Abstract
Background: People of black African (BA) ethnicity are at a disproportionately high risk of type 2 diabetes (T2D) and develop the disease at a younger age and at a lower body mass index than their white European (WE) peers. Ethnic distinctions in the pathophysiology of T2D are hypothesised to account for some of these observations. The underlying mechanisms are poorly understood, but they may involve variations in beta cell function and insulin clearance.Aims: To assess ethnic differences in beta cell function and insulin clearance – and their relationships with other metabolic parameters - in white European (WE) and black African (BA) men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and T2D
Methods: The following measurements were taken in 100 men, 50 WE (23 NGT/8 IGT/19 T2D) and 50 BA (23 NGT/8 IGT/19 T2D): 1. Insulin secretion, endogenous insulin clearance and incretin secretion during a mixed meal tolerance test 2. Insulin secretion and endogenous insulin clearance during a 2 hour hyperglycaemic clamp 3. Whole-body and hepatic-specific insulin sensitivity and metabolic clearance rate of insulin during a hyperinsulinaemic-euglycaemic clamp with infusion of stable glucose isotope and 4. Quantification of visceral fat and hepatic fat by magnetic resonance imaging .
Results: Black African ethnicity was associated with lower insulin secretion rates following adjustment for insulin sensitivity, age, glycaemia and adiposity (P=0.013). BA men had lower endogenous insulin clearance compared with WE men, with the difference persisting after adjustment for insulin sensitivity and hepatic fat (P=0.001). During the hyperglycaemic clamp, there was an ethnic difference in the relationship between insulin sensitivity and insulin clearance, with the association being significantly stronger in the WE men (Pinteraction<0.001).
Conclusions: Earlier and more severe beta cell dysfunction may contribute to the increased risk of glucose intolerance in BA populations. Low insulin clearance appears to determine peripheral insulin levels independently of insulin sensitivity in BA subjects and may help to compensate for deficiencies in insulin secretion. However, under conditions of excessive beta cell stimulation, low insulin clearance leads to a marked hyperinsulinaemia in healthy BA men, which may itself be pathogenic. A better understanding of the heterogeneity of T2D aetiology may allow more effective interventions to be tailored to this ethnic group.
| Date of Award | 1 Sept 2021 |
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| Original language | English |
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| Supervisor | Louise Goff (Supervisor) & Stephanie Amiel (Supervisor) |