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.