Lean non-alcoholic fatty liver disease and risk of incident diabetes in a euglycaemic population undergoing health check-ups: A cohort study

Introduction: Convincing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and an increased risk of diabetes; however, the association between lean NAFLD and incident diabetes, and especially differences according to gender, have not been reported thus far. This study therefore aimed to investigate whether lean NAFLD and overweight/obese NAFLD confer the same excess risk of new-onset diabetes in both genders. Methods: Our longitudinal study was performed in 14,482 euglycaemic adults who had participated in a health checkup programme. Fatty liver was diagnosed by abdominal ultrasonography. The outcome of interest was incident diabetes. Results: Over the median 6.0 years of follow-up, 356 cases of diabetes were diagnosed. After adjusting for sociodemographic and other potential confounders, the fully adjusted HR (95% CI) for incident diabetes in lean NAFLD vs lean without NAFLD patients was 2.58 (95% CI: 1.68–3.97) in the total cohort. Corresponding HRs were 5.53 (95% CI: 2.30–13.30) and 2.02 (95% CI: 1.24–3.31) for women and men, respectively. Post-hoc analysis revealed that the relative risk for developing diabetes was similar between lean and overweight/obese NAFLD groups whether in the entire study population or in subgroups stratified by gender (all P > 0.05). Conclusion: Lean NAFLD is indeed a risk factor for incident type 2 diabetes in both genders, although the effect appeared to be more pronounced in women than in men. Further investigations are now needed to obtain a better understanding of the natural history of NAFLD in lean subjects.