Association of Hepatic Steatosis and Fibrosis Indices With Insulin Sensitivity and Inflammation in the POP-ABC Study.

Context: The cardiometabolic significance of subclinical liver fat in otherwise healthy individuals is unclear. Objective: This work aimed to evaluate the association of hepatic steatosis/fibrosis with cardiometabolic risk markers and incident prediabetes among healthy adults. Methods: This is a post hoc analysis of data from the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. The participants underwent assessments, including clinical examination, oral glucose tolerance test, insulin sensitivity, insulin secretion, plasma high-sensitivity C-reactive protein (hsCRP), and adiponectin levels, with the primary outcome of incident prediabetes during 5-year follow-up. Liver steatosis and fibrosis were assessed using the hepatic steatosis index (HSI) and the Fibrosis-4 (Fib-4) index, and participants were stratified by baseline quartiles (Q) of each index. Results: Among 343 (193 African American, 150 European American) participants (mean age 44.2 ± 10.6 years, body mass index 30.2 ± 7.28, fasting glucose 91.8 ± 6.80 mg/dL, and 2-hour glucose 125 ± 26.5 mg/dL), the mean baseline HSI was 39.7 ± 8.21 and Fib-4 index was 0.80 ± 0.41. Baseline HSI correlated with insulin sensitivity (r = -0.44; P < .0001), hsCRP (r = 0.37; P < .0001), and adiponectin (r = -0.24; P < .0001), as did Fib-4 index: insulin sensitivity (r = 0.14; P = .046), hsCRP (r = -0.17; P = .0021), adiponectin (r = -0.22; P < .0001). During 5 years of follow-up, prediabetes occurred in 16.2%, 21.6%, 31.5%, and 30.6% among participants in Q1 to Q4 of baseline HSI, respectively (log-rank P = .02). The prediabetes hazard ratio was 1.138 (95% CI, 1.027-1.261) for baseline HSI. Conclusion: Among initially normoglycemic individuals, hepatic steatosis predicted progression to prediabetes, probably via mechanisms that involve insulin resistance and inflammation.