Recent studies showed that hepatic insulin clearance is lower in African Americans (AA) than European Americans (EA). The aim of this work is to elucidate the possible genetic/epigenetic versus lifestyle causes. The frequently-sampled intravenous glucose tolerance test (FSIGT) was performed in 142 children [38 AA, 69 EA, 28 HA (Hispanic Americans), both sexes, age 7-13 years, mean BMI = 19 kg/m2, basal plasma glucose = 99 mg/dL, insulin = 78 pmol/L, C-peptide = 511 pmol/L]. Mathematical modeling provided hepatic (FEL) and extra-hepatic (CLP) insulin clearance values. Two-way analysis of covariance was done (groups: sex and ethnicity, covariates: age, Tanner stage and body fat from DXA). Data are mean (standard error). FEL was lower in AA than EA (18% (2%) vs. 31% (3%), p=0.001), but no difference was observed in HA. CLP was not different among ethnicities. Partial correlation was calculated between FEL, CLP and 1) diet composition (energy intake, % of calories from carbohydrate, fat, protein), 2) physical activity (PA: light, moderate, hard, very hard), 3) admixture scores (African, European, Amerindian). FEL was positively correlated with the European admixture score (r=0.3, p<0.01), and negatively with the African one (r=-0.3, p=0.001); FEL was negatively associated with moderate PA in all the subjects (r=-0.2, p=0.01), and with hard PA in EA (r=-0.4, p<0.01). CLP was positively correlated with moderate PA in AA (r=0.4, p=0.02). Concerning diet, FEL was only correlated with % of calories from fat in EA (r=0.3, p=0.01). Because of its negative association with the African admixture, but positive with the European one, the lower hepatic insulin clearance might be genetic in origin, possibly resulting in hyperinsulinemia and diabetes risk. Our data also suggest that detrimental effects of lower insulin clearance might be mitigated by lifestyle changes such as exercise: moderate PA in AA could lead to a normalization of insulinemia by increasing extra-hepatic insulin clearance.
F. Piccinini: None. B. Gower: None. J.R. Fernandez: None. R.N. Bergman: Consultant; Self; Zafgen, Inc.
National Institute of Diabetes and Digestive and Kidney Diseases (DK067426); Nutrition Obesity Research Center (DK56336); National Institutes of Health (M01RR00032)