We assessed differences in mitochondrial function in gluteal (gSAT) and abdominal subcutaneous adipose tissue (aSAT) at baseline and in response to 12-weeks of exercise training; and examined depot-specific associations with body fat distribution and insulin sensitivity (S_I). Obese, black South African women (n = 45) were randomized into exercise (n = 23) or control (n = 22) groups. Exercise group completed 12-weeks of aerobic and resistance training (n = 20), while the control group (n = 15) continued usual behaviours. Mitochondrial function (high-resolution respirometry and fluorometry) in gSAT and aSAT, S_I (frequently sampled intravenous glucose tolerance test), body composition (dual-energy X-ray absorptiometry), and ectopic fat (MRI) were assessed pre- and post-intervention. At baseline, gSAT had higher mitochondrial respiratory capacity and hydrogen peroxide (H₂O₂) production than aSAT (p < 0.05). Higher gSAT respiration was associated with higher gynoid fat (p < 0.05). Higher gSAT H₂O₂ production and lower aSAT mitochondrial respiration were independently associated with lower S_I (p < 0.05). In response to training, S_I improved and gynoid fat decreased (p < 0.05), while H₂O₂ production reduced in both depots, and mtDNA decreased in gSAT (p < 0.05). Mitochondrial respiration increased in aSAT and correlated with a decrease in body fat and an increase in soleus and hepatic fat content (p < 0.05). This study highlights the importance of understanding the differences in mitochondrial function in multiple SAT depots when investigating the pathophysiology of insulin resistance and associated risk factors such as body fat distribution and ectopic lipid deposition. Furthermore, we highlight the benefits of exercise training in stimulating positive adaptations in mitochondrial function in gluteal and abdominal SAT depots.

Type 2 diabetes (T2D) is a global public health priority, particularly for populations of black African-Caribbean ethnicity, who suffer disproportionately high rates of the disease. While the mechanisms underlying the development of T2D are well documented, there is growing evidence describing distinctions among black African-Caribbean populations. In the present paper, we review the evidence describing the impact of black African-Caribbean ethnicity on T2D pathophysiology. Ethnic differences were first recognised through evidence that metabolic syndrome diagnostic criteria fail to detect T2D risk in black populations due to less central obesity and dyslipidaemia. Subsequently more detailed investigations have recognised other mechanistic differences, particularly lower visceral and hepatic fat accumulation and a distinctly hyperinsulinaemic response to glucose stimulation. While epidemiological studies have reported exaggerated insulin resistance in black populations, more detailed and direct measures of insulin sensitivity have provided evidence that insulin sensitivity is not markedly different to other ethnic groups and does not explain the hyperinsulinaemia that is exhibited. These findings lead us to hypothesise that ectopic fat does not play a pivotal role in driving insulin resistance in black populations. Furthermore, we hypothesise that hyperinsulinaemia is driven by lower rates of hepatic insulin clearance rather than heightened insulin resistance and is a primary defect rather than occurring in compensation for insulin resistance. These hypotheses are being investigated in our ongoing South London Diabetes and Ethnicity Phenotyping study, which will enable a more detailed understanding of ethnic distinctions in the pathophysiology of T2D between men of black African and white European ethnicity.

Aims/hypothesis Type 2 diabetes is more prevalent in black African than white European populations although, paradoxically, black African individuals present with lower levels of visceral fat, which has a known association with insulin resistance. Insulin resistance occurs at a tissue-specific level; however, no study has simultaneously compared whole body, skeletal muscle, hepatic and adipose tissue insulin sensitivity between black and white men. We hypothesised that, in those with early type 2 diabetes, black (West) African men (BAM) have greater hepatic and adipose tissue insulin sensitivity, compared with white European men (WEM), because of their reduced visceral fat. Methods Eighteen BAM and 15 WEM with type 2 diabetes underwent a two-stage hyperinsulinaemic–euglycaemic clamp with stable glucose and glycerol isotope tracers to assess tissue-specific insulin sensitivity and a magnetic resonance imaging scan to assess body composition. Results We found no ethnic differences in whole body, skeletal muscle, hepatic or adipose tissue insulin sensitivity between BAM and WEM. This finding occurred in the presence of lower visceral fat in BAM (3.72 vs 5.68 kg [mean difference −1.96, 95% CI −3.30, 0.62]; p = 0.01). There was an association between skeletal muscle and adipose tissue insulin sensitivity in WEM that was not present in BAM (r = 0.78, p < 0.01 vs r = 0.25 p = 0.37). Conclusions/interpretation Our data suggest that in type 2 diabetes there are no ethnic differences in whole body, skeletal muscle, hepatic and adipose tissue insulin sensitivity between black and white men, despite differences in visceral adipose tissue, and that impaired lipolysis may not be contributing to skeletal muscle insulin resistance in men of black African ethnicity.

Introduction: It is increasingly recognized that type 2 diabetes (T2D) is a heterogenous disease with ethnic variations. Differences in insulin secretion, insulin resistance and ectopic fat are thought to contribute to these variations. Therefore, we aimed to compare postprandial insulin secretion and the relationships between insulin secretion, insulin sensitivity and pancreatic fat in men of black West African (BA) and white European (WE) ancestry. Research design and methods: A cross-sectional, observational study in which 23 WE and 23 BA men with normal glucose tolerance, matched for body mass index, underwent a mixed meal tolerance test with C peptide modeling to measure beta cell insulin secretion, an MRI to quantify intrapancreatic lipid (IPL), and a hyperinsulinemic-euglycemic clamp to measure whole-body insulin sensitivity. Results: Postprandial insulin secretion was lower in BA versus WE men following adjustment for insulin sensitivity (estimated marginal means, BA vs WE: 40.5 (95% CI 31.8 to 49.2) × 10³ vs 56.4 (95% CI 48.9 to 63.8) × 10³ pmol/m² body surface area × 180 min, p=0.008). There was a significantly different relationship by ethnicity between IPL and insulin secretion, with a stronger relationship in WE than in BA (r=0.59 vs r=0.39, interaction p=0.036); however, IPL was not a predictor of insulin secretion in either ethnic group following adjustment for insulin sensitivity. Conclusions: Ethnicity is an independent determinant of beta cell function in black and white men. In response to a meal, healthy BA men exhibit lower insulin secretion compared with their WE counterparts for their given insulin sensitivity. Ethnic differences in beta cell function may contribute to the greater risk of T2D in populations of African ancestry.

Objective: We investigated the effects of a 12-week exercise intervention on insulin sensitivity (SI) and hyperinsulinemia and associated changes in regional and ectopic fat. Research design and methods: Healthy, black South African women with obesity (mean age 23±3.5 y) and of isiXhosa ancestry were randomised into a 12-week aerobic and resistance exercise training group (n=23) and a no exercise group (control, n=22). Pre and post-intervention testing included assessment of SI, insulin response to glucose (AIRg), insulin secretion rate (ISR), hepatic insulin extraction (FEL) and disposition index (DI) (AIRg x SI) (frequently sampled intravenous glucose tolerance test); fat mass and regional adiposity (dual-energy X-ray absorptiometry); hepatic, pancreatic and skeletal muscle fat content and abdominal subcutaneous and visceral adipose tissue volumes (magnetic resonance imaging). Results: Exercise training increased VO2peak (mean ± standard deviation: 24.9±2.42 to 27.6±3.39 ml/kg/min, p<0.001), SI (2.0 (1.2-2.8) to 2.2 (1.5-3.7) (mU/l)-1min-1, p=0.005) and DI (median (interquartile range): 6.1 (3.6-7.1) to 6.5 (5.6-9.2) x103 arbitrary units, p=0.028), and decreased gynoid fat mass (18.5±1.7 to 18.2±1.6%, p<0.001) and body weight (84.1±8.7 to 83.3±.9.7 kg, p=0.038). None of these changes were observed in the control group, but body weight increased (p=0.030). AIRg, ISR and FEL, VAT, SAT and ectopic fat were unaltered after exercise training. The increase in SI and DI were not associated with changes in regional or ectopic fat. Conclusion: Exercise training increased SI independent from changes in hyperinsulinemia and ectopic fat, suggesting that ectopic fat might not be a principal determinant of insulin resistance in this cohort.