Abstract
Background: Although recent evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and an increased risk of diabetes, the association between lean NAFLD and incident diabetes is unclear. This study aimed to investigate whether lean NAFLD and overweight/obese NAFLD have similar or dissimilar effects on the risk of new-onset diabetes.Methods: A longitudinal study was performed in 14,482 euglycemic adults who participated in a health check-up program. Fatty liver was diagnosed by abdominal ultrasonography. The outcome of interest was incident diabetes.Cox proportional hazards regression models were applied to calculate HRs with 95% CIs for future diabetes risk.Results: During the median 6.0 years of follow-up, 356 cases of diabetes occurred. Despite a low probability of hepatic fibrosis indicated by the BAAT score, lean NAFLD was positively associated with an increased risk of diabetes. Moreover, after adjusting for sociodemographic and potential confounders, the fullyadjusted HRs (95% CIs) for incident diabetes between lean NAFLD and overweight/obese NAFLD to the reference (lean without NAFLD) were 2.58 (95% CI 1.68 to 3.97) and 2.52 (95% CI 1.79 to 3.55), respectively. In post hoc analysis, the HR (95% CI) for diabetes comparing lean NAFLD to obese/overweight NAFLD was 1.02 (95% CI 0.68 to 1.54, p = 0.909). The results were robust to challenges in multiple subgroup analyses and appeared to be more pronounced for female participants (p for interaction = 0.005).Conclusions: In this cohort study, lean patients with NAFLD had a risk of incident type 2 diabetes similar to that of overweight/obese ones with NAFLD. These findings suggest that lean NAFLD is not a benign condition. Further investigations are needed to gain a better understanding of the pathogenesis and natural history of NAFLD in lean subjects.
Increased risk of osteoporosis in patients with nonalcoholic fatty liver disease: A population-based retrospective cohort study
