Depression, diabetes, their comorbidity and all-cause and cause-specific mortality: a prospective cohort study

ABSTRACT Aims/hypothesis To investigate the risk of all-cause and cause-specific mortality among participants with neither, one, or both of diabetes and depression in a large prospective cohort study in the United Kingdom. Methods Our study population included 499,830 UK Biobank participants without schizophrenia and bipolar disorder at baseline. Type 1 or type 2 diabetes and depression were identified using self-reported diagnoses, prescribed medication and hospital records. Mortality was identified from death records using the primary cause of death to define cause-specific mortality. We performed Cox proportional hazards models to estimate the risk of all-cause mortality and mortality due to cancer, circulatory disease and causes of death other than circulatory disease or cancer among participants with either depression (n=41,791) or diabetes alone (n=22,677) and with comorbid diabetes and depression (n=3,597), compared to the group with neither condition (n=431,765) adjusting for sociodemographic and lifestyle factors, comorbidities, and history of CVD or cancer. We investigated for interaction between diabetes and depression. Results During a median of 6.8 (IQR: 6.1 – 7.5) years of follow-up, there were 13,724 deaths (cancer (n=7,976), circulatory disease (n=2,827), and other causes (n=2,921)). Adjusted hazard ratios of all-cause mortality and mortality due to cancer, circulatory disease and other causes were highest among people with comorbid depression and diabetes (HRs 2.16, 95% CI 1.94 – 2.42; 1.62, 95% CI 1.35 – 1.93; 2.22 95% CI 1.80 – 2.73 and 3.60, 95% CI 2.93 – 4.42, respectively). Among those with comorbid diabetes and depression, the risks of all-cause, cancer and other mortality exceeded the sum of the risks due to diabetes and depression alone. Conclusions/interpretation We confirmed the negative impact of depression and diabetes on mortality outcomes, and also identified that comorbid depression and diabetes had synergistic effects on all-cause mortality which was largely driven by deaths due to cancer and causes other than circulatory disease and cancer. RESEARCH IN CONTEXT What is already known about this subject? - Comorbid depression is common in individuals with diabetes and associated with increased risks of all-cause and cardiovascular mortality - The mortality risk among people with comorbid diabetes and depression might exceed the sum of the risks associated with each disorder alone - There is limited knowledge about the individual and joint effects of depression and diabetes on risk of death from specific causes. What is the key question? - What is the risk of all-cause and cause-specific mortality associated with neither, one, or both of diabetes (of any type) and depression? What are the new findings? - In a large prospective cohort study in the United Kingdom, comorbid depression and diabetes had synergistic effects on all-cause mortality which was largely driven by deaths due to cancer and causes other than circulatory disease and cancer How might this impact on clinical practice in the foreseeable future? - These findings help identify individuals at high risk of adverse events, and suggest a need for cost-effective interventions to support psychological well-being and risk reduction in people with diabetes