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

doi:10.1111/dom.14101

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 journal › Article › peer-review

Abstract

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 language	English
Pages (from-to)	1808-1817
Number of pages	10
Journal	Diabetes, Obesity and Metabolism
Volume	22
Issue number	10
DOIs	https://doi.org/10.1111/dom.14101
Publication status	Published - 2 Jun 2020

Keywords

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

Access to Document

10.1111/dom.14101

Cite this

Ladwa, M., Bello, O., Hakim, O., Shojaee-Moradie, F., Boselli, L., Charles-Edwards, G., Stadler, M., Peacock, J. L., Umpleby, A. M., Amiel, S. A., Bonadonna, R. C., & Goff, L. M. (2020). Insulin clearance as the major player in the hyperinsulinaemia of black African men without diabetes. Diabetes, Obesity and Metabolism, 22(10), 1808-1817. https://doi.org/10.1111/dom.14101

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title = "Insulin clearance as the major player in the hyperinsulinaemia of black African men without diabetes",

abstract = "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.",

keywords = "African Americans, African Continental Ancestry Group, Diabetes Mellitus, Glucose Clamp Technique, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Male",

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

note = "{\textcopyright} 2020 John Wiley & Sons Ltd.",

year = "2020",

month = jun,

day = "2",

doi = "10.1111/dom.14101",

language = "English",

volume = "22",

pages = "1808--1817",

journal = "Diabetes, Obesity and Metabolism",

issn = "1463-1326",

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number = "10",

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TY - JOUR

T1 - Insulin clearance as the major player in the hyperinsulinaemia of black African men without diabetes

AU - Ladwa, Meera

AU - Bello, Oluwatoyosi

AU - Hakim, Olah

AU - Shojaee-Moradie, Fariba

AU - Boselli, Linda

AU - Charles-Edwards, Geoff

AU - Stadler, Marietta

AU - Peacock, Janet L

AU - Umpleby, Anne Margot

AU - Amiel, Stephanie A

AU - Bonadonna, Riccardo C

AU - Goff, Louise M

PY - 2020/6/2

Y1 - 2020/6/2

N2 - 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.

AB - 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.

KW - African Americans

KW - African Continental Ancestry Group

KW - Diabetes Mellitus

KW - Glucose Clamp Technique

KW - Humans

KW - Hyperinsulinism

KW - Insulin

KW - Insulin Resistance

KW - Male

U2 - 10.1111/dom.14101

DO - 10.1111/dom.14101

M3 - Article

C2 - 32488928

SN - 1463-1326

VL - 22

SP - 1808

EP - 1817

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 10

ER -