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Introduction: We codesigned an intervention with a low-resourced community with the aim to investigate the effects of time-restricted eating (TRE) on changes in body weight and associated cardiometabolic outcomes in South African women living with overweight/obesity and HIV who have initiated dolutegravir (DTG)-based antiretroviral therapy (ART)., Methods and Analysis: Women with overweight or obesity (body mass index ≥25 kg/m², no upper limit), aged 20-45 years, living with HIV and in a low-resourced community, and receiving DTG-based ART for less than 2 years will be recruited from a community healthcare centre in Khayelitsha, Cape Town (n=152). Participants will be randomised 1:1 to the TRE group (n=76) or standard of care control group (n=76) for 12 months. The TRE group will be required to restrict their eating window to ~8-10 hours/day and will receive nutritional information sessions at baseline and at 3, 6, 9 and 12 months. The primary outcome of body weight will be assessed at baseline and monthly. Cardiometabolic measures will be reported as secondary outcomes. At baseline, 6- and 12 months, an oral glucose tolerance test (to estimate insulin sensitivity and beta-cell function), questionnaires (sociodemographic, food insecurity, quality of life, social support and sleep quality) and a quantified food frequency questionnaire (total energy and macronutrient composition) will be completed. Every 3 months, appetite ratings, bioelectrical impedance (fat mass and fat-free mass), fasting venous bloods (glucose, insulin, gut hormones and systemic inflammation) and process evaluation (qualitative interviews) will be completed. Monthly monitoring will also include anthropometry and blood pressure., Ethics and Dissemination: The study is conducted in accordance with the Declaration of Helsinki and has been approved by the Human Research Ethics Committee of the University of Cape Town (628/2021). Verbal and written consent is required from study participants. Results of this study will be published in peer-reviewed journals and presented at conferences., Trial Registration Number: PACTR202302484999720., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Human Immunodeficiency Virus (HIV) and type 2 diabetes (T2D) are amongst the leading causes of death in South Africa. The preferred first-line anti-retroviral treatment contains dolutegravir (DTG), shown to increase body weight, may compound the already high rates of obesity and associated risk for T2D. South Africa has widespread food insecurity, making traditional dietary strategies difficult to implement. Time-restricted eating (TRE) may be an appropriate intervention in resource-limited communities., Methods: This article outlines the development and feasibility testing of a TRE intervention to inform the design of a TRE randomised controlled trial in women (20-45 years old) living with overweight/obesity and HIV, receiving DTG-based treatment from a resource-limited community in Cape Town, South Africa. Factors influencing TRE adoption were identified using the Capability, Opportunity, Motivation - Behaviour model and the Theoretical Domains Framework, combining in-depth interviews (IDIs) and focus group discussions. Participants from the IDIs went on to participate in a single arm 4-week TRE pilot trial where feasibility was explored in terms of reach, acceptability, applicability, and implementation integrity. An iterative, thematic analysis approach was employed to analyse the qualitative data., Results: Participants included 33 isiXhosa-speaking women (mean age 37.1 years, mean BMI 35.9 kg/m 2 ). Thematic analysis identified psychological capability (knowledge of fasting), social influences (cultural preferences, family support), and reflective motivation (awareness of weight, health impact, motivation for TRE) as key factors influencing adoption of TRE for weight management. In a 4-week TRE pilot trial (n = 12), retention was 100%. Positive outcomes perceived included improved energy, appetite control and weight loss. TRE was perceived as acceptable, easy, and enjoyable. Family support facilitated adherence, while habitual and social eating and drinking practices were barriers. Compliance was high, aided by self-selected eating times, reminders, and weekly calls. Recommendations included the incorporation of dietary education sessions and text messages to provide additional support and reminders., Conclusions: This study indicates that TRE is a feasible weight management strategy in women living with overweight/obesity and HIV, receiving DTG-based treatment in a resource-limited community. These findings will ensure that the forthcoming TRE randomised controlled trial is adapted and optimised to the local South African context., (© 2024. The Author(s).)

Objective: To determine whether vitamin D supplementation influences grip strength, explosive leg power, cardiorespiratory fitness and risk of exercise-induced bronchoconstriction (EIB) in South African schoolchildren., Methods: Substudy (n=450) in Cape Town schoolchildren aged 8-11 years nested within a phase 3 randomised placebo-controlled trial (ViDiKids). The intervention was weekly oral doses of 10 000 IU vitamin D 3 (n=228) or placebo (n=222) for 3 years. Outcome measures were serum 25-hydroxyvitamin D 3 (25(OH)D 3 ) concentrations, grip strength, standing long jump distance, peak oxygen uptake (VO 2peak , determined using 20 m multistage shuttle run tests) and the proportion of children with EIB, measured at end-study., Results: 64.7% of participants had serum 25(OH)D 3 concentrations <75 nmol/L at baseline. At 3-year follow-up, children randomised to vitamin D versus placebo had higher mean serum 25(OH)D 3 concentrations (97.6 vs 58.8 nmol/L, respectively; adjusted mean difference 39.9 nmol/L, 95% CI 36.1 to 43.6). However, this was not associated with end-study differences in grip strength, standing long jump distance, VO 2peak or risk of EIB., Conclusion: A 3-year course of weekly oral supplementation with 10 000 IU vitamin D 3 elevated serum 25(OH)D 3 concentrations in South African schoolchildren but did not influence muscle strength, exercise capacity or risk of EIB., Competing Interests: ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord, DSM Nutritional Products, Thornton & Ross and Hyphens Pharma. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord, Synergy Biologics and Cytoplan; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma; receipt of consultancy fees from DSM Nutritional Products and Qiagen; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref NCT04641195) and unpaid work as a Programme Committee member for the Vitamin D Workshop., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2024 The Author(s). Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

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(β)-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 (β = 0.124, P < .001) and β-cell function (β = 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Objectives: This research program involves two phases to identify enablers and barriers to diabetes care for Aboriginal people on Ngarrindjeri country; and co-design a strength-based metabolic syndrome and Type 2 Diabetes (T2D) remission program with the Ngarrindjeri community., Study Design: A study protocol on qualitative research., Methods: The study will recruit Aboriginal people living on Ngarrindjeri country above 18 years of age with a diagnosis of metabolic syndrome or T2D. Recruitment for phases one and two will occur through the Aboriginal Health Team at the Riverland Mallee Coorong Local Health Network. The lived experiences of T2D will be explored with 10-15 Aboriginal participants, through an Aboriginal conversational technique called 'yarning' (60-90 min) in phase 1. Elders and senior community representatives (n = 20-30) will participate in four co-design workshops (2-4 h) in phase 2. Qualitative data will be transcribed and thematically analysed (NVivo version 12). The analysis will focus on protective factors for the Cultural Determinants of Health. Ethics approval was obtained from Aboriginal Health Research Ethics Committee in South Australia (04-22-1009), and Flinders University Human Research Ethics Committee (5847)., Results: This work will be used to pilot the co-designed diabetes remission trial. Outcomes will be published in peer-reviewed journals, presented at conferences, focusing on following best practice guidelines from the Australian Institute of Aboriginal and Torres Strait Islander Studies and National Health and Medical Research Council. Research translation will occur through digital posters, manuals, and infographics., Conclusions: The findings will be summarised to all Aboriginal organisations involved in this study, along with peak bodies, stakeholders, Aboriginal Services, and interested participants., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd on behalf of The Royal Society for Public Health.)

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 D 3 (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 D 3 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 D 3 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., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Madlala, Myer, Geffen, Meyer, Mendham, Goedecke, Bengtson, Jao and Dugas.)

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) cm 3 ) 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)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Phiri, Micklesfield, Mendham, Goedecke and de Villiers.)

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., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

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.

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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

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.

The role of ectopic fat, insulin secretion and clearance in the preservation ofβ-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 β-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 (β 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.

This study aimed to investigate differences in physical activity (PA) patterns and the associations between objectively measured 24-h movement behaviors and musculoskeletal measures (muscle strength, muscle mass, physical performance, and bone mineral density) in a high-income and a low-income community. This cross-sectional study recruited independent living older adults aged 60-85 years from high-income Scottish (n = 150) and low-income South African (n = 138) settings. Participants completed demographic and health questionnaires, and testing included body composition and bone mineral density (dual energy X-ray absorptiometry), physical performance (grip strength, gait speed), and PA (accelerometry). Participants accumulated similar amounts of weekly total PA, however, the Scottish cohort engaged in more moderate-to-vigorous intensity PA (MVPA) and sedentary behavior (SB), while the South African cohort spent more time sleeping and in light intensity PA (LPA). From compositional data analysis, more time spent in MVPA relative to the other movement behaviors was positively associated with higher muscle mass ( p < 0.001) and strength ( p = 0.001) in the Scottish cohort. Conversely, more time spent in MVPA was associated with faster gait speed ( p < 0.001) and greater hip bone mineral density ( p = 0.011) in the South African cohort. Our findings confirm the beneficial role of MVPA in both high- and low-income cohorts, however, the relationship MVPA had with components of musculoskeletal health in older adults differed between settings.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mendham, Lundin-Olsson, Goedecke, Micklesfield, Christensen, Gallagher, Myburgh, Odunitan-Wayas, Lambert, Kalula, Hunter and Brooks.)

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/m 2 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.

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/m 2 ). 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.

Purpose: To assess the efficacy of a combined light exposure and sleep hygiene intervention to improve team-sport performance following eastward long-haul transmeridian travel., Methods: Twenty physically trained males underwent testing at 09:00 and 17:00 hours local time on 4 consecutive days at home (baseline) and the first 4 days following 21 hours of air travel east across 8 time zones. In a randomized, matched-pairs design, participants traveled with (INT; n = 10) or without (CON; n = 10) a light exposure and sleep hygiene intervention. Performance was assessed via countermovement jump, 20-m sprint, T test, and Yo-Yo Intermittent Recovery Level 1 tests, together with perceptual measures of jet lag, fatigue, mood, and motivation. Sleep was measured using wrist activity monitors in conjunction with self-report diaries., Results: Magnitude-based inference and standardized effect-size analysis indicated there was a very likely improvement in the mean change in countermovement jump peak power (effect size 1.10, ±0.55), and likely improvement in 5-m (0.54, ±0.67) and 20-m (0.74, ±0.71) sprint time in INT compared with CON across the 4 days posttravel. Sleep duration was most likely greater in INT both during travel (1.61, ±0.82) and across the 4 nights following travel (1.28, ±0.58) compared with CON. Finally, perceived mood and motivation were likely worse (0.73, ±0.88 and 0.63, ±0.87) across the 4 days posttravel in CON compared with INT., Conclusions: Combined light exposure and sleep hygiene improved speed and power but not intermittent-sprint performance up to 96 hours following long-haul transmeridian travel. The reduction of sleep disruption during and following travel is a likely contributor to improved performance.

Background: Improving sleep quality and reducing depressive symptoms may be target mechanisms for intervention-based research aimed at reducing cardiometabolic risk in low-income communities. This study assessed the effects of exercise training on depressive symptoms and sleep in obese women for a low socioeconomic community. The secondary aim explored associations between changes in depressive symptoms and sleep with changes in cardiorespiratory fitness and cardiometabolic risk factors., Methods: Participants were randomized into exercise (n = 20) or control (n = 15) groups. The exercise group completed 12 weeks of combined resistance and aerobic training (40-60 min, 4 d/wk), and the control group maintained habitual diet and activity. Preintervention and postintervention testing included questionnaires on symptoms of depression, psychological distress, and sleep quality. Sedentary time, peak oxygen consumption, body mass index, and insulin sensitivity were measured objectively. Sleep duration (accelerometry) was assessed at preintervention and weeks 4, 8, and 12., Results: Exercise training reduced depressive symptoms (P = .002) and improved sleep quality (P < .001) and sleep efficiency (P = .005). Reduced depressive symptoms were associated with improved peak oxygen consumption (rho = -.600, P < .001), and improved sleep quality correlated with reduced sedentary time (rho = .415, P = .018)., Conclusion: These results highlight the potential for community-based exercise interventions to simultaneously address multiple comorbidities in a low-income setting.

Objective: This study assessed the changes in red blood cell total phospholipid (RBC-TPL) and subcutaneous adipose tissue (SAT) fatty acid (FA) composition in response to 12 weeks of exercise training in South African women with obesity and the associations with changes in cardiometabolic risk factors., Methods: Previously sedentary women were randomized into control (n = 15) or exercise (n = 20) groups. RBC-TPL and SAT FA profiles, SAT gene expression, systemic inflammatory markers, liver fat, and insulin sensitivity (S I ) were measured before and after the intervention., Results: Compared with control, exercise training induced decreases in RBC-TPL dihomo-γ-linolenic acid content and stearoyl-CoA desaturase-1 and increased delta-5 desaturase-estimated activity (P < 0.05). In the combined group, these changes correlated with changes in circulating leptin and TNFα (P < 0.05), as well as lower liver fat (P < 0.01). Exercise training decreased saturated FA (lauric and myristic acids) and increased polyunsaturated FA (eicosadienoic and adrenic acids) (P < 0.05) in abdominal SAT, whereas γ-linolenic acid decreased (P < 0.01) in gluteal SAT. These changes in RBC-TPL and SAT FA compositions were not associated with changes in SAT gene expression and S I ., Conclusions: Exercise training alters RBC-TPL desaturase activities, which correlate with lower liver fat and systemic inflammation but not with the improvement of S I ., (© 2020 The Authors. Obesity published by Wiley Periodicals LLC., on behalf of The Obesity Society (TOS).)

Objective: We investigated the effects of a 12-week exercise intervention on insulin sensitivity (SI) and hyperinsulinemia and associated changes in regional and ectopic fat., Research Design and Methods: Healthy, black South African women with obesity (mean age 23 ± 3.5 years) and of isiXhosa ancestry were randomised into a 12-week aerobic and resistance exercise training group (n = 23) and a no exercise group (control, n = 22). Pre and post-intervention testing included assessment of SI, insulin response to glucose (AIRg), insulin secretion rate (ISR), hepatic insulin extraction (FEL) and disposition index (DI) (AIRg × SI) (frequently sampled i.v. glucose tolerance test); fat mass and regional adiposity (dual-energy X-ray absorptiometry); hepatic, pancreatic and skeletal muscle fat content and abdominal s.c. and visceral adipose tissue volumes (MRI)., Results: Exercise training increased VO2peak (mean ± s.d.: 24.9 ± 2.42 to 27.6 ± 3.39 mL/kg/min, P < 0.001), SI (2.0 (1.2-2.8) to 2.2 (1.5-3.7) (mU/l)-1 min-1, P = 0.005) and DI (median (interquartile range): 6.1 (3.6-7.1) to 6.5 (5.6-9.2) × 103 arbitrary units, P = 0.028), and decreased gynoid fat mass (18.5 ± 1.7 to 18.2 ± 1.6%, P < 0.001) and body weight (84.1 ± 8.7 to 83.3 ± .9.7 kg, P = 0.038). None of these changes were observed in the control group, but body weight increased (P = 0.030). AIRg, ISR and FEL, VAT, SAT and ectopic fat were unaltered after exercise training. The increase in SI and DI were not associated with changes in regional or ectopic fat., Conclusion: Exercise training increased SI independent from changes in hyperinsulinemia and ectopic fat, suggesting that ectopic fat might not be a principal determinant of insulin resistance in this cohort.

The differential associations of adipose depots with metabolic risk during obesity have been proposed to be controlled by environmental and genetic factors. We evaluated the regional differences in transcriptome signatures between abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) in obese black South African women and tested the hypothesis that 12-week exercise training alters gene expression patterns in a depot-specific manner. Twelve young women performed 12-weeks of supervised aerobic and resistance training. Pre- and post-intervention measurements included peak oxygen consumption (VO 2peak ), whole-body composition and unbiased gene expression analysis of SAT depots. VO 2peak increased, body weight decreased, and body fat distribution improved with exercise training (p < 0.05). The expression of 15 genes, mainly associated with embryonic development, differed between SAT depots at baseline, whereas 318 genes were differentially expressed post-training (p < 0.05). Four developmental genes were differentially expressed between these depots at both time points (HOXA5, DMRT2, DMRT3 and CSN1S1). Exercise training induced changes in the expression of genes associated with immune and inflammatory responses, and lipid metabolism in gSAT, and muscle-associated processes in aSAT. This study showed differences in developmental processes regulating SAT distribution and expandability of distinct depots, and depot-specific adaptation to exercise training in black South African women with obesity.

A bstract : Background and Aims: During positive energy balance, excess lipid storage in subcutaneous adipose tissue (SAT) is associated with increased lipolysis. Elevated circulating fatty acid (FA) concentrations from both SAT lipolysis and dietary fat intake may result in visceral adipose tissue (VAT) accumulation, impairment of glucose metabolism, altogether increasing obesity-associated metabolic risks. We aimed to test the hypothesis that FA composition of red blood cell total phospholipids (RBC-TPL) and SAT is associated with body fat centralisation (VAT/SAT ratio) and insulin sensitivity (S I ) in black South African women with obesity., Methods: Participants' ( n = 41) body fat composition and distribution, S I , and RBC-TPL, abdominal and gluteal SAT (gSAT) FA composition (gas-liquid chromatography) were measured., Results: RBC-TPL contained higher proportions of saturated fatty acids (SFAs) than SAT ( p < 0.001), which were associated with lower S I ( p < 0.05). Mono-unsaturated fatty acids (MUFAs) and stearoyl-CoA desaturase-1 (SCD1)-16 were lower, while poly-unsaturated fatty acids (PUFAs), and delta-5 and delta-6 desaturase indices were higher in RBC-TPL than SAT ( p < 0.001). Interestingly, FA profiles differed between SAT depots with higher SFAs and lower MUFAs, SCD1-16 and SCD1-18 indices in abdominal compared to gluteal SAT ( p < 0.01). In both SAT depots, higher SFAs and lower PUFAs (n-3 and n-6) correlated with lower VAT/SAT ratio; and lower PUFAs (n-3 and n-6) and higher total MUFA correlated with higher S I ., Conclusion: Our findings confirm the relationships between the FA composition of RBC-TPL and SAT and metabolic risk in black women with obesity, which are dependent on both the FA class, and the tissue type/blood compartment in which they are distributed., Competing Interests: The authors declare no conflict of interest.

We assessed differences in mitochondrial function in gluteal (gSAT) and abdominal subcutaneous adipose tissue (aSAT) at baseline and in response to 12-weeks of exercise training; and examined depot-specific associations with body fat distribution and insulin sensitivity (S I ). Obese, black South African women (n = 45) were randomized into exercise (n = 23) or control (n = 22) groups. Exercise group completed 12-weeks of aerobic and resistance training (n = 20), while the control group (n = 15) continued usual behaviours. Mitochondrial function (high-resolution respirometry and fluorometry) in gSAT and aSAT, S I (frequently sampled intravenous glucose tolerance test), body composition (dual-energy X-ray absorptiometry), and ectopic fat (MRI) were assessed pre- and post-intervention. At baseline, gSAT had higher mitochondrial respiratory capacity and hydrogen peroxide (H 2 O 2 ) production than aSAT (p < 0.05). Higher gSAT respiration was associated with higher gynoid fat (p < 0.05). Higher gSAT H 2 O 2 production and lower aSAT mitochondrial respiration were independently associated with lower S I (p < 0.05). In response to training, S I improved and gynoid fat decreased (p < 0.05), while H 2 O 2 production reduced in both depots, and mtDNA decreased in gSAT (p < 0.05). Mitochondrial respiration increased in aSAT and correlated with a decrease in body fat and an increase in soleus and hepatic fat content (p < 0.05). This study highlights the importance of understanding the differences in mitochondrial function in multiple SAT depots when investigating the pathophysiology of insulin resistance and associated risk factors such as body fat distribution and ectopic lipid deposition. Furthermore, we highlight the benefits of exercise training in stimulating positive adaptations in mitochondrial function in gluteal and abdominal SAT depots.

This 12-week exercise intervention study assessed changes in cardiorespiratory fitness (CRF), energy expenditure (EE), and substrate utilisation at rest and during exercise in obese, black South African (SA) women and explored associations with changes in body composition. Black SA women (body mass index: 30-40 kg·m -2 , age: 20-35 years) were randomised into control (CTL; n = 15, maintaining usual activity) or exercise (EXE; n = 20; 12 weeks, 4 days·week -1 , 40-60 min·day -1 at >70% peak heart rate) groups. Pre- and post-intervention testing included peak oxygen consumption, resting and steady state (50% peak oxygen consumption) EE, respiratory exchange, and body composition (dual-energy X-ray absorptiometry). Dietary intake (4-day) and daily step-count (ActivPAL, activPAL3c; PAL Technologies Ltd, Glasgow, UK) was collected at pre-testing and at 4, 8, and 12 weeks. EXE increased peak oxygen consumption (24.9 ± 2.4 to 27.6 ± 3.4 mL·min -1 ·kg -1 ; p < 0.001) and steady state fat oxidation rates (7.5 ± 2.5 to 9.0 ± 2.7 mg·min -1 ·kg -1 fat-free soft tissue mass; p = 0.003) (same relative exercise intensity). CTL remained unchanged ( p > 0.05). EXE reduced proportional gynoid fat mass (percentage total fat mass, p = 0.002). Baseline resting carbohydrate oxidation rates ( p = 0.036) and steady state fat oxidation rates ( p = 0.021) explained 60.6% of the variability in Δgynoid fat mass ( p < 0.001) in EXE. This 12-week exercise intervention improved CRF and steady state fat oxidation rates. Greater reliance on fat oxidation at baseline promoted proportional reductions in gynoid, not visceral, fat mass in response to exercise training. Novelty Combined exercise training in obese black South African women increased cardiorespiratory fitness and rates of fat oxidation during steady state exercise. Exercise training reduced proportional gynoid, not visceral, fat, potentially representing an ethnic/sex-specific response. Baseline substrate utilisation (resting and steady state exercise (50% peak oxygen uptake)) predicted changes in gynoid fat mass.

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 ( VO 2 peak ), serum and SAT inflammatory and oxidative stress markers were measured from 15 (control group) and 20 (exercise group) women and insulin sensitivity (S I ; frequently sampled intravenous glucose tolerance test) was estimated. Following the intervention, VO 2 peak (9.8%), body fat composition (1-3%) and S I (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 S I . 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 S I ., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

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 .

Background: The pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D., Objective: The objective of the study was to examine the mechanisms underlying the changes in insulin sensitivity and secretion in response to a 12-week exercise intervention in obese black South African (SA) women., Methods: A total of 45 obese (body mass index, BMI: 30-40 kg/m 2 ) black SA women were randomized into a control (n=22) or experimental (exercise; n=23) group. The exercise group completed 12 weeks of supervised combined aerobic and resistance training (40-60 min, 4 days/week), while the control group maintained their typical physical activity patterns, and both groups were requested not to change their dietary patterns. Before and following the 12-week intervention period, insulin sensitivity and secretion (frequently sampled intravenous glucose tolerance test) and its primary and secondary determinants were measured. Dietary intake, sleep quality and quantity, physical activity, and sedentary behaviors were measured every 4 weeks., Results: The final sample included 20 exercise and 15 control participants. Baseline sociodemographics, cardiorespiratory fitness, anthropometry, cardiometabolic risk factors, physical activity, and diet did not differ between the groups (P>.05)., Conclusions: The study describes a research protocol for an exercise intervention to understand the mechanisms underlying insulin sensitivity and secretion in obese black SA women and aims to identify causal pathways underlying the high prevalence of insulin resistance and risk for T2D in black SA women, targeting specific areas for therapeutic intervention., Trial Registration: Pan African Clinical Trial Registry PACTR201711002789113; http://www.pactr.org/ATMWeb/ appmanager/atm/atmregistry?&#95;nfpb=true&&#95;pageLabel=portals&#95;app&#95;atmregistry&#95;portal&#95;page&#95;13 (Archived by WebCite at http://www.webcitation.org/6xLEFqKr0)., (©Julia H Goedecke, Amy E Mendham, Louise Clamp, Pamela A Nono Nankam, Melony C Fortuin-de Smidt, Lindokuhle Phiri, Lisa K Micklesfield, Dheshnie Keswell, Nicholas J Woudberg, Sandrine Lecour, Ali Alhamud, Mamadou Kaba, Faith M Lutomia, Paul J van Jaarsveld, Anniza de Villiers, Steven E Kahn, Elin Chorell, Jon Hauksson, Tommy Olsson. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 18.04.2018.)

Purpose: This study aimed to determine the recovery timeline of sleep, subjective jet lag and fatigue, and team sport physical performance after east and west long-haul travel., Methods: Ten physically trained men underwent testing at 0900 h and 1700 h local time on four consecutive days 2 wk before outbound travel (BASE), and the first 4 d after 21 h of outbound (WEST) and return (EAST) air travel across eight time zones between Australia and Qatar. Data collection included performance (countermovement jump, 20-m sprint, and Yo-Yo intermittent recovery level 1 [YYIR1] test) and perceptual (jet lag, motivation, perceived exertion, and physical feeling) measures. In addition, sleep was measured via wrist activity monitors and self-report diaries throughout the aforementioned data collection periods., Results: Compared with the corresponding day at BASE, the reduction in YYIR1 distance after EAST was significantly different from the increase in WEST on day 1 after travel (P < 0.001). On day 2, significantly slower 20-m sprint times were detected in EAST compared with WEST (P = 0.03), with large effect sizes (ES) also indicating a greater reduction in YYIR1 distance in EAST compared with WEST (d = 1.06). Mean sleep onset and offset were significantly later and mean time in bed and sleep duration were significantly reduced across the 4 d in EAST compared with BASE and WEST (P < 0.05). Lastly, mean jet lag, fatigue, and motivation ratings across the 4 d were significantly worse in EAST compared with BASE and WEST (P < 0.05) and WEST compared with BASE (P < 0.05)., Conclusions: Long-haul transmeridian travel can impede team sport physical performance. Specifically, east travel has a greater detrimental effect on sleep, subjective jet lag, fatigue, and motivation. Consequently, maximal and intermittent sprint performance is also reduced after east travel, particularly within 72 h after arrival.

In 2012, the World Health Organization Global Status Report on noncommunicable diseases showed that 7.4 million deaths were due to ischemic heart disease. Consequently, cardiovascular disease is a significant health burden, especially when partnered with comorbidities such as obesity, metabolic syndrome, and type 2 diabetes mellitus. Of note, these diseases can all be induced or exacerbated by diet. Carbohydrates, in particular, fructose and glucose, generally form the largest part of the human diet. Accumulating evidence from animal studies suggests that if large amounts of fructose are consumed either in isolation or in combination with glucose (fructose-containing sugars), myocardial susceptibility to ischemia/reperfusion (I/R) injury increases. However, the underlying mechanisms that predisposes the myocardium to I/R injury in the fructose model are not elucidated, and no single mechanistic pathway has been described. Based on all available data on this topic, this review describes previously investigated mechanisms and highlights 3 main mechanistic pathways whereby fructose has shown to increase myocardial susceptibility to I/R injury. These pathways include (1) increased reactive oxygen species, resulting in reduced nitric oxide synthase and coronary flow; (2) elevated plasma fatty acids and insulin, leading to increased cardiac triglyceride content and lipotoxicity; and (3) disrupted myocardial calcium handling/homeostasis. Moreover, we highlight various factors that should be taken into account when the fructose animal model is used, such as rat strain, treatment periods, and doses. We argue that failure to do so would result in erratic inferences drawn from the existing body of evidence on fructose animal models., (Copyright © 2017 Elsevier Inc. All rights reserved.)