Abstract
Background: Ectopic fat is thought to play a central role in the pathophysiology of type 2 diabetes (T2D). Despite being disproportionately affected by T2D, black populations typically exhibit lower levels of ectopic fat compared to white populations; this paradox questions the role of ectopic fat in the development of T2D in black populations.Aim: To assess ethnic differences in ectopic fat deposition and their relationships with metabolic parameters of T2D in white European (WE) and black west African (BWA) men at three glycaemic states: normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and T2D.
Methods: Fifty-one WE (23 NGT/10 IGT/18 T2D) and 50 BWA (20 NGT/10 IGT/20 T2D) men were recruited. All participants underwent: 1) a Dixon-magnetic resonance imaging scan to assess visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intrapancreatic lipids (IPL); 2) a proton-magnetic resonance spectroscopy scan to assess intramyocellular lipids (IMCL); 3) a hyperinulinaemic-euglycaemic clamp, with the infusion of glucose and glycerol isotopes, to assess whole-body, hepatic, skeletal muscle and adipose tissue insulin sensitivity; and 4) a hyperglycaemic clamp to assess first- and second-phase insulin secretory function, insulin secretion rate and insulin clearance.
Results: In the combined glycaemic cohorts, VAT, IHL and IPL were significantly lower in the BWA men compared to the WE men (all p<0.05), however, IMCL did not differ by ethnicity (p=0.74). Differences in VAT, IHL, IPL and IMCL by glycaemic state were similar in both ethnic groups, indicated by non-significant ethnicity*glycaemic state interactions (all p>0.05). Relationships between ectopic fat depots and metabolic parameters were generally stronger in the WE men than BWA men. VAT, IHL and IPL showed significant inverse associations with adipose tissue insulin sensitivity in WE men but not BWA men (all p<0.05). Interrelationships between the ectopic fat depots were stronger in WE men than BWA men.
Conclusion: The greater ectopic fat levels in the T2D states compared to the NGT states in both WE and BWA men suggests ectopic fat plays a role in the development of T2D in both ethnic groups; however, the weaker relationships between ectopic fat depots and metabolic parameters of T2D in BWA men suggests ectopic fat may play a lesser role in T2D in BWA men compared with WE men. Furthermore, the lack of association between ectopic fat depots and adipose tissue insulin sensitivity in BWA men suggests that the role of adipose tissue dysfunction in driving ectopic fat storage may differ by ethnicity.
| Date of Award | 1 Mar 2020 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Louise Goff (Supervisor) & Geoffrey Charles-Edwards (Supervisor) |