Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function

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, SI (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 SI (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

Ethnic differences in beta cell function occur independently of insulin sensitivity and pancreatic fat in black and white men

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

The Link between Obesity and Inflammatory Markers in the Development of Type 2 Diabetes in Men of Black African and White European Ethnicity

In this study, we aimed to assess ethnic differences in visceral (VAT), deep subcutaneous (dSAT), and superficial subcutaneous (sSAT) adipose tissue and their relationships with inflammatory markers between white European (WE) and black West African (BWA) men with normal glucose tolerance (NGT) and type 2 diabetes (T2D). Forty-two WE (23 NGT/19 T2D) and 43 BWA (23 NGT/20 T2D) men underwent assessment of plasma inflammatory markers using immunoassays alongside Dixon magnetic resonance imaging to quantify L4-5 VAT, dSAT and sSAT. Despite no ethnic differences in sSAT and dSAT, BWA men exhibited lower VAT (p = 0.002) and dSAT:sSAT (p = 0.047) than WE men. Adiponectin was inversely associated with sSAT in WE (p = 0.041) but positively associated in BWA (p = 0.031) men with T2D. Interleukin-6 (IL-6) was associated with VAT in WE but not in BWA men with NGT (WE: p = 0.009, BWA: p = 0.137) and T2D (WE: p = 0.070, BWA: p = 0.175). IL-6 was associated with dSAT in only WE men with NGT (WE: p = 0.030, BWA: p = 0.833). The only significant ethnicity interaction present was for the relationship between adiponectin and sSAT (Pinteraction = 0.003). The favourable adipose tissue distribution and the weaker relationships between adiposity and inflammation in BWA men suggest that adipose tissue inflammation may play a lesser role in T2D in BWA than WE men

MRI thigh measurements predict whole‐body skeletal muscle mass in patients with type 2 diabetes: a comparison with DXA

Abstract Background Sarcopenia is an age‐related loss of skeletal muscle mass (SMM) and function, associated with falls, frailty, and functional decline. It is more prevalent and often accelerated in people with Type 2 diabetes (T2D), especially when co‐existing with obesity (sarcopenic obesity). Accurate whole‐body SMM measurement, feasible using dual‐energy X‐ray absorptiometry (DXA) or magnetic resonance imaging (MRI), has utility both in clinical practice and in epidemiological and mechanistic research, considering the dual mechanical and metabolic function of skeletal muscle. Compared with MRI, DXA may underestimate age‐related muscle mass by up to 30%, and so direct comparison of DXA/MRI‐derived SMM measurements may be invalid in patients with obesity and T2D, who have potentially even more pronounced sarcopenia/sarcopenic obesity. We aimed to validate single‐slice or multiple‐slice measures of SMM, using MRI, with whole‐body SMM measures derived from DXA scans of appendicular lean soft tissue, specifically in patients with obesity and T2D. Methods We undertook a cross‐sectional study in which we performed paired DXA and whole‐body 3.0‐T MRI on 36 people with T2D and obesity (body mass index [BMI] > 30 kg/m2). Single‐slice and seven‐slice estimates of muscle mass, taken from mid‐thigh/thigh MRI images, respectively, were determined, and compared with whole‐body SMM derived from DXA scans of appendicular lean soft tissue, in men and women separately. Results Seventeen men (age 48.4 ± 8.2 years, BMI 37.5 ± 5.1 kg/m2, body fat 39.1 ± 6.0%) and 19 women (age 51.8 years ± 9.7, BMI 37.8 ± 5.8 kg/m2, body fat 47.6 ± 5.1%) were recruited. Whole‐body SMM estimated by seven‐slice thigh MRI correlated strongly with DXA‐derived SMM in both men (r = 0.94, P < 0.001) and women (r = 0.94, P < 0.001). Single‐slice thigh estimates of whole‐body SMM by MRI also showed strong relationships to DXA‐derived SMM in both men (r = 0.88, P < 0.001) and women (r = 0.87, P < 0.001). There was no evidence of a statistically significant difference when comparing the performance of using single‐slice vs. multiple‐slices to determine SMM (P = 0.10 for males and P = 0.13 for females). Conclusions This study demonstrates that accurate determination of whole‐body SMM is possible using either single‐slice mid‐thigh or seven‐slice thigh MRI in men and women with obesity and T2D in whom there may be significant alterations in body composition. Its application may be of use clinically and in obesity‐related, metabolic, and gerontological research where accurate assessments of body composition add mechanistic insight

Exploring the determinants of ethnic differences in insulin clearance between men of Black African and White European ethnicity

AIM: People of Black African ancestry, who are known to be at disproportionately high risk of type 2 diabetes (T2D), typically exhibit lower hepatic insulin clearance compared with White Europeans. However, the mechanisms underlying this metabolic characteristic are poorly understood. We explored whether low insulin clearance in Black African (BA) men could be explained by insulin resistance, subclinical inflammation or adiponectin concentrations. METHODS: BA and White European (WE) men, categorised as either normal glucose tolerant (NGT) or with T2D, were recruited to undergo the following: a mixed meal tolerance test with C-peptide modelling to determine endogenous insulin clearance; fasting serum adiponectin and cytokine profiles; a hyperinsulinaemic–euglycaemic clamp to measure whole-body insulin sensitivity; and magnetic resonance imaging to quantify visceral adipose tissue. RESULTS: Forty BA (20 NGT and 20 T2D) and 41 WE (23 NGT and 18 T2D) men were studied. BA men had significantly lower insulin clearance (P = 0.011) and lower plasma adiponectin (P = 0.031) compared with WE men. In multiple regression analysis, ethnicity, insulin sensitivity and plasma adiponectin were independent predictors of insulin clearance, while age, visceral adiposity and tumour necrosis factor alpha (TNF-α) did not significantly contribute to the variation. CONCLUSION: These data suggest that adiponectin may play a direct role in the upregulation of insulin clearance beyond its insulin-sensitising properties