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.

The association of menopause with cardiometabolic disease risk factors in women living with and without HIV in sub-Saharan Africa: Results from the AWI-Gen 1 study.

BACKGROUND: Menopause and HIV are associated with cardiometabolic disease. In sub-Saharan Africa there is a growing population of midlife women living with HIV and a high prevalence of cardiometabolic disease. OBJECTIVES: The aim of this study was to determine whether menopause and HIV were associated with cardiometabolic disease risk factors in a population of midlife sub-Saharan African women. STUDY DESIGN: This was a cross-sectional comparison of cardiometabolic disease risk factors between 944 premenopausal women (733 living without HIV and 211 living with HIV) and 1135 postmenopausal women (932 living without HIV and 203 living with HIV) in sub-Saharan Africa. MAIN OUTCOME MEASURES: Anthropometric and cardiometabolic variables were compared between pre- and postmenopausal women living without HIV and between pre- and postmenopausal women living with HIV and between women living without HIV and women living with HIV. RESULTS: The prevalence of HIV was 19.9 %. Age at menopause was lower in women living with HIV than in women living without HIV (48.1 ± 5.1 vs 50.9 ± 4.7 years, p < 0.001). Women living with HIV and receiving efavirenz-based antiretroviral therapy had a lower body mass index (BMI), hip circumference, blood pressure and carotid intima media thickness but higher triglyceride levels and insulin resistance than women living without HIV. Antiretroviral therapy-naïve women living with HIV had lower HDL-cholesterol than women living without HIV. In this study, menopause was associated with higher LDL-C levels, regardless of HIV status. CONCLUSION: The high prevalence of obesity and related cardiometabolic disease risk factors in these midlife sub-Saharan African women is not related to the menopausal transition. The association of cardiometabolic disease risk factors with HIV and antiretroviral therapy is complex and requires further investigation in longitudinal studies, as does the negative association of age at final menstrual period with HIV.

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.

Does Engagement in HIV Care Affect Screening, Diagnosis, and Control of Noncommunicable Diseases in Sub-Saharan Africa? A Systematic Review and Meta-analysis.

Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may provide opportunities to increase access to NCD services in under-resourced environments. We conducted a systematic review and meta-analysis to evaluate whether use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV in sub-Saharan Africa (SSA). A comprehensive search of electronic literature databases for studies published between 01 January 2011 and 31 December 2022 yielded 26 studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR 1.07; 95% CI 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR 2.10, 95% CI 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.

The association of menopause with cardiometabolic disease risk factors in low- and middle-income countries: a systematic review and meta-analyses.

IMPORTANCE: Menopause is an integral part of women's health, and studies in high-income countries have shown an increase in cardiometabolic disease (CMD) risk factors in postmenopausal compared with premenopausal women. However, to date, no study has combined and assessed such studies across low- and middle-income countries. This would better inform early monitoring and intervention strategies for reducing CMD risk factor levels in midlife women in these regions. OBJECTIVE: This study aimed to evaluate evidence from the literature on differences in CMD risk factors between premenopausal and postmenopausal midlife women living in low- and middle-income countries. EVIDENCE REVIEW: A systematic review with meta-analysis of original articles of all study designs from the databases PubMed, PubMed Central, Scopus, and ISI Web of Science was conducted from conception until April 24, 2023. Studies that met the inclusion criteria were included in the analysis. Quality assessment of the articles was done using the Newcastle-Ottawa Scale, adapted for each study design. The study protocol was registered with the International Prospective Register of Systematic Reviews and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. For the meta-analysis, fixed-effects models were used to pool the odds ratios (OR), as measures of association. FINDINGS: Our search identified 4,849 relevant articles: 44 for the systematic review and 16 for the meta-analysis, in accordance with our inclusion criteria. Compared with premenopausal women, the postmenopausal stage was associated with metabolic syndrome (OR, 1.18 [95% CI, 1.11-1.27]), high waist-to-hip ratio (OR, 1.22 [95% CI, 1.12-1.32]), hypertension (OR, 1.10 [95% CI, 1.04-1.16]), elevated triglycerides (OR, 1.16 [95% CI, 1.11-1.21]), and elevated plasma glucose (OR, 1.21 [95% CI, 1.15-1.28]). CONCLUSIONS AND RELEVANCE: This study confirmed that CMD risk factors are present at higher levels in postmenopausal than premenopausal women. This demonstrates an urgent need for public health policies that focus on early monitoring and interventions targeted at reducing CMD risk and related adverse outcomes in midlife women in these nations.

Prevalence of and Risk Factors for Peripheral Artery Disease in Rural South Africa: A Cross-Sectional Analysis of the HAALSI Cohort.

BACKGROUND: The burden of peripheral artery disease (PAD) is increasing in low- and middle-income countries. Existing literature from sub-Saharan Africa is limited and lacks population-representative estimates. We estimated the burden and risk factor profile of PAD for a rural South African population. METHODS AND RESULTS: We used data from 1883 participants from a rural, low-income cohort of South African adults aged 40 to 69 years with available ankle-brachial index measurements. We defined clinical PAD as ankle-brachial index ≤0.90 or >1.40, and borderline PAD as ankle-brachial index >0.90 and ≤1.00. We compared the distribution of sociodemographic variables, biomarkers, and comorbidities across PAD classifications. To identify associated factors, we calculated unadjusted and age-sex-adjusted prevalence ratios (PRs) with log-binomial models. Overall, 6.6% (95% CI, 5.6-7.7) of the sample met the diagnostic criteria for clinical PAD, while 44.7% (95% CI, 42.4-47.0) met the diagnostic criteria for borderline PAD. Age (PR: 1.9 [95% CI, 1.2-3.1] for ages 50-59 years compared with 40-49 years; PR: 2.5 [95% CI, 1.5-4.0] for ages 60-69 years compared with 40-49 years); diagnosed hypertension (PR: 1.53 [95% CI, 1.08-2.17]); and C-reactive protein (PR: 1.08 [95% CI, 1.03-1.12]) were associated with increased prevalence of clinical PAD. All other examined factors were not significantly associated with clinical PAD. CONCLUSIONS: We found high PAD prevalence for younger age groups compared with previous research and a lack of statistical evidence for the influence of traditional risk factors for this rural, low-income population. Future research should focus on identifying the underlying risk factors for PAD in this setting. South African policymakers and clinicians should consider expanded screening for early PAD detection in rural areas.

Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study.

Most hypertension-related genome-wide association studies (GWASs) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure (BP)-related traits (systolic and diastolic BP, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N = 10,775), identifies two novel genome-wide significant signals (p < 5E-08): systolic BP near P2RY1 (rs77846204; intergenic variant, p = 4.95E-08) and pulse pressure near LINC01256 (rs80141533; intergenic variant, p = 1.76E-08). No genome-wide signals are detected for the AWI-Gen GWAS meta-analysis with previous African-ancestry GWASs (UK Biobank (African), Uganda Genome Resource). Suggestive signals (p < 5E-06) are observed for all traits, with 29 SNPs associating with more than one trait and several replicating known associations. Polygenic risk scores (PRSs) developed from studies on different ancestries have limited transferability, with multi-ancestry PRS providing better prediction. This study provides insights into the genetics of BP variation in African populations.

Gaps in the type 2 diabetes care cascade: a national perspective using South Africa's National Health Laboratory Service (NHLS) database.

BACKGROUND: Research out of South Africa estimates the total unmet need for care for those with type 2 diabetes mellitus (diabetes) at 80%. We evaluated the care cascade using South Africa's National Health Laboratory Service (NHLS) database and assessed if HIV infection impacts progression through its stages. METHODS: The cohort includes patients from government facilities with their first glycated hemoglobin A1c (HbA1c) or plasma glucose (fasting (FPG); random (RPG)) measured between January 2012 to March 2015 in the NHLS. Lab-diagnosed diabetes was defined as HbA1c ≥ 6.5%, FPG ≥ 7.0mmol/l, or RPG ≥ 11.1mmol/l. Cascade stages post diagnosis were retention-in-care and glycaemic control (defined as an HbA1c < 7.0% or FPG < 8.0mmol/l or RPG < 10.0mmol/l) over 24-months. We estimated gaps at each stage nationally and by people living with HIV (PLWH) and without (PLWOH). RESULTS: Of the 373,889 patients tested for diabetes, 43.2% had an HbA1c or blood glucose measure indicating a diabetes diagnosis. Amongst those with lab-diagnosed diabetes, 30.9% were retained-in-care (based on diabetes labs) and 8.7% reached glycaemic control by 24-months. Prevalence of lab-diagnosed diabetes in PLWH was 28.6% versus 47.3% in PLWOH. Among those with lab-diagnosed diabetes, 34.3% of PLWH were retained-in-care versus 30.3% PLWOH. Among people retained-in-care, 33.8% of PLWH reached glycaemic control over 24-months versus 28.6% of PLWOH. CONCLUSIONS: In our analysis of South Africa's NHLS database, we observed that 70% of patients diagnosed with diabetes did not maintain in consistent diabetes care, with fewer than 10% reaching glycemic control within 24 months. We noted a disparity in diabetes prevalence between PLWH and PLWOH, potentially linked to different screening methods. These differences underscore the intricacies in care but also emphasize how HIV care practices could guide better management of chronic diseases like diabetes. Our results underscore the imperative for specialized strategies to bolster diabetes care in South Africa.

Diabetes care cascade and associated factors in 10 700 middle-aged adults in four sub-Saharan African countries: a cross-sectional study.

OBJECTIVES: We investigated progression through the care cascade and associated factors for people with diabetes in sub-Saharan Africa to identify attrition stages that may be most appropriate for targeted intervention. DESIGN: Cross-sectional study. SETTING: Community-based study in four sub-Saharan African countries. PARTICIPANTS: 10 700 individuals, aged 40-60 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the diabetes cascade of care defined as the age-adjusted diabetes prevalence (self-report of diabetes, fasting plasma glucose (FPG) ≥7 mmol/L or random plasma glucose ≥11.1 mmol/L) and proportions of those who reported awareness of having diabetes, ever having received treatment for diabetes and those who achieved glycaemic control (FPG <7.2 mmol/L). Secondary outcome measures were factors associated with having diabetes and being aware of the diagnosis. RESULTS: Diabetes prevalence was 5.5% (95% CI 4.4% to 6.5%). Approximately half of those with diabetes were aware (54%; 95% CI 50% to 58%); 73% (95% CI 67% to 79%) of aware individuals reported ever having received treatment. However, only 38% (95% CI 30% to 46%) of those ever having received treatment were adequately controlled. Increasing age (OR 1.1; 95% CI 1.0 to 1.1), urban residence (OR 2.3; 95% CI 1.6 to 3.5), hypertension (OR 1.9; 95% CI 1.5 to 2.4), family history of diabetes (OR 3.9; 95% CI 3.0 to 5.1) and measures of central adiposity were associated with higher odds of having diabetes. Increasing age (OR 1.1; 95% CI 1.0 to 1.1), semi-rural residence (OR 2.5; 95% CI 1.1 to 5.7), secondary education (OR 2.4; 95% CI 1.2 to 4.9), hypertension (OR 1.6; 95% CI 1.0 to 2.4) and known HIV positivity (OR 2.3; 95% CI 1.2 to 4.4) were associated with greater likelihood of awareness of having diabetes. CONCLUSIONS: There is attrition at each stage of the diabetes care cascade in sub-Saharan Africa. Public health strategies should target improving diagnosis in high-risk individuals and intensifying therapy in individuals treated for diabetes.

Cardiometabolic disease risk factors in pre- and postmenopausal women from four sub-Saharan African countries: A cross-sectional study.

OBJECTIVE: To compare the risk factors for cardiometabolic disease between pre- and postmenopausal women from four sub-Saharan African countries. STUDY DESIGN: This cross-sectional study included 3609 women (1740 premenopausal and 1869 postmenopausal) from sites in Ghana (Navrongo), Burkina Faso (Nanoro), Kenya (Nairobi), and South Africa (Soweto and Dikgale). Demographic, anthropometric and cardiometabolic variables were compared between pre- and postmenopausal women, within and across sites using multivariable regression analyses. The sites represent populations at different stages of the health transition, with those in Ghana and Burkina Faso being rural, whilst those in Kenya and South Africa are more urbanised. MAIN OUTCOME MEASURES: Anthropometric and cardiometabolic variables. RESULTS: The prevalence rates of risk factors for cardiometabolic disease were higher in South (Soweto and Dikgale) and East (Nairobi) Africa than in West Africa (Nanoro and Navrongo), irrespective of menopausal status. Regression models in combined West African populations demonstrated that postmenopausal women had a larger waist circumference (ß = 1.28 (95 % CI: 0.58; 1.98) cm), log subcutaneous fat (ß =0.15 (0.10; 0.19)), diastolic (ß = 3.04 (1.47; 4.62) mm Hg) and log systolic (ß = 0.04 (0.02; 0.06)) blood pressure, log carotid intima media thickness (ß = 0.03 (0.01; 0.06)), low-density lipoprotein cholesterol (ß = 0.14 (0.04; 0.23) mmol/L) and log triglyceride (ß= 0.10 (0.04; 0.16)) levels than premenopausal women. No such differences were observed in the South and East African women. CONCLUSIONS: Menopause-related differences in risk factors for cardiometabolic disease were prominent in West but not East or South African study sites. These novel findings should inform cardiometabolic disease prevention strategies in midlife women specific to rural and urban and peri-urban locations in sub-Saharan Africa.

Identifying the prevalence and correlates of multimorbidity in middle-aged men and women: a cross-sectional population-based study in four African countries.

OBJECTIVES: To determine the prevalence of multimorbidity, to identify which chronic conditions cluster together and to identify factors associated with a greater risk for multimorbidity in sub-Saharan Africa (SSA). DESIGN: Cross-sectional, multicentre, population-based study. SETTING: Six urban and rural communities in four sub-Saharan African countries. PARTICIPANTS: Men (n=4808) and women (n=5892) between the ages of 40 and 60 years from the AWI-Gen study. MEASURES: Sociodemographic and anthropometric data, and multimorbidity as defined by the presence of two or more of the following conditions: HIV infection, cardiovascular disease, chronic kidney disease, asthma, diabetes, dyslipidaemia, hypertension. RESULTS: Multimorbidity prevalence was higher in women compared with men (47.2% vs 35%), and higher in South African men and women compared with their East and West African counterparts. The most common disease combination at all sites was dyslipidaemia and hypertension, with this combination being more prevalent in South African women than any single disease (25% vs 21.6%). Age and body mass index were associated with a higher risk of multimorbidity in men and women; however, lifestyle correlates such as smoking and physical activity were different between the sexes. CONCLUSIONS: The high prevalence of multimorbidity in middle-aged adults in SSA is of concern, with women currently at higher risk. This prevalence is expected to increase in men, as well as in the East and West African region with the ongoing epidemiological transition. Identifying common disease clusters and correlates of multimorbidity is critical to providing effective interventions.

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

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

Physical Activity and Its Association With Body Mass Index: A Cross-Sectional Analysis in Middle-Aged Adults From 4 Sub-Saharan African Countries.

BACKGROUND: This study aimed to explore association of self-reported physical activity domains of work, leisure, and transport-related physical activity and body mass index (BMI) in 9388 adult men and women from the Africa-Wits-INDEPTH partnership for Genomic (AWI-Gen) study in Africa. Africa-Wits-INDEPTH partnership for Genomic is a large, population-based cross-sectional cohort with participants from 6 sites from rural and urban areas in 4 sub-Saharan African countries. METHODS: A sex-stratified meta-analysis of cross-sectional data from men and women aged 29-82 years was used to assess the association of physical activity with BMI. RESULTS: Overall, meeting physical activity guidelines of at least 150 minutes per week was associated with 0.82 kg/m2 lower BMI in men (ß = -0.80 kg/m2; 95% confidence interval [CI], -1.14 to -0.47) and 0.68 kg/m2 lower BMI in women (ß = -0.68 kg/m2; 95% CI, -1.03 to -0.33). Sex and site-specific differences were observed in the associations between physical activity domains and BMI. Among those who met physical activity guidelines, there was an inverse association between transport-related physical activity and BMI in men from Nanoro (Burkina Faso) (ß = -0.79 kg/m2; 95% CI, -1.25 to -0.33) as well as work-related physical activity and BMI in Navrongo men (Ghana) (ß = -0.76 kg/m2; 95% CI, -1.25 to -0.27) and Nanoro women (ß = -0.90 kg/m2; 95% CI, -1.44 to -0.36). CONCLUSIONS: Physical activity may be an effective strategy to curb rising obesity in Africa. More studies are needed to assess the impact of sex and geographic location-specific physical activity interventions on obesity.

Does engagement in HIV care affect screening, diagnosis, and control of noncommunicable diseases in sub-Saharan Africa? A systematic review and meta-analysis.

Objective: Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may also provide opportunities to increase access to NCD services in under-resourced environments. We sought to investigate whether reported use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and/or control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV (PLWH) in sub-Saharan Africa (SSA). Design: Systematic review and meta-analysis. Methods: We searched 10 electronic literature databases for studies published between 01 January 2011 and 31 December 2022 using a comprehensive search strategy. We sought studies reporting on screening, diagnosis, treatment, and/or control of NCDs of interest by ART use among non-pregnant adults with HIV ≥16 years of age in SSA. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. Results: Twenty-six studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART, were included. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR: 1.07; 95% CI: 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR: 2.10, 95% CI: 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Conclusion: Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.

Estimating population level 24-h sodium excretion using spot urine samples in older adults in rural South Africa.

BACKGROUND: South Africa has introduced regulations to reduce sodium in processed foods. Assessing salt consumption with 24-h urine collection is logistically challenging and expensive. We assess the accuracy of using spot urine samples to estimate 24-h urine sodium (24hrUNa) excretion at the population level in a cohort of older adults in rural South Africa. METHODS: 24hrUNa excretion was measured and compared to that estimated from matched spot urine samples in 399 individuals, aged 40-75 years, from rural Mpumalanga, South Africa. We used the Tanaka, Kawasaki, International Study of Sodium, Potassium, and Blood Pressure (INTERSALT), and Population Mean Volume (PMV) method to predict 24hrUNa at the individual and population level. RESULTS: The population median 24hrUNa excretion from our samples collected in 2017 was 2.6 g (interquartile range: 1.53-4.21) equal to an average daily salt intake of 6.6 g, whereas 65.4% of participants had a salt excretion above the WHO recommended 5 g/day. Estimated population median 24hrUNa derived from the INTERSALT, both with and without potassium, showed a nonsignificant difference of 0.25 g (P = 0.59) and 0.21 g (P = 0.67), respectively. In contrast, the Tanaka, Kawasaki, and PMV formulas were markedly higher than the measured 24hrUNa, with a median difference of 0.51 g (P = 0.004), 0.99 g (P = 0.00), and 1.05 g (P = 0.00) respectively. All formulas however performed poorly when predicting an individual's 24hrUNa. CONCLUSION: In this population, the INTERSALT formulas are a well suited and cost-effective alternative to 24-h urine collection for the evaluation of population median 24hrUNa excretion. This could play an important role for governments and public health agencies in evaluating local salt regulations and identifying at-risk populations.

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.

Non-HDL-C and LDL-C/HDL-C are associated with self-reported cardiovascular disease in a rural West African population: Analysis of an array of lipid metrics in an AWI-Gen sub-study.

Few studies have compared the utility of serum levels of lipid fractions in cardiovascular disease (CVD) risk assessment in sub-Saharan Africa (SSA). The current study interrogated this question among men and women aged 40-60 years in rural northern Ghana. This was a cross-sectional study in which data was collected on socio-demography, behaviour, health history, anthropometry and lipid levels. Adjusted multivariable logistic regression models were used to assess the association of various lipid metrics with CVD. All tests were considered statistically significant at P<0.05. Data were available for 1839 participants. The prevalence of self-reported CVD was 1.6% (n = 29). Non-HDL-C (median (interquartile range): 2.4 (1.9-3.0) vs 2.0 (1.6-2.5) mmol/L; P = 0.009), LDL-C/HDL-C (1.8 (1.4-2.4) vs 1.5 (1.1-2.6); P = 0.019) and TC/HDL-C (3.3 (2.9-3.9) vs 2.9 (2.4-3.5); P = 0.003) were all significantly higher in participants with self-reported CVD compared to those without. However, after adjusting for socioeconomic status (SES) and meals from vendors in a logistic regression model, only non-HDL-C (odds ratio [95% CIs]): (1.58 [1.05, 2.39]), P = 0.029 and LDL-C/HDL-C levels (odds ratio [95% CIs]): (1.26 [1.00, 1.59]), P = 0.045 remained significantly associated with self-reported CVD. While our findings suggest non-HDL-C and LDL-C/HDL-C measures may be appropriate biomarkers for assessing CVD risk in this population, further studies using established clinical endpoints are required to validate these findings in sub-Saharan Africans.

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

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

Menopause is associated with bone loss, particularly at the distal radius, in black South African women: Findings from the Study of Women Entering and in Endocrine Transition (SWEET).

Menopause transition is associated with accelerated bone loss, though data are limited from sub-Saharan African (SSA). Our objective was to describe bone density, geometry and estimated strength in women by menopause status and to explore whether patterns differed within those living with HIV. METHODS: Radius and tibia peripheral QCT data were collected for Black South African women (n = 430) aged 40-61 years with verified menopause and HIV status. pQCT outcomes were distal 4 % radius and tibia total cross-sectional area (CSA), total volumetric bone mineral density (vBMD), and compressive bone strength (BSIc); proximal 66 % radius and 38 % tibia cortical vBMD, total CSA, cortical thickness, and Stress-strain Index (SSI). Linear regression assessed associations between pre, peri-, and postmenopausal groups and pQCT outcomes adjusting for age, height, and weight, and then stratified by HIV status. Mean [95%CI] and tests for trend (p-trend) across menopausal groups are presented. RESULTS: Women were mean (SD) age 49.2 (5.3) years, with a body mass index (BMI) of 32.4 (6.3) m/kg2, and 18 % were living with HIV. After adjustment, later menopause stage was associated with lower 4 % radius total mean [95%CIs] vBMD (premenopause: 345.7 [335.8,355.5] vs. postmenopause: 330.1 [322.7,337.6] mg/cm3, p-trend = 0.017) and BSIc (premenopause: 0.39 [0.37,0.41] vs. postmenopause: 0.36 [0.35,0.37] g2/cm4; p-trend = 0.012). Similar trends were observed at the 66 % radius for cortical vBMD (premenopause: 1146.8 [1138.9,1154.6] vs. postmenopause: 1136.1 [1130.1,1142.0] mg/cm3; p-trend = 0.028) and cortical thickness (premenopause: 2.01 [1.95,2.06] vs. postmenopause: 1.93 [1.89,1.98] mm; p-trend = 0.036). After stratification by HIV status a similar patten was observed in women with HIV (cortical vBMD premenopause: 1152.9 [1128.5,1177.2] mg/cm3 vs. postmenopause: 1123.6 [1106.0,1141.2] mg/cm3, p-trend = 0.048). Total CSA varied little by menopause or HIV status at either radius sites; few differences were found at the tibia. CONCLUSION: In black South African women, menopause is associated with lower bone density and strength at the distal radius, a common site of osteoporotic fracture, in addition to lower cortical density and thickness at the proximal radius. Although the sample size was small, following stratification by HIV, women living with HIV had evidence of lower cortical density across menopause stages, unlike those without HIV. These findings raise concern for the incidence of Colles' fractures in postmenopausal women in South Africa; longitudinal studies of fracture incidence and implications of living with HIV are required.

The negative association of lower body fat mass with cardiometabolic disease risk factors is partially mediated by adiponectin.

Gluteofemoral fat correlates negatively with a number of cardiometabolic disease risk factors, but the mechanisms involved in these relationships are unknown. The aim of this study was to test the hypothesis that gluteofemoral fat attenuates the risk of cardiometabolic disease by increasing blood adiponectin levels. This was a cross-sectional study in which arm, leg, gluteofemoral, abdominal s.c. and visceral fat levels were measured by dual-energy X-ray absorptiometry in 648 African females. Fasting serum adiponectin, lipid, insulin and plasma glucose levels and blood pressure were measured. Relationships between variables were analysed using multivariable linear regression and structural equation modelling. Adiponectin correlated positively (ß = 0.45, P < 0.0001) with gluteofemoral fat in a multivariable regression model that included age, height, and arm, s.c. and visceral fat levels. In further regression models, there was a negative correlation of gluteofemoral fat with fasting glucose (ß = -0.28; P < 0.0001) and triglyceride levels (ß = -0.29; P < 0.0001) and insulin resistance (HOMA; ß = -0.26; P < 0.0001). Structural equation modelling demonstrated that adiponectin mediated 20.7% (P < 0.01) of the association of gluteofemoral fat with insulin resistance and 16.1% (P < 0.01) of the association with triglyceride levels but only 6.67% (P = 0.31) of the association with glucose levels. These results demonstrate that gluteofemoral and leg fat are positively associated with adiponectin levels and that the negative association of lower body fat with insulin resistance and triglyceride levels may partially be mediated by this adipokine. Further studies are required to determine other factors that mediate the effect of lower body fat on cardiometabolic disease risk factors.