Although it has been hypothesized that the diabetes-depression relation is bidirectional, few studies have addressed this hypothesis in a prospective setting.
A total of 65 381 women aged 50 to 75 years in 1996 were observed until 2006. Clinical depression was defined as having diagnosed depression or using antidepressants, and depressed mood was defined as having clinical depression or severe depressive symptoms, ie, a 5-item Mental Health Index (MHI-5) score of 52 or less. Self-reported type 2 diabetes mellitus was confirmed by means of a supplementary questionnaire validated by medical record review.
During 10 years of follow-up (531 097 person-years), 2844 incident cases of type 2 diabetes mellitus were documented. Compared with referents (MHI-5 score of 86-100) who had the best depressive symptom scores, participants with increased severity of symptoms (MHI-5 scores of 76-85 or 53-75, or depressed mood) showed a monotonic elevated risk of developing type 2 diabetes (P for trend = .002 in the multivariable-adjusted model). The relative risk for individuals with depressed mood was 1.17 (95% confidence interval [CI], 1.05-1.30) after adjustment for various covariates, and participants using antidepressants were at a particularly higher relative risk (1.25; 95% CI, 1.10-1.41). In a parallel analysis, 7415 cases of incident clinical depression were documented (474 722 person-years). Compared with nondiabetic subjects, those with diabetes had a relative risk (95% CI) of developing clinical depression after controlling for all covariates of 1.29 (1.18-1.40), and it was 1.25 (1.09-1.42), 1.24 (1.09-1.41), and 1.53 (1.26-1.85) in diabetic subjects without medications, with oral hypoglycemic agents, and with insulin therapy, respectively. These associations remained significant after adjustment for diabetes-related comorbidities.
Our results provide compelling evidence that the diabetes-depression association is bidirectional.