Ethnic differences in beta cell function and pancreatic fat in Black African and White European men across a spectrum of glucose tolerance

TY - JOUR

T1 - Ethnic differences in beta cell function and pancreatic fat in Black African and White European men across a spectrum of glucose tolerance

AU - Whelehan, Gráinne

AU - Hakim, Olah

AU - Ladwa, Meera

AU - Bello, Oluwatoyosi

AU - Bodicoat, Danielle H

AU - Umpleby, A Margot

AU - Amiel, Stephanie A

AU - Goff, Louise M

PY - 2025/8/6

Y1 - 2025/8/6

N2 - People of Black African (BA) ancestry are disproportionately affected by type 2 diabetes when compared with people of White European (WE) descent, despite lower levels of ectopic fat. Impaired beta cell function is a key pathophysiological feature of type 2 diabetes. It remains to be determined whether an associative relationship exists between intrapancreatic lipid (IPL) accumulation and beta cell function, and whether this differs by ethnicity. Fifty-three BA (23 normal glucose tolerance, 11 impaired glucose tolerance and 19 type 2 diabetes) and 51 WE (23/13/15) men underwent a hyperglycaemic clamp and mixed-meal tolerance test to assess insulin secretion and beta cell function, a hyperinsulinaemic-euglycaemic clamp to measure insulin sensitivity and Dixon MRI to determine IPL. Associations between IPL and beta cell function were assessed using linear regression. IPL was lower in BA compared with WE men (mean ± SD; 7.6 ± 2.6% vs 8.8 ± 3.7%, p=0.038), but after adjustment for waist circumference this ethnic difference no longer occurred (p=0.278). BA men with type 2 diabetes had lower total insulin secretion response to the mixed-meal (p=0.001) and hyperglycaemic clamp (p=0.002), but no ethnic differences were observed in the disposition index within glucose tolerance groups. IPL was inversely associated with beta cell function in the WE but not the BA men, but after adjustment for confounders these associations were not significant. Ethnic differences were apparent as beta cell function was inversely associated with IPL in the WE, but not BA, men. However, in both ethnic groups, this relationship appears secondary to other factors, such as adiposity, in the pathogenesis of type 2 diabetes. [Abstract copyright: © 2025. The Author(s).]

AB - People of Black African (BA) ancestry are disproportionately affected by type 2 diabetes when compared with people of White European (WE) descent, despite lower levels of ectopic fat. Impaired beta cell function is a key pathophysiological feature of type 2 diabetes. It remains to be determined whether an associative relationship exists between intrapancreatic lipid (IPL) accumulation and beta cell function, and whether this differs by ethnicity. Fifty-three BA (23 normal glucose tolerance, 11 impaired glucose tolerance and 19 type 2 diabetes) and 51 WE (23/13/15) men underwent a hyperglycaemic clamp and mixed-meal tolerance test to assess insulin secretion and beta cell function, a hyperinsulinaemic-euglycaemic clamp to measure insulin sensitivity and Dixon MRI to determine IPL. Associations between IPL and beta cell function were assessed using linear regression. IPL was lower in BA compared with WE men (mean ± SD; 7.6 ± 2.6% vs 8.8 ± 3.7%, p=0.038), but after adjustment for waist circumference this ethnic difference no longer occurred (p=0.278). BA men with type 2 diabetes had lower total insulin secretion response to the mixed-meal (p=0.001) and hyperglycaemic clamp (p=0.002), but no ethnic differences were observed in the disposition index within glucose tolerance groups. IPL was inversely associated with beta cell function in the WE but not the BA men, but after adjustment for confounders these associations were not significant. Ethnic differences were apparent as beta cell function was inversely associated with IPL in the WE, but not BA, men. However, in both ethnic groups, this relationship appears secondary to other factors, such as adiposity, in the pathogenesis of type 2 diabetes. [Abstract copyright: © 2025. The Author(s).]

KW - Insulin secretion

KW - Acute insulin response

KW - Beta cell function

KW - Ethnic differences

U2 - 10.1007/s00125-025-06514-3

DO - 10.1007/s00125-025-06514-3

M3 - Article

C2 - 40768046

SN - 0012-186X

JO - Diabetologia

JF - Diabetologia

ER -