Nearly one in three children with nonalcoholic fatty liver disease have abnormal glucose metabolism, and this co-morbidity is also associated with a greater risk of nonalcoholic steatohepatitis, according to a cross-sectional study published online Aug. 1 in JAMA Pediatrics.
The study used data from 675 children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) who were enrolled in the NASH Clinical Research Network. The mean age of the children was 12.6 years, and they had a mean BMI of 32.5. Most of the children in the study were boys and Hispanic.
Overall, 23.4% of study participants had prediabetes and 6.5% met the clinical criteria for type 2 diabetes. However, girls with NAFLD had a 60% greater risk of prediabetes and a fivefold greater risk of type 2 diabetes than boys, even after controlling for BMI and waist circumference (JAMA Pediatr. 2016 Aug 1. doi: 10.1001/jamapediatrics.2016.1971), reported Dr. Kimberly P. Newton and her coauthors.
The researchers also noted a significant association between nonalcoholic steatohepatitis (NASH) and glucose metabolism. Individuals with type 2 diabetes were three times more likely to also have NASH, while those with prediabetes had a 90% higher incidence of NASH, compared with individuals with normal glucose metabolism. They also found that those with NASH had significantly higher mean fasting glucose and insulin concentrations than children without NASH.
Dr. Newton, of the University of California, San Diego, and her coauthors wrote that while abnormal glucose metabolism is known to be common in adults with NAFLD, and that type diabetes is a risk factor for progression to NASH and liver-related mortality, the association in children with NAFLD is less well understood.
“Among our cohort, the prevalence of children with type 2 diabetes was much higher than would be expected based on contributions from obesity alone,” they wrote. “Although systemic insulin resistance is believed be important in the pathogenesis of both pediatric NAFLD and type 2 diabetes, to our knowledge, there are no longitudinal studies that evaluate the cause-effect relationship between these two associated conditions.”
The authors drew particular attention to the threefold higher odds of NASH in children with NAFLD and type 2 diabetes, pointing out that while the prognostic implications of NASH in childhood are not fully known, the NASH phenotype is associated with a “substantially” greater risk of cirrhosis. This risk is likely to be compounded by the presence of type 2 diabetes.
“Our study advances the literature by showing that as early as childhood, prediabetes and type 2 diabetes emerge as clear risk factors for NASH with potential downstream implications for future morbidity and mortality.”
Commenting on the greater incidence of prediabetes and type 2 diabetes among girls with NAFLD, the authors said this had been observed in other studies and that sex differences represented a major unmet research need.
The Nonalcoholic Steatohepatitis Clinical Research Network is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was received from the National Center for Advancing Translational Sciences. The researchers reported no conflicts of interest.
