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.

The authors have declared no competing interest.

BH has received funding from the National Natural Science Foundation of China [grant number 82302148]. YY has received funding from the Key Science and Technology Program of Shaanxi Province [grant number 2023-YBSF-331] and Fourth Military Medical University [grant number 2023XC045]. GBC has received funding from the National Natural Science Foundation of China [grant number 82471936].

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The study used ONLY openly available human data that were originally located at UK Biobank.

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