Fatty liver index and risk of type 2 diabetes of adults with normoglycemia: Insights into insulin sensitivity and beta-cell function.

The fatty liver index (FLI) is a simple tool used to assess metabolic dysfunction-associated fatty liver disease (MAFLD). Previous studies have shown the utility of the FLI as an early predictor of diabetes for patients with prediabetes. We evaluated whether the FLI could predict the development of type 2 diabetes mellitus (T2DM) with normal glucose tolerance (NGT) by performing a retrospective assessment of a community-based cohort over the course of 18 years. We analyzed data of 6,083 adults with NGT available from the Korean Genome and Epidemiology Study database. Participants were stratified into the following three groups based on the FLI: low, FLI < 30; intermediate, FLI 30-59; and high, FLI ≥ 60. Cox proportional hazards regression models evaluated the T2DM risk differences. Insulin sensitivity and secretion markers were compared using multivariate linear regression and an analysis of covariance. The predictability of the FLI for T2DM was analyzed by comparing the area under the receiver-operator characteristic (ROC) curve (AUC) values from the ROC analysis. The cumulative incidence of T2DM was 31.9% for the high FLI group; however, it was 11.3% for the low FLI group (log-rank test, P < 0.0001). For individuals with NGT, a high FLI was associated with an increased T2DM risk (hazard ratio [HR], 3.42; 95% confidence interval [CI], 2.91-4.00). After adjusting for insulin sensitivity and secretion markers, FLI remained an independent predictor of T2DM (HR, 1.96, 95% CI, 1.54-2.50). The homeostasis model assessment of insulin resistance results and composite insulin sensitivity index of the high FLI group were higher than those of the other groups (P < 0.0001). However, the disposition index and insulin secretion-sensitivity index-2 of the high FLI group were lower than those of the intermediate FLI group (P = 0.027 and P = 0.011, respectively). The ROC analysis confirmed that the FLI had the highest predictive ability for T2DM (AUC, 0.654; P < 0.05) development in individuals with NGT compared to other insulin sensitivity and secretion markers. The FLI is an early predictor of T2DM that reflects underlying insulin sensitivity and β-cell function. These findings underscore the role of liver steatosis in the early T2DM pathogenesis and highlight the need for early preventive lifestyle interventions among individuals with normoglycemia and high FLI values.