Alanine Aminotransferase Levels and Fatty Liver in Childhood Obesity: Associations with Insulin Resistance, Adiponectin, and Visceral Fat
Tania S. Burgert,
Sara E. Taksali,
James Dziura,
T. Robin Goodman,
Catherine W. Yeckel,
Xenophon Papademetris,
R. Todd Constable,
Ram Weiss,
William V. Tamborlane,
Mary Savoye,
Aisha A. Seyal and
Sonia Caprio
Departments of Pediatrics (T.S.B., S.E.T., C.W.Y., R.W., W.V.T., M.S., A.A.S., S.C.) and Diagnostic Radiology (T.R.G., X.P., R.T.C.), and the General Clinical Research Center (J.D.), Yale University School of Medicine, New Haven, Connecticut 06520
Address all correspondence and requests for reprints to: Dr. Sonia Caprio, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208064, New Haven, Connecticut 06520. E-mail: sonia.caprio{at}yale.edu.
Background: Concurrent with the rise in obesity, nonalcoholicfatty liver disease is recognized as the leading cause of serumaminotransferase elevations in obese youth. Nevertheless, thecomplete metabolic phenotype associated with abnormalities inbiomarkers of liver injury and intrahepatic fat accumulationremains to be established.
Methods: In a multiethnic cohort of 392 obese adolescents, alanineaminotransferase (ALT) levels were related with parameters ofinsulin sensitivity, glucose, and lipid metabolism as well asadipocytokines and biomarkers of inflammation. A subset of 72adolescents had determination of abdominal fat partitioningand intrahepatic fat accumulation using magnetic resonance imaging.
Findings: Elevated ALT (>35 U/liter) was found in 14% ofadolescents, with a predominance of male gender and white/Hispanicrace/ethnicity. After adjusting for potential confounders, risingALT was associated with reduced insulin sensitivity and glucosetolerance as well as rising free fatty acids and triglycerides.Worsening of glucose and lipid metabolism was already evidentas ALT levels rose into the upper half of the normal range (18–35U/liter). When hepatic fat fraction was assessed using fastmagnetic resonance imaging, 32% of subjects had an increasedhepatic fat fraction, which was associated with decreased insulinsensitivity and adiponectin, and increased triglycerides, visceralfat, and deep to superficial sc fat ratio. The prevalence ofthe metabolic syndrome was significantly greater in those withfatty liver.
Interpretation: Deterioration in glucose and lipid metabolismis associated even with modest ALT elevations. Hepatic fat accumulationin childhood obesity is strongly associated with the triad ofinsulin resistance, increased visceral fat, and hypoadiponectinemia.Hence, hepatic steatosis may be a core feature of the metabolicsyndrome.
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