Adiponectin in youth -: relationship to visceral adiposity, insulin sensitivity, and β-cell function

OBJECTIVE - Adiponectin is an adipose tissue protein that enhances insulin sensitivity and has antiatherogenic properties. The present study investigated the relationship of adiponectin levels in adolescents to 1) obesity and body fat distribution and 2) insulin sensitivity and the components of syndrome X. RESEARCH DESIGN AND METHODS - Twenty-three normal-weight and 26 obese adolescents had fasting adiponectin, lipid profile, and proinsulin measurements performed. Hepatic and peripheral insulin sensitivity were assessed with constant-rate [6,6-H-2(2)]glucose infusion and a 3-h hyperinsulinemic-euglycemic clamp, respectively. Body composition was evaluated by dual-energy X-ray absorptiometry, and visceral adipose tissue (VAT) and subcutaneous adipose tissue were measured by computed tomography scan at the L-4-L-5 level. RESULTS - Obese adolescents had similar to50% lower adiponectin than normal-weight adolescents. Moreover, obese adolescents with high (111.8 +/- 9.3 cm(2)) versus low (55.4 +/- 2.1 cm(2)) VAT had lower adiponectin levels (6.2 +/- 0.9 vs. 9.0 +/- 1.0 mug/ml, P = 0.05). Plasma adiponectin correlated positively with peripheral and hepatic insulin sensitivity (r = 0.67, P < 0.001 and r = 0.54, P < 0.001, respectively) and HDL (r = 0.52, P < 0.001) and negatively with fasting proinsulin and the proinsulin-to-insulin ratio (r = -0.64, P < 0.001 and r = -0.43, P = 0.003, respectively). In a multiple regression analysis, adiponectin, independently and together with BMI, explained 73% (R-2 = 0.73, P < 0.001) of the variance in insulin sensitivity. Adiponectin, but not adiposity, was the significant independent determinant of the proinsulin-to-insulin ratio (R-2 = 0.18, P = 0.008) and of HDL (R-2 = 0.45, P < 0.001). CONCLUSIONS - in summary, hypoadiponectinemia in youth is a strong and independent correlate of insulin resistance, beta-cell dysfunction, visceral adiposity, and syndrome X. The antidiabetogenic and antiatherogenic properties of adiponectin are evident early in life and compromised in youth-onset obesity.