Ethnic differences in hepatic and systemic insulin sensitivity and their associated determinants in obese black and white South African women

Abstract

Aims/hypothesis There is evidence to suggest that ectopic fat deposition in liver and skeletal muscle may differ between black and white women resulting in organ-specific differences in insulin sensitivity. Accordingly, the aim of the study was to examine ethnic differences in hepatic and peripheral insulin sensitivity, and the association with hepatic and skeletal muscle lipid content, and skeletal muscle gene expression. Methods In a cross-sectional study including 30 obese premenopausal black and white women, body composition (dual energy x-ray absorptiometry), liver fat and skeletal muscle (soleus and tibialis anterior) fat accumulation (proton-magnetic resonance spectroscopy), skeletal muscle gene expression, insulin sensitivity (two-step isotope labelled, hyperinsulinaemic–euglycaemic clamp with 10 mU m–2 min–1 and 40 mU m–2 min–1 insulin infusions), and serum adipokines were measured. Results We found that, although whole-body insulin sensitivity was not different, obese white women presented with lower hepatic insulin sensitivity than black women (% suppression of endogenous glucose production [% supp EGP], median [interquartile range (IQR)]: 17 [5–51] vs 56 [29–100] %, p=0.002). While liver fat tended to be lower (p=0.065) and skeletal muscle fat deposition tended to be higher (p=0.074) in black compared with white women, associations with insulin sensitivity were only observed in black women (% supp EGP vs liver fat: r=–0.57, p<0.05 and % supp EGP vs soleus fat: r=–0.56, p<0.05). Conclusions/interpretation These findings may suggest that black women are more sensitive to the effects of ectopic lipid deposition than white women.

Ethnic differences in intrahepatic lipid and its association with hepatic insulin sensitivity and insulin clearance between men of black and white ethnicity with early type 2 diabetes

“…Consistently, insulin clearance has been shown to be lower in black populations compared with white populations . However, investigations of ethnic differences in hepatic insulin sensitivity have shown inconsistent findings . We have previously reported similar hepatic insulin sensitivity but lower insulin clearance in black West African (BWA) compared with white European (WE) men .…”

“…This could indicate a decreased effect of IHL on hepatic insulin sensitivity in the insulin‐stimulated state compared with the basal state in WE men. To our knowledge only one other study has investigated the relationship between IHL and hepatic insulin sensitivity using the hyperinsulinemic euglycaemic clamp with infusion of isotopically labelled glucose; the authors found that IHL was associated with hepatic insulin sensitivity in obese black South African women but not in obese white South African women, which contradicts our findings. There are several potential explanations for this, such as glycaemic state; our study included participants with T2D whereas the South African women were normal glucose‐tolerant.…”

“…4 However, investigations of ethnic differences in hepatic insulin sensitivity have shown inconsistent findings. [5][6][7] We have previously reported similar hepatic insulin sensitivity but lower insulin clearance in black West African (BWA) compared with white European (WE) men. 8,9 Despite the literature reporting ethnic differences in IHL, hepatic insulin sensitivity and insulin clearance between black and white populations, these have not previously been investigated in a single study to understand their relationships and how ethnicity impacts on these in the development of T2D in black populations.…”

Ethnicity and Type 2 diabetes in the UK

“…However, there is evidence that black populations may be more sensitive to the negative effects of liver fat accumulation [65]. In adults, contradictory findings have been reported; liver fat has been found to be inversely associated with hepatic insulin sensitivity in black but not white women [69], however, the opposite was found in black vs. white men, where liver fat was inversely associated with hepatic insulin sensitivity in white but not black men [70]. This suggests that there are not only ethnic disparities, but also gender differences in the role of ectopic fat in the pathophysiology of Type 2 diabetes within the black ethnic groups where further research is required.…”

Protective role of physical activity on type 2 diabetes: Analysis of effect modification by race–ethnicity

“…Previous studies have linked IMAT, defined as the adipose tissue found within the muscle fascia, to a decrease in S i through inhibition of the insulin signaling pathway, leading to compromised insulin‐stimulated glucose uptake and decreased S i . A recent study by Goedecke et al showed that in NHB women, increased IMCL, defined as the accumulation of lipid particles within the muscle cell, and muscle fat percentage (IMAT) in the soleus were significantly correlated with lower S i . In NHW women, there was no relationship between IMCL and S i .…”