 20.0 +/- 5.9 nmol/48 h by days 39 to 40 and paralleled the decline in plasma glucose values, the majority of which occurred in the first seven days. Concentrations of serum cholesterol and triglycerides decreased. Balances for nitrogen, potassium, and magnesium were negative at -1.7 g/24 h, -2.2 mEq/24 h, and -2.9 mg/dL, respectively. Blood pressure decreased without orthostasis. Resting metabolic rate fell a mean of 18% but remained within normal limits. Triiodothyronine levels also declined. Twenty-four-hour ambulatory electrocardiographic readings disclosed no significant bradyarrhythmia or tachyarrhythmia for any patient. These studies, based on a limited number of subjects, demonstrate that a highly supplemented controlled low-energy diet is a safe and efficacious treatment for diabetes and obesity, leading to significant decreases in weight, blood pressure, and levels of plasma glucose and plasma lipids. Such diets may be the optimal initial treatment of moderate to markedly obese patients with non-insulin-dependent diabetes.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Diet, Reducing; Electrocardiography; Electrolytes; Energy Metabolism; Female; Hospitalization; Humans; Middle Aged; Monitoring, Physiologic; Obesity; Physical Exertion

Topics: Adult; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus; Diltiazem; Double-Blind Method; Electrocardiography; Female; Glucose Tolerance Test; Humans; Obesity; Risk Factors

Naloxone, an opiate antagonist, was given as an intravenous bolus (5 mg) in both lean and obese healthy subjects. In lean people, there was a slight trend for insulin and C-peptide concentrations to decrease below baseline values with no glucose change. Obese subjects showed an exaggerated suppression of insulin and C-peptide and a slight decrease of glucose. Glucagon was suppressed in both groups. An infusion of human beta-endorphin (0.05 mg/h) produced only minor changes in plasma glucose, insulin, glucagon, and C-peptide concentrations in lean subjects, but caused marked increments in obese. Glucagon rose in both groups, but its response was greater in obese subjects. A ten-day treatment with naloxone (1.2 mg twice a day) did not change the metabolic and hormonal responses to an oral glucose load (75 g) in lean but significantly inhibited the insulin and C-peptide responses to glucose in obese people. These results suggest that an increased opiate drive to the pancreatic beta-cell and an increased responsiveness of insulin to beta-endorphin are present in human obesity.

Topics: Adult; beta-Endorphin; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Naloxone; Obesity

The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes.

Topics: Adult; Age Factors; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Obesity; Pedigree; Sex Factors

Six matched groups of obese patients underwent 3-week selective hypocaloric regimens which consisted of a 240 or 480 kcal/day liquid formula diets for groups 1-4 and an 800 kcal/day conventional diet for groups 5 and 6. Carbohydrate intake ranged from 19 to 112 g/day so that for each energy level two different amounts of carbohydrates were administered. Body weight loss was similar in groups 1-4 and significantly lower in groups 5 and 6. During treatment fasting serum insulin (but not serum C-peptide) levels and the daily urine excretion rate of C-peptide showed quite a similar fall in all groups. Fasting glucagon levels did not change. The rate of ketogenesis which developed during each nutritional treatment was inversely related to the amount of dietary carbohydrates; moreover, a significant correlation was found between percent variation of ketoacids and those of fasting IRI (r = -0.42; p less than 0.01) and glucose (r = -0.52; p less than 0.01) concentrations, but not with those of fasting C-peptide and its daily urine excretion rate. In conclusion, it seems that during underfeeding (1) low- and high-carbohydrate-containing regimens are substantially equipotent stimuli secretagogues of insulin secretion, and (2) carbohydrate (or glucose) availability affects ketogenesis even through noninsulin-mediated mechanisms.

Topics: Adult; Blood Glucose; C-Peptide; Diet, Reducing; Dietary Carbohydrates; Energy Intake; Fasting; Female; Glucagon; Humans; Insulin; Ketone Bodies; Male; Obesity

Serum lipids and lipoproteins were studied in 149 non-insulin-dependent diabetic subjects treated with diet or oral drugs (75 men, 74 women) and in 101 nondiabetic control subjects (49 men, 52 women) in relation to endogenous insulin secretion capacity measured by plasma C-peptide response to intravenous glucagon. Serum HDL- and HDL2-cholesterol concentrations were lower and VLDL-cholesterol and total and VLDL-triglyceride concentrations higher in subjects with high C-peptide response (above the median) than in subjects with low C-peptide response (lower or equal to median) both in diabetic and control subjects of both sexes. Adjustment for the effect of obesity abolished these differences in serum lipids and lipoproteins in diabetic subjects but not in control subjects. This may indicate that obesity has stronger influence on serum lipids in diabetic subjects than in nondiabetic subjects.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Insulin; Insulin Secretion; Lipids; Lipoproteins; Male; Middle Aged; Obesity

One hundred grams of glucose with 50 microCi U-14C-glucose were given orally to 17 women with widely varying amounts of body fat. Radioactivity and glucose metabolism in vitro were then measured in adipose tissue obtained by needle biopsies in the abdominal and femoral regions after four hours. Radioactivity in triglycerides was then measured in repeated biopsies 1 day, 1 week, and monthly up to 7 months after glucose administration. Glucose label in triglycerides after four hours was higher in abdominal than femoral adipocytes in obese women. It increased slightly during the following week, and then decreased exponentially with a half-life of 12 months in the abdominal region and 19 months in the femoral region. Uptake of glucose carbon in total body fat was estimated from the triglyceride label measured and determinations of body fat mass, and found to be in the order of less than 4% of given glucose. The studies in vitro suggested that much of the glucose taken up in adipose tissue is converted to lactate. If this is the case in vivo, then glucose uptake in adipose tissue might well be of significance for total body glucose homeostasis, particularly in obese subjects, amounting to maximally perhaps one third to one half of the oral glucose given. The majority of this glucose uptake would then, however, leave adipose tissue again as lactate. The shorter half-life of label in abdominal adipocytes is in agreement with findings of increased lipolysis in these adipocytes in vitro.

Topics: Abdomen; Adipose Tissue; Adult; Blood Glucose; C-Peptide; Female; Glucose; Humans; Insulin; Lactates; Lactic Acid; Lipolysis; Middle Aged; Obesity; Thigh; Triglycerides

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 2; Diet, Diabetic; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Phenotype

The importance of androgenic activity in mediating the effects of obesity and body fat topography on splanchnic insulin metabolism and peripheral insulin sensitivity was studied in 19 nonhirsute premenopausal women with a wide range of ideal body weight [percent ideal body weight (% IBW), 78-202%] and body fat distribution pattern [waist to hip girth ratio (WHR), 0.67-0.91]. Turnover kinetics of peripheral plasma C-peptide and insulin were measured, and estimates of pancreatic insulin production (PIP) and the hepatic extraction fraction (HEF) were calculated. The peripheral insulin sensitivity index (M/I) was determined during an euglycemic insulin clamp study. Androgenic activity was assessed by estimating the plasma level of sex hormone-binding globulin (SHBG) and percentage of free testosterone (% FT). After iv glucose stimulation, PIP ranged from 40-254 mU/min X m2 and correlated highly with % IBW (r = 0.78; P less than 0.01). Insulin HEF ranged from 5-69% of the pancreatic production and was inversely proportional to WHR (r = -0.60; P less than 0.01). Increasing WHR also correlated with the diminution in M/I (r = -0.47; P less than 0.05), which, in turn, correlated with the decline in the HEF of insulin (r = 0.60; P less than 0.01). Since PIP, HEF, and M/I correlated with SHBG and % FT, and since the degree of androgenic activity correlated with % IBW and WHR, partial regression analysis was performed. After adjusting for the effects of SHBG and % FT, the relationship between % IBW and PIP remained unaltered, whereas the correlation between WHR and HEF or M/I and their relationship to each other were either markedly reduced or became insignificant. Thus, in premenopausal women, the increase in pancreatic insulin production with increasing weight is independent of the degree of androgenic activity. On the other hand, the decline in hepatic insulin extraction and diminution in peripheral insulin sensitivity with upper body fat localization are in part mediated by increased androgenic activity. This association may account for the pronounced hyperinsulinemia and insulin resistance characteristic of this form of obesity.

Topics: Adipose Tissue; Adolescent; Adult; Age Factors; Androgens; Blood Glucose; Body Weight; C-Peptide; Female; Humans; Insulin; Liver; Menopause; Metabolic Clearance Rate; Obesity; Splanchnic Circulation

To determine the effects of different hypocaloric diets on insulin secretion, 24-h urine C-peptide was measured in 11 obese subjects on a weight-maintaining baseline diet, and the results were compared with values obtained during 14-day periods of diets containing 400 kcal/day of only protein (n = 6) or glucose (n = 5), followed by 14 days of fasting and 14 days of refeeding on 800-1000 kcal/day. A significant positive correlation between total caloric intake and urine C-peptide excretion was found once the C-peptide excretion reached steady state after several days on each diet. Multiple regression analysis showed no contribution of body weight to urine C-peptide during the different diets. In contrast, a significant correlation was found between body weight and urine C-peptide in the fasting state. A marked and identical decrease of approximately 75% in urine C-peptide occurred over the first 5-7 days of the two 400-kcal diets, followed by a further decrease during fasting to 5% of baseline values. Refeeding was associated with a progressive increase. Plasma insulin and C-peptide followed the same trends as found for urine C-peptide, although the magnitude of change was much smaller. C-peptide clearance was not assessed because of the variation in plasma levels on eating meals. However, the same responses were found when C-peptide excretion was factored for creatinine excretion. Thus, the major determinant of urine C-peptide excretion appears to be food intake, and adaptations take 5-7 days to reach steady state.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Body Weight; C-Peptide; Energy Intake; Energy Metabolism; Fasting; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity

Immunoreactive C-peptide was evaluated in the plasma and pancreas of Aston ob/ob and C57BL/KsJ db/db mice in relation to disturbances in pancreatic B-cell function. At 18-24 weeks of age, ob/ob and db/db mice displayed hyperglycaemia (1.6 and 3.8 fold increases respectively) and hyperinsulinaemia (10.8 and 5.1 fold increases respectively) despite a similar pancreatic insulin content to their respective non-diabetic lean control mice. Immunoreactive C-peptide concentrations in the plasma and pancreas of the mutants corresponded with the degree of hyperinsulinaemia and pancreatic insulin content, and the insulin: C-peptide molar ratios in both mutants were similar to lean controls. In ob/ob mice parenteral glucose administration decreased plasma insulin and C-peptide concentrations, despite markedly raised glucose concentrations. However, administration of a low dose of insulin (5 U/kg) to lean mice and much higher doses of insulin (50 and 120 U/kg) to ob/ob mice markedly decreased plasma glucose and C-peptide concentrations. When the rate and extent of insulin-induced glucose suppression observed in ob/ob mice was mimicked in lean mice, an almost complete (95%) inhibition of C-peptide was achieved compared with a 57% decrease in the ob/ob mutant. Injection of ob/ob mice with glucose to counter the insulin-induced hypoglycaemia failed to affect the fall of C-peptide concentrations. The data suggest that the metabolic processing of insulin and C-peptide are undisturbed in obese-diabetic mice, and that the impaired suppression of circulating C-peptide by insulin-hypoglycaemia in ob/ob mice predominantly reflects impaired feedback inhibition by insulin.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glucose; Insulin; Kinetics; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Obese; Obesity; Radioimmunoassay

To determine whether the severity of insulin resistance in obesity, as assessed by the traditional hyperinsulinemic glucose clamp, reflects the severity of resistance present during changing insulin concentrations, such as occur after meal ingestion, 9 moderately obese and 12 lean subjects were studied on 2 occasions: once during a primed continuous insulin infusion and once during a variable 8-step insulin infusion. Identical amounts of insulin were given on each occasion, and euglycemia was maintained by a glucose infusion. Stimulation of isotopically determined glucose utilization above the basal value was lower in the obese than in the lean subjects during the variable [2.4 +/- 0.5 (+/- SEM) vs. 5.4 +/- 0.7 g/m2; P = 0.004] and the constant (2.9 +/- 0.7 vs 4.2 +/- 0.9 g/m2; P = 0.32) insulin infusions; however, the differences were only significant with the variable insulin infusion. The variable insulin infusion also was associated with lower rates of activation of glucose utilization (slope, 0-90 min, 0.27 +/- 0.05 vs. 0.55 +/- 0.09 mg/m2 X min 2; P = 0.01) in obese compared to lean subjects. In contrast, rates of activation during the low constant infusion (0.24 +/- 0.05 vs. 0.29 +/- 0.06 mg/m2 X min 2; P = 0.51) did not differ in the lean and obese subjects. Despite identical amounts of insulin, stimulation of glucose utilization was greater (P less than 0.03) during the variable than during the constant insulin infusion in the lean subjects. In contrast, stimulation during the variable and constant insulin infusions was equal in the obese subjects. These observations indicate that insulin resistance in obesity is due to a defect in the rate as well as absolute response achieved and suggest that under conditions of daily living the contribution of insulin resistance to impaired carbohydrate tolerance is greater than that previously estimated by a constant insulin infusion.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Glucagon; Glucose; Humans; Insulin; Insulin Resistance; Kinetics; Middle Aged; Obesity

This study examined the relationship between the C-peptide response to intravenous glucagon and mixed meal stimulation and the 24 h urinary excretion rate of C-peptide and its urinary excretion during the glucagon test in nine control subjects, eighteen Type 1 (insulin-dependent) and twenty-two Type 2 (non-insulin-dependent) diabetic patients. Compared to controls (61.0 +/- 7.1 micrograms), the 24-h urine excretion rate of C-peptide was 8.2 +/- 3.1 micrograms (p less than 0.001) in Type 1 and 89.8 +/- 12.9 micrograms (p = NS) in Type 2 diabetic patients. C-peptide urinary excretion rate during the glucagon test was 6.92 +/- 1.11 micrograms, 0.42 +/- 0.10 microgram (p less than 0.001) and 6.47 +/- 1.13 micrograms (p = NS) respectively. Fasting serum C-peptide values were 1.53 +/- 0.16 ng/ml in controls, 0.42 +/- 0.09 ng/ml in Type 1 (p less than 0.0001) and 2.08 +/- 0.22 ng/ml in Type 2 diabetics (p = NS); C-peptide areas under the curve after glucagon stimulation were, respectively, 241.6 +/- 20.3 ng/ml, 29.2 +/- 5.9 ng/ml (p less than 0.0001) and 170.9 +/- 17.9 ng/ml (p less than 0.03) and after the meal test they were 204.7 +/- 15.6, 68.7 +/- 19.8 ng/ml (p less than 0.0001) and 265.5 +/- 32.9 ng/ml (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Food; Glucagon; Humans; Islets of Langerhans; Male; Obesity

We recently reported a new case of abnormal insulinemia with LeuA3 insulin. Herein, we measured urinary insulin clearance during oral glucose tolerance tests in proband with abnormal insulinemia (44-yr-old female), three affected family members, two unaffected family members, two other hyperinsulinemic patients with obesity, five non-insulin-dependent diabetic patients, and five normal control subjects. Urinary insulin-to-creatinine clearance ratio in the proband and her affected family members was 0.22 X 10(-3) +/- 0.07 (mean +/- SD, n = 4) and was markedly reduced compared with those of other groups: 1.73 X 10(-3) in two unaffected family members, 2.77 X 10(-3) in two other hyperinsulinemic patients with obesity, 2.99 X 10(-3) +/- 1.48 in five non-insulin-dependent diabetic patients, and 2.54 X 10(-3) +/- 0.67 in five normal control subjects. In contrast, urinary C-peptide clearance in these groups was not significantly different from controls. Binding of immunopurified insulins extracted from urine of the patients with abnormal insulinemia to guinea pig kidney membrane was slightly decreased (71% of standard insulin), in contrast with the observation that serum insulin of the proband had much less receptor-binding activity. Reverse-phase HPLC analysis of the immunopurified insulin of the proband revealed that the ratios of normal insulin to abnormal insulin were 8:3 in urine and 1:7 in serum, respectively. These results suggest that excretion of abnormal insulin in urine is much less than that of normal insulin.

Topics: Adult; Animals; C-Peptide; Creatinine; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Guinea Pigs; Humans; Hyperinsulinism; Insulin; Kidney; Male; Metabolic Clearance Rate; Obesity; Radioimmunoassay; Radioligand Assay

The effects of small increases in plasma insulin on hepatic glucose production are incompletely understood. To partially elucidate this issue we have studied seven obese subjects with the euglycemic clamp technique with a low-dose insulin infusion rate of 15 mU X m-2 X min-1 over 3 h. Basal insulin levels were 24 +/- 7 microU/ml and increased to steady-state levels of 35 +/- 3 microU/ml during insulin infusion. Endogenous insulin secretion, quantitated by C-peptide measurements, decreased by 58% of the basal value after peripheral insulin infusion. Based on C-peptide measurements and the contribution of the peripheral insulin infusion to the circulating insulin concentrations, calculated portal insulin levels either decreased or remained unchanged during the clamp studies. Basal glucagon levels were 165 +/- 18 and did not change during the insulin infusion. The basal glucose disposal rate was 86 +/- 2 mg X m-2 X min-1 and did not increase significantly during the clamp studies. In contrast, hepatic glucose output (HGO) was suppressed by 82 +/- 5% of the basal value. In summary, in a group of insulin-resistant obese subjects, glucose-clamp studies were performed at peripheral insulin levels of 35 +/- 3 microU/ml; glucose disposal did not increase, whereas HGO was suppressed by 82%. At the same time, glucagon levels remained constant and estimated portal insulin levels either decreased or remained unchanged. These findings suggest that insulin can suppress HGO through indirect extrahepatic actions.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucagon; Glucose; Glucose Tolerance Test; Humans; Insulin; Kinetics; Liver; Male; Obesity

Insulin sensitivity was studied in nine nondiabetic massively obese patients (one male and eight females ages 39.0 +/- 2.7 years, body mass index 47.1 +/- 1) by the euglycemic clamp technique (40 microU/m2/min) and compared to seven lean control subjects (three males and three females, ages 34.8 +/- 2.5 years, body mass index 23 +/- 1.1). Fasting plasma glucose, immunoreactive insulin, and C-peptide concentrations were higher in the massively obese patients than in the controls (P less than 0.025). Following exogenous insulin infusion, immunoreactive glucagon and C-peptide concentrations decreased similarly in the massively obese patients and controls, indicating normal sensitivity of the alpha and beta cell to insulin. Glucose uptake (M) expressed either as mg X min-1 of fat free mass was significantly reduced in the massively obese patients compared to the controls (P less than 0.001). Similarly, the M/I ratio (glucose uptake per unit of insulin) was significantly reduced in the massively obese patients (P less than 0.001). Free fatty acids and glycerol concentrations measured in the fasting state were significantly elevated in the massively obese patients (free fatty acids 678 +/- 51 v 467 +/- 55 mumol/L, P less than 0.05; glycerol 97 +/- 9 v 59 +/- 11 mumol/L, P less than 0.02). The effects of insulin on antilipolysis was assessed by measuring the reductions in free fatty acids and glycerol concentration during the glucose clamp study. Although the absolute levels remained higher in the massively obese patients, inhibition of lipolysis was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Female; Glycerol; Humans; Hydroxybutyrates; Insulin; Male; Metabolic Clearance Rate; Obesity

The effect of variations in glucose tolerance on insulin's ability to regulate glucose uptake and plasma glucose and FFA concentrations was assessed in 22 obese individuals [8 with normal glucose tolerance, 7 with impaired glucose tolerance (IGT), and 7 with noninsulin-dependent diabetes mellitus (NIDDM)]. Patients with IGT had ambient insulin levels that were higher than normal, associated with elevated postprandial glucose levels and a marked reduction in insulin-stimulated glucose uptake. On the other hand, plasma FFA levels were relatively normal in IGT, possibly because of the hyperinsulinemia. Patients with NIDDM were also hyperinsulinemic, with insulin levels throughout the day that were approximately twice normal. Hyperinsulinemia in patients with NIDDM was associated with a significant decline in insulin-stimulated glucose uptake as well as with significant increases in both ambient plasma glucose and FFA concentrations. Thus, and in contrast to patients with IGT, plasma FFA metabolism in NIDDM was grossly abnormal, despite the concomitant hyperinsulinemia. These data indicate that insulin resistance in obese individuals varies as a function of degree of glucose tolerance, and insulin resistance in patients with NIDDM involves defects in the regulation of both plasma glucose and FFA metabolism.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Fasting; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Obesity

Glucose tolerance tests were performed with fourteen cynomolgus monkeys. They were divided into two groups with regard to the serum glucose level at the time of routine health-examination. Nine of them had normal glucose level (below 123 mg/dl, the normal group) and the other five monkeys exhibited hyperglycemia (the abnormal group). Fifty per cent glucose solution was administered into the saphenous vein at a dose of 4 ml/head. Blood samples were taken just before and 5, 10, 20, 30, 60 and 120 minutes after the glucose administration. K-value (K = 0.693/t 1/2 X 100) as the decreasing rate of serum glucose during from 5 to 60 minutes after the administration was calculated. Average K-value for eight monkeys of the normal group was 3.12 +/- 0.48. Both immunoreactive insulin level (IRI) and C-peptide immunoreactivity (CPR) increased just after the glucose administration and began to decrease 5 to 30 minutes after the administration in all the eight animals. Remaining one animal (No. 009) of the normal group showed 1.03 in K-value. For the abnormal group, K-value averaged 0.75 +/- 0.25. IRI was slightly higher in this group than in the 8 monkeys of the normal group. Furthermore, the abnormal group did not show any definite change of a certain trend in IRI and CPR. In conclusion, the former 8 monkeys were judged to be normal in the function of pancreatic beta-cells, and the latter 5 monkeys and No. 009 monkey were judged to be suffering from type II (noninsulin dependent) diabetes mellitus at different stages of the disease.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Insulin; Macaca; Macaca fascicularis; Monkey Diseases; Obesity; Pancreas

According to our previous study, hyperinsulinism develops not before 10 years of age despite the presence of obesity but during the maturation years of 10-20. We aimed here at examining the growth-related islet B-cell change together with pituitary activity in non-familial juvenile obesity. Measurement of 24 h urine hormones was shown to be useful for evaluation of the diurnal hormones in plasma. In 56 non-obese and obese juveniles, a significantly positive correlation was found between age (6-18 years) and 24 h urine insulin and c-peptide, thus indicating that the age-related absolute value of body weight significantly affects insulin and c-peptide excretions both in non-obese and obese subjects. Consequently, urinary insulin and c-peptide excretions per kg of body weight were highly similar between obese and non-obese juveniles. However, when the lower specific gravity of fat mass compared with lean body mass and the relative shortage of circulating plasma in fat tissues are taken into consideration, it is obvious that obesity by itself specifically augments this physiologic B-cell maturation between 10 and 20 years of age. The possible interactions of growth hormone and pituitary gonadotropin in hyperinsulinism are discussed.

Topics: Adolescent; Aging; Body Height; Body Weight; C-Peptide; Child; Female; Gonadotropins, Pituitary; Growth Hormone; Humans; Hyperinsulinism; Insulin; Islets of Langerhans; Male; Obesity; Pituitary Gland

Topics: Adolescent; Age Factors; Biguanides; Buformin; C-Peptide; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Insulin; Obesity; Peptides

Insulin clearance and secretion determine the plasma insulin concentration. To elucidate the significance of these parameters in man, we employed the euglycemic insulin clamp technique to measure insulin sensitivity, insulin responsiveness, and insulin clearance, and we calculated the basal insulin delivery rate. In 27 patients (six normal, six obese, ten hyperthyroid, and five with Cushing's syndrome), insulin was infused at rates of 0.3, 1, 3, or 10 mU/Kg/min, and insulin concentration and glucose utilization were measured. C-peptide concentrations were measured before and during insulin infusion and decreased significantly, indicating a reduction of endogenous insulin secretion to 62% of basal in normals and a similar reduction in the other groups. Maximal responsiveness to insulin was a glucose utilization rate of 450 +/- 20 mg/min/m2 in normals, unchanged in obese, 42% increased in hyperthyroid, and 34% decreased in Cushing's syndrome patients. Sensitivity to insulin was decreased in all three abnormal groups. Insulin clearance rates were 1,050 +/- 80 mL/min/m2 for normals, not significantly changed in obese, 45% increased in hyperthyroid, and 33% decreased in Cushing's syndrome patients. All three abnormal groups showed hyperinsulinemia compared to normal. The basal insulin delivery rates were calculated as 7.0 +/- 0.3 mU/min/m2, with a threefold increase in obese and in hyperthyroid and no significant change in Cushing's syndrome patients. Insulin clearance correlated well with insulin responsiveness (r = .65, P less than 0.001), but poorly with insulin sensitivity (r = .36).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; C-Peptide; Cushing Syndrome; Female; Humans; Hyperthyroidism; Insulin; Male; Metabolic Clearance Rate; Obesity

Topics: Adolescent; Adult; C-Peptide; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Liver; Middle Aged; Obesity

Obese men and women with the same body fat mass, as well as obese women in another study, were divided into groups with male or female type of body fat distribution, but again with similar body fat mass. The participants were examined with measurements of body composition, including muscle fiber distribution, as well as circulatory and metabolic variables before and after physical training under controlled conditions. Obese men had higher lean body mass, blood pressure, blood glucose and plasma insulin, C-peptide, cholesterol and triglyceride concentrations than age- and body fat-matched obese women. Obese women with male type of adipose tissue distribution showed the same differences (except cholesterol) in comparisons with women with female type of adipose tissue distribution. The women with male type obesity were also more insulin resistant in glucose clamp measurements, and had male type of muscle fiber distribution. Physical training in the group of obese men resulted in a decrease of body fat, a further increase of lean body mass, an increase of fast twitch, aerobic type, muscle fibres as well as lower plasma insulin, cholesterol and triglyceride concentrations and lower blood pressure. Obese women with male type distribution of adipose tissue responded to physical training essentially like men. The insulin sensitivity was improved to the same level as in obese women with female type of adipose tissue distribution. In contrast, the latter women showed an increase of body fat and no metabolic improvements after training. These results show that obese women with male type of body fat distribution also have male characteristics of muscle mass, morphology and function. It is suggested that the obesity complications associated with this condition are improved by physical training because of an adaptation to a negative energy balance, in combination with an improvement of insulin sensitivity of the muscle mass. In contrast, the failure of obese women with female type of adipose tissue distribution to adapt to a negative energy balance during physical training is probably explaining their failure to decrease body fat and to improve metabolism during physical training.

Topics: Adipose Tissue; Adult; Blood Glucose; C-Peptide; Energy Metabolism; Female; Humans; Insulin; Lipids; Male; Middle Aged; Muscles; Obesity; Physical Education and Training; Sex Factors; Somatotypes

Plasma concentrations of fibronectin, free insulin, C-peptide and plasma glucose were determined in 40 morbidly obese subjects and in 51 normal weight controls, matched for sex and age. All plasma concentrations were significantly elevated (p less than 0.01) among the obese subjects. A significant correlation (r = 0.34, p less than 0.05) between plasma fibronectin and plasma free insulin was found among the obese patients, but not among the controls (r = -0.02, p greater than 0.05). No significant correlation was found between plasma fibronectin and plasma C-peptide, neither in the obese patients nor in the controls (obese r = 0.06, controls r = 0.02; p greater than 0.05). Plasma fibronectin was insignificantly correlated with body weight (obese r = 0.21, controls r = 0.15; p greater than 0.05) and percentage overweight (obese r = 0.27, controls r = 0.04; p greater than 0.05). The raised level of circulating insulin may in part explain the excess of plasma fibronectin obese subjects.

Topics: Adult; Blood Glucose; C-Peptide; Female; Fibronectins; Humans; Insulin; Male; Middle Aged; Obesity; Obesity, Morbid

The effects of obesity and body fat distribution on splanchnic insulin metabolism and the relationship to peripheral insulin sensitivity were assessed in 6 nonobese and 16 obese premenopausal women. When compared with the nonobese women, obese women had significantly greater prehepatic production and portal vein levels of insulin both basally and following glucose stimulation. This increase correlated with the degree of adiposity but not with waist-to-hip girth ratio (WHR). WHR, however, correlated inversely with the hepatic extraction fraction and directly with the posthepatic delivery of insulin. The latter correlated with the degree of peripheral insulinemia. The decline in hepatic insulin extraction with increasing WHR also correlated with the accompanying diminution in peripheral insulin sensitivity. Increasing adiposity is thus associated with insulin hypersecretion. The pronounced hyperinsulinemia of upper body fat localization, however, is due to an additional defect in hepatic insulin extraction. This defect is closely allied with the decline in peripheral insulin sensitivity.

Topics: Adipose Tissue; Adult; C-Peptide; Female; Glucose; Humans; Insulin; Kinetics; Liver; Obesity; Viscera

The levels of plasma insulin and C-peptide during exercise and subsequent recovery have been determined in obese non-diabetics, obese diabetics Type II and middle-aged female controls. It has been found that exercise reduces levels of peptides both in the control and in the obese non-diabetic group. This effect of acute exercise was found blunted in the obese diabetic group. Non-diabetic obese subjects pretreated with phentolamine showed no reduction either in plasma insulin or C-peptide levels during exercise. During the recovery, the level of plasma insulin returned promptly to the pre-exercise value in the control group but increased above the resting value in obese subjects, both non-diabetic and diabetic. In controls and non-diabetic obese the increment of C-peptide: insulin molar ratio occurred early after the onset of exercise and then returned to the resting value despite the exercise being continued. The plasma C-peptide:insulin molar ratios were reduced during the first 15 min of recovery period in obese non-diabetic subjects and returned to normal in the next 15 min. The latter may suggest that reduced insulin removal could also contribute to the increase in plasma insulin values in the obese during recovery.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Middle Aged; Obesity; Phentolamine; Physical Exertion

Pancreatic beta cell function in response to glucose was assessed in three different groups of offspring of conjugal diabetic parents (OCDP): those with normal glucose tolerance, those with impaired glucose tolerance (IGT), and those with diabetes. Serum immunoreactive insulin (IRI), C-peptide (CP), insulin/glucose (I/G) ratio, and IRI/CP ratios were estimated at fasting and 90 min after glucose load. Insulin secretion, measured as CP, was found to be low even in normal nonobese OCDP, but the change was not reflected in IRI value as the IRI/CP ratio was found to be elevated. The values decreased with increasing glucose intolerance. In obese OCDP, all the parameters were abnormal even among those with normal glucose tolerance, and further deterioration occurred with increasing glucose intolerance. The study shows that insulin secretory defects are detectable even in normal OCDP, and these changes deteriorate with increasing glucose intolerance. Differences are noted in the peripheral concentrations of IRI and CP between obese and nonobese OCDP before development of diabetes. After development of diabetes mellitus, these differences disappear, and the CP and IRI values in both groups are similar and low.

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; India; Insulin; Male; Obesity

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diet, Reducing; Female; Humans; Obesity

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Middle Aged; Obesity

We have studied the effect of insulin hypoglycemia on the secretion of pancreatic polypeptide (PP) in 14 obese subjects with normal glucose tolerance and in 6 normal controls. Infusion of insulin 0.1 U/kg/h in controls and 0.12 U/kg/h in the obese, for one hour, produced a progressive hypoglycemia, similar in both groups (nadir 2 mmol/l at 50 min). The secretion of PP was less in obese subjects than in controls (peak 116 mmol/l vs 184 pmol/l, P less than 0.01) (integrated secretion sigma delta PP 288 vs 472 pmol/l, P less than 0.01) and was also delayed in the obese subjects beginning at 50 min instead of 40 min. The secretion of glucagon and of C-peptide were not different in the two groups, but the integrated response of ACTH was higher in the obese (sigma delta ACTH 52 pmol/l vs 25 pmol/l, P less than 0.01). The secretory response of growth hormone (STH) was smaller in the obese group (peak 8.6 +/- 1.28 vs 21.4 +/- 6.4 ng/ml, P less than 0.01). The reduced secretion of PP in obese subjects could be due to impaired sensitivity to hypoglycemia of the central control mechanism for PP release. The similarity of the reductions in the secretion of both PP and STH support this hypothesis, although a reduction in the secretory capacity of pancreatic PP cells cannot be excluded.

Topics: Adrenocorticotropic Hormone; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Male; Obesity; Pancreatic Polypeptide

To examine whether decreased insulin secretion during starvation is related to a change in the ability of insulin to inhibit its own secretion, plasma C-peptide was measured after plasma insulin levels were acutely raised by intravenous (IV) insulin infusion in a dose of 40 and 80 mU/M2/min in obese subjects before and after a 72 hour fast. Plasma glucose concentration was maintained +/- 4% of basal levels by a variable glucose infusion. During the 80 mU infusion, at plasma insulin levels of 200 microU/mL, plasma C-peptide fell by 0.17 pmol/mL in the fed state. In the fasted state, despite basal levels that were 36% lower, C-peptide decreased by 0.21 pmol/mL. Highly significant increases in percent suppression after fasting were noted during both 40 mU and 80 mU studies. The plasma C-peptide response was related to the insulin infusion dose in both the fed and fasted state. In contrast, alpha cell suppression by insulin, as determined by plasma glucagon levels, was not altered by fasting. It is concluded that enhanced inhibitory influences of insulin on the beta cell during starvation may be a physiologically important mechanism for diminished insulin secretion during the transition from the fed to the fasting state.

Topics: Adult; Blood Glucose; C-Peptide; Feedback; Glucagon; Humans; Insulin; Insulin Secretion; Middle Aged; Obesity; Starvation

To evaluate the suppressive effect of biosynthetic human insulin (BHI; 2.5 U/m2 . h) on basal and glucose-stimulated insulin secretion in healthy and obese hyperinsulinemic subjects, the plasma C-peptide response was measured during maintenance of euglycemia and hyperglycemia by means of the glucose clamp technique. In five healthy subjects in whom arterial insulin concentration was increased to 94 +/- 8 microU/mL, but euglycemia was maintained at the fasting level. C-peptide concentration fell from 1.3 +/- 1.0 ng/mL by 21 +/- 8% (P less than 0.05). When hyperglycemia of 7 mmol/L above basal was induced by a variable glucose infusion, the C-peptide response was similar in the control (5.0 +/- 0.6 ng/mL) and BHI experiments (4.7 +/- 0.6 ng/mL) and was paralleled by an identical increase in plasma insulin above the prevailing insulin concentration. In seven obese patients plasma C-peptide fell from 3.5 +/- 0.4 to 2.8 +/- 0.5 ng/mL (P less than 0.05) when BHI was infused at the same rate of euglycemia maintained as in the lean subjects. As in healthy subjects, however, the plasma C-peptide response to the hyperglycemic stimulus (8.7 +/- 0.9 ng/mL) was not altered by BHI (7.9 +/- 0.8 ng/mL). Glucose utilization as determined by the glucose infusion rate necessary to maintain the desired glucose level was reduced by half in the obese patients compared with that of normal subjects. From these data we conclude that in healthy as well as obese hyperinsulinemic subjects, insulin at concentrations capable of suppressing its basal secretion fails to suppress its glucose-stimulated secretion.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Depression, Chemical; Female; Glucose; Humans; Hyperinsulinism; Infusions, Parenteral; Insulin; Male; Nonsuppressible Insulin-Like Activity; Obesity

A series of variables involved in glucose handling were monitored before and after gastric bypass operation for morbid obesity. Blood glucose, insulin, C-peptide, gastric inhibitory polypeptide (GIP), pancreatic polypeptide (PP), and gastrin were measured basally and after an oral glucose load. Blood glucose, insulin, C-peptide, and PP were also measured after an intravenous glucose load. Adrenocortical function was evaluated by measuring plasma cortisol and urinary excretion of 17-hydroxy-corticosteroids and 17-ketosteroids. Nine subjects were examined before and 3 and 12 months after operation. Glucose tolerance improved postoperatively concomitant with decreased basal levels of C-peptide and insulin, increased hepatic insulin extraction, and evidence of reduced adrenocortical function. Parallel with reduced insulin resistance, support for an increase in both insulin secretion and removal was obtained postoperatively. It is concluded that the considerable endocrine abnormalities seen in morbid obesity can be normalized after gastric bypass operation and weight reduction.

Topics: Adult; Blood Glucose; C-Peptide; Female; Gastric Inhibitory Polypeptide; Gastrins; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Obesity; Pancreatic Polypeptide; Stomach

We evaluated beta-cell secretory capacity over 60 minutes in response to oral glucose (75 g) followed 30 minutes later by the intravenous injection of tolbutamide 0,5 g and glucagon 1 mg (combined) in 10 black and 8 white obese non-diabetic female volunteers. Thirty minutes after oral glucose administration both insulin and C-peptide levels were significantly higher in the white group. The levels of both substances after tolbutamide-glucagon stimulation were likewise higher in the white group at all times, being significantly so 30 minutes after the injection. Hepatic extraction of insulin, calculated as the C-peptide: insulin molar ratio, was similar in both groups. These results indicate that the beta-cell secretory capacity of black obese subjects is less than that of whites. In response to insulin-induced hypoglycaemia in 6 of the black and 5 of the white subjects, the pancreatic glucagon rise was lower in the black group, despite greater falls in plasma glucose levels. In view of this finding it is possible that blacks may be at risk of slower recovery from insulin-induced hypoglycaemia.

Topics: Adult; Black or African American; Blood Glucose; C-Peptide; Female; Glucagon; Glucose; Humans; Insulin; Islets of Langerhans; Obesity; Time Factors; Tolbutamide; White People

We studied two obese type II diabetic patients before, during, and after 3 yr of continuous iv insulin infusion, delivered by means of totally implanted insulin infusion pumps. Tolerance of the devices was excellent, and no side-effects or episodes of significant hypoglycemia occurred. Glycosuria was eliminated, and mean 24-h plasma glucose and hemoglobin A1c levels decreased in both patients and remained in or near the normal range for 3 yr. Improvements were also noted in serum triglyceride concentrations and vitreous fluorescein concentrations after iv fluorescein injection. Euglycemic insulin clamp studies showed that no significant change in glucose disposal rate occurred after 6 and 12 months of treatment. However, some improvement in insulin secretion during hyperglycemic insulin clamp studies occurred in both patients after 6 months of insulin infusion. Evaluation of the insulin-glycerol mixture used in the pump revealed that moderate degradation of insulin occurred in the pump during the 21-day flow cycle, resulting in 6-12% increases in fasting blood glucose levels; in addition, higher mol wt species of immunoreactive insulin were present in the patients' serum. We conclude that long term continuous iv infusion of insulin using a totally implantable infusion pump is practical in type II diabetic patients, is acceptable to patients, and is capable of providing near-normal glycemic control.

Topics: Blood Glucose; C-Peptide; Chromatography, Gel; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glycerol; Humans; Insulin; Insulin Antibodies; Insulin Infusion Systems; Male; Middle Aged; Obesity; Time Factors

To assess the mechanisms for the elevation of free fatty acids in noninsulin-dependent diabetes, free fatty acid metabolism and lipid and carbohydrate oxidation were compared in 14 obese diabetic Pima Indians and in 13 age-, sex-, and weight-matched nondiabetics. The studies were repeated in 10 of the diabetics after 1 mo of oral hypoglycemic therapy. Fasting plasma glucose concentrations were elevated in diabetics (242 +/- 14 vs. 97 +/- 3 mg/dl, P less than 0.01) and decreased to 142 +/- 12 (P less than 0.01) after therapy. Fasting free fatty acid concentrations were elevated in diabetics (477 +/- 26 vs. 390 +/- 39 mumol/liter, P less than 0.01) and declined to normal values after therapy (336 +/- 32, P less than 0.01). Although free fatty acid transport rate was correlated with obesity (r = 0.75, P less than 0.001), the transport of free fatty acid was not higher in diabetics than in nondiabetics and did not change after therapy. On the other hand, the fractional catabolic rate for free fatty acid was significantly lower in untreated diabetics (0.55 +/- 0.04 vs. 0.71 +/- 0.06 min-1, P less than 0.05); it increased after therapy to 0.80 +/- 0.09 min-1, P less than 0.05, and was inversely correlated with fasting glucose (r = -0.52, P less than 0.01). In diabetics after therapy, lipid oxidation rates fell significantly (from 1.35 +/- 0.06 to 1.05 +/- 0.01 mg/min per kg fat-free mass, P less than 0.01), whereas carbohydrate oxidation increased (from 1.21 +/- 0.10 to 1.73 +/- 0.13 mg/min per kg fat-free mass, P less than 0.01); changes in lipid and carbohydrate oxidation were correlated (r = 0.72, P less than 0.02), and in all subjects lipid oxidation accounted for only approximately 40% of free fatty acid transport. The data suggest that in noninsulin-dependent diabetics, although free fatty acid production may be elevated because of obesity, the elevations in plasma free fatty acid concentrations are also a result of reduced removal, and fractional clearance of free fatty acid appears to be closely related to diabetic control. Furthermore, the increase in fractional clearance rate, despite a marked decrease in lipid oxidation, suggests that the clearance defect in the diabetics is due to an impairment in reesterification, which is restored after therapy.

Topics: Adult; Biological Transport, Active; Blood Glucose; Body Composition; C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Food; Humans; Insulin; Lipid Metabolism; Male; Obesity

The authors have studied insulin receptors on peripheral blood monocytes and insulin sensitivity, evaluated by simultaneous infusion of glucose, insulin and somatostatin in 10 control subjects and in 20 obese patients with normal glucose tolerance. The obese patients have been divided into two groups, normo (NO) and hyperinsulinemic (HO), according to the total insulin response during OGTT. We considered HO patients with insulin response higher than M + 2DS of controls. Obese patients showed, in comparison to the controls, a lower specific binding and higher degree of insulin resistance. The subdivision of obese patients allowed us to distinguish two groups. The first was characterized by basal hyperinsulinemia, normal insulin response to the stimulus, reduced number of insulin receptors and normal or slightly reduced sensitivity. The second group showed high basal and after stimulus insulinemic values, reduced number of insulin receptors and high level of insulin resistance. When we compared the two groups of obeses we found that the first has a shorter duration of obesity and lower blood glucose values after OGTT. However both groups show the same reduction of insulin bound and the same degree of basal hyperinsulinemia. These data suggest that a reduction of insulin receptors is not the main factor responsible for insulin resistance in obesity. Furthermore, the presence of basal hyperinsulinemia and normal insulin sensitivity in our first group suggests that the modification of basal insulin concentrations is not dependent on the presence of insulin resistance.

Topics: Adult; Blood Glucose; C-Peptide; Glucagon; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Middle Aged; Obesity; Receptor, Insulin

Topics: Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Liver; Male; Obesity

Insulin resistance has been measured in man by nonsteady state tracer methodology. Increase in overall glucose utilization and suppression of glucose production was measured when hyperglycemia was achieved either by infusing glucagon or glucose. With the first method, insulin resistance was assessed in obese man and in lean hypertriglyceridemic patients. With the second method, insulin resistance was assessed in lean mild type II diabetics. These methodologies can only assess deficiences in overall glucose utilization and glucose production, but cannot delineate the defect in glucose uptake by the liver. However, if a given metabolic event is essentially characteristic of only one organ, metabolic abnormalities specific to that organ can be detected in vivo provided there is a probe specific to that metabolic pathway. Therefore, in lean mild type II diabetics the liver glucose futile cycle was assessed by a double tracer method. Previously it was shown that liver glucose futile cycling is increased in diabetic dogs. In healthy control subjects in basal state and during glucose infusion, the futile cycle could not be detected, but it represented a major part of glucose metabolism in liver of type II diabetics. It appears, therefore, that most of the glucose taken up by the liver during the glucose challenge in diabetics reenters the blood stream without being oxidized or polymerized. On the basis of these studies, it was concluded that excessive hyperglycemia in the diabetics during glucose infusion is due to a decrease in irreversible glucose uptake (impaired phosphorylation and futile cycling) and to a decrease in suppression of glucose production. The relative contribution of the liver and periphery to hyperglycemia seems to be almost equivalent. The mechanism behind the increased glucose cycle activity is not clear. It may be due to a relative decrease of glycogen synthase or increase in glucose-6-phosphatase or both. These observations in mild lean type II diabetics may have implications also in some other types of diabetes, since we have observed that futile cycling is even more marked in obese type II diabetics and that it could account in part for the diabetogenic effect of growth hormone in acromegalics.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose; Homeostasis; Humans; Insulin; Insulin Resistance; Obesity; Reference Values

There is a large amount of epidemiological and clinical evidence for associations among obesity, impaired glucose tolerance, and arterial hypertension; nevertheless, the pathophysiological mechanisms underlying these associations have not yet been elucidated. In this article, some working hypotheses are discussed, and original data are presented from two studies focusing on these pathophysiological interrelations. A case-control study of obese normotensive and hypertensive patients, matched for sex, age, and degree of overweight, has shown that obese patients with associated arterial hypertension have higher fasting serum insulin levels and reduced glucose tolerance compared with their normotensive peers. A second study compared subjects with impaired glucose tolerance with a control group of clinically healthy individuals of comparable sex, age, and body mass index, and it revealed that impaired glucose tolerance is associated with significantly higher blood pressure levels, independent of body weight. The results of the two studies together suggest that the association between hypertension and impaired glucose tolerance is independent of overweight; they also give some support to the hypothesis that hyperinsulinemia may contribute to the development of high blood pressure in obese patients.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Coronary Disease; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Male; Middle Aged; Obesity; Risk

The study was designed to evaluate whether the correlation occurring in simple obesity between insulin resistance and peripheral hyperinsulinemia corresponds to a relationship between insulin resistance and insulin overproduction by the pancreas. In addition, the study investigated the relation existing in simple obesity between insulin resistance and insulin metabolism. For these purposes, we measured and correlated: (1) insulin sensitivity, estimated by glucose disappearance rate from plasma after intravenous insulin injection; (2) insulin secretion by the pancreas, estimated by fasting C-peptide levels in peripheral blood; (3) insulin metabolism, estimated by means of C-peptide: insulin molar ratio in peripheral blood. Twenty-five subjects (20 females, five males) aged 21 to 59 years were studied. All were obese and had a normal glucose tolerance. Glucose disappearance rate from plasma after i.v. insulin injection averaged 3.65 +/- 0.42 mg/dl/min (mean +/- s.e.m.). Fasting C-peptide was 0.90 +/- 0.09 nmol/l. Fasting C-peptide: insulin molar ratio averaged 5.94 +/- 0.48. Negative correlations were found between glucose disappearance rates after i.v. insulin injection, ie, insulin sensitivity, and fasting concentrations of both insulin (r = -0.806, P less than 0.001) and C-peptide (r = -0.525, P less than 0.01). A positive relationship was found between glucose disappearance rate from plasma after i.v. insulin injection and fasting C-peptide: insulin molar ratio, ie, insulin metabolism (r = 0.707, P less than 0.001). We conclude that in simple obesity insulin overproduction by the pancreas is negatively related to insulin resistance, and insulin resistance and impaired insulin metabolism are strictly related phenomena.

Topics: Adult; Blood Glucose; C-Peptide; Fasting; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Kinetics; Male; Middle Aged; Obesity; Pancreas

The effects of prior high-intensity cycle exercise (85% VO2 max) to muscular exhaustion on basal and insulin-stimulated glucose metabolism were studied in obese, insulin-resistant, and normal subjects. Six obese (30.4% fat) and six lean (14.5% fat) adult males underwent two separate, two-level hyperinsulinemic-euglycemic clamp studies (100-min infusions at 40 and 400 mU/m2/min), with and without exercise 12 h earlier. Carbohydrate oxidation was estimated by indirect calorimetry using a ventilated hood system, and endogenous glucose production by D-(3-3H)-glucose infusion. Glycogen content and glycogen synthase activity (GS %l) were measured in vastus lateralis muscle biopsies before and at the end of each insulin clamp procedure. After exercise, the obese and lean subjects had comparably low muscle glycogen concentrations (0.10 versus 0.08 mg/g protein, respectively), and equal activation of muscle GS activity (54.4 versus 45.3 GS %l, respectively). In the obese subjects, insulin-stimulated glucose disposal was increased significantly, but not totally corrected to normal. In both groups there was a comparable increase in nonoxidative glucose disposal (NOGD), whereas glucose oxidation was decreased and lipid oxidation was increased. Thus, the major effect of prior exercise was to increase insulin-stimulated glucose disposal in the obese subjects and to alter the pathways of glucose metabolism to favor NOGD and decrease glucose oxidation. No correlation was found between the exercise-induced increase in GS %l and NOGD, except in the normal subjects during maximal insulin stimulation. Thus, glycogen synthase activity does not appear to be rate-limiting for NOGD at physiologic insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Glucose; Glucose Tolerance Test; Glycogen; Glycogen Synthase; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Muscles; Obesity; Oxidation-Reduction; Physical Exertion; Urea

The effect of euglycemic hyperinsulinism on branched-chain amino acids (BCAA; valine, isoleucine and leucine) was evaluated in five obese subjects and five controls. A continuous intravenous insulin infusion raised plasma insulin to a steady-state level. An artificial endocrine pancrease that infused glucose was used to sustain euglycemia. Basal and steady-state insulin levels were significantly higher in the obese subjects than in the controls. The amount of glucose infused to maintain euglycemia and its ratio to steady-state insulin levels was significantly lower in the obese subjects, suggesting an impaired insulin action on glucose metabolism. Basal BCAA levels were similar in the two groups of subjects. During insulin infusion the decremental areas of BCAA below basal levels were significantly lower in the obese patients (63 +/- 5 nmol/mL X min v 143 +/- 8 nmol/mL X min, P less than 0.001), as was the ratio of the decremental areas of BCAA to the incremental areas of insulin (1.11 +/- 0.05 nmol/microU v 3.30 +/- 0.24 nmol/microU, P less than 0.001). Our data suggest that insulin resistance in obesity reduces hormonal effects on glucose as well as on BCAA metabolism.

Topics: Amino Acids, Branched-Chain; C-Peptide; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Time Factors

The ability of varying levels of circulating insulin to suppress alpha- and beta-cell secretion was assessed by plasma glucagon and C-peptide measurement in 6 obese and 6 nonobese subjects maintained in a euglycemic state, with an insulin concentration elevated by 10, 20, or 100 microU/ml above basal levels by a primed-continuous infusion of insulin. The 10-microU/ml increase did not suppress C-peptide levels significantly in either group. However, incremental increases in plasma insulin of approximately 20 and 100 microU/ml above basal suppressed plasma C-peptide by 0.27 +/- 0.14 and 0.53 +/- 0.07 pmol/ml, respectively, in the obese subjects (14% and 31% of the basal values of 2.20 +/- 0.18 and 2.19 +/- 0.26 pmol/ml, respectively) and by 0.16 +/- 0.06 and 0.17 +/- 0.06 pmol/ml in the nonobese subjects (20% and 25% the basal values of 0.74 +/- 0.11 and 0.78 +/- 0.11 pmol/ml, respectively). Plasma glucagon levels were suppressed to a similar degree in each group in a dose-related manner during both the 20-microU/ml and 100-microU/ml clamps. We were unable to identify an increment of insulin that suppressed C-peptide and/or glucagon in one group but not in another. These data demonstrate inhibition of alpha- and beta-cell secretion by insulin within its physiologic range in both non-obese and obese man, and exclude insulin resistance of alpha- and beta-cells in obese individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Glucagon; Humans; Insulin; Insulin Infusion Systems; Insulin Resistance; Islets of Langerhans; Male; Obesity

Ten severely obese women were subjected to physical training for three months on ad libitum diet. Under metabolic ward conditions oral glucose tolerance test was performed before and after the training period with the same energy intake quantitatively and qualitatively, and glucose, insulin, connecting (C)-peptide, gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) were determined. In confirmation of previous work, physical training caused no decrease in body fat in these severely obese subjects, and no change in body cell mass or glucose tolerance, while insulin and blood pressure decreased. The control of dietary conditions demonstrated that the latter phenomena were not due to quantitative or qualitative changes in the diet. C-peptide concentrations decreased also, indicating effects of physical training in obesity on insulin production. GIP is believed to be a gastrointestinal factor facilitating insulin secretion (Incretin). Previous work has indicated that gastrointestinal factor(s) are involved in the insulin lowering effect seen after physical training. It is possible that GIP is contributing to this phenomenon.

Topics: Adipose Tissue; Blood Glucose; Body Composition; C-Peptide; Cholesterol; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Obesity; Pancreatic Polypeptide; Physical Exertion; Triglycerides

Two main methods are available for assessing insulin sensitivity with the hyperinsulinaemic euglycaemic clamp technique: one employs a glucose-controlled insulin infusion system (the Biostator) with automatic feedback control; the second depends on frequent glucose measurement and the use of an algorithm and a pocket calculator ('manual') to determine the glucose infusion rate. The amount of glucose infused is a measure of insulin sensitivity. The efficiency of the two methods was compared in nine normal subjects (seven lean, two obese). After an overnight fast subjects were infused with insulin at 50 mU X kg-1 X h-1 for 2 h; this rate was doubled during the first 10 min for the manual technique. Blood glucose averaged 4.7 +/- 0.1 and 4.8 +/- 0.1 mmol/l from 0 to 120 min for Biostator and manual techniques and did not deviate significantly from the desired level. Variability of the clamp was also similar over the same period (coefficient of variation 5.1 +/- 0.6% and 6.4 +/- 0.7%, Biostator and manual). Glucose infused to maintain steady state from 60 to 120 min was higher, however, with the manual than the Biostator method (5.7 +/- 0.6 versus 4.4 +/- 0.6 mg X kg-1 X min-1, p less than 0.01) even when the loading dose was omitted, although the two methods correlated closely (p less than 0.05). Glucose infusion rate varied more from minute to minute with the Biostator (coefficient of variation 28.8 +/- 3% versus 12.2 +/- 2.1%). Steady-state serum insulin levels (30-120 min) were the same during both methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Drug Administration Schedule; Female; Glucagon; Humans; Hydrocortisone; Infusions, Parenteral; Insulin; Insulin Infusion Systems; Male; Obesity

In the present study insulin and C-peptide responses to oral glucose as well as C-peptide to insulin ratios and relations were evaluated in 10 nondiabetic obese female subjects with reactive hypoglycemia and in 10 age- and weight-matched controls. Insulin levels and incremental areas did not differ significantly in the two groups, whereas C-peptide concentrations and incremental areas were significantly higher in the obese group with reactive hypoglycemia. C-peptide to insulin molar ratio increments after glucose load as well as relations between incremental areas of the two peptides were significantly higher in obese subjects with reactive hypoglycemia than in controls. Our results suggest that B-cell response to oral glucose as well as insulin uptake by the liver in obese subjects with reactive hypoglycemia are greater than in controls.

Topics: C-Peptide; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Secretion; Liver; Obesity; Time Factors

Changes in the secretion and metabolism of insulin were measured by estimating serum C-peptide and insulin and their ratio during oral GTT in 30 non obese and 12 obese NIDDM patients. The mean IRI and CP responses were low in both groups of patients, compared to weight-matched controls. The reduction in CP was more marked than the reduction in IRI. The molar ratio of insulin and CP was found to be elevated in the patients, probably indicating reduced hepatic and peripheral extraction of insulin. It was noted that the elevated IRI/CP ratio was a 1) a common feature in NIDDM, irrespective of the body weight, 2) it is present even under basal conditions when the insulin levels are the lowest, 3) it appears to be independent of the concentration of insulin reaching the liver, and 4) obese patients appear to have an exaggerated defect compared to their non obese counterparts.

Topics: Adult; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Liver; Male; Middle Aged; Obesity

Insulin and C-peptide levels in peripheral blood in the fasting state and after an oral glucose load were measured in 65 nondiabetic, obese subjects and 65 age- and sex-matched nondiabetic normal weight subjects. Fasting insulin and C-peptide levels were significantly higher in obese than in nonobese subjects, whereas 1 and 2 h after the oral glucose load only insulin concentrations were significantly higher in the obese subjects. C-peptide to insulin molar ratios, as well as the relation between the incremental areas of the two peptides, were used as relative measures of hepatic insulin extraction. In the fasting state the ratios between C-peptide and insulin were similar in obese and nonobese subjects, whereas after glucose they were significantly lower in the obese individuals. Similarly, the relations between C-peptide and insulin incremental areas were significantly lower in obese than in nonobese subjects. The comparison of the corresponding plasma levels and areas of C-peptide and insulin after glucose showed that for the same C-peptide value, the insulin value was higher in the obese group. Last, in obese subjects the parameter used as an estimate of hepatic removal of insulin after oral glucose inversely correlated with the fasting insulin concentration and the insulin incremental area after glucose. These results suggest that in obesity peripheral hyperinsulinemia depends on pancreatic hypersecretion of insulin in the fasting state and impaired hepatic insulin metabolism after oral glucose loading.

Topics: Adult; Blood Glucose; C-Peptide; Fasting; Female; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Islets of Langerhans; Liver; Male; Middle Aged; Obesity

Serum C-peptide and insulin responses to oral glucose load were measured in 69 offspring of conjugal diabetic parents (OCDP). The insulin responses were varied. The non obese OCDP showed higher mean insulin levels than non obese controls while the obese OCDP did not have significant differences in the mean insulin responses compared to obese controls. The C-peptide levels were, however, low in both obese and non-obese OCDP. The IRI/CP ratios were elevated in both groups of OCDP. These results suggest that OCDP have low beta cell function and also possibly a change in the metabolism of insulin at the hepatic level, which is more pronounced in non obese OCDP.

Topics: Adolescent; Adult; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Obesity

The effects of prolonged fasting and refeeding on insulin secretion were examined in seven obese non-diabetic subjects. Plasma insulin and C-peptide concentrations were measured before and after fasting for 7 days, and after refeeding with a low caloric diet. Urine C-peptide excretion during 24 h was determined daily during the study period. Plasma insulin and C-peptide levels fell by about 50 percent during fasting and returned to the prefasting values after refeeding. During fasting the 24-h urine C-peptide excretion was markedly diminished; after 7 days it was less than 10 percent of the prefasting level; on refeeding a low caloric diet, it increased significantly although not to the initial basal values. It is concluded that in human obesity pancreatic insulin secretion is markedly diminished by prolonged fasting.

Topics: Adult; Blood Glucose; C-Peptide; Fasting; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity

Fasting serum C-peptide immunoreactivity was determined on Nauruans, a Micronesian population with a high prevalence of diabetes. In Micronesian subjects neither age nor gender had a significant effect on fasting serum C-peptide. In non-diabetic subjects, as has been shown previously for Caucasiod subjects, both obesity and fasting plasma glucose levels were determinants of fasting serum C-peptide. Obesity was the major determinant. Taken overall, mean fasting serum C-peptide increased then possibly fell in subjects grouped by increasing 2-h post-glucose plasma glucose levels. Mean fasting serum C-peptide in newly-diagnosed diabetic subjects was greater than that in non-diabetic subjects with a similar degree of obesity, supporting the concept that the transition to diabetes may be associated with an increase in insulin resistance. The data for non-diabetic subjects were compared with serum C-peptide measured in the same laboratory on samples from a Caucasoid population in Busselton, Western Australia. There was no difference in fasting serum C-peptide level between Micronesian and Caucasoid subjects approximately matched for obesity and fasting plasma glucose levels.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Fasting; Female; Humans; Male; Micronesia; Middle Aged; Obesity; Racial Groups

Using a combined infusion of somatostatin, insulin and glucose, insulin resistance was assessed in vivo in two groups of females with polycystic ovaries (PCO), obese (PB-PCO) and normal weight (NO-PCO) and in two groups of matched (for age, sex and body mass index) controls (OB and NO). A steady state plasma glucose (SSPG) and insulin (SSPI) was attained after 90 min. OB-PCO and NO-PCO showed higher SSPG with respect to matched controls. The SSPG levels were related to body mass index (r = 0.69; P less than 0.001). The SSPG values were significantly correlated with the fasting insulin levels (r = 0.47; P less than 0.003). Gonadotrophin and steroid peripheral blood concentrations were also evaluated in the PCO females. A significant correlation was found between the SSPG values and the dehydroepiandrosterone sulphate levels (r = 0.46; P less than 0.05) and between the fasting insulin levels and the androstenedione concentrations (r = 0.64; P less than 0.01). Moreover, significant correlation coefficients were found between the glucose to insulin ratio and the A (r = -0.59; P less than 0.01) and the DHEA-S (r = -0.50; P less than 0.05) plasma levels. Finally, no relationship between body mass index and A or DHEA-S levels was found in PCO females considered as a group. We conclude that insulin resistance is present in females with PCO and it is mainly due to the presence of obesity, but other factors such as androgen levels, probably of adrenal sources, must be considered as a cause.

Topics: Adult; Androstenedione; Blood Glucose; C-Peptide; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Glucose Tolerance Test; Humans; Insulin; Obesity; Polycystic Ovary Syndrome; Somatostatin

We have determined total body carbohydrate and lipid oxidation rates in response to a standard breakfast in nine obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and in seven age- and weight-matched controls. The patients with NIDDM were studied twice, once while in poor glycemic control (fasting blood glucose concentration 267 +/- 24 mg/dl, urinary glucose excretion 28.9 +/- 6.3 g/24 h) and again after modest glycemic improvement following 2 mo of fiber treatment (fasting blood glucose 227 +/- 19 mg/dl, urinary glucose excretion 10.7 +/- 1.9 g/24 h). Basal carbohydrate (CHO) oxidation rates were normal in patients with NIDDM before and after fiber treatment. However, in patients before fiber treatment the rise in CHO oxidation rates, the reciprocal fall in lipid oxidation rates, and the rise in serum insulin and C-peptide concentrations after the breakfast were all severely blunted. In addition, storage of ingested CHO was significantly reduced (from 55% to 32%, P less than 0.05). After fiber treatment, postbreakfast CHO oxidation rates had improved and were no longer significantly lower than control values. In contrast, CHO storage remained suppressed. We conclude that (1) basal CHO oxidation remained normal but that postbreakfast CHO oxidation was impaired in our obese patients with NIDDM. This impairment, however, appeared to be a relatively late event, occurring only during severely uncontrolled NIDDM. (2) Inability to dispose of CHO by storage appeared to be an earlier defect with a greater impact on glucose tolerance than the impairment of CHO oxidation.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Calorimetry; Carbohydrate Metabolism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fiber; Eating; Fatty Acids, Nonesterified; Female; Humans; Insulin; Lipid Metabolism; Male; Middle Aged; Obesity; Oxidation-Reduction

We have investigated whole body protein turnover in the fasted state in five normal men, five male Type 1 diabetic patients off insulin therapy, and five obese women, using IV 13C-leucine as a tracer. In diabetic patients, there was, as expected, a greater net loss of protein in the fasted state than in normal subjects. However, contrary to animal and studies in vitro, our diabetic patients in the fasted state showed a greater rate of protein synthesis than normal subjects (p less than 0.01). The increased net loss of protein in diabetic patients compared with normal subjects arose because, in the diabetic patients, protein breakdown was increased even more than protein synthesis under the conditions of this study. Plasma leucine concentration was higher in diabetic and in insulin-insensitive obese patients than in normal subjects (p less than 0.01), and higher in diabetic than in obese patients (p less than 0.05). The rate of protein synthesis per kg lean body mass was also higher in diabetic patients than in obese or normal subjects (p less than 0.01), and higher in obese than normal subjects (p less than 0.05). We conclude that, in human subjects, whole body leucine and protein metabolism are very sensitive to the action of insulin.

Topics: Adult; Bicarbonates; Blood Glucose; C-Peptide; Carbon Isotopes; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Leucine; Male; Obesity; Proteins; Reference Values; Sodium Bicarbonate

To elucidate if there are alterations in insulin metabolic clearance in obesity under basal conditions, plasma insulin and C-peptide were measured in 22 obese patients and 8 normal subjects, and the plasma C-peptide to insulin molar ratio was used as an index of hepatic insulin extraction. In obese patients, the C-peptide to insulin molar ratio correlated indirectly with basal plasma insulin levels (r = 0.71; P less than 0.001), being low in the obese patients with higher insulin levels and within the normal range in obese patients in which insulin levels were similar to those of control subjects. It is suggested that hepatic insulin extraction is decreased in obesity, even under basal conditions, but this alteration is only manifested when plasma insulin levels are high.

Topics: Adult; C-Peptide; Humans; Insulin; Liver; Metabolic Clearance Rate; Obesity

The fact that hyperinsulinemia occurs in simple obesity and mild glucose intolerance has been well established. Altered hepatic insulin extraction may influence the levels of circulating hormone. The simultaneous measurement of insulin and C-peptide concentrations in peripheral blood enables an in vivo estimation of hepatic insulin removal. To evaluate hepatic insulin extraction, insulin and C-peptide responses to oral glucose were studied in 176 obese and nonobese subjects with normal, impaired, or diabetic glucose tolerance. Insulin levels as well as insulin incremental areas in glucose intolerant subjects were significantly higher than in weight-matched controls. The levels of C-peptide as well as C-peptide incremental areas were only slightly enhanced in subjects with impaired glucose tolerance, whereas they were reduced in subjects with diabetic tolerance. The molar ratios of C-peptide to insulin, both in the fasting state and after ingestion of glucose, as well as the relationship between the incremental areas of the two peptides were used as measures of hepatic insulin extraction. They were significantly reduced in glucose intolerant subjects and, to a lesser extent, in nondiabetic obese subjects. These results indicate that peripheral hyperinsulinemia in subjects with simple obesity or impaired glucose tolerance is a result of both pancreatic hypersecretion and diminished hepatic insulin extraction. In subjects with a more severe degree of glucose intolerance, decreased hepatic insulin removal is the primary cause of hyperinsulinemia.

Topics: Adolescent; Adult; Body Weight; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Liver; Male; Middle Aged; Obesity

Topics: Adult; Aged; Aging; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Liver; Male; Obesity

The hyperinsulinemia of obesity could result from a decrease in the metabolic clearance rate of insulin (MCR-I), an increase in the secretory rate of insulin (SR-I), or a combination of both these processes. Because C-peptide and insulin are secreted in an equimolar ratio, the plasma concentrations of C-peptide (C) and insulin (I) are inversely proportional to their rates of metabolic clearance (C/I = MCR-I/MCR-C). We obtained 24-h integrated concentrations (IC) of insulin (IC-I) and C-peptide (IC-C) in 23 obese and 45 nonobese subjects over a period of normal activity and food intake. The IC-I was 69% higher in the obese subjects (P less than 0.0001). A 13% increase in the IC-C (P = 0.04), with a constant rate of C-peptide clearance, indicates a proportionate increase in SR-I. A 33% decrease in the IC-C/IC-I in the obese group (P less than 0.005) reflects a decrease in MCR-I; hence, 75% of the hyperinsulinemia is due to a decrease in the clearance of insulin. Because peripheral MCR-I (pMCR-I) is similar in obese and nonobese subjects, the decrease in MCR-I may be due to a decrease in the hepatic clearance of insulin. This conclusion was supported by our comparison of 24-h IC-C/IC-I ratios in the obese and nonobese subjects. Whereas the 24-h IC-C/IC-I of the nonobese resembled the fasting state, the 24-h IC-C/IC-I of the obese resembled the postprandial state, when insulin removal by the liver is known to be suppressed. These data are consistent with a decreased 24-h hepatic MCR-I (hMCR-I) as the cause of the hyperinsulinemia of obesity.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Height; Body Weight; C-Peptide; Fasting; Female; Humans; Hyperinsulinism; Insulin; Male; Metabolic Clearance Rate; Middle Aged; Obesity

To examine the possibility that the decrease of hyperinsulinemia and blood pressure in obesity associated with physical training is mediated via adaptations in the adrenergic nervous system, a pure beta-adrenergic agonist (isoproterenol) or an alpha-adrenergic antagonist (phentolamine) was infused before and during an oral glucose tolerance test before and after physical training. A number of circulatory, metabolic, and endocrine factors under adrenergic control were followed. Physical training was associated with an augmented beta-agonist response in blood pressure, heart rate, blood glucose, plasma insulin, connecting (C) peptide, and pancreatic polypeptide (PP) but not in plasma glucagon and gastric inhibitory polypeptide. Physical training also resulted in higher values of C-peptide and PP values after alpha-adrenergic blockade. It was concluded that physical training probably is associated with an augmented sensitivity of the beta-adrenergic nervous system. This might also be the case with the alpha-adrenergic system. It was suggested that this in turn might be due to a decreased firing in the adrenergic nervous system leading secondarily to an increased sensitivity in the effector cells. It was hypothesized that such decreased firing could provide a background to explain lower blood pressure and plasma insulin after physical training.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Female; Glucose Tolerance Test; Heart Rate; Humans; Insulin; Isoproterenol; Obesity; Pancreatic Polypeptide; Phentolamine; Physical Education and Training; Sympathetic Nervous System

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Humans; Male; Obesity; Peptides

The effects of somatostatin (SRIF) infusion on blood sugar, immunoreactive insulin (IRI), immunoreactive glucagon (IRG) and C-peptide after administration of oral glucose load (100 g) to 23 obese subjects were examined. The latter were divided in two groups according to oral glucose tolerance (OGTT): (1) normal OGT; (2) impaired OGT. During SRIF infusion IRI and C-peptide response to oral glucose was significantly reduced in both groups as compared with the response under saline infusion. Blood sugar values fell markedly in the second group. After SRIF infusion ended a marked increase in C-peptide, IRG and blood sugar was observed. The results suggest that SRIF infusion is only able to inhibit the release of IRI and IRG temporarily. They do not demonstrate if the behaviour of blood sugar is influenced by variations of these hormones or by the direct effect of SRIF infusion on absorption of the glucose load.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Obesity; Pancreatic Hormones; Radioimmunoassay; Somatostatin

To differentiate peripheral and hepatic insulin resistance in hyperinsulinaemic overweight Type 2 (non-insulin-dependent) diabetic patients (n = 17; 143 +/- 4% ideal body weight; mean +/- SEM) arterial concentrations and splanchnic exchange of glucose, pyruvate, lactate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate, as well as the insulin production rate, were determined before and during oral glucose loads of 25 g or 100 g. Insulin production rate, hepatic insulin retention and splanchnic exchange of glucose and metabolites were estimated by means of the hepatic venous catheter technique. In the basal state insulin production rate was greater in overweight Type 2 diabetic patients (2.57 +/- 0.28 pmol.kg-1. min-1) than in healthy control subjects (1.68 +/- 0.17 pmol.kg-1.min-1; p less than 0.01). After ingestion of 25 g glucose, the cumulative insulin production rate exceeded normal values (p less than 0.05), but was below normal with 100 g glucose (p less than 0.01). Relative insulin trapping by the splanchnic bed in the diabetic patients was 54 +/- 3%, not different from normal. Following a 100 g glucose load, splanchnic insulin retention fell by 20% in the patients, and less consistently so in healthy controls. Splanchnic glucose output was normal in the diabetic patients both in the basal state and after glucose ingestion although the induced arterial blood glucose levels were greater in the diabetic patients than in control subjects (p less than 0.005). Splanchnic output of pyruvate (p less than 0.025), lactate (p less than 0.01), and beta-hydroxybutyrate (p less than 0.005) were greater in the basal state in the diabetic patients than in healthy subjects. However, no difference in splanchnic exchange was seen between the two groups in their metabolites' respective response to glucose ingestion. These data suggest that obese hyperinsulinaemic Type 2 diabetic patients may represent a subgroup of diabetic patients with predominantly peripheral, but compensated hepatic, insulin resistance being associated with an increased basal insulin production rate which only exhausts after ingestion of a large glucose load.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Liver; Male; Middle Aged; Obesity; Splanchnic Circulation

Topics: Adult; C-Peptide; Female; Humans; Insulin; Obesity; Peptides; Polycystic Ovary Syndrome

The same dose (1 mg) of intravenous glucagon, administered in two consecutive pulses, demonstrates that insulin and C-peptide secretory responses in obese patients exceed those of normal weight subjects. The analysis of the molar ratio of serum immunoreactive C-peptide (IRCP) to serum immunoreactive insulin (IRI) which revealed significant differences between obese and control groups suggests that higher plasma insulin levels in obesity may result not only from a greater response to glucagon loads and from an impaired sensitivity to endogenous insulin by target tissues, but also from a decreased hepatic removal and destruction of the hormone. Perhaps an anomaly in the hepatic handling of insulin exists in obese subjects and thus a greater amount of the hormone reaches the periphery contributing to hyperinsulinemia, as observed in hyperglycemic and hyperinsulinemic obese (ob/ ob) mice.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucagon; Humans; Insulin; Male; Obesity; Peptides; Radioimmunoassay; Stimulation, Chemical; Time Factors

Seven out of 206 subjects investigated at 6-mth intervals with a glucose tolerance test developed non-insulin dependent diabetes. The mean fasting serum C-peptide concentration in the diabetic subjects was greater at the time of diagnosis of diabetes than 6 mth prior to diagnosis (1.25 and 1.01 nmol/l respectively, p less than 0.05). There was no significant difference in mean ideal body weight and maximum post-glucose serum C-peptide reactivity (CPR) before and at diagnosis. There was no change in mean fasting CPR during a similar 6 mth period (0.84 and 0.84 nmol/l respectively) in 17 subjects with normal glucose tolerance matched with the diabetics for age and ideal body weight. It is postulated that at least in some subjects the transition to diabetes is accompanied by an increase in insulin resistance.

Topics: C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Obesity; Quality Control; Time Factors

Twenty-four hour integrated concentrations of growth hormone (IC-GH) were significantly lower in young, obese subjects than in young subjects who were lean. Significant inverse correlations were found between IC-GH and body mass index (BMI) as well as the IC-GH and the 24 hr integrated concentrations of insulin (IC-I) and C-peptide (IC-C) in obese subjects below 30 yr of age. Since IC-GH decreases with age, the effect of obesity on IC-GH could not be demonstrated in the older subjects; a weak inverse correlation (p less than 0.05) between IC-GH and IC-C was found. Prolactin was significantly lower in the older subjects but did not correlate with IC-GH and was similar in lean and obese. Lipid deposition in adipose cells is promoted by high concentrations of insulin as well as low concentrations of growth hormone. We found a significant correlation between the IC-I/IC-GH ratio and BMI of both the young and older subjects. Correlations between these two factors do not necessarily imply a cause and effect relationship. It is plausible, however, that the elevated IC-I/IC-GH of the obese may facilitate their lipid storage and counter their efforts at weight reduction.

Topics: Adolescent; Adult; Age Factors; Body Weight; C-Peptide; Female; Growth Hormone; Humans; Insulin; Male; Middle Aged; Obesity; Peptides; Prolactin

Direct methods for measuring the secretion rate of insulin are too cumbersome for clinical application. Since C-peptide is secreted in an equimolar ratio with insulin and is excreted into the urine, measuring the urinary excretion rate of C-peptide (U-C) could serve as an indicator of its secretion rate (SR-C) if its urinary clearance (UCI-C) is constant and unaffected by plasma C-peptide concentration, body mass, or diabetes. We measured clearance ratios of C-peptide/creatinine (CR) in the fasting state and integrated 0-1, 1-3, and 3-5 h after 100 g of glucose p.o. as well as over a full 24-h in eight obese, eight lean, and six maturity-onset diabetic subjects. CR did not differ significantly when values in the fasting state were compared with those in the postprandial periods and was therefore unaffected by plasma C-peptide concentration. Furthermore, CR was similar in the lean, obese, and diabetic subjects. SR-C, determined as the product of the metabolic clearance rate of C-peptide and its fasting or integrated plasma concentrations, correlated significantly with U-C in all the subjects (r = 0.87, P less than 0.0001). The correlation of U-C with SR-C in the diabetic subjects alone was also significant (r = 0.88, P less than 0.0001). In conclusion, our data support the use of U-C as an indirect measure of SR-C and therefore of SR-I.

Topics: Adult; C-Peptide; Diabetes Mellitus; Fasting; Humans; Insulin; Insulin Secretion; Metabolic Clearance Rate; Obesity; Peptides

Topics: Adolescent; Adult; Age Factors; Aged; Blood Glucose; C-Peptide; Child; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Obesity; Pancreatic Function Tests; Peptides

Insulin secretion and insulin resistance were examined in seven obese type II diabetics before and after control of plasma glucose levels without weight loss. Control was achieved by regular insulin injection (60-205 U/day in four doses). After 10 days of therapy, plasma insulin and C-peptide responses to oral glucose were significantly improved. Insulin-induced glucose rates, estimated by the glucose clamp technique, averaged 1.08 +/- 0.30 mg/kg. min (mean +/- SEM; n = 7) before treatment and were unchanged (1.08 +/- 0.25) after treatment. These indicate that short term control of plasma glucose improved insulin secretion but not insulin sensitivity. The impaired insulin secretion and insulin sensitivity in type II diabetics appears to be, in part, secondary to metabolic abnormalities associated with hyperglycemia.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Obesity

A comparative study was carried out on B cell response to alternative intravenous glucagon (1.0 mg) and intravenous glucose (0.33 g per kg body weight) in healthy non-obese persons (c-NOb), healthy obese persons (C-Ob), non-obese non-insulin-dependent diabetics (NIDD-NOb) and obese non-insulin-dependent diabetics (NIDD-Ob). Each group comprised ten subjects. C-peptide (CP immunoassay using antiserum M 1230) and IRI in the serum were measured for each test. After glucose load in B-cell responses were significantly lower in both the diabetic groups than in the normal groups. After glucagon injection there were no significant differences in IRI and CP levels between NIDD-NOb and C-NOb, however, significantly lower levels of serum CP were noted among NIDD-Ob in comparison to C-Ob with a lack of these differences in IRI levels. This phenomenon is well reflected by the molar IRI/CP ratio expressed as a percentage. In the fasting state IRI accounted in C-Ob for 8.8 +/- 3.5 per cent of CP, while in NIDD-Ob for up to 25. +/- 10.4 percent of CP (P = 0.0004). In the latter group of patients, the IRI/CP ratio after glucagon reached the highest values (over 30 per cent) observed in this study. These data suggest the important role in insulin disposal played by the liver in non-insulin-dependent diabetes associated with obesity. Another explanation for these data is that more proinsulin is secreted in this group of patients as compared to other groups.

Topics: C-Peptide; Diabetes Mellitus; Glucagon; Glucose; Humans; Insulin; Obesity; Peptides

A new in vivo test of insulin sensitivity is described. It utilizes closed-loop insulin delivery device (GCIIS, Biostator) capable of infusing glucose and insulin according to preselected algorithms. In euglycemic patients, insulin was infused by GCIIS to maintain euglycemia in the face of challenges with gradually increasing doses on intravenously administered glucose. Under the described experimental conditions, the endogenous insulin release was minimized as evidenced by serum C-peptide levels of less than 2 ng/ml, and thus the peripheral disposal of glucose should have depended entirely on the exogenous insulin. The amount of the insulin infused was considered to be a measure of peripheral insulin sensitivity. The test was applied to normal and non diabetic obese individuals, and to diabetics, both insulin dependent and independent. Significant insulin resistance was demonstrated in the obese and diabetic patients. In two obese females, the test was repeated after a prolonged period of starvation, and showed marked increase in insulin sensitivity. In two poorly controlled insulin dependent diabetics, marked increase in insulin sensitivity was also observed, here following a prolonged period of euglycemia (48 hours). It is concluded that the GCIIS controlled insulin sensitivity test is a simple, reliable test of peripheral insulin sensitivity, most convenient for clinical and experimental studies in vivo.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Infusion Systems; Kinetics; Obesity

We investigated the possible existence of a negative short-loop feedback of circulating insulin on the parent beta cell in 10 lean Caucasians, 10 obese Caucasians, and 10 obese Pima Indians. Plasma insulin levels were raised acutely by 100 microunits per milliliter for 90 minutes, and plasma glucose was maintained by the "clamp" technique. C-peptide levels were suppressed in all groups to approximately 50 per cent of basal values. However, the obese groups had absolute C-peptide levels much higher than those of the lean group. During the hour after infusion, the rate and magnitude of C-peptide recovery in the obese groups were higher than in the lean group. Thus, negative short-loop insulin-beta-cell feedback was operative in both the lean and obese states. Despite this suppression, the insulin-secretion rate in obese subjects was still greater than that in non-obese subjects. Inadequate feedback suppression may account in part for the prevailing hyperinsulinemia of the obese.

Topics: Adult; Blood Glucose; C-Peptide; Feedback; Female; Glucagon; Humans; Indians, North American; Insulin; Insulin Secretion; Islets of Langerhans; Male; Obesity

Hypersecretion of immunoreactive gastric inhibitory polypeptide (IRGIP) has been reported previously in patients with diabetes mellitus (DM) and obesity. To ascertain the relative contribution of glucose intolerance and obesity to the abnormalities of IRGIP secretion, 114 subjects were studied during a standard oral glucose (75 g) tolerance test; responses of glucose, insulin, C-peptide, IRGIP, and glucagon were evaluated. The subjects were divided into six subgroups according to body weight and the degree of glucose intolerance. In normal weight subjects, the IRGIP response to oral glucose was significantly higher in the patients with impaired glucose tolerance (IGT) and DM than in the healthy control subjects (P less than 0.05). In the obese subjects, no significant differences in mean IRGIP responses could be detected among control, IGT, and DM subjects. In spite of similar IRGIP responses, the obese IGT patients did release more insulin than the obese control subjects, suggesting that incretin factors other than GIP may be operative in this condition. When obese and nonobese patients were compared, the obese subjects with normal glucose tolerance released a greater amount of IRGIP and insulin than the normal weight controls, whereas no significant difference between obese and nonobese could be found within the IGT and DM groups. We conclude that in the absence of obesity, glucose intolerance may induce IRGIP hypersecretion. On the other hand, obesity is associated with IRGIP hypersecretion, and glucose intolerance has no further effect, indicating a different pathogenetic mechanism for the IRGIP abnormalities. In both the obese and nonobese diabetic groups, IRGIP hypersecretion was associated with a failure of plasma glucagon levels to fall after oral glucose; this effect might be related to the glucagonotropic action of this peptide.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Obesity

Ninety obese "diabetic" patients, including 55 treated with insulin injection, were characterized by measurement of levels of insulin or connecting peptide of proinsulin (C peptide) induced during oral glucose tolerance testing. After reduction of body weight to ideal values, patients whose peak serum insulin levels were initially 64 microunits/mL or greater had reductions of blood glucose values from 227 +/- 24 to 122 +/- 10 mg/dL (fasting) and from 400 +/- 49 to 160 +/- 11 mg/dL (two hours postprandial); at C-peptide peaks of 6.0 ng/mL or greater, these blood glucose values fell from 244 +/- 30 to 118 +/- 12 mg/mL and from 400 +/- 51 to 160 +/- 16 mg/dL, respectively. Patients with peak values of less than 60 microunits/ml for insulin or less than 6.0 ng/mL for C peptide did not normalize the blood glucose concentration after weight loss. This critical level of insulin secretory reserve separating these groups was similar to that previously reported for avoidance of diabetic retinopathy and neuropathy. These results suggest that levels of insulin or C peptide induced during glucose tolerance testing distinguish between two types of hyperglycemic obesity-insulin-dependent diabetes mellitus and insulin-resistant obesity. Blood glucose levels alone did not identify these groups. Among consecutive hyperglycemic obese patients, 36% achieved normoglycemia by weight loss alone, including 33% of those previously treated with insulin injection.

Topics: Adult; Body Weight; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Peptides

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Obesity

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Fasting; Female; Humans; Male; Middle Aged; Obesity; Peptides

Topics: Adolescent; C-Peptide; Carbohydrate Metabolism; Child; Child, Preschool; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Male; Obesity; Peptides

10 obese subjects with latent glucose-intolerance we studied before and after a "short term" treatment with an oral antidiabetic drug, phenformina (100 mg/day for 14 days). The parameters we evaluated, were: basal IRI, C-peptide immunoreactive (IRCP), IRCP/IRI ratio, areas elicited by values of IRI after oral glucose tolerance test (OGTT), basal H-Prl, before and after the phenformin (F) treatment. Our data show that F decreases the basal IRI values but not IRCP values, so the IRCP/IRI ratio is significantly higher. No difference is found in the basal H-Prl values.

Topics: Adult; C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Obesity; Phenformin; Prediabetic State; Prolactin

Peripheral plasma insulin and C-peptide concentrations during oral glucose tolerance tests were measured in 7 severely obese and 12 normal weight nondiabetic subjects. The insulin and C-peptide levels as well as incremental areas under the plasma curves were 2--5 times higher in the obese subjects (P less than 0.05). The C-peptide to insulin molar ratios as well as the relation between incremental areas under the plasma curves of the two peptides were used as relative measures of the hepatic insulin extraction. They were both reduced in the obese subjects, which suggests that decreased insulin removal may contribute to the hyperinsulinemia of obesity. Sixty minutes after the oral glucose load, all of the obese patients had higher peripheral venous insulin concentrations compared with those found in normal subjects with similar C-peptide levels. This suggests that the reduced insulin extraction is not entirely explained by increased beta-cell secretory activity, but is also a specific consequence of obesity.

Topics: Blood Glucose; C-Peptide; Fasting; Glucose Tolerance Test; Humans; Insulin; Obesity; Peptides; Reference Values

The relationship between plasma glucose, serum insulin, serum C-peptide and obesity was studied in 320 fasting high school students (13-18 years old), as part of a Busselton population study. For males and females respectively plasma glucose was 4.5 +/- 0.4 and 4.4 +/- 0.5 mmol/l (mean +/- SD), serum insulin 0.51 +/- 0.35 and 0.69 +/- 0.39 log10 (nmol/l X 100), and serum C-peptide 0.48 +/- 0.15 and 0.55 +/- 0.14 nmol/l. These sex differences were not statistically significant. Plasma glucose correlated with C-peptide (r = 0.21, p < 0.001) and insulin (r = 0.32, p < 0.001), indicating greater secretion where fasting glucose was higher. Obesity, measured as skin fold thickness, was also associated with serum C-peptide (r = 0.32, p < 0.001) and insulin (r = 0.37, p < 0.001).

Topics: Adolescent; Blood Glucose; C-Peptide; Fasting; Female; Humans; Insulin; Male; Obesity; Peptides; Sex Factors; Skinfold Thickness

After the iv injection of 2 micrograms isoproterenol, peripheral plasma insulin and C-peptide concentrations were measured in 16 nonobese normal subjects and 53 maturity-onset diabetic subjects. Basal insulin (P < 0.01) and C-peptide (P < 0.05) levels were increased in obese diabetic subjects compared to nonobese normal subjects. Isoproterenol-stimulated insulin (P < 0.01) and C-peptide (P < 0.05) increments were increased in obese diabetic subjects compared to nonobese diabetic subjects. Hepatic insulin extraction, measured by comparing the ratios of insulin increment to C-peptide increment after isoproterenol injection, was decreased in both nonobese and obese diabetics compared to normals (P < 0.05). No significant differences in the ratios were found between nonobese and obese diabetics or between patients on diet or sulfonylurea therapy. Age, sex, duration of disease, familial predisposition to diabetes, and diabetic retinopathy did not influence the ratios. Isoproterenol-stimulated C-peptide increments (P < 0.05) and fasting blood glucose levels (P < 0.05) were decreased in diabetics showing decreased hepatic insulin extraction compared to diabetics with normal hepatic insulin extraction. Isoproterenol-stimulated insulin increments in diabetics showing decreased hepatic insulin extraction were higher than in normals (P < 0.05). These studies indicate that hepatic insulin extraction decreases in nonobese and obese diabetic subjects. It might be postulated that the lesser amount of secreted insulin is able to show biological activities more efficiently in diabetics with decreased hepatic insulin extraction.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Secretion; Isoproterenol; Kinetics; Middle Aged; Obesity; Peptides; Reference Values; Sulfonylurea Compounds

Topics: Adolescent; Adult; C-Peptide; Child; Diabetes Mellitus; Female; Glucagon; Glucose; Humans; Injections, Intravenous; Insulin; Male; Middle Aged; Obesity; Peptides; Stimulation, Chemical

Three groups of ten similar obese children were infused with one of three protocols. Protocol I glucose only (1.15 mM/min/m2). protocol II, glucose, insulin (42 mM/min/m2). Protocol III, glucose insulin, propanolol (0.04 mg/min/m2) adrenalin (3 micrograms/min/m2). Eighteen newly diagnosed diabetic children without acidosis received glucose according to protocol II. Thirteen normal adults (controls) received glucose infusion according to protocol I. Protocols I and II were well tolerated and gave consistent results but Protocol III was not well tolerated and did not give interpretable results. In obese children steady state blood glucose levels are significantly higher than in controls but this difference was only moderate (8.8 + 0.7 mM, against 6.6 +/- 0.4 mM for protocol I). There was no difference in insulin levels. In diabetic children the steady state was more rarely obtained after a 120 min infusion and blood glucose levels were higher than in the controls or in obese children.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Epinephrine; Glucose; Humans; Insulin; Insulin Resistance; Obesity; Propranolol

In this paper, we have compared the results obtained for hemoglobin A1c and C-peptide concentrations, was not convenient for the diagnosis of anomalies in the regulation of carbohydrate metabolism in obesity or in latent diabetes. Nevertheless, hemoglobin A1c allowed us to check carbohydrate metabolism and to discriminate diabetes treated by oral therapy from insulin dependent diabetes; in these latter cases, hemoglobin A1c concentration varied inversely as C-peptide concentration as it was shown by the method of factor analysis in particular "principal components analysis". In the control of insulin dependent diabetes in a remission, hemoglobin A1c allowed assessment of the regulation of carbohydrate metabolism after suppression of insulin therapy. Thus, hemoglobin A1c is an index of the adaptation of insulin secretion in anomalies of carbohydrate metabolism.

Topics: C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus; Glycosides; Hemoglobin A; Humans; Hypoglycemic Agents; Insulin; Obesity; Peptides

The levels of glucose, immunoreactive insulin and C-peptide were studied in 13 obese patients and 10 control subjects, in basal conditions and after an oral glucose load (OGTT). The IRI and C-peptide levels were higher in the obese patients than in the controls either during fasting or during the OGTT. The C-peptide/IRI ratio decreased after the oral glucose load in both groups studied. However in the obese subjects the values for the C-peptide/IRI ratio were lower than those found in the controls during the same observation period. These results suggest the hypothesis that in the obese patients the high IRI levels which reflect an increased insulin secretion, are, at least in part, due to an early saturation of the hepatic degradation of insulin and/or to a decrease in the specific receptor sites normally present in the cell membranes.

Topics: Adult; Antigens; C-Peptide; Female; Humans; Insulin; Male; Middle Aged; Obesity; Peptides

Peripheral serum insulin and C-peptide concentrations during oral glucose tolerance tests were measured in 10 nondiabetic Pima Indians and 10 nondiabetic Caucasians with varying degrees of obesity. Although both insulin and C-peptide levels were elevated in the Indians compared to the Caucasians (p less than 0.05), hepatic insulin extraction, measured by comparing the C-peptide to insulin ratios, was similar over a wide range of insulin concentrations in both groups. The ratios of C-peptide to insulin were independent of the degree of obesity. These studies indicate that the peripheral hyperinsulinemia in Pima Indians and obese subjects is due in general to pancreatic hypersecretion rather than to diminished hepatic extraction of insulin.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Indians, North American; Insulin; Male; Middle Aged; Obesity; Peptides; White People

The correlation between plasma C-peptide immunoreactivity (CPR) and immunoreactive insulin (IRI) was investigated during the oral glucose tolerance test in 20 normals, 127 diabetics, and 39 non-diabetics with chronic liver or renal disorders. When all subjects were included, the increment of CPR 30 minutes after glucose load (deltaCPR) correlated well with that of IRI (deltaIRI) (r = 0.66, p less than 0.001), but the return of CPR towards the basal level was delayed as compared with IRI. The positive correlation was also observed between the sum of 6 IRI and that of 6 CPR values during the glucose tolerance test in diabetics and controls (r = 0.53, p less than 0.001). deltaCPR/deltaBS (30 min.) was also well correlated with deltaIRI/deltaBS (30 min.), and was specifically low in diabetics. Insulin-treated maturity-onset diabetics showed low but considerable CPR responses while no CPR responses were observed in insulin-treated juvenile diabetics. In each plasma sample, CPR always exceeded IRI on the molar basis. At fasting CPR/IRI ratio was 15.6 +/- 1.7 (mean +/- SE) in normals and 14.9 +/- 1.3 approximately 16.9 +/- 1.0 in diabetics. In chronic liver diseases IRI response was augmented while CPR response was not different from that of controls, and the molar ratio of CPR/IRI was significantly low (9.5 +/- 1.1). On the contrary, it exceeded that of normals in chronic renal diseases (35.7 +/- 14.9). It is concluded that, first, the plasma CPR response appears to be a valuable indicator of pancreatic B-cell function, and second, it is, nevertheless, modified in chronic liver or renal disorders.

Topics: Adolescent; Adult; Antigens; C-Peptide; Child; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Tolerance Test; Humans; Insulin; Kidney Diseases; Liver Diseases; Male; Middle Aged; Obesity; Peptides

We measured circulating hemoglobin A1 (HbA1) and fasting plasma C-peptide concentrations in 100 diabetic patients. Pancreatic insulin reserve showed a negative correlation with HbA1 concentrations in nonobese, insulin-treated patients but not in obese patients, whether they were treated with insulin, oral agent, or diet alone. Patients with fasting C-peptide concentrations above 0.1 pmol/ml had significantly better metabolic control than did those with lower values. Anti-insulin antibodies were measured in 37 patients. There was no correlation between metabolic control and the affinity constants or binding capacities of these antibodies.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Glycosides; Hemoglobin A; Humans; Insulin; Insulin Antibodies; Middle Aged; Obesity; Peptides

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Insulin; Obesity; Peptides; Prediabetic State

Sixteen adult-onset diabetics, who were thought by current criteria to be well controlled on diet alone, had substantially elevated overnight, basal plasma glucose concentrations. Chlorpropamide had a sufficiently prolonged stimulatory effect on the beta cells such that normal basal plasma glucose levels were obtained in 13 patients. Both basal plasma C-peptide levels and the C-peptide response to meals became normal, with improved postprandial glycemia. Diurnal plasma triglyceride levels were reduced. Plasma growth hormone levels were normal both before and after therapy. When diet alone is insufficient to maintain basal normoglycemia in mild diabetes, chlorporpamide is as effective as basal insulin supplements in producing normal basal plasma glucose levels.

Topics: Blood Glucose; C-Peptide; Capillary Fragility; Chlorpropamide; Circadian Rhythm; Depression, Chemical; Diabetes Mellitus; Growth Hormone; Humans; Hydroxybutyrates; Insulin, Long-Acting; Lactates; Obesity; Physical Exertion; Triglycerides

Topics: Animals; C-Peptide; Insulin; Kinetics; Liver; Obesity; Peptides; Swine

Diabetes is an endocrine deficiency disease, a logical treatment of which is hormone replacement therapy. Many patients who are thought to be controlled by diet alone continue to have high plasma-glucose levels. As the rise in the basal plasma glucose concentration is the predominant glucose abnormality of diabetes, treatment should be aimed primarily at producing basal normoglycaemia. 18 mild, maturity onset diabetics have been treated with a basal insulin supplement provided by single daily injections of insulin zinc suspension (crystalline) 'Ultralente'. Overnight basal normoglycaemia has been obtained with markedly reduced plasma-glucose levels during the day. Plama-triglyceride levels have become normal in most patients. The required insulin dose need not be determined empirically, but can be calculated from the basal plasma-glucose level and the degree of obesity. There is minimum risk of hypoglycaemia, and rigid dietary restriction is unnecessary. As mild diabetics are prone to complications, treatment with basal insulin supplements may be beneficial when diet alone fails to produce basal normoglycaemia.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Diet, Diabetic; Follow-Up Studies; Humans; Injections, Subcutaneous; Insulin, Long-Acting; Middle Aged; Obesity; Triglycerides

Topics: C-Peptide; Diabetes Mellitus; Humans; Obesity; Peptides; Radioimmunoassay