Co-occurrence patterns and related risk factors of type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) are interrelated metabolic disorders worldwide. We aimed to characterize global co-occurrence patterns of T2DM and MASLD from a spatial perspective and to identify shared risk factors. METHODS: We extracted incidence rates of T2DM and MASLD and exposure rates of 68 risk factors among individuals aged ≥ 20 years, derived from Global Burden of Disease Study 2021. Three co-occurrence areas were classified based on four quartiles of both diseases incidence. Interpretable machine learning and negative binomial linear mixed-effects model were applied to identify and quantify effects of risk factors. We calculated population-attributable fraction (PAF) to evaluate incidence burden of T2DM and MASLD attributable to identified risk factors. RESULTS: Fifty-nine countries were classified as consistent, 71 as T2DM-dominant, and 74 as MASLD-dominant. Three areas overlap spatially with exposure rates to metabolic, environmental, and behavioral risk factors. After feature selection, we identified nine risk factors with substantial effects on the comorbidity. Functionally, T2DM incidence was mainly attributable to metabolic risks (PAF = 35.28%) and behavioral risks (11.78%), whereas MASLD incidence was attributable to behavioral risks (28.84%), environmental risks (21.65%), and metabolic risks (14.63%). Overall, 42.9% of T2DM incidence and 52.41% of MASLD incidence were attributed to cumulative exposure to risk factors, with specific combinations and variations of these factors significantly impacting the disparate co-occurrence patterns worldwide. CONCLUSION: Comorbidity of T2DM and MASLD is a prevalent global health issue. Co-management of T2DM and MASLD can proceed from interventions targeting corresponding modifiable risk factors.