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Life sciences · Journal article
Frontiers in Medicine · September 16, 2026
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Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition globally, yet its prospective association with incident type 2 diabetes mellitus (T2DM) in the general health check-up population requires further elucidation. This study aimed to investigate whether baseline MAFLD increases the risk of new-onset T2DM in a health check-up cohort. Materials and methods This retrospective cohort study initially screened 1,520 individuals from the health check-up database; after applying strict exclusion criteria (including baseline T2DM, other liver diseases, malignancy, missing key data, and loss to follow-up), 186 participants without baseline T2DM were finally included. These participants underwent annual health examinations at Shanxi Bethune Hospital Health Check-up Center from 2020 to 2024. Baseline anthropometric measurements, biochemical parameters, and medical histories were collected. The primary outcome was new-onset T2DM over 5 years. Associations were analyzed using Kaplan–Meier methods and multivariable Cox regression. The primary analysis was adjusted for age, sex, and body mass index (BMI); a fully adjusted model including additional metabolic covariates was performed as a sensitivity analysis. Results Over a median 60-month follow-up, 22 new T2DM cases occurred. The 5-year cumulative incidence of T2DM was significantly higher in the MAFLD group than in the non-MAFLD group (18.9% vs. 5.6%, p = 0.001). Multivariable Cox regression suggested that MAFLD was associated with an increased risk of new-onset T2DM (adjusted HR = 3.15, 95%CI: 1.58–6.28, p = 0.001 for age, sex, and BMI; a fully adjusted sensitivity analysis yielded HR = 2.71, 95%CI: 1.33–5.52, p = 0.006), with preliminary findings for both lean MAFLD (HR = 2.88, 95%CI: 1.10–7.54, based on a small subgroup of 15 participants) and overweight/obese MAFLD (HR = 2.65, 95%CI: 1.22–5.76, both from fully adjusted sensitivity models). Sensitivity and stratified analyses were generally consistent with the primary association, although the small number of events in subgroup analyses limited the statistical power and precluded definitive conclusions. Conclusion Baseline MAFLD may be associated with an increased risk of new-onset T2DM within 5 years in a health check-up population, although these preliminary findings require confirmation in larger studies. Both lean and overweight/obese MAFLD subtypes showed associations with an elevated risk of T2DM in exploratory analyses, although the finding for lean MAFLD (based on only 15 individuals and 3 T2DM events) should be considered hypothesis-generating and preliminary and requires validation in larger cohorts. Early screening and lifestyle interventions for individuals with MAFLD are of paramount clinical importance for diabetes prevention.