Regional adiposity and insulin sensitivity - interactions with menopause and HIV in middle-aged Black African women.

OBJECTIVE: To explore depot-specific functional aspects of adipose tissue, examining the putative role for menopause and HIV status on insulin sensitivity (SI) and beta-cell function in Black South African women. METHODS: Women (n = 92) from the Middle-Aged Soweto Cohort, including premenopausal HIV-negative (n = 21); premenopausal women living with HIV (WLWH; n = 11); postmenopausal HIV-negative (n = 42); postmenopausal WLWH (n = 18) underwent the following tests: body composition (dual energy x-ray absorptiometry); fasting bloods for sex hormones, inflammation and adipokines; frequently sampled intravenous glucose tolerance test for SI and beta-cell function (disposition index, DI); abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) biopsies for cell size and mRNA expression of adipokines, inflammation, and estrogen receptors [ER]. RESULTS: Depot-specific associations between gene expression and insulin parameters did not differ by HIV or menopause status. Pooled analysis showed significant models for SI (P = 0.002) and DI (P = 0.003). Higher SI was associated with lower leptin and CD11c expression in aSAT and higher adiponectin in gSAT. Higher DI was associated with higher aSAT and gSAT expression of adiponectin, LPL, ERα, and PPARγ, and lower leptin in aSAT. WLWH had higher expression of adiponectin and lower expression of leptin in both aSAT (P = 0.002 and P = 0.005) and gSAT (P = 0.004 and P = 0.002), respectively, and a larger proportion of smaller cells in aSAT (P < 0.001). CONCLUSION: Insulin sensitivity and beta cell function were distinctively associated with aSAT and gSAT. While menopause did not influence these relationships, HIV had a significant effect on adipose tissue, characterised by variations in cell size distribution and transcript levels within the depots.

SHBG, Free Testosterone, and Type 2 Diabetes Risk in Middle-aged African Men: A Longitudinal Study.

Objectives: To investigate longitudinal changes in SHBG and free testosterone (free T) levels among Black middle-aged African men, with and without coexistent HIV, and explore associations with incident dysglycaemia and measures of glucose metabolism. Design: This longitudinal study enrolled 407 Black South African middle-aged men, comprising primarily 322 men living without HIV (MLWOH) and 85 men living with HIV (MLWH), with normal fasting glucose at enrollment. Follow-up assessments were conducted after 3.1 ± 1.5 years. Methods: At baseline and follow-up, SHBG, albumin, and total testosterone were measured and free T was calculated. An oral glucose tolerance test at follow-up determined dysglycaemia (impaired fasting glucose, impaired glucose tolerance, type 2 diabetes) and glucose metabolism parameters including insulin sensitivity (Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and beta(ß)-cell function (disposition index). The primary analysis focussed on MLWOH, with a subanalysis on MLWH to explore whether associations in MLWOH differed from MLWH. Results: The prevalence of dysglycaemia at follow-up was 17% (n = 55) in MLWOH. Higher baseline SHBG was associated with a lower risk of incident dysglycaemia (odds ratio 0.966; 95% confidence interval 0.945-0.987) and positively associated with insulin sensitivity (ß = 0.124, P < .001) and ß-cell function (ß = 0.194, P = .001) at follow-up. Free T did not predict dysglycaemia. In MLWH, dysglycaemia prevalence at follow-up was 12% (n = 10). Neither baseline SHBG nor free T were associated with incident dysglycaemia and glucose metabolism parameters in MLWH. Conclusion: SHBG levels predict the development of dysglycaemia in middle-aged African men but do not exhibit the same predictive value in MLWH.

Variability of polygenic prediction for body mass index in Africa.

BACKGROUND: Polygenic prediction studies in continental Africans are scarce. Africa's genetic and environmental diversity pose a challenge that limits the generalizability of polygenic risk scores (PRS) for body mass index (BMI) within the continent. Studies to understand the factors that affect PRS variability within Africa are required. METHODS: Using the first multi-ancestry genome-wide association study (GWAS) meta-analysis for BMI involving continental Africans, we derived a multi-ancestry PRS and compared its performance to a European ancestry-specific PRS in continental Africans (AWI-Gen study) and a European cohort (Estonian Biobank). We then evaluated the factors affecting the performance of the PRS in Africans which included fine-mapping resolution, allele frequencies, linkage disequilibrium patterns, and PRS-environment interactions. RESULTS: Polygenic prediction of BMI in continental Africans is poor compared to that in European ancestry individuals. However, we show that the multi-ancestry PRS is more predictive than the European ancestry-specific PRS due to its improved fine-mapping resolution. We noted regional variation in polygenic prediction across Africa's East, South, and West regions, which was driven by a complex interplay of the PRS with environmental factors, such as physical activity, smoking, alcohol intake, and socioeconomic status. CONCLUSIONS: Our findings highlight the role of gene-environment interactions in PRS prediction variability in Africa. PRS methods that correct for these interactions, coupled with the increased representation of Africans in GWAS, may improve PRS prediction in Africa.

Inflammatory markers in pregnancy are associated with postpartum weight in South African women living with HIV on antiretroviral therapy.

BACKGROUND: Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH. SETTING: A total of 57 pregnant PWH enrolled at ≤14 weeks gestation (T1) in Gugulethu antenatal care clinic in Cape Town and followed through 48 weeks PP were included. METHODS: Plasma soluble (s) CD14, sCD163, leptin, tumour necrosis factor receptor 1 (TNFR-1), resistin, adiponectin, and interleukin-6 (IL-6) were assayed in duplicate using the Luminex platform. We considered each inflammatory marker at T1 (n=57) and T3 (29-36 weeks gestation, n=31) as a separate exposure of interest. Linear mixed effects models were fit to examine whether each exposure was associated with average PPW and PPW trajectories; linear regression was used for associations with PPW change between T1 and 48 weeks. RESULTS: Median age was 32 years (IQR, 29-35), 98% were multigravida, and 49% had a BMI≥30 kg/m2. Higher T1 sCD14 levels were associated with higher average weight through 48 weeks PP (ß = 0.002, p=0.04), and T3 sCD14 with higher PPW gain (ß = 0.007, p=0.04). Leptin (ß = 0.414, p<0.01), TNFR-1 (ß = 11.048, p<0.01) and resistin (ß = 0.714, p=0.01) at T3 were associated with higher average PPW, and IL-6 (ß = 2.266, p=0.02) with PPW gain. CONCLUSION: These findings suggest that low-grade inflammation in pregnancy may play a role in postpartum obesity, pointing to potential mechanisms with implications for long-term cardiometabolic health in PWH.

Silhouette showcards confirm altered obesity-associated body image perception in international cohort study of African-origin populations.

OBJECTIVES: Given the increasing prevalence of obesity and need for effective interventions, there is a growing interest in understanding how an individual's body image can inform obesity prevention and management. This study's objective was to examine the use of silhouette showcards to measure body size perception compared with measured body mass index, and assess body size dissatisfaction, in three different African-origin populations spanning the epidemiological transition. An ancillary objective was to investigate associations between body size perception and dissatisfaction with diabetes and hypertension. SETTING: Research visits were completed in local research clinics in respective countries. PARTICIPANTS: Seven hundred and fifty-one African-origin participants from the USA and the Republic of Seychelles (both high-income countries), and Ghana (low/middle-income country). PRIMARY AND SECONDARY OUTCOME MEASURES: Silhouette showcards were used to measure perceived body size and body size dissatisfaction. Objectively measured body size was measured using a scale and stadiometer. Diabetes was defined as fasting blood glucose ≥126 mg/dL and hypertension was defined as ≥130 mm Hg/80 mm Hg. RESULTS: Most women and men from the USA and Seychelles had 'Perceived minus Actual weight status Discrepancy' scores less than 0, meaning they underestimated their actual body size. Similarly, most overweight or obese men and women also underestimated their body size, while normal weight men and women were accurately able to estimate their body size. Finally, participants with diabetes were able to accurately estimate their body size and similarly desired a smaller body size. CONCLUSIONS: This study highlights that overweight and obese women and men from countries spanning the epidemiological transition were unable to accurately perceive their actual body size. Understanding people's perception of their body size is critical to implementing successful obesity prevention programmes across the epidemiological transition.

Postprandial glucose variability and clusters of sex hormones, liver enzymes, and cardiometabolic factors in a South African cohort of African ancestry.

INTRODUCTION: This study aimed to, first, determine the clusters of sex hormones, liver enzymes, and cardiometabolic factors associated with postprandial glucose (PPG) and, second to evaluate the variation these clusters account for jointly and independently with polygenic risk scores (PRSs) in South Africans of African ancestry men and women. RESEARCH DESIGN AND METHODS: PPG was calculated as the integrated area under the curve for glucose during the oral glucose tolerance test (OGTT) using the trapezoidal rule in 794 participants from the Middle-aged Soweto Cohort. Principal component analysis was used to cluster sex hormones, liver enzymes, and cardiometabolic factors, stratified by sex. Multivariable linear regression was used to assess the proportion of variance in PPG accounted for by principal components (PCs) and type 2 diabetes (T2D) PRS while adjusting for selected covariates in men and women. RESULTS: The T2D PRS did not contribute to the PPG variability in both men and women. In men, the PCs' cluster of sex hormones, liver enzymes, and cardiometabolic explained 10.6% of the variance in PPG, with PC1 (peripheral fat), PC2 (liver enzymes and steroid hormones), and PC3 (lipids and peripheral fat) contributing significantly to PPG. In women, PC factors of sex hormones, cardiometabolic factors, and liver enzymes explained a similar amount of the variance in PPG (10.8%), with PC1 (central fat) and PC2 (lipids and liver enzymes) contributing significantly to PPG. CONCLUSIONS: We demonstrated that inter-individual differences in PPG responses to an OGTT may be differentially explained by body fat distribution, serum lipids, liver enzymes, and steroid hormones in men and women.

Cardiometabolic Health in Pregnancy and Postpartum: Findings From a Prospective Cohort Study in South Africa.

Background: The cardiometabolic impact of HIV infection and treatment with antiretroviral therapy (ART) in pregnancy and the postpartum period remains unclear. Methods: We enrolled pregnant persons with (PHIV) and without HIV in Cape Town, South Africa, who were ≥18 years old at 24-28 weeks' gestation and followed them up to 32 months postpartum. We estimated associations between HIV status and cardiometabolic risk including body mass index (BMI), obesity (BMI ≥30 kg/m2), blood pressure (BP; elevated systolic BP ≥130 and/or diastolic ≥85 mmHg), lipid levels, and metabolic syndrome according to the Joint Interim Statement criteria using multivariable log binomial or linear regression models. Subgroup analyses compared PHIV on efavirenz (EFV)- vs dolutegravir (DTG)-based ART. Results: Among 400 participants (n = 200 without HIV, n = 200 PHIV), 52% had prepregnancy obesity and 9% had elevated BP. Postpartum, 57% were classified with obesity, 31% had elevated BP, and 29% had metabolic syndrome. In multivariable analyses, HIV was associated with a lower BMI prepregnancy but not postpartum; however, mean indices were in the obese range regardless of HIV status. Neither BMI nor obesity prepregnancy or postpartum differed by ART regimen. Among PHIV, participants on DTG had higher levels of elevated BP in pregnancy and postpartum, compared with PHIV on EFV. Conclusions: We observed high levels of obesity, elevated BP, and metabolic syndrome in the perinatal period but few differences by HIV status. Participants on DTG may be more likely to have elevated BP in pregnancy and postpartum. Monitoring of cardiometabolic health for pregnant persons on DTG is warranted.

Measurement of body composition in postpartum South African women living with and without HIV infection.

Background: While several methodologies are available to measure adiposity, few have been validated in sub-Saharan African (SSA) and none in postpartum African women living with HIV (WLHIV). We compared bioelectrical impendence analysis (BIA) and air displacement plethysmography (ADP) against dual x-ray absorptiometry (DXA) in South African women and examined differences by HIV and body mass index (BMI) status. Methods: Lin's concordance correlation coefficient (CCC) test was used to examine fat mass (FM), fat free mass (FFM), and total body fat percent (%BF) difference between BIA vs. DXA, and ADP vs. DXA in women living with HIV (n = 57) and without HIV (n = 25). The Bland Altman test was used to assess mean differences and the direction of bias. Results: The median age was 31 years (IQR, 26-35) and months postpartum were 11 (IQR, 7-16), 44% of the women had obesity. Lin's CCC for BIA and ADP vs. DXA were both 0.80 for %BF and 0.97 for FM, and 0.86 and 0.80 for FFM, respectively. Mean differences (DXA-BIA and ADP estimates) were 0.22 ± 4.54% (p = 0.54) and 3.35 ± 3.27% (p < 0.01) for %BF, -0.82 ± 3.56 kg (p = 0.06) and 1.43 ± 2.68 kg (p = 0.01) for FM, -1.38 ± 3.61 kg (p = 0.01) and - 3.34 ± 2.37 kg (p < 0.01) for FFM, respectively. BIA overestimated %BF in WLHIV and underestimated it in women with obesity. Conclusion: Body composition measurements using BIA and ADP correlated well with DXA, thereby providing alternative, safe tools for measuring postpartum FM and FFM in SSA women, including WLHIV.

Prevalence of obesity, hypertension and diabetes among people living with HIV in South Africa: a systematic review and meta-analysis.

BACKGROUND: HIV has become a manageable chronic condition due to the success and scale-up of antiretroviral therapy (ART). Globally, South Africa has the highest number of people living with HIV (PLHIV) and research evidence indicates that countries with the highest burden of PLHIV have a substantial burden of obesity, hypertension (HPT) and type 2 diabetes (T2D). We sought to summarize the burden of these three common NCDs among PLHIV in South Africa. METHODS: In this systematic review, multiple databases were searched for articles reporting on the prevalence of obesity, HPT, and T2D among PLHIV in South Africa published since journal inception until March 2022. A meta-analysis was conducted using random-effects models to obtain pooled prevalence estimates of the three NCDs. Heterogeneity was assessed using X2 test on Cochran's Q statistic. RESULTS: We included 32 studies, with 19, 22 and 18 studies reporting the prevalence of obesity, HPT, and T2D among PLHIV, respectively. The overall prevalence of obesity, HPT, and T2D was 23.2% [95% CI 17.6; 29.9], 25.5% [95% CI 15.6; 38.7], and 6.1% [95% CI 3.8; 9.7] respectively. The prevalence of obesity was significantly higher among women (P = 0.034) compared to men, however the prevalence of HPT and T2D did not differ by sex. The prevalence of each of the three NCDs did not differ significantly between rural, urban, and peri-urban areas. The prevalence of obesity and T2D was higher in studies conducted between 2013 and 2022 compared to studies conducted between 2000 and 2012, while the prevalence of HPT was higher between 2000 and 2012 compared to between 2013 and 2022. CONCLUSIONS: These findings suggest that South Africa is experiencing a syndemic of NCDs among people PLHIV highlighting the need to increase cost-effective interventions and management strategies that involve integrated HIV and NCD care in the South African setting.

Associations of HIV and antiretroviral therapy with gestational diabetes in South Africa.

OBJECTIVE: To estimate associations of HIV status and antiretroviral (ART) regimen with gestational diabetes (GDM) and postpartum glucose metabolism. DESIGN: Prospective cohort study. METHODS: We enrolled pregnant persons with HIV (PWH) and without HIV in Cape Town, South Africa who were at least 18 years of age at 24-28 weeks' gestation and followed up to 26 months postpartum. Participants were tested for GDM in pregnancy and for diabetes postpartum using a 75 g 2 h oral glucose tolerance test (OGTT) and diagnosed via WHO criteria. We estimated associations of HIV status and ART regime [efavirenz (EFV) versus dolutegravir (DTG)] with GDM and postpartum impaired glucose metabolism using multivariable log binomial or linear regression models. RESULTS: Among 397 participants [median age 30 (interquartile range (IQR) 25-34; n  = 198 without HIV, n  = 199 PWH], the prevalence of GDM was 6% (9 PWH versus 3% without HIV). In multivariable analyses, PWH were at higher risk of GDM [risk ratio (RR) 3.9, 95% confidence interval (CI) 1.4-10.7] after adjustment for prepregnancy BMI and other confounders. GDM risk did not differ by ART regimen (unadjusted prevalence 8.1% DTG versus 5.6% EFV, adjusted RR 1.1, 95% CI 0.2-6.6). Few participants had diabetes, impaired glucose tolerance (IGT), or impaired fasting glucose postpartum ( n  = 13, 6%) with no differences by HIV or ART status. CONCLUSION: In a setting of universal GDM testing, PWH had an increased risk of impaired glucose metabolism during pregnancy but not postpartum. Among PWH, GDM risk was similar regardless of EFV or DTG use. Given concerns about DTG and weight gain, diabetes risk should continue to be monitored.

The Impact of Human Immunodeficiency Virus and Menopause on Bone Mineral Density: A Longitudinal Study of Urban-Dwelling South African Women.

An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively; 34/205 (13.6%) women ≥50 years had a total hip (TH) or lumbar spine (LS) T-score ≤ -2.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference -0.013 [95% confidence interval -0.026, -0.001] g/cm2 , p = 0.040) and gained more weight 1.96 [0.32, 3.60] kg; p = 0.019 than HIV-uninfected women. After adjusting for age, baseline weight, weight change, and follow-up time, the transition from pre- to postmenopause was associated with greater TB BMD losses in women with HIV (-0.092 [-0.042, -0.142] g/cm2 ; p = 0.001) than without HIV (-0.038 [-0.016, -0.060] g/cm2 , p = 0.001; interaction p = 0.034). Similarly, in women who were postmenopausal at both time points, those with HIV lost more TB BMD (-0.070 [-0.031, -0.108], p = 0.001) than women without HIV (-0.036 [-0.015, -0.057], p = 0.001, interaction p = 0.049). Findings were consistent but weaker at the LS and TH. Menopause-related bone loss is greater in women with HIV, suggesting women with HIV may be at greater risk of osteoporotic fractures. HIV services should consider routine bone health assessment in midlife women as part of long-term HIV care delivery. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Targeted proteomics identifies potential biomarkers of dysglycaemia, beta cell function and insulin sensitivity in Black African men and women.

AIMS/HYPOTHESIS: Using a targeted proteomics approach, we aimed to identify and validate circulating proteins associated with impaired glucose metabolism (IGM) and type 2 diabetes in a Black South African cohort. In addition, we assessed sex-specific associations between the validated proteins and pathophysiological pathways of type 2 diabetes. METHODS: This cross-sectional study included Black South African men (n=380) and women (n=375) who were part of the Middle-Aged Soweto Cohort (MASC). Dual-energy x-ray absorptiometry was used to determine fat mass and visceral adipose tissue, and fasting venous blood samples were collected for analysis of glucose, insulin and C-peptide and for targeted proteomics, measuring a total of 184 pre-selected protein biomarkers. An OGTT was performed on participants without diabetes, and peripheral insulin sensitivity (Matsuda index), HOMA-IR, basal insulin clearance, insulin secretion (C-peptide index) and beta cell function (disposition index) were estimated. Participants were classified as having normal glucose tolerance (NGT; n=546), IGM (n=116) or type 2 diabetes (n=93). Proteins associated with dysglycaemia (IGM or type 2 diabetes) in the MASC were validated in the Swedish EpiHealth cohort (NGT, n=1706; impaired fasting glucose, n=550; type 2 diabetes, n=210). RESULTS: We identified 73 proteins associated with dysglycaemia in the MASC, of which 34 were validated in the EpiHealth cohort. Among these validated proteins, 11 were associated with various measures of insulin dynamics, with the largest number of proteins being associated with HOMA-IR. In sex-specific analyses, IGF-binding protein 2 (IGFBP2) was associated with lower HOMA-IR in women (coefficient -0.35; 95% CI -0.44, -0.25) and men (coefficient -0.09; 95% CI -0.15, -0.03). Metalloproteinase inhibitor 4 (TIMP4) was associated with higher insulin secretion (coefficient 0.05; 95% CI 0.001, 0.11; p for interaction=0.025) and beta cell function (coefficient 0.06; 95% CI 0.02, 0.09; p for interaction=0.013) in women only. In contrast, a stronger positive association between IGFBP2 and insulin sensitivity determined using an OGTT (coefficient 0.38; 95% CI 0.27, 0.49) was observed in men (p for interaction=0.004). A posteriori analysis showed that the associations between TIMP4 and insulin dynamics were not mediated by adiposity. In contrast, most of the associations between IGFBP2 and insulin dynamics, except for insulin secretion, were mediated by either fat mass index or visceral adipose tissue in men and women. Fat mass index was the strongest mediator between IGFBP2 and insulin sensitivity (total effect mediated 40.7%; 95% CI 37.0, 43.6) and IGFBP2 and HOMA-IR (total effect mediated 39.1%; 95% CI 31.1, 43.5) in men. CONCLUSIONS/INTERPRETATION: We validated 34 proteins that were associated with type 2 diabetes, of which 11 were associated with measures of type 2 diabetes pathophysiology such as peripheral insulin sensitivity and beta cell function. This study highlights biomarkers that are similar between cohorts of different ancestry, with different lifestyles and sociodemographic profiles. The African-specific biomarkers identified require validation in African cohorts to identify risk markers and increase our understanding of the pathophysiology of type 2 diabetes in African populations.

Changes in subcutaneous adipose tissue microRNA expression in response to exercise training in obese African women.

The mechanisms that underlie exercise-induced adaptations in adipose tissue have not been elucidated, yet, accumulating studies suggest an important role for microRNAs (miRNAs). This study aimed to investigate miRNA expression in gluteal subcutaneous adipose tissue (GSAT) in response to a 12-week exercise intervention in South African women with obesity, and to assess depot-specific differences in miRNA expression in GSAT and abdominal subcutaneous adipose tissue (ASAT). In addition, the association between exercise-induced changes in miRNA expression and metabolic risk was evaluated. Women underwent 12-weeks of supervised aerobic and resistance training (n = 19) or maintained their regular physical activity during this period (n = 12). Exercise-induced miRNAs were identified in GSAT using Illumina sequencing, followed by analysis of differentially expressed miRNAs in GSAT and ASAT using quantitative real-time PCR. Associations between the changes (pre- and post-exercise training) in miRNA expression and metabolic parameters were evaluated using Spearman's correlation tests. Exercise training significantly increased the expression of miR-155-5p (1.5-fold, p = 0.045), miR-329-3p (2.1-fold, p < 0.001) and miR-377-3p (1.7-fold, p = 0.013) in GSAT, but not in ASAT. In addition, a novel miRNA, MYN0617, was identified in GSAT, with low expression in ASAT. The exercise-induced differences in miRNA expression were correlated with each other and associated with changes in high-density lipoprotein concentrations. Exercise training induced adipose-depot specific miRNA expression within subcutaneous adipose tissue depots from South African women with obesity. The significance of the association between exercise-induced miRNAs and metabolic risk warrants further investigation.

Association of Longitudinal Nutrient Patterns with Body Composition in Black Middle-Aged South African Women: A Five-Year Follow-Up Study.

This study aimed to evaluate the association of longitudinal nutrient patterns with body composition in a cohort of 132 black South African middle-aged women over five years. Nutrient patterns were identified using principal component analysis at baseline and follow-up 5 years later. Associations between nutrient patterns and repeated body composition measures were evaluated using generalized estimating equations, before and after adjusting for baseline education and repeated measures of age, socio-economic status, physical activity and employment. The animal-driven nutrient pattern was associated with increases in repeated measures of visceral adipose tissue (VAT) (ß coefficient, 5.79 [95% CI, 0.01-11.57] cm2), fat mass index (FMI) (0.47 [0.01-0.93] kg·m-2) and lean mass index (LMI) (0.50 [0.18-1.17] kg·m-2) (p < 0.05) after adjustment. Vitamin C, sugar, and potassium-driven nutrient pattern was associated with higher FMI (0.50 [0.12-0.88] kg·m-2) and LMI (0.58 [0.07-1.10] kg·m-2) before and after adjustment (p < 0.05). These findings suggest that dietary interventions to curb obesity in black middle-aged South African women should focus on attenuation of nutrient patterns centred on added sugar, animal fat and animal protein.

Perceptions and experiences of young Black South African women with obesity from a low socioeconomic community after following a 12-week structured exercise intervention.

Background: Previous research has shown that Black South African (SA) women perceive a bigger body size to be acceptable and desirable, but nonetheless have shown interest in participating in community-based exercise programmes. This study aimed to investigate perceptions and experiences of participating in a 12-week exercise intervention designed to study the mechanisms of insulin sensitivity and secretion in young Black SA women with obesity. Methods: Qualitative data was collected from young (23 ± 2.9 years) Black SA women (n = 17) residing in a low-income setting in Cape Town, who took part in a 12-week structured exercise intervention. Focus group discussions (FGDs) and in-depth interviews (IDIs) were conducted 1-4 months after the completion of the intervention. These were all audio recorded and took between 45 and 60 min. The recordings were transcribed, translated and qualitative content analysis, entailing a systematic process of coding and identification of salient themes, was conducted using the ATLAS.ti software. Results: Six broad themes were identified from participants' experiences and perceptions: motivational factors, acceptability of the programme, barriers, sustainability and influencing others, benefits of being physically active, definitions and perceptions of exercise. Anticipated weight loss and financial remuneration were identified as motivational factors for enrolment and retention in the exercise programme. Aspects of the training environment and feelings of wellness appeared in the acceptability, sustainability and benefits themes, whereas time scheduling and travel constraints were regarded as barriers. Exercise was perceived as the maintenance of a healthy body, and in some cases, only relevant for specific groups. Conclusion: Financial considerations played an important role in participants enrolling and staying in the 12-week exercise intervention. Participants liked many aspects of the intervention and identified physical and mental benefits that seemingly outweighed the barriers and disliked aspects of the programme. Optimizing the acceptability of exercise programmes and maximizing the opportunity for participants to experience improved mental well-being may contribute to attracting and retaining young Black SA women in exercise programmes.

Pathophysiology of type 2 diabetes in sub-Saharan Africans.

Sub-Saharan Africa (SSA) is the region with the highest projected rates of increase in type 2 diabetes (129% by 2045), which will exacerbate the already high prevalence of type 2 diabetes complications and comorbidities in SSA. In addition, SSA is grappling with poverty-related health problems and infectious diseases and is also undergoing the most rapid rates of urbanisation globally. These socioenvironmental and lifestyle factors may interact with genetic factors to alter the pathophysiological sequence leading to type 2 diabetes in sub-Saharan African populations. Indeed, current evidence from SSA and the diaspora suggests that the pathophysiology of type 2 diabetes in Black Africans is different from that in their European counterparts. Studies from the diaspora suggest that insulin clearance is the primary defect underlying the development of type 2 diabetes. We propose that, among Black Africans from SSA, hyperinsulinaemia due to a combination of both increased insulin secretion and reduced hepatic insulin clearance is the primary defect, which promotes obesity and insulin resistance, exacerbating the hyperinsulinaemia and eventually leading to beta cell failure and type 2 diabetes. Nonetheless, the current understanding of the pathogenesis of type 2 diabetes and the clinical guidelines for preventing and managing the disease are largely based on studies including participants of predominately White European ancestry. In this review, we summarise the existing knowledge base and data from the only non-pharmacological intervention that explores the pathophysiology of type 2 diabetes in SSA. We also highlight factors that may influence the pathogenesis of type 2 diabetes in SSA, such as social determinants, infectious diseases and genetic and epigenetic influences.

Physical behaviors and their association with type 2 diabetes mellitus risk markers in urban South African middle-aged adults: an isotemporal substitutionapproach.

INTRODUCTION: To examine the associations between physical behaviors and type 2 diabetes mellitus (T2DM) risk markers in middle-aged South African men and women. RESEARCH DESIGN AND METHODS: This cross-sectional study included middle-aged men (n=403; age: median (IQR), 53.0 (47.8-58.8) years) and women (n=324; 53.4 (49.1-58.1) years) from Soweto, South Africa. Total movement volume (average movement in milli-g) and time (minutes/day) spent in different physical behaviors, including awake sitting/lying, standing, light intensity physical activity (LPA) and moderate-to-vigorous intensity physical activity (MVPA), were determined by combining the signals from two triaxial accelerometers worn simultaneously on the hip and thigh. All participants completed an oral glucose tolerance test, from which indicators of diabetes risk were derived. Associations between physical behaviors and T2DM risk were adjusted for sociodemographic factors and body composition. RESULTS: Total movement volume was inversely associated with measures of fasting and 2-hour glucose and directly associated with insulin sensitivity, basal insulin clearance, and beta-cell function, but these associations were not independent of fat mass, except for basal insulin clearance in women. In men, replacing 30 min of sitting/lying, standing or LPA with the same amount of MVPA time was associated with 1.2-1.4 mmol/L lower fasting glucose and 12.3-13.4 mgl2/mUmin higher insulin sensitivity. In women, substituting sitting/lying with the same amount of standing time or LPA was associated with 0.5-0.8 mmol/L lower fasting glucose. Substituting 30 min sitting/lying with the same amount of standing time was also associated with 3.2 mgl2/mUmin higher insulin sensitivity, and substituting 30 min of sitting/lying, standing or LPA with the same amount of MVPA time was associated with 0.25-0.29 ng/mIU higher basal insulin clearance in women. CONCLUSION: MVPA is important in reducing T2DM risk in men and women, but LPA appears to be important in women only. Longitudinal and intervention studies warranted to provide more specific PA recommendations.

A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity.

We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the effect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and post-exercise training adaptations in obesity and metabolic related parameters. Exercise (n = 19) participants underwent 12-weeks of supervised aerobic and resistance training while controls (n = 12) continued their usual behaviours. FKBP5 methylation was measured in GSAT and ASAT using pyrosequencing. SNP and gene expression analyses were conducted using quantitative real-time PCR. Exercise training induced FKBP5 hypermethylation at two CpG dinucleotides within intron 7. When stratified based on the rs1360780 SNP, participants with the CT genotype displayed FKBP5 hypermethylation in GSAT (p < 0.05), and ASAT displayed in both CC and CT carriers. CC allele carriers displayed improved cardiorespiratory fitness, insulin sensitivity, gynoid fat mass, and waist circumference (p < 0.05) in response to exercise training, and these parameters were attenuated in women with the CT genotype. These findings provide a basis for future studies in larger cohorts, which should assess whether FKBP5 methylation and/or genetic variants such as the rs1360780 SNP could have a significant impact on responsiveness to exercise interventions.

Physical Behaviors and Their Association With Adiposity in Men and Women From a Low-Resourced African Setting.

BACKGROUND: We first explored the associations between physical behaviors and total and regional adiposity. Second, we examined how reallocating time in different physical behaviors was associated with total body fat mass in men and women from a low-income South African setting. METHODS: This cross-sectional study included a sample of 692 participants (384 men and 308 women) aged 41-72 years. Physical behaviors were measured using integrated hip and thigh accelerometry to estimate total movement volume and time spent in sleeping, sitting/lying, standing, light physical activity, and moderate to vigorous physical activity (MVPA). Total body fat mass and regional adiposity were measured using dual-energy X-ray absorptiometry. RESULTS: The associations between total movement volume and measures of regional obesity were mediated by total body adiposity. In men, reallocating 30 minutes of sitting/lying to 30 minutes of MVPA was associated with 1.0% lower fat mass. In women, reallocation of 30 minutes of sitting/lying to MVPA and 30 minutes of standing to MVPA were associated with a 0.3% and 1.4% lower fat mass, respectively. CONCLUSIONS: Although the association between physical behaviors and fat mass differed between men and women, the overall public health message is similar; reallocating sedentary time to MVPA is associated with a reduction in fat mass in both men and women.