Adiponectina, TNF- alfa e IL-6 em pacientes portadores de obesidade grave : relação com a sensibilidade a insulina e com a tolerancia a glicose / Adiponectin, TNF- alfa and IL-6 in severe patients : relation to insulin sensitivity and glucose tolerance

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Obesity is associated with a cluster of metabolic alterations such as insulin resistance, hypertension, and dyslipidemia and with a low-grade systemic inflammation, which is presumed to play a role in the development of insulin resistance, cardiovascular disease (CVD) and type 2 diabetes mellitus (DM). Adipocytokines or adipokines are synthesized by adipose tissue, released into the circulation and may act as signaling molecules. High circulating levels of Tumor Necrosis Factor-Alpha (TNF-α) and Interleukin-6 (IL-6) in adipose tissue have been demonstrated in obesity. Adiponectin, abundantly expressed in white adipose tissue, seems to play a protective role against atherosclerosis and insulin resistance but is decreased in obesity. The role of insulin sensitivity and insulin levels on the modulation of adiponectin concentrations in humans remains unclear. Aim: to evaluate the acute insulin effect on circulating adiponectin, TNF-α, IL-6 and C-reactive protein (CRP) and their relationship with insulin resistance in normal subjects and in class III obese subjects with normal (NGT) or impaired glucose tolerance (IGT). Methods: 32 obese, 15 NGT, 11 IGT and 6 DM subjects (BMI=50.2±2.2; 48.3±2.2 and 51.0±3.0Kg/m2) and 9 lean subjects (CT 22.3±0.6Kg/m2) received an OGTT and a 3h-euglycemic clamp (insulin infusion - 40μU/min·m2). Adiponectin, TNF-α, IL-6 and CRP were assayed at fasting and at 180min of insulin infusion. BIA was performed before the study to assess body composition. Results: Obese patients were insulin resistant (M:NGT=28.5±3.4; IGT=23.3±1.6 and DM=16.8±3.4; all p<0.001 vs. CT=52.5±2.7 μmol/KgFFM·min). Fasting TNF-α IL-6 and CRP were similar among obese subgroups, higher than CT (p<0.01) and related to BMI and/or fat mass. Adiponectin was lower in obese (NGT=7.55±1.26; IGT=5.55±0.95; DM=3.31±0.75 vs. CT=11.56±1.37 μg/ml) and directly and independently related to M after adjustment for waist, fat mass and BMI (p<0.001). Insulin infusion lowered adiponectin only in obese subjects and little affected the other cytokines. Discussion: In severely obese subjects, TNF-α, IL-6 and CRP are increased independently of glucose tolerance status, and are not affected in the short-term by insulin. Adiponectin levels are decreased in these subjects, according to the glucose tolerance degree, and are downregulated by insulin infusion. More importantly, the persistent hyperinsulinemia can contribute to reduce the adiponectin expression, contributing to further insulin resistance and hyperinsulinemia.

ASSUNTO(S)

citocinas insulin resistance morbid obesity resistencia a insulina cytokines obesidade morbida

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