Intrahepatic fat, irrespective of ethnicity, is associated with reduced endogenous insulin clearance and hepatic insulin resistance in obese youths: a cross-sectional and longitudinal study from the Yale Pediatric NAFLD cohort.

AIMS: Non-Alcoholic Fatty Liver Disease (NAFLD) has been associated with reduced endogenous insulin clearance (EIC) and hepatic insulin resistance (HIRI). These relationships, however, might be differentially affected by the ethnic background, as populations of African ancestry are typically featured with reduced intrahepatic fat content (HFF%) but impaired EIC. Therefore, we evaluated the influence of the ethnicity on the relationships between HFF%, EIC and HIRI.

METHODS: The HFF% was quantified by magnetic resonance imaging in a multi-ethnic cohort of 632 obese youths from 7 to 18 years of age at baseline and after a 2-year follow-up. Insulin secretion rate (ISR), EIC and HIRI were estimated by modeling glucose, insulin, and C-peptide data during 9-point oral glucose tolerance tests.

RESULTS: African American youths exhibited the lowest HFF% and a prevalence of NAFLD less than half of Caucasians and one-third of Hispanics. Furthermore, African Americans had lower EIC and glucose-stimulated ISR, despite similar HIRI and plasma insulin levels, compared with Caucasians and Hispanics. EIC and HIRI were markedly reduced in individuals with NAFLD and declined across group-specific HFF% tertiles in all ethnic groups. Consistently, the HFF% correlated with EIC and HIRI, irrespective of the ethnic background, after adjustment for age, sex, ethnicity, adiposity, waist-hip ratio, pubertal status, and plasma glucose levels. An increased HFF% at follow-up was associated with decreased EIC and increased HIRI across all groups.

CONCLUSIONS: Intrahepatic lipid accumulation is associated with reduced insulin clearance and hepatic insulin sensitivity in obese youths, irrespective of their ethnic background.