Medical Technology

Depression and Diabetes Synergistically Boost All-Cause Death

The study covered in this summary was published in as a preprint and has not yet been peer reviewed.

Key Takeaways

  • People with depression and diabetes are at an increased risk for all-cause death, including death due to cancer, circulatory disease, or other causes.

  • Depression and diabetes appeared to act synergistically in their effect on all-cause mortality even after adjustment for potential confounders.

  • The combined effect on death appears largely driven by cancer and other causes but not by circulatory diseases.

Why This Matters

  • This is the first report to quantify the effects of comorbid depression and diabetes on mortality from cancer and on other causes of death not including circulatory disease.

  • The findings suggest potential benefits from treating depression in people with diabetes, and the potential for finding additional useful interventions with further research.

Study Design

  • The study included 499,830 people from the UK Biobank, a prospective cohort study, who were 40 to 69 years old at baseline and enrolled at any of 22 UK sites during 2006-2010 with follow-up by linkage to national datasets.

  • The cohort excluded people with a history of bipolar disorder or schizophrenia and those with incomplete data.

Key Results

  • At baseline, 86% of study subjects had neither depression nor diabetes, 8% had depression alone, 5% had diabetes alone, 1% had both. Their median age was 58 years old.

  • During a median of 6.8 years of follow-up, there were 13,724 deaths (2.7%). Of which, 7976 (1.6%) were due to cancer, 2827 (0.6%) due to circulatory disease, and 2921 (0.6%) due to other causes.

  • After full adjustment for potential confounders and when compared with those with neither depression nor diabetes, the risk of all-cause mortality was 26% higher among people with depression alone, 62% higher among people with diabetes alone, and 116% higher among people with comorbid diabetes and depression. All three of these between-group differences were significant.

  • The risks of all-cause mortality, death due to cancer, and death from other causes each exceeded the sum of the risks due to diabetes and depression alone, suggesting an interaction on the additive scale. However, statistical evidence of an additive interaction only existed for all-cause and cancer mortality.

  • The synergistic effect of depression on all-cause mortality exceeded the expected additive effect due to either disorder alone and was largely driven by cancer and by causes other than circulatory disease and cancer.


  • Selection bias might have influenced some of the results.

  • Potential misclassifications existed because of underreports at baseline of depression, diabetes, or both; misclassifications of exposure status; and underestimates of the mortality risks associated with depression and diabetes.

  • Updates to exposure status during follow-up were not feasible.

  • Follow-up may have missed a small number of deaths occurring outside the UK. This likely occurred at about the same rate across the four exposure groups but may have biased the findings toward null.

  • The analysis included adjustment for key, potentially confounding factors but residual confounding might explain some of the observed effect.


This is a summary of a preprint research study, “Depression, diabetes, their comorbidity and all-cause and cause-specific mortality: a prospective cohort study,” written by researchers at the University of Edinburgh, College of Medicine and Veterinary Medicine, Usher Institute, Centre for Population Health Sciences on medRxiv provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. Follow him on Twitter: @mitchelzoler.

For more diabetes and endocrinology news, follow Medscape on Twitter and Facebook.

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