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Submitted on May 10, 2006
Accepted on August 9, 2006
Department of Pediatrics, the General Clinical Research Center, and the Department of Diagnostic Radiologyof the Yale University School of Medicine
* To whom correspondence should be addressed. E-mail: sonia.caprio{at}yale.edu.
Background: Concurrent with the rise in obesity, NAFLD is recognized as the leading cause of serum aminotransferase elevations in obese youth. Nevertheless, the complete metabolic phenotype associated with abnormalities in biomarkers of liver injury and intrahepatic fat accumulation remains to be established.
Methods: In a multi-ethnic cohort of 392 obese adolescents, ALT levels were related with parameters of insulin sensitivity, glucose and lipid metabolism, as well as adipocytokines and biomarkers of inflammation. A subset of 72 adolescents had determination of abdominal fat partitioning and intra-hepatic fat accumulation using MRI.
Findings: Elevated ALT (> 35U/L) was found in 14% of adolescents, with a predominance of male gender and white/Hispanic race/ethnicity. After adjusting for potential confounders, rising ALT was associated with reduced insulin sensitivity and glucose tolerance, as well as rising free fatty acids and triglycerides. Worsening of glucose and lipid metabolism was already evident as ALT levels rose into the upper half of the normal range (18U/L-35U/L). When hepatic fat fraction (HFF) was assessed using fast-MRI, 32% of subjects had an increased HFF, which was associated with decreased insulin sensitivity and adiponectin, and increased triglycerides, visceral fat, and deep-to-superficial sc fat ratio. The prevalence of the metabolic syndrome was significantly greater in those with fatty liver.
Interpretation: Deterioration in glucose and lipid metabolism is associated even with modest ALT elevations. Hepatic fat accumulation in childhood obesity is strongly associated with the triad of insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence, hepatic steatosis may be a core feature of the metabolic syndrome.
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