ORLANDO – according to a review of 503 adolescents at the Yale University pediatric obesity clinic in New Haven, Conn.
As childhood obesity rates have climbed – the prevalence is now estimated to be around 20% – there’s been a corresponding increase in pediatric NAFLD, but it’s not very well characterized in children, and “there are many gaps in our knowledge,” said Nicola Santoro, MD, PhD, an assistant professor of pediatric endocrinology at Yale, and senior author of.
The goal of the work was to begin to plug the gaps. The children had baseline abdominal MRIs to quantify their hepatic fat content, along with oral glucose tolerance tests and genotyping for three single nucleotide polymorphisms (SNPs) strongly associated with the condition (PNPLA3 rs738409, GCKR rs1260326, and TM6SF2 rs58542926). MRI and metabolic testing were repeated at a mean of 2.27 years in 133 children.
The subjects were 13 years old on average, with a mean body mass index z-score of 2.52; 191 were white, 134 black, and 178 Hispanic. NAFLD was defined as a hepatic fat content of at least 5.5%.
The prevalence of fatty liver was 41.6% but ranged widely by ethnicity, with NAFLD diagnosed in 60% of Hispanic, 43% of white, but only 16% of black children. Among all three groups, prevalence was higher among boys.
Although NAFLD was least common among black children, when it was present, it was worse. Black children with NAFLD, compared with others, had the highest fasting glucose and 2-hour glucose levels; the highest insulin and C-peptide levels, and the highest hemoglobin A1c, despite similar age and gender distribution across the groups.
The findings translated to a higher prevalence of prediabetes and type 2 diabetes mellitus (66.6%), compared with white (24.4%) and Hispanic children (31.1%) with NAFLD.
Among 76 children who didn’t have NAFLD at baseline, 17 were diagnosed with the condition at follow-up. Progressors, compared with nonprogressors, showed higher baseline C-peptide levels (about 1,250 pmol/L versus 1,000 pmol/L) and greater weight gain (increase, versus a loss of, about 0.1 point on body mass index z-scores). Black children were the least likely to progress to NAFLD.
Increasing BMI z-score, higher baseline fasting C-peptide levels, and nonblack race strongly predicted progression (area under the curve = 0.887). The risk of progression was even higher when a NAFLD SNP was on board (AUC equal to or greater than 0.96).
Of 57 children with NAFLD at baseline, 13 didn’t meet the definition at follow-up, but regression turned out to be harder to predict. Regressors showed lower intrahepatic fat fractions at baseline (about 10% versus 20%), and a lowering of BMI z-scores at follow-up. Adding SNPs didn’t improve the model (AUC = 0.756).