Endocrine Abstracts

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease in Western countries and identifies people at high risk to develop metabolic and cardiovascular disease. Fatty liver has been associated with reduced endogenous insulin clearance (EIC) and hepatic insulin resistance (HIRI), which are early features of type 2 diabetes. These relationships however might be differentially affected by the ethnic background, as populations of African ancestry typically have reduced intrahepatic fat content (HFF%) associated with impaired insulin clearance and sensitivity. Therefore, the aim of this study was to evaluatethe impact of the ethnicity on the relationships between HFF%, EIC and HIRI.

Methods: We analyzed cross-sectional and longitudinal data from the Yale Pediatric NAFLD cohort, a large (n = 620) and well characterized cohort of overweight and obese adolescents from the three most prevalent racial and ethnic groups in the United States. The HFF% was quantified by a validated magnetic resonance imaging (MRI) method at baseline and after a median follow up of 2 years. Insulin secretion rate (ISR), EIC and HIRI were assessed during 3-hour, 9-point oral glucose tolerance tests (OGTTs) by modeling glucose, insulin, and C-peptide data.

Results: African Americans (n = 172) exhibited the lowest HFF% and a prevalence of NAFLD less than half of Caucasians (n = 229) and one third of Hispanics (n = 231). Furthermore, African Americans had lower EIC and glucose-stimulated ISR, but similar HIRI and plasma insulin levels, compared with other ethnic groups. The HFF% correlated with EIC (std. β = −0.13, P = 0.0003) and HIRI (std. β = 0.17, P < 0.0001), irrespective of the ethnic background, after adjustment for age, sex, ethnicity, BMI z-score, pubertal status, and plasma glucose levels. African Americans showed a lower susceptibility to intrahepatic fat accumulation at follow up, with a two-fold higher (52%) prevalence of adolescents whose HFF% remained stable (change < ± 1%) compared with Caucasians (28%) and Hispanics (20%) (P = 0.036). Nevertheless, changes in HFF% over timewere associated with changes in EIC (r = −0.25, P = 0.02) and HIRI (r = 0.22, P = 0.04) across all groups, without ethnic differences.

Conclusions: This study demonstrates that intrahepatic fat accumulation is associated with reduced EIC and HIRI in obese youths, irrespective of their ethnic background. Our data dissect the metabolic characteristics of populations of African ancestry and provide novel evidence about the pathogenetic role of liver steatosis in the development of hepatic metabolic abnormalities associated with type 2 diabetes progression.