Healthcare burden of comorbid depression and type 2 diabetes and conventional risk factors – a population-based mediation analysis of 0.5 million Chinese people

BACKGROUND Limited population-based analyses of associations of comorbid depression and diabetes have tested metabolic risk factors as mediating variables for the association between depression and clinical outcomes. METHODOLOGY We included Chinese adults with type 2 diabetes attending structured diabetes risk assessment in Hong Kong between 1 January 2000 and 30 June 2024. Depression was identified using International Classification of Disease-9 codes or prescription of anti-depressants. People with baseline cardiovascular disease or end-stage kidney disease (ESKD) were excluded. We estimated the hazard ratio (HR) of cardiovascular diseases, ESKD, all-cause death associated with depression compared to those without depression. We examined the mediating effects of eight cardiometabolic risk factors in these risk associations. RESULTS Among 571,129 people with type 2 diabetes, 7.5% had depression (mean age 60.4 years, 66.1% women, mean HbA1c 7.2%). People with depression had greater number of all-cause hospitalisation and longer length of stay. Compared to no depression, depression was associated with higher hazards for incident cardiovascular disease (HR: 1.21 [1.17, 1.24]), all-cause death (HR: 1.30 [1.26, 1.33]), but not ESKD (HR 0.95 [0.89, 1.01]), adjusted for age, sex and diabetes duration. Mediation analyses revealed the association between depression, cardiovascular disease and all-cause death were mediated predominantly by the direct effect of depression. CONCLUSION Depression is associated with greater risks for incident cardiovascular disease and all-cause death in people with type 2 diabetes. Mediation analyses revealed minor contributions from metabolic risk factors on these associations, highlighting the need for enhanced screening for depression and integrated care.