Impact of bariatric surgeries on diabetes outcomes / Impacto da cirurgia bariátrica no resultado do diabetes

Obesity and type 2-diabetes (T2D) are associated to dramatically high morbidity and mortality, and their incidence and prevalence are increasing rapidly. Bariatric surgeries, including a variety of gastrointestinal surgical procedures achieve substantial and sustained weight loss in morbidly obese patients, strongly improves diabetes and hypertension control or prevalence, quality of life, decreases incidence of stroke, myocardial infarction and obstructive sleep apnea among other favorable clinical outcomes. Most important, mortality rates decreases. The objectives of this narrative review were the effectiveness of bariatric procedures on diabetes remission or improvement and the implicated mechanisms. It was found that bariatric surgeries induce high rates of short and long-term diabetes remission (from 60 to 95% or improved control), according to the surgical intervention, with low frequency of perioperative and postoperative complications. Rates of diabetes recurrence are not well known, but the time free-of-disease should ameliorate diabetes complications and mortality. The mechanisms are still not completely understood; encompass improved insulin action, better b-cell function, higher adiponectin, lower inflammation and complex changes of hormones of the entero-insular axis, GLP-1 and glucose dependent insulinotropic polypeptide (GIP). Insulin action improves proportionally to weight loss (WL), in most types of surgery, but normalizes after Bilio-pancreatic diversion even in still obese people. b-cell function improves more after bypass than after restrictive surgeries, but does not normalize and baseline function predicts diabetes remission. Efforts to understand mechanisms and predictive factors for diabetes remission may optimize surgical interventions for metabolic disorders even in less obese patients. Finally and more important, they might drive the development of new clinical approaches for T2D...

Overcoming metabolic syndrome in severe obesity: adiponectin as a marker of insulin sensitivity and HDL-cholesterol improvements after gastric bypass / Reversão da síndrome metabólica na obesidade mórbida: adiponectina como um marcador da sensibilização à insulina e do aumento do HDL-colesterol após o bypass gástrico

OBJECTIVE: To assess the relationship between adiponectin and metabolic parameters in severely obese women during surgical-induced weight loss. METHODS: Nineteen lean (CT - BMI:21.2 ± 0.3 kg.m²), 14 overweight/class II obese (OB/OW - BMI: 29.7 ± 0.7 kg/m²) and 8 morbidly obese (OBIII - BMI: 56.4 ± 3.6 kg/m²) were evaluated by hyperinsulinemic-euglycemic clamp, adiponectin, and lipids. OBIII were evaluated at 5th and 16th month post-operatively. RESULTS: Compared to lean, obese groups had lower adiponectin (OB/OW: 9.4 ± 0.9, OBIII: 7.1 ± 1.3 versus 12.2 ± 0.9 ng/dL; p < 0.01), lower HDL-cholesterol (OB/OW:1.05 ± 0.05, OBIII: 0.88 ± 0.04 versus 1.22 ± 0.07 mmol/L; p < 0.01) and insulin resistance-IR (glucose uptake, M-value - OB/OW: 43.6 ± 2.7, OBIII: 32.4 ± 3.2 versus 20.0 ± 1.8 umol/kgFFM.min; p < 0.001). Considering all subjects, adiponectin levels were inversely correlated to BMI and waist circumference, and directly to M-value and HDL-cholesterol (p < 0.01). During weight loss, improvements in IR (Study III: 36.1 ± 3.9 umol/kg/FFM.min, p < 0.0001), adiponectin (11.8 ± 1.4 ng/dL, p = 0.006) and HDL-cholesterol were observed (1.10 ± 0.04 mmol/L, p = 0.007). Moreover, HDL-cholesterol improvement was significantly and independently related to variations of adiponectin and BMI (r² = 0.86; p < 0.0002). CONCLUSIONS: The improvements of IR and adiponectin were related to surgical-induced weight loss, suggesting an important role of adiponectin in HDL-cholesterol regulation.

OBJETIVO: Identificar a relação entre adiponectina e parâmetros metabólicos em mulheres obesas mórbidas durante o emagrecimento por bypass gástrico. MÉTODOS: Dezenove magras (CT - IMC: 21,2 ± 0,3 kg/m²), 14 com sobrepeso/obesidade classe II (OB/OW - IMC: 29,7 ± 0,7 kg/m²) e oito obesas classe III (OBIII - IMC:56,4 ± 3,6 kg/m²) foram avaliadas pelo clamp euglicêmico-hiperinsulinêmico, adiponectina e lípides. OBIII submeteram-se aos mesmos testes no quinto e décimo-sexto mês pós-operatório. RESULTADOS: comparados a CT, os grupos obesos tiveram menor adiponectinemia (OB/OW: 9,4 ± 0,9, OBIII: 7,1 ± 1,3 versus 12,2 ± 0,9 ng/dL; p < 0,01), menor HDL-colesterol (OB/OW: 1,05 ± 0,05, OBIII: 0,88 ± 0,04 versus 1,22 ± 0,07 mmol/L; p < 0,01) e resistência insulínica - RI (captação de glicose, M - OB/OW:43,6 ± 2,7, OBIII:32,4 ± 3,2 versus 20,0 ± 1,8 umol/kgFFM.min; p < 0,001). Analisando todos os voluntários: adiponectina correlacionou-se negativamente com IMC, circunferência da cintura e positivamente ao M-clamp e HDL-colesterol (p < 0,01). No emagrecimento, houve melhora da RI (Estudo III:36,1 ± 3,9 umol/kgFFM.min, p < 0,0001), adiponectina (11,8 ± 1,4 ng/dL, p = 0,006) e HDL-colesterol (1,10 ± 0,04 mmol/L, p = 0,007). Aumentos do HDL-colesterol foram significativa e independentemente relacionados às variações da adiponectina e IMC (r² = 0,86; p < 0,0002). CONCLUSÕES: A melhora da RI e adiponectina no emagrecimento induzido por bypass gástrico sugerem um importante papel da adiponectina na regulação do HDL-colesterol.

Peroxisome proliferator-activated receptor y2 Pro115Gln and G972R insulin substrate receptor-1 variants in obesity and insulin resistance

Objective: The association among IRS-IG972R and PPAR-gama2Pro1l5Gln gene variants and insulin resistance is controversial. This study aimed to investigate the relationship between PPAR-gama2Pro115Gln and IRS-IG972R variants to in­sulin resistance. Design and Setting: This prospective study was developed in the University Hospital of Unicamp. Methods: We studied the prevalence of these mutations in 67 lean and 64 obese subjects (91 women and 40 men, 18 to 67 years old) evaluating metabolic and obesity parameters. Both genetic variants were detected by restriction fragment length polymorphism assays. Insulin sensitivity was estimated through the insulin resistance index; Body Mass Index (BMI), waist, fat and fat-free mass, indirect calorimetry, blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting plasma glucose, insulin and serum uric acid were also measured. Results: Genetic analysis showed that 5 (3.8%) individuals presented mutations in the PPAR-gama2 gene, all of them homozygotes, whereas polymorphism of the IRS-l gene was found in 12 (9.1 %) cases, all in heterozygosis. There was no correla­tion between the genetic profile and insulin resistance or any ofthe anthropometric, hemodynamic and biochemical parame­ters measured in the obese group. The rate of PPAR-gama2 and IRS-l variants was similar in lean and obese subjects. Among the PPAR-gama2Pro1l5Gln carriers, 3 were insulin resistant (p equal 0.05 HOMA-IR greater that 75th). Conclusion: We suggest that there is a trend to the asso­ciation between the PPAR -gama2Pro 115, but not the IRS-l G972R gene mutation to insulin resistance in the Brazilian population, that needs to be confirmed in larger samples.