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Background  Central obesity is a major risk factor for diabetes but many obese individuals never develop diabetes, suggesting the presence of important effect modifiers. Depression has emerged as a key risk factor for poor glycemic control, but to our knowledge, no previous work has investigated whether depression amplifies the effect of central obesity on glucoregulation.    Methods and Findings  We used a national sample of adults without prevalent diabetes (MIDUS; N = 919) to test for synergy between central obesity and depression in the development of diabetes 10 years later. We found that depression amplified the association of waist-to-hip ratio (WHR) with incident diabetes adjusted for age, race, gender, education, physical activity, and sleep problems ( p  = 0.01 for test of interaction). The relative risk for incident diabetes per every 0.1 increment in WHR was 1.75 (95% CI: 1.31; 2.33) in those without depression and 3.78 in those with depression (95% CI: 2.14; 6.66).    Conclusions  These results confirm the role of depression as a robust risk factor for the development of diabetes and for the first time, demonstrate a synergy between depression and central obesity. Identifying and addressing depression could prove to be an effective approach to preventing diabetes in at risk individuals. Ultimately, elucidating the interplay among risk factors from different domains will be key to understanding multifactorial diseases such as diabetes and informing theory-based, patient-centered interventions aimed at reducing diabetes risk.

Depression Amplifies the Influence of Central Obesity on 10-Year Incidence of Diabetes: Findings from MIDUS