Decreased plasma adiponectin concentrations in nondiabetic women with elevated homeostasis model assessment ratios

OBJECTIVE: Whether the adipocyte-derived protein adiponectin is associated with insulin resistance independently of the effects of adiposity and the diabetic state is an important question. We explored, in a cross-sectional study of 486 Japanese nondiabetic women, the relationship between the calculated insulin resistance (homeostasis model assessment ratio (HOMA-R)) and adiponectin levels determined using a validated sandwich ELISA. DESIGN AND METHODS: All participants were stratified into tertiles for HOMA-R (approximately <1.5, 1.5< or = approximately <3.0, 3.0< or = approximately ) and the differences across tertiles of continuous variables were tested with ANOVA. Two-way ANOVA was used to determine possible relationships for plasma adiponectin between tertiles of HOMA-R and several stratified parameters. Multiple regression analyses were performed with HOMA-R or fasting serum insulin as dependent variable, and diastolic blood pressure (BP), body mass index (BMI), serum triglyceride (TG), leptin and adiponectin as independent determinants. RESULTS: Mean plasma adiponectin in the high HOMA-R group decreased compared with that in the low HOMA-R group both before (mean+/-s.e.m. 6.2+/-0.6 vs 9.2+/-0.3 microg/ml, P<0.001) and after adjustment for body fat mass (BFM) as kg or percent (0.31+/-0.04 vs 0.69+/-0.03, 0.18+/-0.02 vs 0.34+/-0.01, both P<0.001). HOMA-R was inversely associated with adiponectin levels both before (r=-0.37, P<0.001) and after adjustment for BFM (r=-0.49, -0.46, both P<0.001). After covariate adjustment for age, diastolic BP, BMI and serum TG, HOMA-R retained a significant correlation with adiponectin/BFM (kg). Both adiponectin and leptin were the significant determinants of HOMA-R or fasting insulin in multiple regression models. CONCLUSIONS: Adiponectin was inversely associated with insulin resistance in nondiabetic subjects, independently from age, BP, adiposity and serum lipids. Because adiponectin is thought to have an anti-atherogenic action, the presence of hypoadiponectinemia may predispose subjects to atherosclerosis, and may progress the atherogenesis in insulin resistance.