Nonalcoholic fatty liver disease (NAFLD) is prevalent in people with type 2 diabetes (T2D) . Here, we evaluated the association of NAFLD (assessed by HSI and Fib-4 score) with prediabetes risk and related mechanisms in healthy, normoglycemic (NGT) White and Black offspring of parents with T2D enrolled in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. The primary outcome of POP-ABC was progression from NGT to prediabetes during ∼5-yr followup. Baseline assessments included clinical exam, OGTT, LFTs, hsCRP and adiponectin levels. Assessments during year 1 included insulin sensitivity (ISI, euglycemic clamp) and insulin secretion (AIR) . Baseline HSI ([8 × ALT/AST] + BMI + [2 if female]) and FIB-4 score ([age × AST]/[platelets count × √ALT]) values were used to stratify the cohort by quartiles (Q1 to Q4) .
The cohort (N 376; 159 White, 217 Black) mean age at baseline was 44.2 ± 10.6 yr, BMI 30.2 ± 7.23 kg/m2, with 343 (91%) evaluable subjects. The baseline fasting glucose was 90.9 ± 7.70 mg/dl and 2-hr glucose was 125 ± 26.5 mg/dl. During 5 years of followup, prediabetes occurred in 16.2, 21.6, 31.5 and 30.6% among participants in Q1 to Q4 of baseline HSI, respectively. Kaplan-Meier analysis showed higher probability of prediabetes with increasing baseline HSI (P=0.02) . Fib-4 scores were uncoupled from prediabetes rates. HSI correlated robustly with ISI (r=−0.438, P <0.0001) ; FIB-4 correlated weakly with ISI (r=0.14, P= 0.0459) , and both showed weak correlation with AIR that was insignificant after controlling for ISI. HSI (r=0.456, P <0.0001) and Fib-4 (r=0.164, P=0.0032) associated directly with hsCRP and inversely with adiponectin (HSI: r=−0.235, P <0.0001; Fib-4: r=−0.156, P=0.0051) . Hepatic steatosis increases incident prediabetes risk via mechanisms that involve insulin resistance and inflammation.
B.Colon barreto: None. S.Ebenibo: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi.
American Diabetes Association (7-07-MN-13) ; National Institutes of Health (R01 DK067269)