23 research outputs found
Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation
A randomized, controlled trial of 3.0 mg of liraglutide in weight management
BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P<0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)
Metabolic syndrome, insulin resistance and other cardiovascular risk factors in university students
AGE AND GENDER MAY INFLUENCE THE RESULTS OF ROUX-EN-Y GASTRIC BYPASS? Metabolic syndrome parameters
Comparison of Metabolic Effects of Surgical-Induced Massive Weight Loss in Patients with Long-Term Remission Versus Non-remission of Type 2 Diabetes
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The aim of this study was to evaluate the pathophysiological mechanisms underlying the non-remission of type 2 diabetes in Roux-en-Y gastric bypass (RYGB) patients. A group of patients not in remission (NR) was formed ( = 13). A remission group (R) was composed of patients who had undergone normalization of fasting glycemia and A1c, without anti-diabetic drugs and matched for selected baseline characteristics (i.e., duration of disease, previous BMI, final BMI, fat distribution, and age; = 15). A control group of lean subjects ( = 41) was formed. The NR group had higher uric acid (5.1 vs. 3.9 mg/dL), number of leukocytes (6,866.9 vs. 5,423.6), hs-CRP (0.27 vs. 0.12 mg/dL), MCP-1 (118.4 vs. 64.4 ng/mL), HOMA-IR, and AUC(glucose) but lower adiponectin (9.4 vs. 15.4 ng/mL), leptin (12.7 vs. 20.7 ng/mL), and AUC(GLP-1) in comparison to R group; the NR group also had lower leptin and higher adiponectin, HOMA-IR, AUC(glucose), AUC(C-peptide), AUC(glucagon), and AUC(GLP-1) than controls. The R group had lower MCP-1 and higher adiponectin compared to controls. Insulin sensitivity was significantly lower in the NR group than in the R and control groups. The insulin secretion index values were lower in the NR group than in the R and control groups. This study found greater insulin resistance, lower insulin secretion, persistent adiposopathy and chronic subclinical inflammation, and less robust incretin response in the NR group despite a similar level of weight loss. Persistently altered pathophysiological mechanisms can be related to the lack of remission of type 2 diabetes after RYGB.226910917Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP
Sibutramine enhances insulin sensitivity ameliorating metabolic parameters in a double-blind, randomized, placebo-controlled trial
Aim: To assess the effect of sibutramine-assisted weight reduction program on insulin sensitivity and metabolic parameters in obese normal glucose tolerant individuals over a period of 24 weeks. Research Design and Methods: A double-blind, placebo-controlled, parallel, prospective clinical trial was carried out at our medical centre. Forty female normal glucose tolerant patients, body mass index: 34.3 +/- 2.9 kg/m(2) and age: 41.1 +/- 9.9 (range: 19-58 years), were randomized to placebo or sibutramine, 10 mg once daily. Results: Seventeen patients from sibutramine group and 14 placebo had completed the study protocol. Significant weight change was seen in sibutramine (p < 0.01) (-5.6 kg or -6.1% vs. +0.9 kg or +1.1% in placebo). Insulin sensitivity enhanced in sibutramine group (K-itt: from 4.03 +/- 1.97 to 5.09 +/- 2.48%/min; p < 0.05). Homeostasis model assessment-IR (HOMA-IR) decreased from 7.8 +/- 6.9 to 5.6 +/- 4.5 (p < 0.05). HOMA-β also decreased from 508 +/- 381 to 374 +/- 256 (p < 0.05). No changes were observed in the placebo control group regarding insulin sensitivity or secretion. Concomitant reductions were observed in the sibutramine group in lipid parameters (triglycerides and high-density lipoprotein-cholesterol), uric acid and gamma-glutamyl transferase (p < 0.05). Conclusions: Sibutramine has demonstrated efficacy in reducing weight in non-diabetic women along with amelioration in insulin sensitivity and additional improvement in metabolic parameters.5533834
Acute Effect of Roux-En-Y Gastric Bypass on Whole-Body Insulin Sensitivity: A Study with the Euglycemic-Hyperinsulinemic Clamp
Context: Insulin resistance ameliorates after bariatric surgery, yet there is still a need for data on the acute effect of Roux-en-Y gastric bypass (RYGBP) on insulin sensitivity. Objective: The objective of the study was to describe the acute effect of RYGBP on insulin sensitivity, measured by both the euglycemic-hyperinsulinemic clamp and homeostasis model assessment insulin resistance index (HOMA-IR). Design and Setting: Evaluations were conducted before and 1 month after RYGBP at State University of Campinas (Sao Paulo, Brazil). Patients: Patients included 19 premenopausal women with metabolic syndrome aged 35.3 (6.7) yr, body mass index 45.50 (3.74) kg/m(2) [mean (SD)]. Six had mild type 2 diabetes, seven impaired glucose tolerance, and six normal glucose tolerance. Interventions and Main Outcome Measures: The volunteers underwent RYGBP either alone or combined with omentectomy. Euglycemic-hyperinsulinemic clamp, HOMA-IR, nonesterified fatty acids, leptin, ultrasensitive C-reactive protein, adiponectin, and IL-6 were assessed at baseline and 4.5 (0.9) wk postoperatively. Results: Fasting glucose decreased [99.2 (13.1) to 83.6 (8.1) mg/dl, P < 0.01] along with a reduction in fasting insulin [30.4 (17.0) to 11.4 (6.3) mU/liter, P < 0.01]. M value did not improve postoperatively [25.82 (6.30) to 22.02 (6.05) mu mol/kg(FFM) . min] despite of a decrease in body weight [114.8 (14.5) to 102.3 (14.5) kg, P < 0.001]. This finding was discordant to the observation of an improvement in HOMA-IR [3.85 (2.10) to 1.42 (0.76), P < 0.01]. Nonesterified fatty acids increased. Leptin and C-reactive protein decreased. IL-6 and adiponectin remained unchanged. Conclusions: A month after RYGBP, fasting glucose metabolism improves independent of a change in peripheral insulin sensitivity. (J Clin Endocrinol Metab 95: 3871-3875, 2010)O TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE FEVEREIRO DE 2015.95838713875Fundacao de Apoio a Pesquisa do Estado de Sao Paulo, Sao Paulo, Brazil [05/58627-2]U.S. Department of Veterans AffairsFundacao de Apoio a Pesquisa do Estado de Sao Paulo, Sao Paulo, Brazil [05/58627-2
Surgery for Nonobese Type 2 Diabetic Patients: An Interventional Study with Duodenal-Jejunal Exclusion
A 24-week interventional prospective trial was performed to compare the benefits of open duodenal-jejunal exclusion surgery (GJB) with a matched control group on standard medical care. One-hundred eighty patients were screened for the surgical approach. Twelve patients accepted to be operated and presented the full eligibility criteria for surgery that includes overweight BMI (25-29.9 kg/m2), T2DM diagnosis for less than 15 years, insulin-treated patients, no history of major complications, preserved beta-cell function, and absence of autoimmunity. A matched control group (CG) of patients whom refused surgical treatment was placed to receive standard care. Patients had age of 50 (5) years, time of diagnosis 9 years (range, 3 to 15 years), time of insulin usage 6 months (range, 3 to 48 months), fasting glucose (FG), 9.8 (2.5) mg/dL, and glycated hemoglobin (A1C) 8.90 (2.12)%. At 24 weeks after surgery, patients experienced greater reductions on FG (14% vs. 7% on CG), A1C (from 8.78 to 7.84 in GJB-p < 0.01 and 8.93 to 8.71 in CG; p < 0.05 between groups) and reductions on average daily insulin requirement (93% vs. 29%, p < 0.01). Ten patients stopped insulin usage in GJB but they remain taking oral medications. No differences were observed in both groups regarding BMI, body distribution and composition, blood pressure, and lipids. In conclusion, duodenal-jejunal exclusion was an effective treatment for nonobese T2DM subjects. GJB was superior to standard care in achieving better glycemic control along with reduction in insulin requirements.1981077108
Visceral Fat Resection in Humans: Effect on Insulin Sensitivity, Beta-Cell Function, Adipokines, and Inflammatory Markers
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Objective: The visceral fat is linked to insulin resistance, the metabolic syndrome, type 2 diabetes and an increased cardiovascular risk, but it is not clear whether it has a causative role. Design and Methods: Surgical resection of this fat depot is a research model to address this issue. Twenty premenopausal women with metabolic syndrome and grade III obesity were randomized to undergo Roux-en-Y gastric bypass (RYGBP) either alone or combined with omentectomy. Insulin sensitivity (IS; euglycemic-hyperinsulinemic clamp), acute insulin response to glucose (AIR; intravenous glucose tolerance test), disposition index (DI = AIR x IS measured by clamp), lipid profile, adipokine profile (leptin, adiponectin, resistin, visfatin, interleukin-6, TNF-alpha, MCP-1), ultra-sensitive C-reactive protein (CRP), body composition, and abdominal fat echography were assessed prior to surgery and 1, 6, and 12 months post-surgery. Results: Omentectomy was associated with greater weight loss at all time points. IS improved similarly in both groups. Omentectomy was associated to lower CRP after 12 months, but it did not influence adipokines and other metabolic parameters. Among non-diabetic subjects, omentectomy was associated with a preservation of baseline AIR after 12 months (as opposed to deterioration in the control group) and a greater DI after 6 and 12 months. Conclusion: Although omentectomy did not enhance the effect of RYGBP on insulin sensitivity and adipokines, it was associated with a preservation of insulin secretion, a greater weight loss, and lower CRP.213E182E189Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)US Department of Veterans AffairsFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [05/58627-2