Background: Associations of insulin resistance and glycemia with liver enzymes have not been well studied in a young, heterogeneous Hispanic/Latino population. We aimed to assess these associations, and to examine the role of endothelial dysfunction as a potential mediator.
Methods: We examined 1,275 participants aged 8-16 years from the Hispanic Community Children’s Health Study/Study of Latino Youth (SOL Youth) (2012-14). We examined the distribution of liver enzymes (alanine transaminase [ALT], aspartate transaminase [AST], and gamma-glutamyl transpeptidase [GGT]), the pediatric nonalcoholic fatty liver disease (NAFLD) fibrosis index (PNFI), glycemic markers (fasting glucose and hemoglobin A1c [HbA1c]), and insulin resistance (HOMA-IR) by age, sex, and body mass index (BMI). We assessed the adjusted cross-sectional associations of insulin resistance and hyperglycemia (as continuous variables) with elevated liver enzymes and PNFI (as binary variables) using Poisson regression to obtain prevalence ratios (PRs).
Results: Boys were more likely than girls to have elevated liver enzyme levels (15 vs 10%, 5 vs 2%, 26 vs 16%, and 12 vs 11% had elevated ALT, AST, GGT, and PNFI, respectively) and hyperglycemia (15 vs 6% and 9 vs 8% had elevated glucose and HbA1c), but less likely to be insulin resistant (47 vs 59%). Obese children (BMI≥95th percentile) were more likely to have higher liver enzyme levels, hyperglycemia, and insulin resistance than non-obese children. Only HOMA-IR was associated with elevated liver enzymes and PNFI in multivariable models (Figure). After additional adjustment for PAI-1, and e-selectin (markers of endothelial dysfunction), only the associations of HOMA-IR with GGT and PNFI remained statistically significant (PRs and 95% CIs: 1.43 [1.03, 1.98] and 1.85 [1.33, 2.56], respectively).
Conclusions: Among a large sample of Hispanic/Latino youths, insulin resistance was associated with NAFLD. It is possible that these associations are partially mediated by endothelial dysfunction.