ß-Cell Glucagon-Like Peptide-1 Receptor Contributes to Improved Glucose Tolerance After Vertical Sleeve Gastrectomy.

Vertical sleeve gastrectomy (VSG) produces high rates of type 2 diabetes remission; however, the mechanisms responsible for this remain incompletely defined. Glucagon-like peptide-1 (GLP-1) is a gut hormone that contributes to the maintenance of glucose homeostasis and is elevated after VSG. VSG-induced increases in postprandial GLP-1 secretion have been proposed to contribute to the glucoregulatory benefits of VSG; however, previous work has been equivocal. In order to test the contribution of enhanced ß-cell GLP-1 receptor (GLP-1R) signaling we used a ß-cell-specific tamoxifen-inducible GLP-1R knockout mouse model. Male ß-cell-specific Glp-1r(ß-cell+/+) wild type (WT) and Glp-1r(ß-cell-/-) knockout (KO) littermates were placed on a high-fat diet for 6 weeks and then switched to high-fat diet supplemented with tamoxifen for the rest of the study. Mice underwent sham or VSG surgery after 2 weeks of tamoxifen diet and were fed ad libitum postoperatively. Mice underwent oral glucose tolerance testing at 3 weeks and were euthanized at 6 weeks after surgery. VSG reduced body weight and food intake independent of genotype. However, glucose tolerance was only improved in VSG WT compared with sham WT, whereas VSG KO had impaired glucose tolerance relative to VSG WT. Augmentation of glucose-stimulated insulin secretion during the oral glucose tolerance test was blunted in VSG KO compared with VSG WT. Therefore, our data suggest that enhanced ß-cell GLP-1R signaling contributes to improved glucose regulation after VSG by promoting increased glucose-stimulated insulin secretion.

Glycemic and lipid metabolic disorders in diabetic and non-diabetic patients bmi < 35 or > 35 before gastric bypass.

INTRODUCTION: Obesity and diabetes are diseases with high prevalence worldwide. There is currently no effective medical treatment for combat the weight gain. It is precursor of diseases such as diabetes or metabolic syndrome. It is necessary to know if weight gain has cumulative effects on the glycemic and lipid metabolism as precursors of complications or comorbidities. PATIENTS AND METHODS: We studied 131 patients (78 nondiabetic and 53 diabetic), 37 BMI ≤35 (3 BMI < 25, 18 BMI 25-29.9, 16 BMI 30-34.9) and 94 BMI ≥35 (81 BMI 35-49.9 and 13 BMI ≥50).We analyzed BMI, gender, diabetes and the time of evolution. Lipid profile, glucose, HbA1c and C-peptide evaluated after 12-hour fasting. RESULTS: Diabetic and diabese patients showed high triglycerides. Non-diabetics have impaired glucose (58% BMI < 35 and 36% BMI > 35). The 20% of non-diabetics BMI < 35 had high C-peptide, and 19% of BMI > 35 had high levels. The 5% of diabetics BMI < 35 had low Cpeptide and 36% of BMI > 35 had high levels. HbA1c was higher in 40% of non-diabetic patients BMI < 35 compared to 13% BMI > 35. CONCLUSIONS: Glucose and triglycerides increase with age and years of development of T2DM. Age of 51 and more, and men are more affected. The weight increase has cumulative effect by altering the metabolism favoring the onset of diabetes and comorbidities. Despite having intensive control treatment of diabetes, it continues its deleterious effects on patients through the years.

Introducción: La obesidad y la diabetes son enfermedades de alta prevalencia a nivel mundial. Actualmente no existe un tratamiento médico eficaz para combatir el aumento de peso. La obesidad es precursora de enfermedades tales como la diabetes o el síndrome metabólico. Es necesario saber si el aumento de peso tiene efectos acumulativos sobre el metabolismo de la glucemia y los lípidos como precursores de complicaciones o comorbilidades. Pacientes y métodos: Se estudiaron 131 pacientes (78 no diabéticos y 53 diabéticos), 37 IMC ≤35 (3 IMC < 25, 18 IMC 25-29,9, 16 IMC 30-34,9) y 94 IMC ≥35 (81 IMC 35- 49,9 y 13 de IMC ≥50). Se analizó el IMC, el género, la diabetes y su tiempo de evolución. El perfil lipídico, glucosa, HbA1c y el péptido C fueron evaluados después de un ayuno de 12 horas. Resultados: Los pacientes diabéticos y diabesos mostraron niveles altos de triglicéridos. Los pacientes no diabéticos tienen alteración de la glucosa (58% IMC 35). El 20% de los no diabéticos IMC 35 tenían niveles altos. El 5% de los diabéticos IMC < 35 tenía bajos niveles de péptido C y 36% de IMC > 35 tenían niveles altos. HbA1c fue mayor en 40% de pacientes no diabéticos IMC < 35 frente al 13% de IMC > 35. Conclusiones: La glucosa y los triglicéridos aumentan con la edad y los años de evolución de la DMT2. La edad de ≥51 años y los hombres son los más afectados. El aumento de peso tiene efecto acumulativo alterando el metabolismo favoreciendo la aparición de la diabetes y sus comorbilidades. A pesar de tener un tratamiento de control intensivo de la diabetes, esta continúa con sus efectos nocivos sobre los pacientes a través de los años.

GLP-1 and adiponectin: effect of weight loss after dietary restriction and gastric bypass in morbidly obese patients with normal and abnormal glucose metabolism.

BACKGROUND: It has been proposed that there is improvement in glucose and insulin metabolism after weight loss in patients who underwent diet restriction and bariatric surgery. METHODS: Eleven normal glucose tolerant (NGT) morbidly obese patients [body mass index (BMI), 46.1+/-2.27 g/m2] and eight abnormal glucose metabolism (AGM) obese patients (BMI, 51.20 kg/m2) were submitted to diet-restriction and bariatric surgery. Prospective study on weight loss changes, over the glucose, insulin metabolism, glucagon-like peptide-1 (GLP-1), and adiponectin levels were evaluated by oral glucose tolerance test during three periods: T1 (first evaluation), T2 (pre-surgery), and T3 (9 months after surgery). RESULTS: Insulin levels improved after surgery. T1 was 131.1+/-17.60 pmol/l in the NGT group and 197.57+/-57.94 pmol/l in the AGM group, and T3 was 72.48+/-3.67 pmol/l in the NGT group and 61.2+/-9.33 pmol/l in the AGM group. The major reduction was at the first hour of the glucose load as well as fasting levels. At 9 months after surgery (T3), GLP-1 levels at 30 and 60 min had significantly increased in both groups. It was observed that the AGM group had higher levels of GLP-1 at 30 min (34.06+/-6.18 pmol/l) when compared to the NGT group (22.69+/-4.04 pmol/l). Homeostasis model assessment of insulin resistance from the NGT and AGM groups had a significant reduction at periods T3 in relation to T1 and T2. Adiponectin levels had increased concentration in both groups before and after surgical weight loss. However, it did not have any statistical difference between periods T1 vs. T2. CONCLUSIONS: Weight loss by surgery leads to improvement in the metabolism of carbohydrates in relation to sensitivity to the insulin, contributing to the reduction of type 2 diabetes incidence. This improvement also was expressed by the improvement of the levels of adiponectin and GLP-1.