Insulin clearance as the major player in the hyperinsulinaemia of black African men without diabetes.

AIMS Despite their low levels of ectopic fat accumulation, populations of African ancestry exhibit hyperinsulinaemia and increased metabolic risk. We aimed to investigate relationships between insulin clearance, insulin secretion, hepatic fat accumulation and insulin sensitivity in black African (BA) and white European (WE) men. METHODS 23 BA and 23 WE men with normal glucose tolerance, matched for age and body mass index, underwent a hyperglycaemic clamp to measure insulin secretion and clearance; hyperinsulinaemic-euglycaemic clamp with stable glucose isotope infusion to measure whole-body and hepatic-specific insulin sensitivity; and magnetic resonance imaging to quantify intrahepatic lipid (IHL) RESULTS: BA men had higher glucose-stimulated peripheral insulin levels (48.1 (35.5, 65.2) x 103 vs 29.9 (23.3, 38.4) x103 pmol L-1 x min, p = 0.017) and lower endogeneous insulin clearance (771.6 (227.8) vs 1381 (534.3) mL m-2 BSA min -1 , p < 0.001) compared with WE men. There were no ethnic differences in beta cell insulin secretion or beta cell responsivity to glucose, even after adjustment for prevailing insulin sensitivity. In WE men, endogenous insulin clearance was correlated with whole-body insulin sensitivity (r = 0.691, p = 0.001) and inversely correlated with IHL (r = -0.674, p = 0.001). These associations were not found in BA men. CONCLUSIONS While normally glucose tolerant BA men have similar insulin secretory responses to their WE counterparts, they have markedly lower insulin clearance, which does not appear to be explained by either insulin resistance or hepatic fat accumulation. Low insulin clearance may be the primary mechanism of hyperinsulinaemia in populations of African origin. This article is protected by copyright. All rights reserved.