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

Meera Ladwa, Oluwatoyosi Bello, Olah Hakim, Fariba Shojaee-Moradie, Linda Boselli, Geoff Charles-Edwards, Marietta Stadler, Janet L Peacock, Anne Margot Umpleby, Stephanie A Amiel, Riccardo C Bonadonna, Louise M Goff

Research output: Contribution to journalArticlepeer-review


AIM: To investigate relationships between insulin clearance, insulin secretion, hepatic fat accumulation and insulin sensitivity in black African (BA) and white European (WE) men.

METHODS: Twenty-three BA and twenty-three 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] × 103 vs. 29.9 [23.3, 38.4] × 103 pmol L-1  × min, P = .017) and lower endogeneous insulin clearance (771.6 [227.8] vs. 1381 [534.3] mL m-2 body surface area min -1 , P < .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 = .001) and inversely correlated with IHL (r = -0.674, P = .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.

Original languageEnglish
Pages (from-to)1808-1817
Number of pages10
JournalDiabetes, Obesity and Metabolism
Issue number10
Publication statusPublished - 2 Jun 2020


  • African Americans
  • African Continental Ancestry Group
  • Diabetes Mellitus
  • Glucose Clamp Technique
  • Humans
  • Hyperinsulinism
  • Insulin
  • Insulin Resistance
  • Male

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