Exploration of barriers and enablers to diabetes care for Aboriginal people on rural Ngarrindjeri Country.

ISSUES ADDRESSED: Addressing the disproportionate burden of type 2 diabetes prevalence in Aboriginal communities is critical. Current literature on diabetes care for Aboriginal people is primarily focused on remote demographics and overwhelmingly dominated by Western biomedical models and deficit paradigms. This qualitative research project adopted a strengths-based approach to explore the barriers and enablers to diabetes care for Aboriginal people on Ngarrindjeri Country in rural South Australia. METHODS: Knowledge Interface methodology guided the research as Aboriginal and Western research methods were drawn upon. Data collection occurred using three yarning sessions held on Ngarrindjeri Country. Yarns were transcribed and deidentified before a qualitative thematic analysis was conducted, guided by Dadirri and a constructivist approach to grounded theory. RESULTS: A total of 15 participants attended the yarns. Major barriers identified by participants were underscored by the ongoing impacts of colonisation. This was combated by a current of survival as participants identified enablers to diabetes care, namely a history of healthy community, working at the knowledge interface, motivators for action, and an abundance of community skills and leadership. CONCLUSIONS: Despite the raft of barriers detailed by participants throughout the diabetes care journey, Aboriginal people on Ngarrindjeri Country were found to be uniquely positioned to address diabetes prevalence and management. SO WHAT?: Health promotion efforts with Aboriginal people on Ngarrindjeri Country must acknowledge the sustained impacts of colonisation, while building on the abundance of community enablers, skills and strengths. Opportunities present to do so by adopting holistic, community-led initiatives that shift away from the dominant biomedical approach to diabetes care.

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.

Influence of vitamin D supplementation on growth, body composition, pubertal development and spirometry in South African schoolchildren: a randomised controlled trial (ViDiKids).

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. DESIGN: Phase 3 double-blind randomised placebo-controlled trial. SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline. INTERVENTIONS: Oral vitamin D3 (10 000 IU/week) versus placebo for 3 years. MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy. RESULTS: Mean serum 25-hydroxyvitamin D3 concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass. CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D3 boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.

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.

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.

Effects of concurrent exercise training on body composition, systemic inflammation, and components of metabolic syndrome in inactive academics: a randomised controlled trial.

PURPOSE: Low physical activity in the academic workplace may increase the risk of cardiometabolic disease. This randomised controlled trial investigated the effect of 14 weeks of concurrent exercise training (CT) on components of metabolic syndrome, body composition, insulin resistance, and markers of systemic inflammation in inactive academics. METHODS: 59 inactive academics were randomised into a CT (n = 29) or wait-list control group (n = 30). CT performed supervised training at an onsite facility 3 times per week for 14 weeks and cardiometabolic health was assessed pre- and post-intervention. Aerobic capacity was measured via a metabolic cart. Dual-Energy X-ray Absorptiometry measured fat mass, lean mass, and central adiposity. Fasting blood samples were analysed for interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), glucose, and lipid profile. RESULTS: Following the intervention, there was a decrease in fat mass (mean ± SD; - 1.3 ± 1.4%), android fat mass (median (IQR); - 0.06 (0.27) kg), and visceral adipose tissue (median (IQR); - 66 (110) cm3) in CT, but not control. Lean mass (median (IQR); 1.35 (1.86) kg) and aerobic capacity (mean ± SD; 4.0 ± 3.1 mL/kg/min) increased in CT, but not in control. There were no changes in IL-6, TNF-a, HOMA-IR, glucose, or lipid profile in response to the intervention (P > 0.05). Changes in insulin resistance were positively associated with IL-6 in the control group only (coefficients [95%CI]; 5.957 [2.961, 8.953]). CONCLUSION: Implementing combined aerobic and resistance exercise training programs in academic institutions may be an appropriate intervention to increase physical activity and reduce risk factors associated with cardiometabolic disease. TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry on the 23rd of April, 2019 (ACTRN12619000608167).

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.

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 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.

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.

Targeted proteomics of appendicular skeletal muscle mass and handgrip strength in black South Africans: a cross-sectional study.

Although appendicular skeletal muscle mass (ASM) and handgrip strength (HGS) are key components of sarcopenia, their underlying biological mechanisms remain poorly understood. We aimed to investigate associations of circulating biomarkers with ASM and HGS in middle-aged black South Africans. This study consisted of 934 black South Africans (469 men and 465 women, aged 41-72 years) from the Middle-aged Soweto cohort. Linear regression models were used to examine relationships between 182 biomarkers (measured with proximity extension assay) and dual-energy X-ray absorptiometry-measured ASM and dynamometer-measured HGS. Age, height, sex, smoking, alcohol, food insecurity, physical activity, visceral adipose tissue, HIV and menopausal status were included as confounders. Regression models showing sex-interactions were stratified by sex. The Benjamini-Hochberg false discovery rate (FDR) was used to control for multiple testing, and FDR-adjusted P values were reported. In the total sample, 10 biomarkers were associated with higher ASM and 29 with lower ASM (P < 0.05). Out of these 39 biomarkers, 8 were also associated with lower HGS (P < 0.05). MMP-7 was associated with lower HGS only (P = 0.011) in the total sample. Sex-interactions (P < 0.05) were identified for 52 biomarkers for ASM, and 6 for HGS. For men, LEP, MEPE and SCF were associated with higher ASM (P < 0.001, = 0.004, = 0.006, respectively), and MEPE and SCF were also associated with higher HGS (P = 0.001, 0.012, respectively). Also in men, 37 biomarkers were associated with lower ASM (P < 0.05), with none of these being associated with lower HGS. Furthermore, DLK-1 and MYOGLOBIN were associated with higher HGS only (P = 0.004, 0.006, respectively), while GAL-9 was associated with lower HGS only (P = 0.005), among men. For women, LEP, CD163, IL6, TNF-R1 and TNF-R2 were associated with higher ASM (P < 0.001, = 0.014, = 0.027, = 0.014, = 0.048, respectively), while IGFBP-2, CTRC and RAGE were associated with lower ASM (P = 0.043, 0.001, 0.014, respectively). No biomarker was associated with HGS in women. In conclusion, most biomarkers were associated with ASM and not HGS, and the associations of biomarkers with ASM and HGS displayed sex-specificity in middle-aged black South Africans. Proteomic studies should examine ASM and HGS individually. Future research should also consider sexual dimorphism in the pathophysiology of sarcopenia for development of sex-specific treatment and diagnostic methods.

Physical Activity Behaviors of a Middle-Age South African Cohort as Determined by Integrated Hip and Thigh Accelerometry.

PURPOSE: Descriptive studies of objectively measured physical activity behaviors in African populations are rare. We developed a method of combining hip and thigh accelerometery signals to quantify and describe physical behaviors in middle-age South African men and women. METHODS: We integrated signals from two triaxial accelerometers worn simultaneously during free-living, in a subsample of the Middle-age Soweto Cohort ( n = 794; mean (SD) age, 53.7 (6.3) yr). Acceleration time series from the accelerometers were combined and movement-related acceleration was derived using Euclidean Norm Minus One (in milligrams), to determine total movement volume (mean Euclidean Norm Minus One) and nonmovement time (<28 m g ), light-intensity physical activity (LPA; 28-85 m g ), and moderate- to vigorous-intensity physical activity (MVPA; >85 m g ); thigh pitch angle and a sleep diary were used to divide nonmovement time (in minutes per day) into sleep, awake sitting/lying, and standing. Sociodemographic factors were self-reported, and weight and height were measured. RESULTS: Mean (SD) wear time was 128 (48) h. Movement volume was 15.0 (6.5) m g for men and 12.2 (3.4) m g for women. Men spent more time in MVPA and sitting/lying, whereas women spent more time standing. Age was inversely associated with movement volume, MVPA, and LPA. When compared with their normal-weight counterparts, men who were overweight or obese spent less time in MVPA, whereas women who were overweight or obese spent less time in LPA and more time sitting/lying. Socioeconomic status was inversely associated with total movement volume, MVPA, and time spent sleeping, and positively associated with time spent sitting/lying, in both men and women. CONCLUSIONS: Integrating signals from hip and thigh accelerometers enables characterization of physical behaviors that can be applied in an African population.

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.

Sarcopenic Obesity in Africa: A Call for Diagnostic Methods and Appropriate Interventions.

This perspective aims to highlight the lack of current knowledge on sarcopenic obesity in Africa and to call for diagnostic methods and appropriate interventions. Sarcopenic obesity has been defined as obesity that occurs in combination with low muscle mass and function, which is typically evident in older adults. However, there has been no clear consensus on population-specific diagnostic criterion, which includes both gold-standard measures that can be used in a more advanced health care system, and surrogate measures that can be used in low-income settings with limited resources and funding. Importantly, low and middle-income countries (LMICs) across Africa are in an ongoing state of economic and social transition, which has contributed to an increase in the aging population, alongside the added burden of poverty, obesity, and associated co-morbidities. It is anticipated that alongside the increased prevalence of obesity, these countries will further experience an increase in age-related musculoskeletal diseases such as sarcopenia. The developmental origins of health and disease (DOHaD) approach will allow clinicians and researchers to consider developmental trajectories, and the influence of the environment, for targeting high-risk individuals and communities for treatment and/or prevention-based interventions that are implemented throughout all stages of the life course. Once a valid and reliable diagnostic criterion is developed, we can firstly assess the prevalence and burden of sarcopenic obesity in LMICs in Africa, and secondly, develop appropriate and sustainable interventions that target improved dietary and physical activity behaviors throughout the life course.

ß-cell function in black South African women: exploratory associations with insulin clearance, visceral and ectopic fat.

The role of ectopic fat, insulin secretion and clearance in the preservation ofß-cell function in black African women with obesity who typically present with hyperinsulinaemia is not clear. We aim to examine the associations between disposition index (DI, an estimate of ß-cell function), insulin secretion and clearance and ectopic fat deposition. This is a cross-sectional study of 43 black South African women (age 20-35 years) with obesity (BMI 30-40 kg/m2) and without type 2 diabetes that measured the following: DI, insulin sensitivity (SI), acute insulin response (AIRg), insulin secretion rate (ISR), hepatic insulin extraction and peripheral insulin clearance (frequently sampled i.v. glucose tolerance test); pancreatic and hepatic fat, visceral adipose tissue (VAT) and abdominal s.c. adipose tissue (aSAT) volume (MRI), intra-myocellular (IMCL) and extra-myocellular fat content (EMCL) (magnetic resonance spectroscopy). DI correlated positively with peripheral insulin clearance (ß 55.80, P = 0.002). Higher DI was associated with lower VAT, pancreatic fat and soleus fat, but VAT explained most of the variance in DI (32%). Additionally, higher first phase ISR (P = 0.033) and lower hepatic insulin extraction (P = 0.022) were associated with lower VAT, independent from SI, rather than with ectopic fat. In conclusion, peripheral insulin clearance emerged as an important correlate of DI. However, VAT was the main determinant of a lower DI above ectopic fat depots. Importantly, VAT, but not ectopic fat, is associated with both lower insulin secretion and higher hepatic insulin extraction. Prevention of VAT accumulation in young black African women should, therefore, be an important target for beta cell preservation.

Food Security, Dietary Intake, and Foodways of Urban Low-Income Older South African Women: An Exploratory Study.

This cross-sectional study explored the differences in sociodemographics, dietary intake, and household foodways (cultural, socioeconomic practices that affect food purchase, consumption, and preferences) of food secure and food insecure older women living in a low-income urban setting in South Africa. Women (n = 122) aged 60-85 years old were recruited, a sociodemographic questionnaire was completed, and food security categories were determined. The categories were dichotomised into food secure (food secure and mild food insecurity) and food insecure (moderate and severe). A one-week quantified food frequency questionnaire was administered. Height and weight were measured to calculate body mass index (BMI, kg/m2). Most participants (>90%) were overweight/obese, unmarried/widowed, and breadwinners with a low monthly household income. Food insecure participants (36.9%) more frequently borrowed money for food (57.8% vs. 39.0%, p = 0.04), ate less so that their children could have more to eat (64.4%. vs. 27.3%, p = 0.001), and had higher housing density (1.2 vs. 1.0, p = 0.03), compared to their food-secure counterparts. Overall, <30% of participants met the WHO (Geneva, Switzerland) recommended daily servings of healthy foods (fruits, vegetables, and dairy products), but >60% perceived that they consumed an adequate amount of healthy foods. The overall low-quality diet of our cohort was associated with poor nutritional perceptions and choices, coupled with financial constraints.