C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance.

OBJECTIVE: The C-174G promoter polymorphism of the interleukin (IL)-6 gene was found to influence transcriptional activity and plasma IL-6 levels in humans. We addressed the question of whether the C-174G IL-6 polymorphism contributes to variation of insulin sensitivity. RESEARCH DESIGN AND METHODS: Two cohorts of subjects were genotyped. Cohort 1 includes 275 nondiabetic subjects who underwent a euglycemic-hyperinsulinemic clamp. Cohort 2 includes 77 patients with morbid obesity who underwent laparoscopic adjustable gastric banding (LAGB). RESULTS: The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In cohort 1, insulin sensitivity was reduced in carriers of the -174G/G genotype as compared with subjects carrying the C allele (P = 0.004). Carriers of -174G/G displayed significantly higher plasma IL-6 levels in comparison with carriers of the C allele. In a stepwise linear regression analysis, the C-174G polymorphism was independently associated with insulin sensitivity; however, after inclusion of plasma IL-6 concentrations, the polymorphism was excluded from the model explaining insulin sensitivity variability, thus suggesting that the polymorphism was affecting insulin sensitivity by regulating IL-6 plasma levels. IL-6 mRNA levels were measured by real-time RT-PCR in subcutaneous fat obtained from obese patients of cohort 2 during LAGB. Carriers of -174G/G showed increased IL-6 expression compared with subjects carrying the C allele (P = 0.04). There was a significant correlation between adipose IL-6 mRNA expression and insulin resistance assessed by homeostasis model assessment (rho = 0.28, P = 0.014). CONCLUSIONS: These results indicate that the -174G/G genotype of the IL-6 gene may contribute to variations in insulin sensitivity.

Laparoscopic adjustable gastric banding for the treatment of morbid (grade 3) obesity and its metabolic complications: a three-year study.

Weight loss ameliorates arterial hypertension and glucose metabolism in obese patients, but the dietary approach is unsatisfactory because obesity relapses. Durable reduction of body weight, obtained through major nonreversible surgical procedures, such as jejunal and gastric bypass, allows improvement of glucose metabolism and arterial blood pressure in morbid (grade 3) obesity. Laparoscopic adjustable gastric banding (LAGB) is a minimally invasive and reversible surgical procedure that yields a significant reduction of gastric volume and hunger sensation. In this study, 143 patients with grade 3 obesity [27 men and 116 women; age, 42.9 +/- 0.83 yr; body mass index (BMI), 44.9 +/- 0.53 kg/m(2); normal glucose tolerance (NGT; n = 77); impaired glucose tolerance (IGT; n = 47); type 2 diabetes mellitus (T2DM; n = 19)] underwent LAGB and a 3-yr follow-up for clinical (BMI, waist circumference, waist to hip ratio, and arterial blood pressure) and metabolic variables (glycosylated hemoglobin, fasting insulin and glucose, insulin and glucose response to oral glucose tolerance test, homeostasis model assessment index, total and high-density lipoprotein cholesterol, triglycerides, uric acid, and transaminases). At baseline and 1 yr after LAGB, patients underwent computerized tomography and ultrasound evaluation of visceral and sc adipose tissue. One-year metabolic results were compared with 120 obese patients (51 men and 69 women; age, 42.9 +/- 1.11 yr; BMI, 43.6 +/- 0.46 kg/m(2); NGT, n = 66; IGT, n = 8; T2DM, n = 46) receiving standard dietary treatment. LAGB induced a significant and persistent weight loss and decrease of blood pressure. Greater metabolic effects were observed in T2DM patients than in NGT and IGT patients, so that at 3 yr glycosylated hemoglobin was no longer different in NGT and T2DM subjects. Clinical and metabolic improvements were proportional to the amount of weight loss. LAGB induced a greater reduction of visceral fat than sc fat. At 1-yr evaluation, weight loss and metabolic improvements were greater in LAGB-treated than diet-treated patients. We conclude that LAGB is an effective treatment of grade 3 obesity in inducing long-lasting reduction of body weight and arterial blood pressure, modifying body fat distribution, and improving glucose and lipid metabolism, especially in T2DM.