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.

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.

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.

Waist circumference thresholds predicting incident dysglycaemia and type 2 diabetes in Black African men and women.

AIMS: To determine the waist circumference (WC) thresholds for the prediction of incident dysglycaemia and type 2 diabetes (T2D) in Black South African (SA) men and women and to compare these to the advocated International Diabetes Federation (IDF) Europid thresholds. MATERIALS AND METHODS: In this prospective study, Black SA men (n = 502) and women (n = 527) from the Middle-aged Sowetan Cohort study who had normal or impaired fasting glucose at baseline (2011-2015) were followed up until 2017 to 2018. Baseline measurements included anthropometry, blood pressure and fasting glucose, HDL cholesterol and triglyceride concentrations. At follow-up, glucose tolerance was assessed using an oral glucose tolerance test. The Youden index was used to determine the optimal threshold of WC to predict incident dysglycaemia and T2D. RESULTS: In men, the optimal WC threshold was 96.8 cm for both dysglycaemia and T2D (sensitivity: 56% and 70%; specificity: 74% and 70%, respectively), and had higher specificity (P < 0.001) than the IDF threshold of 94 cm. In women, the optimal WC threshold for incident dysglycaemia was 91.8 cm (sensitivity 86%, specificity 37%) and for T2D it was 95.8 cm (sensitivity 85%, specificity 45%), which had lower sensitivity, but higher specificity to predict incident dysglycaemia and T2D than the IDF threshold of 80 cm (sensitivity: 97% and 100%; specificity: 12% and 11%, respectively)). CONCLUSIONS: We show for the first time using prospective cohort data from Africa that the IDF Europid WC thresholds are not appropriate for an African population, and show that African-specific WC thresholds perform better than the IDF Europid thresholds to predict incident dysglycaemia and T2D.

Exercise training improves mitochondrial respiration and is associated with an altered intramuscular phospholipid signature in women with obesity.

AIMS/HYPOTHESIS: We sought to determine putative relationships among improved mitochondrial respiration, insulin sensitivity and altered skeletal muscle lipids and metabolite signature in response to combined aerobic and resistance training in women with obesity. METHODS: This study reports a secondary analysis of a randomised controlled trial including additional measures of mitochondrial respiration, skeletal muscle lipidomics, metabolomics and protein content. Women with obesity were randomised into 12 weeks of combined aerobic and resistance exercise training (n = 20) or control (n = 15) groups. Pre- and post-intervention testing included peak oxygen consumption, whole-body insulin sensitivity (intravenous glucose tolerance test), skeletal muscle mitochondrial respiration (high-resolution respirometry), lipidomics and metabolomics (mass spectrometry) and lipid content (magnetic resonance imaging and spectroscopy). Proteins involved in glucose transport (i.e. GLUT4) and lipid turnover (i.e. sphingomyelin synthase 1 and 2) were assessed by western blotting. RESULTS: The original randomised controlled trial showed that exercise training increased insulin sensitivity (median [IQR]; 3.4 [2.0-4.6] to 3.6 [2.4-6.2] x10-5 pmol l-1 min-1), peak oxygen consumption (mean ± SD; 24.9 ± 2.4 to 27.6 ± 3.4 ml kg-1 min-1), and decreased body weight (84.1 ± 8.7 to 83.3 ± 9.7 kg), with an increase in weight (pre intervention, 87.8± 10.9 to post intervention 88.8 ± 11.0 kg) in the control group (interaction p < 0.05). The current study shows an increase in mitochondrial respiration and content in response to exercise training (interaction p < 0.05). The metabolite and lipid signature at baseline were significantly associated with mitochondrial respiratory capacity (p < 0.05) but were not associated with whole-body insulin sensitivity or GLUT4 protein content. Exercise training significantly altered the skeletal muscle lipid profile, increasing specific diacylglycerol(32:2) and ceramide(d18:1/24:0) levels, without changes in other intermediates or total content of diacylglycerol and ceramide. The total content of cardiolipin, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) increased with exercise training with a decrease in the PC:PE ratios containing 22:5 and 20:4 fatty acids. These changes were associated with content-driven increases in mitochondrial respiration (p < 0.05), but not with the increase in whole-body insulin sensitivity or GLUT4 protein content. Exercise training increased sphingomyelin synthase 1 (p < 0.05), with no change in plasma-membrane-located sphingomyelin synthase 2. CONCLUSIONS/INTERPRETATION: The major findings of our study were that exercise training altered specific intramuscular lipid intermediates, associated with content-driven increases in mitochondrial respiration but not whole-body insulin sensitivity. This highlights the benefits of exercise training and presents putative target pathways for preventing lipotoxicity in skeletal muscle, which is typically associated with the development of type 2 diabetes.

Understanding factors associated with sarcopenic obesity in older African women from a low-income setting: a cross-sectional analysis.

BACKGROUND: High rates of food insecurity, obesity and obesity-related comorbidities in ageing South African (SA) women may amplify the risk of developing sarcopenic obesity. This study aimed to investigate the prevalence and correlates of sarcopenic obesity and its diagnostic components [grip strength, appendicular skeletal muscle mass (ASM) and body mass index (BMI)] in older SA women from a low-income setting. METHODS: This cross-sectional study recruited black SA women between the ages of 60-85 years (n = 122) from a low-income community. Testing included a fasting blood sample (markers of cardiometabolic risk, HIV), whole body and regional muscle and fat mass (dual-energy absorptiometry x-ray), anthropometry, blood pressure, functional movement tests, current medication use, demographic and health questionnaires, physical activity (PA; accelerometery), household food insecurity access scale, and a one-week quantified food frequency questionnaire. Foundation for the National Institutes of Health (FNIH) criteria (grip strength and ASM, adjusted for BMI) were used to classify sarcopenia. Participants with sarcopenia alongside a BMI of > 30.0 kg/m2 were classified as having sarcopenic obesity. Prevalence using other criteria (European Working Group on Sarcopenia in Older People, Asian Working Group for Sarcopenia and the International Working Group for Sarcopenia) were also explored. RESULTS: The prevalence of sarcopenia was 27.9%, which comprised of sarcopenia without obesity (3.3%) and sarcopenic obesity (24.6%). Other classification criteria showed that sarcopenia ranged from 0.8-14.7%, including 0.8-9.8% without obesity and 0-4.9% with sarcopenic obesity. Using multivariate-discriminant analysis (OPLS-DA) those with sarcopenic obesity presented with a descriptive profile of higher C-reactive protein, waist circumference, food security and sedentary time than women without sarcopenic obesity (p = 0.046). A similar profile described women with low BMI-adjusted grip strength (p < 0.001). CONCLUSIONS: The majority of women with sarcopenia were also obese (88%). We show a large discrepancy in the diagnostic criteria and the potential for significantly underestimating the prevalence of sarcopenia if BMI is not adjusted for. The main variables common to women with sarcopenic obesity were higher food security, lower PA and chronic inflammation. Our data highlights the importance of addressing obesity within these low-income communities to ensure the prevention of sarcopenic obesity and that quality of life is maintained with ageing.

Changes in systemic and subcutaneous adipose tissue inflammation and oxidative stress in response to exercise training in obese black African women.

KEY POINTS: Inflammation and oxidative stress are interrelated during obesity and contribute to the development of insulin resistance; and exercise training represents a key component in the management of these conditions. Black African women, despite high gluteal subcutaneous adipose tissue (SAT) and less visceral fat, are less insulin sensitive than their white counterparts. Exercise training improved systemic oxidative stress in obese black women, which was related to gynoid fat reduction and not insulin sensitivity. Inflammatory markers changed depot-specifically in response to exercise training, increasing in gluteal SAT without changing in abdominal SAT. The increase of inflammatory state in gluteal SAT after exercise training is suggested to result from tissue remodelling consecutive to the reduction of gynoid fat but does not contribute to the improvement of whole-body insulin sensitivity in obese black South African women. ABSTRACT: Inflammation and oxidative stress are interrelated during obesity and contribute to the development of insulin resistance. Exercise training represents a key component in the management of obesity. We evaluated the effects of 12 weeks' combined resistance and aerobic exercise training on systemic and abdominal vs. gluteal subcutaneous adipose tissue (SAT) inflammatory and oxidative status in obese black South African women. Before and after the intervention, body composition (dual energy X-ray absorptiometry), cardio-respiratory fitness ( VO2peak ), serum and SAT inflammatory and oxidative stress markers were measured from 15 (control group) and 20 (exercise group) women and insulin sensitivity (SI ; frequently sampled intravenous glucose tolerance test) was estimated. Following the intervention, VO2peak (9.8%), body fat composition (1-3%) and SI (9%) improved, serum thiobarbituric acid reactive substances (TBARS) decreased (6.5%), and catalase activity increased (23%) in the exercise compared to the control group (P < 0.05), without changes in circulating inflammatory markers. The mRNA content of interleukin-10, tumour necrosis factor α, nuclear factor κB and macrophage migration inhibitory factor increased in the gluteal SAT exercise compared to the control group P < 0.05), with no changes in abdominal SAT. These changes of inflammatory profile in gluteal SAT, in addition to the reduction of circulating TBARS, correlated with the reduction of gynoid fat, but not with the improvement of SI . The changes in systemic oxidative stress markers and gluteal SAT inflammatory genes correlated with the reduction in gynoid fat but were not directly associated with the exercise-induced improvements in SI .

Exercise intervention alters HDL subclass distribution and function in obese women.

BACKGROUND: Obesity is associated with a change in high-density lipoprotein (HDL) function and subclass. Exercise training reduces cardiovascular risk in obese patients. We aimed to explore the effect of an exercise training stimulus on HDL functionality and subclass in obese women. METHODS: Thirty-two obese black South African women were randomly assigned to exercise (combined aerobic and resistance exercise) or control (no exercise) conditions for 12-weeks. Pre- and post-testing included venous blood sampling for analysis of lipid profile and HDL functionality, by measuring cellular cholesterol efflux capacity, reduction in endothelial vascular cell adhesion molecule (VCAM) expression (anti-inflammatory function), paraoxonase (PON) (antioxidative function) and platelet activating factor acetylhydrolase (PAF-AH) activities (anti-thrombotic function). PON-1 and PAF-AH expression were determined in serum and in isolated HDL using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. RESULTS: Exercise training resulted in a decrease in body mass index (- 1.0 ± 0.5% vs + 1.2 ± 0.6%, p = 0.010), PON activity (- 8.7 ± 2.4% vs + 1.1 ± 3.0%, p = 0.021), PAF-AH serum expression (- 22.1 ± 8.0% vs + 16.9 ± 9.8, p = 0.002), and the distribution of small HDL subclasses (- 10.1 ± 5.4% vs + 15.7 ± 6.6%, p = 0.004) compared to controls. Exercise did not alter HDL cellular cholesterol efflux capacity and anti-inflammatory function. CONCLUSIONS: These results demonstrate the potential for exercise training to modify HDL subclass distribution and HDL function in obese women. TRIAL REGISTRATION: Clinical trials number: PACTR201711002789113 .

Perceptions relating to body size, weight loss and weight-loss interventions in black South African women: a qualitative study.

OBJECTIVE: A higher tolerance for a larger body size has been associated with obesity in black South African (SA) women. The aim of the present study was to explore perceptions regarding body size and weight loss in a sample of black women from a low-income community in Cape Town, SA. DESIGN: Qualitative pilot study including five focus groups. Data were analysed using thematic analysis. SETTING: Khayelitsha, Cape Town, SA. SUBJECTS: Twenty-one black SA women. RESULTS: The majority of participants had positive perceptions of overweight/obesity, which were influenced by community and cultural perceptions, but some inconsistencies were observed as overweight/obesity was also associated with ill health. Participants identified many benefits to weight loss, but due to the association with sickness, they were concerned about being stigmatised in their community. Although participants had knowledge about healthy eating, the main barrier to eating healthily included the perceived higher cost of healthier food and food insecurity. All participants saw exercise as a strategy to lose weight and improve health, and were interested in participating in a community-based exercise intervention, but negative community perceptions and conflicting views regarding who should lead the intervention were identified as barriers. CONCLUSIONS: These findings highlight the complexities surrounding participants' perceptions regarding body size, weight loss and weight-loss interventions, and emphasise low socio-economic status as a barrier to change. The study also highlights the strong influence of cultural ideals and community perceptions on personal perceptions. These findings underscore the necessity for culturally appropriate weight-loss interventions in low-income, transitioning communities.

Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution.

BACKGROUND: Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease. METHODS: We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. RESULTS: PON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p < 0.05), regardless of PON-1 protein levels. Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p <0.05) and HDL-associated PAF-AH expression compared to obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups. CONCLUSIONS: Our data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk.

Protection from Cardiovascular Disease Due to Increased High-Density Lipoprotein Cholesterol in African Black Populations: Myth or Reality?

The burden of cardiovascular disease (CVD) in sub-Saharan Africa has increased over the last decade. Despite this, African Black populations present with relatively low incidences of coronary heart disease and ischemic heart disease, which may be attributed to their lower total cholesterol, triglycerides and low-density lipoprotein cholesterol concentrations, compared with White populations. Commensurate with these lower lipid levels, it was believed that high-density lipoprotein cholesterol (HDL-C) concentrations would be higher in Black populations compared with their White counterparts. This is based on data from previous studies of African and African American populations; however, recent studies conducted in Africa found similar or lower HDL-C concentrations in Black compared with White individuals. Current research, therefore, suggests that HDL-C may not be a good indicator of cardiovascular risk and future research should focus on HDL quality (vs quantity), by measuring HDL functionality and subclass.

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

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.

Lean and obese dietary phenotypes: differences in energy and substrate metabolism and appetite.

This study aimed to characterise lean and obese phenotypes according to diet and body composition, and to compare fasting and postprandial appetite and metabolic profiles following a high-fat test meal. A total of ten lean (BMI40 and 30 kg/m2) high-fat consumers (OHF; >40 % energy from fat) were recruited. Before and following the test meal (4727 kJ (1130 kcal), 77 % fat, 20 % carbohydrate (CHO) and 3 % protein), fasting plasma glucose, insulin, leptin, ghrelin, peptide YY (PYY), RER, RMR and subjective appetite ratings (AR) were measured for 6 h. Thereafter, subjects consumed a self-selected portion of a standardised post-test meal (40 % fat, 45 % CHO and 15 % protein) and reported AR. Fasting (P=0·01) and postprandial (P<0·001) fat oxidation was significantly higher in LHF than in LLF but was not different between LHF and OHF. Although similar between the lean groups, fasting and postprandial energy expenditures were significantly higher in OHF compared with LHF (P<0·01). Despite similar AR across groups, LLF consumed a relatively greater quantity of the post-test meal than did LHF (7·87 (sd 2·96) v. 7·23 (sd 2·67) g/kg, P=0·013). The lean groups showed appropriate changes in plasma ghrelin and PYY following the test meal, whereas the OHF group showed a blunted response. In conclusion, the LHF phenotype had a greater capacity for fat oxidation, which may be protective against weight gain. OHF individuals had a blunted appetite hormone response to the high-fat test meal, which may subsequently increase energy intake, driving further weight gain.

Meeting physical activity guidelines is associated with reduced risk for cardiovascular disease in black South African women; a 5.5-year follow-up study.

BACKGROUND: Low levels of physical activity (PA) have been associated with increased risk for cardiovascular disease (CVD) and type 2 diabetes (T2D), but few studies have examined whether meeting international PA guidelines is associated with reduced risk in a black South African (SA) population. The aims of this study were to compare body composition and cardio-metabolic risk factors for CVD and T2D between active and inactive groups (part 1, cross-sectional analysis) and, to determine whether PA level predicts changes in body composition and cardio-metabolic risk factors for CVD and T2D at follow-up after 5.5-years (part 2, longitudinal analysis). METHODS: Part 1 included a sample of 240 apparently healthy black SA women (26 ± 7 years) who underwent the following measurements at baseline: PA (Global Physical Activity Questionnaire (GPAQ)), body composition and regional fat distribution (dual-energy x-ray absorptiometry and computerised tomography), blood pressure, fasting glucose, insulin and lipid concentrations. For part 2, a sub-sample of women (n = 57) underwent the same measurements after a 5.5-year period. RESULTS: At baseline, 61% of women were classified as meeting the guidelines for moderate- to vigorous-intensity physical activity (MVPA) according to GPAQ. Women who were active had significantly lower body weight (p < 0.001), body fat (BMI, fat mass, % body fat, waist circumference, central and appendicular fat mass, all p < 0.001), and measures of insulin resistance (fasting serum insulin and HOMA-IR, both p = 0.01), and higher high-density lipoprotein cholesterol (p = 0.041), compared to the inactive group. At follow-up, all body fat measures increased significantly in both groups and diastolic blood pressure decreased significantly in those who were active at baseline, but did not change in those who were inactive. CONCLUSIONS: Meeting PA guidelines was associated with decreased risk for CVD and T2D in black SA women, but did not prevent the increase in body fat over time. Interventions promoting physical activity to specifically address obesity in this high-risk group are recommended.

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.

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.