Highlights
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Objectives/hypotheses
The aim of this study was to investigate the risks of all-cause and cause-specific mortality among participants without diabetes, with 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 or bipolar disorder at baseline. Type 1 and type 2 diabetes and depression were identified through self-reported diagnoses, prescribed medications, 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 from cancer, circulatory disease, and causes of death other than circulatory disease or cancer among participants with depression ( n = 41,791) or diabetes ( n = 22,677) alone and with comorbid diabetes and depression ( n = 3,597) compared to the group without any condition ( n = 431,765), adjusting for sociodemographic and lifestyle factors, comorbidities, and history of CVD or cancer. We also investigated the 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 = 7976; circulatory disease, n = 2827; other causes, n = 2921).
Adjusted HRs for all-cause mortality and mortality from cancer, circulatory disease, and other causes were highest among people with comorbid depression and diabetes (HR 2.16 [95% CI: 1.94, 2.42]; 1.62 [95% CI: 1.35, 1.93], 2.22 [95% CI: 1.80 to 2.73] and 3.60 [95% CI: 2.93 to 4 ,42], respectively).
The risks of mortality from all causes, cancer, and other causes among people with comorbid depression and diabetes exceeded the sum of the risks due to diabetes and depression alone.
Conclusions/interpretation
We confirmed that depression and diabetes individually are associated with increased risk of mortality and also identified that comorbid depression and diabetes have synergistic effects on the risk of all-cause mortality that is largely driven by cancer deaths and causes other than circulatory disease and cancer.
Possible explanations for these findings
The mechanisms underlying the synergistic effect of depression and diabetes on mortality risk remain to be established. As we found synergistic effects of depression and diabetes for the risk of different causes of mortality, it is unlikely that the underlying mechanism is organ- or disease-specific.
A more general explanation for the excess risk of mortality among people affected by depression and diabetes is that depression may make it difficult to adopt and maintain a healthy lifestyle, including smoking cessation and self-management. For example, depression has been shown to be a risk factor for medical non-adherence among people with comorbidities, which could lead to adverse effects such as poor glycemic control in people with comorbid depression and diabetes.
Second, people with physical-mental comorbidity may receive suboptimal quality of care, which in turn may increase the risk of adverse events. As such, the negative consequences of depression and diabetes may be compounded among people with comorbid depression and diabetes due to the lack of successful treatment or self-management strategies for both conditions. However, more research is needed to further explore this hypothesis.
Final message
In summary, we found that people with depression and diabetes were at high risk for all-cause mortality and mortality from cancer, circulatory disease, and causes other than circulatory disease or cancer. In the fully adjusted model, the combined association between depression and diabetes was additive for the risk of circulatory mortality and synergistic (i.e., supra-additive) for the risk of cancer and mortality from causes other than circulatory disease and cancer. Although some progress has been made in the past, our findings highlight the need for more research and the potential to improve the treatment of depression, particularly in people with diabetes.
