c-peptide and Weight-Loss

The study evaluated the predictive role of preoperative fasting C-peptide, hemoglobin (Hb)A1c, fasting plasma glucose (FPG), and body mass index (BMI) levels on diabetes remission in patients with type 2 diabetes following bariatric surgery.. Medline, PubMed, Central, and Google Scholar databases of up to September 7, 2016 were searched using the following terms: type 2 diabetes mellitus, gastric bypass, Roux-en-Y, anastomosis, C-peptide, weight loss, HbA/HbA1c, predictive/predictor.. Meta-analysis of the pooled data indicated that fasting C-peptide was predictive of increased chance of remission of type 2 diabetes (pooled difference in means = 0.93, 95% confidence interval [CI] = 0.61 to 1.25, p < .001). The analysis also found that FPG (pooled standardized mean difference = -0.42, 95% CI: -0.64 to -0.20, p < .004) and HbA1c levels (pooled difference in means = -1.05, 95% CI: -1.48 to -0.62, p < .001) were associated with reduced odds of type 2 diabetes remission. BMI was not found to be associated with remission (pooled difference in means = 0.29, 95% CI: 0.30 to 0.88, p = .343). In general, subgroup analysis, which evaluated the pooled data from the retrospective and prospective studies separately, gave similar results.. Preoperative fasting plasma C-peptide was associated with increased type 2 diabetes remission after bariatric surgery, whereas baseline HbA1c and FPG levels were associated with reduced chance of remission. These parameters may be used as a guideline in weighing the risks and benefits for surgical intervention in patients with type 2 diabetes.

Topics: Bariatric Surgery; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Glycated Hemoglobin; Humans; Obesity, Morbid; Predictive Value of Tests; Risk Assessment; Treatment Outcome; Weight Loss

The impact of bariatric surgery beyond its effect on weight loss has entailed a change in the way of regarding it. The term metabolic surgery has become more popular to designate those interventions that aim at resolving diseases that have been traditionally considered as of exclusive medical management, such as type 2 diabetes mellitus (T2D). Recommendations for metabolic surgery have been largely addressed and discussed in worldwide meetings, but no definitive consensus has been reached yet. Rates of diabetes remission after metabolic surgery have been one of the most debated hot topics, with heterogeneity being a current concern. This review aims to identify and clarify controversies regarding metabolic surgery, by focusing on a critical analysis of T2D remission rates achieved with different bariatric procedures, and using different criteria for its definition. Indications for metabolic surgery for patients with T2D who are not morbidly obese are also discussed.

Topics: Age Factors; Bariatric Surgery; C-Peptide; Combined Modality Therapy; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Obesity, Morbid; Patient Selection; Prognosis; Remission Induction; Sex Factors; Treatment Outcome; Weight Loss

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

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

Liraglutide is associated with blood pressure reduction in patients with type 2 diabetes. However, it is not known whether this blood pressure reduction can be predicted prior to treatment initiation, and to what extent it correlates with weight loss and with improved glycemic control during follow-up. We analyzed data from a double-blind, placebo-controlled trial, in which 124 insulin-treated patients with type 2 diabetes were randomized to liraglutide or placebo. We evaluated various baseline variables as potential predictors of systolic blood pressure (SBP) reduction, and evaluated whether changes in SBP correlated with weight loss and with improved glycemic control. A greater reduction in SBP among liraglutide-treated patients was predicted by higher baseline values of SBP (P < 0.0001) and diastolic blood pressure (P = 0.012), and by lower baseline values of mean glucose measured by continuous glucose monitoring (CGM; P = 0.044), and serum fasting C-peptide (P = 0.015). The regression coefficients differed significantly between the liraglutide group and the placebo group only for diastolic blood pressure (P = 0.037) and mean CGM (P = 0.021). During the trial period, SBP reduction correlated directly with change in body weight and BMI, but not with change in HbA1c. We conclude that patients with lower mean CGM values at baseline responded to liraglutide with a larger reduction in SBP, and that improved HbA1c during follow-up was not associated with reductions of SBP. Our data suggest that some patients with type 2 diabetes may benefit from liraglutide in terms of weight and SBP reduction.

Topics: Adult; Aftercare; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Blood Pressure; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Liraglutide; Male; Middle Aged; Placebos; Sweden; Weight Loss

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

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

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) cause weight loss and metabolic improvement, but results of published studies are contradictory.. The aim of this study was to compare the effects of SG and RYGB on ghrelin, leptin, and glucose homeostasis in a randomized controlled trial.. University hospital, Poland.. Seventy-two morbidly obese patients were randomly selected to undergo either SG (n = 36) or RYGB (n = 36). Fasting ghrelin, leptin, glucose, insulin, C-peptide, glucagon, glycated hemoglobin, and homeostasis model assessment of insulin resistance were assessed preoperatively and at 1, 6, and 12 months postoperatively. No differences were found in anthropometric and biochemical parameters between the study groups at baseline.. Sixty-nine (95.8%) patients completed the study. Percentage of excess weight loss at 12 months was 67.6±19.3% after SG and 64.2±18.5% after RYGB (P>.05). Fasting ghrelin levels decreased 1 month after SG (from 76.8 pmol/L to 35.3 pmol/L; P<.05) and remained reduced until 12 months (41.6 pmol/L; P<.05) but increased 12 months after RYGB from 74.6 pmol/L to 130.2 pmol/L (P<.05). Leptin, glucose, insulin, and C-peptide concentrations and glycated hemoglobin and homeostasis model assessment of insulin resistance values decreased significantly in both groups during 12 months.. RYGB and SG induce comparable weight loss and improvement in metabolism of glucose. Ghrelin levels decrease after SG and increase after RYGB, but this difference does not affect similar outcomes of these procedures during 1-year follow-up. The contribution of ghrelin to weight loss or metabolic benefits after bariatric surgery is not straightforward, but rather influenced by multiple factors.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Female; Gastrectomy; Gastric Bypass; Ghrelin; Glucagon; Glycated Hemoglobin; Homeostasis; Humans; Insulin Resistance; Laparoscopy; Leptin; Male; Middle Aged; Obesity, Morbid; Operative Time; Prospective Studies; Weight Loss; Young Adult

To evaluate early changes in glycemia, insulin physiology and gut hormone responses to an easily tolerated and slowly ingested solid, low-carbohydrate mixed meal test (MMT) following laparoscopic adjustable gastric banding (LAGB) or Roux-en-Y gastric bypass (RYGB) surgery.. This was a prospective non-randomized study. Plasma glucose, insulin and c-peptide (to estimate hepatic insulin extraction; %HIE), incretins (GIP, aGLP-1) and pancreatic polypeptide (PP) responses to the MMT were measured at 4-8 weeks before and after surgery in obese, metabolically healthy patients (RYGB=10F or LAGB =7F/1M). Supplementary clamp data on basal endogenous glucose production (EGP) and peripheral insulin action (Rd=rate of glucose disposal) and metabolic clearance rates of insulin (MCR-INS) were available in five of the RYGB patients. Repeated measures were appropriately accounted for in the analyses.. RYGB results in distinctly different changes in plasma glucose, insulin and gut hormone response patterns to a solid, slowly ingested low-carbohydrate MMT versus LAGB. Altered nutrient delivery, along with indirect evidence for changes in hepatic and peripheral insulin physiology, are consistent with the greater early improvement in glycemia observed after RYGB versus LAGB surgery.

Topics: Adult; Blood Glucose; C-Peptide; Diet, Carbohydrate-Restricted; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucose Clamp Technique; Humans; Incretins; Insulin; Male; Meals; Obesity, Morbid; Postoperative Care; Postprandial Period; Prospective Studies; Treatment Outcome; Weight Loss

Hyperglycemia improves when patients with type 2 diabetes are placed on a weight-loss diet. Improvement typically occurs soon after diet implementation. This rapid response could result from low fuel supply (calories), lower carbohydrate content of the weight-loss diet, and/or weight loss per se. To differentiate these effects, glucose, insulin, C-peptide and glucagon were determined during the last 24 h of a 3-day period without food (severe calorie restriction) and a calorie-sufficient, carbohydrate-free diet.. Seven subjects with untreated type 2 diabetes were studied. A randomized-crossover design with a 4-week washout period between arms was used.. Results from both the calorie-sufficient, carbohydrate-free diet and the 3-day fast were compared with the initial standard diet consisting of 55% carbohydrate, 15% protein and 30% fat.. The overnight fasting glucose concentration decreased from 196 (standard diet) to 160 (carbohydrate-free diet) to 127 mg/dl (fasting). The 24 h glucose and insulin area responses decreased by 35% and 48% on day 3 of the carbohydrate-free diet, and by 49% and 69% after fasting. Overnight basal insulin and glucagon remained unchanged.. Short-term fasting dramatically lowered overnight fasting and 24 h integrated glucose concentrations. Carbohydrate restriction per se could account for 71% of the reduction. Insulin could not entirely explain the glucose responses. In the absence of carbohydrate, the net insulin response was 28% of the standard diet. Glucagon did not contribute to the metabolic adaptations observed.

Topics: Aged; Blood Glucose; C-Peptide; Caloric Restriction; Cross-Over Studies; Diabetes Mellitus, Type 2; Diet, Carbohydrate-Restricted; Diet, Reducing; Fasting; Glucagon; Hospitals, Veterans; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Weight Loss

It is not known whether calorie restriction (CR) has additive benefits to those from exercise (EX)-induced weight loss. We hypothesized that weight loss from CR and EX (CREX) improves insulin sensitivity more than matched weight loss induced by EX or CR alone and that the incretin system may be involved in adaptations to CR.. Sedentary, overweight men and women (n = 52, 45-65 years of age) were randomized to undergo 6-8% weight loss by using CR, EX, or CREX. Glucose, insulin, C-peptide, insulin sensitivity, and incretin hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) were measured during frequently sampled oral glucose tolerance tests (FSOGTTs). Incretin effects on insulin secretion were measured by comparing insulin secretion rates from the FSOGTTs to those from a glycemia-matched glucose infusion.. Despite similar weight losses in all groups, insulin sensitivity index values increased twofold more in the CREX group (2.09 ± 0.35 μM/kg/pM × 100) than in the CR (0.89 ± 0.39 μM/kg/pM × 100) and EX (1.04 ± 0.39 μM/kg/pM × 100) groups. Postprandial GLP-1 concentrations decreased only in the CR group (P = 0.04); GIP concentrations decreased in all groups. Incretin effects on insulin secretion were unchanged.. CR and EX have additive beneficial effects on glucoregulation. Furthermore, the adaptations to CR may involve reductions in postprandial GLP-1 concentrations. These findings underscore the importance of promoting both CR and EX for optimal health. However, because data from participants who withdrew from the study and from those who did not adhere to the intervention were excluded, the results may be limited to individuals who are capable of adhering to a healthy lifestyle intervention.

Topics: Adaptation, Physiological; Aged; Blood Glucose; C-Peptide; Caloric Restriction; Energy Intake; Energy Metabolism; Exercise Therapy; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin Resistance; Insulin Secretion; Life Style; Male; Middle Aged; Overweight; Postprandial Period; Weight Loss

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

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

To compare long term effects of two bariatric procedures for Chinese type 2 diabetes mellitus (T2DM) patients with a body mass index (BMI) of 28-35 kg/m(2).. Sixty four T2DM patients with Glycated hemoglobin A1c (HbA1c) ≧ 7.0 % were randomly assigned to receive laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedure. Weight, percentage of excess weight loss (%EWL), BMI, waist circumference, HbA1c, fasting blood glucose (FBG), and C-peptide were measured. Serum lipid levels were also measured during three-year postoperative follow-up visits.. Fifty five patients completed the 36-month follow-up. Both groups had similar baseline anthropometric and biochemical measures. At the end point, 22 patients (78.6 %) in SG group and 23 patients (85.2 %) in RYGB group achieved complete remission of diabetes mellitus with HbA1c < 6.0 % (P = 0.525) and without taking diabetic medications, and 25 patients in each group (89.3 % vs. 92.6 %) gained successful treatment of diabetes with HbA1c≦6.5 % (P = 0.100). Change in HbA1c, FBG and C peptide were comparable in the two groups. The RYGB group had significantly greater weight loss than the SG group [percentage of total weight loss (%TWL) of 31.0 % vs. 27.1 % (P = 0.049), %EWL of 92.3 % vs. 81.9 % (P = 0.003), and change in BMI of 11.0 vs. 9.1 kg/m(2)(P = 0.017), respectively]. Serum lipids in each group were also greatly improved.. In this three-year study, SG had similar positive effects on diabetes and dyslipidemia compared to RYGB in Chinese T2DM patients with BMI of 28-35 kg/m(2). Longer term follow-ups and larger sample studies are needed to confirm these outcomes, however.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastrectomy; Gastric Bypass; Glycated Hemoglobin; Humans; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Treatment Outcome; Weight Loss

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

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

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

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

The effects of marked weight loss, induced by Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgeries, on insulin sensitivity, β-cell function and the metabolic response to a mixed meal were evaluated.. Fourteen nondiabetic insulin-resistant patients who were scheduled to undergo SG (n = 7) or RYGB (n = 7) procedures completed a hyperinsulinemic-euglycemic clamp procedure and a mixed-meal tolerance test before surgery and after losing ∼20% of their initial body weight.. Insulin sensitivity (insulin-stimulated glucose disposal during a clamp procedure), oral glucose tolerance (postprandial plasma glucose area under the curve), and β-cell function (insulin secretion in relationship to insulin sensitivity) improved after weight loss, and were not different between surgical groups. The metabolic response to meal ingestion was similar after RYGB or SG, manifested by rapid delivery of ingested glucose into the systemic circulation and a large early postprandial increase in plasma glucose, insulin, and C-peptide concentrations in both groups.. When matched on weight loss, RYGB and SG surgeries result in similar improvements in the two major factors involved in regulating plasma glucose homeostasis, insulin sensitivity and β-cell function in obese people without diabetes.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Female; Gastrectomy; Gastric Bypass; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Obesity, Morbid; Postprandial Period; Weight Loss

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

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

The popularity of high-protein diets for weight reduction is immense. However, the potential benefits from altering the source of dietary protein rather than the amount is scarcely investigated. In the present study, we examined the effects of fish protein supplement on glucose and lipid metabolism in overweight adults. A total of thirty-four overweight adults were randomised to 8 weeks' supplementation with fish protein or placebo tablets (controls). The intake of fish protein supplement was 3 g/d for the first 4 weeks and 6 g/d for the last 4 weeks. In this study, 8 weeks of fish protein supplementation resulted in lower values of fasting glucose (P< 0·05), 2 h postprandial glucose (P< 0·05) and glucose-area under the curve (AUC) (five measurements over 2 h, P< 0·05) after fish protein supplementation compared to controls. Glucose-AUC was decreased after 8 weeks with fish protein supplement compared to baseline (P< 0·05), concomitant with increased 30 min and decreased 90 min and 2 h insulin C-peptide level (P< 0·05), and reduced LDL-cholesterol (P< 0·05). Body muscle % was increased (P< 0·05) and body fat % was reduced (P< 0·05) after 4 weeks' supplementation. Physical activity and energy and macronutrients intake did not change during the course of the study. In conclusion, short-term daily supplementation with a low dose of fish protein may have beneficial effects on blood levels of glucose and LDL-cholesterol as well as glucose tolerance and body composition in overweight adults. The long-term effects of fish protein supplementation is of interest in the context of using more fish as a protein source in the diet, and the effects of inclusion of fish in the diet of individuals with low glucose tolerance should be evaluated.

Topics: Adult; Aged; Animals; Area Under Curve; Blood Glucose; Body Composition; C-Peptide; Cholesterol, LDL; Dietary Supplements; Double-Blind Method; Female; Fish Proteins; Fishes; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Overweight; Postprandial Period; Time Factors; Weight Loss; Young Adult

Given that the repetitive loss and regain of body weight, termed weight cycling, is a prevalent phenomenon that has been associated with negative physiological and psychological outcomes, the purpose of this study was to investigate weight change and physiological outcomes in women with a lifetime history of weight cycling enrolled in a 12-month diet and/or exercise intervention.. 439 overweight, inactive, postmenopausal women were randomized to: i) dietary weight loss with a 10% weight loss goal (N=118); ii) moderate-to-vigorous intensity aerobic exercise for 45 min/day, 5 days/week (n=117); ii) both dietary weight loss and exercise (n=117); or iv) control (n=87). Women were categorized as non-, moderate- (≥3 losses of ≥4.5 kg), or severe-cyclers (≥3 losses of ≥9.1 kg). Trend tests and linear regression were used to compare adherence and changes in weight, body composition, blood pressure, insulin, C-peptide, glucose, insulin resistance (HOMA-IR), C-reactive protein, leptin, adiponectin, and interleukin-6 between cyclers and non-cyclers.. Moderate (n=103) and severe (n=77) cyclers were heavier and had less favorable metabolic profiles than non-cyclers at baseline. There were, however, no significant differences in adherence to the lifestyle interventions. Weight-cyclers (combined) had a greater improvement in HOMA-IR compared to non-cyclers participating in the exercise only intervention (P=.03), but no differences were apparent in the other groups.. A history of weight cycling does not impede successful participation in lifestyle interventions or alter the benefits of diet and/or exercise on body composition and metabolic outcomes.

Topics: Adiponectin; Blood Glucose; Blood Pressure; Body Composition; C-Peptide; C-Reactive Protein; Diet, Reducing; Exercise; Female; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Linear Models; Middle Aged; Overweight; Postmenopause; Weight Gain; Weight Loss

This study evaluated the effect of vildagliptin + metformin on glycemic control and β-cell function in type 2 diabetes patients.. One hundred seventy-one type 2 diabetes patients, naive to antidiabetes therapy and with poor glycemic control, were instructed to take metformin for 8±2 months up to a mean dosage of 2,500±500 mg/day; then they were randomly assigned to add vildaglipin 50 mg twice a day or placebo for 12 months. We evaluated at 3, 6, 9, and 12 months: body mass index, glycemic control, fasting plasma insulin, homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment β-cell function index (HOMA-β), fasting plasma proinsulin, proinsulin/fasting plasma insulin ratio, C-peptide, glucagon, adiponectin, and high-sensitivity C-reactive protein. Before and at 12 months after the addition of vildagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation, to assess insulin sensitivity and insulin secretion.. After 12 months of treatment, vildagliptin + metformin gave a better decrease of body weight, glycemic control, HOMA-IR, and glucagon and a better increase of HOMA-β compared with placebo + metformin. Regarding the measures of β-cell function, treatment-induced changes in M-value, first- and second-phase C-peptide response to glucose, and C-peptide response to arginine were significantly higher in the vildagliptin + metformin group compared with the placebo + metformin group.. The addition of vildagliptin to metformin gave a better improvement of glycemic control, insulin resistance, and β-cell function compared with metformin alone.

Topics: Adamantane; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Metformin; Middle Aged; Nitriles; Pyrrolidines; Vildagliptin; Weight Loss

To investigate the effect of 4 weeks of treatment with liraglutide on insulin dose and glycemic control in type 1 diabetic patients with and without residual β-cell function.. Ten type 1 diabetic patients with residual β-cell function (C-peptide positive) and 19 without (C-peptide negative) were studied. All C-peptide-positive patients were treated with liraglutide plus insulin, whereas C-peptide-negative patients were randomly assigned to liraglutide plus insulin or insulin monotherapy. Continuous glucose monitoring with identical food intake and physical activity was performed before (week 0) and during (week 4) treatment. Differences in insulin dose; HbA1c; time spent with blood glucose<3.9, >10, and 3.9-9.9 mmol/L; and body weight were evaluated.. Insulin dose decreased from 0.50±0.06 to 0.31±0.08 units/kg per day (P<0.001) in C-peptide-positive patients and from 0.72±0.08 to 0.59±0.06 units/kg per day (P<0.01) in C-peptide-negative patients treated with liraglutide but did not change with insulin monotherapy. HbA1c decreased in both liraglutide-treated groups. The percent reduction in daily insulin dose was positively correlated with β-cell function at baseline, and two patients discontinued insulin treatment. In C-peptide-positive patients, time spent with blood glucose<3.9 mmol/L decreased from 3.0 to 1.0 h (P=0.03). A total of 18 of 19 patients treated with liraglutide lost weight during treatment (mean [range] -2.3±0.3 kg [-0.5 to -5.1]; P<0.001). Transient gastrointestinal adverse effects occurred in almost all patients treated with liraglutide.. Treatment with liraglutide in type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Exercise Test; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Insulin-Secreting Cells; Liraglutide; Male; Middle Aged; Weight Loss

Comprehensive lifestyle interventions are effective in preventing diabetes and restoring glucose regulation; however, the key stimulus for change has not been identified and effects in older individuals are not established. The aim of the study was to investigate the independent and combined effects of dietary weight loss and exercise on insulin sensitivity and restoration of normal fasting glucose in middle-aged and older women.. Four-arm RCT, conducted between 2005 and 2009 and data analyzed in 2010.. 439 inactive, overweight/obese postmenopausal women.. Women were assigned to: dietary weight loss (n=118); exercise (n=117); exercise+diet (n=117); or control (n=87). The diet intervention was a group-based reduced-calorie program with a 10% weight-loss goal. The exercise intervention was 45 min/day, 5 days/week of moderate-to-vigorous intensity aerobic activity.. 12-month change in serum insulin, C-peptide, fasting glucose, and whole body insulin resistance (HOMA-IR).. A significant improvement in HOMA-IR was detected in the diet (-24%, p<0.001) and exercise+ diet (-26%, p<0.001) groups but not in the exercise (-9%, p=0.22) group compared with controls (-2%); these effects were similar in middle-aged (50-60 years) and older women (aged 60-75 years). Among those with impaired fasting glucose (5.6-6.9 mmol/L) at baseline (n=143; 33%), the odds (95% CI) of regressing to normal fasting glucose after adjusting for weight loss and baseline levels were 2.5 (0.8, 8.4); 2.76 (0.8, 10.0); and 3.1 (1.0, 9.9) in the diet, exercise+diet, and exercise group, respectively, compared with controls.. Dietary weight loss, with or without exercise, significantly improved insulin resistance. Older women derived as much benefit as did the younger postmenopausal women.. This study is registered at Clinicaltrials.govNCT00470119.

Topics: Age Factors; Aged; Blood Glucose; Body Mass Index; C-Peptide; Diet, Reducing; Exercise; Female; Follow-Up Studies; Humans; Insulin; Insulin Resistance; Life Style; Middle Aged; Postmenopause; Weight Loss

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Insulin resistance and hyperinsulinaemia are, in some prospective studies, linked to an increased cardiovascular risk, at least in men. We tested the hypothesis that hyperinsulinaemia may be reduced by non-pharmacological methods independently of other cardiovascular risk factors.. In a non-pharmacological intervention study for 1 year three groups of subjects (hypertensives as well as normotensives) were selected after stratification for insulin level at baseline. Half of the hyperinsulinaemic subjects were randomly assigned to active intervention with physical exercise and dietary regulation (HI-A group), the other half were followed passively during the study period (HI-P group). Normo-insulinaemics and hypo(low)-insulinaemics also underwent active intervention (NI-A and LI-A groups, respectively).. Primary health care in Sweden.. During the 1-year follow-up subjects in the HI-A group reduced their weight, waist:hip ratio and systolic and diastolic blood pressure, as well as their low:high-density lipoprotein (LDL:HDL)-cholesterol ratio. Glucose levels before and during an oral glucose tolerance test did not change. However, plasma insulin and plasma-C-peptide decreased both in the fasting state and after 1 and 2 h of oral glucose tolerance testing. This decrease was independent of the previously mentioned reduction in weight, waist:hip ratio, blood pressure and LDL:HDL-cholesterol ratio. No reduction in insulin levels was seen in the HI-P, NI-A or LI-A groups, but in the HI-P group there was a slight decrease in fasting plasma-C-peptide levels. In the HI-A group dietary improvements were observed during the study period, with a reduction in energy intake, fat consumption and cholesterol intake. Fibre intake was increased. No major changes were seen in the HI-P group.. We conclude that in hypertensive and normotensive subjects with hyperinsulinaemia insulin levels can be reduced by active non-pharmacological treatment for 1 year without altering glucose tolerance. This shows that insulin resistance may be lowered by non-pharmacological treatment, which may be of considerable importance, and not only for hypertensives.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholesterol, HDL; Female; Follow-Up Studies; Humans; Hyperinsulinism; Hypertension; Insulin; Insulin Resistance; Life Style; Male; Middle Aged; Multivariate Analysis; Smoking Prevention; Surveys and Questionnaires; Sweden; Weight Loss

Altogether twenty-six elderly subjects (aged 65-74 years) with persistent impaired glucose tolerance (World Health Organization (1985) criteria) identified in a population-based study, were randomly treated either with chromium-rich yeast (160 micrograms Cr/d) or with placebo for 6 months. The 24 h urinary Cr increased from 0.13 (SE 0.03) to 0.40 (SE 0.06) micrograms/d in the Cr group (n 13) but no change was found in the placebo group (n 11) (0.13 (SE 0.02) v. 0.11 (SE 0.02) micrograms/d). No significant change was observed in the oral glucose tolerance test (glucose dose 75 g; 0, 1 and 2 h blood glucose respectively): 5.3 (SE 0.1), 9.3 (SE 0.3), 8.2 (SE 0.3) mmol/l v. 5.0 (SE 0.1), 8.5 (SE 0.4), 7.3(SE 0.5) mmol/l in the Cr group; 4.9 (SE 0.2), 9.2 (SE 0.6), 8.1 (SE 0.3) mmol/l v. 4.8 (SE 0.2), 8.5 (SE 0.5), 7.0 (SE 0.6) mmol/l in the placebo group (baseline v. 6 months). Glycosylated haemoglobin, plasma insulin, C-peptide and apolipoprotein A1 and B levels remained unchanged, and no improvement was seen in serum total cholesterol (6.2 (SE 0.3) v. 6.4 (SE 0.3) mmol/l for the Cr group, 6.2 (SE 0.4) v. 6.5 (SE 0.3) mmol/l for the placebo group), high-density-lipoprotein-cholesterol (1.1 (SE 0.1) v. 1.2 (SE 0.1) mmol/l for the Cr group, 1.0 (SE 0.1) v. 1.1 (SE 0.1) mmol/l for the placebo group) or triacylglycerols (2.5 (SE 0.4) v. 2.0 (SE 0.4) mmol/l for the Cr group, 2.4 (SE 0.2) v. 2.5 (SE 0.2) mmol/l for the placebo group). The present results indicate that Cr supplementation does not improve glucose tolerance or serum lipid levels in elderly subjects with stable impaired glucose tolerance.

Topics: Aged; Blood Glucose; Body Mass Index; C-Peptide; Chromium; Diabetes Mellitus; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Insulin; Lipids; Male; Weight Loss

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

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

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

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

One-anastomosis gastric bypass (OAGB) is as effective as Roux-en-Y gastric bypass (RYGB) regarding weight loss and diabetes remission. However, there are no data on gut hormone secretions after OAGB. The aim of this study was to compare fasting and postprandial secretions of gut and pancreatic hormones in OAGB versus RYGB patients.. Twenty-nine patients, 16 OAGB- and 13 RYGB-operated, underwent a liquid mixed-meal tolerance test at 2 years' post-surgery. Blood was sampled before and 15, 30, 60, 90, and 120 min after meal for plasma measurement of glucose, C-peptide, insulin, glucagon, GLP-1, GIP, GLP-2, PYY, and ghrelin.. Percentage of total weight loss 2 years post-surgery were -33.9 ± 1.8% for OAGB and -31.2 ± 1.6% for RYGB (p = 0.6). Four patients with persistent diabetes were excluded for further analysis. Fasting and postprandial glucose levels (peaks and area under curve values) were similar between groups. HOMA index was lower in the OAGB group (0.8 ± 0.1 vs 1.3 ± 0.2 in RYGB, p < 0.05). Levels of C-peptide (or insulin) measured at 30 min were significantly lower in OAGB vs RYGB patients (6.9 ± 0.5 vs 9.7 ± 1.1 µg/l, p < 0.05). No difference was observed between OAGB and RYGB groups for GLP-1, GLP-2, PYY, or ghrelin postprandial secretions, but GIP tended to be lower in OAGB vs RYGB patients (756 ± 155 vs 1100 ± 188 pg/ml for postprandial peak concentrations, p = 0.06).. This is the first clinical study showing that OAGB procedure, like RYGB, results in high postprandial secretions of gut hormones, in particular GLP-1.. Clinical Trials NCT03482895.

Topics: Anastomosis, Roux-en-Y; Blood Glucose; C-Peptide; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Obesity, Morbid; Pilot Projects; Weight Loss

Obesity has become a global problem that poses a serious threat to human health. Laparoscopic sleeve gastrectomy (LSG) is an effective long-term treatment. However, the weight loss of some patients after LSG is still insufficient. It is necessary to investigate the factors associated with inadequate weight loss after LSG.. The objective of this study was to explore whether preoperative insulin secretion could be associated with weight loss after LSG in patients with obesity.. This is a single-center prospective cohort study conducted in a university hospital.. Patients from a prospective database who underwent LSG were analyzed. All 178 participants underwent a 75-g oral glucose tolerance test (OGTT) to assess preoperative insulin and c-peptide secretion before LSG. The areas under the curve (AUCs) for glucose, insulin, and c-peptide were determined in the OGTT. The percentage of excess weight loss (%EWL) and the percentage of total weight loss (%TWL) were used to estimate the effect of weight loss after LSG. Regression models were used to assess the correlation between preoperative insulin and c-peptide secretion with %EWL ≥75% and TWL ≥35% at 12 months after LSG.. The AUCs of insulin and c-peptide were significantly lower in the %EWL ≥75% and %TWL ≥35% groups at 0-30 minutes, 0-60 minutes, and 0-120 minutes during the OGTT. At 30, 60, and 120 minutes during the OGTT, c-peptide levels were significantly lower in the %EWL ≥75% group and %TWL ≥35% group. The preoperative c-peptide level at 30 minutes during the OGTT (C. The rate of weight loss after LSG is low among patients with preoperative hyperinsulinemia. The preoperative c-peptide level at 30 minutes during the OGTT is associated with weight loss after LSG.

Topics: Body Mass Index; C-Peptide; Gastrectomy; Glucose; Humans; Insulin; Laparoscopy; Obesity, Morbid; Prospective Studies; Retrospective Studies; Treatment Outcome; Weight Loss

To investigate the predictive value of baseline serum triglyceride (TG) levels for improvements of metabolism after laparoscopic sleeve gastrectomy (LSG).. In the whole cohort, the metabolic parameters were significantly improved at 6 months after LSG. BMI and waist circumference (WC) decreased significantly in the two groups. The ΔBMI among group A and group B were 11.42±3.23 vs 9.13±2.77 kg/m. Obese patients with baseline TG levels under 1.7 mmol/L had greater loss of weight at six months follow-up later LSG. This finding suggests that baseline TG level may have a predictive value for weight loss, at least in the short-term follow-up.

Topics: Adult; Anthropometry; Blood Glucose; Body Mass Index; C-Peptide; Female; Gastrectomy; Homeostasis; Humans; Insulin; Insulin Resistance; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Odds Ratio; Postoperative Period; Regression Analysis; Retrospective Studies; Triglycerides; Weight Loss

Few studies have addressed the effect of bariatric surgery on factors related to energy balance, including resting energy expenditure (REE) and thermic effect of food (TEF). To our knowledge, very few studies have examined changes in REE and none have investigated modifications in TEF after sleeve gastrectomy (SG) performed in adolescents.. To assess energy expenditure in females who underwent SG as adolescents and matched-control participants as preliminary data about the potential of SG to confer differences in postprandial energy expenditure.. Children's Hospital Medical Center, Cincinnati, Ohio, United States.. In this observational study, REE and respiratory quotient (RQ) were measured via indirect calorimetry, followed by a standardized meal and assessment of TEF and postprandial RQ. Plasma drawn before and every 15 minutes after the meal was assayed for insulin, glucose, and C-peptide. Usual dietary intake was estimated using 24-hour recall interviews.. Fasting REE and RQ were similar between surgical and control groups. Postmeal TEF also did not differ between groups. The surgical group had higher RQ early in the postprandial period, whereas the control group RQ was higher after 125 minutes post meal. Compared with the control group, the surgical group had lower postprandial glucose, higher insulin and C-peptide, and consumed less daily energy during usual intake.. Postprandial RQ was consistent with the rapid gastric emptying typical of SG, yet we observed no group differences in REE or TEF. These findings may have been due to limited statistical power. More comprehensive studies of EE after SG are warranted.

Topics: Adolescent; C-Peptide; Child; Energy Metabolism; Female; Gastrectomy; Humans; Ohio; Weight Loss

The aim of this study was to observe the clinical features of type 2 diabetes mellitus (T2DM) patients with ketosis as the initial symptom, and investigate its differences from clinical features of non-ketotic T2DM patients.. A total of 385 T2DM patients treated in our hospital from 2014 to 2017 were selected and divided into ketosis-prone T2DM group and non-ketotic T2DM group. Ketosis-prone T2DM patients refer to DM patients with the urine ketone body++ or above or the blood ketone body ≥1.0 mmol/L when treated. Fasting venous blood was collected from all patients in the early morning at 2 d after admission to detect the liver function, renal function, blood glucose, triglyceride, total cholesterol, glycosylated hemoglobin and fasting C-peptide, glutamic acid decarboxylase antibody (GAD-Ab) and islet cell antibody (ICA) were also detected, and the 24 h urine specimen was retained to detect the 24 h urine microalbumin excretion rate.. The proportion of male in ketosis-prone T2DM group was significantly higher than that in non-ketotic T2DM group (P<0.01). Patients in ketosis-prone T2DM group was younger than those in non-ketotic T2DM group (P<0.05). The number of days from initial symptom to treatment in ketosis-prone T2DM group was smaller than that in non-ketotic T2DM group (P<0.05). The fasting C-peptide level in ketosis-prone T2DM group was significantly lower than that in non-ketotic T2DM group (P<0.05). The degree of weight loss and level of glycosylated hemoglobin in ketosis-prone T2DM group were significantly higher than those in non-ketotic T2DM group (P<0.05).. Ketosis-prone T2DM patients are characterized by lower age at onset, higher proportion of male, shorter duration of disease, poorer islet function, higher blood glucose and more significant weight loss than non-ketotic T2DM patients.

Topics: Adult; Age Factors; Autoantibodies; Body Mass Index; C-Peptide; C-Reactive Protein; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Disease Susceptibility; Female; Glycated Hemoglobin; Humans; Ketosis; Lipids; Male; Middle Aged; Risk Factors; Sex Factors; Weight Loss

We aimed to test the hypothesis that addition of glucagon-like peptide-1 receptor agonists (GLP-1RAs) to insulin in C-peptide-positive patients with type 1 diabetes (T1D) will result in a reduction in glycated haemoglobin (HbA1c) with reduced insulin requirements and a rise in C-peptide concentrations. We conducted a retrospective analysis of 11 normal-weight patients with T1D consecutively treated with a GLP-1RA in addition to insulin. Paired t tests were used to compare the changes in HbA1c, insulin doses, body weight, body mass index, and C-peptide concentrations prior to and 12 ± 1 weeks after GLP-1RA therapy. At the end of 12 ± 1 weeks of GLP-1RA therapy, HbA1c fell from 10.74 ± 0.96% (95 ± 10.5 mmol/mol) to 7.4 ± 0.58% (58 ± 6.3mmol/mol) (P < 0.01), body weight fell from 71 ± 2.0 to 69 ± 2 kg (P = 0.06), and total insulin dose was reduced by 64% from 33 ± 6 to 11 ± 5 units (P < 0.01). Five out of 10 patients did not require any insulin. C-peptide concentrations increased significantly from 0.43 ± 0.09 ng/ml (0.14 ± 0.02 nmol/L) to 1.42 ± 0.42ng/ml (0.47 ± 0.13 nmol/L) (P = 0.01). Addition of GLP-1RA therapy to insulin in normal-weight patients with T1D led to a reduction in HbA1c with reduced insulin requirements, a 3.5-fold increase in C-peptide concentrations and freedom from insulin therapy in 50% of patients who tolerated the GLP-1RA therapy over a period of 12 ± 1 weeks.

Topics: Adult; Autoantibodies; Body Weight; C-Peptide; Deprescriptions; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin; Liraglutide; Male; Middle Aged; Recombinant Fusion Proteins; Retrospective Studies; Treatment Outcome; Weight Loss

In type 1 diabetes mellitus, the levels of insulin and C-peptide decrease at the periphery and in CNS. C-peptide potentiates the regulatory effects of insulin. We studied the effects of single and repeated (over 7 days) individual and combined nasal administration of C-peptide (10 μg/day) and insulin (20 μg/day) on activity of Akt kinase and kinase-3β-glycogen synthase (GSK3β), the components of 3-phosphoinositide pathway, in the hypothalamus of intact rats and rats with mild streptozotocin-induced type 1 diabetes mellitus. Phosphorylation of Akt kinase at Thr

Topics: Administration, Intranasal; Animals; C-Peptide; Diabetes Mellitus, Experimental; Drug Synergism; Glycemic Index; Glycogen Synthase Kinase 3 beta; Hypothalamus; Insulin; Male; Phosphatidylinositols; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Streptozocin; Weight Loss

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

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

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

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

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

To evaluate the Roux-en-Y gastric bypass (GBP) procedure for patients suffering from type 2 diabetes mellitus (T2DM) with body mass index (BMI) <28 kg/m. Thirty-one patients suffering from T2DM were selected to undergo laparoscopic Roux-en-Y gastric bypass surgery and were enrolled at Beijing Shijitan Hospital between November 2012 and December 2014. The fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), C-peptide, fasting insulin (FINS) and glucagon-like peptide-1 (GLP-1) of all patients were measured before and at 1, 3, 6 months after surgery. The results were compared and analyzed.. Thirty-one patients suffering from T2DM successfully underwent GBP surgery (a mean age of 46 years), 14 were male and 17 were female. Among them, 7 patients had hypertriglyceridemia (HTG). The patients were followed up for 6 months. No major complications were found. The average BMI was 26.5 ± 1.4 kg/m. This research shows that the GBP procedure is safe and effective for T2DM patients with BMI <28 kg/m

Topics: Adult; Aged; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Bypass; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Insulin; Laparoscopy; Male; Middle Aged; Remission Induction; Triglycerides; Weight Loss; Young Adult

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

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

Cases of type 1 diabetes mellitus in children aged younger than 6 years in Taiwan has increased in the past 10 years. This retrospective study aimed to review the management experience of such patients in a single center.. From January 2004 to June 2015, 52 newly diagnosed diabetic children younger than 6 years who had regular follow-up for > 1 year were enrolled, as well as 94 older diabetic children for comparison. Their medical records were thoroughly reviewed.. The most common symptoms and signs were polyuria, polydipsia, dry lips, weight loss, and nocturia. Among the children younger than 6 years, 87% had ketoacidosis upon diagnosis-significantly higher than that of the older age group-and 88% had at least one islet cell autoantibody detected. Their serum C-peptide levels were significantly lower and the frequency of insulin autoantibodies detected was significantly higher compared with the older age group (37% vs. 10%). The remission rate of the young diabetic patients was significantly lower than that of the older age group (40% vs. 59%), but there was no difference in time of onset and duration of remission between the two groups.. Autoimmune destruction of pancreatic β-cells is an important cause of type 1 diabetes mellitus in Taiwanese children aged younger than 6 years. These patients usually have a low insulin reserve and severe ketoacidosis upon diagnosis. A high index of suspicion in the presence of classic symptoms of diabetes in young children is important to prevent complications.

Topics: Adolescent; Age Factors; Autoantibodies; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Lip; Male; Nocturia; Polydipsia; Polyuria; Symptom Assessment; Taiwan; Weight Loss

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

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

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

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

The prevalence of early-onset type 2 diabetes mellitus (T2DM), which responds poorly to medical treatment, is increasing. Bariatric surgery has been well recognized for its effectiveness in the remission of T2DM, but its effectiveness and durability in the remission of early-onset T2DM has not yet been explored.. To compare the short- and long-term outcomes of bariatric surgery with a specific focus on the rate of remission of T2DM in patients with early-onset (age <40 years) and late-onset (age ≥40 years) T2DM.. In this cohort study, 558 Taiwanese patients (339 with early-onset T2DM and 219 with late-onset T2DM) with a body mass index (calculated as weight in kilograms divided by height in meters squared) above 25 underwent bariatric surgery to ameliorate T2DM between January 1, 2007, and December 31, 2013. Patients were followed up for at least 1 year. Preoperative, perioperative, and postoperative clinical and laboratory data were prospectively collected and compared between the 2 groups.. Rate of remission of T2DM (hemoglobin A1C <6.0% without antiglycemic medication) was the primary outcome measure.. Of the 558 patients (345 women) in the study, mean (SD) ages were 33.5 (7.5) for those with early-onset T2DM and 50.6 (6.5) with late onset T2DM. Those with early-onset T2DM had higher mean (SD) preoperative BMI and hemoglobin A1C values (39.4 [8.5] and 8.7% [3.8%] of total hemoglobin [to convert hemoglobin to a proportion of total hemoglobin, multiply by 0.01], respectively) than did patients with late-onset T2DM (36.7 [7.5] and 8.2% [1.6%], respectively). Distribution of surgical procedures and major complications were similar between the 2 groups. At 1 year, patients with early-onset T2DM achieved greater weight loss than those with late-onset T2DM, although the difference was not statistically significant. A higher rate of complete remission of T2DM was observed in patients with early-onset T2DM than in those with late-onset disease (193 [56.9%] vs 110 [50.2%]; P = .02). At 5 years, patients with early-onset T2DM still maintained a higher rate of weight loss (mean [SD], 30.4% [11.8%] vs 21.6% [11.7%]; P = .002) and higher rate of remission (47 of 72 [65.3%] vs 26 of 48 [54.2%]; P = .04) than did those with late-onset disease. Age at bariatric surgery, duration of T2DM, and preoperative C-peptide level were independent predictors of remission. The remission rate was directly related to extent of weight loss. Multivariate analysis confirmed the higher rate of remission in the group with early-onset T2DM.. This article describes the largest long-term study examining bariatric surgery for patients with early-onset T2DM. Bariatric surgery may achieve better and more long-lasting glycemic control in select patients with early-onset T2DM than in those with late-onset T2DM.

Topics: Adult; Age of Onset; Bariatric Surgery; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Male; Middle Aged; Patient Selection; Remission Induction; Time Factors; Treatment Outcome; Weight Loss

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

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

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prognosis; Retrospective Studies; Sitagliptin Phosphate; Treatment Outcome; Weight Loss

Bariatric surgery has proven results for diabetes remission in obese diabetics. Despite this, a lot of ambiguity exists around patient selection. The objectives of this study are the following: (1) evaluation of results of laparoscopic Roux-en-y gastric bypass (LRYGB) in obese type 2 diabetic (T2DM) Indian patients at 5 years and (2) to define predictors of success after surgery.. This is a prospective observational study. One hundred six Indian patients underwent LRYGB from January 2004 to July 2009. Patients were evaluated for percent excess weight loss (%EWL) and remission of T2DM. Mean age 50.34 ± 9.08 years, mean waist circumference 129.8 ± 20.8 cm, mean weight 119.2 ± 23.6 kg, mean BMI 45.01 ± 7.9 kg/m(2), and mean duration of diabetes 8.2 ± 6.2 years.. At 5 years, mean EWL% was 61.4 ± 20.3, mean weight regain of 8.6 ± 6.2 kg was seen in 63.6 %, mean glycosylated hemoglobin dropped from 8.7 ± 2.1 to 6.2 ± 01.3 %, mean triglycerides declined by 31 %, and serum high density lipoprotein rose by 18.4 %. Mean low-density lipoprotein levels declined by 6.8 %. Age, BMI, fasting C-peptide levels, duration of T2DM, and pre-op use of insulin emerged as significant predictors of success after surgery. One hundred percent remission was seen in patients with T2DM <5 years.. LRYGB is safe and efficacious for long-term remission of T2DM (BMI ≥ 35 kg/m(2)). In a country with the second largest population of type 2 diabetics in the world, predictors of success after surgery can help in prioritizing patients who have a greater chance to benefit from metabolic surgery.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glycated Hemoglobin; Humans; India; Laparoscopy; Lipoproteins, LDL; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Treatment Outcome; Triglycerides; Waist Circumference; Weight Loss

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

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

Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (β-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI ≥ 27 kg/m(2) were divided based on weight loss at 1 year: < 5% (non-responders, n 56) and ≥ 5% (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9.5% of their weight when compared with non-responders who lost only 0.8% of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P = 0.0003) and disposition index (P = 0.02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8.9 (SD 12.5) v. 3.6 (SD 10.7) nmol/l, P = 0.05). However, it had not been associated with amelioration of insulin sensitivity and β-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or β-cell function.

Topics: Aged; Body Composition; Body Mass Index; C-Peptide; Dietary Supplements; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Life Style; Linear Models; Male; Middle Aged; Prediabetic State; Prospective Studies; Vitamin D; Weight Loss

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

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

Ectopic fat accumulation in liver and skeletal muscle may be an essential link between abdominal obesity, insulin resistance and increased risk of cardiovascular disease after menopause. We hypothesized that a diet containing a relatively high content of protein and unsaturated fat [mainly monounsaturated fatty acids (MUFAs)] but limited carbohydrates and saturated fat would reduce lipid content in liver and muscle and increase insulin sensitivity in postmenopausal women.. Ten healthy, nonsmoking postmenopausal women with a body mass index (BMI) >27 (28-35) kg m(-2) were included in the study.. Participants were instructed to consume an ad libitum Palaeolithic-type diet intended to provide approximately 30 energy percentage (E%) protein, 40 E% fat (mainly MUFAs) and 30 E% carbohydrate. Intramyocellular lipid (IMCL) levels in calf muscles and liver triglyceride levels were quantified using proton magnetic resonance spectroscopy ((1) H-MRS) before and 5 weeks after dietary intervention. Insulin sensitivity was estimated by homoeostasis model assessment (HOMA) indices and the euglycaemic hyperinsulinaemic clamp technique.. Mean energy intake decreased by 25% with a weight loss of 4.5 kg. BMI, waist and hip circumference, waist/hip ratio and abdominal sagittal diameter also decreased significantly, as did diastolic blood pressure (mean -7 mmHg), levels of fasting serum glucose, cholesterol, triglycerides, LDL/HDL cholesterol, apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), urinary C-peptide and HOMA indices. Whole-body insulin sensitivity did not change. Liver triglyceride levels decreased by 49%, whereas IMCL levels in skeletal muscle were not significantly altered.. A modified Palaeolithic-type diet has strong and tissue-specific effects on ectopic lipid deposition in postmenopausal women.

Topics: Adipose Tissue; Apolipoproteins A; Apolipoproteins B; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Fatty Acids, Monounsaturated; Fatty Liver; Female; Follow-Up Studies; Glucose Clamp Technique; Humans; Insulin Resistance; Magnetic Resonance Spectroscopy; Middle Aged; Motor Activity; Muscle, Skeletal; Obesity, Abdominal; Postmenopause; Retrospective Studies; Triglycerides; Waist Circumference; Weight Loss

To evaluate whether preoperative measurement of fasting plasma C-peptide levels is useful to predict diabetes outcome after Roux-en-Y gastric bypass (RYGB) surgery.. Diabetes outcome after RYGB was evaluated in 126 obese patients: 41 non-diabetic controls (NDC), 29 with impaired glucose tolerance (IGT) and 56 had type 2 diabetes mellitus (T2DM). Body weight, fasting plasma glucose, fasting C-peptide levels, and HbA1c were measured at baseline and 3.6 ± 0.16 years after GBS. Complete resolution of diabetes was defined as: fasting glucose <7.0 mmol/l, HbA1c <6.5 %, achieved without anti-diabetic medication.. Patients with complete resolution of diabetes had a more recent diagnosis of T2DM, lower preoperative HbA1c levels and lower daily doses of metformin and insulin use. These parameters were related to postoperative HbA1c levels but they failed to mark the specific patients who had not reached complete resolution of T2DM. Fasting preoperative C-peptide levels had better predictive power: 90 % of T2DM patients with preoperative fasting C-peptide levels >1.0 nmol/l achieved a postoperative HbA1c <6.5 %, and 74 % achieved complete resolution of their diabetes. In contrast, none of the T2DM patients with a preoperative fasting C-peptide <1.0 nmol/l attained these goals.. A preoperative fasting plasma C-peptide level <1.0 nmol/l in severely obese T2DM patients indicates partial β-cell failure, and is associated with a markedly reduced chance of complete resolution of T2DM after RYGB. We therefore advocate measuring C-peptide levels in all diabetic patients up for bariatric surgery to improve the prediction of outcome.

Topics: Adult; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Follow-Up Studies; Gastric Bypass; Glycated Hemoglobin; Humans; Male; Middle Aged; Netherlands; Obesity, Morbid; Postoperative Period; Predictive Value of Tests; Preoperative Period; Remission Induction; Retrospective Studies; Treatment Outcome; Weight Loss

Controversy exists regarding type 2 diabetes (T2D) remission rates after bariatric surgery (BS) due to heterogeneity in its definition and patients' baseline features. We evaluate T2D remission using recent criteria, according to preoperative characteristics and insulin therapy (IT).. We performed a retrospective study from a cohort of 657 BS from a single center (2006-2011), of which 141 (57.4 % women) had T2D. We evaluated anthropometric and glucose metabolism parameters before surgery and at 1-year follow-up. T2D remission was defined according to 2009 consensus criteria: HbA1c <6%, fasting glucose (FG) <100 mg/dL, and absence of pharmacologic treatment. We analyzed diabetes remission according to previous treatment.. Preoperative characteristic were (mean ± SD): age 53.9 ± 9.8 years, BMI 43.7 ± 5.6 kg/m2, T2D duration 7.4 ± 7.6 years, FG 160.0 ± 54.6 mg/dL, HbA1c 7.6 ± 1.6%. Fifty-six (39.7%) individuals had IT. At 1-year follow-up, 74 patients (52.5%) had diabetes remission. Percentage weight loss (%WL) and percentage excess weight loss (%EWL) were associated to remission (35.5 ± 8.1 vs. 30.2 ± 9.5 %, p = 0.001; 73.6 ± 18.4 vs. 66.3 ± 22.8%, p = 0.037, respectively). Duration of diabetes, age, and female sex were associated to nonremission: 10.3 ± 9.4 vs. 4.7 ± 3.8 years, p < 0.001; 55.1 ± 9.3 vs. 51.2 ± 9.9 years, p = 0.017; 58.9 vs. 33.3%, p = 0.004, respectively. Prior treatment revealed differences in remission rates: 67.1 % in case of oral therapy (OT) vs. 30.4% in IT, p < 0.001. OR for T2D remission in patients with previous IT, compared to those with only OT, were 0.157-0.327 (p < 0.05), adjusting by different models.. Consensus criteria reveal lower T2D remission rates after BS than previously reported. Prior insulin use is a main setback for remission.

Topics: Adult; Aged; Analysis of Variance; Biliopancreatic Diversion; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Bypass; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Preoperative Period; Remission Induction; Retrospective Studies; Spain; Treatment Outcome; Weight Loss

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

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

Metabolic surgery causes the remission of type 2 diabetes mellitus (T2DM), hypertension, and hyperlipidemia to varying degrees, depending on the patient characteristics and the surgical procedure. The aim of this study was to find predictors for the remission of T2DM and hypertension after biliopancreatic diversion with duodenal switch (BPDDS).. Eighty patients with T2DM were followed up for 2 years or more after BPDDS, and changes in body weight and metabolic status were noted. Remission was defined as fasting glucose <7 mmol/l with HbA1C <6.5 %, blood pressure <140/90 mmHg, and low-density lipoprotein (LDL) <2.6 mmol without the use of medication.. Preoperatively, the mean age was 44 years, body mass index (BMI) was 48 kg/m(2), and duration of diabetes was 5 years. Of the 80 patients, 38 patients were using insulin, 48 patients were using antihypertensives, and 38 patients were using a lipid-lowering drug. Five percent of the patients had recommended levels for HbA1C, blood pressure, and LDL prior to the operation. The remission rate at 2 years was 94 % for T2DM, 54 % for hypertension, and 86 % for LDL hyperlipidemia. Preoperative predictors for nonremission of T2DM were a higher BMI, insulin usage, and low insulin C-peptide, and for hypertension, older age and more severe hypertension. Postoperative weight loss was important for both.. Surgical intervention with BPDDS is an effective treatment of T2DM, hypertension, and hyperlipidemia. The duration of T2DM and age of the patient are the most important preoperative predictors for the remission of T2DM and hypertension, respectively.

Topics: Adult; Antihypertensive Agents; Biliopancreatic Diversion; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Duodenum; Female; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Male; Metabolic Syndrome; Predictive Value of Tests; Remission Induction; Time Factors; Treatment Outcome; Weight Loss

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

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

To assess factors influencing glycaemic control following gastric bypass surgery in patients with Type 2 diabetes and BMI< 30 kg/m(2) .. Prospective longitudinal study of 103 patients with inadequate glycaemic control who underwent gastric bypass surgery at Soonchunhyang University, Seoul, Korea (n = 66) and Min-Sheng General Hospital, Taipei, Taiwan (n = 37). Procedures were performed August 2009 to January 2011. Key outcome measures were excellent glycaemic control of Type 2 diabetes defined as HbA1c < 42 mmol/mol (≤6%); inadequate response defined as HbA1c > 53 mmol/mol (> 7%). Analysis was conducted using binary logistic regression, and cut-points obtained from receiver operator characteristics.. Excellent glycaemic control was achieved in 31 (30%) at 1 year. Diabetes duration of < 7 years and BMI > 27 kg/m(2) provided independent predictors and useful cut-points. Likelihood of excellent glycaemic control for an individual could be estimated using loge (Odds) = -6.7 + (0.26 × BMI) + (-1.2 × diabetes duration). Baseline BMI of < 27 kg/m(2) and baseline C-peptide of < 2.0ng/ml, best predicted a poor glycaemic response. In those with favourable baseline characteristics percentage weight loss (%WL) had a dominant influence on glycaemic outcomes. Baseline C-peptide (> 2.4 ng/ml) and subsequent percentage weight loss (> 16%) were associated with excellent glycaemic control. Higher BMI was associated with greater percentage weight loss.. In patients with Type 2 diabetes and BMI < 30 kg/m(2) , glycaemic response to gastric bypass is predicted by higher baseline BMI, shorter disease duration and higher fasting C-peptide. Post-surgery weight loss has a dominant effect. Baseline BMI and weight loss have a major influence on outcomes.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Gastric Bypass; Glycated Hemoglobin; Humans; Laparoscopy; Male; Middle Aged; Prospective Studies; Treatment Outcome; Weight Loss; Young Adult

C-peptide is a surrogate of the pancreatic beta cell mass. However, the clinical significance of C-peptide in a diabetic patient after bariatric surgery has not been studied clearly.. From February 2005 to January 2009, a total of 205 (124 females and 81 males) consecutive morbidly obese patients with type 2 diabetes mellitus (T2DM) enrolled in a surgically supervised weight loss program with at least 1 year follow-up were examined. Among them, 147 patients (71.7%) received gastric bypass procedures, while the other 58 patients (28.3%) received restrictive-type procedures.. The mean C-peptide before the surgery was 5.3 ± 3.5 ng/ml. One hundred nineteen patients (58.0%) had an elevated C-peptide (>4 ng/ml), while 2 patients (1.0%) had a low C-peptide (<1.0 ng/ml). Multivariate analysis confirmed that waist circumference, triglycerides, and HbA1c were the independent predictors for the elevation of C-peptide. It was observed that the mean C-peptide levels decreased to 1.7 ± 0.9 ng/ml 1 year after bariatric surgery with a mean reduction of 64.1%. One year after surgery, 160 patients (78.0%) out of a total of 205 patients had a remission of their T2DM. Patients in the bypass group had a higher diabetes remission rate (91.2%; 134 out of 147) in comparison to patients in the restrictive group (44.8%; 26 out of 58, p < 0.001). The diabetes remission rates for those with preoperative C-peptide <3, 3-6, and > 6 ng/ml were 26 out of 47 (55.3%), 87 out of 108 (82.0%), and 47 out of 52 (90.3%), p < 0.001, respectively.. Baseline C-peptide is commonly elevated in morbidly obese patients with T2DM. There was a marked reduction in C-peptide after a significant weight reduction 1 year after surgery with a T2DM remission rate of 78.0%. Thus, bariatric surgery is recommended for obesity-related T2DM patients with elevated C-peptide.

Topics: Adolescent; Adult; Bariatric Surgery; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Middle Aged; Obesity, Morbid; Predictive Value of Tests; Remission Induction; Treatment Outcome; Weight Loss; Young Adult

Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping).. We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance.. Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests.. Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.

Topics: Adult; Appetite; C-Peptide; Cholecystokinin; Confounding Factors, Epidemiologic; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Leptin; Male; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Somatostatin; Time Factors; Weight Loss

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

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

Our group has reported a high incidence of reactive hypoglycemia following Roux-en-Y gastric bypass (RYGB) with specific interest in postprandial insulin and the ratio of 1- to 2-h serum glucose levels. The purpose of this study is to compare the 6-month response to oral glucose challenge in patients undergoing RYGB, duodenal switch (DS), and vertical sleeve gastrectomy (VSG).. Thirty-eight patients meeting the NIH criteria for bariatric surgery who have reached the 6-month postoperative mark are the basis of this report. Preoperatively and at 6 months follow-up, patients underwent blood draw to determine levels of fasting glucose, fasting insulin, HbA1c, C peptide, and 2 h oral liquid glucose challenge test (OGTT). HOMA-IR and 1 to 2 h ratios of glucose and fasting to 1 h ratio of insulin were calculated.. All patients underwent a successful laparoscopic bariatric procedure (VSG =13, DS =13, and RYGB = 12). All operations reduced BMI, HgbA1c, fasting glucose, and fasting insulin. HOMA IR and glucose tolerance improved with all procedures. In response to OGTT at 6 months, there was a 20-fold increase in insulin at 1 h in RYGB, which was not seen in DS. At 6 months, 1-h insulin was markedly lower in DS (p < .05), yet HbA1C was also lower in DS (p < .05). This resulted in 1- to 2-h glucose ratio of 1.9 for RYGB, 1.8 for VSG, and 1.3 for DS (p < .05).. All operations improve insulin sensitivity and decrease HgbA1c. Six-month weight loss was substantial in all groups between 22-29% excess body weight. RYGB results in marked rise in glucose following challenge with corresponding rise in 1-h insulin. VSG has a similar response to RYGB. In comparison, at 6 months following surgery, DS causes a much lower rise in 1-h insulin, with this difference being statistically significant at p < .05. As a result, DS results in a less abrupt reduction in blood glucose. Although 1-h insulin is lower, DS patients had the lowest HbA1C at 6 months (p < .05). We believe that these findings have important implications for the choice of bariatric procedure for both diabetic and non-diabetic patients.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Duodenum; Female; Follow-Up Studies; Gastric Bypass; Gastroplasty; Glucose Tolerance Test; Glycated Hemoglobin; Homeostasis; Humans; Hypoglycemia; Insulin Resistance; Male; Obesity, Morbid; Prospective Studies; Treatment Outcome; Weight Loss

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

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

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

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

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

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

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

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

Recently, vaspin was identified as a novel adipokine with insulin-sensitizing effects that might be implicated in endogenous glucose regulation. Our objective was to evaluate the impact of acute weight loss and metabolic changes on serum vaspin concentrations in morbidly obese subjects following laparoscopic Roux-en-Y gastric bypass (RYGB) surgery.. Longitudinal, clinical intervention study in 33 morbidly obese subjects before and 12 months after RYGB was conducted. Fasting serum concentrations of vaspin were measured by a commercially available ELISA and correlated with BMI, parameters of insulin sensitivity, and other biochemical measurements. Fasting insulin sensitivity was estimated using the homeostasis model assessment (HOMA) of insulin resistance.. RYGB-induced weight loss resulted in a reduction of circulating vaspin, leptin, insulin, and C-peptide levels as well as of BMI, HbA1c, and HOMA (p < 0.0001, respectively). Changes in serum vaspin concentrations correlated positively with those in HOMA, insulin, C-peptide, HbA1c, and leptin (p < 0.05, respectively) levels. The association between percent change of vaspin and HOMA remained significant even after the adjustment for RYGB-induced changes in BMI.. Following RYGB surgery, changes in serum vaspin concentrations correlate significantly with the reduction of circulating leptin, insulin, and C-peptide levels and with the amelioration of insulin sensitivity. However, further studies have to elucidate whether vaspin is only a biomarker for body-weight-related changes of insulin sensitivity or whether it is implicated in the regulation of human glucose homeostasis.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; Female; Gastric Bypass; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Menopause; Obesity, Morbid; Serpins; Weight Loss

Prolactin (PRL) has been proposed to play an important role in the pathophysiology of obesity. To further elucidate the relationship between PRL and obesity-related metabolic disturbances, we performed a large cross-sectional study and also reassessed serum PRL levels in a subsample approximately 1 year after gastric bypass surgery.. In the cross-sectional part of the study, we assessed basal serum PRL levels in 344 obese subjects (68% women; BMI mean+/-SD, 44.3+/-6.6 kg/m2; range 27.0-67.0 kg/m2) along with measurements of glucose, insulin, C-peptide, triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, high sensitive (hs) C-reactive protein, and fat mass assessed by bioelectrical impedance analysis. In 38 patients, we reassessed PRL levels approximately 1 year after they have undergone a gastric bypass operation.. Women displayed higher basal PRL levels than men (9.0+/-4.8 vs. 7.9+/-3.6 microg/l, P=0.03). Basal PRL levels were neither significantly correlated with the BMI of the subjects (r=-0.05, P=0.77) nor with any other of the assessed variables (all r<0.16, P>0.06) even after adjusting for the influence of sex. After massive surgically induced weight loss that on average almost approached 50 kg, basal serum PRL levels remained completely unchanged (before vs. after, 9.1+/-6.0 vs. 9.2+/-4.6 microg/l, P=0.86). However, preoperative PRL levels significantly correlated with that assessed after the operation (r=0.47; P=0.005).. In contrast to our expectation, we could detect neither any significant association between basal PRL levels and the degree of obesity or related metabolic disturbances nor any systematic changes in basal concentrations of the hormone after massive weight loss. In sum, our data do not support the notion of a major role of PRL in the pathophysiology of obesity.

Topics: Adiposity; Adolescent; Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; C-Reactive Protein; Cholesterol; Cross-Sectional Studies; Female; Follow-Up Studies; Gastric Bypass; Humans; Insulin; Male; Metabolic Syndrome; Middle Aged; Obesity, Morbid; Prolactin; Treatment Outcome; Triglycerides; Weight Loss; Young Adult

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

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

To analyze the time trend of the nationwide incidence of type 2 diabetes in children and adolescents < or = 15 years of age compared with type 1 diabetes between 1999 and 2007 in Austria.. In a prospective, population-based incidence study, all newly diagnosed patients with diabetes < or = 15 years of age were registered by the Austrian Diabetes Incidence Study Group. The Diabetes type was classified on the basis of clinical and laboratory findings according to ADA criteria. Time trends were estimated by linear regression models.. During the observation period, 1881 patients with type 1 diabetes and 34 patients with type 2 diabetes could be identified. Sixty-two percent of patients with type 2 diabetes were female, 56% had a positive family history for type 2 diabetes, and 74% presented with diabetes-specific symptoms. The incidence of type 1 diabetes in Austria increased from 12.0 to 18.4/100,000 (P < .001) and the incidence of type 2 diabetes remained stable below 0.6/100 000 (P = .706).. The incidence of type 2 diabetes in Austrian children is 10-fold lower than reported in other regions and did not increase over the last 8 years. During the same time period, a significant rise in the incidence of type 1 diabetes was observed.

Topics: Adolescent; Austria; Bacterial Infections; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Ethnicity; Female; Genetic Predisposition to Disease; Humans; Incidence; Male; Mycoses; Polyuria; Prospective Studies; Sex Distribution; Time Factors; Weight Loss

A 61-year-old overweight woman had been diagnosed with diabetes mellitus, hypertension and hypothyreosis. Treatment with antidiabetic and antihypertensive medication and thyroxine had been started. Blood sugar had been increasing despite medication and she had started using insulin. In 2003 she used 150 IE insulin per day. She tried hard to adhere to a recommended diet, but gradually became fatter, maximum weight was 120 kg. She started on a low carbohydrate diet on her own and lost 14 kg during 5 months. She had some hypoglycemic episodes and sought advice at Dr. Fedon Lindberg's Clinic. Her low carbohydrate diet was continued, endurance exercise was included, medication with metformin was started and during 8 months she was off insulin and showed much lower blood sugar values than before. She lost 14 kg during this period. She was motivated for loosing more weight and starter on a VLCD (very low caloric diet). She lost another 9 kg on this diet. She than started regular resistance training and her weight stabilized on 80 kg. Her HbA1c value has been reduced from 8.9 to 5.4% and her total/HDL cholesterol ratio has been reduced from 5.4 to 1.7. Her C-peptide value increased in the period when insulin was reduced, but is now reduced to 700 pmol/L. Micro-CRP has been reduced from 9.0 mg/L to 0.4 mg/L. With a low carbohydrate diet and exercise this woman no longer has diabetes or severe overweight. It is our opinion that many patients with type 2 diabetes can manage without medication (especially insulin) by reducing the intake of carbohydrates considerably.

Topics: C-Peptide; Caloric Restriction; Diabetes Mellitus, Type 2; Diet, Carbohydrate-Restricted; Exercise Therapy; Female; Humans; Hypertension; Hypoglycemic Agents; Hypothyroidism; Insulin; Metformin; Middle Aged; Overweight; Weight Loss

Topics: C-Peptide; Caloric Restriction; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Overweight; Weight Loss

Physical activity improves insulin sensitivity and metabolic control in patients with type 2 diabetes. Moreover, regular exercise can reduce systemic levels of immune markers associated with diabetes development. As patients with physical impairments are not able to exercise sufficiently, the aim of this study was to investigate whether high-frequency external muscle stimulation (hfEMS) improves metabolic and immunologic parameters in patients with type 2 diabetes and might therefore serve as complementary lifestyle therapy. Sixteen patients (12 men/4 women, age 57+/-11 years (mean+/-SD); BMI 34.5+/-5.2 kg/m (2); HbA1c 7.4+/-1.1%) on oral antihyperglycaemic therapy were enrolled in this study. After a run-in phase of 2 weeks, every patient received an hfEMS device (HITOP 191, gbo-Medizintechnik AG, Rimbach/Germany) for daily treatment of femoral musculature for 6 weeks. Thereafter, patients were followed up for additional 4 weeks without hfEMS treatment. At each visit, clinical parameters were assessed and blood samples were drawn for metabolic and immunologic parameters. Immune markers (cytokines, chemokines, adipokines and acute-phase proteins) representative for the different arms of the immune system were analysed. hfEMS treatment resulted in significant reductions of body weight (-1.2 kg [-2.7 kg; -0.5 kg]; p<0.05; median [25th percentile; 75th percentile]), BMI (-0.4 kg/m (2) [-0.8 kg/m (2); -0.1 kg/m (2)]; p<0.05) and HbA1c (-0.4% [-0.9%; -0.1%]; p<0.05) which were sustained during the follow-up period. Systemic levels of IL-18 tended to be increased after hfEMS treatment (171 vs. 149 pg/ml; p=0.06), while all other immune markers remained virtually unchanged. Treatment with hfEMS in this first proof-of-principle study has beneficial effects on body weight and improves glycaemic control in patients with type 2 diabetes, which may be associated with changes in subclinical inflammation. Taken together, hfEMS might represent an additional treatment option for patients with type 2 diabetes not being able to exercise.

Topics: Administration, Oral; Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Exercise; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Interleukin-18; Male; Middle Aged; Motor Activity; Muscle, Skeletal; Physical Stimulation; Psychomotor Performance; Weight Loss

There is experimental evidence that a source of fatty acids (FAs) that is either exogenous or endogenous is necessary to support normal insulin secretion. Therefore, FAs comodulate the glucose-induced pancreatic insulin secretion. To assess the role of FAs, 16 morbidly obese nondiabetic patients and 6 healthy volunteers were studied. The controls and the obese subjects, before and after diet-induced weight loss, spent 24 h in a calorimetric chamber, where they consumed standardized meals. Hourly blood samples were drawn from a central venous catheter for the measurement of glucose, C-peptide, and nonesterified fatty acid (NEFA) concentrations. Insulin sensitivity was measured (as the M value) by euglycemic hyperinsulinemic clamp. In the present study, we propose a mathematical model in which insulin secretion rate (ISR) is expressed as a function of both plasma glucose and NEFA concentrations. Model parameters, obtained by fitting the individual experimental data of plasma C-peptide concentration, gave an estimated ISR comparable with that obtained by the deconvolution method. To evaluate the performance of the model in an experimental condition in which incretin effect was minimized, previous data on insulin secretion following a butter load and subsequent hyperglycemic clamp were reanalyzed. This model of nutrient-stimulated insulin secretion is the first attempt to represent in a simple way the interaction between glucose and NEFA in the regulation of insulin secretion in the beta-cell and explains, at least in part, the "potentiation factor" used in previous models to account for other control factors different from glucose after either an intravenous infusion of glucose or a mixed meal.

Topics: Blood Glucose; C-Peptide; Circadian Rhythm; Eating; Fatty Acids, Nonesterified; Glucose Clamp Technique; Humans; Hyperglycemia; Insulin; Insulin Secretion; Insulin-Secreting Cells; Models, Biological; Obesity, Morbid; Osmolar Concentration; Weight Loss

Topics: C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Secreting Cells; Insulin, Long-Acting; Metformin; Peptides; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Venoms; Weight Gain; Weight Loss

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

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

Currently, there are no data in the literature regarding the pathophysiological mechanisms involved in the rapid resolution of type 2 diabetes after bariatric surgery, which was reported as an additional benefit of the surgical treatment for morbid obesity. With this question in mind, insulin sensitivity, using euglycemic-hyperinsulinemic clamp, and insulin secretion, by the C-peptide deconvolution method after an oral glucose load, together with the circulating levels of intestinal incretins and adipocytokines, have been studied in 10 diabetic morbidly obese subjects before and shortly after biliopancreatic diversion (BPD) to avoid the weight loss interference. Diabetes disappeared 1 week after BPD, while insulin sensitivity (32.96 +/- 4.3 to 65.73 +/- 3.22 mumol . kg fat-free mass(-1) . min(-1) at 1 week and to 64.73 +/- 3.42 mumol . kg fat-free mass(-1) . min(-1) at 4 weeks; P < 0.0001) was fully normalized. Fasting insulin secretion rate (148.16 +/- 20.07 to 70.0.2 +/- 8.14 and 83.24 +/- 8.28 pmol/min per m(2); P < 0.01) and total insulin output (43.76 +/- 4.07 to 25.48 +/- 1.69 and 30.50 +/- 4.71 nmol/m(2); P < 0.05) dramatically decreased, while a significant improvement in beta-cell glucose sensitivity was observed. Both fasting and glucose-stimulated gastrointestinal polypeptide (13.40 +/- 1.99 to 6.58 +/- 1.72 pmol/l at 1 week and 5.83 +/- 0.80 pmol/l at 4 weeks) significantly (P < 0.001) decreased, while glucagon-like peptide 1 significantly increased (1.75 +/- 0.16 to 3.42 +/- 0.41 pmol/l at 1 week and 3.62 +/- 0.21 pmol/l at 4 weeks; P < 0.001). BPD determines a prompt reversibility of type 2 diabetes by normalizing peripheral insulin sensitivity and enhancing beta-cell sensitivity to glucose, these changes occurring very early after the operation. This operation may affect the enteroinsular axis function by diverting nutrients away from the proximal gastrointestinal tract and by delivering incompletely digested nutrients to the ileum.

Topics: Adiponectin; Area Under Curve; Bariatric Surgery; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Glucose Clamp Technique; Humans; Insulin; Middle Aged; Obesity, Morbid; Postoperative Period; Weight Loss

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

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

Obesity is linked to the insulin resistance syndrome (IRS), type 2 diabetes (T2D) and cardiovascular disease. Markers of chronic subclinical inflammation such as high-sensitive C-reactive protein (hs-CRP) and interleukin 6 (IL-6) are closely related to insulin resistance and obesity. Recent evidence suggests that adiponectin, a protein whose circulating levels are decreased in obesity, has anti-inflammatory properties, and also appears to enhance potently insulin action and therefore appears to function as a signal produced by adipose tissue that influences whole-body glucose metabolism.. We investigated the cross-sectional and longitudinal association of adiponectin with CRP and IL-6 in 41 morbidly obese women with different stages of glucose tolerance before and 17 months after significant weight loss induced by gastric surgery. Adiponectin was measured by RIA. CRP and IL-6 were determined by commercially available ELISA systems.. Weight loss induced a significant shift from T2D (preoperatively 34% vs postoperatively 2%) to impaired glucose tolerance (IGT) (37% preoperatively vs 30% postoperatively) and normal glucose tolerance (NGT) (29% preoperatively vs 68% postoperatively). Preoperatively adiponectin levels were negatively correlated with CRP (r=-0.59, P<0.0006), IL-6 (r=-0.42, P<0.02) and leukocytes (r=-0.41, P<0.007). After gastroplasty, adiponectin concentrations increased significantly (15.4+/-8.2 vs 19.8+/-6.2 microg/ml, P<0.005) associated with changes of weight and body mass index (r=-0.45, P<0.007; r=-0.35, P<0.04). Furthermore, preoperative CRP was significantly associated with changes in adiponectin even after adjustment for sex, age, preoperative body mass index (BMI) impaired glucose metabolism and changes in BMI and changes in BMI (standardized beta 0.61, P=0.005).. Levels of adiponectin, which are associated with markers of chronic subclinical inflammation, could be significantly increased after weight loss in morbidly obese patients. This increase was more pronounced in patients with NGT compared to those with T2D and IGT. Preoperative levels of CRP are predictive for changes of adiponectin after weight loss.

Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; C-Peptide; C-Reactive Protein; Chi-Square Distribution; Cross-Sectional Studies; Female; Gastroplasty; Glycated Hemoglobin; Humans; Inflammation; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-6; Longitudinal Studies; Middle Aged; Obesity, Morbid; Weight Loss

Insulin hypersecretion and insulin resistance are physiologically linked features of obesity. We tested whether extreme hypersecretion impairs beta-cell function under free-living conditions and whether major weight loss modifies insulin hypersecretion, insulin sensitivity, and beta-cell function. Plasma glucose, C-peptide, and free fatty acid concentrations were measured at hourly intervals during 24 h of normal life (including calorie-standardized meals) in 20 morbidly obese nondiabetic patients (BMI 48.4 +/- 1.7 kg/m2) and 7 nonobese age- and sex-matched control subjects; 8 of the obese patients were restudied 6 months and 2 years following biliopancreatic diversion. Insulin secretion was reconstructed from C-peptide levels by deconvolution and related to concurrent glucose levels through a mathematical model incorporating key features of beta-cell function: rate sensitivity, beta-cell glucose sensitivity, and potentiation. Insulin sensitivity (by the euglycemic insulin clamp technique) was reduced by 50% in obese subjects (23.1 +/- 2.5 of obese subjects vs. 52.9 +/- 4.9 micromol.min(-1) . kg(FFM)(-1) of control subjects, means +/- SE, P = 0.0004) as was mean 24-h insulin clearance (median 809 [interquartile range 451] vs. 1,553 [520] ml.min(-1) . m(-2), P < 0.001) due to a 50% reduction in hepatic insulin extraction (P < 0.01). Over 24 h, insulin secretion was doubled in obese subjects (468 nmol [202] in obese subjects vs. 235 [85] of control subjects, P=0.0002). Despite the hypersecretion, beta-cell glucose sensitivity, rate sensitivity, and potentiation were similar in obese and control subjects. Six months postoperatively (weight loss = 33 +/- 3 kg), both insulin hypersecretion (282 nmol [213]) and insulin sensitivity (51.6 +/- 3.7 micromol.min(-1).kg(FFM)(-1)) were normalized. At 2 years (weight loss = 50 +/- 8 kg), insulin sensitivity was supernormal (68.7 +/- 3.3 micromol.min(-1).kg(FFM)(-1)) and insulin secretion was lower than normal (167 nmol [37]) (both P < 0.05 vs. control subjects). In conclusion, severe uncomplicated obesity is characterized by gross insulin hypersecretion and insulin resistance, but the dynamic aspects of beta-cell function are intact. Malabsorptive bariatric surgery corrects both the insulin hypersecretion and the insulin resistance at a time when BMI is still high. With continued weight loss over a 2-year period, moderately obese subjects become supersensitive to insulin and, correspondingly, insulin hyposecretors.

Topics: Adult; Biliopancreatic Diversion; Blood Glucose; Body Mass Index; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Male; Obesity, Morbid; Weight Loss

To evaluate the effect of massive weight loss on insulin sensitivity, soluble adhesion molecules, and markers of the insulin resistance syndrome (IRS).. Eighteen morbidly obese patients underwent gastric banding and were evaluated before and 6 and 12 months after surgery. Total insulin secretion, hepatic insulin extraction, and insulin sensitivity were analyzed by oral glucose-tolerance test model analysis. In addition, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, leptin, high-sensitivity C-reactive protein, plasminogen activating factor-1 (PAI-1), and tissue plasminogen activator were measured.. BMI dropped from 45.22 +/- 5.62 to 36.99 +/- 4.34 kg/m(2) after 6 months and 33.72 +/- 5.55 kg/m(2) after 12 months (both p < 0.0001). This intervention resulted in a significant reduction of blood pressure (p < 0.00001), triglycerides (p < 0.01), fasting blood glucose (p = 0.03), basal insulin (p < 0.001), and basal C-peptide (p = 0.008) levels. Total insulin secretion decreased (p < 0.05), whereas hepatic insulin extraction (p < 0.05) and oral glucose insulin sensitivity index (p < 0.0001) increased compared with baseline. Leptin (p < 0.0001) and E-selectin levels decreased significantly after 6 and 12 months (p = 0.05), whereas significantly lower levels of intercellular adhesion molecule-1 and PAI-1 were only seen after 6 months. Subclinical inflammation, measured by high-sensitivity C-reactive protein, was lowered to normal ranges. No changes were observed in vascular cell adhesion molecule-1 and tissue plasminogen activator levels.. Although gastric banding ameliorates several features of the IRS, including 29.05% improvement in insulin sensitivity and blood pressure and reduction of soluble adhesion molecules and PAI-1, considerable weight loss did not normalize all components of the IRS in morbidly obese patients.

Topics: Adult; Arteriosclerosis; C-Peptide; Cell Adhesion Molecules; E-Selectin; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Leptin; Male; Obesity, Morbid; Plasminogen Activators; Stomach; Vascular Cell Adhesion Molecule-1; Weight Loss

To examine the impact of important weight loss on insulin inhibition of its own secretion during experimentally induced hyperinsulinemia under euglycemic conditions.. Longitudinal, clinical intervention study--bariatric surgery (vertical banded gastroplasty--gastric bypass--Capella technique), re-evaluation after 4 and 14 months.. Nine obese patients class III (BMI=54.6+/-2.6 kg/m2) and nine lean subjects (BMI=22.7+/-0.7 kg/m2).. Euglycemic hyperinsulinemic clamp (insulin infusion: 40 mU/min m2), C-peptide plasma levels, electrical bioimpedance methodology, and oral glucose tolerance test (OGTT).. BMI was reduced in the follow-up: 44.5+/-2.2 and 33.9+/-1.5 kg/m2 at 4 and 14 months. Insulin-induced glucose uptake was markedly reduced in obese patients (19.5+/-1.9 micromol/min kg FFM) and improved with weight loss, but in the third study, it was still lower than that observed in controls (35.9+/-4.0 vs 52.9+/-2.2 micromol/min kg FFM). Insulin-induced inhibition of its own secretion was blunted in obese patients (19.9+/-5.7%, relative to fasting values), and completely reversed to values similar to that of lean ones in the second and third studies (-60.8+/-4.2 and -54.0+/-6.1%, respectively).. Weight loss in severe obesity improved insulin-induced glucose uptake, and completely normalized the insulin inhibition on its own secretion.

Topics: Adult; Analysis of Variance; Blood Glucose; C-Peptide; Fasting; Female; Gastroplasty; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Longitudinal Studies; Male; Obesity, Morbid; Weight Loss

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

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

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

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

The present study was conducted in order to analyze the relationship existing between leptin and insulin levels in massive weight loss and weight recovery. Thirteen patients with severe obesity, 14 patients with anorexia nervosa and 13 healthy control subjects were studied. The patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet for 12 weeks. They were evaluated prior to (body mass index [BMI] 51.2 +/- 8.8 Kg/m2) and after drastic weight loss (BMI 40.6 +/- 6.7 Kg/m2). Patients with anorexia nervosa were treated exclusively with nutritional therapy during 12 weeks, and they were evaluated at their lowest weight status (BMI 16.2 +/- 2.2 Kg/m2) and after weight recovery (BMI 17.9 +/- 2.3 Kg/m2). The BMI of the normal subjects was in the normal range of 20 to 27 Kg/m2 (average 22.8 +/- 2.6 Kg/m2). BMI, percentage of body fat, waist circumference, and serum levels of leptin, insulin, and C-peptide were determined in each patient and normal subject. In severely obese patients, serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 51.8 +/- 22.3 to 23.7 +/- 10.2 ng/ml; insulin: from 27.1 +/- 13.3 to 17.2 +/- 7.2 mU/ml). In patients with anorexia nervosa, the mean serum leptin levels were significantly higher after weight recovery (5.5 +/- 3.2 vs 7.6 +/- 6 ng/ml). Serum leptin in the severe obesity group correlated positively with BMI, percentage body fat and waist circumference before and after weight loss. In those patients suffering from anorexia nervosa, serum leptin correlated positively with the BMI, percentage of body fat, and waist circumference in the low weight state and after weight recovery. In addition, their serum insulin correlated with BMI and waist circumference after weight recovery. These data reveal that serum leptin concentration correlates significantly with the BMI and body fat content 1) in subjects with a range of weight and caloric intake, 2) in obese patients after drastic weight loss; 3) in anorexic patients after weight gain; and that hyper- or normoinsulinemia do not seem to have any influence on the leptin changes caused by weight loss or gain.

Topics: Adipose Tissue; Adolescent; Adult; Anorexia Nervosa; Anthropometry; Body Mass Index; C-Peptide; Combined Modality Therapy; Female; Gastroplasty; Humans; Hyperinsulinism; Insulin; Leptin; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Weight Gain; Weight Loss

Obesity is a rapidly increasing health problem among US youth. Hyperinsulinemia is associated with obesity and has been found to be a contributory factor for the development of cardiovascular disease in the obese. It has been suggested that hyperinsulinemia of obesity is a result of increased insulin secretion caused by insulin resistance. However, it has been shown in adults that decreased hepatic insulin clearance (HIC) is the primary cause of hyperinsulinemia in this population.. We studied 15 obese children and adolescents (11 F, 4 M; 8.6 to 18.1 years) before and 10 weeks after their enrollment in a multidisciplinary weight reduction program, which included a protein-sparing modified fast, a moderate intensity progressive exercise program, and a behavior-modification intervention.. All patients lost weight (P < 0.05). Measurements of immunoreactive insulin (IRI) and C-peptide reactivity (CPR) were performed before the program and at 10 weeks. IRI levels dropped significantly, whereas CPR levels did not change. CPR/IRI molar ratios, considered an indirect estimation of HIC, rose significantly after weight loss.. Our data suggest that hyperinsulinemia seen in obese children and adolescents is caused by decreased HIC. The cause for this decrease remains unknown, but it is reversible upon weight loss.

Topics: Adolescent; Behavior Therapy; C-Peptide; Child; Diet, Reducing; Exercise; Female; Humans; Insulin; Liver; Male; Obesity; Weight Loss

No consensus exists as to the best approach for treating markedly symptomatic patients with new-onset (or diet-treated) type 2 diabetes. Therefore, based on the experience of one successful case, further studies were undertaken to determine the safety and efficacy of maximal dose glyburide (10 mg, twice daily, in patients < 65 yr of age) or half the dose (10 mg, daily, in patients > or = 65 yr of age) for treating these patients. Fifty-five patients with polyuria, polydipsia, nocturia, involuntary weight loss, and blood glucose concentrations of 300 mg/dL or greater were treated following protocols that used maximal dose ( < 65 yr of age) or half-maximal dose ( > or = 65 yr of age) sulfonylurea agent therapy. Data were collected retrospectively in 30 patients and prospectively in 25. Patients in the prospective group differed only in that more laboratory measurements were obtained, and less strict guidelines for using insulin were adopted. Data were collected in both groups at baseline and 1 week and 4 months after starting the sulfonylurea agent therapy. Patients responded rapidly with a fall in blood glucose levels from 456 +/- 12 mg/dL at baseline to 202 +/- 10 mg/dL at 1 week to 120 +/- 5 mg/dL at 4 months. Glycated hemoglobin levels fell from 18.1 +/- 0.4% at baseline to 8.1 +/- 0.2% ( P < 0.0001) at 4 months. Most patients had symptomatic improvement within 3 days. Seventeen patients had positive (small or larger) urinary ketones, and 5 had positive serum ketones. Insulin to glucose and C peptide to glucose ratios improved maximally at 1 week, indicating rapid reversal of glucotoxicity on the beta-cell. At 4 months, 11 patients were receiving diet therapy alone, 29 were receiving submaximal dose sulfonylurea agent therapy, 6 remained on maximal dose sulfonylurea agent therapy, and only 3 were receiving insulin therapy. Six patients were lost to follow-up. No patient experienced hypoglycemia in the first 2 weeks of treatment. Maximal dose sulfonylurea agent therapy is a safe and effective method for treating patients with markedly symptomatic type 2 diabetes. Patients improve rapidly and are able to avoid the immediate institution of long term insulin therapy.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glyburide; Humans; Hypoglycemic Agents; Insulin; Ketones; Male; Middle Aged; Polyuria; Prospective Studies; Retrospective Studies; Urination Disorders; Weight Loss

To study the effects of a very low calorie diet (VLCD) on glucose and lipid metabolism in obese subjects, in particular, the effects on insulin sensitivity and the activities of the key enzymes of glucose disposal, glycogen synthase (GS) and the pyruvate dehydrogenase complex (PDHC).. Clinical dietary intervention study (1.67 MJ (400 kcal)/day) until weight loss of > 10%.. 11 (seven male, four female) non-diabetic, obese subjects (age: 27-62 y; BMI: 40.5 +/- 1.4 kg/m2).. Whole body glucose disposal (by euglycemic hyperinsulinemic clamp), respiratory quotient (RQ), resting energy expenditure (REE), glucose and lipid oxidation (by indirect calorimetry), insulin-stimulated PDHC and GS activity (in muscle biopsies) both before and immediately after VLCD (i.e. while still in a hypocaloric state), serum hormone and metabolite levels throughout the dietary period.. Weight loss was accompanied by reduced insulin and elevated NEFA levels, improved insulin sensitivity due to increased nonoxidative glycolysis with no increase in PDHC or GS activities. The rate of weight loss was inversely related to the initial RQ. PDHCa was strongly age-related.. A low RQ may be used as a predictor of the efficacy of VLCD treatment and that while VLCD improves nonoxidative glycolytic flux, changes in oxidative glucose disposal and muscle glucose storage are prevented by high NEFA availability during this catabolic phase of dietary intervention.

Topics: Adult; Anthropometry; Blood Glucose; Blood Pressure; C-Peptide; Diet, Reducing; Energy Intake; Energy Metabolism; Fasting; Fatty Acids, Nonesterified; Female; Glycogen Synthase; Humans; Insulin; Lipids; Male; Middle Aged; Muscles; Obesity; Pyruvate Dehydrogenase Complex; Weight Loss

To characterize differences in metabolic indices as well as body composition in two ethnic groups.. Eight black and eight white obese urban women were studied.. Eight black and eight white obse (BMI > 34) urban women (BW, WW) were matched for age, BMI, WHR, diet and physical activity and investigated before and after 12 weeks of Dexfenfluramine treatment.. Anthropometric measurements; Post 75 g OGTT, plasma glucose, insulin and C-peptide levels were done. FFA and lactate levels were done at onset. Skinfold thickness with Harpenden calipers, bio-impedance for analyses of body composition and CT scan for assessment of regional adiposity (at onset and after 3 months).. In the postabsorptive state the WW had significantly higher plasma total cholesterol and triglyceride levels and an unfavourable HDL : total cholesterol ratio. Their FFA levels were significantly lower (324 +/- 51 vs 985 +/- 84 mumol/l; p < 0.0001) and their lactate levels were significantly higher (3045 +/- 245 vs 1938 +/- 358 mumol/l; p < 0.001) as compared with the BW. During a 75 g OGTT the BW had significantly higher glucose levels at 1 h (8.6 +/- 0.8 vs 5.1 +/- 0.4 mmol/l; p < 0.005) and 2 h (7.6 +/- 0.6 vs 4.4 +/- 0.3 mmol/l) but not at fasting. In contrast the BW had lower insulin concentrations (fasting: 77 +/- 9 vs 139 +/- 19 pmol/l; p < 0.04 and 1 h 318 +/- 56 vs 624 +/- 75 pmol/l; p < 0.005), and C-peptide concentrations (fasting: 400 +/- 99 vs 1600 +/- 99 pmol/l; p < 0.000 04, 1 h 1400 +/- 433 vs 5966 +/- 333 pmol/l; p < 0.0007 and 2 h 1266 +/- 333 vs 4066 +/- 366 pmol/l; p < 0.0005). CT scan measurements showed that the WW had significantly more visceral fat than the BW (148.5 +/- 2.0 vs 115.5 +/- 6.9 cm2; p < 0.05) but lost less weight during Dexfenfluramine treatment (-4 kg vs -9 kg). Despite this, the WW lost more visceral fat than the BW (-27.3 cm2/-18.5%; p < 0.03 vs -15.5 cm2/-13.2%; p < 0.04). In contrast the BW had a larger reduction in subcutaneous (SC) fat (-13.9% vs -1.7%; p < 0.01), with the greatest reduction in the SC gluteofemoral adipose tissue (widest hip circumference -20.8% vs -0.2%; p < 0.001) and mid-femur region (-13.1% vs -0.7%; p < 0.08).. Weight loss in obese black women is associated with a major reduction in SC fat mass with the most active mobilization of fat tissue occurring in the gluteofemoral area. In contrast the WW had more visceral fat that was more readily mobilized. The difference in adipose tissue distribution and pattern of mobilization was associated with lower plasma insulin, C-peptide and triglyceride concentrations in the BW despite increased FFA and glucose levels. These data suggest that plasma insulin concentrations are important in regulating differences in regional adipose tissue metabolism as well as the serum lipid profile.

Topics: Adipose Tissue; Adult; Anthropometry; Appetite Depressants; Black or African American; Black People; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Cholesterol; Fatty Acids, Nonesterified; Female; Fenfluramine; Humans; Insulin; Lactates; Obesity; Skinfold Thickness; South Africa; Tomography, X-Ray Computed; Triglycerides; Weight Loss; White People

Subjects with overt non-insulin-dependent diabetes mellitus (NIDDM) were studied in comparison to obese nondiabetic control subjects and patients with subclinical diabetes. Pancreatic insulin secretion rates were measured by deconvolution of peripheral C-peptide over a 24-h period while subjects consumed an isocaloric mixed diet. Subjects were then placed on caloric restriction for at least 6 weeks, during which time body weight fell by at least 10%. Refeeding with solid mixed meals was then resumed for at least 2 weeks until isocaloric intake was attained, and then the meal profiles were repeated. Before weight loss, insulin, C-peptide, and insulin secretion rates were significantly higher in subjects with subclinical diabetes than in the other two groups. Proinsulin concentrations were significantly greater in the two diabetic groups than in control subjects, but, when expressed as a percentage of the total insulin immunoreactivity, the differences were significant only in the group with overt diabetes. Weight loss because of hypocaloric feeding resulted in a significant increase in the rate of clearance of endogenously secreted insulin but did not affect the clearance of C-peptide. In obese subjects and those with subclinical diabetes, weight loss was associated with a reduction in insulin secretion rates, presumably as a result of improvements in insulin sensitivity. In patients with overt diabetes and hyperglycemia, weight loss improved beta-cell responsiveness to glucose and was associated with an increase in insulin clearance and a reduction in proinsulin immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Humans; Insulin; Metabolic Clearance Rate; Middle Aged; Obesity; Proinsulin; Reference Values; Weight Loss

The effects of two low-energy diets on serum insulin concentrations and weight loss in obese hyperinsulinemic females were compared during a 12-wk period. The first diet (n = 15) was designed to evoke a low insulin response (ID), and the second (n = 15) was a conventionally balanced diet (ND). After a 12-wk washout period, seven and nine subjects who had been on the ID and ND, respectively, changed to the alternative diet for 12 wk. Variables studied were basal and 30- and 120-min concentrations of blood glucose, insulin, and C-peptide after an oral glucose load; body weight; and energy intake. Mean (+/- SD) weight was significantly reduced after ID and ND (9.35 +/- 2.49 and 7.41 +/- 4.23, respectively). The mean weight loss was more after ID. Fasting insulin concentrations decreased more after ID compared with ND (91.3 +/- 61.8 vs 21.0 +/- 71.5 pmol/L; P < 0.05). We conclude that ID significantly reduces serum insulin concentrations and weight in obese hyperinsulinemic females.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Complications; Diabetes Mellitus; Diet, Diabetic; Energy Intake; Fasting; Female; Humans; Hyperinsulinism; Insulin; Obesity; Weight Loss

Very Low Calorie Diet (VLCD) is known to induce not only weight loss, but also an improvement of metabolic control, in obese type II diabetics. In order to evaluate the therapeutical efficacy of cycles of VLCD shorter than those previously described, 29 obese type II diabetics and 31 obese nondiabetic subjects were entered as inpatients and prescribed a 450 kcal/day diet for 15 days. Metabolic results obtained were similar to those achieved with longer cycles of VLCD, showing that 15 days are sufficient to induce a BMI decrease in diabetic (BMI from 35.3 +/- 4.8 to 33.3 +/- 4.6 after VLCD) and nondiabetic patients (BMI from 40.5 +/- 7.4 to 38.1 +/- 7.2 after VLCD), a desired fall of blood glucose levels and the decrease of daily insulin needs in insulin-treated patients. Glucagon tests were performed before and after VLCD in order to study possible modifications of insulin secretion. Although we did not observe any significant increase of C-peptide basal or peak levels (nM/ml) either in diabetic (basal levels before VLDC: 1.2 +/- 0.4 and peak levels 2.4 +/- 0.7; basal after VLCD 1.23 +/- 0.6 and peak 2.6 +/- 0.7) and nondiabetic patients (basal levels before VLDC 1.0 +/- 0.3 and peak levels 2.5 +/- 0.4; basal after VLCD 0.9 +/- 0.3 and peak 2.4 +/- 0.6). The rise of the C-peptide/glycemia ratio is an index of an improvement of insulin biological activity, which could be partly responsible for the therapeutical effects of VLCD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Female; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Receptor, Insulin; Weight Loss

This study investigated the effects of a drastic weight reduction on insulin secretion rate (ISR), insulin metabolic clearance rate (MCRI) and insulin sensitivity (SI) in severely obese subjects. A frequently sampled intravenous glucose tolerance test (FSIVGTT, 0.3 g/kg) was performed before and 8 +/- 1 months after a vertical ring gastroplasty in 12 overnight-fasted obese non-diabetic subjects; the results were compared to those obtained in 12 lean controls matched for age and sex. ISR was derived by deconvolution of plasma C-peptide levels; MCRI was obtained by dividing the area under the curve (AUC180 min) of ISR by the corresponding AUC of plasma insulin levels (IRI); the SI and the glucose effectiveness index (SG) were calculated by Bergman's minimal model. Before gastroplasty, obese subjects showed significantly higher ISR (P < 0.02), lower MCRI (P < 0.001), lower SI (P < 0.001) but similar SG when compared to lean controls. After gastroplasty (reduction of body weight from 104.8 +/- 3.8 to 73.4 +/- 3.6 kg and of BMI from 37.9 +/- 0.8 to 26.5 +/- 0.9 kg/m2; P < 0.001), ISR only decreased from 53,125 +/- 7968 to 42,302 +/- 3716 pmol/180 min (not significant) while AUC-IRI dramatically fell from 53,626 +/- 6378 to 21,111 +/- 2584 pmol.min/l; P < 0.001); consequently, MCRI markedly increased from 526 +/- 96 to 1257 +/- 150 ml/min/m2; P < 0.01). SI significantly rose from 3.12 +/- 0.45 to 7.10 +/- 1.20 x 10(-4) l/mU/min (P < 0.005) while SG remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Body Composition; C-Peptide; Female; Gastroplasty; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Kinetics; Male; Metabolic Clearance Rate; Obesity, Morbid; Weight Loss

To examine the cause of hyperinsulinemia in obesity, we determined plasma glucose, insulin, and C peptide responses to glucose (75g), arginine (0.5 g/kg body weight), and glucagon (1mg) in seven normal subjects and 20 obese subjects before and after weight loss by very low calorie diet therapy (Optifast, 240 kcal/day for 8 to 12 weeks). Integrated insulin and C peptide secretion in response to three different stimuli were markedly increased before weight loss and were significantly decreased following weight loss in response to glucose (mean +/- s.e. 36.6 +/- 6.4 vs. 18.4 +/- 2.6; 148.2 +/- 12.0 vs. 113.1 +/- 8.7 pmol/ml/h; P < 0.01), arginine (13.8 +/- 2.2 vs. 8.2 +/- 2.1; 94.8 +/- 11.2 vs. 66.0 +/- 6.1 pmol/ml/h; P < 0.01), and glucagon (16.5 +/- 2.7 vs. 10.7 +/- 1.5; 89.0 +/- 6.0 vs. 68.7 +/- 4.8 pmol/m/h; P < 0.01). The molar ratio of integrated C peptide to integrated insulin in response to all three stimuli was markedly decreased before, and this ratio significantly increased following weight loss (mean +/- s.e., 5.01 +/- 0.41 vs. 7.45 +/- 0.65; P < 0.01), and to arginine (7.78 +/- 0.61 vs. 10.97 +/- 1.28; P < 0.05), but not to glucagon (6.72 +/- 0.60 vs. 7.47 +/- 0.66). These findings suggest that both increased insulin secretion and decreased insulin clearance contribute to hyperinsulinemia in obese subjects. Improvement in these abnormalities to all three stimuli after weight loss also suggests that hyperinsulinemia in obesity is a consequence of the obesity itself rather than a pre-existing disorder.

Topics: Adolescent; Adult; Arginine; Blood Glucose; Body Mass Index; C-Peptide; Energy Intake; Glucagon; Glucose; Humans; Insulin; Insulin Secretion; Kinetics; Male; Obesity; Weight Loss

A reduced thermic response and an impaired activation of the sympathetic nervous system (SNS) has been reported after oral glucose in human obesity. It is, however, not known whether the reduced SNS activity returns to normal along with weight reduction. The thermic effect of glucose was lower in eight obese patients than in matched control subjects (1.7% vs 9.2%, p less than 0.002). The increase in arterial norepinephrine after glucose was also blunted in the obese patients. After a 30-kg weight loss their glucose and lipid profiles were markedly improved but the thermic effect of glucose was still lower than that of the control subjects (4.2%, p less than 0.001). The glucose-induced arterial norepinephrine response remained diminished in the reduced obese patients whereas the changes in plasma epinephrine were similar in all three groups. The results suggest that a defective SNS may be a cause in the development of obesity.

Topics: Adult; Blood Glucose; Body Temperature Regulation; C-Peptide; Energy Metabolism; Epinephrine; Female; Glucagon; Glucose; Humans; Insulin; Male; Middle Aged; Norepinephrine; Obesity; Sympathetic Nervous System; Weight Loss

Impairment in pancreatic production of insulin, a cardinal feature of noninsulin dependent diabetes mellitus (NIDDM), was quantified and the kinetics of insulin secretion characterized in six obese individuals with NIDDM before and after weight loss (18.0 +/- 3.0 kg, mean +/- SEM) using a validated mathematical model that employs C-peptide as a marker of the in vivo rate of insulin secretion. The metabolic clearance of C-peptide, assessed by decay analysis after bolus injection of biosynthetic human C-peptide, was not changed by weight loss (0.143 +/- 0.009 L/min.m2 vs. 0.137 +/- 0.010 L/min.m2). Kinetic parameters from each individual's decay curve before and after weight loss were used to derive accurate rates of secretion during the basal (postabsorptive) state, an oral glucose tolerance test and two hyperglycemic clamps. Basal rates of insulin secretion declined 20 +/- 5 pmol/min.m2 (96 +/- 15 to 76 +/- 15 pmol/min.m2, P less than 0.05) concomitant with decreases of 6.9 +/- 0.9 mmol/L in fasting serum glucose (13.7 +/- 1.0 to 6.8 +/- 0.7 mmol/L, P less than 0.05), 60 +/- 14 pmol/L in serum insulin (134 +/- 30 to 74 +/- 15 pmol/L, P less than 0.05), and 0.15 +/- 0.03 pmol/ml in plasma C-peptide (0.67 +/- 0.11 to 0.52 +/- 0.08 pmol/ml, P less than 0.05) concentrations. As expected, weight loss resulted in improved glucose tolerance as measured by the glycemic profiles during the oral glucose tolerance test (P less than 0.05 analysis of variance). The insulin secretory response before weight loss showed a markedly reduced ability to respond appropriately to an increase in the ambient serum glucose. After weight loss, the pancreatic response was more dynamic (P less than 0.05, analysis of variance) and parralleled the moment-to-moment changes in glycemia. Insulin production above basal doubled (11.2 +/- 3.2 to 24.5 +/- 5.8 nmol/6h.m2, P less than 0.05) and peak rates of insulin secretion above basal tripled (55 +/- 16 to 157 +/- 32 pmol/min/m2, P less than 0.05). To assess the beta-cell response to glucose per se and the changes associated with weight reduction, two hyperglycemic clamps were performed at steady state glucose levels in the range characteristic of individuals with severe NIDDM. At a fixed glycemia of 20 mmol/L, average rates of insulin secretion increased almost 2-fold with treatment (161 +/- 41 to 277 +/- 60 pmol/min.m2, P less than 0.05). At an increment of 6 mmol/L glucose above prevailing fasting glucose levels, the average rate of insu

Topics: Analysis of Variance; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Models, Theoretical; Obesity; Weight Loss

In order to characterize Type I diabetes at its clinical onset in French children, we studied HLA-DR alleles, beta-cell function and autoantibodies to islet-cell antigens and insulin in 115 patients aged 1.8-17 years. Beta-cell function was markedly impaired, but with an unexpectedly wide range of individual variations. These variations showed no correlation with HLA alleles or circulating autoantibodies, as opposed to observations made by others. Age, however, had a clear influence on the degree of impairment of residual insulin secretion, the younger children having the more deteriorated beta-cell secretory capacity conditioning the severity of clinical manifestations (weight loss, ketonuria, ketoacidosis) and initial hyperglycemia.

Topics: Adolescent; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; France; HLA-DR Antigens; Humans; Infant; Insulin Antibodies; Male; Polyuria; Weight Loss

We studied a group of obese hyperandrogenic amenorrheic women to determine the effects of weight loss on anthropometry, hormonal status, menstrual cycles, ovulation, and fertility. Fourteen women had polycystic ovaries, two the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome, one hirsutism of adrenal origin, and three idiopathic chronic anovulation. The duration of amenorrhea before the study ranged from 3-17 months [mean, 8.6 +/- 4.5 (+/- SD)]. All women ate a hypocaloric diet for a period of 8.0 +/- 2.4 months. Weight loss ranged from 4.8 to 15.2 kg (mean, 9.7 +/- 3.1 kg; 1.35 +/- 0.56 kg/month) and the waist to hip ratio, which was used as a measurement of body fat distribution, decreased from 0.86 +/- 0.1 to 0.81 +/- 0.06 (P less than 0.0001). The women's mean plasma testosterone and LH concentrations decreased significantly (P less than 0.001 and P less than 0.005, respectively). A significant positive correlation was found between the decreases in plasma testosterone levels and the decreases in glucose-stimulated insulin levels. Moreover, the decreases in the waist to hip ratio correlated positively with the decreases in glucose-stimulated insulin levels and inversely with the decreases in plasma 17 beta-estradiol. No relationships were found between weight loss and the changes in plasma insulin, steroid, and gonadotropin concentrations. The responsiveness to the weight reduction program was evaluated by comparing the number of menstrual cycles during the study period with the number reported before it. Eight women had significantly improved menstrual cyclicity (responders), while 12 did not (nonresponders). The clinical characteristics and hormone values were similar in responder and nonresponder women. In the group as a whole, 33% of the menstrual cycles during the study were ovulatory, and 4 pregnancies occurred. Hirsutism improved significantly in more than half of the women, as did acanthosis nigricans when present. We conclude that weight loss is beneficial in all obese hyperandrogenic women regardless of the presence of polycystic ovaries, the degree of hyperandrogenism, and the degree and distribution of obesity.

Topics: Adult; Amenorrhea; Androgens; Blood Glucose; C-Peptide; Female; Hormones; Humans; Insulin; Menstrual Cycle; Obesity; Ovulation; Weight Loss

Decreased food intake and weight loss are seen in eating and depressive disorders. No satisfactory pathophysiological mechanisms have been proposed to explain those findings. While it should be kept in mind that the etiology of those diseases is still unclear, it seems reasonable to propose that the maintenance of anorectic behavior in the eating disorders as well as the decreased food intake of major depression, leading to continued weight loss seen in both conditions, are either caused or mediated by insulin in levels which are elevated but insufficient to cause hypoglycemia. A brief review is made of the role of insulin in satiety and in the control of body weight, and of the newly available techniques to accurately quantify secretion, hepatic extraction, and post-hepatic delivery rates of insulin. Neural, metabolic, and endocrine stimuli affect insulin secretion. The hypothesis is therefore compatible with several etiologic factors leading to hyperinsulinemia in anorexia nervosa and major depression, and resulting in decreased food intake and weight loss.

Topics: Anorexia Nervosa; C-Peptide; Depressive Disorder; Eating; Humans; Hyperinsulinism; Insulin; Liver; Weight Loss

The effect of weight reduction on fasting serum lipids and lipoproteins and adipose tissue lipoprotein lipase responsiveness to insulin was assessed immediately after and 3 mo subsequent to a mean 11.7% weight reduction in 14 women. Whereas reduction in fasting serum triglycerides persisted after 3 mo, reductions in serum cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein (HDL) cholesterol were not found at 3 mo. In fact, at 3 mo, levels of HDL cholesterol were higher than before weight reduction. Maintenance of the reduced-obese state also increased the HDL2-to-HDL3 cholesterol ratio (P less than 0.01), an effect strongly associated with the change in the responsiveness of adipose tissue lipoprotein lipase to insulin (r = 0.821, P less than 0.001). Moreover, after maintenance of the reduced-obese state, the HDL2-to-HDL3 cholesterol ratio also increased after the ingestion of corn oil and a 6-h insulin-glucose infusion, a response not present before weight reduction. Thus the effect of weight reduction on serum lipids and lipoproteins was not only time dependent, but for HDL, was strongly associated with changes in adipose tissue metabolism.

Topics: Adipose Tissue; Adult; Basal Metabolism; Blood Glucose; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Insulin; Lipoproteins, HDL; Obesity; Triglycerides; Weight Loss

Topics: Abdomen; Adipose Tissue; C-Peptide; Diet, Reducing; Energy Intake; Female; Humans; Insulin; Liver; Obesity; Weight Loss

Sixty-one patients with non-insulin-dependent diabetes mellitus and fasting blood glucose of 12.0 +/- 0.6 mmol/l were studied before and after dietary treatment in an outpatient setting. At the start of the study 33 patients were obese (body mass index greater than 27.0 kg/m2). Twenty patients were newly diagnosed, median known duration of diabetes in the others was 5 years. Beta-cell function was measured by the release of C-peptide after i.v. injection of 1 mg glucagon (area under the curve of C-peptide = AUC-cp), as well as calculated according to the formulae of Matthews. Insulin action was estimated by measurement of fasting blood glucose, insulin and free fatty acids (FFA) concentrations. Non-obese patients showed more severe beta-cell deficiency than the obese ones (AUC-cp 2586 +/- 158 vs. 3294 +/- 277 pmol/l per 15 min), and did not improve in metabolic control during treatment. In the obese patients three response patterns to treatment were observed: weight loss and improvement in metabolic control accompanied primarily with increased beta-cell function or increased insulin action, or worsening of metabolic control. Those with less impaired beta-cell function and shorter known duration of diabetes showed the most favourable response.. non-obese type 2 diabetes patients with fasting glucose levels above 10 mmol/l do not improve on dietary treatment alone; in obese type 2 diabetics weight reduction is essential and results in metabolic improvement, irrespective of the preceding fasting blood glucose concentrations. Improved beta-cell function as well as increased insulin action are responsible for this improvement.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Weight Loss

To study the relationship between childhood obesity, weight loss, hyperinsulinaemia and the erythrocyte insulin receptor, we measured the plasma concentrations of immunoreactive insulin (IRI) and C-peptide and the binding of 125I-insulin to erythrocytes in 12 obese children with a mean age +/- SD of 11.4 +/- 2.5 years and a mean relative weight score +/- SD of 4.8 +/- 1.4 and 12 age-matched normal-weight children. Eight obese children were re-evaluated after 1 year's participation in a weight reduction programme. The obese children had higher fasting plasma concentrations of IRI (P less than 0.01) and C-peptide (P less than 0.05) and a lower C-peptide to IRI molar ratio (P less than 0.01) than the normal-weight children. The obese children had in addition a reduced erythrocyte insulin binding (P less than 0.05 or less) over the physiological range of circulating insulin concentration. There was a negative correlation (r = -0.60; P less than 0.01) between the insulin tracer binding and the relative weight. The weight reduction programme resulted in a decrease of 1.0 SD (P less than 0.05) in the mean relative weight score. At the end of the therapy the obese children had lower fasting blood glucose levels (P less than 0.05) and lower plasma IRI concentrations at 90 min (P less than 0.05) after an oral glucose load than at the onset of therapy. There were no significant differences between the insulin binding characteristics at the commencement and at the end of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Child; Erythrocytes; Female; Humans; Insulin; Male; Obesity; Receptor, Insulin; Weight Loss