c-peptide and Glucose-Intolerance

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Autoantibodies; Autoimmune Diseases; C-Peptide; Dexamethasone; Diazoxide; Diet, Diabetic; Female; Glucose; Glucose Intolerance; Humans; Hyperinsulinism; Hypoglycemia; Immunosuppressive Agents; Insulin; Liver Neoplasms; Polyethylene Glycols; Proinsulin; Sigmoid Neoplasms

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

Topics: Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Postprandial Period; Severity of Illness Index; Time Factors

The incidence of type 2 diabetes mellitus (T2DM) in children and adolescents has substantially increased over the past decade. This is attributed to obesity, insulin resistance and deficient beta-cell function. In children a pubertal increase in insulin resistance and an inability to mount an adequate beta-cell insulin response results in hyperglycemia. Adults with T2DM have a diminished first phase response to intravenous glucose and a delayed early insulin response to oral glucose. Long-term studies show progressive loss of beta-cell function in T2DM in adults; however, such long-term studies are not available in children. To characterize beta- and alpha-cell function in African-American adolescents with established T2DM, we used mixed meal, intravenous glucagon and oral glucose tolerance testing and compared them to obese non-diabetic controls. T2DM was defined as fasting C-peptide >0.232 nmol/l and absent autoimmune markers. BETA-CELL FUNCTION: Meal testing in 24 children and adolescents with T2DM, mean age 14 years, BMI 30 kg/m2, Tanner stage II-V, HbA1c 8.9%, were compared with BMI- and age-matched controls. Forty percent presented with DKA. Half were treated with insulin and half with diet/oral anti-diabetic agents. Although absolute C-peptide response in both groups was similar, the incremental rise in C-peptide relative to plasma glucose in the patients with T2DM compared to controls was 40% and 35% lower 30 and 60 min after the meal, p <0.007 and p <0.026. Glucagon testing in 20 pediatric patients with T2DM compared with 15 matched controls showed significantly lower 6 min stimulated C-peptide relative to the ambient plasma glucose in patients with T2DM compared to controls (0.039 +/- 0.026 vs 0.062 +/- 0.033, p <0.05). The clinical utility is that 78% of patients with a 6 min C-peptide <1.4 nmol required insulin, while 81% of those >1.4 nmol required oral anti-diabetic agents, p <0.0001. Furthermore, the duration of T2DM up to 5 years after diagnosis was associated with lower fasting and glucagon-stimulated C-peptide levels, implying worsening beta-cell function over time, even in children and adolescents. ALPHA-CELL FUNCTION: During meal testing, children and adolescents with T2DM had less suppression of plasma glucagon than non-diabetic controls; this was more severe with longer duration of T2DM and poorer glycemic control. BETA-CELL RECOVERY: In African-American and Hispanic adults, intensive treatment of blood glucose may achieve beta-cell. T2DM in children, as in adults, is characterized by insulin deficiency relative to insulin resistance. Plasma C-peptide levels may be clinically useful in guiding therapeutic choices, since patients with lower levels required insulin treatment; beta-cell function is also diminished with longer duration of T2DM. The possibility exists that in children, as in adults, intensive glycemic regulation may allow for beta-cell recovery and preservation. Thus, optimum beta- and alpha-cell function are central to the prevention of DM and maintenance of good glycemic control in African-American and Hispanic children and adolescents with T2DM.

Topics: Adolescent; Adult; Black People; Body Mass Index; C-Peptide; Child; Diabetes Mellitus, Type 2; Food; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Puberty

As a low-carbohydrate diet and the use of sodium-glucose transporter-2 inhibitors are both known to increase D-beta-hydroxybutyrate levels, the effect of these levels on glucose metabolism has attracted attention. We investigated the acute effects of ketone monoester (KM) ingestion on blood glucose levels during the 75-g oral glucose tolerance test (OGTT) in participants with impaired glucose tolerance.. Nine Japanese adults aged 48-62 years (4 men, 5 women) with impaired glucose tolerance participated in this study. After participants fasted overnight, we carried out OGTT for 180 min with and without KM ingestion on two separate days in a randomized cross-over design. We compared the area under the curve (AUC) of D-beta-hydroxybutyrate, glucose, insulin, C-peptide, glucagon and free fatty acids during OGTT.. The AUC of D-beta-hydroxybutyrate during OGTT was significantly higher with KM than without KM (KM 5995.3 ± 1257.1 mmol/L·h; without KM 116.1 ± 33.9 mmol/L·h, P < 0.0001), and the AUC of glucose with KM was significantly lower than that without KM (KM 406.6 ± 70.6 mg/dL·h; without KM 483.2 ± 74.3 mg/dL·h, P < 0.0001). This improved glucose excursion was associated with enhanced AUC of insulin during the first half (0-90 min) of OGTT, even though the AUC of C-peptide during this period was unchanged. In contrast, the AUC of insulin, C-peptide, glucagon and free fatty acids during 180 min of OGTT were similar in both conditions.. The ingestion of KM decreased the AUC of glucose during 75-g OGTT in Japanese individuals with impaired glucose tolerance, and the mechanism might involve elevated levels of circulating early phase insulin.

Topics: 3-Hydroxybutyric Acid; Area Under Curve; Blood Glucose; C-Peptide; Cross-Over Studies; Eating; Fatty Acids, Nonesterified; Female; Glucagon; Glucose; Glucose Intolerance; Glucose Tolerance Test; Glycemic Control; Humans; Insulin; Ketones; Male; Middle Aged

This study aimed to determine whether L-arginine supplementation lasting for 18 months maintained long-lasting effects on diabetes incidence, insulin secretion and sensitivity, oxidative stress, and endothelial function during 108 months among subjects at high risk of developing type 2 diabetes.. One hundred and forty-four middle-aged subjects with impaired glucose tolerance and metabolic syndrome were randomized in 2006 to an L-arginine supplementation (6.4 g orally/day) or placebo therapy lasting 18 months. This period was followed by a 90-month follow-up. The primary outcome was a diagnosis of diabetes during the 108 month study period. Secondary outcomes included changes in insulin secretion (proinsulin/c-peptide ratio), insulin sensitivity (IGI/HOMA-IR), oxidative stress (AOPPs), and vascular function. After the 18 month participation, subjects that were still free of diabetes and willing to continue their participation (104 subjects) were further followed until diabetes diagnosis, with a time span of about 9 years from baseline.. Although results derived from the 18 month of the intervention study demonstrated no differences in the probability of becoming diabetics, at the end of the study, the cumulative incidence of diabetes was of 40.6% in the L-arginine group and of 57.4% in the placebo group. The adjusted HR for diabetes (L-arginine vs. placebo) was 0.66; 95% CI 0.48, 0.91; p < 0.02). Proinsulin/c-peptide ratio (p < 0.001), IGI/HOMA-IR (p < 0.01), and AOPP (p < 0.05) levels were ameliorated in L-arginine compared to placebo.. These results may suggest that the administration of L-arginine could delay the development of T2DM for a long period. This effect could be mediated, in some extent, by L-arginine-induced reduction in oxidative stress.

Topics: Administration, Oral; Arginine; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diet; Endothelial Cells; Exercise; Follow-Up Studies; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Metabolic Syndrome; Middle Aged; Oxidative Stress; Sample Size; Surveys and Questionnaires; Treatment Outcome

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

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

To examine the lipid and glycaemic effects of 52 weeks of treatment with evolocumab.. The Durable Effect of PCSK9 Antibody Compared with Placebo Study (DESCARTES) was a 52-week placebo-controlled trial of evolocumab that randomized 905 patients from 88 study centres in 9 countries, with 901 receiving at least one dose of study drug. For this post-hoc analysis, DESCARTES patients were categorized by baseline glycaemic status: type 2 diabetes, impaired fasting glucose (IFG), metabolic syndrome (MetS) or none of these. Monthly subcutaneous evolocumab (420 mg) or placebo was administered. The main outcomes measured were percentage change in LDL-cholesterol (LDL-C) at week 52 and safety.. A total of 413 patients had dysglycaemia (120, type 2 diabetes; 293, IFG), 289 had MetS (194 also had IFG) and 393 had none of these conditions. At week 52, evolocumab reduced LDL-C by >50% in all subgroups, with favourable effects on other lipids. No significant differences in fasting plasma glucose, HbA1c, insulin, C-peptide or HOMA indices were seen in any subgroup between evolocumab and placebo at week 52. The overall incidence of new-onset diabetes mellitus did not differ between placebo (6.6%) and evolocumab (5.6%); in those with baseline normoglycaemia, the incidences were 1.9% and 2.7%, respectively. Incidences of AEs were similar in evolocumab- and placebo-treated patients.. Evolocumab showed encouraging safety and efficacy at 52 weeks in patients with or without dysglycaemia or MetS. Changes in glycaemic parameters did not differ between evolocumab- and placebo-treated patients within the glycaemic subgroups examined.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Blood Glucose; C-Peptide; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypercholesterolemia; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Treatment Outcome; Triglycerides

To assess the efficacy and tolerability of saxagliptin and C-peptide secretion in patients with diagnosed type 2 diabetes classified as glutamic acid decarboxylase antibody (GADA)-positive or GADA-negative.. Post hoc analysis of data pooled from five randomized, placebo-controlled, 24-week phase 3 studies (n = 2709) was conducted. We evaluated mean change from baseline at week 24 in HbA1c , fasting plasma glucose, postprandial plasma glucose, fasting and postprandial C-peptide, and HOMA2-%β and the proportion of patients achieving HbA1c  < 7% (53 mmol/mol) at week 24.. Saxagliptin produced greater adjusted mean reductions from baseline in HbA1c versus placebo for GADA-negative [difference vs placebo (95% CI), -0.62% (-0.71% to -0.54%); -6.8 mmol/mol (-7.8, -5.9)] and GADA-positive patients [-0.64% (-1.01% to -0.27%); -7.0 mmol/mol (-11.0, -3.0)]. Consistently, saxagliptin produced a greater reduction from baseline in fasting plasma glucose and postprandial plasma glucose versus placebo in GADA-positive versus GADA-negative patients, and more patients achieved HbA1c  < 7% (53 mmol/mol) with saxagliptin versus placebo in both GADA-negative and GADA-positive patients. Saxagliptin increased β-cell function as assessed by HOMA2-%β and postprandial C-peptide area under the curve from baseline in patients in both GADA-positive and GADA-negative patients. Adverse events and hypoglycaemic events were similar across treatment groups and GADA categories.. Saxagliptin was effective in lowering blood glucose levels and generally well tolerated in GADA-positive patients. Interestingly, saxagliptin appears to improve β-cell function in these patients, although a longer treatment duration may be needed to confirm this finding.

Topics: Adamantane; Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucose Intolerance; Humans; Latent Autoimmune Diabetes in Adults; Male; Middle Aged; Young Adult

Peripheral muscarinic acetylcholine receptors regulate insulin and glucagon release in rodents but their importance for similar roles in humans is unclear. Bethanechol, an acetylcholine analogue that does not cross the blood-brain barrier, was used to examine the role of peripheral muscarinic signaling on glucose homeostasis in humans with normal glucose tolerance (NGT; n = 10), impaired glucose tolerance (IGT; n = 11), and type 2 diabetes mellitus (T2DM; n = 9). Subjects received four liquid meal tolerance tests, each with a different dose of oral bethanechol (0, 50, 100, or 150 mg) given 60 min before a meal containing acetaminophen. Plasma pancreatic polypeptide (PP), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucose, glucagon, C-peptide, and acetaminophen concentrations were measured. Insulin secretion rates (ISRs) were calculated from C-peptide levels. Acetaminophen and PP concentrations were surrogate markers for gastric emptying and cholinergic input to islets. The 150 mg dose of bethanechol increased the PP response 2-fold only in the IGT group, amplified GLP-1 release in the IGT and T2DM groups, and augmented the GIP response only in the NGT group. However, bethanechol did not alter ISRs or plasma glucose, glucagon, or acetaminophen concentrations in any group. Prior studies showed infusion of xenin-25, an intestinal peptide, delays gastric emptying and reduces GLP-1 release but not ISRs when normalized to plasma glucose levels. Analysis of archived plasma samples from this study showed xenin-25 amplified postprandial PP responses ~4-fold in subjects with NGT, IGT, and T2DM. Thus, increasing postprandial cholinergic input to islets augments insulin secretion in mice but not humans.. ClinicalTrials.gov NCT01434901.

Topics: Administration, Oral; Adult; Bethanechol; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Intolerance; Hormones; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Muscarinic Agonists; Neurotensin; Non-Randomized Controlled Trials as Topic; Pancreatic Polypeptide; Postprandial Period

This study was a randomized, double-blind placebo-controlled trial to assess the efficacy of 4 weeks of mulberry leaf aqueous extract (MLAE) supplementation (5 g/day) for postprandial glycemic control in 36 subjects with impaired fasting glucose (IFG) tolerance. Postprandial responses in the glucose, insulin, and C-peptide levels were measured after a carbohydrate load both at baseline and after 4 weeks of MLAE supplementation. The postprandial glycemic response was attenuated in the MLAE group after the treatment period, particularly 30 and 60 min after loading (P=.003 and 0.0325 for glucose, P=.0005 and .0350 for insulin, and P=.0151 and .0864 for C-peptide). Additionally, the incremental area under the curve for insulin was significantly lower in the MLAE group than in the placebo group (P=.0207). Four weeks of MLAE supplementation improved postprandial glycemic control in individuals with IFG tolerance.

Topics: Area Under Curve; Biological Assay; Blood Glucose; C-Peptide; Dietary Supplements; Double-Blind Method; Fasting; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Morus; Phytotherapy; Plant Extracts; Plant Leaves; Postprandial Period; Prediabetic State

To investigate the effect of parenteral insulin therapy on endogenous insulin secretion in the Diabetes Prevention Trial-Type 1 (DPT-1).. In the parenteral insulin arm of DPT-1, subjects without diabetes at high risk of future type 1 diabetes randomized to active treatment received a yearly 4-day intravenous insulin infusion (IV-I) and daily subcutaneous insulin (SC-I). To examine the effects of these insulin therapies on endogenous insulin secretion, C-peptide and glucose levels were compared during oral glucose tolerance tests (OGTTs) performed on and off IV-I and SC-I. Forty-six paired OGTTs were performed in 30 subjects from DPT-1 to determine the effect of IV-I. Twenty paired OGTTs were performed in 15 subjects from DPT-1 to determine the effect of SC-I.. IV-I suppressed fasting and OGTT-stimulated C-peptide (62% and 40%, respectively), and it significantly lowered fasting glucose (67.4 ± 4.5 mg/dL during IV-I vs. 90.9 ± 1.8 mg/dL off insulin; P < 0.05). By contrast, post-OGTT glucose levels were significantly higher during IV-I: Glucose during IV-I versus off insulin at 120 min was 203.9 ± 15.1 vs. 151.6 ± 10.2 mg/dL, respectively (P < 0.05); 49% of OGTTs became transiently diabetic (>200 mg/dL at 120 min) when receiving IV-I. Fasting glucose was significantly lower when receiving SC-I versus when off insulin (85 ± 3 vs. 94 ± 2 mg/dL, respectively; P < 0.05), but SC-I did not significantly alter fasting or OGTT-stimulated C-peptide compared with being off insulin.. These data demonstrate that the IV-I used in the DPT-1 markedly suppressed endogenous insulin secretion, which was frequently associated with postprandial glucose intolerance. SC-I, however, did not.

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Fasting; Female; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Secretion; Male; Postprandial Period; Risk Factors; Young Adult

Patients with latent autoimmune diabetes in adults (LADA) express autoantibodies against the 65-kDa isoform of GAD (GADA). Intervention with recombinant human GAD65 formulated with aluminium hydroxide (GAD-alum) given twice subcutaneously to LADA patients at intervals of 4 weeks was safe and did not compromise β-cell function in a Phase II clinical trial. GADA affinity has been shown to predict progression to type 1 diabetes. Here, we asked whether GADA affinity was affected by the GAD65 antigen-specific vaccination and/or associated with β-cell function in participants of this trial.. GADA affinity was measured in sera of 46 LADA patients obtained prior to the first week and 20 weeks after the second injection with GAD-alum or placebo using competitive binding experiments with [125I]-labeled and unlabeled human GAD65.. At baseline, GADA affinities ranged from 1.9 × 10(7) to 5.0 × 10(12) L/mol (median 2.8 × 10(10) L/mol) and were correlated with GADA titers (r = 0.47; P = 0.0009), fasting (r = -0.37; P = 0.01) and stimulated (r = -0.40; P = 0.006) C-peptide concentrations, and HbA1c (r = 0.39; P = 0.007). No significant changes in affinity were observed from baseline to week 24. Patients with GADA affinities in the lower first quartile (<4 × 10(9) L/mol) had better preserved fasting C-peptide concentrations at baseline than those with higher affinities (mean 1.02 vs. 0.66 nmol/L; P = 0.004) and retained higher concentrations over 30 months of follow-up (mean 1.26 vs. 0.62 nmol/L; P = 0.01).. Intervention with GAD-alum in LADA patients had no effect on GADA affinity. Our data suggest that patients with low GADA affinity have a prolonged preservation of residual β-cell function.

Topics: Adult; Aged; Alum Compounds; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Disease Progression; Double-Blind Method; Female; Glucose Intolerance; Glutamate Decarboxylase; Humans; Insulin-Secreting Cells; Male; Middle Aged; Vaccination; Vaccines, Synthetic

Animal studies indicate that osteocalcin (OC), particularly the undercarboxylated isoform (unOC), affects insulin sensitivity and secretion, but definitive data from humans are lacking.. The objectives of the study were to determine whether total OC and unOC are independently associated with insulin sensitivity and β-cell response in overweight/obese adults; whether glucose tolerance status affects these associations; and whether the associations are independent of bone formation, as reflected in procollagen type 1 amino propeptide (P1NP).. This was a cross-sectional study conducted at a university research center involving 63 overweight/obese adults with normal (n = 39) or impaired fasting glucose (IFG; n = 24).. Serum concentrations of total/undercarboxylated OC and P1NP were assessed by RIA; insulin sensitivity was determined by iv glucose tolerance test (S(I)-IVGTT), liquid meal test (S(I) meal), and homeostasis model assessment of insulin resistance; β-cell response to glucose [basal β-cell response to glucose; dynamic β-cell response to glucose; static β-cell response to glucose; and total β-cell response to glucose] was derived using C-peptide modeling of meal test data; and intraabdominal adipose tissue was measured using computed tomography scanning.. Multiple linear regression, adjusting for intraabdominal adipose tissue and P1NP, revealed that total OC was positively associated with S(I)-iv glucose tolerance test (P < .01) in the total sample. OC was not associated with S(I) meal or homeostasis model assessment of insulin resistance. In participants with IFG, unOC was positively associated with static β-cell response to glucose and total β-cell response to glucose (P < .05), independent of insulin sensitivity.. In overweight/obese individuals, total OC may be associated with skeletal muscle but not hepatic insulin sensitivity. unOC is uniquely associated with β-cell function only in individuals with IFG. Further research is needed to probe the causal inference of these relationships and to determine whether indirect nutrient sensing pathways underlie these associations.

Topics: Adult; Biomarkers; Body Mass Index; C-Peptide; Cohort Studies; Cross-Sectional Studies; Female; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Intra-Abdominal Fat; Liver; Male; Middle Aged; Models, Biological; Muscle, Skeletal; Osteocalcin; Overweight; Peptide Fragments; Procollagen; Protein Processing, Post-Translational; Young Adult

The insulinotropic effect of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) is impaired in patients with type 2 diabetes. It remains unclear whether this impairment is a primary pathophysiological trait or a consequence of developing diabetes. Therefore, we aimed to investigate the insulinotropic effect of GIP and GLP-1 compared with placebo before and after 12 d of glucose homeostatic dysregulation in healthy subjects.. The insulinotropic effect was measured using hyperglycemic clamps and infusion of physiological doses of GIP, GLP-1, or saline in 10 healthy Caucasian males before and after intervention using a high-calorie diet, sedentary lifestyle, and administration of prednisolone (37.5 mg once daily) for 12 d.. The intervention resulted in increased insulin resistance according to the homeostatic model assessment (1.2 ± 0.2 vs. 2.6 ± 0.5, P = 0.01), and glucose tolerance deteriorated as assessed by the area under curve for plasma glucose during a 75-g oral glucose tolerance test (730 ± 30 vs. 846 ± 57 mm for 2 h, P = 0.021). The subjects compensated for the change in insulin resistance by significantly increasing their postintervention insulin responses during saline infusion by 2.9 ± 0.5-fold (P = 0.001) but were unable to do so in response to incretin hormones (which caused insignificant increases of only 1.78 ± 0.3 and 1.38 ± 0.3-fold, P value not significant).. These data show that impairment of the insulinotropic effect of both GIP and GLP-1 can be induced in healthy male subjects without risk factors for type 2 diabetes, indicating that the reduced insulinotropic effect of the incretin hormones observed in type 2 diabetes most likely is a consequence of insulin resistance and glucose intolerance rather than a primary event causing the disease.

Topics: Adult; Blood Glucose; C-Peptide; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Incretins; Infusions, Intravenous; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Kinetics; Male; Severity of Illness Index; Young Adult

Glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion (GSIS). This response is blunted in type 2 diabetes (T2DM). Xenin-25 is a 25-amino acid neurotensin-related peptide that amplifies GIP-mediated GSIS in hyperglycemic mice. This study determines if xenin-25 amplifies GIP-mediated GSIS in humans with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or T2DM. Each fasting subject received graded glucose infusions to progressively raise plasma glucose concentrations, along with vehicle alone, GIP, xenin-25, or GIP plus xenin-25. Plasma glucose, insulin, C-peptide, and glucagon levels and insulin secretion rates (ISRs) were determined. GIP amplified GSIS in all groups. Initially, this response was rapid, profound, transient, and essentially glucose independent. Thereafter, ISRs increased as a function of plasma glucose. Although magnitudes of insulin secretory responses to GIP were similar in all groups, ISRs were not restored to normal in subjects with IGT and T2DM. Xenin-25 alone had no effect on ISRs or plasma glucagon levels, but the combination of GIP plus xenin-25 transiently increased ISR and plasma glucagon levels in subjects with NGT and IGT but not T2DM. Since xenin-25 signaling to islets is mediated by a cholinergic relay, impaired islet responses in T2DM may reflect defective neuronal, rather than GIP, signaling.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucose; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Neurotensin

Fibroblast growth factor 21 (FGF21), an endocrine factor predominantly secreted from liver, possesses multiple beneficial effect on energy metabolism and insulin sensitivity in animals. This study aimed to investigate the acute change of serum FGF21 in response to glucose challenge in humans.. A 75-g oral glucose tolerance test was performed among 20 healthy subjects, 18 with impaired glucose tolerance (IGT) and 21 with type 2 diabetes mellitus (T2DM). Blood samples were collected for measurement of FGF21 and other biochemical parameters. The associations of FGF21 with insulin and other metabolic parameters were analyzed.. Fasting serum FGF21 levels increased progressively from healthy, IGT to T2DM subjects (P < 0.05 for global trend). After oral glucose administration, the serum FGF21 level showed a similar biphasic change in all three groups. It declined to a nadir level at 60 min and then increased gradually to its peak level at 180 min. FGF21 levels at different time points of oral glucose tolerance test negatively correlated with glucose levels in all subjects, and the fold change of serum FGF21 at different time points (compared with the basal level) were inversely associated with fold changes of insulin (P = 0.012) and C-peptide (P = 0.043) levels in healthy subjects but not in IGT and T2DM patients.. The dynamic change of circulating FGF21 was associated with alterations in insulin levels in response to glucose challenge in humans. These findings support the role of FGF21 as a potential regulator of insulin secretion and glucose metabolism in humans.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Fibroblast Growth Factors; Glucose; Glucose Intolerance; Glucose Tolerance Test; Health; Humans; Insulin; Insulin Resistance; Male; Matched-Pair Analysis

The present analysis tests the hypothesis that quantifiable disruption of the glucose-stimulated insulin-secretion dose-response pathway mediates impaired fasting glycemia (IFG) and type 2 diabetes mellitus (DM). To this end, adults with normal and impaired fasting glycemia (NFG, n = 30), IFG (n = 32), and DM (n = 14) were given a mixed meal containing 75 g glucose. C-peptide and glucose were measured over 4 h, 13 times in NFG and IFG and 16 times in DM (age range 50-57 yr, body mass index 28-32 kg/m(2)). Wavelet-based deconvolution analysis was used to estimate time-varying C-peptide secretion rates. Logistic dose-response functions were constructed analytically of the sensitivity, potency, and efficacy (in the pharmacological sense of slope, one-half maximal stimulation, and maximal effect) of glucose's stimulation of prehepatic insulin (C-peptide) secretion. A hysteresis changepoint time, demarcating unequal glucose potencies for onset and recovery pathways, was estimated simultaneously. According to this methodology, NFG subjects exhibited distinct onset and recovery potencies of glucose in stimulating C-peptide secretion (6.5 and 8.5 mM), thereby defining in vivo hysteresis (potency shift -2.0 mM). IFG patients manifested reduced glucose onset potency (8.6 mM), and diminished C-peptide hysteretic shift (-0.80 mM). DM patients had markedly decreased glucose potency (18.8 mM), reversal of C-peptide's hysteretic shift (+4.5 mM), and 30% lower C-peptide sensitivity to glucose stimulation. From these data, we conclude that a dynamic dose-response model of glucose-dependent control of C-peptide secretion can identify disruption of in vivo hysteresis in patients with IFG and DM. Pathway-defined analytic models of this kind may aid in the search for prediabetes biomarkers.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Eating; Fasting; Female; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Logistic Models; Male; Middle Aged; Osmolar Concentration; Prediabetic State; Secretory Pathway; Time Factors

Glucocorticoids (GCs) are regarded as diabetogenic because they impair insulin sensitivity and islet-cell function. This study assessed whether treatment with the glucagon-like peptide receptor agonist (GLP-1 RA) exenatide (EXE) could prevent GC-induced glucose intolerance.. A randomized, placebo-controlled, double-blind, crossover study in eight healthy men (age: 23.5 [20.0-28.3] years; BMI: 26.4 [24.3-28.0] kg/m(2)) was conducted. Participants received three therapeutic regimens for 2 consecutive days: 1) 80 mg of oral prednisolone (PRED) every day (q.d.) and intravenous (IV) EXE infusion (PRED+EXE); 2) 80 mg of oral PRED q.d. and IV saline infusion (PRED+SAL); and 3) oral placebo-PRED q.d. and intravenous saline infusion (PLB+SAL). On day 1, glucose tolerance was assessed during a meal challenge test. On day 2, participants underwent a clamp procedure to measure insulin secretion and insulin sensitivity.. PRED+SAL treatment increased postprandial glucose levels (vs. PLB+SAL, P = 0.012), which was prevented by concomitant EXE (vs. PLB+SAL, P = NS). EXE reduced PRED-induced hyperglucagonemia during the meal challenge (P = 0.018) and decreased gastric emptying (vs. PRED+SAL, P = 0.028; vs. PLB+SAL, P = 0.046). PRED+SAL decreased first-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL, P = 0.017 and P = 0.05, respectively), whereas PRED+EXE improved first- and second-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL; P = 0.017, 0.012, and 0.093, respectively).. The GLP-1 RA EXE prevented PRED-induced glucose intolerance and islet-cell dysfunction in healthy humans. Incretin-based therapies should be explored as a potential strategy to prevent steroid diabetes.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Cross-Over Studies; Exenatide; Glucagon-Like Peptide 1; Glucocorticoids; Glucose Clamp Technique; Glucose Intolerance; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemic Agents; Insulin Resistance; Islets of Langerhans; Male; Peptides; Prednisone; Venoms; Young Adult

We tested the hypotheses that in nondiabetic individuals, partial inhibition of insulin secretion with the ATP-sensitive K(+) channel agonist (opener) diazoxide, compared with placebo, results in higher plasma glucose and higher plasma glucagon concentrations after a mixed meal and after administration of the sulfonylurea glimepiride.. Plasma glucose, insulin, C-peptide, and glucagon concentrations were measured every 30 min from -60 through 180 min with random-sequence, double-blind administration of diazoxide (6.0 mg/kg) or placebo at -30 and 1 min, ingestion of a formula mixed meal (Ensure Plus) at 0 min after diazoxide and after placebo and, on a separate occasion, ingestion of glimepiride (4.0 mg) at 0 min (with glucose infused to prevent hypoglycemia) after diazoxide and after placebo in 11 healthy young adults.. With diazoxide administration, insulin (P = 0.0016) and C-peptide (P = 0.0287) concentrations were decreased and glucose concentrations were increased (e.g., 180-min values of 106 ± 4 mg/dL [5.9 ± 0.2 mmol/L] compared with 87 ± 2 mg/dL [4.8 ± 0.1 mmol/L] with placebo; P < 0.0001), but glucagon concentrations were no different after the mixed meal. Similarly, with diazoxide, C-peptide concentrations were decreased (P = 0.0015) and glucose concentrations were increased (P < 0.0001), but glucagon concentrations declined similarly after glimepiride administration.. Partial inhibition of insulin secretion results in impairment of glucose tolerance after a mixed meal and after glimepiride administration in the absence of a difference in glucagon secretion. They underscore the primary glucoregulatory role of insulin and support the evidence that β-cell secretion is not the only regulator of α-cell glucagon secretion.

Topics: Adult; Blood Glucose; C-Peptide; Diazoxide; Female; Glucagon; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; KATP Channels; Male; Sulfonylurea Compounds; Young Adult

It is clinically relevant and of physiological interest to investigate whether GH-induced insulin resistance depends on the timing of GH exposure relative to when insulin sensitivity is assessed.. GH-induced insulin resistance is rapidly reversible.. Eight male GH-deficient patients underwent a 6-h euglycemic-hyperinsulinemic glucose clamp thrice in a randomized crossover design receiving either no GH (study 0), a 7-h GH infusion (0.2-0.3 mg in total) that terminated 5 h before the clamp (study 1), or a similar GH infusion timed to continue during the first hour of the clamp (study 2). A muscle biopsy was obtained 30 min into the clamp. The patients were compared with eight healthy untreated control subjects (study c).. The glucose infusion rate, indirect calorimetry, and free fatty acid metabolism were assessed. In muscle biopsies, protein phosphorylation of signal transducer and activator of transcription 5, Akt, and Akt substrate 160 (phospho-Akt substrate signal) and gene expression of IGF-I and SOCS1-3 were assessed.. Insulin sensitivity differed significantly between the GH-deficiency studies (P = 0.005) with distinct insulin resistance in study 2 and increased insulin sensitivity in study 0 [area under the glucose infusion rate curve (mg/kg · min): 1663 ± 151 (study 0) vs. 1482 ± 166 (study 1) vs. 1123 ± 136 (study 2) vs. 1492 ± 229 (control group)]. Free fatty acid levels and lipid oxidation were elevated in response to GH exposure but became suppressed during the clamp. IGF-I and SOCS3 gene expression was increased in study 2.. Very-low-dose GH exposure evokes acute insulin resistance that subsides after 5 h. This time-dependent reversibility should be considered when assessing the impact of GH on glucose homeostasis.

Topics: Acute Disease; Adult; Aged; Biopsy; Blood Glucose; C-Peptide; Calorimetry, Indirect; Cross-Over Studies; Fatty Acids, Nonesterified; Gene Expression; Glucose Clamp Technique; Glucose Intolerance; Human Growth Hormone; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Male; Middle Aged; Muscle, Skeletal; Signal Transduction; Suppressor of Cytokine Signaling Proteins

To provide an initial evaluation of insulin sensitivity and secretion indices derived from a standard liquid meal tolerance test protocol in subjects with normal (NFG), impaired fasting glucose (IFG) or type 2 diabetes mellitus.. Areas under the curve (AUC) for glucose, insulin and C-peptide from pre-meal to 120 min after consumption of a liquid meal were calculated, as were homeostasis model assessments of insulin resistance (HOMA2-IR) and the Matsuda index of insulin sensitivity.. Subjects with NFG (n = 19), IFG (n = 19), and diabetes (n = 35) had mean +/- SEM HOMA2-IR values of 1.0 +/- 0.1, 1.6 +/- 0.2 and 2.5 +/- 0.3 and Matsuda insulin sensitivity index values of 15.6 +/- 2.0, 8.8 +/- 1.2 and 6.0 +/- 0.6, respectively. The log-transformed values for these variables were highly correlated overall and within each fasting glucose category (r = -0.91 to -0.94, all p < 0.001). Values for the product of the insulin/glucose AUC ratio and the Matsuda index, an indicator of the ability of the pancreas to match insulin secretion to the degree of insulin resistance, were 995.6 +/- 80.7 (NFG), 684.0 +/- 57.3 (IFG) and 188.3 +/- 16.1 (diabetes) and discriminated significantly between fasting glucose categories (p < 0.001 for each comparison).. These results provide initial evidence to support the usefulness of a standard liquid meal tolerance test for evaluation of insulin secretion and sensitivity in clinical and population studies.

Topics: Area Under Curve; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged

Improved glucose tolerance to sequential glucose loading (Staub-Traugott effect) is an important determinant of day-to-day glycemic exposure. Its mechanisms have not been clearly established. We recruited 17 healthy volunteers to receive two sequential oral glucose tolerance tests (OGTTs), at time 0 min and 180 min (Study I). The protocol was repeated on a separate day (Study II) except that plasma glucose was clamped at 8.3 mmol/l between 60 and 180 min. beta-Cell function was analyzed by mathematical modeling of C-peptide concentrations. In a subgroup, glucose kinetics were measured by a triple-tracer technique (infusion of [6,6-(2)H(2)]glucose and labeling of the 2 glucose loads with [1-(2)H]glucose and [U-(13)C]glucose). In both Studies I and II, the plasma glucose response to the second OGTT equaled 84 +/- 2% (P = 0.003) of the response to the first OGTT. Absolute insulin secretion was lower (37.8 +/- 4.3 vs. 42.8 +/- 5.1 nmol/m(2), P = 0.02), but glucose potentiation (i.e., higher secretion at the same glycemia) was stronger (1.08 +/- 0.02- vs. 0.92 +/- 0.02-fold, P = 0.006), the increment being higher in Study II (+36 +/- 5%) than Study I (+19 +/- 6%, P < 0.05). In pooled data, a higher glucose area during the first OGTT was associated with a higher potentiation during the second OGTT (rho=0.60, P = 0.002). Neither insulin clearance nor glucose clearance differed between loads, and appearance of glucose over 3 h totalled 60 +/- 6 g for the first load and 52 +/- 5 g for the second load (P = not significant). Fasting endogenous glucose production [13.3 +/- 0.6 micromol x min(-1) x kg fat-free mass (FFM)(-1)] averaged 6.0 +/- 3.8 micromol x min(-1) x kg FFM(-1) between 0 and 180 min and 1.7 +/- 2.6 between 180 and 360 min (P < 0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect.

Topics: Adult; Blood Glucose; C-Peptide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Signal Transduction

We examined whether parenteral regular insulin can prevent diabetes in IA-2 antibody-positive (IA-2A+) relatives of type 1 diabetic patients, using a trial protocol that differed substantially from that of the Diabetes Prevention Trial-1.. Twenty-five IA-2A+ relatives received regular human insulin twice a day for 36 months, during which time they were followed (median [interquartile range; IQR]: 47 [19-66] months) for glucose tolerance, HbA(1c) and islet autoantibodies, together with 25 IA-2A+ relatives (observation/control group) who fulfilled the same inclusion criteria, but were observed for 52 [27-67] months (P=0.58).. Twelve (48%) insulin-treated relatives and 15 (60%) relatives in the control group developed diabetes. There was no difference in diabetes-free survival between the two groups (P=0.97). Five-year progression (95% confidence interval) was 44% (25-69) in the insulin-treated group and 49% (29-70) in the observation group. At inclusion, progressors tended to have a higher pro-insulin/C-peptide ratio than non-progressors when measured 2 hours after a standardized glucose load (median [IQR]: 2.7% [1.8-4.3] vs. 1.6% [1.1-2.1]; P=0.01). No major hypoglycaemic episodes or significant increases in body mass index or diabetes autoantibodies were observed.. Prophylactic injections of regular human insulin were well tolerated, but failed to prevent type 1 diabetes onset in IA-2A+ relatives.

Topics: Adolescent; Adult; Autoantibodies; Belgium; Body Mass Index; C-Peptide; Child; Confidence Intervals; Diabetes Mellitus, Type 1; Female; Genetic Predisposition to Disease; Genotype; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Male; Pedigree; Proinsulin; Time Factors; Young Adult

This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT).. A 12-week, double-blind, randomized, parallel-group study comparing vildagliptin (50 mg q.d.) and placebo was conducted in 179 subjects with IGT (2-h glucose 9.1 mmol/l, A1C 5.9%). Plasma levels of intact glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and at week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to end point in the total and incremental (Delta) area under the curve (AUC)(0-2 h) for these analytes were assessed by ANCOVA; glucose AUC(0-2 h) was the primary outcome variable.. Relative to placebo, vildagliptin increased GLP-1 (DeltaAUC, +6.0 +/- 1.2 pmol x l(-1) x h(-1), P < 0.001) and GIP (DeltaAUC, +46.8 +/- 5.4 pmol . l(-1) x h(-1), P < 0.001) and decreased glucagon (DeltaAUC, -3.0 +/- 1.0 pmol x l(-1) x h(-1), P = 0.003). Although postprandial insulin levels were unaffected (DeltaAUC, +20.8 +/- 35.7 pmol x l(-1) x h(-1), P = 0.561), prandial glucose excursions were reduced (DeltaAUC, -1.0 +/- 0.3 mmol x l(-1) x h(-1), P < 0.001), representing an approximately 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC(0-2 h)/glucose AUC(0-2 h) was significantly increased (+6.4 +/- 2.0 pmol x min(-1) x m(-2) x mmol x l(-1), P = 0.002). Adverse event profiles were similar in the two treatment groups, and no hypoglycemia was reported.. The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT, with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.

Topics: Adamantane; Blood Glucose; C-Peptide; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Intolerance; Humans; Inulin; Kinetics; Male; Nitriles; Placebos; Postprandial Period; Pyrrolidines; Vildagliptin

Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance.. A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT.. Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4.2 +/- 0.3 vs. 5.4 +/- 0.4 10(-4) min(-1) (microU/ml)(-1); OGTT: 440 +/- 7 vs. 472 +/- 9 ml min(-1) m(-2)). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 +/- 5 vs. 124 +/- 7 pmol min(-1) m(-2) mm(-1), P = 0.0407) and insulin secretion at 5 mm glucose (168 +/- 9 vs. 206 +/- 10 pmol min(-1) m(-2), P = 0.003).. Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Pregnancy; Prognosis; Recovery of Function; Sensitivity and Specificity

Modest elevations in circulating IGF-I levels have been suggested to protect against the development of glucose intolerance in insulin-resistant subjects. To further understand the interactions of GH and IGF-I on beta-cell function and post-load glucose tolerance in glucose-intolerant subjects predisposed to diabetes, we performed a pilot study in 12 subjects with impaired glucose tolerance and the metabolic syndrome using a low GH dose (1.7 microg/kg per day) known to increase endogenous IGF-I production.. Fourteen daily GH or placebo injections in a double-blind cross-over study.. Baseline and post-treatment oral glucose tolerance tests were performed. The homeostasis model assessment and the insulinogenic index was used to estimate fasting insulin sensitivity (S(I)) and beta-cell function respectively, whereas changes in the incremental area under the curve were used to estimate post-load glucose tolerance (DeltaAUC(glu)) and post-load insulin levels (DeltaAUC(ins)).. GH increased total IGF-I (P<0.02), free IGF-I (P<0.04) and fasting insulin (P<0.04) levels, but did not modify plasma IGF-binding proteins (IGFBPs)-1 and -3, fasting glucose, non-esterified fatty acid and C-peptide levels, and fasting S(I). After oral glucose intake, glucose tolerance improved (P<0.03), but post-load insulin levels and beta-cell function remained unchanged.. Short-term low-dose GH administration induced fasting hyperinsulinaemia possibly by reducing insulin clearance but improved post-load glucose tolerance, suggesting that increased bioavailable IGF-I enhanced post-load S(I) without altering beta-cell function. Longer-term studies are required to ascertain whether these positive effects on post-load glucose tolerance and the preservation of beta-cell function can be sustained by this GH dose in these high-risk subjects.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cross-Over Studies; Fatty Acids, Nonesterified; Female; Glucose Intolerance; Glucose Tolerance Test; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Islets of Langerhans; Male; Metabolic Syndrome; Middle Aged; Prospective Studies

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

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

African Americans (AA) have greater prevalence of type 2 diabetes mellitus (DM), and nondiabetic AA have demonstrated increased insulin resistance when compared with Caucasian Americans (CA). The objective of this study was to examine the impact of chronic use of an insulin sensitizer on glucose metabolism in normal glucose tolerant AA at risk for DM (previous gestational diabetes mellitus [GDM] or first-degree relative with DM). Forty-nine high-risk AA received 200 mg/d troglitazone (TRO) versus 81 age-, weight-, and body mass index (BMI)-matched high-risk AA who received placebo (PLA) for 24 months. Yearly anthropometric measurements, oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT) were performed. Biochemical parameters were monitored quarterly. There was no significant change in anthropometric measurements over 24 months in TRO versus PLA. There were no significant differences in serum glucose, insulin, or C-peptide incremental area under the curve (AUC) in TRO versus PLA at baseline or 24 months for OGTT and FSIVGTT. The insulin sensitivity (S(I)) for TRO and PLA increased from baseline to 24 months by 17% and 16%, respectively. The TRO demonstrated a 26% increase in insulin/glucose ratio versus 1% increase in the PLA at 24 months. The disposition index (DI) increased 33% from baseline in TRO versus 21% increase in PLA. Modest improvement in glucose metabolism was seen in TRO when compared with PLA. TRO was well tolerated without significant reported adverse events. Based on our current data, the treatment of normal glucose tolerant high-risk AA with thiazolidinedione (TZD) may be beneficial to "reset" and protect glucose metabolism by improving insulin responses. Because of the potential drug-related risks associated with use of TZD and the proven positive impact of diet and exercise in prevention of DM, studies of longer duration with examination of other potentially beneficial parameters, such as cardiovascular indices and inflammatory markers will be necessary to justify the cost in the nondiabetic population.

Topics: Adult; Black People; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Chromans; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Genetic Predisposition to Disease; Glucose Intolerance; Homeostasis; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipids; Male; Placebos; Skinfold Thickness; Thiazoles; Thiazolidinediones; Troglitazone

Although it is well established that severe chronic hyperglycemia is associated with microvascular disease, it is not known whether transient hyperglycemia similar to that observed with impaired glucose tolerance or early Type 2 diabetes contributes to this pathology by altering microvascular function. To test the hypothesis that acute hyperglycemia decreases microvascular vasodilator responsiveness in human skin, we measured the cutaneous vasodilator response to local warming. This response can be divided into two phases, an initial peak that relies predominantly on local sensory nerves and a second slower phase that is largely dependent on endothelial nitric oxide. We reasoned that a change in one or both phases would indicate a change in the corresponding mechanism(s) with hyperglycemia. Twenty-eight healthy volunteers (14 women, 14 men) were randomly divided into three groups, corresponding to 6 h of euglycemia (n = 8), 6 h when glucose was clamped at approximately 7 mmol/l (n = 10), or 6 h when glucose was varied to mimic a postprandial pattern (i.e., peak glucose approximately 11.1 mmol/l) commonly observed in individuals with impaired glucose tolerance (n = 10). Insulin concentrations in all instances were maintained at approximately 65 pmol/l by means of continuous infusions of somatostatin and insulin. Glucagon and growth hormone were also continuously infused to maintain their basal concentrations. Despite substantial differences in both the level and pattern of glucose concentrations, neither maximum cutaneous vasodilation nor the pattern of the vasodilator response to local warming differed over the 6 h of study. We conclude that acute hyperglycemia similar to levels commonly observed in people with either early Type 2 diabetes or impaired glucose tolerance does not alter the vasodilator response to local warming of the skin in humans.

Topics: Acute Disease; Adult; Blood Glucose; Blood Vessels; C-Peptide; Female; Glucose Intolerance; Hemodynamics; Hot Temperature; Humans; Hyperglycemia; Insulin; Male; Osmolar Concentration; Reference Values; Regional Blood Flow; Skin; Time Factors

Topics: Adult; Area Under Curve; Blood Glucose; C-Peptide; Dietary Carbohydrates; Dietary Fiber; Glucose Intolerance; Humans; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Resistance; Liver Cirrhosis; Male; Middle Aged; Pilot Projects; Postprandial Period

The effect of melatonin on human carbohydrate metabolism is not yet clear. We investigated whether melatonin influences glucose tolerance and insulin sensitivity in aged women.. Twenty-two postmenopausal women of whom 14 were on hormone replacement therapy.. After an overnight fast, at 0800 hours on two nonconsecutive days, placebo or melatonin (1 mg) were administered randomly and in a double blind fashion. Forty-five minutes later, an oral glucose tolerance test (75 g; OGTT) was performed in 13 women. In another nine women insulin-dependent (Si) and -independent (Sg) glucose utilization was tested by a frequently sampled intravenous glucose tolerance test (FSIGT).. Areas under the response curve to OGTT (AUC) for glucose (1420 +/- 59 vs. 1250 +/- 55 mmol x min/l; P < 0.01), and C-peptide (42,0980 +/- 45,320 vs. 33,528 +/- 15,779 pmol x min/l; P < 0.02) were higher following melatonin than placebo, while Si values were lower (2.6 +/- 0.28 units vs. 3.49 +/- 0.4 units; P < 0.03). Si modifications induced by melatonin were inversely related to Si values of the placebo day (r(2) = 0.538; P < 0.025).. The present results indicate that in aged women administration of 1 mg of melatonin reduces glucose tolerance and insulin sensitivity. The present data may have both physiological and clinical implications.

Topics: Analysis of Variance; Area Under Curve; Blood Glucose; C-Peptide; Estradiol; Estrogen Replacement Therapy; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Linear Models; Melatonin; Middle Aged; Postmenopause

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

The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

Topics: Adult; C-Peptide; Coenzymes; Deafness; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; DNA, Mitochondrial; Family Health; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Hearing; Humans; Lactic Acid; Male; Middle Aged; Mothers; Point Mutation; Time Factors; Treatment Outcome; Ubiquinone

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 primary purpose of this study was to assess the effects of 12 weeks of treatment with either troglitazone, an investigational thiazolidinedione that acts as an insulin-action enhancer, or placebo in patients with impaired glucose tolerance (IGT).. A total of 51 subjects with IGT between 24 and 77 years of age were enrolled in this multicenter, double-blind, placebo-controlled, parallel group study (troglitazone, 25 patients; placebo, 26 patients). Patients were randomly assigned to receive either 400 mg troglitazone (every morning [QAM]) or placebo (QAM). The main outcome measure was the oral glucose tolerance test (OGTT) assessing glucose, insulin, and C-peptide levels in the fasting state and every 30 min up to 2 h after ingesting the glucose load. Fasting serum levels of HbA1c, fructosamine, lipids, and blood pressure were also measured.. A total of 46 patients completed the study. The glucose, insulin, and C-peptide responses after a glucose load were significantly reduced at 6 and 12 weeks in the troglitazone treatment group. After 6 weeks of treatment, 75% (n = 18) of those taking troglitazone had improved to normal glucose tolerance, whereas only 38% (n = 9) of those of placebo showed improvement (P = 0.008). After 12 weeks of treatment, 80% (n = 16) of the troglitazone treatment group had normalized their glucose tolerance, while only 48% (n = 10) of those on placebo had converted to normal (P = 0.016). Fasting triglyceride levels in the troglitazone treatment group had decreased by 40 mg/dl (0.45 mmol/l) (P = 0.0016). Other lipid measurements, blood pressure, glycosylated hemoglobin, and fructosamine were normal at baseline for both treatment groups and remained normal throughout the study.. The glycemic response after a glucose load is statistically and clinically significantly improved for patients with IGT treated with troglitazone.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chromans; Double-Blind Method; Ethnicity; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Middle Aged; Prospective Studies; Thiazoles; Thiazolidinediones; Time Factors; Triglycerides; Troglitazone

We investigated how fasting or postprandial insulin levels were altered by treatment with acarbose or sulfonylureas. Plasma glucose and serum insulin, C-peptide, and proinsulin levels were measured before as well as 1 and 2 h after breakfast in 23 patients with non-insulin-dependent diabetes mellitus and 17 patients with impaired glucose tolerance. In the diabetic patients, 12 weeks of acarbose therapy decreased the postprandial levels of glucose (1 h: -60.0%; 2 h: -67.6%), insulin (1 h: -67.5%; 2 h: -72.2%) and proinsulin (1 h: -55.2%; 2 h: -46.7%), and proinsulin (1 h: -20.9%; 2 h: -57.5%). In contrast, sulfonylurea treatment increased postprandial insulin and proinsulin levels. Since increased in the serum insulin or proinsulin levels are associated with a higher risk of cardiovascular disease, the present findings suggest that the acarbose-induced reduction of the postprandial serum insulin or proinsulin responses to food intake might be useful for preventing vascular complications in patients with diabetes.

Topics: Acarbose; Aged; Blood Glucose; C-Peptide; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Fasting; Gliclazide; Glucose Intolerance; Glycated Hemoglobin; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Middle Aged; Postprandial Period; Proinsulin; Time Factors; Tolbutamide; Triglycerides; Trisaccharides

Cisapride is used widely for the treatment of diabetic gastroparesis. There is some evidence that cisapride may influence insulin secretion. The aim of this study was to evaluate the effect of cisapride on plasma concentrations of glucose, insulin and C-peptide in response to oral and intravenous glucose loads. Twelve normal subjects took cisapride and placebo, each for 10 days using a randomized, double-blind, crossover design. In each treatment phase, the plasma glucose, insulin and C-peptide response to intravenous (0.5 g/kg) and oral (75 g) glucose loads was evaluated on separate days. Gastric emptying of the oral glucose load was also measured. After the intravenous glucose load, plasma concentrations of C-peptide were higher (P< 0.01) on cisapride when compared with placebo (e.g. peak C-peptide 2.08+/-0.25 nmol/L vs 1.78+/-0.22 nmol/L, P< 0.01) while there was no significant difference in plasma glucose or insulin. Cisapride had no effect on the rate of gastric emptying of the oral glucose load. Mean plasma concentrations of insulin and C-peptide were higher after oral glucose on cisapride than placebo, but these differences were not significantly different. These observations indicate that cisapride may increase glucose-stimulated insulin secretion.

Topics: Administration, Oral; Adult; C-Peptide; Cisapride; Female; Gastrointestinal Agents; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Injections, Intravenous; Insulin; Male; Osmolar Concentration; Piperidines; Reference Values

Insulin sensitivity was measured by insulin tolerance test using KITT as an index of insulin mediated glucose metabolism in 9 non-obese healthy offspring of conjugal diabetic parents (OCDP) and 9 non-obese NIDDM patients. The mean KITT value in the offspring of conjugal diabetic parents was 3.85 +/- 1.64 min-1 x 100 which was lower (P < 0.05) than the value of 5.49 +/- 1.9 min-1 x 100 in the control subjects. While, the mean KITT value in NIDDM patients was 1.85 +/- 0.9 min-1 x 100 which was significantly lower (P < 0.001) than that in the control subjects. Estimation of plasma immunoreactive insulin (IRI) and C-peptide in these subjects and in subjects with impaired glucose tolerance (IGT) showed significantly higher levels of insulin than that in the control subjects but there was no corresponding increase in the C-peptide levels. The mean area under the insulin curve (IRI) was 242 +/- 69 microU/ml in the control subjects versus 527 +/- 206 microU/ml in IGT (P < 0.001), 648 +/- 215 microU/ml in NIDDM (P < 0.001) and 466 +/- 130 microU/ml in OCDP (P < 0.001). These results suggest that 1) healthy offspring of two type II diabetic parents have decreased insulin sensitivity and insulin resistance is present in all the NIDDM patients, 2) peripheral hyperinsulinism is a common feature in healthy offspring of conjugal diabetic parents, and in subjects with IGT and mild NIDDM and this hyperinsulinism is not due to increased B-Cell secretion but due to some metabolic alterations of insulin occurring at the extra pancreatic levels.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male

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

This study was conducted to determine whether improvements in glucose tolerance could be observed after a single bout of resistance exercise in young (27.1 +/- 1.24 yr) control subjects, older (53.3 +/- 1.7 yr) patients with non-insulin-dependent diabetes mellitus (NIDDM), and older (50.7 +/- 1.9 yr) age-matched control subjects. Each subject was screened for fitness level and any contraindications to exercise before inclusion in the study. A 75-g oral glucose tolerance test was administered 2 wk after the subjects were screened, and the subjects were familiarized with the exercise equipment. The maximum weight that could be lifted with one repetition was determined on seven Nautilus machines that utilized the upper and lower body. After a 48-h rest period, a 3-set x 10-repetition protocol based on the subject's one repetition maximum was completed by each participant on each machine. Eighteen hours after the lifting protocol, a second oral glucose tolerance test was administered. There was no change in the pre- to post-exercise glucose levels in any of the treatment groups, but the total insulin responses (area under the curve) of the young control and NIDDM groups were significantly lower after exercise: from 6.93 +/- 0.8 x 10(3) to 5.38 +/- 0.65 x 10(3) pM in the young control group and from 9.83 +/- 1.95 x 10(3) to 7.77 +/- 1.50 x 10(3) pM in the NIDDM group. The postexercise C-peptide levels were unchanged in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 2; Exercise; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Oxygen Consumption; Weight Lifting

Glucose intolerance or diabetes mellitus, hyperlipidemia, obesity and hypertension may have a close interrelation based on insulin resistance. We selected 28 impaired glucose tolerance (IGT) patients with hyperlipidemia. The IGT patients demonstrated hypertriglyceridemia associated with hyperinsulinemia, a typical manifestation of insulin resistance. Administration of bezafibrate at 400 mg/day for 4 weeks to the IGT patients with hypertriglyceridemia resulted in an improvement of the plasma glucose level and insulin response to 75 g oral glucose loading associated with a concomitant decrease in non-esterified fatty acids. The ratio of the level of serum C-peptide to that of insulin after a 75 g oral glucose tolerance test (OGTT) was augmented after 4 weeks of bezafibrate administration. However, reduction of the cholesterol level with pravastatin did not alter these parameters. These results suggest that treatment to reduce the level of serum triglycerides, but not that of cholesterol, may have a beneficial effect for improving insulin resistance even in the non-obese subjects with IGT and decreasing the risk of coronary heart disease.

Topics: Bezafibrate; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypercholesterolemia; Hyperlipidemias; Insulin; Male; Middle Aged; Pravastatin

To evaluate whether beta-cell hyperfunction characterizes glucose intolerant states per se independent of fasting glycemia, we conducted a case-control study among 430 subjects who were classified, by NDGG criteria, as having normal glucose tolerance (n = 230, 130M/130F), nondiagnostic tolerance (NDT, n = 100, 50M/50F) and impaired glucose tolerance (IGT, n = 100, 50M/50F). Thirty-four subjects (17M/17F) with normal glucose tolerance were matched by age, sex, body mass index (BMI), waist-to-hip ratio (WHR), fasting glucose and HbA1c with 30 NDT (15M/15F) and 30 IGT (15M/15F) subjects. The continuous and significant increase in insulin and C-peptide levels across categories of glucose tolerance (from normal to NDT to IGT) was no longer evident in the case-control study: at a fasting plasma glucose ranging from 5.2-5.5 mmol/L (HbA1c was 5%) the concentration of fasting C-peptide was 0.793 +/- 225 nmol/L (mean +/- SD) in subjects with normal glucose tolerance, 0.805 +/- 200 nmol/L in NDT and 0.807 +/- 231 nmol/L in IGT subjects (p = NS). Similarly, plasma concentrations of triglycerides and blood pressure values were similar when subjects of different categories were compared at the same level of glycemia. Sixteen normal subjects were rendered mildly hyperglycemic by a 24-h glucose infusion to match the fasting glucose level of NDT (1 mg/kg/min) and IGT (2 mg/kg/min) subjects. At the same fasting glucose level, normal subjects presented elevations of fasting C-peptide significantly (p < 0.01) higher than subjects belonging to the NDT and IGT categories.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Case-Control Studies; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Middle Aged; Triglycerides

To better understand abnormal insulin production (IP) in states of carbohydrate intolerance, insulin release was quantified following equimolar (2.4 mmol/kg) infusions of glucose, arginine, and valine in healthy subjects ([HS] age, 45 +/- 3 years; body mass index [BMI, kg/m2], 26.3 +/- 2.4; means +/- SEM), obese subjects with impaired glucose tolerance ([IGT] age, 43 +/- 5 years; BMI, 35.4 +/- 2.4), and non-obese patients with chronic non-insulin-dependent diabetes mellitus ([NIDDM] age, 55 +/- 3 years; BMI, 26.4 +/- 1.4; duration of disease, 13 +/- 3 years). There were eight subjects per group. Incremental IP (metabolic clearance rate of C-peptide [MCRCP] x total incremental area under the curve of plasma C-peptide [AUCCP], pmol/kg) following substrate infusion was as follows: glucose: HS, 227 +/- 14; IGT, 1,050 +/- 184 (P < .001 v HS); NIDDM, 114 +/- 27 (P < .001 v HS); arginine: HS, 139 +/- 23; IGT, 488 +/- 106 (P < .01 v HS); NIDDM, 206 +/- 47; and valine: HS, 21 +/- 7; IGT, 32 +/- 10; NIDDM, 54 +/- 12 (P < .01 v HS). The fractional clearance rate ([FCR] k, %/min) was impaired in IGT and NIDDM for glucose (HS, 3.9 +/- 0.4; IGT, 2.3 +/- 0.3 [P < .01 v HS]; NIDDM, 1.4 +/- 0.1 [P < .001 v HS]), arginine (2.4 +/- 0.1; 1.9 +/- 0.2 [P < .01 v HS]; 1.9 +/- 0.2 [P < .01 v HS]), and valine (0.95 +/- 0.06; 0.65 +/- 0.09 [P < .05 v HS]; 0.74 +/- 0.1 [P < .05 v HS]).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arginine; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose; Glucose Intolerance; Humans; Injections, Intravenous; Insulin; Male; Middle Aged; Valine

To ascertain whether childbearing would decrease oral glucose-stimulated insulin and C-peptide levels and increase the risk of NIDDM and impaired glucose tolerance in a population of Hispanic and non-Hispanic white women residing in the San Luis Valley of Colorado. Several investigators have related childbearing to subsequent abnormal glucose tolerance.. In a population-based case-control epidemiological study, diabetic patients 20-74 yr of age (n = 196) and randomly sampled control women subjects (n = 735) underwent a glucose tolerance test, a physical examination, and an in-person standardized interview. The relations between the live-birth number and fasting and oral glucose stimulated glucose, insulin and C-peptide concentrations, and NIDDM and impaired glucose tolerance were estimated using linear or logistic regression to adjust for extraneous variables.. In women selected as control subjects, the live-birth number was related to a significant decrease in the sum of 1- and 2-h C-peptide concentrations (coefficient = -0.077, P < 0.001) and the logarithm of the sum of 1- and 2-h insulin concentrations (coefficient = -0.014, P = 0.02). After adjustment for subscapular skin-fold thickness, the relative odds of NIDDM for the live-birth number, which was small and of borderline significance, diminished (odds ratio = 1.04 for one birth, P = 0.18). Findings were similar for impaired glucose tolerance.. Childbearing was related to lower C-peptide and insulin levels in Hispanic and non-Hispanic women of the San Luis Valley. It had little apparent effect on later risk of NIDDM or impaired glucose tolerance.

Topics: Adult; Age Factors; Aged; Blood Glucose; C-Peptide; Colorado; Diabetes Mellitus, Type 2; Ethnicity; Female; Glucose Intolerance; Glucose Tolerance Test; Hispanic or Latino; Humans; Insulin; Medical History Taking; Middle Aged; Parity; Pregnancy; Regression Analysis; Risk Factors; White People

This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies' association with clinical characteristics and HLA-DR-DQ genes.. This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency.. IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD.. IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.

Topics: Autoantibodies; C-Peptide; Cation Transport Proteins; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose Intolerance; Glutamate Decarboxylase; Glycated Hemoglobin; HLA-DR Antigens; Humans; Insulinoma; Pancreatic Neoplasms; Zinc Transporter 8

The objective of this study is to explore the relationship between red blood cell distribution and islet β-cell function indexes in patients with Latent Autoimmune Diabetes in Adults.. A total of 487 LADA patients were enrolled in this cross-sectional study. Patients were divided into three groups according to RDW tertiles. Clinical and laboratory measurements of age, height, weight, duration of diabetes, blood pressure, RDW, glycosylated hemoglobin A1c (HbA1c), C-peptide and blood lipids were performed. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were assessed using homeostasis model assessment (HOMA) based on fasting blood glucose (FBG) and fasting C-peptide index (FCP). Correlations and multiple linear regressions were implemented to determine the association of RDW and islet function indexes.. As the increase of serum RDW level, the presence of β-cell secretion increased(P < 0.05). Correlation analysis indicated that there were significant correlations between RDW and male sex, age, duration, TG, Cr, FCP, and HOMA-β in all subjects. Multiple linear regressions indicated that RDW was significantly correlated with HOMA-β in the total population in both unadjusted and adjusted analysis. This finding could be reproduced in the subgroup of low GAD titers for HOMA-β. RDW were significantly associated with HbA1c in LADA patients with high GAD titers, but the correlation was not found in subgroup with low GAD titers in either unadjusted analyses or adjusted analysis.. RDW is associated with β-cell function assessed by HOMA-β after adjusting for covariates in LADA patients with low GAD titers.

Topics: Adult; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Erythrocytes; Glucose Intolerance; Glycated Hemoglobin; Humans; Latent Autoimmune Diabetes in Adults; Male

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. 13 persons were diagnosed with T2DM, 119 had impaired fasting blood glucose (IFG) and/or impaired glucose tolerance (IGT). 1074 participants showed normal results and formed a control group. A higher frequency of minor allele G was found in the IFG/IGT group in comparison with controls. The GG constellation was present in 23% of diabetics, in 17% of IFG/IGT probands and in 11% of controls. Compared to CC and CG genotypes, GG homozygotes showed higher stimulated glycemia levels during the OGTT. Homozygous as well as heterozygous carriers of the G allele showed lower very early phase of insulin and C-peptide secretion with unchanged insulin sensitivity. These differences remained significant after excluding diabetics and the IFG/IGT group from the analysis. No associations of the genotype with the shape of OGTT-based trajectories, with glucagon or with chronobiological patterns were observed. However, the shape of the trajectories differed significantly between men and women.. In a representative sample of the Czech population, the G allele of the rs10830963 polymorphism is associated with impaired early phase of beta cell function, and this is evident even in healthy individuals.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Kinetics; Male; Prediabetic State; Receptor, Melatonin, MT2

We aimed to explore the performance of detrended fluctuation function (DFF) in distinguishing patients with latent autoimmune diabetes in adults (LADA) from type 2 diabetes mellitus (T2DM) with glucose data derived from continuous glucose monitoring.. In total, 71 LADA and 152 T2DM patients were enrolled. Correlations between glucose parameters including time in range (TIR), mean glucose, standard deviation (SD), mean amplitude of glucose excursions (MAGE), coefficient of variation (CV), DFF and fasting and 2-hour postprandial C-peptide (FCP, 2hCP) were analyzed and compared. Receiver operating characteristics curve (ROC) analysis and 10-fold cross-validation were employed to explore and validate the performance of DFF in diabetes classification respectively.. Patients with LADA had a higher mean glucose, lower TIR, greater SD, MAGE and CV than those of T2DM (. A more violent glucose fluctuation pattern was marked in patients with LADA than T2DM. We first proposed the possible role of DFF in distinguishing patients with LADA from T2DM in our study population, which may assist in diabetes classification.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Latent Autoimmune Diabetes in Adults

Adult women with Turner syndrome (TS) have a high prevalence of diabetes and β-cell dysfunction that increases morbidity and mortality, but it is unknown if there is β-cell dysfunction present in youth with TS. This study aimed to determine the prevalence of β-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity (SI) and insulin secretion.. Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam, and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine β-cell function.. Twenty-one TS girls (35%) met criteria for prediabetes. Impaired fasting glucose was present in 18% of girls with TS and 3% HC (p value = 0.02). Impaired glucose tolerance was present in 23% of TS girls and 0% HC (p value <0.001). The hemoglobin A1c was not different between TS and HC (median 5%, p = 0.42). Youth with TS had significant reductions in SI, β-cell responsivity (Φ), and disposition index (DI) compared to HC. These differences remained significant when controlling for body mass index z-score (p values: 0.0006, 0.002, <0.0001 for SI, Φ total, DI, respectively).. β-Cell dysfunction is present in youth with TS compared to controls. The presence of both reduced insulin secretion and SI suggest a unique TS-related glycemic phenotype. Based on the data from this study, we strongly suggest that providers employ serial OGTT to screen for glucose abnormalities in TS youth.

Topics: Adolescent; Blood Glucose; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Phenotype; Prediabetic State; Prevalence; Turner Syndrome

To examine the hypothesis that, based on their glucose curves during a seven-point oral glucose tolerance test, people at elevated type 2 diabetes risk can be divided into subgroups with different clinical profiles at baseline and different degrees of subsequent glycaemic deterioration.. We included 2126 participants at elevated type 2 diabetes risk from the Diabetes Research on Patient Stratification (IMI-DIRECT) study. Latent class trajectory analysis was used to identify subgroups from a seven-point oral glucose tolerance test at baseline and follow-up. Linear models quantified the associations between the subgroups with glycaemic traits at baseline and 18 months.. At baseline, we identified four glucose curve subgroups, labelled in order of increasing peak levels as 1-4. Participants in Subgroups 2-4, were more likely to have higher insulin resistance (homeostatic model assessment) and a lower Matsuda index, than those in Subgroup 1. Overall, participants in Subgroups 3 and 4, had higher glycaemic trait values, with the exception of the Matsuda and insulinogenic indices. At 18 months, change in homeostatic model assessment of insulin resistance was higher in Subgroup 4 (β = 0.36, 95% CI 0.13-0.58), Subgroup 3 (β = 0.30; 95% CI 0.10-0.50) and Subgroup 2 (β = 0.18; 95% CI 0.04-0.32), compared to Subgroup 1. The same was observed for C-peptide and insulin. Five subgroups were identified at follow-up, and the majority of participants remained in the same subgroup or progressed to higher peak subgroups after 18 months.. Using data from a frequently sampled oral glucose tolerance test, glucose curve patterns associated with different clinical characteristics and different rates of subsequent glycaemic deterioration can be identified.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Latent Class Analysis; Male; Middle Aged; Risk Assessment

PAX6 is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of PAX6 gene is the main cause of a rare disease, congenital aniridia (CA). This case-control study aims to investigate the effects of PAX6 mutations on glucose metabolism and insulin secretion in families with CA.. In all, 21 families with CA were screened by Sanger sequencing. Patients with PAX6 mutations and CA (cases) and age-matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated.. Among 21 CA families, heterozygous PAX6 mutations were detected in five families. Among cases (n = 10) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (n = 12), two had IGT. The levels of haemoglobin A1c were 36 ± 4 mmol/mol (5.57 ± 0.46%) and 32 ± 5 mmol/L (5.21 ± 0.54%) in the cases and the controls, respectively (p = 0.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425 ± 4390) were significantly higher than that of the controls (3709 ± 1769) (p = 0.032).. PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients.

Topics: Adult; Aniridia; C-Peptide; Case-Control Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glycated Hemoglobin; Heterozygote; Humans; Insulin; Male; Middle Aged; Mutation; PAX6 Transcription Factor; Proinsulin

The fasting proinsulin to insulin ratio is elevated in people with type 2 diabetes and has been suggested as a marker of β-cell health. However, its utility in discriminating between individuals with varying degrees of β-cell dysfunction is unclear. Proinsulin has a very different half-life to insulin and unlike insulin does not undergo hepatic extraction prior to reaching the systemic circulation. Given these limitations, we sought to examine the relationship between fasting and postprandial concentrations of β-cell polypeptides (proinsulin, insulin and C-peptide) in people with normal and impaired glucose tolerance in differing metabolic environments.. Subjects were studied on two occasions in random order while undergoing an oral challenge. During one study day, free fatty acids were elevated (to induce insulin resistance) by infusion of Intralipid with heparin. Proinsulin to insulin and proinsulin to C-peptide ratios were calculated for the 0-, 30-, 60- and 240-minute time points. Insulin action (Si) and β-cell responsivity (Φ) indices were calculated using the oral minimal model.. The fasting proinsulin to c-peptide or fasting proinsulin to insulin ratios did not differ between groups and did not predict subsequent β-cell responsivity to glucose during the glycerol or Intralipid study days in either group.. Among nondiabetic individuals, the fasting proinsulin to insulin ratio is not a useful marker of β-cell function.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Proinsulin

The urinary C-peptide/creatinine ratio (UCPCR) is low in patients with type 1 diabetes mellitus, but it has not been well characterized in patients with type 2 diabetes mellitus (T2DM). We aimed to measure the UCPCRs in patients with T2DM and explore the relationships among UCPCR, insulin resistance (IR), and chronic vascular complications of diabetes.. A cross-sectional study was performed of 1299 Chinese hospitalized patients with T2DM. Binary logistic regression was used to evaluate the relationships between the chronic vascular complications of diabetes and UCPCR. K-means analysis was used to allocate participants to subgroups with five to six variables (age at diagnosis, body mass index [BMI], glycosylated hemoglobin, homoeostasis model assessment 2-estimated beta-cell function (HOMA2-B), and HOMA2-insulin resistance (HOMA2-IR), with or without UCPCR).. UCPCR positively correlated with HOMA2-IR (r = 0.448, P < .001). After adjustment for sex, age, duration of diabetes, and other cardiovascular risk factors, UCPCR was positively associated with diabetic kidney disease (DKD) (odds ratio [OR] = 1.198, 95% CI 1.019-1.408, P = .029) and coronary heart disease (CHD) (OR = 1.312, 95% CI 1.079-1.594, P = .006). When UCPCR was added, cluster analysis using the six variables identified five subgroups of T2DM, characterized by differing age at diagnosis, BMI, beta-cell function, IR, and prevalence of vascular complications.. UCPCR is positively associated with IR, DKD, and CHD and represents a promising biomarker that could refine the classification of T2DM.. 背景: 1型糖尿病患者尿C肽/肌酐比值水平低。但尿C肽/肌酐比值在2型糖尿病患者中并没有被充分评估, 本研究拟测定2型糖尿病患者的尿C肽/肌酐比值水平, 探讨尿C肽/肌酐比值与胰岛素抵抗及糖尿病慢性血管并发症的相关性, 并评估尿C肽/肌酐比值改善2型糖尿病精准分型的可能性。 方法: 本研究共纳入北京大学人民医院内分泌科住院2型糖尿病患者1299名。采集所有患者的临床资料, 测定其空腹尿C肽/肌酐比, 通过二元Logistic回归分析尿C肽/肌酐比值与糖尿病血管并发症的相关性。并分别用传统的五个变量[诊断年龄, 体重指数, 糖化血红蛋白, 改良稳态模型计算的β细胞功能指数(HOMA2-B)及胰岛素抵抗指数(HOMR2-IR)]和加入尿C肽/肌酐比值后的六个变量, 通过相同的k-means聚类算法对2型糖尿病患者进行聚类分组, 比较不同亚组的临床特点。 结果: 尿C肽/肌酐比值与HOMA2-IR水平 (r=0.448, P<0.001)正相关。在调整了性别, 年龄, 病程及其他心血管疾病危险因素后, 尿C肽/肌酐比值水平与糖尿病肾病 [比值比(OR) =1.198, 95%CI (1.019, 1.408), P=0.029]及冠状动脉粥样硬化性心脏病的发生风险呈正相关 [OR=1.312, 95%CI (1.079, 1.594), P=0.006]。在五个传统临床变量基础上, 加入尿C肽/肌酐比值后再进行聚类分型, 可以清晰地将患者分为五组:两组具有早发糖尿病特征[早发胰岛素缺乏型糖尿病(n=350)和早发胰岛素抵抗型糖尿病(n=176)], 两组具有晚发糖尿病特征[晚发胰岛素缺乏型糖尿病(n=318)和晚发胰岛素抵抗型糖尿病(n=133)]及轻型糖尿病(n=299)。各组间诊断年龄, 体重指数, 胰岛β细胞功能, 胰岛素抵抗水平以及糖尿病血管并发症比例显著不同。 结论: 尿C肽/肌酐比值与胰岛素抵抗水平及糖尿病肾病, 冠状动脉粥样硬化性心脏病发生风险正相关。在传统临床变量基础上引入尿C肽/肌酐比值, 可以改善2型糖尿病的精准分型。.

Topics: Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucose Intolerance; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Prognosis

Post-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear.. To understand the relationship of hypoglycemia with meal-related glucose excursion and insulin secretion, we analyzed plasma glucose, insulin, C-peptide, glucagon and incretins obtained during standardized mixed-meal tolerance tests (MMTT) in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF).. Hypoglycemia, defined as glucose <70 mg/dL, occurred in 9/34 subjects at 150 (range:120-210) minutes following initial meal ingestion. Hypoglycemia[+] and hypoglycemia[-] groups did not differ in gender, age, lung function, HbA1c, or BMI. While 11/14 hypoglycemia[-] individuals displayed normal glucose tolerance (NGT), only 2/9 hypoglycemia[+] had NGT. Peak glucose was higher in hypoglycemia[+] vs hypoglycemia[-]. Compared to hypoglycemia[-] NGT, hypoglycemia[+] exhibited lower early-phase insulin secretion (ISR-AUC. Hypoglycemia is common in PI-CF following MMTT and is associated with early glucose dysregulation (higher peak glucose), more impaired early-phase insulin secretion (lower ISR-AUC

Topics: Adolescent; Area Under Curve; Blood Glucose; C-Peptide; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemia; Incretins; Insulin; Insulin Secretion; Male; Young Adult

Autoimmune pancreatitis (AIP) is frequently complicated by diabetes mellitus (DM), but DM associated with AIP is reported to improve after steroid therapy. The aim of this study is to investigate glucose intolerance during steroid therapy according to the onset of DM.. Sixty-one patients who underwent steroid therapy for AIP were included into this study. We evaluated C peptide index (CPI), homeostasis model assessment for insulin resistance (HOMA-R), and the pancreatic diameter at AIP diagnosis and after 4 weeks, 1 year, and 2 years of steroid therapy. Patients were categorized into three groups according to DM onset: Pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM).. Forty-three patients (71%) had DM: 15 pDM and 28 cDM. At AIP diagnosis, CPI was lower in patients with pDM (0.7, P = 0.007) and cDM (0.9, P = 0.018) than nDM (1.3). After 4 weeks of steroid therapy, CPI improved in cDM (P < 0.001) and in nDM (P = 0.021). After 2 years of steroid therapy, HOMA-R increased (2.1-3.0, P = 0.007) but CPI gradually improved (1.0-2.1, P = 0.004). DM improved in 23% of cDM, and 55% of insulin users in cDM discontinued using insulin. Pancreatic atrophy was seen in 30%, and was associated with DM.. DM in patients with AIP was associated with impaired insulin secretion rather than insulin resistance. Insulin secretion improved during steroid therapy for AIP in patients with concurrent DM. Thus, glucose intolerance can be an indication for AIP treatment.

Topics: Aged; Anti-Inflammatory Agents; Atrophy; Autoimmune Pancreatitis; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Intolerance; Homeostasis; Humans; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Pancreas; Prednisolone

To study the incidence of glucose intolerance in CP patients without diabetes by performing oral glucose tolerance test (OGTT).. We screened consecutive Indian CP patients without diabetes over 6 months by performing OGTT and correlated with physical characteristics and glycated hemoglobin (HbA1c). We also compared c-peptide and pancreatic polypeptide response in different groups based on OGTT. Relevant statistical tests were performed. P < 0.05 was considered significant.. Total of 171 patients were screened. Mean duration of CP was 5.03 ± 4.32 years. 55 were detected to have prediabetes and 40 DM on OGTT. CP patients with diabetes and prediabetes had significantly dilated pancreatic duct compared to non-diabetic CP (4.2 ± 2.7 mm, 3.6 ± 2.7 mm, 2.84 ± 2.25 mm; p = 0.018). Fasting blood glucose (FBS) and 2-hour OGTT were 109.35 ± 19.06, 97.47 ± 11.94, 85.24 ± 9.95 and 236.13 ± 31.42, 154.65 ± 19.53, 112.89 ± 16.32 in patients with DM, prediabetes and CP patients without diabetes (p < 0.0001). There was a good c-peptide response (p = 0.001) and reduced pancreatic polypeptide response (p = 0.003) in CP patients compared to controls.. Early in the course of disease reduced pancreatic polypeptide response in the presence of good c-peptide response may result in development of DM.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Intolerance; Humans; Male; Pancreatitis, Chronic

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

We investigated associations between glucose tolerance and β-cell function using a series of estimation methods in a population-based study.. Data from the Dynamics of Lifestyle and Neighborhood Community on Health Study were analyzed. A total of 489 participants (263 women) were divided into three groups: normal glucose tolerance (NGT), prediabetes (PDM) and diabetes group. We estimated β-cell function by the homeostasis model assessment of β-cell function, proinsulin level (PI), C-peptide index, proinsulin-to-C-peptide ratio (PI/CPR) and proinsulin-to-insulin ratio. Because data on all five parameters of β-cell function showed skewed distributions, the values of these parameters were normalized by natural logarithmic (ln) transformation. Next, the association between glucose tolerance and β-cell function among participants without diabetes was examined. In this analysis, glucose tolerance was assessed based on glycated hemoglobin levels.. In the crude analysis, ln(PI) and ln(PI/CPR) were significantly higher in the diabetes group than those in the PDM and NGT groups, and these parameters were significantly higher in the PDM group than in the NGT group. Only ln(PI) in the PDM group was significantly higher compared with that in the NGT group after adjustment for age, sex and body mass index (ln[PI]: PDM group 2.38 pmol/L, 95% confidence interval 2.29-2.47 pmol/L; NGT group 2.17 pmol/L, 95% confidence interval 2.12-2.22 pmol/L; P < 0.05). In addition, ln(PI) levels were significantly and positively correlated with glycated hemoglobin quartile in participants without diabetes.. Our results showed that PI was the most sensitive to reflect glucose intolerance.

Topics: Adult; Aged; Biomarkers; Blood Glucose; C-Peptide; Cross-Sectional Studies; Female; Follow-Up Studies; Glucose Intolerance; Humans; Insulin; Male; Middle Aged; Prognosis; Proinsulin

The current era of large-scale clinical trials in diabetes has generated thousands of biological samples from study participants that are being stored long-term under frozen conditions for the future measurement of analytes of interest. Insulin and C-peptide are two such analytes that can provide insight into underlying pathophysiological processes (insulin sensitivity and β-cell function). However, the validity of the inferences that may be drawn from such future measurements is contingent on the stability of these analytes after long-term frozen storage. We conducted the present study to determine the stability of insulin and C-peptide concentrations that were first measured on fresh serum at the time of collection, followed by frozen storage at -80°C for >5 years and then repeat measurement. Bland-Altman analyses revealed good agreement between the repeated insulin measurements and between the repeated C-peptide measurements. The concordance correlation coefficient (CCC) confirmed reproducibility for both insulin (CCC 0.98, 95% confidence interval [CI] 0.96-0.99) and C-peptide (CCC 0.91, 95% CI 0.84-0.95); thus, insulin and C-peptide measurements are both stable and reproducible after long-term frozen storage of serum samples.

Topics: Adult; Blood Specimen Collection; C-Peptide; Cryopreservation; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Reproducibility of Results; Serum; Time Factors

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are highly pathophysiologic heterogeneous prediabetes conditions that can occur in all age groups, from youth to elderly people.. We evaluated whether distinct age-related phenotypes exist among individuals with IFG or IGT.. 479 young (aged 18 to 35 years), 699 adult (45 to 55 years) and 240 older (≥65 years) subjects underwent an oral glucose tolerance test (OGTT). From the OGTT results, the participants were grouped as follows: young age and normal glucose tolerance (NGT), adult age and NGT, older age and NGT, IFG young subjects, IFG adult subjects, IFG older subjects, IGT young (Y-IGT) subjects, IGT adult (A-IGT) subjects, and IGT older (O-IGT) subjects.. Insulin sensitivity and secretion, insulin clearance, and β-cell function.. Peripheral insulin sensitivity assessed using the Matsuda index, basal and glucose-stimulated insulin secretion, and β-cell function estimated using the disposition index were decreased in IFG adult subjects and IFG older subjects compared with IFG young subjects. A-IGT and Y-IGT subjects exhibited a progressively greater degree of hepatic insulin resistance assessed using the liver insulin resistance index, and reduced insulin clearance compared with O-IGT subjects. In contrast, the Matsuda index did not differ among Y-IGT, A-IGT, and O-IGT subjects. Basal and glucose-stimulated insulin secretion and β-cell function were lower in A-IGT and O-IGT subjects compared with Y-IGT individuals.. Subjects with IFG or IGT exhibited different age-related pathophysiologic characteristics. A more precise phenotyping of subjects with IGT or IFG could help to better design individualized preventive approaches to counteract diabetes progression.

Topics: Adolescent; Adult; Age Factors; Aged; Blood Glucose; Body Mass Index; C-Peptide; Cholesterol, HDL; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Prediabetic State; Triglycerides; Young Adult

β-Cell dysfunction is central to the pathogenesis of impaired glucose tolerance (IGT) and type 2 diabetes. Compared with adults, youth have hyperresponsive β-cells and their decline in β-cell function appears to be more rapid. However, there are no direct comparisons of β-cell responses to pharmacological intervention between the two age-groups. The Restoring Insulin Secretion (RISE) Adult Medication Study and the RISE Pediatric Medication Study compared interventions to improve or preserve β-cell function. Obese youth (

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Glargine; Insulin Resistance; Male; Metformin; Middle Aged

The Restoring Insulin Secretion (RISE) Adult Medication Study compared pharmacological approaches targeted to improve β-cell function in individuals with impaired glucose tolerance (IGT) or treatment-naive type 2 diabetes of <12 months duration.. All three active treatments produced on-treatment reductions in weight and improvements in HbA. In adults with IGT or recently diagnosed type 2 diabetes, interventions that improved β-cell function during active treatment failed to produce persistent benefits after treatment withdrawal. These observations suggest that continued intervention may be required to alter the progressive β-cell dysfunction in IGT or early type 2 diabetes.

Topics: Adult; Arginine; B-Lymphocytes; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin Resistance; Liraglutide; Male; Metformin; Middle Aged; Withholding Treatment

To investigate any associations between blood glucose (BG) and lipid levels in patients with different glucose tolerance statuses, including type 2 diabetes (T2DM) and impaired glucose regulation (IGR) cases as well as normal glucose tolerance (NGT) individuals.. A total of 354 participants were recruited to this study including 174 in the T2DM group, 112 in the IGR group and 68 in the NGT group. We compared BG, insulin and C-peptide (CP), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) serum levels during a 3 h oral glucose tolerance test (OGTT) in the 3 groups.. Basic overall HbA1c serum concentration percentages were 5.52, 6.33 and 9.76% for the NTG, IGR and T2DM cases. During the OGTT, insulin secretion in the IGR group was almost double that of the T2DM group. CP levels were highest in the IGR patients and OGTT related BG concentrations were highest in the T2DM group followed by IGR, but in the IGR group hyperglycemia was less pronounced than in T2DM patients (P <  0.001). Compared to the NGT group, TC, TG and LDL-C serum concentrations were significantly higher (P ≤ 0.001) and HDL-C concentrations were significantly lower (P ≤ 0.001) in IGR and T2DM cases compared to the NTG group.. IGR led to similar unfavorable blood lipid patterns compared with T2DM patients and an imbalance of insulin and CP serum concentrations during an OGTT.

Topics: Adult; Aged; C-Peptide; Female; Glucose; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lipids; Male; Middle Aged

Maturity-Onset Diabetes of the Young (MODY) type 4 or PDX1 -MODY is a rare form of monogenic diabetes caused by heterozygous variants in PDX1 . Pancreatic developmental anomalies related to PDX1 are reported only in neonatal diabetes cases. Here, we describe dorsal pancreatic agenesis in 2 patients with PDX1 -MODY. The proband presented with diabetes since 14 years of age and maintained regular glycemic control with low doses of basal insulin and detectable C-peptide levels after 38 years with diabetes. A diagnosis of MODY was suspected. Targeted next-generation sequencing identified a heterozygous variant in PDX1 : c.188delC/p.Pro63Argfs*60. Computed tomography revealed caudal pancreatic agenesis. Low fecal elastase indicated exocrine insufficiency. His son had impaired glucose tolerance, presented similar pancreatic agenesis, and harbored the same allelic variant. The unusual presentation in this Brazilian family enabled expansion upon a rare disease phenotype, demonstrating the possibility of detecting pancreatic malformation even in cases of PDX1 -related diabetes diagnosed after the first year of life. This finding can improve the management of MODY4 patients, leading to precocious investigation of pancreatic dysgenesis and exocrine dysfunction.

Topics: Brazil; C-Peptide; Child, Preschool; Congenital Abnormalities; Diabetes Mellitus, Type 2; Glucose Intolerance; Heterozygote; Homeodomain Proteins; Humans; Male; Middle Aged; Mutation; Pancreas; Pancreatic Elastase; Phenotype; Rare Diseases; Trans-Activators

To examine the relationship between hormones involved in bone remodeling and glucose metabolism alterations in prediabetes.. OPN was higher in IGR compared to NGT (5.3 ± 0.5 vs. 3.3 ± 0.2 μg/mL; p = 0.008) and in isolated IGT compared to IFG and IFG-IGT (6.3 ± 0.5 vs. 4.5 ± 0.3 and 5.4 ± 0.5 μg/mL; p = 0.02). OCN was similar in IFG and NGT but lower in IGT and IFG-IGT compared to NGT (7.2 ± 0.3 and 5.4 ± 0.2 vs. 8.3 ± 0.3 ng/mL; p < 0.01). OPN was positively correlated with HbA1c, fasting and 2 h plasma glucose and PTH. OCN was negatively correlated with body fat, 2 h plasma glucose, insulin and positively correlated with Stumvoll index. OPG correlated with TGD/SSPI (r = - 0.29; p < 0.05), EGP, and hepatic insulin resistance index in IGR (r = 0.51, r = 0.43; p < 0.01). There was no correlation between PTH and insulin sensitivity or Beta-cell function parameters.. In prediabetes, hormones known to be involved in bone remodeling may affect glucose metabolism before overt T2DM occurs with tissue-specific mechanisms.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Fasting; Female; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin; Prediabetic State

To investigate whether children and adolescents exhibiting an impaired glucose metabolism are more obese at treatment entry and less likely to reduce their degree of obesity during treatment.. The present study is a longitudinal observational study, including children and adolescents from the Children's Obesity Clinic, Holbaek, Denmark. Anthropometrics, pubertal development, socioeconomic status (SES), and fasting concentrations of plasma glucose, serum insulin, serum C-peptide, and whole blood glycosylated hemoglobin (HbA1c) were collected at treatment entry and at follow-up. Proxies of Homeostasis Model Assessment 2-insulin sensitivity (HOMA2-IS) and Homeostasis Model Assessment 2-β-cell function (HOMA2-B) were calculated with the Homeostasis Model Assessment 2 program.. In total, 569 (333 boys) patients, median 11.5 years of age (range 6-22 years), and median body mass index (BMI) z-score 2.94 (range 1.34-5.54) were included. The mean BMI z-score reduction was 0.31 (±0.46) after 13 months (range 6-18) of treatment. At treatment entry, patients with impaired estimates of glucose metabolism were more obese than normoglycemic patients. Baseline concentration of C-peptide was associated with a lower weight loss during treatment in girls (P = .02). Reduction in the insulin concentrations was associated with reduction in BMI z-score in both sexes (P < .0001, P = .0005). During treatment, values of glucose, HbA1c, HOMA2-IS, and HOMA2-B did not change or impact the treatment outcome, regardless of age, sex, SES, or degree of obesity at treatment entry.. The capability to reduce weight during multidisciplinary treatment in children and adolescents with overweight/obesity is not influenced by an impaired glucose metabolism at study entry or during the course of treatment.

Topics: Adolescent; Blood Glucose; Body Mass Index; C-Peptide; Child; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Insulin; Longitudinal Studies; Male; Pediatric Obesity; Prediabetic State; Weight Loss; Weight Reduction Programs; Young Adult

Insulin secretion (IS) declines with age, which increases the risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older adults. IS is regulated by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is lower in older adults and that this decline is associated with β-cell dysfunction.. A total of 40 young (25 ± 3 years) and 53 older (74 ± 7 years) lean nondiabetic subjects underwent a 2-hour oral glucose tolerance test (OGTT). Based on the OGTT, subjects were divided into three groups: young subjects with normal glucose tolerance (Y-NGT; n = 40), older subjects with normal glucose tolerance (O-NGT; n = 32), and older subjects with IGT (O-IGT; n = 21).. Plasma insulin, C-peptide, GLP-1, and GIP concentrations were measured every 15 to 30 minutes. We quantitated insulin sensitivity (Matsuda index) and insulin secretory rate (ISR) by deconvolution of C-peptide with the calculation of β-cell glucose sensitivity.. Matsuda index, early phase ISR (0 to 30 minutes), and parameters of β-cell function were lower in O-IGT than in Y-NGT subjects but not in O-NGT subjects. GLP-1 concentrations were elevated in both older groups [GLP-1 area under the curve (AUC)0-120 was 2.8 ± 0.1 in Y-NGT, 3.8 ± 0.5 in O-NGT, and 3.7 ± 0.4 nmol/L∙120 minutes in O-IGT subjects; P < 0.05], whereas GIP secretion was higher in O-NGT than in Y-NGT subjects (GIP AUC0-120 was 4.7 ± 0.3 in Y-NGT, 6.0 ± 0.4 in O-NGT, and 4.8 ± 0.3 nmol/L∙120 minutes in O-IGT subjects; P < 0.05).. Aging is associated with an exaggerated GLP-1 secretory response. However, it was not sufficient to increase insulin first-phase release in O-IGT and overcome insulin resistance.

Topics: Adult; Aged; Aging; Blood Glucose; C-Peptide; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male

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

To examine the association of connecting peptide (C-peptide) and the risks of postpartum diabetes and pre-diabetes among women with prior gestational diabetes.. A cross-sectional study of 1263 women with prior gestational diabetes was carried out at 1-5years after delivery in Tianjin, China. Logistic regression was used to assess the associations of C-peptide and the risks of diabetes and pre-diabetes.. The multivariable-adjusted odds ratios based on different levels of C-peptide (0-33%, 34-66%, 67-90%, and >90% as C-peptide cutpoints) were 1.00, 1.93 (95% confidence interval [CI] 0.85-4.39), 2.49 (95% CI 1.06-5.87), and 3.88 (95% CI 1.35-11.1) for diabetes (P for trend <0.0001), and 1.00, 1.66 (95% CI 1.18-2.36), 2.38 (95% CI 1.56-3.62) and 2.35 (95% CI 1.27-4.37) for pre-diabetes (P for trend <0.0001), respectively. Restricted cubic splines models showed a positive linear association of C-peptide as a continuous variable with the risks of type 2 diabetes and pre-diabetes. The positive association was significant when stratified by healthy weight and overweight participants.. We found a positive association between serum C-peptide levels and the risks of diabetes and pre-diabetes among Chinese women with prior gestational diabetes. Our finding suggested that elevated C-peptide levels may be a predictor of diabetes and pre-diabetes.

Topics: Adult; Biomarkers; C-Peptide; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Disease Susceptibility; Female; Glucose Intolerance; Health Surveys; Humans; Incidence; Prediabetic State; Pregnancy; Prevalence; Risk; Up-Regulation

The objectives of the study were to investigate serum ANGPTL8 concentrations in different glucose metabolic statuses and to explore the correlations between serum ANGPTL8 levels and various metabolic parameters. Serum ANGPTL8 levels were determined using ELISA in 22 subjects with NGT (normal glucose tolerance), 74 subjects with IGR (impaired glucose regulation), and 33 subjects with T2DM (type 2 diabetes mellitus). Subjects with IFG, IGT, CGI, and T2DM had higher levels of serum ANGPTL8 than subjects with NGT. Serum ANGPTL8 was positively correlated with FPG, fasting C-peptide, and postprandial C-peptide and negatively correlated with BETA/IR when adjusted for age and BMI. Multivariate analysis suggested FPG and fasting C-peptide as independent factors associated with serum ANGPTL8 levels. Serum ANGPTL8 concentrations were significantly increased in IGR and T2DM. Serum ANGPTL8 might play a role in the pathological mechanism of glucose intolerance.

Topics: Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Biomarkers; Blood Glucose; C-Peptide; Case-Control Studies; Chi-Square Distribution; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Male; Middle Aged; Multivariate Analysis; Peptide Hormones; Prediabetic State; Up-Regulation

The pre-absorptive cephalic phase of insulin secretion is elicited during the first ten min of a meal and before glucose levels rise. Its importance for insulin release during the post-absorptive phase has been well documented in animals but its presence or importance in man has become increasingly controversial. We here examined the presence of an early cephalic phase of insulin release in 31 well matched individuals without (n = 15) or with (n = 16) a known family history of type 2 diabetes (first-degree relatives; FDR). We also examined the potential differences in individuals with or without impaired fasting (IFG) and impaired glucose tolerance (IGT). We here demonstrate that a cephalic phase of insulin secretion was present in all individuals examined and without any differences between control persons and FDR or IFG/IGT. However, the overall importance of the cephalic phase is conjectural since it was unrelated to the subsequent post-absorptive insulin release or glucose tolerance. One of the best predictors of the incremental cephalic phase of insulin release was fasting insulin level and, thus, a relation to degree of insulin sensitivity is likely. In conclusion, an early pre-absorptive and cephalic phase of insulin release is robustly present in man. However, we could not document any relation to family history of Type 2 diabetes nor to the post-absorptive phase and, thus, confirm its importance for subsequent degree of insulin release or glucose tolerance.

Topics: Adult; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Eating; Fasting; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Meals; Middle Aged; Pedigree

The purpose of this study was to examine whether the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions: A: baseline; B: after 21 days of treatment with St. John's wort; and C: at least 6 weeks after the last capsule of St. John's wort was ingested. Plasma glucose, serum insulin and C-peptide levels were measured during an oral glucose tolerance test and used for estimation of area under the concentration-time curve (AUC) as well as indices of insulin sensitivity and insulin secretion. We found that treatment with St. John's wort increased total and incremental glucose AUC and 2-hr plasma glucose levels. Surprisingly, this effect was sustained and even further increased 6 weeks after the last capsule of St. John's wort was taken. No effect on indices of insulin sensitivity was seen, but indices of insulin secretion were reduced even after adjustment for insulin sensitivity. In conclusion, this study indicates that long-term treatment with St. John's wort may impair glucose tolerance by reducing insulin secretion in young, healthy men. The unregulated use of this over-the-counter drug might be a risk factor for impaired glucose tolerance and type 2 diabetes.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Dose-Response Relationship, Drug; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypericum; Insulin; Insulin Resistance; Insulin Secretion; Male; Plants, Medicinal; Sample Size; Young Adult

Elevated testosterone levels during prenatal life lead to hyperandrogenism and insulin resistance in adult females. This study evaluated whether prenatal testosterone exposure leads to the development of insulin resistance in adult male rats in order to assess the influence of gonadal hormones on glucose homeostasis in these animals. Male offspring of pregnant rats treated with testosterone propionate or its vehicle (control) were examined. A subset of male offspring was orchiectomized at 7 wk of age and reared to adulthood. At 24 wk of age, fat weights, plasma testosterone, glucose homeostasis, pancreas morphology, and gastrocnemius insulin receptor (IR) beta levels were examined. The pups born to testosterone-treated mothers were smaller at birth and remained smaller through adult life, with levels of fat deposition relatively similar to those in controls. Testosterone exposure during prenatal life induced hyperinsulinemia paralleled by an increased HOMA-IR index in a fasting state and glucose intolerance and exaggerated insulin responses following a glucose tolerance test. Prenatal androgen-exposed males had more circulating testosterone during adult life. Gonadectomy prevented hyperandrogenism, reversed hyperinsulinemia, and attenuated glucose-induced insulin responses but did not alter glucose intolerance in these rats. Prenatal androgen-exposed males had decreased pancreatic islet numbers, size, and beta-cell area along with decreased expression of IR in gastrocnemius muscles. Gonadectomy restored pancreatic islet numbers, size, and beta-cell area but did not normalize IRbeta expression. This study shows that prenatal testosterone exposure leads to a defective pancreas and skeletal muscle function in male offspring. Hyperinsulinemia during adult life is gonad-dependent, but glucose intolerance appears to be independent of postnatal testosterone levels.

Topics: Animals; Blood Glucose; Body Weight; C-Peptide; Female; Glucose Intolerance; Hyperandrogenism; Hyperinsulinism; Insulin-Secreting Cells; Islets of Langerhans; Male; Muscle, Skeletal; Orchiectomy; Pancreas; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Testosterone; Testosterone Propionate

Glucagon-like peptide-1 (GLP-1) is a powerful insulin secretagogue that is secreted in response to meal ingestion. The ability to quantify the effect of GLP-1 on insulin secretion could provide insights into the pathogenesis and treatment of diabetes. We used a modification of a model of GLP-1 action on insulin secretion using data from a hyperglycemic clamp with concomitant GLP-1 infusion. We tested this model using data from a mixed meal test (MMT), thereby measuring GLP-1-induced potentiation of insulin secretion in response to a meal.. The GLP-1 model is based on the oral C-peptide minimal model and assumes that over-basal insulin secretion depends linearly on GLP-1 concentration through the parameter Π, representing the β-cell sensitivity to GLP-1. The model was tested on 62 subjects across the spectrum of glucose tolerance (age, 53 ± 1 years; body mass index, 29.7 ± 0.6 kg/m(2)) studied with an MMT and provided a precise estimate of both β-cell responsivity and Π indices. By combining Π with a measure of L-cell responsivity to glucose, one obtains a potentiation index (PI) (i.e., a measure of the L-cell's function in relation to prevailing β-cell sensitivity to GLP-1).. Model-based measurement of GLP-1-induced insulin secretion demonstrates that the PI is significantly reduced in people with impaired glucose tolerance, compared with those with normal glucose tolerance.. We describe a model that can quantitate the GLP-1-based contribution to insulin secretion in response to meal ingestion. This methodology will allow a better understanding of β-cell function at various stages of glucose tolerance.

Topics: Blood Glucose; C-Peptide; Eating; Glucagon-Like Peptide 1; Glucose Clamp Technique; Glucose Intolerance; Healthy Volunteers; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Linear Models; Meals; Middle Aged

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

Intravenous glucose tolerance testing (IVGTT) is a common test of β-cell function in which a glucose load is administered and insulin and/or C-peptide responses are monitored. Since the first IVGTT may be more stressful and stress may alter β-cell secretion or hepatic insulin extraction, we asked whether there was a first test effect.. Insulin and C-peptide responses were compared from two sequential IVGTTs performed within 6 months during staging for the Diabetes Prevention Trial-Type 1 (DPT-1) in 368 people at high risk for type 1 diabetes. Insulin data (1+3 min) were used because the first phase insulin response (and peak insulin concentration) occurs within this time frame. Areas under the curve (AUC) calculations represent early insulin or C-peptide responses from 0 through 10 min post-glucose challenge.. More than half of all subjects were found to have first test values lower than the second. This was true for all measures of both insulin and C-peptide but the frequency was significantly different only for insulin measures corrected for basal and for insulin AUC (p < 0.05). However, for subjects (n = 99) whose 1+3 min insulin response was <10th percentile on the first test, there was a significant increase on the second test (p < 0.05). The C-peptide: insulin ratio did not change significantly between tests, indicating that differences are due to changes in β-cell secretion rather than hepatic insulin uptake.. A statistically significant first test effect occurs during the IVGTT attributable to variations in insulin secretion rather than hepatic uptake.

Topics: Adolescent; Adult; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Family Health; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Insulin Secretion; Insulin-Secreting Cells; Liver; Middle Aged; Reproducibility of Results; Risk; Stress, Psychological; Young Adult

This study investigated the relationship between GAD autoantibody (GADA) titers and changing of β-cell function in patients with latent autoimmune diabetes in adults (LADA).. This 3-year prospective study enrolled 95 subjects from 15 Chinese cities including 25 high-titer (GADA ≥180 units/mL) LADA patients, 42 low-titer (GADA <180 units/mL) LADA patients, and 28 type 2 diabetic patients, the latter two groups as controls of similar age, sex, and BMI. Clinical characteristics were determined annually, including glycosylated hemoglobin (HbA1c), fasting C-peptide (FCP), and 2-h postprandial C-peptide (PCP).. Despite similar initial FCP and PCP, FCP and PCP both decreased more in subjects with high GADA titer (FCP from mean 0.49 nmol/L at entry to 0.13 nmol/L at the third year; P < 0.05) than with low GADA titer (FCP from mean 0.48 to 0.38 nmol/L) and type 2 diabetes (FCP from mean 0.47 to 0.36 nmol/L); the latter two groups being similar. After 3 years, residual β-cell function (FCP >0.2 nmol/L) was detected in only 42% with an initial high GADA titer compared with 90% with a low GADA titer and 97% with type 2 diabetes (P < 0.01 for both). GADA positivity at the third year persisted more in subjects with initially high GADA (92%) than with low GADA (26%) titers (P < 0.01).. In selected LADA patients, initial GADA titers identified subjects with different degrees of persistent autoimmunity and disease progression. LADA patients with a low GADA titer had metabolic phenotypes and loss of β-cell function similar to type 2 diabetic patients.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Autoimmunity; C-Peptide; China; Diabetes Mellitus, Type 2; Disease Progression; Fasting; Female; Follow-Up Studies; Glucose Intolerance; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Insulin-Secreting Cells; Male; Middle Aged; Prospective Studies

Patients with psoriasis have increased risk of type 2 diabetes. The pathophysiology is largely unknown, but it is hypothesized that systemic inflammation causes insulin resistance. Insulin sensitivity has only been sparsely investigated in patients with psoriasis, and previous studies have used suboptimal methodology. The hyperinsulinemic euglycemic clamp remains the gold standard for quantifying whole-body insulin sensitivity.. We sought to investigate if normal glucose-tolerant patients with psoriasis exhibit impaired insulin sensitivity.. Three-hour hyperinsulinemic euglycemic clamps were performed in 16 patients with moderate to severe, untreated psoriasis and 16 matched control subjects.. The 2 groups were similar with regard to age, gender, body mass index, body composition, physical activity, fasting plasma glucose, and glycosylated hemoglobin. Mean ± SEM psoriasis duration was 23 ± 3 years and Psoriasis Area and Severity Index score was 12.7 ± 1.4. Patients with psoriasis exhibited reduced insulin sensitivity compared with control subjects (median M-value 4.5 [range 1.6-14.0] vs 7.4 [range 2.1-10.8] mg/kg/min, P = .046). There were no differences between groups in plasma glucose, insulin, C-peptide, and glucagon during the clamp.. The classic hyperinsulinemic euglycemic clamp technique does not allow assessment of endogenous glucose production.. Patients with psoriasis were more insulin resistant compared with healthy control subjects. This supports that psoriasis may be a prediabetic condition.

Topics: Adult; Anthropometry; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Glucagon; Gluconeogenesis; Glucose Clamp Technique; Glucose Intolerance; Humans; Hyperinsulinism; Inflammation; Insulin; Insulin Resistance; Male; Middle Aged; Prediabetic State; Psoriasis; Risk

Pancreatic beta-cell mass contributes to glucose tolerance. The aim of this study was to evaluate the relationships between human beta-cell mass and various clinical parameters, including insulin secretory capacity. The study included 32 Japanese patients who underwent pancreatectomy and were naive to oral hypoglycemic agents and insulin. They were classified into those with normal glucose tolerance (n=13), impaired glucose tolerance (n=9) and diabetes (n=10), and their insulin secretory capacity and insulin resistance were evaluated. Immunohistochemistry was used to determine relative beta-cell area (%) which represented the proportion of insulin-positive cell area to whole pancreatic section. Increment of C-peptide immunoreactivity level by glucagon test (ΔC-peptide, increment of serum C-peptide [nmol/L] at 6 min after intravenous injection of 1-mg glucagon; r=0.64, p=0.002), homeostasis model assessment of beta-cell function (HOMA-beta, fasting immunoreactive insulin [μIU/mL] x 20 / (fasting plasma glucose [mmol/L] - 3.5); r=0.50, p=0.003), C-peptide index (CPI, fasting C-peptide [nmol/L] / fasting plasma glucose [mmol/L]; r=0.36, p=0.042), and fasting immunoreactive insulin (F-IRI [pmol/L]; r=0.36, p=0.044) correlated significantly and positively with the relative beta-cell area. The area under the curve of plasma glucose level from 0 to 120 min by 75 g-OGTT (AUC0-120) also correlated significantly and inversely with the relative beta-cell area (r=-0.36, p=0.045). Stepwise multiple regression analysis identified ΔC-peptide as the only independent and significant determinant of the relative beta-cell area. We conclude that ΔC-peptide, HOMA-beta, CPI, F-IRI and AUC0-120 correlated closely with the relative beta-cell area, and ΔC-peptide was the most valuable index for the prediction of the area.

Topics: Aged; Blood Glucose; C-Peptide; Cell Count; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged

Small protein or lipid preloads are able to improve glucose tolerance to a different extent and through different and poorly defined mechanisms. We aimed at quantifying the effect of a mixed protein and lipid preload and at evaluating the underlying mechanisms.. Volunteers with normal (NGT, n = 12) or impaired (IGT, n = 13) glucose tolerance and patients with type 2 diabetes (n = 10) underwent two OGTTs coupled to the double glucose tracer protocol, preceded by either 50 g of parmesan cheese, a boiled egg and 300 ml of water, or 500 ml of water. We measured plasma glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), pancreatic polypeptide (PP), NEFA and glucose tracers, and calculated glucose fluxes, beta cell function variables, insulin sensitivity and clearance.. After the nutrient preload, the OGTT-induced rise of plasma glucose was lower than after water alone in each study group. This reduction—more pronounced across classes of glucose tolerance (NGT -32%, IGT -37%, type 2 diabetes -49%; p < 0.002)—was the result of different combinations of slower exogenous glucose rate of appearance, improved beta cell function and reduced insulin clearance, in this order of relevance, which were associated with an only mild stimulation of GIP and GLP-1.. After a non-glucidic nutrient preload, glucose tolerance improved in proportion to the degree of its baseline deterioration through mechanisms that appear particularly effective in type 2 diabetes. Exploiting the physiological responses to nutrient ingestion might reveal, at least in the first stages of the diabetic disease, a potent tool to improve daily life glycaemic control.. ClinicalTrials.gov NCT02342834 FUNDING: This work was supported by grants from the University of Pisa (Fondi di Ateneo) and by FCT grant (PIC/IC/82956/2007).

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Proteins; Female; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Young Adult

Global disruption of the GH receptor in mice (GHR-/-) produces a large and reproducible extension in lifespan. Since lack of GH action in muscle resulting in improved glucose homeostasis is potentially a mechanism by which GHR-/- mice are long-lived, and since no information on muscle-specific GHR disruption in females is available, we generated and characterized a line of muscle-specific GHR disrupted (MuGHRKO) mice. As expected, male MuGHRKO mice had improved fasting blood glucose, insulin, c-peptide, and glucose tolerance. In contrast, female MuGHRKO mice exhibited normal glucose, insulin, and glucose tolerance. Body weight was mildly but significantly altered in opposite directions in males (decreased) and females (increased) compared to controls. Grip strength and treadmill endurance were unchanged with advanced age in both sexes, suggesting that the direct action of GH on muscle has minimal effect on age-related musculoskeletal frailty. Longevity was unchanged in both sexes at Ohio University and significantly increased for males at University of Michigan. These data suggest that removal of GHR in muscle of male MuGHRKO mice replicates some of the health benefits seen in global GHR-/- mice including improvements to glucose homeostasis and smaller body weight in males, which may explain the trends observed in lifespan.

Topics: Animals; Blood Glucose; Body Composition; Body Weight; C-Peptide; Carrier Proteins; Energy Metabolism; Female; Glucose Intolerance; Health Status; Insulin; Longevity; Male; Mice; Mice, Knockout; Muscle Strength; Muscle, Skeletal; Physical Endurance; Sex Characteristics

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

To investigate the clinical features of non-alcoholic fatty liver disease (NAFLD) and its relationship with serum C-peptide levels in patients with latent autoimmune diabetes in adults (LADA).. A total of 155 patients with LADA who had no drinking history and were hospitalized in department of endocrinology and metabolism from January 2007 to June 2009 were divided into two groups, including patients with LADA but without NAFLD and patients with both LADA and NAFLD, according to Chinese medical association's guidelines of NAFLD and hepatic ultrasound result. Their clinical data and results of laboratory examinations were collected and analyzed, including medications, blood pressure, weight, height, waist circumference, hip circumference, fasting plasma glucose, 2 h postprandial plasma glucose, fasting C-peptide, 2 h postprandial C-peptide, hemoglobin A1c, renal function, liver function, blood lipid and C-reactive protein. The clinical features between two groups were compared and the relationship between serum C-peptide and NAFLD were also analyzed.. Compared to the patients with LADA but without NAFLD, patients with both LADA and NAFLD had higher alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γ-GT) (all P<0.01), but the serum total bilirubin (TBI) and direct bilirubin (DBI) level had no significant inter-group difference (P>0.05). The patients with both LADA and NAFLD had higher fasting C-peptide [0.62(0.33-0.93) vs 0.17 (0.05-0.50) nmol/L, P<0.001], 2 h postprandial C-peptide [1.57(0.78-1.88) vs 0.42(0.06-1.01) nmol/L, P<0.001] and more severe insulin resistance [0.8(1.0-2.5) vs 0.6(0.2-1.3), P<0.001]. Logistic regression analysis showed that there was a significant association between fasting C-peptide and the presence of NAFLD after controlling other confounding factors in patients with LADA.. The patients with both LADA and NAFLD had more severe metabolic disorders and insulin resistance. Serum fasting C peptide was independently associated with the presence of NAFLD in patients with LADA.

Topics: Adult; Alanine Transaminase; Asian People; Aspartate Aminotransferases; C-Peptide; C-Reactive Protein; Diabetes Mellitus, Type 1; gamma-Glutamyltransferase; Glucose Intolerance; Glycated Hemoglobin; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Waist Circumference

Oral glucose elicits a higher insulin secretory response than intravenous glucose at matched glucose concentrations. This potentiation, known as the incretin effect, is typically expressed as the difference between the total insulin response to oral vs intravenous glucose. This approach does not describe the dynamics of insulin secretion potentiation. We developed a model for the simultaneous analysis of oral and isoglycaemic intravenous glucose responses to dissect the impact of hyperglycaemia and incretin effect on insulin secretion and beta cell function.. Fifty individuals (23 with normal glucose tolerance [NGT], 17 with impaired glucose tolerance [IGT] and ten with type 2 diabetes) received an OGTT and an isoglycaemic test with measurement of plasma glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Our model featured an incretin potentiation factor (PINCR) for the dose–response function relating insulin secretion to glucose concentration, and an effect on early secretion (rate sensitivity).. In NGT, PINCR rapidly increased and remained sustained during the whole OGTT (mean PINCR>1, p<0.009). The increase was transient in IGT and virtually absent in diabetes. Mean PINCR was significantly but loosely correlated with GLP-1 AUC (r=0.49, p<0.006), while the relationship was not significant for GIP. An incretin effect on rate sensitivity was present in all groups (p<0.002).. The onset of the incretin effect is rapid and sustained in NGT, transient in IGT and virtually absent in diabetes. The profiles of the incretin effect are poorly related to those of the incretin hormones.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Incretins; Insulin; Male; Middle Aged; Models, Theoretical

The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes.. We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated.. Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide < 5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects.. In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Disease Progression; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Health Status Indicators; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Prediabetic State; Risk

Functional dyspepsia is predominantly attributed to gastric sensorimotor dysfunctions. The contribution of intestinal chemosensitivity to symptoms is not understood. We evaluated symptoms and plasma hormones during enteral nutrient infusion and the association with impaired glucose tolerance and quality-of-life (QOL) scores in patients with functional dyspepsia vs. healthy controls.. Enteral hormonal responses and symptoms were measured during isocaloric and isovolumic dextrose and lipid infusions into the duodenum in 30 patients with functional dyspepsia (n=27) or nausea and vomiting (n=3) and 35 healthy controls. Infusions were administered in randomized order over 120 min each, with a 120-min washout. Cholecystokinin, glucose-dependent insulinotropic peptide, glucagon-like peptide 1 (GLP1), and peptide YY were measured during infusions.. Moderate or more severe symptoms during lipid (4 controls vs. 14 patients) and dextrose (1 control vs. 12 patients) infusions were more prevalent in patients than controls (P≤0.01), associated with higher dyspepsia symptom score (P=0.01), worse QOL (P=0.01), and greater plasma hormone concentrations (e.g., GLP1 during lipid infusion). Moderate or more severe symptoms during enteral infusion explained 18%, and depression score explained 21%, of interpatient variation in QOL. Eight patients had impaired glucose tolerance, associated with greater plasma GLP1 and peptide YY concentrations during dextrose and lipid infusions, respectively.. Increased sensitivity to enteral dextrose and lipid infusions was associated with greater plasma enteral hormone concentrations, more severe daily symptoms, and worse QOL in functional dyspepsia. These observations are consistent with the hypothesis that enteral hormones mediate increased intestinal sensitivity to nutrients in functional dyspepsia.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Cholecystokinin; Duodenum; Dyspepsia; Enteral Nutrition; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Glucose; Glucose Intolerance; Humans; Lipids; Male; Peptide YY; Quality of Life; Severity of Illness Index

The C-peptide index (CPI), a ratio of serum C-peptide to plasma glucose levels, is a readily measured index of β-cell function. The difference in the physiological features reflected by the index measured under fasting (F-CPI) or postprandial (PP-CPI) conditions has remained unclear, however.. We investigated the relationship of the two CPIs to indexes of insulin secretion measured with an oral glucose tolerance test (OGTT) or with hyperglycemic and hyperinsulinemic-euglycemic clamp analyses as well as to disposition indexes (indexes of insulin secretion adjusted for insulin sensitivity) calculated from OGTT- or clamp-based analyses. We also examined the relationship between glucose tolerance and the clamp-based disposition index.. The clamp-based disposition index declined progressively from normal glucose tolerance to impaired glucose tolerance to Type 2 diabetes, and it strongly correlated with the 2-h plasma glucose level during an OGTT. For patients with Type 2 diabetes, both F-CPI and PP-CPI correlated with indexes of insulin secretion including HOMA-β, the insulinogenic index, the ratio of the area under the insulin curve to that under the glucose curve during an OGTT, the serum C-peptide level after glucagon challenge, as well as early and total insulin secretion measured with a hyperglycemic clamp. PP-CPI, but not F-CPI, was significantly correlated with clamp-based and OGTT-based disposition indexes.. F-CPI was correlated only with unadjusted indexes of insulin secretion, whereas PP-CPI was correlated with such indexes as well as with those adjusted for insulin sensitivity. The better clinical utility of PP-CPI might be attributable to these physiological characteristics.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Glucose; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Postprandial Period

People with prediabetes are at high risk of developing diabetes.. The objective of this study was to determine the pathogenesis of fasting and postprandial hyperglycemia in prediabetes.. Glucose production, gluconeogenesis, glycogenolysis, and glucose disappearance were measured before and during a hyperinsulinemic clamp using [6,6-(2)H2]glucose and the deuterated water method corrected for transaldolase exchange.. The study was conducted at the Mayo Clinic Clinical Research Unit.. Subjects with impaired fasting glucose (IFG)/normal glucose tolerance (NGT) (n = 14), IFG/impaired glucose tolerance (IGT) (n = 18), and normal fasting glucose (NFG)/NGT (n = 16) were studied.. A hyperinsulinemic clamp was used.. Glucose production, glucose disappearance, gluconeogenesis, and glycogenolysis were measured.. Fasting glucose production was higher (P < .0001) in subjects with IFG/NGT than in those with NFG/NGT because of increased rates of gluconeogenesis (P = .003). On the other hand, insulin-induced suppression of glucose production, gluconeogenesis, glycogenolysis, and stimulation of glucose disappearance all were normal. Although fasting glucose production also was increased (P = .0002) in subjects with IFG/IGT, insulin-induced suppression of glucose production, gluconeogenesis, and glycogenolysis and stimulation of glucose disappearance were impaired (P = .005).. Fasting hyperglycemia is due to excessive glucose production in people with either IFG/NGT or IFG/IGT. Both insulin action and postprandial glucose concentrations are normal in IFG/NGT but abnormal in IFG/IGT. This finding suggests that hepatic and extrahepatic insulin resistance causes or exacerbates postprandial glucose intolerance in IFG/IGT. Elevated gluconeogenesis in the fasting state in IFG/NGT and impaired insulin-induced suppression of both gluconeogenesis and glycogenolysis in IFG/IGT suggest that alteration in the regulation of these pathways occurs early in the evolution of type 2 diabetes.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Carbon Isotopes; Diabetes Mellitus, Type 2; Fasting; Female; Glucagon; Gluconeogenesis; Glucose Clamp Technique; Glucose Intolerance; Glycogenolysis; Humans; Hyperglycemia; Hyperinsulinism; Insulin; Liver; Male; Middle Aged; Prediabetic State

Our aim was to compare traditional C-peptide-based method and insulin-based method with standardized kinetic parameters in the estimation of prehepatic insulin secretion rate (ISR). One-hundred thirty-four subjects with varying degrees of glucose tolerance received an insulin-modified intravenous glucose tolerance test and a standard oral glucose tolerance test with measurement of plasma insulin and C-peptide. From the intravenous glucose tolerance test, we determined insulin kinetics parameters and selected standardized kinetic parameters based on mean values in a selected subgroup. We computed ISR from insulin concentration during the oral glucose tolerance test using these parameters and compared ISR with the standard C-peptide deconvolution approach. We then performed the same comparison in an independent data set (231 subjects). In the first data set, total ISRs from insulin and C-peptide were highly correlated (R(2) = 0.75, P < .0001), although on average different (103 ± 6 vs 108 ± 3 nmol, P < .001). Good correlation was also found in the second data set (R(2) = 0.54, P < .0001). The insulin method somewhat overestimated total ISR (85 ± 5 vs 67 ± 3 nmol, P = .002), in part because of differences in insulin assay. Similar results were obtained for fasting ISR. Despite the modest bias, the insulin and C-peptide methods were consistent in predicting differences between groups (eg, obese vs nonobese) and relationships with other physiological variables (eg, body mass index, insulin resistance). The insulin method estimated first-phase ISR peak similarly to the C-peptide method and better than the simple use of insulin concentration. The insulin-based ISR method compares favorably with the C-peptide approach. The method will be particularly useful in data sets lacking C-peptide to assess β-cell function through models requiring prehepatic secretion.

Topics: Adult; Algorithms; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Metabolism Disorders; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Insulin Secretion; Insulin-Secreting Cells; Kinetics; Male; Models, Statistical; Pancreatic Function Tests

Impaired growth and nutritional status in CF may be related to progressive insulin deficiency before CF-Related Diabetes has established. Aim of this study was to analyse the association of circulating insulin with nutritional status and lung function in CF patients with normal glucose tolerance (NGT).. We performed OGTT in 152 consecutive CF patients aged 8-20 years: 115 of them had NGT and were included in the study. Areas under the curves (AUC) of glucose, insulin and c-peptide after 120 min were calculated. Quartiles (Q) of increasing fasting insulin (fINS-Q) and c-peptide (fCP-Q) levels were calculated in CF patients. Respiratory function parameters (FEV1, FVC), Standard Deviation Scores (SDS) of height, weight and BMI were compared between Q1 and the three higher Q. Multiple regression analysis was used to analyse the association of fasting insulin, c-peptide or OGTT derived indices with nutritional or respiratory parameters.. Compared to patients in fINS-Q4 or fCP-Q4, those in fINS-Q1 or in fCP-Q1 respectively showed lower levels of insulin AUC or c-peptide AUC (both P < 0.0001), weight-SDS (P = 0.013, P = 0.007), BMI-SDS (P = 0.010, P = 0.002), FEV1 (P = 0.076, P = 0.013) and FVC (P = 0.101, P = 0.009). Age- and gender-adjusted regression analysis showed significant associations of fINS and fCP with SDS of BMI (P = 0.023 and P = 0.001 respectively), fCP was significant associated with FEV1 (P = 0.01). AUC insulin/AUC glucose ratio (P < 0.0001) and AUC c-peptide/AUC glucose ratio (P = 0.0001) were significantly associated with FEV1.. Insulin deficiency in CF patients with NGT has a significant impact on clinical outcomes.

Topics: Adolescent; Area Under Curve; Blood Glucose; C-Peptide; Child; Cystic Fibrosis; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Linear Models; Male; Nutritional Status; Respiration; Retrospective Studies; Young Adult

Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment.. Among 77,885 twins in the Danish Twin Registry, 155 of the most BW-discordant MZ twin pairs (median BW difference 0.5 kg) were assessed using a 2 h oral glucose tolerance test with sampling of plasma (p-)glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. HOMA for beta cell function (HOMA-β) and insulin resistance (HOMA-IR), and also insulin sensitivity index (BIGTT-SI) and acute insulin response (BIGTT-AIR), were calculated. Subgroup analyses were performed in those with: (1) double verification of BW difference; (2) difference in BW >0.5 kg; and (3) no overt metabolic disease (type 2 diabetes, hyperlipidaemia or thyroid disease).. No intra-pair differences in p-glucose, insulin, C-peptide, incretin hormones, HOMA-β, HOMA-IR or BIGTT-SI were identified. p-Glucose at 120 min was higher in the twins with the highest BW without metabolic disease, and BIGTT-AIR was higher in those with the highest BW although not in pairs with a BW difference of >0.5 kg.. BW-discordant MZ twins provide no evidence for a detrimental effect of low BW on glucose metabolism in adulthood once genetic factors and rearing environment are controlled for.

Topics: Adult; Aged; Analysis of Variance; Birth Weight; Blood Glucose; C-Peptide; Denmark; Diabetes Mellitus, Type 2; Disease Susceptibility; Female; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant, Low Birth Weight; Infant, Newborn; Insulin Resistance; Logistic Models; Male; Middle Aged; Risk Factors; Surveys and Questionnaires; Twins, Monozygotic

We aimed to analyze the shape of the glucose, insulin, and C-peptide curves during a 3-h oral glucose tolerance test (OGTT). Another aim was defining an index of shape taking into account the whole OGTT pattern. Five-hundred ninety-two OGTT curves were analyzed, mainly from women with former gestational diabetes, with glycemic concentrations characterized by normal glucose tolerance (n = 411), impaired glucose metabolism (n = 134), and Type 2 diabetes (n = 47). Glucose curves were classified according to their shape (monophasic, biphasic, triphasic, and 4/5-phases), and the metabolic condition of the subjects, divided according to the glucose shape stratification, was analyzed. Indices of shape based on the discrete second-order derivative of the curve patterns were also defined. We found that the majority of the glucose curves were monophasic (n = 262). Complex shapes were less frequent but not rare (n = 37 for the 4/5-phases shape, i.e., three peaks). There was a tendency toward the amelioration of the metabolic condition for increasing complexity of the shape, as indicated by lower glucose concentrations, improved insulin sensitivity and β-cell function. The shape index computed on C-peptide, WHOSH(CP) (WHole-Ogtt-SHape-index-C-peptide), showed a progressive increase [monophasic: 0.93 ± 0.04 (dimensionless); 4/5-phases: 1.35 ± 0.14], and it showed properties typical of β-cell function indices. We also found that the type of glucose shape is often associated to similar insulin and C-peptide shape. In conclusion, OGTT curves can be characterized by high variability, and complex OGTT shape is associated with better glucose tolerance. WHOSH(CP) (WHole-Ogtt-SHape-index) may be a powerful index of β-cell function much simpler than model-based indices.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Pregnancy; Time Factors

Laparoscopic adjustable gastric banding (LAGB) provides weight loss in obese individuals and is associated with improved glucose homeostasis and resolution of type 2 diabetes. However, in most available reports, potentially inappropriate methodology has been applied when measuring the impact of LAGB on glucose intolerance. In order to clarify the applicability of the diagnostic 75 g-oral glucose tolerance test (OGTT) to measure the effect of LAGB on glucose metabolism, we investigated the effect of LAGB on gastric emptying for liquids as well as pancreatic and incretin hormone responses.. Eight obese patients (three with normal glucose tolerance, three with impaired glucose tolerance, and two with type 2 diabetes; age 47.5 ± 1.1 years (mean±SEM); body mass index 44 ± 1 kg/m²; HbA(1)c 6.2 ± 0.4%) underwent a 75 g-oral glucose tolerance test with 1 g acetaminophen before and ~6 weeks after LAGB.. A small weight reduction was seen after LAGB (125 ± 8 vs. 121 ± 8 kg, P = 0.014). No differences in determinants of gastric emptying were observed before and after LAGB (area under the serum acetaminophen curve 10.1 ± 0.6 vs. 9.8 ± 0.5 mM x 4 h, P = 0.8; peak acetaminophen concentration 62 ± 3 vs. 61 ± 3 μM, P = 0.8; acetaminophen peak time 98 ± 6 vs. 100 ± 6 min, P = 0.9). No differences in plasma glucose, insulin, C-peptide, glucagon, glucose-dependent insulinotropic polypeptide, or glucagon-like peptide-1 responses to the OGTT were observed before as compared to after LAGB.. OGTT can be used to evaluate glucose tolerance in obese patients before and after LAGB without bias from changes in gastric emptying. LAGB has no direct impact on incretin hormone secretion.

Topics: Acetaminophen; Adult; C-Peptide; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastroplasty; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Laparoscopy; Male; Middle Aged

We evaluated the relationship between insulin resistance (IR) and insulin secretion with the metabolic syndrome (MS) in 885 subjects (377 men/508 women, age 49±11 years, BMI 29±5.2kgm(-2)) at risk of diabetes enrolled in the genetics, pathophysiology and evolution of type 2 diabetes (GENFIEV) study.. All subjects underwent a 75-g oral glucose tolerance test (OGTT) for the estimation of plasma levels of glucose and C-peptide, as well as fasting insulin and lipid profile. IR was arbitrarily defined as HOMA-IR value above the 75th centile of normal glucose tolerance (NGT) subjects. Overall MS prevalence (National Cholesterol Treatment Panel-Adult Treatment Panel (NCEP-ATPIII) criteria) was 33%, 19% in subjects with NGT, 42% in impaired fasting glucose (IFG), 34% in impaired glucose tolerance (IGT), 74% in IFG+IGT subjects, and 56% in newly diagnosed diabetic patients. Prevalence was slightly higher with IDF criteria. MS prevalence was >50% in subjects with 2h glucose >7.8mmoll(-1), independently of fasting plasma glucose. IR prevalence was higher in subjects with MS than in those without (63% vs. 23%; p<0.0001) and increased from 54% to 73% and 88% in the presence of three, four or five traits, respectively. IR occurred in 42% of subjects with non-diabetic alterations of glucose homeostasis, being the highest in those with IFG+IGT (IFG+IGT 53%, IFG 45%, IGT 38%; p<0.0001). Individuals with MS were more IR irrespective of glucose tolerance (p<0.0001) with no difference in insulinogenic index. Hypertriglyceridaemia (OR: 3.38; Confidence Interval, CI: 2.294.99), abdominal obesity (3.26; CI: 2.18-4.89), hyperglycaemia (3.02; CI: 1.80-5.07) and hypertension (1.69; CI: 1.12-2.55) were all associated with IR.. These results show that in subjects with altered glucose tolerance (in particular IFG+IGT) MS prevalence is high and is generally associated to IR. Some combinations of traits of MS may significantly contribute to identify subjects with IR.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Hypertension; Insulin Resistance; Italy; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Prediabetic State; Prevalence; Risk Factors

Cystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.. To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.. A total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.. Fifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6  pmol/min per m(2) per mM, P<0.001) and decreased significantly with age by -2.7  pmol/min per m(2) per mM per year (confidence interval (CI) -4.5 to -0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.. The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.

Topics: Adolescent; Adult; C-Peptide; Cystic Fibrosis; Diabetes Mellitus; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male

Common polymorphisms in the transcription factor 7-like 2 gene (TCF7L2) have been associated with type 2 diabetes in different populations and recently with LADA, but not with type 1 diabetes. The aim of our study was to investigate association between the rs7903146 polymorphism in the TCF7L2 gene and LADA in Polish patients. Link between the "high risk for type 2 diabetes genotype" with clinical features was analyzed. 68 newly diagnosed patients with LADA and 195 healthy controls were genotyped for the rs7903146 polymorphism in the TCF7L2 gene using the PCR-based RFLP method. Fasting C peptide level was measured by ELISA. We observed increased frequencies of the TT genotype of the rs7903146 polymorphism in the TCF7L2 gene in LADA patients compared to controls (15 vs. 6%, P = 0.03). Fasting C peptide serum concentration was significantly lower in group of patients with LADA carrying the TT genotype (P < 0.01). In conclusion, the data from this study confirmed previous results showing genetic similarities between patients with LADA and type 2 diabetes. Non-autoimmune mechanism may be related to beta cell dysfunction in patients with LADA.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; DNA Primers; Fasting; Female; Glucose Intolerance; Humans; Male; Middle Aged; Polymorphism, Genetic; Predictive Value of Tests; Reference Values; TCF Transcription Factors; Transcription Factor 7-Like 2 Protein

Diabetes mellitus (DM) affects 30% to 60% of patients with hereditary hemochromatosis (HH). The underlying pathophysiology of DM in patients with hemochromatosis has not been fully elucidated. We studied both insulin secretion and insulin sensitivity in a cohort of patients with HH. We studied glucose metabolism in 53 newly diagnosed HH patients using a standard 75-g oral glucose tolerance test. Basal and stimulated insulin sensitivities were calculated using the quantitative insulin sensitivity check index and oral glucose insulin sensitivity index, respectively. beta-Cell function was assessed using C-peptide concentrations during the oral glucose tolerance test after adjusting for ambient insulin sensitivity. Twenty healthy subjects served as the control group. Fifteen subjects (28%) with HH had abnormal glucose tolerance (AGT). Seven (13%) had DM, and 8 (15%) had impaired glucose tolerance. As well as higher fasting glucose and glycated hemoglobin, those with AGT had a higher fasting insulin and C-peptide levels compared with those with normal glucose tolerance (NGT) (all Ps < .05). Insulin sensitivity measurements showed that the subjects in HH group with AGT were more insulin resistant than the subjects with NGT and controls subjects (P < .05). No significant changes were observed between the groups with NGT and AGT regarding hepatic insulin extraction and both indices related to insulin release in subjects with HH. Our cohort of patients with hemochromatosis and AGT had features similar to typical type 2 DM patients. These findings challenge the traditional view that DM in hemochromatosis is due primarily to iron-induced beta-cell failure.

Topics: Adult; Aged; Anthropometry; Area Under Curve; Blood Glucose; C-Peptide; Female; Glucose; Glucose Intolerance; Glucose Tolerance Test; Hemochromatosis; Humans; Ireland; Iron Overload; Male; Middle Aged; Pancreatic Function Tests; Prospective Studies

Relatives of type 1 diabetic patients are at enhanced risk of developing diabetes. We investigated the mode of onset of hyperglycemia and how insulin sensitivity and beta-cell function contribute to the progression to the disease.. In 328 islet cell autoantibody-positive, nondiabetic relatives from the observational arms of the Diabetes Prevention Trial-1 Study (median age 11 years [interquartile range 8], sequential OGTTs (2,143 in total) were performed at baseline, every 6 months, and 2.7 years [2.7] later, when 115 subjects became diabetic. Beta-cell glucose sensitivity (slope of the insulin-secretion/plasma glucose dose-response function) and insulin sensitivity were obtained by mathematical modeling of the OGTT glucose/C-peptide responses.. In progressors, baseline insulin sensitivity, fasting insulin secretion, and total postglucose insulin output were similar to those of nonprogressors, whereas beta-cell glucose sensitivity was impaired (median 48 pmol/min per m2 per mmol/l [interquartile range 36] vs. 87 pmol/min per m2 per mmol/l [67]; P < 0.0001) and predicted incident diabetes (P < 0.0001) independently of sex, age, BMI, and clinical risk. In progressors, 2-h glucose levels changed little until 0.78 years before diagnosis, when they started to rise rapidly (approximately 13 mmol x l(-1) x year(-1)); glucose sensitivity began to decline significantly (P < 0.0001) earlier (1.45 years before diagnosis) than the plasma glucose surge. During this anticipation phase, both insulin secretion and insulin sensitivity were essentially stable.. In high-risk relatives, beta-cell glucose sensitivity is impaired and is a strong predictor of diabetes progression. The time trajectories of plasma glucose are frequently biphasic, with a slow linear increase followed by a rapid surge, and are anticipated by a further deterioration of beta-cell glucose sensitivity.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Disease Progression; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Kaplan-Meier Estimate; Male; Models, Biological; Predictive Value of Tests; Risk Factors

The pathogenesis of type 2 diabetes is characterized by insulin resistance and beta-cell dysfunction. Pancreatic fat load may add to the development of beta-cell dysfunction. The aim was to thoroughly quantify the fat content of pancreas sections (caput, corpus, and cauda) and to compare the impact of pancreatic, intrahepatic, and visceral fat on insulin secretion in humans.. Fifty-one subjects were subjected to an oral glucose tolerance test (OGTT) with glucose, insulin, and C-peptide measurements [28 subjects displayed normal glucose tolerance, 23 impaired fasting glycemia (IFG)] and/or impaired glucose tolerance (IGT)], and also to whole-body magnetic resonance imaging (MRI), pancreas MRI, and liver magnetic resonance spectroscopy (MRS).. After adjustment for gender and age, the mean pancreatic fat content was positively associated with body mass index (BMI), visceral adipose tissue (VAT), and waist circumference (all p < or = 0.0013). The mean pancreatic fat content was negatively associated with OGTT-based measures of insulin secretion (all p < or = 0.03). Analysis of the subgroups of glucose tolerance showed that this was restricted to subjects with IGT and/or IFG. Visceral fat also represented a determinant of beta-cell function in individuals with IGT and/or IFG (all p < or = 0.02), whereas intrahepatic fat did not. In a stepwise multivariate regression analysis, pancreatic fat turned out to be a stronger determinant of impaired insulin secretion than visceral fat.. Pancreatic fat is negatively associated with insulin secretion in subjects with IGT/IFG and, therefore, might represent an additional pathogenetic factor leading to beta-cell dysfunction.

Topics: Adipose Tissue; Area Under Curve; Blood Glucose; C-Peptide; Fasting; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Intra-Abdominal Fat; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Pancreas; Regression Analysis; Waist Circumference

It is commonly thought that hyperglycaemia results from insufficient compensation of insulin secretion for insulin resistance. To verify this hypothesis, we assessed beta cell function and insulin sensitivity (IS) in a large cohort of volunteers with normal glucose tolerance (NGT) or impaired glucose regulation (IGR), i.e. impaired glucose tolerance or impaired fasting glucose.. In men and women with NGT (n=1,123) or IGR(n=156) (age 44 +/- 8 years, BMI 25+/-4 kg/m2, mean +/- SD)we measured: (1) IS by clamp; (2) insulin secretion rates(ISR) and beta cell glucose sensitivity (=slope of the insulin secretion/plasma glucose dose-response) by C-peptide deconvolution and OGTT modelling; and (3) acute insulin response to intravenous glucose.. After controlling for centre, sex, age and BMI, fasting and total ISR were inversely related to IS in both groups,whereas beta cell glucose sensitivity was not. Acute insulin response was reciprocally related to IS in both groups, but the relationships were incompatible with inadequate compensation and significance was lost after controlling for fasting ISR. InIGR vs NGT, IS was impaired (92 [75] vs 133 [86] micromol min(-1)[kg fat-free mass](-1) [nmol/l](-1), median [interquartile range],p<0.0001) as was beta cell glucose sensitivity (69 [46] vs 119[83] pmol min(-1) m(-2) [nmol/l](-1), p<0.0001), whereas fasting and total ISR were increased (35% and 25%, respectively, p<0.0001). In fully adjusted models, beta cell glucose sensitivity was the strongest determinant of OGTT glucose levels.. Insulin resistance normally upregulates the secretory tone, with no evidence of defective compensation in IGR. In contrast, beta cell glucose sensitivity is independent of insulin resistance, but a key determinant of glucose tolerance. This suggests that hyperglycaemia results from an intrinsic beta cell defect rather than from inadequate compensation for insulin resistance.

Topics: Adult; Blood Glucose; C-Peptide; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Patch-Clamp Techniques

The mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) pathway is a critical signaling component in the development of obesity-linked insulin resistance and operates a nutrient-sensing negative feedback loop toward the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway. Whereas acute treatment of insulin target cells with the mTOR complex 1 (mTORC1) inhibitor rapamycin prevents nutrient-induced insulin resistance, the chronic effect of rapamycin on insulin sensitivity and glucose metabolism in vivo remains elusive.. To assess the metabolic effects of chronic inhibition of the mTORC1/S6K1 pathway, rats were treated with rapamycin (2 mg/kg/day) or vehicle for 15 days before metabolic phenotyping.. Chronic rapamycin treatment reduced adiposity and fat cell number, which was associated with a coordinated downregulation of genes involved in both lipid uptake and output. Rapamycin treatment also promoted insulin resistance, severe glucose intolerance, and increased gluconeogenesis. The latter was associated with elevated expression of hepatic gluconeogenic master genes, PEPCK and G6Pase, and increased expression of the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) as well as enhanced nuclear recruitment of FoxO1, CRTC2, and CREB. These changes were observed despite normal activation of the insulin receptor substrate/PI 3-kinase/Akt axis in liver of rapamycin-treated rats, as expected from the blockade of the mTORC1/S6K1 negative feedback loop.. These findings unravel a novel mechanism by which mTORC1/S6K1 controls gluconeogenesis through modulation of several key transcriptional factors. The robust induction of the gluconeogenic program in liver of rapamycin-treated rats underlies the development of severe glucose intolerance even in the face of preserved hepatic insulin signaling to Akt and despite a modest reduction in adiposity.

Topics: Adipocytes; Adipose Tissue; Animals; Blood Glucose; C-Peptide; Down-Regulation; Fatty Acids, Nonesterified; Glucagon; Glucose Intolerance; Hyperlipidemias; Immunosuppressive Agents; Insulin; Liver; Male; Mice; Muscle, Skeletal; Polymerase Chain Reaction; Pyruvates; Rats; Rats, Sprague-Dawley; RNA; Sirolimus; Triglycerides

Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production. After TIPS, BCM increased by 4.8 kg [confidence interval (CI): 2.7-7.3]. Fasting (f)-insulin increased from 123 +/- 81 to 193 +/- 124 pmol/l (P = 0.03), whereas f-glucose was unchanged (6.0 +/- 0.8 vs. 6.2 +/- 1.0 mmol/l). Glucose and insulin oral glucose tolerance test area under the curve increased by 14% (CI: 7-22%) and 53% (CI: 14-90%), respectively, P < 0.05. The C-peptide-to-insulin ratio decreased by 21% (CI: 8-35%, P = 0.01). Insulin sensitivity based on glucose infusion rate (4.69 +/- 1.82 vs. 4.85 +/- 2.37 mg.kg(-1).min(-1)) and glucose tracer-based rate of disappearance were unchanged (5.01 +/- 1.61 vs. 4.97 +/- 2.13 mg.kg(-1).min(-1)). Despite a further increase in peripheral hyperinsulinemia, f-endogenous glucose production did not change between study days (2.01 +/- 0.42 vs. 2.42 +/- 0.58 mg.kg(-1).min(-1)) and was suppressed equally by insulin (1.1 +/- 0.1 vs. 1.0 +/- 0.1 mg.kg(-1).min(-1)). Insulin clearance, growth hormone, cortisol, and glucagon levels were unchanged. BCM improvement did not correlate with the measured variables. After TIPS, BCM rose, despite enhanced hyperinsulinemia and aggravated glucose intolerance, but unchanged peripheral and hepatic insulin sensitivity. This apparent discrepancy may be ascribed to shunt-related decreased insulin exposure to the liver cells. However, the anabolic effect of TIPS seems not to be related to improvements in insulin sensitivity and remains mechanistically unexplained.

Topics: Body Composition; C-Peptide; Diabetes Mellitus; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glucagon; Glucose; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Liver; Liver Cirrhosis; Male; Middle Aged; Portasystemic Shunt, Transjugular Intrahepatic; Predictive Value of Tests; Rest

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

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

Disturbances in glucose metabolism are of importance for violent behaviour in men, but studies in women are lacking. We used the 5h-oral glucose tolerance test (OGTT) in this study of 17 female psychiatric patients, selected for violent behaviour directed against themselves (deliberate self-harm) and 17 healthy controls matched for age and BMI. Following OGTT, patients had higher glucose levels at 30 min (p=0.007) and increased glucagon area under the curve (p=0.011). Since a co-morbid eating disorder might affect results, we as a post-hoc analysis subgrouped the patients and found that the increased glucagon levels only were present in patients with an eating disorder. In contrast, those without an eating disorder showed a significantly lower p-glucose nadir (p=0.015) and unaltered glucagon levels compared to controls. There were no significant differences in insulin and C-peptide levels between patients and controls. We conclude that deliberate self-harm in women may be associated with alterations in carbohydrate metabolism in certain groups. Eating disorder is a confounding factor.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Comorbidity; Feeding and Eating Disorders; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Self-Injurious Behavior; Young Adult

Recently, variants in WFS1 have been shown to be associated with type 2 diabetes. We aimed to examine metabolic risk phenotypes of WFS1 variants in glucose-tolerant people and in individuals with abnormal glucose regulation.. The type 2 diabetes-associated WFS1 variant rs734312 (His611Arg) was studied in the population-based Inter99 cohort involving 4,568 glucose-tolerant individuals and 1,471 individuals with treatment-naive abnormal glucose regulation, and in an additional 3,733 treated type 2 diabetes patients.. The WFS1 rs734312 showed a borderline significant association with type 2 diabetes with directions and relative risks consistent with previous reports. In individuals with abnormal glucose regulation, the diabetogenic risk A allele of rs734312 was associated in an allele-dependent manner with a decrease in insulinogenic index (p = 0.025) and decreased 30-min serum insulin levels (p = 0.047) after an oral glucose load. In glucose-tolerant individuals the same allele was associated with increased fasting serum insulin concentration (p = 0.019) and homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.026). To study the complex interaction of WFS1 rs734312 on insulin release and insulin resistance we introduced Hotelling's T (2) test. Assuming bivariate normal distribution, we constructed standard error ellipses of the insulinogenic index and HOMA-IR when stratified according to glucose tolerance status around the means of each WFS1 rs734312 genotype level. The interaction term between individuals with normal glucose tolerance and abnormal glucose regulation on the insulinogenic index and HOMA-IR was significantly associated with the traits (p = 0.0017).. Type 2 diabetes-associated risk alleles of WFS1 are associated with estimates of a decreased pancreatic beta cell function among middle-aged individuals with abnormal glucose regulation.

Topics: Blood Glucose; C-Peptide; Denmark; Diabetes Mellitus, Type 2; Gene Frequency; Genotype; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin-Secreting Cells; Membrane Proteins; Middle Aged; Polymorphism, Genetic; Prediabetic State; Reference Values

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

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

The impact of strategies for prevention of type 2 diabetes in isolated impaired fasting glycaemia (i-IFG) vs isolated impaired glucose tolerance (i-IGT) may differ depending on the underlying pathophysiology. We examined insulin secretion during OGTTs and IVGTTs, hepatic and peripheral insulin action, and glucagon and incretin hormone secretion in individuals with i-IFG (n = 18), i-IGT (n = 28) and normal glucose tolerance (NGT, n = 20).. Glucose tolerance status was confirmed by a repeated OGTT, during which circulating insulin, glucagon, glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels were measured. A euglycaemic-hyperinsulinaemic clamp with [3-3H]glucose preceded by an IVGTT was performed.. Absolute first-phase insulin secretion during IVGTT was decreased in i-IFG (p = 0.026), but not in i-IGT (p = 0.892) compared with NGT. Hepatic insulin sensitivity was normal in i-IFG and i-IGT individuals (p > or = 0.179). Individuals with i-IGT had peripheral insulin resistance (p = 0.003 vs NGT), and consequently the disposition index (DI; insulin secretion x insulin sensitivity) during IVGTT (DI(IVGTT))) was reduced in both i-IFG and i-IGT (p < 0.005 vs NGT). In contrast, the DI during OGTT (DI(OGTT)) was decreased only in i-IGT (p < 0.001), but not in i-IFG (p = 0.143) compared with NGT. Decreased levels of GIP in i-IGT (p = 0.045 vs NGT) vs increased levels of GLP-1 in i-IFG (p = 0.013 vs NGT) during the OGTT may partially explain these discrepancies. Basal and post-load glucagon levels were significantly increased in both i-IFG and i-IGT individuals (p < or = 0.001 vs NGT).. We propose that differentiated preventive initiatives in prediabetic individuals should be tested, targeting the specific underlying metabolic defects.

Topics: Blood Glucose; Body Composition; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Gastric Inhibitory Polypeptide; Glucagon-Secreting Cells; Glucose Intolerance; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin-Secreting Cells; Myocardial Ischemia; Prediabetic State

We assessed the extent to which both standard and alternative indexes from 2-h oral glucose tolerance testing predict type 1 diabetes and whether oral glucose tolerance tests (OGTTs) predict type 1 diabetes in individuals with normal glucose tolerance.. The prediction of type 1 diabetes from baseline OGTTs was studied in 704 Diabetes Prevention Trial-Type 1 participants (islet-cell autoantibody [ICA]-positive relatives of type 1 diabetic patients). The maximum follow-up was 7.4 years. Analyses utilized receiver-operator curves (ROCs), proportional hazards models, and survival curves.. ROC areas under the curve (ROCAUCs) for both the AUC glucose (0.73 +/- 0.02) and an OGTT prediction index (0.78 +/- 0.02) were higher (P < 0.001) than those for the fasting (0.53 +/- 0.02) and 2-h glucose (0.66 +/- 0.02). ROCAUCs for the 60- and 90-min glucose (0.71 +/- 0.02 and 0.72 +/- 0.02, respectively) were also higher (P < 0.01) than those for the fasting and 2-h glucose. Among individuals with normal glucose tolerance, OGTTs were highly predictive, with 4th versus 1st quartile hazard ratios for the 2-h glucose, AUC glucose, and OGTT prediction index ranging from 3.77 to 5.30 (P < 0.001 for all).. Certain alternative OGTT indexes appear to better predict type 1 diabetes than standard OGTT indexes in ICA-positive relatives of type 1 diabetic patients. Moreover, even among those with normal glucose tolerance, OGTTs are strongly predictive. This suggests that subtle metabolic abnormalities are present several years before the diagnosis of type 1 diabetes.

Topics: Area Under Curve; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Predictive Value of Tests; Proportional Hazards Models; Reference Values; Reproducibility of Results; Risk Assessment; ROC Curve; Sensitivity and Specificity; Time Factors

To assess the beta-cell function in individuals with mitochondrial DNA A3243G mutation with normal glucose tolerance (NGT) or diabetes mellitus (DM). Furthermore, in diabetic individuals, we evaluated the effect of coenzyme Q10 supplementation on insulin secretory response.. Eight mutation-positive individuals with NGT (n = 4) or DM (n = 4) were studied. beta-Cell function was evaluated by C-peptide levels before and after a mixed liquid meal (Sustacal) challenge and by first-phase insulin response.. Fasting and Sustacal-stimulated C-peptide levels were significantly lower in diabetic patients than that in controls (area under the curve: 104.1 +/- 75.7 vs 520.8 +/- 173.8, P = 0.001), whereas in individuals with NGT, this response was preserved (area under the curve: 537.8 +/- 74.3 vs 520.8 +/- 179.8, P = 0.87). The duration of diabetes was negatively correlated with fasting C-peptide levels (r = -0.961, P = 0.038). Among the 3 patients with residual insulin secretion, the short-term treatment with coenzyme Q10 (3 months) improved C-peptide levels in 2 of them. The first-phase insulin response was diminished in 2 individuals with NGT, the oldest ones.. We showed an impaired insulin secretory capacity in individuals carrying the A3243G mutation, this possibly being the primary defect contributing to the development of DM. In addition, our data suggest that this could be a functional defect.

Topics: Adult; C-Peptide; Coenzymes; Diabetes Mellitus; DNA, Mitochondrial; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Male; Pedigree; Point Mutation; RNA, Transfer, Leu; Ubiquinone; Vitamins

To determine the contribution of hepatic insulin resistance to the pathogenesis of impaired fasting glucose (IFG).. Endogenous glucose production (EGP) and glucose disposal were measured in 31 subjects with IFG and 28 subjects with normal fasting glucose (NFG) after an overnight fast and during a clamp when endogenous secretion was inhibited with somatostatin and insulin infused at rates that approximated portal insulin concentrations present in IFG subjects after an overnight fast (approximately 80 pmol/l, "preprandial") or within 30 min of eating (approximately 300 pmol/l, "prandial").. Despite higher (P < 0.001) insulin and C-peptide concentrations and visceral fat (P < 0.05), fasting EGP and glucose disposal did not differ between IFG and NFG subjects, implying hepatic and extrahepatic insulin resistance. This was confirmed during preprandial insulin infusion when glucose disposal was lower (P < 0.05) and EGP higher (P < 0.05) in IFG than in NFG subjects. Higher EGP was due to increased (P < 0.05) rates of gluconeogenesis in IFG. EGP was comparably suppressed in IFG and NFG groups during prandial insulin infusion, indicating that hepatic insulin resistance was mild. Glucose disposal remained lower (P < 0.01) in IFG than in NFG subjects.. Hepatic and extrahepatic insulin resistance contribute to fasting hyperglycemia in IFG with the former being due at least in part to impaired insulin-induced suppression of gluconeogenesis. However, since hepatic insulin resistance is mild and near-maximal suppression of EGP occurs at portal insulin concentrations typically present in IFG subjects within 30 min of eating, extrahepatic (but not hepatic) insulin resistance coupled with accompanying defects in insulin secretion is the primary cause of postprandial hyperglycemia.

Topics: Adipose Tissue; Blood Glucose; Body Mass Index; C-Peptide; Fasting; Female; Glucagon; Gluconeogenesis; Glucose Intolerance; Humans; Hyperglycemia; Insulin Resistance; Liver; Male; Middle Aged; Reference Values

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

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

Although acute alkaloid caffeine (CAF) ingestion results in an impaired glucose tolerance, chronic coffee (RCOF) ingestion decreases the risk of developing type 2 diabetes. This study examines the hypothesis that CAF ingestion impairs glucose tolerance to a greater extent than RCOF and that the ingestion of decaffeinated coffee (DECAF) results in a positive effect. Eleven healthy males underwent 4 double-blinded randomized trials. Each trial included the ingestion of either: 1) CAF in capsule form (4.45 mg/kg body weight), 2) RCOF (4.45 mg/kg body weight caffeine), 3) dextrose (placebo, PL) in capsule form, or 4) DECAF (equal in volume to the RCOF trial), followed 1-h later by a 2-h oral glucose tolerance test. Blood samples were collected at baseline (-30), 0 (time of treatment ingestion), 60 (initiation of oral glucose tolerance test), 75, 90, 120, 150, and 180 min. Area under the curve for glucose and insulin were higher (P < or = 0.05) following CAF than both PL and DECAF and, although a similar trend (P = 0.07) was observed following RCOF compared with DECAF, the effect was less pronounced. Interestingly, DECAF resulted in a 50% lower glucose response (P < or = 0.05) than PL, suggesting that the effects of PL and DECAF on glucose tolerance are not the same. These findings suggest that the effects of CAF and RCOF are not identical and may provide a partial explanation as to why acute CAF ingestion impairs glucose tolerance while chronic RCOF ingestion protects against type 2 diabetes.

Topics: Alkaloids; Blood Glucose; C-Peptide; Caffeine; Coffee; Epinephrine; Fatty Acids, Nonesterified; Glucose Intolerance; Humans; Insulin; Kinetics; Male; Xanthines

Some studies have found that people with type 2 diabetes mellitus are at increased risk of neoplasms, especially colorectal cancer (CRC). In other studies it is also suggested that there is a higher incidence of diabetes mellitus in patients with CRC. The aims of this study were to assess whether the incidence of type 2 diabetes mellitus and impaired glucose tolerance (IGT) are higher in subjects with CRC and to determine the difference between diabetic subjects and healthy controls regarding glucose metabolism (glycaemia, insulinaemia, serum levels of C-peptide) as well as insulin resistance and sensitivity.. The study included a total of 80 subjects: 40 enrolled patients (20 M, 20 F) with newly diagnosed sporadic colorectal cancer and 40 subjects with endoscopically excluded CRC or adenomas serving as controls. Subjects were matched for gender, age and body mass index (BMI) (age +/- 5 years BMI +/- 1 kg/m2). A 75-g oral glucose tolerance test was performed after an overnight fast. Samples for glycaemia, serum levels of C-peptide and insulin were taken at 0, 30, 60, 90, 120 and 150 min of the study. HOMA-IR, EIR, EIR/HOMA-IR indexes were calculated.. There was a significantly higher incidence of impaired glucose metabolism (IGM-diabetes mellitus or IGT) in CRC subjects. No differences were found in levels of glucose, insulin or C-peptide. Insulinaemia and C-peptide curves showed a shift typical of diabetes, in the form of a delayed insulin release peak. The HOMA-IR, EIR as well as the EIR/HOMA-IR indexes showed no differences between groups.. A significantly higher incidence of IGM appears to occur in CRC patients than in the healthy population. This phenomenon is not dependent on age and body-weight, which may suggest that it is cancer that predisposes to diabetes rather than the other way round. The neoplastic process in the colon is not associated with hyperinsulinaemia or insulin resistance, but in CRC patients, pancreatic B-cell dysfunction typical of the early stages of diabetes is seen.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; C-Peptide; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Prevalence; Prognosis; Retrospective Studies; Risk Factors

Thirty-two subjects with impaired fasting glucose (IFG) and 28 subjects with normal fasting glucose (NFG) ingested a labeled meal and 75 g glucose (oral glucose tolerance test) on separate occasions. Fasting glucose, insulin, and C-peptide were higher (P < 0.05) in subjects with IFG than in those with NFG, whereas endogenous glucose production (EGP) did not differ, indicating hepatic insulin resistance. EGP was promptly suppressed, and meal glucose appearance comparably increased following meal ingestion in both groups. In contrast, glucose disappearance (R(d)) immediately after meal ingestion was lower (P < 0.001) in subjects with IFG/impaired glucose tolerance (IGT) and IFG/diabetes but did not differ in subjects with IFG/normal glucose tolerance (NGT) or NFG/NGT. Net insulin action (S(i)) and insulin-stimulated glucose disposal (S(i)*) were reduced (P < 0.001, ANOVA) in subjects with NFG/IGT, IFG/IGT, and IFG/diabetes but did not differ in subjects with NFG/NGT or IFG/NGT. Defective insulin secretion also contributed to lower postprandial R(d) since disposition indexes were lower (P < 0.001, ANOVA) in subjects with NFG/IGT, IFG/IGT, and IFG/diabetes but did not differ in subjects with NFG/NGT and IFG/NGT. We conclude that postprandial hyperglycemia in individuals with early diabetes is due to lower rates of glucose disappearance rather than increased meal appearance or impaired suppression of EGP, regardless of their fasting glucose. In contrast, insulin secretion, action, and the pattern of postprandial turnover are essentially normal in individuals with isolated IFG.

Topics: Blood Glucose; C-Peptide; Fasting; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Secretion; Kinetics; Male; Middle Aged; Postprandial Period; Prediabetic State; Reference Values

To investigate early secretory defects in prediabetes, we evaluated beta-Cell function and insulin sensitivity (M value, by euglycemic clamp) in 26 normotolerant first-degree relatives of type 2 diabetic patients (FDR) and 17 age- and weight-matched control subjects. beta-Cell function was assessed by modeling analysis of glucose and C-peptide concentrations measured during 24 h of standardized living conditions. Fasting and total insulin secretion (ISR) were increased in FDR, as was ISR at a reference 5 mM glucose level (ISR5, 107 +/- 6 vs. 87 +/- 6 pmol x min(-1) x m(-2), P < 0.05). ISR5 was inversely related to M in controls (ISR5 = k/M1.23, rho = -0.74, P < 0.005) but not in FDR; when M was accounted for (by calculating a compensation index ISR5 x M1.23), compensation for insulin resistance was impaired in FDR (10.8 +/- 1.0 vs. 13.4 +/- 0.6 units, P < 0.05). Potentiation of ISR, expressing relative transient increases in glucose-stimulated ISR during meals, was impaired in FDR (1.29 +/- 0.08 vs. 1.62 +/- 0.08 during 1st meal, P < 0.02). Moreover, the potentiation time course was related to glucose-dependent insulin-releasing polypeptide (GIP) concentrations in both groups, and the sensitivity of potentiation to GIP derived from this relationship tended to be impaired in FDR. Compensation index, potentiation, and sensitivity to GIP were interrelated parameters (P < 0.05 or less). beta-Cell function parameters were also related to mean 24-h glucose levels (r2 = 0.63, P < 0.0001, multivariate model). In conclusion, although in absolute terms ISR is increased in insulin-resistant FDR, beta-cell function shows a cluster of interrelated abnormalities involving compensation for insulin resistance, potentiation, and sensitivity to GIP, suggesting a beta-cell defect in the amplifying pathway of insulin secretion.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diet; Energy Intake; Family; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Clamp Technique; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Linear Models; Male; Models, Biological; Multivariate Analysis; Peptide Fragments; Protein Precursors

We investigated whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are major regulators of glucose tolerance through the stimulation of insulin secretion, contribute to impaired glucose tolerance (IGT) among HIV-infected patients on highly active antiretroviral therapy (HAART).. Eighteen HIV-infected male patients (six lipodystrophic and 12 nonlipodystrophic) with normal glucose tolerance (NGT) were compared with 10 HIV-infected male patients (eight lipodystrophic and two nonlipodystrophic) with IGT. Plasma concentrations of GLP-1 and GIP were determined frequently during a 3-h, 75-g glucose tolerance test. Insulin secretion rates (ISRs) were calculated by deconvolution of C-peptide concentrations.. The incremental area under the curve (incrAUC) for GLP-1 was increased by 250% in IGT patients compared with NGT patients (1455+/-422 vs. 409+/-254 pmol/L/180 min, respectively; P<0.05), whereas the incrAUC for GIP did not differ between the study groups (7689+/-1097 vs. 8041+/-998 pmol/L/180 min, respectively; not significant). In pooled study groups, the GIP incrAUC correlated positively with the ISR incrAUC without adjustment (r=0.38, P<0.05) and following adjustment for glucose incrAUC (r=0.49, P<0.01).. Our data suggest: (1) that glucose-intolerant, HIV-infected male patients may display enhanced GLP-1 responses to oral glucose compared with normal glucose-tolerant HIV-infected male patients, which may represent a compensatory mechanism rather than explain the IGT; (2) that the GIP response may be associated with ISR independently of plasma glucose in nondiabetic HIV-infected males on HAART.

Topics: Adult; Analysis of Variance; Antiretroviral Therapy, Highly Active; Antiviral Agents; Area Under Curve; Blood Glucose; Body Composition; C-Peptide; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose; Glucose Intolerance; Glucose Tolerance Test; HIV Infections; HIV-Associated Lipodystrophy Syndrome; Humans; Male; Peptide Fragments; Protein Precursors

An oral glucose tolerance test (OGTT) was performed in 103 patients with Turner syndrome (TS) who had normal fasting and postprandial glucose levels. The plasma glucose, insulin, C-peptide and proinsulin levels were measured every 30 min during the test. Using a homeostatic model assessment (HOMA) and a quantitative insulin sensitivity check index (QUICKI), the insulin resistance in TS patients was investigated. Diabetes mellitus and impaired glucose tolerance (IGT) were newly diagnosed in two and 18 patients respectively. There was a significant increase in mean plasma glucose, insulin, C-peptide and proinsulin response during an OGTT in the IGT group in contrast to the normal glucose tolerance (NGT) group ( P < 0.05). There was a significant decrease in the quantitative insulin sensitivity check index (QUICKI) in the IGT group in contrast to the NGT group ( P < 0.05). The fasting insulin and triglyceride levels strongly predicted the 2 h glucose level during the OGTT ( P < 0.05).. The oral glucose tolerance test is superior to the fasting and postprandial plasma glucose test for the early detection of abnormalities of carbohydrate metabolism in patients with Turner syndrome.

Topics: Adolescent; Adult; C-Peptide; Child; Child, Preschool; Comorbidity; Glucose; Glucose Intolerance; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Proinsulin; Risk Factors; Turner Syndrome

Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, betaSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the betaSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in betaSSTR5Kd mice pancreata. In addition, betaSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in betaSSTR5Kd mice. Further studies of betaSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.

Topics: Animals; C-Peptide; Chimera; Gene Expression Regulation; Glucose; Glucose Intolerance; Homeostasis; Insulin; Insulin Secretion; Islets of Langerhans; Mice; Receptors, Somatostatin; Somatostatin

Preferential visceral adipose tissue (VAT) accumulation has been clearly associated with insulin resistance. In contrast, the impact of visceral obesity on beta cell function is controversial.. In 62 non-diabetic women and men (age 24-69 years, BMI 21-39 kg/m2), we measured VAT and subcutaneous adipose tissue (SAT) fat mass by magnetic resonance imaging. We also measured insulin secretion and beta cell function by C-peptide deconvolution and physiological modelling of data from a frequently sampled, 75-g, 3-h OGTT, respectively.. VAT (range 0.1-3.1 kg) was strongly related to sex, age and BMI; SAT was related to sex and BMI. Controlling for sex, age, BMI and SAT by multivariate analysis, excess VAT was associated with a clinical phenotype comprising higher plasma glucose levels, BP, heart rate and serum transaminases. The corresponding metabolic phenotype consisted of insulin resistance (partial r=-0.38) and hyperinsulinaemia (partial r=0.29). The latter, however, was appropriate for the degree of insulin resistance regardless of obesity and abdominal fat distribution. Moreover, none of the model-derived parameters describing beta cell function (glucose sensitivity, rate sensitivity and potentiation) was independently associated with excess VAT.. In non-diabetic Caucasian adults of either sex, preferential visceral fat deposition in itself is part of an insulin-resistant phenotype. The insulin secretory response to a physiological challenge is increased to fully compensate for the insulin resistance, but the dynamics of beta cell function (glucose sensitivity, rate sensitivity and potentiation) are largely preserved.

Topics: Adipose Tissue; Adult; Anthropometry; Area Under Curve; Body Weight; C-Peptide; Female; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Lipids; Magnetic Resonance Imaging; Male; Models, Biological; Pancreatic Function Tests; Phenotype

Subjects with impaired glucose tolerance (IGT) are usually overweight and exhibit insulin resistance with a defective compensation of insulin secretion. In this study, we sought to establish the interrelation between insulin secretion and insulin sensitivity after oral glucose in non-obese subjects with IGT and we also examined this interrelation in relation to the 2 main incretins, glucagon-like peptide (GLP-1) and gastric inhibitory polypeptide (GIP). To that end, 13 women with IGT and 17 women with normal glucose tolerance (NGT) underwent an oral glucose tolerance test (OGTT) with measurements of glucose, insulin, C-peptide, GLP-1, and GIP. Insulin secretion (TIS) and insulin sensitivity (OGIS) were assessed using models describing the relationship between glucose, insulin and C-peptide data. These models allowed estimation also of the hepatic extraction of insulin. The age (54.2 +/- 9.7 [mean +/- SD] years) and body mass index (BMI; 26.0 +/- 4.0 kg/m(2)) did not differ between the groups. Subjects with IGT displayed lower TIS during the initial 30 minutes after oral glucose (0.97 +/- 0.17 [mean +/- SEM] v 1.75 +/- 0.23 nmol/L in NGT; P =.018) and lower OGIS (397 +/- 21 v 463 +/- 12 mL/min/m(2); P =.005). The incremental 30-minute TIS times OGIS (reflecting insulin secretion in relation to insulin sensitivity) was significantly reduced in IGT (359 +/- 51 v 774 +/- 91 nmol/min/m(2), P =.001). This measure correlated inversely to the 2-hour glucose level (r = -0.71; P <.001). In contrast, TIS over the whole 180-minute period was higher in IGT (26.2 +/- 2.4 v 20.0 +/- 2.0 nmol/L; P =.035). Hepatic insulin extraction correlated linearly with OGIS (r = 0.71; P <.001), but was not significantly different between the groups although there was a trend with lower extraction in IGT (P =.055). Plasma levels of GLP-1 and GIP increased after oral glucose. Total secretion of these incretin hormones during the 3-hour test did not differ between the 2 groups. However, the 30-minute increase in GLP-1 concentrations was lower in IGT than in NGT (P =.036). We conclude that also in non-obese subjects with IGT, when adiposity is controlled for in relation to NGT, defective early insulin secretion after oral glucose is a key factor. This defective beta-cell function is associated with, and may be caused by, a reduced early GLP-1 response.

Topics: Administration, Oral; Area Under Curve; Blood Glucose; Body Weight; C-Peptide; Case-Control Studies; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Liver; Middle Aged; Peptide Fragments; Protein Precursors; Regression Analysis; Time Factors

Impaired glucose tolerance (IGT) is associated with an increased cardiovascular disease risk. Less is known about cardiovascular disease risk among subjects with impaired fasting glucose (IFG) or with combined IFG and IGT.. To compare body composition, body fat distribution, plasma glucose-insulin homeostasis and plasma lipid-lipoprotein profile between pre-menopausal women having either a normal glucose tolerance (NGT), isolated IFG, isolated IGT or combined IFG and IGT.. Three hundred and thirty-four women with NGT, 11 women with IFG, 35 women with IGT and 10 women with both IFG and IGT were studied.. Women with IFG were characterized by a higher visceral adipose tissue (AT) accumulation than women with NGT (P < 0.05). Also, they were characterized by a higher subcutaneous AT area and by higher body fat mass than NGT and IGT women (P < 0.05). However, their lipid-lipoprotein profile was comparable with that of NGT women, except for reduced HDL-cholesterol concentrations (P < 0.05). After adjustment for visceral AT, women with IFG had lower total cholesterol, LDL-cholesterol and apolipoprotein B (apoB) levels than the three other groups. They also had lower HDL(2)-cholesterol than NGT women and lower total cholesterol/HDL-cholesterol ratio than IGT women. Women with IGT showed higher triglyceride and apoB concentrations and a higher total cholesterol/HDL-cholesterol ratio than women with NGT (P < 0.05). Overall, women with combined IFG and IGT showed body fatness characteristics and alterations in their metabolic risk profile which were essentially similar to women with isolated IGT.. These results indicate that there are significant differences in anthropometric and metabolic variables between pre-menopausal women with IFG vs. IGT and that the association between body fatness-body fat distribution indices and the metabolic profile may differ between IFG and IGT women.

Topics: Adolescent; Adult; Anthropometry; Blood Glucose; C-Peptide; Cardiovascular Diseases; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Middle Aged; Premenopause; Risk Factors

The role of gut-derived incretin, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory peptide [GIP]), in compensatory beta-cell hypersecretion during insulin-resistant states and in transition to beta-cell failure in type 2 diabetes is unknown.. We carried out oral glucose tolerance testing followed by blood sampling 10 times for 2 h on 68 age- and BMI-matched participants of the Baltimore Longitudinal Study on Aging (BLSA) with normal glucose tolerance (34 subjects), impaired glucose tolerance (IGT) (18 subjects with both impaired fasting and 2-h plasma glucose levels), and type 2 diabetes (16 subjects with both diabetic fasting and 2-h plasma glucose levels). We assayed plasma glucose, insulin, C-peptide, glucagon, and intact and total GIP levels and quantitated glucose and hormone responses to the oral glucose tolerance test. We also compared GIP and insulin release and sensitivity indexes between groups.. After glucose ingestion, subjects with IGT had both hyperinsulinemia and hyperemia, while subjects with type 2 diabetes had both beta- and GIP-cell deficiency. In the former group, there was also a significant positive correlation between the augmented plasma intact and total GIP levels and both fasting and post-oral glucose load plasma insulin levels.. Elevated plasma GIP levels are correlated with hyperinsulinemia in the impaired glucose-tolerant state, whereas type 2 diabetes is associated with a failure to secrete adequate amounts of both GIP and insulin, indicating a common pathway of resistance to and eventually failure of glucose responsiveness in beta- and GIP-cells.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Female; Gastric Inhibitory Polypeptide; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Longitudinal Studies; Male; Middle Aged; Reference Values

Diabetes mellitus (DM) is frequently observed in patients with chronic hepatitis caused by hepatitis C virus infection (CHC). The present study was designed to determine the pathogenic factors responsible for glucose intolerance in CHC patients.. A total of 131 patients with CHC were enrolled in this study. Insulin resistance and beta-cell function were determined after 75 g oral glucose tolerance tests.. Glucose intolerance was detected in 27.5% (36/131) of CHC patients; 10 had DM and 26 impaired glucose tolerance. HOMA-R [insulin 0xglucose 0/22.5] was greater in patients with both impaired glucose tolerance and DM than in those with normal glucose tolerance (P<0.01). Matsuda index [10(4)/ (square root) (mean insulinxmean glucosexglucose 0xinsulin 0)] was lower in diabetic patients than in those with normal glucose tolerance (P<0.05). The insulinogenic index [Deltainsulin 30-0/Deltaglucose 30-0] and DeltaC-peptide 30 [DeltaC-peptide 30-0/Deltaglucose 30-0] were significantly lower even in patients with impaired glucose tolerance than in patients with normal glucose tolerance (P<0.01).. Both insulin resistance and beta-cell dysfunction contribute to glucose intolerance in CHC patients.

Topics: Adult; C-Peptide; Female; Glucose Intolerance; Glucose Tolerance Test; Hepatitis C, Chronic; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Liver Cirrhosis; Male; Middle Aged; Prevalence

Type 1 diabetes mellitus (DM) is a frequent complication in patients with beta-thalassemia. It is believed to be due to the damage inflicted by iron overload of the pancreatic beta cells. Liver disorders and genetic influences seem to be additional predisposing factors.. To study the prevalence of diabetes and impaired glucose tolerance (IGT) in transfusion-dependent Egyptian beta-thalassemic patients and to evaluate the possible role of genotyping in the pathogenesis of diabetes associated with beta-thalassemia.. A total of 56 transfusion-dependent beta-thalassemic patients aged 10-31 (mean age=15.9 +/- 5.7 yr), 32 males and 24 females, including 48 thalassemia major and eight thalassemia intermedia; compared to 15 age- and sex-matched controls. All were subjected to history and examination, laboratory investigations: complete blood count (CBC), serum ferritin, liver function tests, hepatitis B and C markers, fasting blood glucose, oral glucose tolerance test (OGTT) and fasting C-peptide. Genotyping for 16 mutations was assessed in thalassemic patients with abnormal glucose tolerance.. The prevalence of diabetes was 10.4% (5 of 48) and IGT was 14.6% (7 of 48) among thalassemia major, whereas, none of thalassemia intermedia had abnormal glucose tolerance. Fasting C-peptide was lower in beta-thalassemic patients compared to controls (p <0.001); the level was significantly higher in patients complicated by diabetes or IGT compared with other thalassemic patients (p <0.001). Chronic hepatitis C was detected in all patients (100%) with abnormal glucose tolerance. Genotyping showed that IVS II nt 745 was detected in 77.7% of cases with abnormal glucose tolerance.. Abnormal glucose tolerance is common in multiply transfused beta-thalassemia major patients, which could be attributed to progressive and early loss of beta-cell mass, along with persistent insulin resistance. Chronic hepatitis C may play a role in the development of abnormal glucose tolerance. An association between diabetes and genotyping IVS II nt 745 was found. Patients with this particular genotype are advised to check their blood glucose every 6 months to detect early occurrence of diabetes.

Topics: Adolescent; Adult; beta-Thalassemia; Blood Transfusion; C-Peptide; Child; Diabetes Mellitus; Egypt; Female; Genotype; Glucose Intolerance; Hepatitis C, Chronic; Humans; Male

The mechanisms responsible for the deterioration in glucose tolerance associated with protease inhibitor-containing regimens in HIV infection are unclear. Insulin resistance has been implicated as a major factor, but the affected tissues have not been identified. Furthermore, beta-cell function has not been evaluated in detail. The present study was therefore undertaken to assess the effects of protease inhibitor-containing regimens on hepatic, muscle, and adipose tissue insulin sensitivity as well as pancreatic beta-cell function. We evaluated beta-cell function in addition to glucose production, glucose disposal, and free fatty acid (FFA) turnover using the hyperglycemic clamp technique in combination with isotopic measurements in 13 HIV-infected patients before and after 12 weeks of treatment and in 14 normal healthy volunteers. beta-Cell function and insulin sensitivity were also assessed by homeostasis model assessment (HOMA). Treatment increased fasting plasma glucose concentrations in all subjects (P < 0.001). Insulin sensitivity as assessed by HOMA and clamp experiments decreased by approximately 50% (P < 0.003). Postabsorptive glucose production was appropriately suppressed for the prevailing hyperinsulinemia, whereas glucose clearance was reduced (P < 0.001). beta-Cell function decreased by approximately 50% (P = 0.002), as assessed by HOMA, and first-phase insulin release decreased by approximately 25%, as assessed by clamp data (P = 0.002). Plasma FFA turnover and clearance both increased significantly (P < 0.001). No differences at baseline or in responses after treatment were observed between drug naïve patients who were started on a nucleoside reverse transcriptase inhibitor (NRTI) plus a protease inhibitor and patients who had been on long-term NRTI treatment and had a protease inhibitor added. The present study indicates that protease inhibitor-containing regimens impair glucose tolerance in HIV-infected patients by two mechanisms: 1) inducement of peripheral insulin resistance in skeletal muscle and adipose tissue and 2) impairment of the ability of the beta-cell to compensate.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Composition; Body Constitution; C-Peptide; CD4 Lymphocyte Count; Fatty Acids, Nonesterified; Female; Glucagon; Glucose Clamp Technique; Glucose Intolerance; Glycated Hemoglobin; Glycerol; HIV Infections; HIV Protease Inhibitors; Homeostasis; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Lipids; Liver; Male; Middle Aged; Muscle, Skeletal; Proinsulin; Viral Load

Several in vitro investigations showed that serum paraoxonase 1 (PON1) that is located on high-density lipoprotein reduces or prevents low-density lipoprotein (LDL) oxidation and therefore retards atherosclerosis. Accordingly, the well documented loss of PON1 activity in patients with overt diabetes mellitus was causally related to the development of micro- and macroangiopathy in the disease course. Because vascular complications start already in prediabetic states, e.g. impaired glucose tolerance (IGT), we investigated serum PON1 activities and circulating levels of oxidized LDL (oxLDL) in 125 IGT subjects, 75 patients with newly diagnosed diabetes mellitus type 2, and 403 individuals with normal glucose tolerance. Using three different substrates (paraoxon, phenylacetate, p-nitrophenylacetate) we found that PON1 activity is not significantly altered in IGT and diabetes mellitus subjects, respectively, when compared with normoglycemic controls. Both IGT subjects and diabetes mellitus patients had significantly increased levels of oxLDL in the circulation. However, serum PON1 activity variations and glutamine/arginine phenotype were not related to the levels of oxLDL. The data suggest that 1) PON1 activity loss is an event occurring later in the course of diabetes mellitus; and 2) PON1 does not affect oxidation of circulating LDL, at least in early diabetes mellitus.

Topics: Adult; Aged; Aryldialkylphosphatase; C-Peptide; Diabetes Mellitus, Type 2; Esterases; Female; Glucose Intolerance; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Lipoproteins, LDL; Male; Middle Aged; Paraoxon; Phenotype; Phenylacetates; Substrate Specificity

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

Impaired glucose tolerance (IGT) is an insulin-resistant state and a risk factor for Type 2 diabetes. The relative roles of insulin resistance and insulin deficiency in IGT have been disputed.. In 40 IGT subjects and 63 sex-, age-, and weight-matched controls with normal glucose tolerance (NGT), we measured (i) indices of insulin sensitivity of fasting glucose production (by tracer glucose) and glucose disposal (M value on a 240 pmol x min(-1) x m(-2) insulin clamp) and (ii) indices of beta-cell function (glucose sensitivity, rate sensitivity, and potentiation) derived from model analysis (Am J Physiol 283:E1159-E1166, 2002) of the insulin secretory response (by C-peptide deconvolution) to oral glucose.. In comparison with NGT, IGT were modestly insulin resistant (M=29+/-2 vs 35+/-2 micromol x min(-1) x kg(FFM)(-1), p=0.01); insulin sensitivity of glucose production also was reduced, in approximate proportion to M. Despite higher baseline insulin secretion rates, IGT was characterized by a 50% reduction in glucose sensitivity [53 (36) vs 102 (123) pmol x min(-1) x m(-2) x mM(-1), median (interquartile range), p=0.001] and impaired potentiation [1.6 (0.8) vs 2.0 (1.5) units, p<0.04] of insulin release, whereas rate sensitivity [1.15 (1.15) vs 1.38 (1.28) nmol x m(-2) x mM(-1)] was not significantly reduced. Glucose sensitivity made the single largest contribution (approximately 50%) to the observed variability of glucose tolerance.. In IGT the defect in glucose sensitivity of insulin release quantitatively predominates over insulin resistance in the genesis of the reduced tolerance to oral glucose.

Topics: Adult; Blood Glucose; C-Peptide; Fasting; Female; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Kinetics; Male; Reference Values

A follow-up study of first-degree relatives of type 2 diabetic patients presented the opportunity to study the association of components of the metabolic syndrome with oral glucose tolerance in these subjects. In 1992, 25 years after the first analysis of the cohort, we performed 75-g oral glucose tolerance tests and measured anthropometric data (body mass index, waist-hip ratio), insulin and C-peptide concentrations, and parameters of lipoprotein metabolism (free fatty acids, triglycerides, cholesterol, HDL cholesterol). Of 135 participants, 71 had normal glucose tolerance (GT), 22 had impaired GT, and 42 had diabetic GT (WHO 1985 criteria). Impaired glucose tolerance and diabetes were significantly (Kruskal-Wallis test) associated with advanced age (p=0.001), higher body mass index (p=0.005) and waist-hip ratio (p=0.027), systolic hypertension (p=0.031), elevated basal insulin concentrations (p<0.001), higher free fatty acids (p<0.001) and triglycerides (p=0.017), and lower HDL cholesterol (p=0.003); no associations were found with total and LDL cholesterol levels (Friedewald's formula, p=0.25). Abnormalities (obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, pathological oral glucose tolerance) were associated with significant deterioriations in all other components of the metabolic syndrome, if their number exceeded three. Disturbances of oral glucose tolerance are present in a high percentage of first-degree relatives after 25 years of follow-up (51% of those tested). Impaired or diabetic glucose tolerance in such a cohort was associated with overweight, hypertension and disturbances of lipoprotein metabolism characteristic of the metabolic syndrome. Hypercholesterolemia (LDL-cholesterol) is not a component of the metabolic syndrome in a German population with a high hereditary burden regarding type 2 diabetes. A metabolic syndrome should certainly be diagnosed if three components are present, although even in the presence of only two components, an elevated risk is evident.

Topics: Aged; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 2; Family; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Lipids; Lipoproteins; Male; Middle Aged; Time Factors

To study the influence of platelet activation and lipid peroxidation in fetal blood on umbilical vascular prostanoid synthesis and placental morphology in diabetic pregnancy.. The concentrations of thromboxane A2 (TxA2) and malondialdehyde (MDA) were determined in umbilical cord plasma in 21 women with diabetes mellitus/impaired glucose tolerance (DM/IGT) and ten healthy women. Segments from the umbilical artery and vein were incubated and prostacyclin (PGI2) and TxA2 metabolites were determined. Prostanoid synthesis was stimulated with calcium ionophore at a second incubation. Histological examination was carried out in samples from the umbilical cord, membranes and placental parenchyma. Non-parametric statistical analysis was used, with a two-tailed p < 0.05 considered statistically significant.. Cord plasma TxA2, but not MDA, was higher among DM/IGT women (p = 0.07). There were indications that cord plasma TxA2, but not MDA, was positively correlated with vascular prostanoid synthesis and synthesis capacity. In the umbilical vein, both the basal and stimulated PGI2 production and the stimulated TxA2 production were lower in the DM/IGT group. Ischemic placental lesions were associated with a high TxA, and a low MDA concentration in cord plasma.. Even in less severe forms of impaired glucose metabolism, disturbances in platelet activation significantly affect both biochemical and morphological vessel wall and tissue functions in the umbilicoplacental unit. This could indicate an abnormal programming of fetal cell functions and designate cases at increased risk of developing cellular and organ damage.

Topics: 6-Ketoprostaglandin F1 alpha; C-Peptide; Embryonic and Fetal Development; Epoprostenol; Female; Fetal Blood; Glucose Intolerance; Glycated Hemoglobin; Humans; Lipid Peroxidation; Malondialdehyde; Placenta; Placenta Diseases; Platelet Activation; Pregnancy; Pregnancy in Diabetics; Thromboxane A2; Thromboxane B2; Umbilical Arteries; Umbilical Veins

The availability of quantitative indexes describing beta-cell function in normal life conditions is important for the characterization of impaired mechanisms of insulin secretion in pathophysiological states. Recently, an oral C-peptide minimal model has been proposed and applied to subjects with normal glucose tolerance (NGT) during graded up-and-down glucose infusion protocols (40-min periods at 4, 8, 16, 8, 4, and 0 mg.kg(-1).min(-1)) and oral glucose tolerance tests. These tests are characterized by slow glucose and C-peptide dynamics, which reproduce prandial conditions. In view of the importance of beta-cell dysfunction in the pathogenesis of type 2 diabetes, our aim was to test and use the oral minimal model in subjects with impaired glucose tolerance (IGT) to identify deranged mechanisms of beta-cell function. Plasma C-peptide and glucose data from graded up-and-down glucose infusions were analyzed in nine NGT and four IGT subjects using the classic deconvolution approach and the oral minimal model, and indexes of beta-cell function were derived. An index of insulin sensitivity was also obtained for each subject from minimal model analysis of glucose and insulin levels achieved during the test. Both deconvolution and minimal model analyses revealed that individuals with IGT have a relative defect in the ability to secrete enough insulin to adequately compensate for insulin resistance. Additionally, minimal model analysis suggests that insulin secretory defect in IGT arises from delays in the timing of the beta-cell response to glucose.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Male; Models, Biological; Predictive Value of Tests; Reaction Time

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

To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD).. Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT).. Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01).. NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.

Topics: Adult; Aged; Asian; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Japan; Lipids; Male; Middle Aged; Risk Factors; Sensitivity and Specificity

To determine whether the impaired glucose tolerance (IGT) state contributes to the deterioration of the metabolic profile in women after taking into account the contribution of visceral adipose tissue (AT) accumulation, as measured by computed tomography.. We studied 203 women with normal glucose tolerance (NGT) and 46 women with IGT, defined as a glycemia between 7.8 and 11.1 mmol/l measured 2 h after a 75-g oral glucose load.. Women with IGT were characterized by a higher visceral AT accumulation and by higher concentrations of fasting plasma glucose, insulin, and C-peptide as well as by higher plasma concentrations of cholesterol, triglycerides, and apolipoprotein B (apoB) and by greater cholesterol-to-HDL-cholesterol ratio, reduced LDL peak particle size, lower HDL-cholesterol and HDL2-cholesterol concentrations, and higher blood pressure (P < 0.01) than women with NGT. When we matched 27 pairs of women for visceral AT and fat mass as well as for menopausal status, differences previously found in LDL-cholesterol, LDL peak particle size, HDL-cholesterol, and HDL2-cholesterol concentrations as well as in the cholesterol-to-HDL-cholesterol ratio and blood pressure were eliminated, whereas triglyceride concentrations remained significantly higher in women with IGT.. A high visceral AT accumulation is a major factor involved in the deterioration of many metabolic variables in women with IGT, with the notable exception of triglyceride concentrations, which remained significantly different between women with NGT and women with IGT after adjustment for visceral fat.

Topics: Adipose Tissue; Adult; Aged; Apolipoproteins; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Cholesterol; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Lipoproteins; Middle Aged; Quebec; Risk Assessment; Risk Factors; Tomography, X-Ray Computed; Triglycerides; Viscera

We tried to characterize the clinical features associated with glucose metabolism in the development of diabetes. Study subjects were glucose-tolerant subjects without a family history of diabetes (normal glucose tolerance [NGT]1 group, n = 15) and with a first-degree diabetes relative (NGT2, n = 9), 12 subjects with impaired glucose tolerance (IGT), and 13 subjects with type 2 diabetes mellitus (DM). The first phase C-peptide secretion (CS1), insulin sensitivity (Si), and glucose effectiveness (Sg) were assessed by the combination of C-peptide 2-compartment model and minimal model analyses. Using these parameters, each group was characterized: CS1 was decreased in NGT2 and IGT compared with NGT1 and further decreased in DM; Si was not different among NGT1, NGT2, and IGT, whereas Si was decreased in DM; CS1 x Si value was decreased in NGT2 compared with NGT1 and decreased in IGT, DM, progressively; Sg was decreased in IGT and DM compared with NGT1 and NGT2. CS1 x Si and Sg values could segregate each group distinctively, although it had a large variety of phenotypes. CS1 x Si value and Sg are assumed to represent the contributions of insulin-dependent and independent mechanisms to glucose tolerance, respectively, and thus, both mechanisms should play an important role in the characterization of pathophysiologic phenotypes of the subjects with various degrees of glucose tolerance.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Computer Simulation; Diabetes Mellitus, Type 2; Fasting; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Middle Aged; Phenotype

To elucidate the causes of the diminished incretin effect in type 2 diabetes mellitus we investigated the secretion of the incretin hormones, glucagon-like peptide-1 and glucose- dependent insulinotropic polypeptide and measured nonesterified fatty acids, and plasma concentrations of insulin, C peptide, pancreatic polypeptide, and glucose during a 4-h mixed meal test in 54 heterogeneous type 2 diabetic patients, 33 matched control subjects with normal glucose tolerance, and 15 unmatched subjects with impaired glucose tolerance. The glucagon-like peptide-1 response in terms of area under the curve from 0-240 min after the start of the meal was significantly decreased in the patients (2482 +/- 145 compared with 3101 +/- 198 pmol/liter.240 min; P = 0.024). In addition, the area under the curve for glucose-dependent insulinotropic polypeptide was slightly decreased. In a multiple regression analysis, a model with diabetes, body mass index, male sex, insulin area under the curve (negative influence), glucose-dependent insulinotropic polypeptide area under the curve (negative influence), and glucagon area under the curve (positive influence) explained 42% of the variability of the glucagon-like peptide-1 response. The impaired glucose tolerance subjects were hyperinsulinemic and generally showed the same abnormalities as the diabetic patients, but to a lesser degree. We conclude that the meal-related glucagon-like peptide-1 response in type 2 diabetes is decreased, which may contribute to the decreased incretin effect in type 2 diabetes.

Topics: Analysis of Variance; Autoantibodies; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Fatty Acids, Nonesterified; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Intolerance; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Pancreatic Polypeptide; Peptide Fragments; Peptides; Protein Precursors; Reference Values

Impaired glucose tolerance and diabetes mellitus have been associated with a prolonged QT interval among select populations. However, these associations remain unclear among the general population.. We examined these relationships using data from 5833 adults aged 40-90 years from NHANES III (1988-1994). Univariate differences in cardiovascular disease (CVD) risk factors were examined across tertiles of heart rate corrected QT (QTc). The association between glucose intolerance, CVD risk factors and a prolonged QTc (> or = 0.440 s) was also assessed with logistic regression adjusting for age, race, gender, education, and heart rate.. Prolonged QTc was observed among 22.0% of persons with normal glucose tolerance (NGT), 29.9% of those with impaired fasting glucose (IFG), and among 42.2% of persons with diabetes. Hypertension, serum cholesterol, obesity, heart rate, and fasting C-peptide and serum insulin levels were associated with prolonged QTc (all: P < or = 0.05). After multivariate adjustment, persons with IFG were 1.2 times (95% CI=0.7-2.0) as likely and persons with diabetes 1.6 times (95% CI=1.1-2.3) as likely to have a prolonged QTc as persons with NGT. In addition, persons with diabetes and two or more additional CVD risk factors were 2.3 times (95% CI=1.3-4.0) as likely to have a prolonged QTc as persons with NGT and no CVD risk factors after multivariate adjustment.. Diabetes was associated with an increased likelihood of prolonged QTc independent of age, race, gender, education, and heart rate. In addition, persons with diabetes and multiple CVD risk factors were more likely to have a prolonged QTc than those with NGT and no additional risk factors, suggesting that these persons may be at increased risk for cardiac arrhythmia and sudden death.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Electrocardiography; Female; Glucose Intolerance; Health Surveys; Heart Diseases; Humans; Insulin; Male; Middle Aged; Multivariate Analysis; Risk Factors

Alterations in carbohydrate metabolism associated with liver cirrhosis are characterized by a high serum insulin level and prolonged hyperglycemia on oral glucose tolerance test (OGTT). We measured plasma glucose, immunoreactive insulin (IRI), and C-peptide immunoreactivity (CPR) levels during a 75-g OGTT before and after varices obliteration in 10 cirrhotic patients with gastric varices. After obliteration, the indocyanine green retention rate was decreased and the portal flow velocity was increased. A significant decline in plasma glucose and IRI levels was also noted on OGTT. Moreover, the plasma glucose and IRI levels declined at 90 and 120 min in OGTT while they increased progressively by 120 min before obliteration. The levels of CPR were similar before and after treatment. These results indicate that decreased portal flow due to extrahepatic shunt and consequent impairment of insulin metabolism play a role in glucose intolerance observed in cirrhotic patients and that shunt occlusion improves glucose metabolism.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Collateral Circulation; Esophageal and Gastric Varices; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant; Insulin; Liver Cirrhosis; Male; Middle Aged; Portal System

To examine whether an elevated blood pressure (BP) level and an impaired reduction in nocturnal BP are already present in nondiabetic first-degree relatives of type 2 diabetic patients.. We examined 253 offspring of type 2 diabetic patients using ambulatory BP monitoring and compared the BP level and profile with 275 offspring of nondiabetic subjects. Anthropometric measures and cholesterol, fasting blood glucose, and insulin levels were also compared between groups.. No significant differences in BP level (P > 0.05) or diurnal BP profile were evident between the nondiabetic glucose-tolerant offspring of type 2 diabetic subjects and the offspring of nondiabetic subjects. BMI (P < 0.05 and P < 0.01, male vs. female), waist-to-hip ratio (P < 0.05), fasting blood glucose (P < 0.01), C-peptide (P < 0.05 and P < 0.01, male vs. female), insulin resistance index (P < 0.05 and P < 0.01, male vs. female), triglycerides (P < 0.05), apolipoprotein B (apoB) (P < 0.01 and P < 0.05, male vs. female), and apoA1/apoB (P < 0.01) were significantly higher in the nondiabetic offspring of type 2 diabetic subjects than in the offspring of nondiabetic subjects.. This study shows a preserved diurnal BP profile and a normal BP level in the nondiabetic glucose-tolerant offspring of type 2 diabetic subjects compared with the offspring of nondiabetic subjects, although the offspring of diabetic patients are characterized by features of the metabolic syndrome.

Topics: Aged; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Circadian Rhythm; Denmark; Diabetes Mellitus, Type 2; Electrocardiography, Ambulatory; Female; Glucose Intolerance; Humans; Insulin Resistance; Male; Middle Aged; Nuclear Family; Prevalence; Reference Values; Risk Factors

This study was undertaken to characterize first and second phase secretory profiles of total and nonglycosylated amylin and insulin and to determine whether excessive glycosylation of amylin or hyperamylinemia is a feature of abnormal glucose tolerance in humans. Plasma concentrations of total and nonglycosylated amylin and serum immunoreactive insulin were measured under identical hyperglycemic conditions using the hyperglycemic clamp technique in subjects with type 2 diabetes, impaired and normal glucose tolerance. Both amylin and insulin concentrations followed a biphasic pattern in subjects with normal and impaired glucose tolerance. In the subjects with normal and impaired glucose tolerance, the second phase amylin concentrations markedly exceeded those of the first phase, whereas the reverse was true for insulin. The first phase concentrations of both peptides were significantly lower in impaired than the normal glucose tolerance subjects. In patients with type 2 diabetes no first phase peak for either amylin or insulin could be identified, and the second phases of both amylin and insulin were significantly lower compared to subjects with normal or impaired glucose tolerance. Nonglycosylated amylin concentrations accounted for 25-45% of total amylin, regardless of glucose tolerance, and mimicked the pattern of total amylin concentrations. In summary: 1) glucose-induced increases in the magnitude of the first and second phase amylin plasma concentrations differed from those of insulin; 2) subjects with impaired glucose tolerance and more strikingly those with type 2 diabetes have impaired amylin responses; and 3) the ratio of nonglycosylated to total amylin is normal irrespective of glucose tolerance. These data imply, in view of many reports describing accumulation of amyloid in the pancreas, that circulating levels of amylin decrease as amyloid deposits accumulate and beta-cell function deteriorates and that the amount of glycosylated amylin in plasma is not increased in patients with type 2 diabetes.

Topics: Amyloid; Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Glycosylation; Humans; Insulin; Insulin Secretion; Islet Amyloid Polypeptide; Male; Middle Aged; Reference Values

Our studies were undertaken to characterise the defective insulin secretion of impaired glucose tolerance (IGT).. We studied 13 normal glucose tolerant subjects (NGT) and 12 subjects with IGT carefully matched for age, sex, BMI and waist-to-hip ratio. A modified hyperglycaemic clamp (10 mmol/1) with a standard 2-h square-wave hyperglycaemia, an additional glucagon-like-peptide (GLP)-1 phase (1.5 pmol x kg(-1) x min(-1) over 80 min) and a final arginine bolus (5 g) was used to assess various phases of insulin secretion rate.. Insulin sensitivity during the second phase of the hyperglycaemic clamp was low in both groups but not significantly different (0.12 +/- 0.021 in NGT vs 0.11 +/- 0.013 micromol x kg(-1) x min(-1) x pmol(-1) in IGT, p = 0.61). First-phase insulin secretion was lower in IGT (1467 +/- 252 vs 3198 +/- 527 pmol x min(-1), p = 0.008) whereas the second phase was not (677 +/- 61 vs 878 +/- 117 pmol x min(-1), p = 0.15). The acute insulin secretory peak in response to GLP-1 was absent in IGT subjects who only produced a late phase of GLP-1-induced insulin secretion rate which was lower (2228 +/- 188 pmol x min(-l)) than in NGT subjects (3056 +/- 327 pmol x min(-1), p = 0.043). Insulin secretion in response to arginine was considerably although not significantly lower in IGT subjects. The relative impairment (per cent of the mean rate for NGT subjects) was greatest for the GLP-1 peak (19 +/- 9%).. In this Caucasian cohort a defective insulin secretion rate is essential for the development of IGT. The variable degrees of impairment of different phases of the insulin secretion rate indicate that several defects contribute to its abnormality in IGT. Defects in the incretin signalling pathway of the beta cell could contribute to the pathogenesis of beta-cell dysfunction of IGT and thus Type II (non-insulin-dependent) diabetes mellitus.

Topics: Adult; Arginine; Blood Glucose; C-Peptide; Fasting; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Clamp Technique; Glucose Intolerance; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Peptide Fragments; Reference Values

Elevated proinsulin secretion and islet amyloid deposition are both features of Type 2 diabetes but their relationship to beta-cell dysfunction is unknown. To determine if islet amyloid polypeptide (IAPP) secretion is disproportionate with other beta-cell products at any stage of glucose intolerance, 116 subjects were studied. Non-diabetic subjects with equivalent body mass index (BMI) were assigned to three groups, (i) normal fasting glucose, fpg<5.5 mmol l(-1); (ii) intermediate fasting glucose, fpg> or =5.5<6.15 mmol l(-1); (iii) impaired fasting glucose (IFG), fpg> or =6.1<7.0 mmol l(-1). Diabetic subjects were divided according to therapy (9 diet, 19 tablet, and 11 insulin). IAPP, C-peptide and proinsulin were measured fasting and at the end of a 1-h glucose infusion. Fasting C-peptide, IAPP and proinsulin were significantly elevated in the IFG group compared with the other non-diabetic groups (P<0.02); fasting IAPP/C-peptide and proinsulin/C-peptide were 1-2% in all non-diabetic groups. Fasting and 1-h proinsulin and proinsulin/C-peptide were higher in diabetic compared with non-diabetic subjects (P<0.01). IAPP and IAPP/C-peptide in diabetic groups were similar to that in non-diabetic subjects but reduced in the insulin-treated group (P<0.01). Proinsulin was disproportionately increased compared with C-peptide and IAPP in Type 2 diabetes particularly in severe beta-cell failure implying more than one concurrent beta-cell pathology.

Topics: Amyloid; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Islet Amyloid Polypeptide; Longitudinal Studies; Male; Middle Aged; Proinsulin; Reference Values

To determine the early biochemical predictors of increased susceptibility to develop diabetes in offspring of African type 2 diabetic parents.. A total of 69 offspring (case subjects) of 26 families in Cameroon with at least one type 2 diabetic parent were studied, and 62 offspring (control subjects) from 25 families in Cameroon with no parent with type 2 diabetes underwent an oral glucose tolerance test. Early insulin secretion was calculated using the ratio of the 0- to 30-min incremental insulin values to the 0- to 30-min incremental glucose. Anthropometric parameters were also measured.. Of the case subjects, 23% were glucose intolerant (4% with diabetes and 19% with impaired glucose tolerance [IGT]) compared with 6.5% (all with IGT) of control subjects (P = 0.02). There was also an increasing prevalence of glucose intolerance, especially IGT with increasing number of glucose-intolerant parents. Fasting serum insulin levels were not different in the two groups; however, at 30 min, the case subjects had lower insulin levels than the control subjects (P < 0.006). Case subjects with IGT had lower 30-min insulin concentration, early insulin secretion, and 2-h insulin levels than those with normal glucose tolerance (NGT) (F = 4.1, P < 0.05; F = 4.1, P < 0.04; and F = 5.1, P < 0.03, respectively). Furthermore, case subjects with NGT and IGT had lower early insulin secretion than control subjects (F = 4. 1, P < 0.03). These differences remained after adjustment for BMI and regardless of the status of parental diabetes. Two-hour insulin concentration showed a positive association (odds ratio = 0.95 CI 0.90-0.99, P = 0.039) with IGT in the case subjects.. Diabetes and IGT are more prevalent in the offspring of African type 2 diabetic parents, and this may be due to an underlying degree of beta-cell impairment marked by reduced early-phase insulin secretion.

Topics: Adult; Body Constitution; Body Mass Index; C-Peptide; Cameroon; Cholesterol; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Parents; Pedigree; Triglycerides

Impaired glucose tolerance (IGT) is frequently associated with an increased fat mass and an altered fat distribution. The adipocyte derived hormone, leptin has been shown to interact with insulin at various levels and may be intimately involved in this process. However, only limited data concerning the interaction of insulin, glucose tolerance and leptin are available and no data exist on the potential influence of bound vs. free circulating leptin. We therefore studied free and bound leptin in 136 patients (77 males, 59 females) with IGT, in relation to plasma glucose, insulin, proinsulin and C-peptide levels as well as serum free and bound leptin concentrations during an oral glucose tolerance test (oGTT). The expected positive relation of free serum leptin levels with body mass index (BMI) was found. Free leptin concentrations were higher in women than in men. Analysis in tertiles revealed a significant relation between free leptin (16-58, 60-160, and 169-932 pmol/l) and mean fasting insulin levels (65, 93, and 100 pmol/l). This relationship remained significant in a multiple regression analysis with BMI and gender as covariates. Similar independent relationships to leptin serum levels were observed for HbA1c and plasma C peptide levels and the proinsulin/insulin ratio but not for plasma glucose and proinsulin levels. These data suggest a fine tuning of leptin by small changes in circulating insulin levels observed in impaired glucose tolerance.

Topics: Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Leptin; Male; Middle Aged; Proinsulin; Proteins; Sex Characteristics

People with type 2 diabetes have defects in both alpha- and beta-cell function. To determine whether lack of suppression of glucagon causes hyperglycemia when insulin secretion is impaired but not when insulin secretion is intact, twenty nondiabetic subjects were studied on two occasions. On both occasions, a "prandial" glucose infusion was given over 5 h while endogenous hormone secretion was inhibited. Insulin was infused so as to mimic either a nondiabetic (n = 10) or diabetic (n = 10) postprandial profile. Glucagon was infused at a rate of 1.25 ng. kg(-1). min(-1), beginning either at time zero to prevent a fall in glucagon (nonsuppressed study day) or at 2 h to create a transient fall in glucagon (suppressed study day). During the "diabetic" insulin profile, lack of glucagon suppression resulted in a marked increase (P < 0.002) in both the peak glucose concentration (11.9 +/- 0.4 vs. 8.9 +/- 0.4 mmol/l) and the area above basal of glucose (927 +/- 77 vs. 546 +/- 112 mmol. l(-1). 6 h) because of impaired (P < 0.001) suppression of glucose production. In contrast, during the "nondiabetic" insulin profile, lack of suppression of glucagon resulted in only a slight increase (P < 0.02) in the peak glucose concentration (9.1 +/- 0.4 vs. 8.4 +/- 0.3 mmol/l) and the area above basal of glucose (654 +/- 146 vs. 488 +/- 118 mmol. l(-1). 6 h). Of interest, when glucagon was suppressed, glucose concentrations differed only minimally during the nondiabetic and diabetic insulin profiles. These data indicate that lack of suppression of glucagon can cause substantial hyperglycemia when insulin availability is limited, therefore implying that inhibitors of glucagon secretion and/or glucagon action are likely to be useful therapeutic agents in such individuals.

Topics: Adult; Blood Glucose; C-Peptide; Carbon Dioxide; Female; Glucagon; Glucose; Glucose Intolerance; Human Growth Hormone; Humans; Insulin; Male

To observe the different changes of plasma insulin and c-peptide in patients with gestational diabetes mellitus (GDM), gestational impaired glucose tolerance (GIGT), normal pregnant women, and to detect the function of beta-cell in patients with gestational impaired glucose metabolism.. Test the plasma insulin, c-peptide in 48 cases of GDM(group I), 39 cases of GIGT (group II), 39 cases of normal pregnant women (group III) and 22 cases of healthy non-pregnant women (group IV) by radioimmunoassay.. (1) In third trimester of group III, insulin, c-peptide levels were higher than those of group IV (P < 0.01). They increased from 28-34 weeks to 38-40 weeks, peaked during delivery. Insulin levels of group I and group II were higher than those of group III (P < 0.01, P < 0.05), but tended to decrease by the end of the third trimester and peaked during delivery. During delivery, there was no significant differences among the three groups. At 28-40 weeks, c-peptide of group I was significantly higher than those in groups II and III (P < 0.01) and was lower than that in group III during delivery (P < 0.05). Insulin and c-peptide of these 3 groups dropped gradually within 2 months after delivery but in group I and II they were significantly higher than those of group III (P < 0.01).. In third trimester insulin and c-peptide of group I-III increased till delivery, the reason maybe associated with insulin resistance. GDM had the same peaking secretion during delivery with normal pregnant women and GIGT group, this maybe due to the stress during delivery. Insulin levels of most GDM and GIGT were still higher than normal after two month postpartum, and should be followed up carefully.

Topics: Adult; C-Peptide; Diabetes, Gestational; Female; Glucose Intolerance; Humans; Insulin; Pregnancy

To study 1) whether abdominal adiposity was present in adult offspring of two NIDDM parents, 2) whether abdominal adiposity was associated with the development of glucose intolerance, and 3) the association of pancreatic beta-cell function with impaired glucose tolerance (IGT) and NIDDM in these groups.. One hundred offspring whose parents both had NIDDM were studied (60 men, 40 women, mean age 34 +/- 6.9 years, BMI 27.4 +/- 4.1 kg/m2). None had a history of glucose intolerance. Nondiabetic control subjects with no family history of diabetes were also studied for comparison (21 men, 19 women, age 36 +/- 10.3 years, BMI 26 +/- 3.7 kg/m2). A standard oral glucose tolerance test was done for all, and plasma glucose, C-peptide, and insulin responses were measured. Abdominal fat measurements at L4-L5 were made using a computed axial tomography scan. Subcutaneous fat (SF), visceral fat (VF), and total fat (TF) areas were measured and VF/SF ratio was calculated. An index of insulin secretion (delta I/G) was derived as the ratio of incremental insulin at 30 min divided by 30-min plasma glucose.. IGT was detected in 32 offspring and diabetes in 21 offspring. Diabetic men had a higher TF area than the other groups. SF, VF, and VF/SF ratios were similar in control men and in offspring with normal glucose tolerance (NGT), IGT, or diabetes. Among control subjects, women had significantly lower VF than men. Female offspring had higher VF than the control subjects, but intragroup variations were absent. Fasting insulin and all C-peptide responses were higher in NGT compared with control subjects (P < 0.02). The 2-h insulin and C-peptide responses were higher in IGT subjects (P < 0.005). In diabetic subjects, the insulin-to-glucose ratio, C-peptide-to-glucose ratio, and delta I/G were significantly low compared with all other groups (P < 0.005). Multiple logistic regression analysis showed that the area of insulin response had a positive association and delta I/G had a negative association with diabetes, while age, sex, BMI, waist-to-hip ratio, abdominal fat areas, fasting and 2-h insulin, area of insulin, and the C-peptide measurements did not show independent associations. Two-hour insulin showed a positive association with IGT, while increasing area of insulin showed a negative association.. Visceral adiposity seemed to precede glucose intolerance only in women, but it had no independent association with IGT or NIDDM. Insulin resistance, indicated by higher plasma insulin response, and insulin secretory defect, indicated by low delta I/G at 30 min, were associated with diabetes. beta-cell defect was not independently associated with IGT. Increased abdominal visceral adiposity does not appear to be a prerequisite for development of IGT or diabetes in Asian Indians with a strong genetic predisposition for diabetes.

Topics: Abdomen; Adipose Tissue; Adult; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; India; Insulin; Islets of Langerhans; Male; Nuclear Family; Postprandial Period; Prediabetic State; Sex Characteristics; Tomography, X-Ray Computed

To evaluate basal pancreatic beta-cell secretion and suppression during infused insulin and the metabolic clearance rate of insulin in women with normal and abnormal glucose tolerance prior to conception and during pregnancy.. Seven women with normal glucose tolerance and nine women with abnormal glucose tolerance during gestation were evaluated prior to conception, in early (12-14 weeks) and late (34-36 weeks) gestation. Basal insulin and C-peptide were measured after an 11-h fast and during the last 40 min of a 2-h hyperinsulinemic-euglycemic clamp at 40 mU.m-2.m-1. Suppression of basal C-peptide was calculated as the steady-state C-peptide/basal C-peptide. The metabolic clearance rate of insulin was calculated by dividing the insulin infusion rate by the steady-state insulin concentration, which was corrected for residual beta-cell secretion.. No significant differences were noted in the following parameters between women with normal and abnormal glucose tolerance with advancing gestation: increase in basal insulin (P = 0.20) and C-peptide (P = 0.12), ability of infused insulin to decrease basal C-peptide concentration (P = 0.22), and metabolic clearance rate of insulin (P = 0.76). There was a significant 65% increase in both basal insulin (P = 0.0005) and C-peptide (P = 0.0002) concentrations in all subjects with advancing gestation. There was a significant (P = 0.0001) decrease in the ability of the infused insulin to decrease basal C-peptide concentration. C-peptide as a percentage of the basal was 64% before conception, 74% in early pregnancy, and 108% in late pregnancy. The metabolic clearance rate of insulin significantly (P = 0.0005) increased with advancing gestation: pregravid 442 ml.m-2.min-1, early pregnancy 514 ml.m-2. min-1, and 526 ml.m-2.min-1 in late pregnancy.. Pregnancy is accompanied by progressive alterations in insulin kinetics, which are partly responsible for the hyperinsulinemia of this condition. These alterations are more likely a homeostatic response to the increased physiological insulin resistance of pregnancy.

Topics: Adult; Blood Glucose; C-Peptide; Creatinine; Female; Fertilization; Glucose Clamp Technique; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Longitudinal Studies; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pregnancy Trimester, Third; Prospective Studies; Time Factors

We aimed to evaluate gestational impaired glucose tolerance (GIGT) in untreated patients using umbilical cord blood insulin and connecting peptide (C-peptide) concentrations to indicate fetal hyperinsulinemia. A 75 g, 2-hour oral glucose tolerance test, evaluated using WHO criteria, was performed in 722 antenatal patients. Cord C-peptide (p = 0.001) and insulin (p = 0.008) concentrations were significantly higher in patients with GIGT in comparison to those with normal glucose tolerance. The WHO test failed to identify abnormal C-peptide concentrations (p = 0.057), but did identify abnormal insulin concentrations (p = 0.006) and cases where either or both were raised (p = 0.002), with a low Youden's index (range 8.1-11.3) in all 3 cases. A significant biochemical difference exists in patients with GIGT. The WHO criteria for GIGT predict abnormal biochemical outcomes, but they do so poorly.

Topics: Biomarkers; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Fetal Diseases; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; Pregnancy; Pregnancy Complications

To evaluate the potential of autoimmune markers in identifying patients with slowly progressive IDDM in the prediabetic state, we screened a population of 151 patients aged 37-70 years with impaired glucose tolerance (IGT) for the presence of islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase (GADA), and antibodies to tyrosine phosphatase IA-2 (IA-2A). Autoantibodies were found in 5 (3.3%) patients with IGT suggesting the presence of an autoimmune-mediated beta cell destruction. All of them were positive for high level ICA (> 20 JDF-U) and 1 ICA positive subject had additional GADA (100 GADA-U). In contrast, none of the subjects had IA-2A or IAA. We here demonstrate a low prevalence of autoimmune diabetes among middle-aged subjects with IGT. ICA and GADA but not IA-2A or IAA may represent autoimmune markers for slowly progressive IDDM before the manifestation of the disease.

Topics: Adult; Age Factors; Aged; Autoantibodies; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Germany; Glucose Intolerance; Glutamate Decarboxylase; Humans; Insulin; Male; Middle Aged; Prevalence; Risk Factors

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Somatostatin; Uremia

Infantile cystinosis, a rare lysosomal storage disease of cystine, leads to Fanconi syndrome and end-stage renal failure. After renal transplantation, no recurrence of the disease occurs in the graft, but other organ involvement becomes evident later in life. Diabetes mellitus has been associated with cystinosis, but the mechanisms of impaired glucose tolerance have not yet been characterized. Here, we studied glucose tolerance, glucose constant decay (k-values), insulin and C-peptide by intravenous glucose tolerance test (IVGTT) in eight patients with infantile cystinosis (three with impaired GFR (CRF) and five after kidney transplantation (KTX)). For comparison, 15 age-matched children with CRF and 15 age-matched KTX patients were analysed. Both early and second insulin secretion phases were diminished in patients with infantile cystinosis, whereas in CRF, k-values were no different from control patients. After renal transplantation, k-values were significantly lower in cystinotic patients with a markedly reduced early insulin secretion phase. There was a significant negative correlation between k-values and age in patients with cystinosis. Repetitive IVGTTs in these patients demonstrated progressive but rather slow loss of first phase insulin secretion and C-peptide production, suggesting a slowly reducing secretion potential of the beta cell due to cystine storage.. Unlike type I diabetes mellitus, glucose intolerance in patients with infantile cystinosis is characterized by a slow, progressive loss of insulin secretion and C-peptide production. For these patients, the data indicate a 50% risk of developing glucose intolerance by the age of 18 years. We recommend to perform intravenous glucose tolerance tests at 5-year intervals.

Topics: Adolescent; Adult; C-Peptide; Child; Child, Preschool; Cystinosis; Diabetes Mellitus; Female; Glucose Intolerance; Humans; Insulin; Insulin Secretion; Kidney Failure, Chronic; Kidney Transplantation; Male

Topics: Adolescent; Adult; beta-Thalassemia; Blood Glucose; C-Peptide; Child; Child, Preschool; Fasting; Glucose Intolerance; Humans; Infant; Insulin; Insulin Resistance; Insulin Secretion; Kinetics; Proinsulin

To examine the significance of alterations in insulin sensitivity index (S(t)), glucose effectiveness (Sg), and beta-cell function in the pathogenesis of type II diabetes in African-Americans with varying degrees of glucose intolerance.. A total of 154 African-Americans residing in Franklin County, Ohio, were studied. There were 101 subjects with normal glucose tolerance (NGT), 36 with impaired glucose tolerance (IGT), and 17 with type II diabetes. An oral glucose tolerance test (OGTT) was performed on each subject. S(t) and Sg were measured by insulin-modified, frequently sampled intravenous glucose tolerance test (FSIGT).. The mean fasting and postprandial serum glucose levels were significantly greater in the diabetic groups when compared with the IGT and NGT groups. In contrast, while fasting serum insulin and C-peptide levels tended to be greater in the type II diabetic and IGT groups, the postprandial responses were blunted at 30 min in the IGT and type II diabetic groups when compared with the NGT group. The mean acute first-phase insulin release after intravenous glucose was blunted also in the IGT and type II diabetic groups when compared with the NGT group. The S(t) was significantly lower in the IGT (1.51 +/- 0.19) and type II diabetic (0.61 +/- 0.15) groups when compared with the NGT group (2.94 +/- 0.20 x 10(-4).min-1.microU-1.ml-1). The Sg was not significantly different in the NGT (2.90 +/- 0.20), IGT (2.47 +/- 0.19), and the type II diabetic (2.35 +/- 0.15 x 10(-2)/min) groups. The glucose effectiveness at theoretical zero insulin concentration (GEZI) followed similar patterns as the Sg. Furthermore, the basal insulin effect (BIE) was significantly lower in the IGT and type II diabetic groups compared with the NGT group. In addition, the glucose decay constant (Kg) was significantly lower (P < 0.001) in the IGT (1.21 +/- 0.13) and the type II diabetic (1.07 +/- 0.12) groups when compared with the NGT group (2.03 +/- 0.10% per minute).. Our present study demonstrates that African-American patients with IGT and mild type II diabetes have significant reduction in beta-cell function, insulin sensitivity, and BEI but have normal and intact Sg and GEZI when compared with NGT subjects. We conclude the following: 1) a reduction in Sg does not appear to play a significant role in the pathogenetic mechanism of IGT and type II diabetes in African-American patients, and 2) the intact Sg in the IGT and type II diabetic groups could serve as a compensatory mechanism for hyperglycemia in African-Americans.

Topics: Adult; Black People; Blood Glucose; Body Constitution; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Postprandial Period; Sensitivity and Specificity; Time Factors

Topics: Adolescent; Adult; Autoantibodies; Blood Glucose; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 1; Diseases in Twins; Female; Glucose Intolerance; Humans; Hypoglycemia; Insulin; Longitudinal Studies; Self Administration; Time Factors; Twins, Monozygotic

Increased triglyceride accumulation has been observed in the diabetic heart, but it is not known whether the abnormalities in myocardial fatty acid metabolism differ between insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients or whether they are present even prior to overt diabetes. Therefore, we studied myocardial fatty acid kinetics with single-photon emission tomography using 123I-heptadecanoic acid (HDA) in four groups of men: impaired glucose tolerance (IGT) (n = 13, age 53 +/- 2 years, mean +/- SEM), IDDM (n = 8, age 43 +/- 3 years), NIDDM (n = 10, age 51 +/- 2 years) and control subjects (n = 8, age 45 +/- 4 years). Echocardiography and myocardial perfusion scintigraphy (IGT and NIDDM groups) were performed to study cardiac function and flow. In the IGT subjects, myocardial HDA beta-oxidation index was reduced by 53% (4.6 +/- 0.4 vs 9.7 +/- 1.0 mumol .min-1.100 g-1, p < 0.01) and HDA uptake by 34% (3.7 +/- 0.2 vs 5.6 +/- 0.3% of injected dose 100g, p < 0.01) compared with the control subjects. The fractional HDA amount used for beta-oxidation was lower in the IGT compared with the control subjects (43 +/- 4 vs 61 +/- 4%, p < 0.05). NIDDM patients also tended to have a lowered HDA beta-oxidation index, whereas IDDM patients had similar myocardial HDA kinetics compared to the control subjects. Myocardial perfusion imaging during the dipyridamole-handgrip stress was normal both in the IGT and NIDDM groups, indicating that abnormal myocardial perfusion could not explain abnormal fatty acid kinetics. In conclusion, even before clinical diabetes, IGT subjects show abnormalities in myocardial fatty acid uptake and kinetics. These abnormalities may be related to disturbed plasma and cellular lipid metabolism.

Topics: Adult; Analysis of Variance; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Echocardiography; Fatty Acids; Fatty Acids, Nonesterified; Glucagon; Glucose Intolerance; Heart; Humans; Iodine Radioisotopes; Male; Middle Aged; Models, Cardiovascular; Myocardium; Reference Values; Tissue Distribution; Tomography, Emission-Computed; Ventricular Function, Left

A case with diabetes mellitus associated with growth hormone (GH)-producing pituitary adenoma is described. A 56-year-old woman who had been treated for diabetes mellitus for 3 years, was admitted for the treatment of hyperglycemia. She showed a few acromegalic features and her plasma GH level was 146 +/- 16 ng/ml. After improvement of plasma glucose level by insulin injection, octreotide therapy (100 micrograms/8 hours) was started. Seven days after the initiation of octreotide therapy, the fasting plasma glucose level was almost normalized without insulin injection. After the octreotide treatment, urinary C-peptide excretion was significantly decreased and the plasma GH level became within normal range. In this case, octreotide appears to have improved the insulin sensitivity by reducing the plasma GH level.

Topics: Acromegaly; Adenoma; Antineoplastic Agents, Hormonal; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Intolerance; Human Growth Hormone; Humans; Hyperglycemia; Insulin Resistance; Middle Aged; Octreotide; Pituitary Neoplasms

This study was undertaken to understand the dynamics of glucose metabolism in healthy non-diabetic subjects older than age 80 (old-old) compared with subjects aged 61 to 79 (young-old), as well as to compare healthy older subjects with impaired glucose tolerance (IGT) with older subjects with normal glucose tolerance (NGT).. A cross sectional, observational study.. A university hospital clinical research center.. There were 28 community-dwelling adults, 10 older than age 80 and 18 aged 61 to 79. Thirteen of these people had NGT and 15 had IGT. Subjects were not taking any medication that interfered with glucose tolerance.. Status of glucose tolerance was determined by an oral glucose tolerance test categorized as NGT or IGT according to WHO criteria. Insulin sensitivity (SI) and glucose effectiveness (SG) were assessed using a tolbutamide-assisted intravenous glucose tolerance test (IVGTT). The data were analyzed using the Minmod modeling program. Glucose tolerance (K(g)) and the acute insulin response to glucose (AIRg) were calculated from the IVGTT.. There were no significant differences between the young-old and old-old in body mass index or in plasma glucose, insulin, or C-peptide levels in the fasting state or during the OGTT. Values for K(g), SI, SG, and AIRg from the IVGTT were similar in the two age groups. When the subjects were classified by glucose tolerance status, the subjects with NGT had age, gender, and body mass index similar to the subjects with IGT. Older people with IGT had a lower K(g) and tended to have higher fasting glucose and similar fasting insulin compared with people with NGT. IGT subjects had lower SI and tended to have lower SG. The AIRg in IGT subjects tended to be low rather than high when compared with older people with NGT.. Otherwise healthy adults more than 80 years of age have measures of glucose metabolism similar to people aged 61 to 79. The presence of IGT in older adults is associated with insulin resistance, regardless of patient age. We hypothesize that the lack of pancreatic islet compensation for insulin resistance may contribute to impaired glucose tolerance in older adults.

Topics: Aged; Aged, 80 and over; Aging; Blood Pressure; C-Peptide; Catecholamines; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Middle Aged

This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness, and hepatic extraction of insulin are altered in subjects with impaired glucose tolerance (IGT). The frequently sampled intravenous glucose tolerance test was performed in postmenopausal women (age 63 yr, body mass index range 21.6-28.9 kg/m2) with IGT (n = 10) or normal glucose tolerance (NGT; n = 10). Insulin sensitivity (S(I)) was significantly lower in IGT than in NGT (P = 0.030). In contrast, insulin secretion was not significantly different between the two groups as determined by area under the curve for insulin and C-peptide, acute insulin response to glucose (AIR(G)), and glucose sensitivity of first-phase (phi1) or of second-phase (phi2) insulin secretion. In NGT (r = -0.68, P = 0.029) but not in IGT (r = -0.05, not significant), S(I) correlated negatively with phi1. The B-cell "adaptation index" (S(I) x phi1) was lower in IGT than in NGT [83 +/- 25 vs. 171 +/- 29 min(-2)/(mmol/l), P = 0.042]. Also, the B-cell "disposition index" (S(I) times AIR(G)) was lower in IGT (83 +/- 25 10(-4) min(-1)) than in NGT (196 +/- 30 10(-4) min(-1), p = 0.011). In contrast, glucose effectiveness or hepatic extraction of insulin was not different between IGT and NGT. We conclude that postmenopausal women with IGT fail to adequately adapt to lowered S(I) by increasing first-phase insulin secretion.

Topics: Analysis of Variance; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Secretion; Middle Aged; Postmenopause; Reference Values; Time Factors; Triglycerides

We tested the hypothesis that glucose intolerance develops in genetically prone subjects when exogenous insulin resistance is induced by dexamethasone (dex) and investigated whether the steroid-induced glucose intolerance is due to impairment of beta-cell function alone and/or insulin resistance. Oral glucose tolerance (OGTT) and intravenous glucose tolerance tests with minimal model analysis were performed before and following 5 days of dex treatment (4 mg/day) in 20 relatives of non-insulin-dependent diabetic (NIDDM) patients and in 20 matched control subjects (age: 29.6 +/- 1.7 vs 29.6 +/- 1.6 years, BMI: 25.1 +/- 1.0 vs 25.1 +/- 0.9 kg/m2). Before dex, glucose tolerance was similar in both groups (2-h plasma glucose concentration (PG): 5.5 +/- 0.2 [range: 3.2-7.0] vs 5.5 +/- 0.2 [3.7-7.4] mmol/l). Although insulin sensitivity (Si) was significantly lower in the relatives before dex, insulin sensitivity was reduced to a similar level during dex in both the relatives and control subjects (0.30 +/- 0.04 vs 0.34 +/- 0.04 10(-4) min(-1) per pmol/l, NS). During dex, the variation in the OGTT 2-h PG was greater in the relatives (8.5 +/- 0.7 [3.9-17.0] vs 7.5 +/- 0.3 [5.7-9.8] mmol/l, F-test p < 0.05) which, by inspection of the data, was caused by seven relatives with a higher PG than the maximal value seen in the control subjects (9.8 mmol/l). These "hyperglycaemic" relatives had diminished first phase insulin secretion (O1) both before and during dex compared with the "normal" relatives and the control subjects (pre-dex O1: 12.6 +/- 3.6 vs 26.4 +/- 4.2 and 24.6 +/- 3.6 (p < 0.05), post-dex O1: 22.2 +/- 6.6 vs 48.0 +/- 7.2 and 46.2 +/- 6.6 respectively (p < 0.05) pmol x l(-1) x min(-1) per mg/dl). However, Si was similar in "hyperglycaemic" and "normal" relatives before dex (0.65 +/- 0.10 vs 0.54 +/- 0.10 10(-4) x min(-1) per pmol/l) and suppressed similarly during dex (0.30 +/- 0.07 vs 0.30 +/- 0.06 10(-4) x min(-1) per pmol/l). Multiple regression analysis confirmed the unique importance of low pre-dex beta-cell function to subsequent development of high 2-h post-dex OGTT plasma glucose levels (R2 = 0.56). In conclusion, exogenous induced insulin resistance by dex will induce impaired or diabetic glucose tolerance in those genetic relatives of NIDDM patients who have impaired beta-cell function (retrospectively) prior to dex exposure. These subjects are therefore unable to enhance their beta-cell response in order to match the dex-induced insulin resistan

Topics: Adult; Blood Glucose; C-Peptide; Cholesterol, HDL; Dexamethasone; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Risk Factors

The authors evaluated the significance of beta cell function, non-insulin-dependent glucose disposal (glucose effectiveness [Sg]), and insulin-dependent glucose disposal (insulin sensitivity) in African immigrants with varying degrees of glucose tolerance. Thirty-two African immigrants residing in Franklin County, Ohio, were studied. There were 16 subjects with normal glucose tolerance (NGT), 11 with intermediate glucose tolerance (IGT), and 5 with type II diabetes mellitus (DM). Insulin sensitivity index and Sg were measured by an insulin-modified, frequently sampled intravenous glucose tolerance test. The mean fasting and post-glucose serum glucose levels were lowest in the NGT, intermediate in the IGT group, and highest in the DM group. Mean serum insulin and c-peptide responses rose briskly by threefold to a peak in the NGT and the IGT groups. In the DM group, mean serum insulin and c-peptide responses were severely blunted to glucose stimulation. The sensitivity index was highest in the NGT (3.09 +/- 0.27), intermediate in the IGT (1.81 +/- 0.47), and lowest in the DM (0.48 +/- 0.28 x 10(-2).mins-1 (microU/ml)-1). The Sg was identical in the NGT (2.78 +/- 0.22) and IGT (2.78 +/- 0.27) groups but was slightly but not significantly lower in the DM (2.20 +/- 0.35 x 10(-2).mins-1). In addition, the glucose decay constant was not statistically different in the NGT (3.00 +/- 0.38) and IGT (2.25 +/- 0.19) group, but the mean values were significantly greater than in the patients with diabetes (0.78 +/- 0.15 percent/mins). The mean disposition index (sensitivity index X beta cell function as assessed by both insulin and c-peptide) was significantly greater in NGT than in the IGT (P<0.05) and in the diabetic group (P<0.001). In summary, the authors demonstrate that, in native African immigrants, type II diabetes is associated with significant reduction in beta cell function, insulin sensitivity, and glucose decay constant, but not in Sg. In patients with intermediate or impaired glucose tolerance, there is moderate insulin resistance and evidence of inadequate compensation by beta cell, but the Sg, the Sg at theoretical insulin concentration, and glucose decay constant remain normal. They conclude that, unlike other ethnic and racial groups, in glucose intolerant native African patients, alterations in Sg or non-insulin dependent glucose disposal (ie, tissue glucose sensitivity) do not appear to play a significant role in the impairment of glucose tolerance a

Topics: Adult; Black People; Blood Glucose; Body Mass Index; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 2; Emigration and Immigration; Fasting; Ghana; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Ohio; Reference Values

Controversy persists about whether hyperinsulinemia and hyperproinsulinemia are independent risk markers for coronary atherosclerosis. A common limitation of most previous studies has been imprecise categorization of disease status in normal and coronary artery disease (CAD) groups. We assessed the relationship of pancreatic beta-cell secretory products and premature CAD in a case-control study of 134 nondiabetic subjects, aged < or = 55 years old, carefully defined for CAD status by catheterization and/or thallium stress studies. Case patients comprised 66 patients with premature CAD, and control subjects (non-CAD group) included 68 patients without CAD but with traditional CAD risk factors and chest pain and/or abnormal electrocardiograms but normal catheterization and/or thallium stress studies. In addition to the CAD and non-CAD group comparison, both groups were compared with a reference group of 27 mixed lean and obese control volunteers. All CAD and non-CAD patients had a 3-h 75-g oral glucose tolerance test with measurement of fasting and post-glucose load immunoreactive insulin (IRI), specific insulin (INS), proinsulin-like material (PI), and C-peptide. Increased fasting insulin and fasting proinsulin levels both were statistically significantly associated with higher odds of being in either the premature CAD and the non-CAD groups when compared with the reference group in a polychotomous logistic regression model (odds ratio of at least 1.20 for a 20% increase in each beta-cell secretory product in both comparisons, P < 0.05). However, increased pancreatic beta-cell secretory hormone levels did not show a statistically significant relative risk for being in the premature CAD group when compared with the non-CAD group. After adjustment for BMI, all statistically significant associations disappeared for IRI, INS, and PI when the odds favoring being in the CAD and non-CAD groups were compared versus the reference group. Furthermore, the odds of being in the premature CAD and non-CAD groups when compared with the reference group were not significantly associated to the ratio of PI to insulin and C-peptide. Thus, although there is a statistically significant association between the odds of having premature CAD with elevated insulin and proinsulin levels compared with the reference group, these findings are equally common in subjects with traditional CAD risk factors without detectable CAD. Furthermore, the association of higher insulin and proinsulin

Topics: Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Chest Pain; Coronary Disease; Diabetes Mellitus; Ethnicity; Female; Glucose Intolerance; Humans; Insulin; Male; Middle Aged; Odds Ratio; Proinsulin; Reference Values; Regression Analysis; Risk Factors; Sex Factors; Smoking

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

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

To evaluate if an increased proinsulin-to-insulin ratio (PI/I) in former gestational diabetes mellitus (GDM) subjects could be a marker for later impairment of glucose tolerance.. This study is a prospective follow-up. In a previous follow-up study of former GDM subjects 3-4 years after an index pregnancy, an increased PI/I was found also in normoglycemic nonobese former GDM subjects compared with control subjects. A 75-g oral glucose tolerance test (OGTT) was performed 3 years after the first follow-up, i.e., 6-7 years after the index pregnancy in 97 of the former GDM subjects and in 23 control subjects. A 75-g OGTT according to the World Health Organization was performed. Glucose, insulin, proinsulin, and C-peptide were determined at 0, 30, 60, 90, 120, 150, and 180 min after the glucose intake.. Since the first follow-up, an additional 3 in 97 (3.1%) and 15 in 97 (15.5%) of the former GDM subjects had NIDDM or impaired glucose tolerance (IGT), respectively. All control subjects still had a normal OGTT. The fasting PI/I at follow-ups 1 and 2 was significantly correlated in the former GDM subjects (r = 0.41, P < 0.001) and in the control group (r = 0.46, P < 0.05). There was no significant correlation between the PI/I in follow-up 1 and the fasting or 2-h glucose values at follow-up 2. If GDM subjects with a PI/I in the upper quartile in the first follow-up were compared with those with a lower PI/I, there were no significant differences in outcome of OGTT in the second follow-up.. The hypothesis that an increased fasting PI/I is a marker for later development of NIDDM or IGT in former GDM subjects could not be supported.

Topics: Adult; Biomarkers; Birth Weight; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Middle Aged; Predictive Value of Tests; Pregnancy; Proinsulin; Reference Values; Statistics, Nonparametric; Time Factors

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

In animals, bypassing the oropharyngeal receptors by intragastric administration of glucose results in glucose intolerance. To determine whether the absence of oral sensory stimulation alters glucose tolerance in humans, we monitored plasma levels of glucose and hormones after intragastric administration of glucose, with and without subjects tasting food. Plasma glucose area under the curve (AUC) was significantly lower after oral sensory stimulation (3,433 +/- 783 vs. 5,643 +/- 1,397 mg.dl-1. 195 min-1; P < 0.03; n = 8). Insulin and C-peptide AUCs were higher during the first one-half of the sampling period (insulin, 5,771 +/- 910 vs. 4,295 +/- 712 microU. ml-1.75 min-1; P < 0.05; C-peptide, 86 +/- 10 vs. 66 +/- 9 ng.ml-1. 75 min-1; P < 0.03) and lower during the second one-half of the sampling period compared with the control condition (1,010 +/- 233 vs. 2,106 microU.ml-1. 120 min-1; P < 0.025; 31 +/- 8 vs. 56 +/- 18 ng.ml-1. 120 min-1; P < 0.05; insulin and C-peptide, respectively). Oral sensory stimulation markedly increased plasma glucagon compared with the control condition (1,258 +/- 621 vs. -2,181 +/- 522 pg.ml-1. 195 min-1; P < 0.002). These data provide evidence in humans that oral sensory stimulation influences glucose metabolism and suggest that the mechanisms elicited by this cephalic stimulation are necessary for normal glucose homeostasis.

Topics: Adult; Blood Glucose; C-Peptide; Glucagon; Glucose; Glucose Intolerance; Humans; Insulin; Intubation, Gastrointestinal; Male; Mouth; Sensation; Stimulation, Chemical

After successful pancreas transplantation, insulin-dependent diabetic patients are characterized by a normal or at worst impaired oral glucose tolerance (World Health Organisation criteria). It is not known which pathophysiological mechanisms cause the difference between normal and impaired oral glucose tolerance. Therefore, we studied 41 patients after successful combined pancreas-kidney transplantation using stimulation in the fasting state with oral glucose (75 g), intravenous glucose (0.33 g/kg) and glucagon bolus injection (1 mg i.v.). Glucose (glucose oxidase), insulin and C-peptide (immunoassay) were measured. Repeated-measures analysis of variance and multiple regression analysis were used to analyse the results which showed: 28 patients had a normal, and 13 patients had an impaired oral glucose tolerance. Impaired oral glucose tolerance was associated with a greatly reduced early phase insulin secretory response (insulin p < 0.0001; C-peptide p = 0.037). Age (p = 0.65), body mass index (p = 0.94), immunosuppressive therapy (cyclosporin A p = 0.84; predniso(lo)ne p = 0.91; azathioprine p = 0.60) and additional clinical parameters were not different. Reduced insulin secretory responses in patients with impaired oral glucose tolerance were also found with intravenous glucose or glucagon stimulations. Exocrine secretion (alpha-amylase in 24-h urine collections) also demonstrated reduced pancreatic function in these patients (-46%; p = 0.04). Multiple regression analysis showed a significant correlation of 120-min glucose with ischaemia time (p = 0.003) and the number of HLA-DR mismatches (p = 0.026), but not with HLA-AB-mismatches (p = 0.084). In conclusion, the pathophysiological basis of impaired oral glucose tolerance after pancreas transplantation is a reduced insulin secretory capacity. Transplant damage is most likely caused by perioperative influences (ischaemia) and by the extent of rejection damage related, for example, to DR-mis-matches.

Topics: Adult; alpha-Amylases; Analysis of Variance; Biomarkers; Blood Glucose; Blood Group Incompatibility; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Insulin; Insulin Secretion; Kidney Transplantation; Male; Pancreas Transplantation; Reference Values; Regression Analysis; Time Factors

Topics: Autoantibodies; C-Peptide; Case-Control Studies; Child; Diabetes Complications; Diabetes Mellitus; Glucose Intolerance; Humans; Oman; Vitiligo

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

Our purpose was to determine the prevalence of autoantibodies to glutamic acid decarboxylase in women who had had gestational diabetes, including those in whom insulin-requiring or non-insulin-requiring diabetes mellitus has since developed.. The study group comprised 734 women with previous gestational diabetes who were consecutive attendees to a follow-up clinic. These women were tested for autoantibodies to glutamic acid decarboxylase with a radioimmunoprecipitation assay. We similarly tested 104 women in whom permanent diabetes mellitus developed after gestational diabetes, of whom 20 were using insulin and 84 were not. Those using insulin also had fasting C-peptide levels measured.. Thirteen of the 734 (1.8%, 95% confidence interval 0.9% to 3.0%) women with previous gestational diabetes were positive for autoantibodies to glutamic acid decarboxylase. Of the 20 women with diabetes treated with insulin, 12 had insulin deficiency confirmed by low levels of C peptide; all 12 were positive for autoantibodies to glutamic acid decarboxylase. Of the 84 women with diabetes not requiring insulin, 6 (7.1%, 95% confidence interval 2.7% to 14.9%) were positive for autoantibodies to glutamic acid decarboxylase.. The prevalence of autoantibodies to glutamic acid decarboxylase in women with previous gestational diabetes was 1.8%. Our data also showed that insulin-dependent diabetes mellitus will develop in 1.7% of women with gestational diabetes. A positive test for autoantibodies to glutamic acid decarboxylase may help in the early identification of insulin-dependent diabetes mellitus. Adult-onset insulin-dependent diabetes mellitus developed in only 5.2% (12/230) of women with previous gestational diabetes who later had diabetes mellitus.

Topics: Adult; Autoantibodies; C-Peptide; Confidence Intervals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Glutamate Decarboxylase; Humans; Middle Aged; Pregnancy; Reference Values; Time Factors

The peripheral hyperinsulinaemia of hypertriglyceridaemic subjects has only been defined using insulin immunoassays in which proinsulin and proinsulin fragments cross-react. Relative contributions of pancreatic secretion and hepatic extraction of insulin to this hyperinsulinaemia have not been studied. We, therefore, reassessed the hyperinsulinaemia of hypertriglyceridaemia by measuring fasting plasma concentrations of intact proinsulin, glucose, insulin, and C-peptide in 24 hypertriglyceridaemic subjects with normal glucose tolerance (n = 14) and with impaired glucose intolerance (n = 10) and in normal subjects (n = 14). Hypertriglyceridaemic subjects had higher (p < 0.01) fasting concentrations of insulin and C-peptide and greater (p < 0.01) fasting insulin: C-peptide molar ratios than in control subjects. Fasting intact proinsulin concentrations were similar in hypertriglyceridaemic subjects with normal glucose tolerance and control subjects but these were lower (p < 0.01) than in hypertriglyceridaemic subjects with impaired glucose tolerance. These results suggest that the fasting peripheral hyperinsulinaemia of hypertriglyceridaemic subjects is due to increased pancreatic secretion and reduced hepatic fractional extraction of insulin. The peripheral hyperinsulinaemia of hypertriglyceridaemia appears to reflect peripheral insulin resistance and is not attributable to elevated proinsulin concentrations which are characteristic of impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus.

Topics: Adult; Blood Glucose; C-Peptide; Cholesterol; Cohort Studies; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypertriglyceridemia; Insulin; Male; Middle Aged; Proinsulin; Reference Values; Triglycerides

The exocrine and endocrine pathophysiology of chronic calcific pancreatitis of the tropics (CCPT) remains elusive. The objective of this study was to evaluate the spectrum and correlates of the exocrine and endocrine pancreatic dysfunction in CCPT. Thirty-seven consecutive patients with a clinico-radiological diagnosis of CCPT were stratified into three subgroups: CCPT-normal glucose tolerance (NGT), CCPT-abnormal glucose tolerance (IGT) and CCPT-diabetes mellitus (DM). Ten ketosis resistant young diabetic (KRDY) patients, 10 classical insulin dependent diabetes mellitus (IDDM) patients and 18 healthy matched controls were included for comparison. Fecal chymotrypsin (FCT) levels and blood C-peptide levels (basal and post i.v. glucagon stimulation) were estimated for assessing the exocrine and endocrine pancreatic functions, respectively. Sonography was performed to evaluate the pancreatic size and ductal diameter. Pancreatic exocrine-endocrine correlation was examined by studying the C-peptide/fecal chymotrypsin ratio (CP/FCT) (CP/FCT of normal controls = 1). Mean FCT levels in all 3 subgroups of CCPT (NGT: 3.4 micrograms/g; IGT: 0.82 microgram/g; DM: 2.4 micrograms/g) were very low (87-96% reduction in exocrine pancreatic dysfunction; mean FCT in healthy controls was 22.8 micrograms/g) (P < 0.0001). In contrast, KRDY and IDDM patients displayed 50-54% reduction in pancreatic acinar function (P < 0.001). Basal and stimulated C-peptide levels progressively fell in the 3 CCPT subsets (NGT: 0.23 and 0.46 > IGT: 0.14 and 0.29 > DM 0.10 and 0.14) (P < 0.01). CCPT patients exhibited pancreatic atrophy and ductal dilation (> 3 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Age of Onset; Analysis of Variance; Blood Glucose; C-Peptide; Calcinosis; Chronic Disease; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Islets of Langerhans; Male; Pancreas; Pancreatitis; Reference Values; Tropical Climate; Ultrasonography

Disproportionate elevation [increased proinsulin/insulin (PI/INS) ratio] of PI immunoreactivity is associated with noninsulin-dependent diabetes mellitus (NIDDM). The nature of this abnormality is not known. To address the question of whether genetic factors contribute to hyperproinsulinemia, we measured fasting levels of PI immunoreactivity, intact INS, and C peptide (CP) in 12 pairs of monozygotic twins discordant for NIDDM for a mean (+/- SEM) period of 9 +/- 3 yr. Thirteen age- and body mass index-matched healthy subjects without any family history of NIDDM acted as controls. The nondiabetic twins had levels of fasting INS, CP, PI, PI/CP, and PI/INS similar to those of control subjects. Fasting levels of PI, and PI/CP and PI/INS ratios were significantly 2- to 3-fold elevated in NIDDM twins compared to those in both nondiabetic twins and control subjects. To investigate whether hyperproinsulinemia in these NIDDM patients was due to a differential elevation of intact PI or conversion intermediates, we analyzed PI profiles in NIDDM twins and normal subjects by high pressure liquid chromatography. PI was heterogeneous and consisted mainly of des(31,32)-PI and intact PI in both NIDDM patients and normal subjects, with no major difference in composition between the groups. Small amounts of des(64,65)-PI (0-11%) were measured in some patients and normal subjects. The results suggest that hyperproinsulinemia is not a genetically determined trait per se in NIDDM. Disproportionately elevated PI levels seem to be related to the actual disease process. Further conversion of intact PI and des(31,32)-PI may be equally impaired in NIDDM.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Case-Control Studies; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; Diseases in Twins; Glucose Intolerance; Humans; Insulin; Proinsulin; Reference Values; Twins, Monozygotic

Recent evidence suggests that the postprandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion (delta 0-10 min insulin area divided by delta 0-10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2-19.4] vs 9.1 [2.6-14.5] mU.mmol-1; p < 0.01). During the clamp, circulating insulin (93 +/- 8 [mean +/- SEM] and 81 +/- 10 mU.l-1) and glucagon (54 +/- 4 and 44 +/- 6 ng.l-1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78 +/- 0.27 vs 4.47 +/- 0.53 mg.kg-1.min-1; p < 0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38 +/- 0.10 and 0.30 +/- 0.18 mg.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Deuterium; Glucagon; Glucose; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Insulin Secretion; Liver; Male; Middle Aged; Radioisotope Dilution Technique; Reference Values; Somatostatin

To examine endocrine states of mothers with normal 75-g oral glucose tolerance tests (GTTs) who gave birth to large for gestational age (LGA) neonates (group I) and to examine those neonates.. We examined plasma glucose levels and serum immunoreactive insulin responses after the 75-g oral GTT was given to group I mothers (N = 34), mothers with an abnormal oral GTT who gave birth to LGA neonates (group II, N = 21), and those with normal oral GTTs having appropriate for gestational age neonates (group III, N = 173). We also examined the infants, checking neonatal birth weight, levels of immunoreactive insulin and C-peptide immunoreactivity in cord sera at birth and the lowest blood sugar level after birth to see if a correlation existed between them.. Group I and II mothers showed higher titers in plasma glucose levels and remarkably enhanced ratios of 60- to 30-minute immunoreactive insulin values (immunoreactive insulin up-ratio) after load compared with those of group III mothers. Cord serum immunoreactive insulin and C-peptide immunoreactivity were significantly higher and the lowest blood sugar level was significantly reduced in group I and II neonates compared with those in group III. We observed a positive correlation between cord serum immunoreactive insulin, C-peptide immunoreactivity, and birth weight, but a negative correlation between cord serum immunoreactive insulin, birth weight, and the lowest blood sugar level in group I and II neonates (strongest tendency in group II), but not in group III neonates.. All of the abnormal carbohydrate metabolic responses in group I mothers and neonates may result in the promotion of growth in LGA fetuses similar to group II, but to a lesser extent. Identification of group I mothers by the immunoreactive insulin up-ratio after oral GTT will help predict the occurrence of LGA neonates and their possible hypoglycemia.

Topics: Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Blood; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Pregnancy; Pregnancy Complications

Vitamin D deficiency reduces insulin secretion and still occurs in East London Asians in whom the prevalence of diabetes mellitus is at least four times that of Caucasians. Vitamin D status was assessed in 44 of 65 non-diabetic subjects 'at risk' of diabetes (spot blood glucose level >6.0 mmol/l <2 h post cibum, or>4.6 mmol/l >2 h post cibum on two separate occasions) and in 15 of 60 age and sex-matched 'low-risk' control subjects who attended for oral glucose tolerance test (OGTT) after screening of 877 omnivorous subjects not known to have diabetes. It was found that 95% of at-risk and 80% of low-risk subjects were vitamin D deficient (serum 25-hydroxy-vitamin D <11 ng/ml). Diabetes was present in 16, impaired glucose tolerance in 12 and normoglycaemia in 19 at-risk subjects, imparied glucose tolerance in 2, and normoglycaemia in 13 low-risk subjects. Correlation of 30-min OGTT blood glucose, specific insulin and C-peptide levels with 25-hydroxy-vitamin D concentrations in 44 at-risk subjects were -0.31 (p=0.04), 0.59 (p=0.0001) and 0.44 (p=0.006). In 15 'not-at-risk' subjects 30-min OGTT specific insulin and C-peptide levels correlated with 25-hydroxy-vitamin D, r=0.39 (p=0.04) and 0.16 (p=0.43), respectively. Serum alkaline phosphatase concentration was higher in at-risk than not-at-risk subjects (59.6 vs 46.5 IU/l, p=0.012); corrected calcium concentrations were comparable (2.38 vs 2.39 mmol/l, p=0.7). Following treatment with 100,000 IU vitamin D by i.m. injection, specific insulin, C-peptide [30 min on OGTT] and 25-hydroxy-vitamin D concentrations had risen 8-12 weeks later [mean +/- DS] from 57 +/- 62 to 96.2 +/- 82.4 mU/l [p=0.0017], 1.0 +/- 0.4 to 1.7 +/- 0.8 pmol/ml [p=0.001] and 3.6 +/- 1.8 to 13.5 +/- 7.4 ng/ml [p=0.0001], (but not to low-risk group values of 179 +/- mU/l, 2.7 +/- 1.14 pmol/ml and 8.16 +/- 6.4 ng/ml), respectively. Both total serum alkaline phosphatase and corrected calcium concentrations rose following vitamin D treatment in the at-risk subjects by 11.1 +/- 8.22 (from 44 to 55 IU/l) and 0.15 +/- 0.18, (2.43 to 2.57 mmol/l), respectively (p=0.004). Abnormal glucose tolerance was unchanged by vitamin D treatment. The value of early and sustained repletion with vitamin D in diabetes prophylaxis should be examined in communities where vitamin D depletion is common.

Topics: Asian People; Bangladesh; Blood Glucose; C-Peptide; Calcifediol; Calcitriol; Diabetes Mellitus; Glucose Intolerance; Humans; Insulin; Insulin Secretion; London; Prevalence; Proinsulin; Reference Values; Regression Analysis; Risk Factors; Statistics, Nonparametric; Vitamin D Deficiency; White People

The effects of heparin-induced non-esterified free fatty acid (NEFA) release on insulin sensitivity index were studied in individuals with varying degrees of glucose intolerance and beta cell dysfunction during the frequently sampled intravenous glucose tolerance test (IVGTT). The groups comprised: Group 1 (n = 5): newly diagnosed Type 2 diabetic patients, Group 2 (n = 11): impaired glucose tolerance patients (IGT), and Group 3 (n = 16): healthy normal glucose tolerance subjects. The serum insulin and c-peptide levels were severely blunted in the diabetic patients when compared to both non-diabetic groups. Mean fasting and post-heparin plasma NEFA levels were approximately 1.8 fold greater (p < 0.05) in the diabetic patients when compared to the other two groups. The mean insulin sensitivity index was lowest in the diabetic patients, intermediate in the IGT patients, and highest in the healthy controls. A significant negative relationship was found between the insulin sensitivity index and stimulated NEFA (r = -0.537, p < 0.008) but not with the fasting NEFA levels in our subjects. In summary, the frequently sampled IVGTT protocol that employs heparin flushes results in marked elevations in NEFA in Type 2 diabetic patients with poor beta cell dysfunction but not in subjects with intermediate or normal glucose tolerance. The higher plasma NEFA levels during heparin injections could worsen the model-derived, insulin sensitivity index and could impair the ability to achieve an acceptable modelling in Type 2 diabetic patients. We therefore suggest heparin should be avoided in such patients when using this protocol.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Fatty Acids, Nonesterified; Female; Glucose Intolerance; Glucose Tolerance Test; Heparin; Humans; Insulin; Kinetics; Male; Middle Aged; Reference Values

Thirty-five patients of insulin-dependent diabetes mellitus (IDDM) were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS) was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI) levels and serum C-peptide radioimmunoreactivity (CPR) as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM.

Topics: Adult; Age of Onset; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Glucose Intolerance; Humans; Hyperlipidemias; Insulin; Male; Triglycerides

Since second-generation (Nisei) Japanese Americans are prone to develop the insulin resistance syndrome, younger third-generation (Sansei) Japanese Americans from a cross-sectional 10% volunteer sample of Sansei men (n = 115) and women (n = 115) 34 years or older in King County, Washington with normal glucose tolerance or IGT were examined for metabolic and adipose risk factors associated with this syndrome. After an overnight 10-h fast, blood samples were taken for measurement of glucose, insulin, C-peptide, lipids, and lipoproteins, followed by a 3-h 75-g oral glucose tolerance test with blood samples taken for glucose, insulin, and C-peptide measurement. BMI (kg/m2), skinfolds, and body fat areas (by computed tomography) were measured. IGT was diagnosed in 19% of the men and 31% of the women. Men with IGT had more adiposity, both overall and in thoracic and visceral sites, had higher fasting plasma insulin and C-peptide, and tended to have higher fasting triglyceride and lower HDL cholesterol than men with normal glucose tolerance. Women with IGT had more thoracic subcutaneous fat and intra-abdominal fat and lower fasting HDL cholesterol than women with normal glucose tolerance, and tended to have higher fasting triglyceride and LDL cholesterol. Women with IGT also had higher fasting plasma insulin than women with normal glucose tolerance but tended to be less hyperinsulinaemic than men. Differences in fasting insulin, C-peptide, and lipids were best predicted by intra-abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adult; Blood Glucose; Body Mass Index; C-Peptide; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Japan; Lipids; Lipoproteins; Male; Middle Aged; Risk Factors; Sex Characteristics; Sex Factors; Skinfold Thickness; Washington

Glucose intolerance and diabetes mellitus are both prevalent in cirrhosis, yet the pathogenesis of impaired glucose metabolism remains unknown. Therefore insulin secretion (hyperglycemic clamp, +125 mg/dl), insulin sensitivity (euglycemic hyperinsulinemic insulin clamp, +10 microU/ml and +50 microU/ml), whole-body glucose oxidation (indirect calorimetry) and glucose turnover ([6,6-2H2]glucose isotope dilution) were evaluated in a homogenous group of cirrhotic patients with glucose intolerance (n = 7) or frank diabetes mellitus (n = 6). The results were compared with those obtained in control subjects (n = 8). In glucose-intolerant patients, whole-body glucose uptake (mainly reflecting glucose utilization by muscle) was significantly impaired in patients during both insulin infusions as a result of decreased stimulation of the two major intracellular pathways of glucose disposal--nonoxidative glucose disposal (i.e., glycogen synthesis) and glucose oxidation. Hepatic glucose production was normal in the basal state and was normally suppressed during stepwise insulin infusion (by 65% and 85%, respectively, p = NS vs. controls). Hyperglycemia-induced increases of plasma C-peptide concentrations were comparable to those in controls (p = NS). In diabetic patients, insulin-mediated glucose uptake was significantly reduced, mainly because of impaired non-oxidative glucose disposal. Glucose oxidation appeared to be reduced, too. Hepatic glucose production was significantly increased in the basal state (3.03 +/- 0.24 vs. 2.34 +/- 0.10 mg/kg min, p < 0.02) and during insulin infusion (+50 microU/ml: 0.67 +/- 0.17 vs. 0.13 +/- 0.08 mg/kg min, p < 0.05) compared with that in controls. Both the first and second phases of beta-cell secretion were significantly reduced in response to steady-state hyperglycemia (both p < 0.01 vs. control values). In conclusion, glucose intolerance in cirrhosis results from two abnormalities that occur simultaneously: (a) insulin resistance of muscle and (b) an inadequate response (even when comparable to that of controls) of the beta-cells to appropriately secrete insulin to overcome the defect in insulin action. Diabetes mellitus in insulin-resistant cirrhotic patients develops as the result of progressive impairment in insulin secretion together with the development of hepatic insulin resistance leading to fasting hyperglycemia and a diabetic glucose tolerance profile.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose; Glucose Clamp Technique; Glucose Intolerance; Humans; Hyperglycemia; Insulin; Lactates; Lactic Acid; Liver Cirrhosis; Male; Middle Aged; Reference Values

We have evaluated the metabolic clearance rate (MCR) of insulin and insulin sensitivity in 12 older patients with cystic fibrosis (CF) using the hyperinsulinemic euglycemic clamp method. Compared with a control group matched accurately for age and body mass index (BMI), the MCR of insulin was significantly enhanced in CF CF = 21.85 +/- 1.17 v controls = 16.01 +/- 0.92 mL/kg/min, P < .005), and this difference persisted after correction for lean body mass ([LBM] CF = 26.32 +/- 1.28 v controls = 19.09 +/- 1.09 mL/kg LBM/min, P < .005). Glucose disposal rates (M) were similar in the two groups during the clamp (CF = 7.28 +/- 0.41 v controls = 6.83 +/- 0.60 mg/kg/min, P > .5), but the insulin sensitivity index, M/I x 100 (I = steady-state insulin concentration), was markedly increased in the CF group (CF = 17.62 +/- 1.30 v controls = 11.75 +/- 0.71, P < .005). In conclusion, the MCR of insulin is enhanced in CF, which is in keeping with previous observations on drug metabolism in this disorder. Second, insulin sensitivity is increased in CF, and this points to a compensatory mechanism to counteract the insulinopenia.

Topics: Adolescent; Adult; C-Peptide; Cystic Fibrosis; Female; Glucose Clamp Technique; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Male; Metabolic Clearance Rate

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

To report studies on an elderly patient with moderate NIDDM associated with marked fasting hyperinsulinemia.. The propositus and several family members were studied by a combination of clinical, biochemical, and molecular genetic approaches to define the underlying genetic defect.. Fasting levels of contrainsulin hormones were normal, and resistance to exogenous insulin was absent. Gel filtration and reverse-phase high-performance liquid chromatography revealed elevated amounts of a structurally abnormal proinsulin intermediate (AC proinsulin). A study of the family of the propositus showed the same abnormality in 4 of 5 members in 3 successive generations. Genetic analysis revealed a point mutation affecting residue 65 of human proinsulin (Arg-->His) in one allele of the insulin gene in the propositus, a defect similar to that described previously in 3 other apparently unrelated lineages.. This family exhibits a clear-cut relationship between increasing age and metabolic decompensation in all the hyperproinsulinemic members, suggesting that (inherited) metabolic stress and age both contribute to development of diabetes mellitus.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; DNA Primers; Exons; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Male; Molecular Sequence Data; Polymerase Chain Reaction; Proinsulin

The effects of impaired glucose tolerance and obesity, in isolation and in combination, on basal (postabsorptive) intermediary metabolism were examined in four groups of subjects (n = 10 for each) matched for age and gender: Group 1: Non-obese healthy controls with normal glucose tolerance (75 g); Group 2: Non-obese subjects with impaired glucose tolerance; Group 3: Morbidly obese subjects with normal glucose tolerance; Group 4: Morbidly obese subjects with impaired glucose tolerance. While there was no significant difference in fasting blood glucose concentrations between the four groups plasma immuno-reactive insulin concentrations were elevated (p < 0.01 or less) in the obese subjects relative to the non-obese subjects within each category of glucose tolerance. Basal immunoreactive insulin concentrations in non-obese subjects with impaired glucose tolerance were also elevated (p < 0.01) relative to the non-obese healthy controls. Concentrations of glycerol (p < 0.01), non-esterified fatty acids (p < 0.01), and total ketone bodies (p < 0.001) were significantly higher in the obese/normal glucose tolerance and obese/impaired glucose tolerance groups relative to their matched non-obese counterparts. Compared with the subjects with normal glucose tolerance, only lactate (p < 0.05) and pyruvate (p < 0.05) concentrations were elevated in the non-obese/impaired glucose tolerance and obese/impaired glucose tolerance groups, respectively. In conclusion, in addition to fasting hyperinsulinaemia the regulation of lipolysis and ketone body metabolism is abnormal in the basal state in morbid obesity. By contrast, despite normal fasting blood glucose concentrations, impaired glucose tolerance is associated with disturbances of other aspects of basal carbohydrate metabolism.

Topics: Adult; Alanine; Analysis of Variance; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Intolerance; Glucose Tolerance Test; Glycerol; Humans; Insulin; Ketone Bodies; Male; Obesity, Morbid; Pyruvates; Reference Values