Abstract
AimPeople 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.MethodsBA 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.ResultsForty 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.ConclusionThese data suggest that adiponectin may play a direct role in the upregulation of insulin clearance beyond its insulin-sensitising properties.
Highlights
A consistently recognised feature of physiology in Black African (BA) populations is low insulin clearance in comparison with White Europeans (WE), with studies indicating up to 74% lower insulin clearance in BA compared with WE1 3 Vol.:(0123456789)Acta Diabetologica subjects [1]
As there is evidence that BA populations may be more insulin resistant compared with other ethnicities [6], it is believed that impaired insulin sensitivity drives their low insulin clearance [7]
The SouL-DeEP study was an observational cross-sectional study aimed at exploring ethnic differences in a range of mechanisms underlying the development of type 2 diabetes (T2D) between men of WE and BA ethnicity with normal glucose tolerant (NGT) and early T2D
Summary
A consistently recognised feature of physiology in Black African (BA) populations is low insulin clearance in comparison with White Europeans (WE), with studies indicating up to 74% lower insulin clearance in BA compared with WE1 3 Vol.:(0123456789)Acta Diabetologica subjects [1]. An emerging counterargument proposes that low hepatic insulin clearance may not be purely compensatory, but a primary abnormality in the development of type 2 diabetes (T2D) [8, 9] According to this hypothesis, defects in hepatic insulin clearance promote chronic hyperinsulinaemia, which in turn leads to insulin receptor desensitisation, target tissue insulin resistance and subsequent glucose intolerance. Defects in hepatic insulin clearance promote chronic hyperinsulinaemia, which in turn leads to insulin receptor desensitisation, target tissue insulin resistance and subsequent glucose intolerance In this model, low hepatic clearance in certain ethnic groups is the a priori risk factor underlying their increased prevalence of T2D and precedes the development of insulin resistance. Supporting this hypothesis, insulin clearance has been identified as an important predictor of T2D development in longitudinal studies of African-Americans [10]
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