Adiponectin, Change in Adiponectin, and Progression to Diabetes in the Diabetes Prevention Program

Abstract

Objective: To determine whether baseline adiponectin level or intervention-associated change in adiponectin level 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 mellitus.

Results: Baseline adiponectin was a strong independent predictor of incident diabetes in all treatment groups [HR per ∼3 μg/ml higher level, 0.61 in lifestyle (ILS), 0.76 in metformin (MET), 0.79 in placebo (PLA), 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 (0.83±0.05 μg/ml ILS (mean±SE), 0.23±0.05 MET, 0.10±0.05 PLA, p<0.001 for increases vs baseline; p<0.01 comparing groups). These increases were associated with reductions in diabetes incidence independent of baseline adiponectin levels in lifestyle and placebo groups, but not in metformin-treated subjects [HR=0.72 in ILS (p<0.001), 0.92 in MET (p=0.18), and 0.89 in PLA (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 of diabetes, even after adjustment for weight. An increase in adiponectin in lifestyle and placebo 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.