Depression is associated with greater risks of incident cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes (T2D), a population-based mediation analysis of 0.5 million Chinese people has shown.
“Our group previously reported a 2-fold higher incidence of cardiovascular [CV] events among patients with depression and T2D, using data from a historic registry established in 1995 that included approximately 7,000 patients with diabetes in Hong Kong,” wrote the researchers from the Chinese University of Hong Kong (CUHK). “However, the study was limited by statistical power, as depression prevalence in the cohort was only 1.9 percent.” [J Affect Disord 2013;149:129-135; J Affect Disord 2026:415:122401]
In a recent population-based mediation analysis, the CUHK researchers used a territory-wide electronic health record database with more than 0.5 million Chinese patients with T2D. A total of 571,129 patients with T2D attending structured diabetes risk assessment in Hong Kong between 1 January 2000 and 30 June 2024 were included.
Depression was identified using International Classification of Disease (ICD)-9 codes or antidepressant prescription. In the cohort, 7.5 percent had depression (mean age, 60.4 years; female, 66.1 percent), while 92.5 percent did not have depression (mean age, 61.4 years; female, 49.3 percent).
Excess risks of CVD and death
After a median follow-up duration of 9 years, the crude incidence rates of CVD, all-cause death, and end-stage kidney disease (ESKD) were 14.2, 18.5, and 3.2 per 1,000 person-years, respectively, in the depression group compared with 15.3, 19.7, and 4.6 per 1,000 person-years in those without depression.
Patients with depression had a greater healthcare burden than those without depression, as reflected by a higher number of all-cause hospitalizations and longer hospital stays.
After adjusting for age, gender, and diabetes duration, depression was associated with higher risks of incidence CVD (hazard ratio [HR], 1.21; 95 percent confidence interval [CI], 1.17–1.24; p<0.001) and all-cause death (HR, 1.30; 95 percent CI, 1.26–1.33; p<0.001).
However, the association between depression and ESKD did not reach statistical significance (HR, 1.20; 95 percent CI, 0.90–1.01; p=0.122).
Sex- and age-stratified crude incidence rates of CVD were higher among middle-aged women with depression vs those without depression. This may be partly explained by the transitional phase of menopause, which is associated with insulin resistance, diabetes development, and increased CV risk.
Driven by direct effect of depression
Patients with depression had a higher baseline prevalence of central obesity (BMI, 26.6 vs 26.1 kg/m2; waist circumference, 94.2 vs 92.2 cm for male; 10.8 vs 10.4 cm for female) and higher baseline level of triglycerides (1.51 vs 1.36 mmol/L).
Nevertheless, mediation analysis revealed that the associations between depression and excess risks of CVD and all-cause death were predominantly driven by the direct effect of depression, with a minor contribution from conventional metabolic risk factors.
Clinical implications
“Results from our study support the need for enhanced depression screening and integrated care in patients with diabetes, particularly in middle-aged women,” wrote the researchers.