Associations between leptin and the leptin / adiponectin ratio and incident Type 2 diabetes in middle-aged men and women: results from the MONICA / KORA Augsburg study 1984-2002.

AIMS: Adipocyte-derived hormones seem to be involved in the development of Type 2 diabetes. Therefore, we assessed the association between the proinflammatory adipokine leptin and incident Type 2 diabetes, taking into account interactions between leptin and the anti-inflammatory adipokine adiponectin. METHODS: Using a case-cohort design, serum levels of adipokines were measured in 460 cases with incident Type 2 diabetes and 1474 non-cases selected from a source population of 7936 middle-aged subjects participating in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) Augsburg cohort study between 1984 and 1995 and followed up until 2002 (mean follow-up 10.9+/-4.7 years). RESULTS: High leptin and low adiponectin levels were associated with an increased Type 2 diabetes risk. The multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) comparing tertile extremes were 1.71 (1.12-2.63) for leptin (top vs. bottom tertile) and 2.65 (1.88-3.76) for adiponectin (bottom vs. top tertile), respectively. There was a significant interaction between leptin and adiponectin, with highest diabetes risk being observed in individuals with high leptin and low adiponectin levels (P = 0.029 for interaction).While the addition of adiponectin to a basic risk factor model improved model prediction (Delta area under the curve 0.011), the change in model prediction was only marginal after the addition of leptin (Delta area under the curve 0.002). CONCLUSIONS: Our findings indicate that the two adipokines leptin and adiponectin interact in modulating Type 2 diabetes risk, but adiponectin is more strongly associated with Type 2 diabetes risk than leptin.