Type 2 Diabetes and Chronic Gastritis/Duodenitis Comorbidity: Additive Risk for Incident Depression and Synergistic Risk for All-Cause Mortality

BackgroundType 2 diabetes (T2D) and chronic gastritis/duodenitis (CGD) are both associated with the onset of depression and mortality. However, the impact of T2D-CGD comorbidity on incident depression and mortality remains unclear. MethodThis retrospective cohort study utilized data from 387,149 participants in the UK Biobank to examine the relationship between T2D-CGD comorbidity, incident depression, and all-cause mortality. OutcomePatients with T2D are more likely to develop CGD compared to those without T2D (odds ratio = 2{middle dot}10, 95% CI = [1{middle dot}97, 2{middle dot}24]). T2D, CGD, and their comorbidity each independently increased risks of depression incidence and all-cause mortality, with T2D-CGD showing the strongest associations for both (depression incidence: adjusted hazard ratio [aHR] = 2{middle dot}29, 95% CI = [1{middle dot}84, 2{middle dot}85]; all-cause mortality: aHR = 2{middle dot}57, 95% CI = [2{middle dot}28, 2{middle dot}88]). The synergistic effect of T2D and CGD on all-cause mortality was 1{middle dot}92 times that of their individual effects combined (synergy index = 1{middle dot}92, 95% CI = [1{middle dot}56, 2{middle dot}31]). The comorbidity was associated with a higher risk of depression and all-cause mortality within 15 years of disease onset. White matter hyperintensity, particularly near the cerebral ventricles, partially mediated the relationship between T2D-CGD comorbidity and incident depression. InterpretationIntegrated screening and long-term monitoring strategies should be prioritized for population with the comorbidity of T2D and CGD, as it significantly elevates the risk of both incident depression and all-cause mortality.