Background: Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) represents a major risk factor for insulin resistance and type 2 diabetes in adolescents.
Methods: To characterize the clinical and genetic features associated with the development of pediatric NAFLD, 503 obese adolescents (191 Caucasians, 134 African Americans, and 178 Hispanics) underwent a MRI to quantify hepatic fat content, an oral glucose tolerance test to assess glucose tolerance and insulin sensitivity, and the genotyping of three SNPs associated with NAFLD (PNPLA3 rs738409, GCKR rs1260326, and TM6SF2 rs58542926). MRI and metabolic assessments were repeated in 133 patients after 2.27±1.44 years.
Results: The prevalence of NAFLD was 42.9% in Caucasians, 15.7% in African Americans, and 59.6% in Hispanics (p<0.0001). Compared to Caucasians and Hispanics with NAFLD, African Americans adolescents with NAFLD had higher fasting glucose (p=0.03), insulin (p=0.0004), C-peptide (p=0.04), 2-h-glucose (p=0.04), HbA1c (p<0.0001), and lower insulin sensitivity (p=0.03), despite similar age (p=0.34) and gender distribution (p=0.37). This translated in a higher prevalence of prediabetes and type 2 diabetes in African Americans (66.6%) compared to Caucasians (24.4%) and Hispanics (31.1%) with NAFLD (p=0.0003). Analysis of the patients without NAFLD at baseline showed that ethnicity (p=0.02), high C-peptide levels (p=0.0006), changes in z-score BMI over time (p=0.0006) and common gene variants were strong predictors of NAFLD development at follow-up (AUROC curve 0.976).
Conclusions: African American obese adolescents are relatively protected from NAFLD, but are more susceptible to the deleterious effects of NAFLD on glucose metabolism. The combination of ethnicity, markers of insulin resistance and genetic factors are strong predictors of pediatric NAFLD.
D. Trico: None. S. Caprio: None. G.R. Umano: None. A. Galderisi: None. M.M. Mata: None. J. Nouws: None. B. Pierpont: None. G. Kim: None. N. Santoro: None.