May 27, 2022Open Access
Depression, diabetes, comorbid depression and diabetes and risk of all-cause and cause-specific mortality: a prospective cohort study
Key Result
Comorbid depression and diabetes synergistically increased the risk of all-cause mortality by 116% (HR 2.16) compared to having neither condition.
Study Design
Type
Cohort (n=499,830)
Multicenter
Yes
Structured PICO
Does comorbid depression and diabetes increase the risk of all-cause and cause-specific mortality compared to either condition alone or neither condition in adults?
P
Population
499,830 UK Biobank participants aged 40-69 years at baseline without a history of schizophrenia or bipolar disorder.
I
Intervention
Presence of depression alone (n=41,791), diabetes alone (n=22,677), or comorbid diabetes and depression (n=3,597)
C
Comparator
Neither depression nor diabetes (n=431,765)
O
Outcome
All-cause mortality and cause-specific mortality (cancer, circulatory disease, and causes other than circulatory disease or cancer)hard clinical
Comorbid depression and diabetes have a synergistic effect on increasing the risk of all-cause mortality, largely driven by cancer and non-circulatory causes.
Main Result
Effect estimate: HR 2.16 (95% CI 1.94-2.42)
Absolute Event Rate: 9.7% vs 2.4%
Limitations
- Low response rate (5.5%) resulting in a relatively healthy cohort, which may introduce selection bias
- Potential misclassification due to under-reporting of depression and diabetes at baseline
- Undiagnosed diabetes was not identified
- Potential misclassification of depression if antidepressants were taken for chronic pain
- Exposure status was not updated during follow-up
- Potential residual confounding
Abstract
AIMS/HYPOTHESIS: The aim of this study was to investigate the risks 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 UK. METHODS: Our study population included 499,830 UK Biobank participants without schizophrenia and bipolar disorder at baseline. Type 1 and 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 from cancer, circulatory disease and causes of death other than circulatory disease or cancer among participants with either depression (n=41,791) or diabetes (n=22,677) alone and with comorbid diabetes and depression (n=3597) compared with the group with neither 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 of all-cause mortality and mortality from 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). The risks of all-cause, cancer and other mortality among those 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 an increased mortality risk and also identified that comorbid depression and diabetes have synergistic effects on the risk of all-cause mortality that are largely driven by deaths from cancer and causes other than circulatory disease and cancer.