Cohort Study of Non-alcoholic Fatty Liver Disease, NAFLD fibrosis score, and the Risk of Incident Diabetes in a Korean population

OBJECTIVES: No study has evaluated an association between non-alcoholic fatty liver disease (NAFLD) severity and the incidence of diabetes. We examined whether NAFLD and its severity-using the NAFLD fibrosis score (NFS)-predict the development of diabetes. METHODS: A cross-sectional study was performed in 43,166 apparently healthy Koreans aged 30-59 years, who underwent a health checkup in 2005 and 2006. Of these, 38,291 subjects without diabetes were followed annually or biennially until December 2011 for the cohort study. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or other identifiable causes. The NFS was used to categorize the severity of fibrosis. Diabetes was defined as fasting serum glucose >= 126 mg/dl, glycated hemoglobin (HbA1c) >= 6.5%, or medication use for diabetes. RESULTS: During 175,996 person-years of follow-up, 2,025 participants developed diabetes. An increase across NAFLD categories was positively associated with an increased risk of diabetes in both the cross-sectional and cohort studies in a dose-response manner (P-trend <0.001). In multivariate-adjusted models, the hazard ratios (95% confidence intervals) for diabetes comparing NAFLD with low NFS and NAFLD with intermediate or high NFS vs. no NAFLD were 2.00 (1.79-2.24) and 4.74 (3.67-6.13), respectively. This association remained significant even in subjects with fasting glucose <100 mg/dl and subjects with HbA1c <5.8%. CONCLUSIONS: In this cohort study of a healthy Korean population, NAFLD and its severity using NFS were independently and strongly associated with increased incidence of diabetes in men and women-even with a euglycemic range of glucose and HbA1c.