Increased risk of type 2 diabetes in subjects with both elevated liver enzymes and ultrasonographically diagnosed nonalcoholic fatty liver disease: A 4-year longitudinal study

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is reported to contribute to the development of type 2 diabetes (T2DM). We aimed to compare the risk for development of T2DM among the four groups of NAFLD status divided by the combined assessment of liver enzyme and ultrasonographic steatosis in a retrospective cohort of Korean subjects. Methods: This study included 7,849 individuals without diabetes who underwent annual health check-ups for 5 consecutive years. Based on the presence or absence of fatty liver on ultrasound and serum alanine aminotransferase (ALT) values at baseline, subjects were classified into controls, an increased ALT group without steatosis, a steatosis group with normal ALT, and a group with both steatosis and elevated ALT (combined abnormality). Results: During a 4-year period, the incidence of diabetes was 3.5% in the control group, 4.6% in the increased ALT group, 7.3% in the steatosis group, and 11.8% in the combined abnormality group. The hazard ratio (HR) (95% confidence interval [CI]) of incident diabetes was increased in the elevated ALT group, the steatosis group, and the combined abnormality group in a stepwise fashion. Subjects with combined abnormality group had a significantly increased HR of 1.64 (1.27-2.13) even after multivariate adjustment. Conclusions: NAFLD subjects with both elevated ALT and ultrasonographic steatosis have significantly increased risk for future diabetes development.