Fasting hyperinsulinemia associates with increased sub-clinical inflammation in first-degree relatives normal glucose tolerant women independently of the metabolic syndrome

Background To evaluate the influence of gender on the relationship between inflammation and hyperinsulinemia in first-degree relatives of type 2 diabetic patients independently of metabolic syndrome. Methods Study group consisted in 217 first-degree relatives with normal glucose tolerance after an oral glucose tolerance test. A logistic analysis, adjusted for age, sex and all the components of the metabolic syndrome, was used to determine the relationship between interleukin-6 (IL-6) and leptin and tertiles of fasting insulin, and to take into account the influence of gender. Results In the whole cohort, IL-6 and leptin were significantly higher and adiponectin significantly lower in the III tertile when corrected for age, body mass index (BMI) and metabolic syndrome components. In women, but not in men, IL-6 and leptin remained significantly higher when corrected for metabolic syndrome. In the whole cohort and in women, univariate correlations between IL-6 concentrations and the parameters under evaluation showed that IL-6 and leptin were positively correlated with age, BMI, waist, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, fasting insulin, ΔAUC insulin area, triglyceride (TG), free fatty acids (FFA) and monocyte chemoattractant protein-1 (MCP-1) and inversely correlated with HDL cholesterol (HDL-C) and adiponectin. In women a forward stepwise linear regression analysis in a model including age, BMI, features of metabolic syndrome, fasting insulin, ΔAUC insulin and insulin sensitivity index (ISI) index revealed that only IL-6 and leptin were independently associated with fasting insulin levels. Conclusions In first-degree relatives normal glucose tolerant women, fasting hyperinsulinemia, independently of the presence of metabolic syndrome, is associated with elevated IL-6 and leptin levels, suggesting an increased cardiovascular risk. Copyright © 2009 John Wiley & Sons, Ltd.