Soluble Tumor Necrosis Factor-α Receptors in Young Obese Subjects With Normal and Impaired Glucose Tolerance

Abstract

OBJECTIVE— Tumor necrosis factor-α (TNF-α) is a possible link between obesity and impaired glucose tolerance (IGT) and type 2 diabetes. Data about TNF-α and soluble forms of its receptors (sTNFR1 and sTNFR2) in IGT are controversial. The aim of the present study was to assess plasma TNF-α, sTNFR1, and sTNFR2 levels and to evaluate the relationships with insulin resistance in obese subjects with IGT. RESEARCH DESIGN AND METHODS— A total of 104 subjects participated in the present study: 30 obese subjects with IGT (obese-IGT), 32 obese subjects with normal glucose tolerance (obese-NGT), and 42 lean healthy control subjects (control-NGT). Anthropometry and blood biochemical parameters were measured and euglycemic-hyperinsulinemic clamp was performed. RESULTS— Obese-IGT subjects were more insulin resistant in comparison with obese-NGT and control-NGT groups; obese-NGT subjects were more insulin resistant than control-NGT. Plasma sTNFR1 and sTNFR2 were markedly higher in both groups of obese subjects in comparison with control-NGT and in the obese-IGT versus obese-NGT group. Plasma sTNFR1 and sTNFR2 were inversely related to insulin sensitivity. Both relationships remained significant after adjustment for age, BMI, waist girth, percent body fat, plasma glucose, insulin, nonesterified fatty acids, cholesterol, and triglycerides. Correlation between sTNFR2 and insulin sensitivity was also present in all the groups analyzed separately, but the correlation between sTNFR1 and insulin sensitivity was present only in the obese-NGT group. CONCLUSIONS— Our data suggest that TNF-α receptors are increased in obese-IGT subjects and are related to insulin resistance. These findings indicate that the TNF-α system might contribute to the development of insulin resistance in glucose-intolerant subjects.