β -Cell Function in Black South African Women: Associations With Insulin Clearance And Ectopic Fat

Abstract Background: The role of ectopic fat, insulin secretion and clearance in the preservation of β-cell function in obese, black African women who typically present with hyperinsulinemia is not clear. We aim to examine the associations between disposition index (DI, a measure of β-cell function), insulin secretion and clearance and ectopic fat deposition. Methods: This is a cross-sectional study of 43 obese (BMI 30-40 kg/m 2 ) black South African ( women (age 20-35 years) without type 2 diabetes that measured the following: DI, insulin sensitivity (S I ), acute insulin response (AIRg), insulin secretion rate (ISR), hepatic insulin extraction and peripheral insulin clearance (frequently-sampled intravenous glucose tolerance test); pancreatic and hepatic fat, visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) volume (magnetic resonance imaging), intramyocellular (IMCL) and extramyocellular fat content (EMCL) (magnetic resonance spectroscopy). DI correlated positively with peripheral insulin clearance before (β 55.80, p=0.002) and after adjusting for hepatic insulin extraction. Higher DI was associated with lower VAT, pancreatic fat and soleus fat, but VAT explained most of the variance in DI (32%). Additionally, higher first phase ISR (p=0.033) and lower hepatic insulin extraction (p=0.022) associated with lower VAT, independent from S I, rather than with ectopic fat. Conclusion: Peripheral insulin clearance emerged as an important determinant of DI, independent from hepatic insulin extraction . However, VAT was the main determinant of a lower DI above ectopic fat depots. Importantly, VAT, but not ectopic fat, was associated with both lower insulin secretion and higher hepatic insulin extraction, independent from S I , and may provide a novel explanation of these findings in obese black South African women.