Adiponectin, change in adiponectin, and progression to diabetes in the diabetes prevention program

OBJECTIVE-To determine whether baseline adiponectin levels or intervention-associated change in adiponectin levels were independently associated with progression to diabetes in the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS-Cox proportional hazards analysis was used to evaluate the contribution of adiponectin and treatment-related change in adiponectin to risk of progression to diabetes. RESULTS-Baseline adiponectin was a strong independent predictor of incident diabetes in all treatment groups (hazard ratio per ∼3 μg/ml higher level; 0.61 in the lifestyle, 0.76 in the metformin, and the 0.79 in placebo groups; all P < 0.001, P = 0.13 comparing groups). Baseline differences in adiponectin between sexes and race/ethnicity groups were not reflected in differences in diabetes risk. DPP interventions increased adiponectin levels ([means ± SE] 0.83 ± 0.05 μg/ml in the lifestyle group, 0.23 ± 0.05 μg/ml in the metformin group, and 0.10 ± 0.05 μg/ml in the placebo group; P < 0.001 for increases versus baseline, P < 0.01 comparing groups). These increases were associated with reductions in diabetes incidence independent of baseline adiponectin levels in the lifestyle and placebo groups but not in the met-formin subjects (hazard ratio 0.72 in the lifestyle group (P < 0.001), 0.92 in the metformin group (P = 0.18), and 0.89 in the placebo group; P = 0.02 per ∼1 μg/ml increase, P = 0.02 comparing groups). In the lifestyle group, adjusting for change in weight reduced, but did not remove, the effect of increased adiponectin. CONCLUSIONS-Adiponectin is a powerful marker of diabetes risk in subjects at high risk for diabetes, even after adjustment for weight. An increase in adiponectin in the lifestyle and placebo groups was associated with a reduction in diabetes risk. However, these changes in adiponectin were comparatively small and less strongly related to diabetes outcome than baseline adiponectin levels.