Glucose dysregulation and hepatic steatosis in obese adolescents: is there a link?

Abstract

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 HMW-adiponectin 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.

Figure 1

Panel A. Prevalence of prediabetes in obese adolescents according to the degree of Liver Fat Content (%) measured by the fast-MRI. The prevalence rates of impaired glucose regulation (IFG, IGT, IFG/IGT) tended to rise across tertiles (p for trend = 0.07). Panel B. Prevalence rate of each component of the Metabolic Syndrome (Ford’s criteria) according to the degree of Liver Fat Content (%) measured by the fast-MRI. There were no differences in waist circumference (WC), Fasting Plasma Glucose (FPG) and Blood pressure (BP) across categories. The prevalence rates for Triglycerides (TG) and HDL (L-HDL) levels were significant differences between Low Liver Fat Content and the remaining groups (P=0.000). P values were adjusted for age, gender and race/ethnicity. White box= Low Liver Fat content Light Gray= Moderate Liver Fat Content Dark Gray= High Liver Fat Content

Figure 2

Panel A. Box-plot for Total Adiponectin according to the degree of Liver Fat Content (%) measured by fast-MRI. P = 0.001, adjusted for age, gender and race/ethnicity. Panel B. Box-plot for HMW-Adiponectin according to the degree of Liver Fat Content (%) measured by fast-MRI. P = 0.001, adjusted for age, gender and race/ethnicity. Panel C. Box-plot for IL-6 according to the degree of Liver Fat Content (%) measured by fast-MRI. P = 0.008, adjusted for age, gender and race/ethnicity.