Exploring the determinants of ethnic differences in insulin clearance between men of Black African and White European ethnicity

TY - JOUR

T1 - Exploring the determinants of ethnic differences in insulin clearance between men of Black African and White European ethnicity

AU - Ladwa, Meera

AU - Bello, Oluwatoyosi

AU - Hakim, Olah

AU - Boselli, Maria Linda

AU - Shojaee-Moradie, Fariba

AU - Umpleby, A. Margot

AU - Peacock, Janet

AU - Amiel, Stephanie A.

AU - Bonadonna, Riccardo C.

AU - Goff, Louise M.

N1 - Funding Information: This research was funded by Diabetes UK, Grant Numbers 12/0004473 and 14/0004967. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Funding Information: LMG, SAA, AMU and JLP were involved in conceptualisation; LMG, SAA, AMU, JLP and RCB were involved in methodology; ML, OB, OH, MLB and FSM were involved in formal analysis; ML, OB, OH and FSM were involved in investigation; ML was involved in writing—original draft preparation; all authors were involved in writing—review and editing; LMG, SAA, AMU, RCB and MLB were involved in supervision; and LMG, SAA, AMU and JLP were involved in funding acquisition. All authors have read and agreed to the published version of the manuscript. JLP was supported by the NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and is an NIHR Senior Investigator. Publisher Copyright: © 2021, The Author(s).

PY - 2021/10/18

Y1 - 2021/10/18

N2 - Aim: People of Black African ancestry, who are known to be at disproportionately high risk of type 2 diabetes (T2D), typically exhibit lower hepatic insulin clearance compared with White Europeans. However, the mechanisms underlying this metabolic characteristic are poorly understood. We explored whether low insulin clearance in Black African (BA) men could be explained by insulin resistance, subclinical inflammation or adiponectin concentrations. Methods: BA and White European (WE) men, categorised as either normal glucose tolerant (NGT) or with T2D, were recruited to undergo the following: a mixed meal tolerance test with C-peptide modelling to determine endogenous insulin clearance; fasting serum adiponectin and cytokine profiles; a hyperinsulinaemic–euglycaemic clamp to measure whole-body insulin sensitivity; and magnetic resonance imaging to quantify visceral adipose tissue. Results: Forty BA (20 NGT and 20 T2D) and 41 WE (23 NGT and 18 T2D) men were studied. BA men had significantly lower insulin clearance (P = 0.011) and lower plasma adiponectin (P = 0.031) compared with WE men. In multiple regression analysis, ethnicity, insulin sensitivity and plasma adiponectin were independent predictors of insulin clearance, while age, visceral adiposity and tumour necrosis factor alpha (TNF-α) did not significantly contribute to the variation. Conclusion: These data suggest that adiponectin may play a direct role in the upregulation of insulin clearance beyond its insulin-sensitising properties.

AB - Aim: People of Black African ancestry, who are known to be at disproportionately high risk of type 2 diabetes (T2D), typically exhibit lower hepatic insulin clearance compared with White Europeans. However, the mechanisms underlying this metabolic characteristic are poorly understood. We explored whether low insulin clearance in Black African (BA) men could be explained by insulin resistance, subclinical inflammation or adiponectin concentrations. Methods: BA and White European (WE) men, categorised as either normal glucose tolerant (NGT) or with T2D, were recruited to undergo the following: a mixed meal tolerance test with C-peptide modelling to determine endogenous insulin clearance; fasting serum adiponectin and cytokine profiles; a hyperinsulinaemic–euglycaemic clamp to measure whole-body insulin sensitivity; and magnetic resonance imaging to quantify visceral adipose tissue. Results: Forty BA (20 NGT and 20 T2D) and 41 WE (23 NGT and 18 T2D) men were studied. BA men had significantly lower insulin clearance (P = 0.011) and lower plasma adiponectin (P = 0.031) compared with WE men. In multiple regression analysis, ethnicity, insulin sensitivity and plasma adiponectin were independent predictors of insulin clearance, while age, visceral adiposity and tumour necrosis factor alpha (TNF-α) did not significantly contribute to the variation. Conclusion: These data suggest that adiponectin may play a direct role in the upregulation of insulin clearance beyond its insulin-sensitising properties.

KW - Adiponectin

KW - African

KW - Ethnicity

KW - Inflammation

KW - Insulin clearance

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85117257286&partnerID=8YFLogxK

U2 - 10.1007/s00592-021-01809-4

DO - 10.1007/s00592-021-01809-4

M3 - Article

AN - SCOPUS:85117257286

SN - 0940-5429

VL - 59

JO - Acta Diabetologica

JF - Acta Diabetologica

IS - 3

ER -