Fatty liver is increasingly common in obese adolescents. We determined its association with glucose dysregulation in 118 (37M/81F) obese adolescents of similar age and percent total fat. Fast-magnetic resonance imaging (MRI) and simple MRI were used to quantify hepatic fat content and abdominal fat distribution. All subjects had a standard oral glucose tolerance test. Insulin sensitivity was estimated by the Matsuda Index and homeostasis model assessment of insulin resistance. Baseline total and high molecular weight (HMW)-adiponectin and interleukin (IL)-6 levels were measured. The cohort was stratified according to tertiles of hepatic fat content. Whereas age and %fat were comparable across tertiles, ethnicity differed in that fewer Blacks and more Whites and Hispanics were in the moderate and high category of hepatic fat fraction (HFF). Visceral and the visceral-to-subcutaneous fat ratio increased and insulin sensitivity decreased across tertiles. Two-hour plasma glucose rose with increasing hepatic steatosis (P < 0.008). 73.7% of the subjects in the high HFF had the metabolic syndrome compared to 19.5% and 30.6%, respectively, in the low and moderate categories. Both total and HMWadiponectin decreased, and IL-6 increased with increasing hepatic steatosis. Conclusion: In obese adolescents, independent of total fat, increasing severity of fatty liver is associated with glucose dysregulation, metabolic syndrome, and with a proinflammatory milieu. (HEPATOLOGY 2009;49: 1896-1903.) E ctopic fat deposition in insulin-sensitive tissues such as liver and muscle strongly correlates with insulin resistance. 1 Previously, we reported that increased intramyocellular fat in obese adolescents was associated with impaired glucose intolerance and insulin resistance. 2 Furthermore, moderate elevation in alanine aminotransferase (ALT) levels, a poor surrogate of fatty liver, was found to be associated with high-normal glucose levels, 3 whereas abnormal ALT levels were reported in youngsters with type 2 diabetes (T2DM), 4 raising the question of a potential role of fatty liver in the onset of T2DM in obese youth. Fatty liver in obese adolescents is becoming increasingly common. [5][6][7] Nevertheless, its role in the dysregulation of glucose metabolism is unclear. We hypothesize that, independent of overall obesity, the severity of hepatic steatosis will strongly affect the presence of prediabetes and diabetes in obese adolescents. Furthermore, we determined if the balance between antiinflammatory markers such as total and high molecular weight (HMW) adiponectin and proinflammatory markers like interleukin-6 (IL-6) would vary as a function of the degree of hepatic steatosis. Using fast-magnetic resonance imaging (MRI) we quantified intrahepatic fat content in a large multiethnic group of obese adolescents matched for age and overall adiposity.
Subjects and Methods
The Cohort. In all, 118 obese adolescents, 13 to 16 years old with a body mass index (BMI)-z score ranging