c-peptide and Obesity--Morbid

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

Our aim is to clarify the features of complete type 2 diabetes mellitus (T2DM) remission in patients who undergo Roux-en Y gastric bypass surgery, to better determine factors affecting the outcome of T2DM surgery. A search was conducted for original studies on Medline, PubMed and Elsevier from inception until October 28, 2014. All of the articles included in this study were assessed with the application of predetermined selection criteria and were divided into two groups: Roux-en Y gastric bypass surgery for T2DM patients in remission or non-remission. The meta-analysis results demonstrated that fasting C-peptide values were significantly associated with increased remission (C-peptide: 95%CI = 0.2-1.0) whereas T2DM duration, patient age, preoperative insulin use, preoperative fasting blood glucose values and preoperative glycosylated haemoglobin values were significantly associated with reduced remission (T2DM duration: 95%CI = -1.2 - -0.7; age: 95%CI = -0.5 - -0.1; percentage of preoperative insulin users: odd ratio = 0.10, 95%CI = 0.07-0.15; preoperative fasting blood glucose: 95%CI = -0.9 - -0.5; preoperative glycosylated haemoglobin: 95%CI = -1.1 - -0.4). However, the results demonstrated that body mass index was not statistically different (body mass index: 95%CI = -0.2-0.6). The results of the systematic review demonstrated that smaller waist circumference; lower total cholesterol, triglycerides and low-density lipoprotein levels, increased higher high-density lipoprotein levels, shorter cardiovascular disease history and less preoperative prevalence of hypertension contribute to the increased postoperative remission rate. Better results are obtained in younger patients with less severe diabetes, a smaller waist circumference, higher preoperative high-density lipoprotein, lower preoperative total cholesterol, triglycerides and low-density lipoprotein levels and fewer other complications of shorter durations.

Topics: Age Factors; Blood Glucose; Body Mass Index; C-Peptide; Cholesterol; Diabetes Mellitus, Type 2; Gastric Bypass; Glycated Hemoglobin; Humans; Hypertension; Hypoglycemic Agents; Insulin; Lipoproteins, HDL; Lipoproteins, LDL; Obesity, Morbid; Prognosis; Remission Induction; Treatment Outcome; Triglycerides

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

Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.. Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35 kg/m 2 , glucagon-stimulated C-peptide of >1.5 ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value <0.05 was defined as significant.. MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45±0.27% to 7.09±0.26%, P =0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and β-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.. RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.

Topics: Adipokines; Adolescent; Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Gastric Bypass; Gastrointestinal Hormones; Glucagon; Glycated Hemoglobin; Humans; Insulin; Liver Diseases; Middle Aged; Obesity, Morbid; Prospective Studies; Sirtuin 1; Young Adult

Altered bile acid (BA) turnover has been suggested to be involved in the improved glucose regulation after Roux-en-Y gastric bypass (RYGB), possibly. Two single-blinded randomized cross-over studies were performed. In study 1, eight RYGB operated participants ingested 200 ml water with 1) CDCA 1.25 g or 2) CDCA 1.25 g + colesevelam 3.75 g on separate days. In study 2, twelve RYGB participants ingested on separate days a mixed meal with addition of 1) CDCA 1.25 g, 2) COL 3.75 g or 3) COL 3.75 g × 2, or 4) no additions.. In study 1, oral intake of CDCA increased circulating BAs, GLP-1, C-peptide, glucagon, and neurotensin. Addition of colesevelam reduced all responses. In study 2, addition of CDCA enhanced meal-induced increases in plasma GLP-1, glucagon and FGF-19 and lowered plasma glucose and C-peptide concentrations, while adding colesevelam lowered circulating BAs but did not affect meal-induced changes in plasma glucose or measured gastrointestinal hormones.. In RYGB-operated persons, exogenous CDCA enhanced meal-stimulated GLP-1 and glucagon secretion but not insulin secretion, while the BA sequestrant colesevelam decreased CDCA-stimulated GLP-1 secretion but did not affect meal-stimulated GLP-1, C-peptide or glucagon secretion, or glucose tolerance. These findings suggest a limited role for endogenous bile acids in the acute regulation of postprandial gut hormone secretion or glucose metabolism after RYGB.

Topics: Adult; Bile Acids and Salts; Blood Glucose; C-Peptide; Colesevelam Hydrochloride; Female; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Male; Middle Aged; Neurotensin; Obesity, Morbid; Postprandial Period; Single-Blind Method

There is limited literature available on the long-term effect of bariatric surgery especially laparoscopic sleeve gastrectomy (LSG) on the incretin hormone response.. Our primary aim was to investigate changes in glucose metabolism and incretin hormone responses in participants with impaired glucose regulation approximately 4 years after LSG. The secondary aim was to examine the long-term incretin hormone changes of biliopancreatic diversion (BPD).. A non-randomised prospective study comprising of 10 participants undergoing LSG and 6 participants undergoing BPD. Serial measurements of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were performed during an oral glucose tolerance test pre-operatively and 1 month, 6 months and at approximately 4-7 years post-operatively. Area under the curve (AUC) was examined at 60 and 120 min.. In the LSG group, a significant reduction in 2-h plasma glucose (2 h PG), HbA1c and HOMA-IR was observed at 4 years. Compared with pre-operative levels, significant increases in post-glucose GLP-1 secretion were observed at 1 and 6 months, but not maintained at 4 years. A linear increase was seen in post-glucose GIP response at 1 month and 6 months and 4 years. Within the BPD group, a reduction in HbA1c along with an increase GLP-1 response was observed at 7 years.. An increase in GLP-1 response was not preserved at 4 years, but a significant increase in GIP response was observed along with improved glycaemic control following LSG.

Topics: Adult; Blood Glucose; C-Peptide; Female; Follow-Up Studies; Gastrectomy; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Homeostasis; Humans; Incretins; Insulin; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Prospective Studies; Time Factors

Postprandial hypoglycaemia (PPHG) is a complication of Roux-en-Y gastric bypass (RYGB) surgery in normoglycaemic individuals. In type 2 diabetes, RYGB improves glucose metabolism, but whether this improvement is related to the later development of PPHG is not known. We investigated the presence and mechanisms of PPHG in individuals with type 2 diabetes undergoing RYGB.. A total of 35 obese individuals with type 2 diabetes underwent an OGTT before and 24 months after surgery. PPHG was defined as a plasma glucose level of ≤3.3 mmol/l when not taking glucose-lowering agents. Insulin sensitivity was assessed by oral glucose insulin sensitivity index and beta-cell function by mathematical modelling of the plasma glucose, insulin and C-peptide concentrations.. After surgery, PPHG occurred in 11 of 35 individuals who underwent RYGB. Before surgery, BMI was lower, glycaemic control less good and time of glucose peak earlier in the PPHG vs No PPHG group, and the duration of diabetes was shorter with PPHG (all p ≤ 0.05). In addition, insulin sensitivity was greater in the PPHG than No PPHG group (p = 0.03). After surgery, BMI and fasting glucose and insulin levels decreased similarly in the two groups; insulin secretion during the first hour of the OGTT increased more in the PPHG than No PPHG group (p = 0.04). Beta-cell glucose sensitivity increased more in individuals with PPHG than those without (p = 0.002). Over the same time interval, the glucagon-like peptide 1 (GLP-1) response was lower in individuals with PPHG before surgery (p = 0.05), and increased more after surgery. At 2 h after glucose ingestion in the OGTT, postsurgery plasma glucagon level was significantly lower in the PPHG than No PPHG group.. In morbidly obese individuals with type 2 diabetes, spontaneous PPHG may occur after bariatric surgery independently of a remission of diabetes. Before surgery, individuals had a shorter duration and were more insulin sensitive. Two years after surgery, these individuals developed greater beta-cell glucose sensitivity, and showed greater insulin and GLP-1 release early in the OGTT.

Topics: C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucose Tolerance Test; Humans; Hypoglycemia; Male; Obesity, Morbid

Laparoscopic sleeve gastrectomy is one of the most common techniques in bariatric surgery, but there is no consensus on the optimal distance from the pylorus to start the gastric transection. The aim of this study is to determine the differences in gastric emptying, gastric distension and metabolic response between two starting distances.. This is a prospective randomised study of 60 patients (30 patients with the section at 3 cm and 30 patients at 8 cm from the pylorus). We calculate at 6 and 12 months from surgery gastric emptying by scintigraphy (T1/2 min), gastric volume by CT scan (cc) and metabolic response by blood sample analysis (glucose, HbA1c, insulin, HOMA-IR, GLP-1, GIP and C-peptide).. Gastric emptying increases the speed significantly in both groups but is greater in the 3-cm group (p < 0.05). Dividing groups into type 2 diabetic patients and non-diabetic patients, the speed in non-diabetic patients is significantly higher for the 3-cm group. Residual volume increases significantly in both groups, and there are no differences between them. One year after surgery, there are significant improvements in the hyperinsulinaemia in the patients of the 3-cm group with respect to the 8-cm group, but only in diabetic patients. No differences between groups are found regarding changes in GLP-1 or GIP.. Gastric emptying is faster in patients with antrum resection. The distance does not influence the gastric emptying of diabetic patients. Other mechanisms may explain metabolic response besides GLP-1 and its association with improvements in diabetes via gastric emptying.

Topics: Adult; Aged; C-Peptide; Female; Gastrectomy; Gastric Emptying; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Organ Size; Prospective Studies; Pylorus; Stomach

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

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 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

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

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

We have previously demonstrated that type 2 diabetes resolves after bariatric surgery. To study the role of NEFA in the prompt normalisation of beta cell glucose sensitivity, insulin secretion and beta cell glucose and lipid metabolism were investigated by a model of nutrient-stimulated insulin secretion using a multiple-meal test.. Hourly glucose, C-peptide and NEFA were measured in nine morbidly obese, type 2 diabetic patients before and 1 week after bariatric surgery and in six matched healthy volunteers over 24 h. A mathematical model of glucose-NEFA comodulation of insulin secretion rate (ISR) was used to compute ISR and beta-oxidation. Insulin sensitivity was measured by an OGTT minimal model.. Beta cell sensitivity to glucose and NEFA was doubled after surgery, while the 24 h insulin secretion decreased from 277.1 +/- 144.4 to 198.0 +/- 107.6 nmol/m(2) (p < 0.02). Insulin sensitivity was restored. The beta-oxidation rate of beta cells was completely normalised (from 0.032 +/- 0.012 x 10(-12) to 0.103 +/- 0.031 x 10(-12) mmol/min per cell, p < 0.005). The best predictor of beta cell function improvement was the duration of diabetes.. Bariatric surgery in type 2 diabetes restores beta-oxidation in beta cells, doubles glucose-NEFA sensitivity and reverses diabetes. It is likely that ISR is reduced to match insulin-sensitivity normalisation, in spite of no significant reduction in NEFA levels. We hypothesise that insulin sensitivity normalisation might appear as a consequence of nutrient exclusion from proximal intestinal transit, and that secondarily the need for insulin secretion diminishes. The insulin sensitivity increase is much higher than usually obtained by insulin-sensitising agents and is independent of weight changes.

Topics: Bariatric Surgery; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Models, Biological; Obesity, Morbid; Oxidation-Reduction; Postoperative Care; Preoperative Care

Due to their lower glycaemic index, leguminous seeds affect human carbohydrate metabolism lesser than do cereals. Problems, however, could arise from side effects, e.g., increasing flatulence.. In 26 healthy subjects, metabolic and symptomatic responses following acute ingestion of equivalent amounts of pure pea starch (NASTAR (Cosucra BV, Rosendaal/The Netherlands), crude yellow pea flour (CPC Deutschland, Germany), and modified and unmodified cornstarches (SNOWFLAKE and SIRONA, Cerestar/Germany) were assessed, i.e., plasma glucose, serum insulin, C-peptide, hydrogen exhalation, and flatulence.. Pure pea starch elicited less hyperglycaemia (minus 47 %), hyperinsulinaemia (minus 54 %), and C-peptide secretion (minus 37 %) as compared to cornstarch (p<0.05), while the responses to modified versus unmodified corn starch were similar (8 subjects, n.s.). Pure pea and corn starches were equally well tolerated, while flatulence and breath hydrogen concentration were increased only after the intake of crude pea flour. Maldigestion of pea flour was calculated to be around 10 % (reference lactulose).. The well-known metabolic advantages of pea starch over cornstarch were confirmed. Tolerability of pure pea starch was excellent, but not of crude pea flour. Provided it has the same technical characteristics, pure pea starch as a "prebiotic" could replace cornstarch in industrial food production.

Topics: Adult; Blood Glucose; Breath Tests; C-Peptide; Chromatography, Gas; Cross-Over Studies; Dietary Carbohydrates; Digestion; Double-Blind Method; Fabaceae; Female; Flatulence; Glucose; Glycated Hemoglobin; Homeostasis; Humans; Hydrogen; Insulin; Male; Obesity, Morbid; Plants, Medicinal; Single-Blind Method; Triglycerides; Zea mays

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

Bariatric surgery is evolving as a successful tool for managing morbid obesity and T2DM. This study aimed to identify predictors of diabetes remission after two types of bariatric procedures.. This prospective study enrolled 172 patients with morbid obesity associated with T2DM scheduled for bariatric surgery. Two laparoscopic bariatric procedures were done; single anastomosis gastric bypass (SAGB, n = 83) and sleeve gastrectomy (LSG, n = 68). Lipid accumulation product index (LAP) and quantitative insulin sensitivity check index (QUICKI) were used to evaluate lipid profile and insulin sensitivity. Two years after surgery condition of DM was evaluated as complete remission (CR), partial remission (PR), or improvement. The primary outcome measure was predictors of diabetes remission.. Two years after surgery, 151 patients were available for evaluation, where 75 patients (49.7%) achieved CR, while PR was found in 36 (23.8%). CR was significantly associated with younger age, shorter duration of DM (p < 0.001, for both), higher C-peptide and GLP-1 levels (p < 0.001 and p = 0.002, respectively), and bypass surgery (p = 0.027). On multivariate analysis, shorter duration of DM, lower BMI, and higher C-peptide levels were the independent factors predicting CR.. Complete remission of T2DM can be achieved in nearly half of the patients two years after SG or SAGB. The duration of diabetes and preoperative BMI and C-peptide levels are the independent factors predicting complete remissions.

Topics: Bariatric Surgery; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Follow-Up Studies; Gastrectomy; Gastric Bypass; Humans; Insulin Resistance; Laparoscopy; Obesity, Morbid; Prospective Studies; Retrospective Studies; Treatment Outcome

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

We evaluated the utility of C peptide as an addition to the DiaRem score for predicting type 2 diabetes (T2D) remission 1 year after bariatric surgery in 175 patients. DiaRem score was significantly correlated with C peptide (r = - .43; p < .001). Both DiaRem and C peptide were significant predictors of remission of T2D (OR (95% CI) = .81 (.75-.86); p < 0001 and OR (95% CI) = 1.35 (1.15-1.60); p < .001, respectively). ROC analysis indicated that DiaRem was a significantly stronger predictor than C peptide (p < .001). Hierarchical regression indicated that C peptide failed to significantly improve the prediction of diabetes remission after accounting for DiaRem (OR (95% CI) = 1.079 (.87-1.26); p = .406). This study does not support the inclusion of C peptide in the DiaRem algorithm.

Topics: Algorithms; Bariatric Surgery; C-Peptide; Diabetes Mellitus, Type 2; Gastric Bypass; Humans; Obesity, Morbid; Remission Induction; Retrospective Studies; Treatment Outcome

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

Several predictors of type 2 diabetes mellitus (T2DM) remission after metabolic surgery have been proposed and used to develop predictive scores. These scores may not be reproducible in diverse geographic regions with different baseline characteristics. This study aimed to identify predictive factors associated with T2DM remission after Roux-en-Y gastric bypass (RYGB) in patients with severe obesity. We hypothesized that the body composition alterations induced by bariatric surgery could also contribute to diabetes remission.. We retrospectively evaluated 100 patients with severe obesity and T2DM who underwent RYGB between 2014 and 2016 for preoperative factors (age, diabetes duration, insulin use, HbA1c, C-peptide plasma level, and basal insulinemia) to identify predictors of T2DM remission (glycemia<126 mg/dL and/or HbA1c<6.5%) at 3 years postoperatively. The potential preoperative predictors were prospectively applied to 20 other patients with obesity and T2DM who underwent RYGB for validation. In addition, 81 patients with severe obesity (33 with T2DM) underwent body composition evaluations by bioelectrical impedance analysis (InBody 770®) 1 year after RYGB for comparison of body composition changes between patients with and those without T2DM.. The retrospective analysis identified only a C-peptide level >3 ng/dL as a positive predictor of 3-year postoperative diabetes remission, which was validated in the prospective phase. There was a significant difference in the postoperative body composition changes between non-diabetic and diabetic patients only in trunk mass.. Preoperative C-peptide levels can be useful for predicting T2DM remission after RYGB. Trunk mass is the most important difference in postoperative body composition changes between non-diabetic and diabetic patients.

Topics: Body Composition; Body Mass Index; C-Peptide; Child, Preschool; Diabetes Mellitus, Type 2; Gastric Bypass; Humans; Obesity, Morbid; Prospective Studies; Remission Induction; Retrospective Studies; Treatment Outcome

To investigate prognostic factors for complete remission in type 2 diabetes mellitus (T2DM) patients who underwent gastric bypass (GBP) and to establish a prognostic model for risk stratification.. We evaluated the baseline clinical features of patients with T2DM who received at Beijing Tian Tan Hospital from April 2012 to December 2015. Complete remission of T2DM was defined as meeting the following criteria: HbA1c < 6.5%, fasting plasma glucose (FPG) < 100 mg/dL, and absence of hypoglycemic drugs for 1 year following GBP.. A total of 101 patients were enrolled in our study, and the complete remission rate of T2DM was 70.3% (71/101). Compared with patients with incomplete remission, patients with complete remission of T2DM had higher C-peptide levels, lower HbA1c, shorter disease duration, better β cell function, and an absence of insulin therapy. HbA1c level, fasting C-peptide, duration of T2DM, and history of medical therapy were important prognostic factors for complete remission of T2DM (P = 0.001, 0.002, 0.01, 0.028, respectively). Patients with HbA1c lower than 7.5%, a history of T2DM shorter than 9.5 years, fasting C-peptide higher than 1.2 ng/mL, and absence of insulin therapy before GBP achieved a higher complete remission rate of T2DM after GBP (AUC of the model was 0.825, 95% CI, 0.741-0.910; P = 0.001).. The duration of T2DM, history of medical therapy, and levels of HbA1c and fasting C-peptide are independent predictors for the prognosis of T2DM patients undergoing GBP. Patients with HbA1c lower than 7.5%, a history of T2DM shorter than 9.5 years, a fasting C-peptide higher than 1.2 ng/mL, and an absence of insulin therapy may have a higher complete remission rate of T2DM after GBP.

Topics: Adult; Aged; Biomarkers; Blood Glucose; C-Peptide; China; Diabetes Mellitus, Type 2; Fasting; Female; Gastric Bypass; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity, Morbid; Prognosis; Time Factors

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

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

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

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

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

Bariatric surgery often results in remission of the diabetic state in obese patients. Increased incretin effect seems to play an important role in the glycemic improvements after Roux-en-Y gastric bypass, but the impact of biliopancreatic diversion (BPD) remains unexplored.. The objective was to elucidate the effect of BPD on the incretin effect and its interplay with beta-cell function and insulin sensitivity (IS) in obese subjects with type 2 diabetes (T2DM).. Twenty-three women were studied: a control group of 13 lean, normal glucose-tolerant women (lean NGT) studied once and 10 obese patients with T2DM studied before, 1 and 12 months after BPD.. The ObeseT2DM group underwent BPD.. The main outcome measure was the change in incretin effect as measured by the isoglycemic intravenous glucose infusion test. Secondary outcomes encompassed IS and beta-cell function.. At baseline, the incretin effect was lower in obese T2DM compared to lean NGT (P < .05). One month after BPD, the incretin effect was not changed, but at 12 months it reached the level of the lean NGT group (P > .05). IS improved (P < .05) 1 month after BPD and at 12 months it resembled the levels of the lean NGT group. Insulin secretory rate and beta-cell glucose sensitivity increased after BPD and achieved levels similar to lean NGT group 1 month after BPD and even higher levels at 12 months (P < .05).. BPD has no acute impact on the reduced incretin effect, but 12 months after surgery the incretin effect normalizes alongside normalization of glucose control, IS and beta-cell function.

Topics: Adult; Biliopancreatic Diversion; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin Resistance; Insulin-Secreting Cells; Middle Aged; Obesity, Morbid; Treatment Outcome

Roux-and-Y gastric bypass (RYGB) rapidly reduces insulin requirements in patients with insulin-dependent type 2 diabetes mellitus (T₂DMi). A too modest reduction in insulin dose may lead to hypoglycaemia in the early postoperative period.. To evaluate a regimen designed to maintain blood glucose levels between 5-15 mmol/l and to prevent hypoglycaemic events (blood glucose <3.5 mmol/l) after RYGB surgery.. The effect of a 75% reduction in insulin dose was studied in 85 T₂DMi patients during the first ten days after RYGB. Patients with severe b-cell failure (fasting C-peptide <0.3 nmol/l) were excluded.. percentage of patients exceeding the upper or lower blood glucose limits, and the number of hypoglycaemic events.. The mean blood glucose level was 12.4±0.3 mmol/l (mean ± SE) on the day of surgery (day 0), 10.7±0.3 mmol/l on day 1, 10.0±0.5 mmol/l on day 2, and 8.3±0.3 on day 10. Of all measurements performed during this ten-day period, 12.4% were above the target range, and 2.6% were <5 mmol/l. There were no hypoglycaemic events during the stay in hospital. During the first week at home 2% of the measurements were <3.5 mmol/l.. A 75% reduction in insulin dose is safe in T₂DMi patients without severe b-cell failure, and prevents hypoglycaemia in the early postoperative period of RYGB in most cases.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Gastric Bypass; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity, Morbid; Perioperative Period; Time Factors

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

To evaluate the association between glucagon-like peptide 1 (GLP-1) secretion and the long-term (>2 years) outcome of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGBP).. Cross-sectional study in 18 T2DM morbidly obese subjects who underwent RYGBP but differed in the long-term outcome of T2DM (remission: G1, n = 6; relapse: G2, n = 6; lack of remission: G3: n = 6). Groups were matched for their sex, age, and body mass index. The GLP-1, glucose, C-peptide, and glucagon responses to a standardized test meal (STM) were evaluated. Insulin secretion and insulin sensitivity were estimated from the STM and by frequently sampling intravenous glucose tolerance test (FSIVGTT). Dual-energy X-ray absorptiometry was used to assess body composition.. Patients in G1 presented a lower area under the curve (AUC0-120) of glucose in response to the STM as compared with G2, and G3 (P < 0.01). In contrast, the AUC0-120 of GLP-1 (P = 0.884) and glucagon (P = 0.630) did not differ significantly among the 3 groups. Indices of insulin secretion adjusted by the prevailing insulin sensitivity derived from STM and FSIVGTT, demonstrated larger β-cell function in subjects in G1 as compared with G2 or G3 (Disposition Index-STM, P = 0.005; DI-FSIVGTT, P = 0.006). Body composition and inflammatory markers did not differ significantly among the 3 study groups.. Our data show that in subjects with T2DM an enhanced GLP-1 response to meal intake is not sufficient to maintain normal glucose tolerance in the long term after RYGBP. Our data suggest that β-cell function is a key determinant of the long-term remission of T2DM after this bariatric surgery technique.

Topics: Absorptiometry, Photon; Aged; Biomarkers; Blood Glucose; Body Composition; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Treatment Outcome

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

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

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

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

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

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

To examine after gastric bypass the effect of peroral versus gastroduodenal feeding on glucose metabolism.. A type 2 diabetic patient was examined on 2 consecutive days 5 weeks after gastric bypass. A standard liquid meal was given on the first day into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C-peptide, glucagon, incretin hormones, peptide YY, and free fatty acids were measured.. Peroral feeding reduced 2-h postprandial plasma glucose (7.8 vs. 11.1 mmol/l) and incremental area under the glucose curve (iAUC) (0.33 vs. 0.49 mmol . l(-1) . min(-1)) compared with gastroduodenal feeding. beta-Cell function (iAUC(Cpeptide/Glu)) was more than twofold improved during peroral feeding, and the glucagon-like peptide (GLP)-1 response increased nearly fivefold.. Improvement in postprandial glucose metabolism after gastric bypass is an immediate and direct consequence of the gastrointestinal rearrangement, associated with exaggerated GLP-1 release and independent of changes in insulin sensitivity, weight loss, and caloric restriction.

Topics: Area Under Curve; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Enteral Nutrition; Fatty Acids, Nonesterified; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Humans; Incretins; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Postprandial Period

The aim of this study is to investigate the effect of body size on insulin-mediated, whole-body glucose uptake (M-value) in morbidly obese (MO) subjects, who have large amounts of fat mass. Furthermore, we aimed at verifying which surrogate insulin-sensitivity index can better substitute the euglycemic clamp values and whether the insulin secretion/insulin resistance index is meaningful also in MO subjects.. The study design is cross-sectional, case-control study of insulin sensitivity--assessed by different methods--and insulin secretion.. One-hundred and sixty-eight subjects ca. 39 years old, with a body mass index (BMI) between 17 and 64 kg m⁻², underwent euglycemic hyperinsulinemic clamp and oral glucose tolerance test (OGTT) with surrogate measures of insulin sensitivity together with body composition by ³H₂O dilution. Insulin secretion rate (ISR) was measured at fast and after OGTT by C-peptide deconvolution.. The population was divided into quartiles of BMI. In the fourth quartile, the best insulin-sensitivity variable between M/I/kg(FFM) and M/I/kg(bw) was the latter, as shown by area under the receiver-operator characteristic (ROC) curve (0.85 vs 0.89). The best index to identify insulin-resistant individuals (lowest distribution quartile: M/I/kg(bw)≤ 29.3 μmol min⁻¹ kg⁻¹ nmol l⁻¹) were Matsuda index and oral glucose insulin sensitivity (OGIS), whereas fasting insulin concentration, QUICKI, and HOMA failed (ROC analysis). M-value declined exponentially as the BMI increased, whereas ISR linearly increased. The insulin secretion/insulin resistance index well applied to MO.. In MO subjects, in which the fat mass is highly represented, fat-free mass cannot be considered the only determinant of insulin sensitivity, thus M-value should be normalized by total body weight. The best surrogates of insulin sensitivity measured by euglycemic clamp are Matsuda index and OGIS. BMI directly affects both insulin sensitivity and ISR and the insulin secretion/insulin resistance index is a valid model to correlate ISR with insulin sensitivity also in MO.

Topics: Adult; Area Under Curve; Blood Glucose; Body Mass Index; Body Size; Body Weight; C-Peptide; Case-Control Studies; Cross-Sectional Studies; Fasting; Female; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Obesity, Morbid

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

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

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

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

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

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

Morbid obesity (MO) is associated with diabetes mellitus-type II (DM-II). Roux-en Y gastric bypass (RNY) has been shown to normalize glucose intolerance in these patients through an incompletely understood mechanism. Gastrointestinal hormonal changes have been suggested as an explanation for resolution of DM II. Preoperatively, 20 MO patients with DM-II were evaluated for demographics and fasting levels of the following: glucose, insulin, C-peptide, glucagon, cortisol, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Each patient underwent RNY with a 15-cc gastric pouch and 150-cm Roux limb. Postoperatively, each of the variables was measured at 2 weeks, 6 weeks, and 12 weeks and compared with the preoperative result using Student t test with significance, P = 0.05. Results are expressed as mean +/- SD. Twenty patients (5 male and 15 female), age 40.3 +/- 7.9 years, weight 146.3 +/- 34.0 kg, height 158.7 +/- 18.7 cm, and BMI 52.7 +/- 8.8, were enrolled in this IRB-approved protocol. Weight and BMI decreased progressively (117.5 +/- 26.9 kg and 47.0 +/- 7.4, P = 0.01, respectively) during the study but reached significance only at 12 weeks. Fasting plasma glucose decreased significantly within 2 weeks after RNY. Insulin and cortisol both approached, but never achieved, significant changes over 12 weeks. GLP-1 increased initially, but not significantly. GIP and C-peptide both decreased significantly. Glucagon remained essentially unchanged over 12 weeks. RNY rapidly normalizes fasting plasma glucose in morbidly obese patients with DM-II. GIP, a gactor in the enteroinsulin axis, decreases and may play a role in the correction of DM-II after gastric bypass.

Topics: Adult; Anastomosis, Roux-en-Y; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Obesity, Morbid; Peptide Fragments; Protein Precursors

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

The peroxisome-proliferator-activated receptor gamma2 (PPAR gamma2) is a transcriptional key regulator of adipocyte differentiation. PPAR gamma2 can be inactivated by phosphorylation of a serine residue at position 114. A point mutation leading to an amino acid exchange at position 115 (Pro115Gln) was shown to preclude serine phosphorylation and to consecutively accelerate adipocyte differentiation emphasizing the pathophysiological relevance of this mutation. So far, four markedly obese heterozygote carriers of the Pro115Gln mutation (body mass index 37.9-47.3 kgxm (-2)) have been identified in a circumscribed study population. In order to evaluate the epidemiological relevance of the Pro115Gln mutation in morbid obesity we screened the DNA of all subjects with a body mass index greater than 35 kgxm (-2) who had participated in a nationwide German epidemiological field survey. There was no homozygote or heterozygote carrier of the Pro115Gln polymorphism among them. We conclude that the Pro115Gln polymorphism within the PPAR gamma2 gene has no relevant epidemiological impact on morbid obesity in Germany. It needs further investigation whether this polymorphism might play a role in related metabolic disorders.

Topics: Adult; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Germany; Glutamine; Glycated Hemoglobin; Humans; Insulin; Middle Aged; Obesity, Morbid; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Proline; Receptors, Cytoplasmic and Nuclear; Transcription Factors

Insulin inhibition of insulin secretion has been described in normal lean subjects. In this study, we examined whether this phenomenon also occurs in the morbidly obese who often have severe peripheral insulin resistance.. Twelve obese patients, normotolerant to glucose (8 F/4 M, body mass index (BMI)=54.8+/-2.5 kg/m(2), 39 y) and 16 lean control subjects (10 F/6 M, BMI=22.0+/-0.5 kg/m(2), 31 y).. An experimental study using various parameters, including an euglycemic hyperinsulinemic clamp (280 pmol/min/m(2) of body surface), an oral glucose tolerance test (OGTT), electrical bioimpedance and indirect calorimetry.. The obese subjects were insulin resistant (M=19.8+/-1.6 vs 48.7+/-2.6 micromol/min kg FFM, P<0.0001) and hyperinsulinemic in the fasted state and after glucose ingestion. Fasting plasma C-peptide levels (obese 1425+/-131 pmol/l vs lean 550+/-63 pmol/l; P<0.0001) decreased less during the clamp in the obese groups (-16.9+/-6.9% vs -43.0+/-5.6% relative to fasting values; P=0.007). In the lean group, the C-peptide decrease during the clamp (percentage variation) was related to insulin sensitivity, M/FFM (r=0.56, P=0.03), even after adjustment for the clamp glucose variation.. We conclude that, in lean subjects, insulin inhibits its own secretion, and this may be related to insulin sensibility. This response is blunted in morbidly obese patients and may have a role in the pathogenesis of fasting hyperinsulinemia in these patients.

Topics: Adult; Body Composition; Body Mass Index; C-Peptide; Calorimetry, Indirect; Case-Control Studies; Electric Impedance; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Obesity, Morbid

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

In obesity, it is well known that basal growth hormone (GH) levels can be suppressed and they may show an impaired response to various stimuli like hypoglycemia, stress, and GHRH. However, the inhibitory effect of hyperglycemia on GH in this condition has not been well studied. We analyzed the GH response to an oral glucose tolerance test (OGTT) in 25 unselected patients with morbid obesity who were not diabetic, glucose intolerant or affected by renal or hepatic disease. Ten (40%) of the 25 subjects had an abnormal response of GH to the OGTT, expressed by a lack of suppression of GH levels below 2 micrograms/L within 60 minutes of glucose administration. Three subjects even had a paradoxal increase of GH levels of more than 50% of the basal level. There was no significant difference between these subjects regarding their age, BMI and, serum levels of glucose, insulin, C peptide, or insulin/glucose ratio. After weight loss, three of four patients normalized their GH response. Thus, we conclude that patients with morbid obesity frequently have an abnormal response of GH to OGTT (40% vs 4-8% in normal subjects). This finding must be taken into consideration when interpreting GH levels in these patients. A normalization of this response can be expected after weight loss.

Topics: Adult; Age Factors; Body Mass Index; C-Peptide; Female; Glucose; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Male; Middle Aged; Obesity, Morbid

A boy affected by severe obesity (kg 117, Body Mass Index 37 kg/m2) and acanthosis nigricans, was treated with octreotide for 150 days (50 micrograms x three daily subcutaneous administrations). Before treatment the patient showed an exaggerated insulin (IRI) and C-peptide (CPR) response to a standard meal with a lowering in after-meal CPR/IRI molar ratio. During octreotide treatment both IRI and CPR response was reduced but CPR/IRI molar ratio rised after meal indicating an increase in hepatic insulin removal. Body weight and acanthosis nigricans were sharply reduced during treatment and the reduction was still maintained six months after the cessation of therapy. Furthermore, IRI and CPR response, as well as the behaviour of CPR/IRI molar ratio, remained within normal range. In conclusion long-term octreotide treatment has been able to correct hyperinsulinemia and to reduce body weight and acanthosis nigricans.

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Hormones; Humans; Hyperinsulinism; Insulin; Male; Obesity, Morbid; Octreotide

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

We evaluated the metabolic response to a standard (75-g) oral-glucose-tolerance test (OGTT) in eight post-obese women (PO) who underwent biliopancreatic diversion and in eight healthy control women (C). All subjects had been weight-stable for > or = 2 y. Blood samples for glucose, insulin, C-peptide, and nonesterified free fatty acids were taken at baseline and during 180 min after the glucose load. Plasma glucose and insulin concentrations at baseline and during the OGTT were similar in the two groups, suggesting the absence of an insulin-resistant state in the PO. Continuous indirect calorimetry was performed throughout the test. Glucose-induced thermogenesis (GIT) was higher in PO than in C (8.6 +/- 2.6 vs 4.3 +/- 1.9%; P < 0.01). These data indicate that GIT and insulin-glucose metabolism are not impaired in postobese patients when a near ideal body weight is reached and maintained after weight loss; this suggests that thermogenic deficiencies and hyperinsulinemia-insulin resistance are alterations secondary to obesity.

Topics: Adult; Biliopancreatic Diversion; Blood Glucose; C-Peptide; Calorimetry, Indirect; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Lipid Metabolism; Obesity, Morbid; Oxidation-Reduction; Postoperative Period

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

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

Topics: Adult; Blood Glucose; C-Peptide; Diet, Reducing; Energy Intake; Female; Fibrinogen; Glucose; Humans; Insulin; Lipids; Middle Aged; Obesity, Morbid

Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 +/- 11.5 v 22.1 +/- 2.2 kg.m-2; mean +/- SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 +/- 3.8 v 2.4 +/- 3.0 mU.L-1, P less than .001) and remained elevated throughout infusion (F = 492, P less than .001), as did C-peptide (F = 22.7, P less than .001). Metabolic clearance rate for insulin (MCRI) at the highest infusion rate was similar (1,048 +/- 425 v 1,018 +/- 357 mL.m-2.min-1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 +/- 108 v 444 +/- 68 mumol.m-2.min-1, P less than .01), as was the basal metabolic clearance rate for glucose (MCRG, 77 +/- 26 v 108 +/- 31 mL.m-2.min-1, P less than .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 +/- 0.5 v 1.9 +/- 0.5 mmol.L-1, P less than .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL.m-2.min-1/mU.L-1, P less than .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were elevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; C-Peptide; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Glucose; Humans; Infusions, Parenteral; Insulin; Ketone Bodies; Metabolic Clearance Rate; Middle Aged; Obesity, Morbid

The published literature on the influence of obesity on intermediary metabolite concentrations does not adequately address the potential confounding effects of the increased prevalence of impaired glucose tolerance in obese subjects. In order to remove this, we studied 109 subjects with proven normal glucose tolerance ranging from underweight to grossly obese (range 15.3-80.9 body mass index). All had blood intermediary metabolites, plasma insulin and C-peptide measured after an overnight fast. Thirty-six (18 from each end of the range of body mass index) received a 3-hour oral glucose tolerance test for metabolites and insulin. Fasting plasma insulin was highly significantly associated with body mass index (r = 0.72; P less than 0.001). Concentrations of lipid intermediaries were better associated with body mass index than with fasting plasma insulin: non-esterified fatty acids (r = 0.36; P less than 0.001), glycerol (r = 0.47; P less than 0.001) and ketone bodies (r = 0.45; P less than 0.001). Fasting concentrations of carbohydrate intermediaries were, however, better correlated with fasting plasma insulin: lactate (r = 0.29; P less than 0.01), pyruvate (r = 0.24; P less than 0.01) and alanine (r = 0.36; P less than 0.001). Glucose concentrations were associated with both to a similar degree (r = 0.33, r = 0.32, respectively; P less than 0.001). After oral glucose, exaggerated rises in plasma insulin and blood glucose were observed in obese subjects but a lesser rise was seen for lactate. Non-esterified fatty acids and ketones, although having higher fasting concentrations in obese subjects, fell to similar concentrations in the two groups after glucose whereas blood glycerol did not fall so far in the obese subjects. The results suggest, even if those subjects with impaired glucose tolerance are excluded, insensitivity to insulin in several aspects of intermediary metabolism in obesity the degree of which may vary in different metabolic pathways or tissues.

Topics: Adult; Alanine; Blood Glucose; Body Mass Index; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Glycerol; Humans; Insulin; Ketone Bodies; Lactates; Male; Middle Aged; Obesity; Obesity, Morbid; Pyruvates; Pyruvic Acid; Regression Analysis

Hyperinsulinemia is a well-recognized entity of simple obesity. It is demonstrated that hyperinsulinemia is associated with upper body fat and fat cell hypertrophy. Androgen excess and lower levels of sex hormone binding globulin (SHBG) may produce fat cell hypertrophy and hyperinsulinemia as well. We measured serum insulin and C-peptide levels during an OGTT in two groups of obese premenopausal women to determine whether the hyperinsulinemia is due to hypersecretion or due to a diminished hepatic extraction of insulin. In this study, we found no correlation between the insulin and C-peptide levels or their ratio and the degree of obesity. However, a significant correlation was found between the waist-to-hip circumference ratio (WHR), used as an index of body fat distribution, and the areas of insulin (r = 0.55; P less than 0.001) and C-peptide (r = 0.51; P less than 0.001). SHBG and free androgen index (FAI) were also significantly related to these areas. The peripheral C-peptide/insulin molar ratio has been assumed to reflect changes in hepatic insulin extraction while the corrected C-peptide response reflects beta-cell function. WHR was negatively related to this ratio (r = -0.44; P less than 0.005) and SHBG showed a positive correlation (r = 0.34; P less than 0.05). Stepwise multiple regression analysis revealed that the 2-h insulin and C-peptide values and both curve areas can be explained up to 40-80% by sex hormones and anthropometric variables. Also the C-peptide/insulin molar ratio is dependent in a first step on WHR (r2 = 0.23; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Adipose Tissue; Adult; Blood Glucose; Body Mass Index; C-Peptide; Female; Follicular Phase; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Obesity, Morbid; Sex Hormone-Binding Globulin; Testosterone

In massively obese patients hyperinsulinemia and insulin insensitivity usually improve with weight loss. To clarify the mechanism of these reversible abnormalities eight nondiabetic massively obese patients were studied before and at intervals (3 months and 1 yr) after weight loss following gastroplasty. Insulin dynamics were studied during the hyperglycemic clamp (change in glucose, 7 mmol L-1 for 2 h) by measuring the area under the insulin and C-peptide response curves, representing, respectively, systemic insulin response and insulin production. Compared to lean age-matched normal subjects the massively obese patients had the expected fasting hyperinsulinemia and an exaggerated insulin response (P less than 0.05). Within 3 months and after an approximately 20% weight loss, they had a marked reduction in the systemic insulin response but no change in the C-peptide response. Therefore, the reduction in insulin response was due to enhanced hepatic insulin clearance rather than reduced insulin production. Thus, the liver serves a gate-keeping role in regulating the systemic insulin response to a glucose challenge. With additional weight loss of 14% and then weight maintenance, insulin clearance was further increased, and a reduction in insulin production became evident, since the C-peptide response was reduced. Exogenous insulin clearance was measured using the euglycemic clamp technique before and after weight loss. Insulin clearance was initially lower in the massively obese patients compared to that in the normal subjects (P less than 0.05) and increased toward normal with weight loss (P less than 0.05). Similarly, insulin sensitivity, as measured by the ratio of glucose metabolised per U endogenous insulin, normalized with weight loss and weight maintenance. Thus, after significant weight loss followed by weight maintenance at a reduced, but not ideal, level, insulin clearance, production, and sensitivity all reverted to normal. These findings suggest that adipose mass per se may not be exclusively responsible for altered insulin and glucose dynamics in obesity and that additional factors associated with obesity, such as nutrient load, adipose distribution, fat cell size, or fatty acid flux, play a contributing role.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Fasting; Female; Glucagon; Humans; Insulin; Male; Metabolic Clearance Rate; Middle Aged; Obesity, Morbid

Plasma concentrations of fibronectin, free insulin, C-peptide and plasma glucose were determined in 40 morbidly obese subjects and in 51 normal weight controls, matched for sex and age. All plasma concentrations were significantly elevated (p less than 0.01) among the obese subjects. A significant correlation (r = 0.34, p less than 0.05) between plasma fibronectin and plasma free insulin was found among the obese patients, but not among the controls (r = -0.02, p greater than 0.05). No significant correlation was found between plasma fibronectin and plasma C-peptide, neither in the obese patients nor in the controls (obese r = 0.06, controls r = 0.02; p greater than 0.05). Plasma fibronectin was insignificantly correlated with body weight (obese r = 0.21, controls r = 0.15; p greater than 0.05) and percentage overweight (obese r = 0.27, controls r = 0.04; p greater than 0.05). The raised level of circulating insulin may in part explain the excess of plasma fibronectin obese subjects.

Topics: Adult; Blood Glucose; C-Peptide; Female; Fibronectins; Humans; Insulin; Male; Middle Aged; Obesity; Obesity, Morbid