The Association between Plasma Adiponectin and Insulin Sensitivity in Humans Depends on Obesity

OBJECTIVE: In humans, low plasma adiponectin concentrations precede a decrease in insulin sensitivity and predict type 2 diabetes independently of obesity. However, it is possible that the contribution of adiponectin to insulin sensitivity is not equally strong over the whole range of obesity. RESEARCH METHODS AND PROCEDURES: We investigated the cross-sectional association between plasma adiponectin levels and insulin sensitivity in different ranges of body fat content [expressed as percentage of body fat (PFAT)] in a large cohort of normal glucose-tolerant subjects (n = 900). All individuals underwent an oral glucose tolerance test (OGTT), and 299 subjects additionally a euglycemic hyperinsulinemic clamp. In longitudinal analyses, the association of adiponectin at baseline with change in insulin sensitivity was investigated in a subgroup of 108 subjects. RESULTS: In cross-sectional analyses, the association between plasma adiponectin and insulin sensitivity, adjusted for age, gender, and PFAT, depended on whether subjects were lean or obese [p for interaction adiponectin x PFAT = <0.001 (OGTT) and 0.002 (clamp)]. Stratified by quartiles of PFAT, adiponectin did not correlate significantly with insulin sensitivity in subjects in the lowest PFAT quartile (R2 = 0.10, p = 0.13, OGTT; and R2 = 0.10, p = 0.57, clamp), whereas the association in the upper PFAT quartile was rather strong (R2 = 0.36, p < 0.0001, OGTT; and R2 = 0.48, p = 0.003, clamp). In longitudinal analyses, plasma adiponectin at baseline preceded change in insulin sensitivity in obese (n = 54, p = 0.03) but not in lean (n = 54, p = 0.68) individuals. DISCUSSION: These data suggest that adiponectin is especially critical in sustaining insulin sensitivity in obese subjects. Thus, interventions to reduce insulin resistance by increasing adiponectin concentrations may be effective particularly in obese, insulin-resistant individuals.