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

Background Type 2 diabetes (T2D) and chronic gastritis/duodenitis (CGD) are both strongly associated with the onset of depression. However, the impact of T2D-CGD comorbidity on incident depression and all-cause mortality remains unclear. Method This 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. Outcome Patients with T2D are more likely to develop CGD compared to those without T2D (OR = 2.10, 95% CI = [1.97, 2.24]). T2D-CGD comorbidity was identified as a significant risk factor for both incident depression (adjusted HR = 2.29, 95% CI = [1.84, 2.85]) and all-cause mortality (adjusted HR = 2.57, 95% CI = [2.28, 2.88]). The synergistic effect of T2D and CGD on all-cause mortality was 1.92 times that of their individual effects combined (synergy index = 1.92, 95% CI = [1.56, 2.31]). 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. Interpretation Integrated 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.