Hepatic Steatosis and High-Normal Fasting Glucose as Risk Factors for Incident Prediabetes

CONTEXT: The role of hepatic steatosis (HS) in the initial stages of developing type 2 diabetes remains unclear. OBJECTIVE: We aimed to clarify the impact of HS indexed by Fatty Liver Index (FLI) and high-normal fasting plasma glucose (FPG) as risk factors for incident prediabetes in a nonobese cohort. METHODS: Data from 1125 participants with ADA-defined normal glucose metabolism (median age 52 years; BMI 23.1 kg/m(2)) were used for retrospective analysis. In the entire population, correlation between normal FPG and FLI was evaluated by multiple regression adjusted for age and sex. Follow-up data from 599 participants in whom 75-g OGTT was repeated 3.7 years later showed that 169 developed prediabetes. This was analyzed by the multivariate Cox proportional hazards model. RESULTS: In the entire population, FLI was positively correlated with FPG (P < 0.01): mean FLI increased from 15.8 at FPG 4.2 mmol/L to 31.6 at FPG 5.5 mmol/L. Analysis of the 599 participants (2061 person-years) by Cox model, adjusted for sex, age, family history of diabetes, ISI(MATSUDA), and Stumvoll-1, clarified an increased risk of prediabetes with high-normal FPG and FLI. Risk was increased 2.2 times with FLI ≥ 16.5 vs FLI < 16.5, P < 0.001, and increased 2.1 times in participants with FPG ≥ 5.3 mmol/L, P < 0.001. Cutoff values (unadjusted) were obtained by ROC at the point of the largest Youden’s index using the entire range of the variables. CONCLUSION: Even among nonobese individuals, HS indexed by FLI and a high-normal FPG (≥ 5.3 mmol/L) are risk factors for prediabetes, independently from insulin.