A model-based approach to estimating the prevalence of disease combinations in South Africa.

BACKGROUND: The development of strategies to better detect and manage patients with multiple long-term conditions requires estimates of the most prevalent condition combinations. However, standard meta-analysis tools are not well suited to synthesising heterogeneous multimorbidity data. METHODS: We developed a statistical model to synthesise data on associations between diseases and nationally representative prevalence estimates and applied the model to South Africa. Published and unpublished data were reviewed, and meta-regression analysis was conducted to assess pairwise associations between 10 conditions: arthritis, asthma, chronic obstructive pulmonary disease (COPD), depression, diabetes, HIV, hypertension, ischaemic heart disease (IHD), stroke and tuberculosis. The national prevalence of each condition in individuals aged 15 and older was then independently estimated, and these estimates were integrated with the ORs from the meta-regressions in a statistical model, to estimate the national prevalence of each condition combination. RESULTS: The strongest disease associations in South Africa are between COPD and asthma (OR 14.6, 95% CI 10.3 to 19.9), COPD and IHD (OR 9.2, 95% CI 8.3 to 10.2) and IHD and stroke (OR 7.2, 95% CI 5.9 to 8.4). The most prevalent condition combinations in individuals aged 15+ are hypertension and arthritis (7.6%, 95% CI 5.8% to 9.5%), hypertension and diabetes (7.5%, 95% CI 6.4% to 8.6%) and hypertension and HIV (4.8%, 95% CI 3.3% to 6.6%). The average numbers of comorbidities are greatest in the case of COPD (2.3, 95% CI 2.1 to 2.6), stroke (2.1, 95% CI 1.8 to 2.4) and IHD (1.9, 95% CI 1.6 to 2.2). CONCLUSION: South Africa has high levels of HIV, hypertension, diabetes and arthritis, by international standards, and these are reflected in the most prevalent condition combinations. However, less prevalent conditions such as COPD, stroke and IHD contribute disproportionately to the multimorbidity burden, with high rates of comorbidity. This modelling approach can be used in other settings to characterise the most important disease combinations and levels of comorbidity.

Phenotype and predictors of insulin independence in adults presenting with diabetic ketoacidosis: a prospective cohort study.

AIMS/HYPOTHESIS: The aim of this work was to describe the phenotype of adults presenting with a first episode of diabetic ketoacidosis (DKA) in Cape Town, South Africa, and identify predictors of insulin independence at 12 and 60 months after presentation. METHODS: A prospective, descriptive cohort study of all individuals, 18 years or older, presenting for the first time with DKA to four public-sector hospitals of the Groote Schuur Academic Health Complex was performed. Clinical, biochemical and laboratory data including GAD antibody and C-peptide status were collected at baseline. Insulin was systematically weaned and stopped in individuals who achieved normoglycaemia within the months after DKA. Individuals were followed for 12 months and then annually until 5 years after initial presentation with ketoacidosis. RESULTS: Eighty-eight individuals newly diagnosed with diabetes when presenting with DKA were included and followed for 5 years. The mean ± SD age was 35±10 years and the median (IQR) BMI at diagnosis was 28.5 (23.3-33.4) kg/m2. Overall, 46% were insulin independent 12 months after diagnosis and 26% remained insulin independent 5 years after presentation. Forty-one participants (47%) tested negative for anti-GAD and anti-IA-2 antibodies and had C-peptide levels >0.3 nmol/l; in this group, 68% were insulin independent at 12 months and 37% at 5 years after diagnosis. The presence of acanthosis nigricans was strongly associated with insulin independence (OR 27.1 [95% CI 7.2, 102.2]; p<0.001); a positive antibody status was associated with a lower likelihood of insulin independence at 12 months (OR 0.10 [95% CI 0.03, 0.36]; p<0.001). On multivariable analysis only acanthosis (OR 11.5 [95% CI 2.5, 53.2]; p=0.004) was predictive of insulin independence 5 years after diagnosis. CONCLUSIONS/INTERPRETATION: The predominant phenotype of adults presenting with a first episode of DKA in Cape Town, South Africa, was that of ketosis-prone type 2 diabetes. These individuals presented with obesity, acanthosis nigricans, negative antibodies and normal C-peptide and could potentially be weaned off insulin at follow-up. Classic type 1 diabetes (lower weight, antibody positivity, low or unrecordable C-peptide levels and long-term insulin dependence) was less common. The simple clinical sign of acanthosis nigricans is a strong predictor of insulin independence at 12 months and 5 years after initial presentation.

Perceptions of Health, Body Size, and Nutritional Risk Factors for Obesity in People with HIV in South Africa.

Metabolic disease is increasing in people with HIV (PWH) in South Africa, but little is known about self-perceptions of body size, health, and nutritional behavior in this population. We performed a cross-sectional analysis of individual-level data from the 2016 South Africa Demographic and Health Survey. This survey measured HIV serostatus and body mass index (BMI). We categorized participants into six BMI groups: 18.5-22 kg/m2, 22-25 kg/m2, 25-27.5 kg/m2, 27.5-30 kg/m2, 30-35 kg/m2, and ≥ 35 kg/m2 and stratified them by HIV serostatus. Our outcomes were self-reported (1) body size and (2) health status among all participants, and intake of (3) chips and (4) sugar-sweetened beverages (SSB) in PWH. We described these metrics and used multivariable regression to evaluate the relationship between the nutritional behaviors and BMI ≥ 25 kg/m2 in PWH only, adjusting for age, sex, educational attainment, and household wealth quintile. Of 6138 participants, 1163 (19.7%) were PWH. Among PWH, < 10% with a BMI 25-30 kg/m2, < 20% with a BMI 30-35 kg/m2 and < 50% with a BMI ≥ 35 kg/m2 self-reported as overweight or obese. PWH reported being in poor health at higher rates than those without HIV at each BMI category except ≥ 35 kg/m2. In adjusted models, SSB consumption was associated with BMI ≥ 25 kg/m2 (1.13 [1.01-1.25], t-statistic = 2.14, p = 0.033) in PWH. Perceptions of body size may challenge efforts to prevent weight gain in PWH in South Africa. SSB intake reduction should be further explored as a modifiable risk factor for obesity.

Multi-country collaborative citizen science projects to co-design cardiovascular disease prevention strategies and advocacy: findings from Ethiopia, Malawi, Rwanda, and South Africa.

BACKGROUND: Cardiovascular diseases (CVD) were responsible for 20.5 million annual deaths globally in 2021, with a disproportionally high burden in sub-Saharan Africa (SSA). There is growing evidence of the use of citizen science and co-design approaches in developing interventions in different fields, but less so in the context of CVD prevention interventions in SSA. This paper reports on the collaborative multi-country project that employed citizen science and a co-design approach to (i) explore CVD risk perceptions, (ii) develop tailored prevention strategies, and (iii) support advocacy in different low-income settings in SSA. METHODS: This is a participatory citizen science study with a co-design component. Data was collected from 205 participants aged 18 to 75 years in rural and urban communities in Malawi, Ethiopia and Rwanda, and urban South Africa. Fifty-one trained citizen scientists used a mobile app-based (EpiCollect) semi-structured survey questionnaire to collect data on CVD risk perceptions from participants purposively selected from two communities per country. Data collected per community included 100-150 photographs and 150-240 voice recordings on CVD risk perceptions, communication and health-seeking intentions. Thematic and comparative analysis were undertaken with the citizen scientists and the results were used to support citizen scientists-led stakeholder advocacy workshops. Findings are presented using bubble graphs based on weighted proportions of key risk factors indicated. RESULTS: Nearly three in every five of the participants interviewed reported having a relative with CVD. The main perceived causes of CVD in all communities were substance use, food-related factors, and litter, followed by physical inactivity, emotional factors, poverty, crime, and violence. The perceived positive factors for cardiovascular health were nutrition, physical activity, green space, and clean/peaceful communities. Multi-level stakeholders (45-84 persons/country) including key decision makers participated in advocacy workshops and supported the identification and prioritization of community-specific CVD prevention strategies and implementation actions. Citizen science-informed CVD risk screening and referral to care interventions were piloted in six communities in three countries with about 4795 adults screened and those at risk referred for care. Health sector stakeholders indicated their support for utilising a citizen-engaged approach in national NCDs prevention programmes. The citizen scientists were excited by the opportunity to lead research and advocacy. CONCLUSION: The collaborative engagement, participatory learning, and co-designing activities enhanced active engagement between citizen scientists, researchers, and stakeholders. This, in turn, provided context-specific insights on CVD prevention in the different SSA settings.

Ubuntu as a mediator in coping with multimorbidity treatment burden in a disadvantaged rural and urban setting in South Africa.

BACKGROUND: People living with multimorbidity in economically precarious circumstances in low- and middle-income countries (LMICs) experience a high workload trying to meet self-management demands. However, in countries such as South Africa, the availability of social networks and support structures may improve patient capacity, especially when networks are governed by cultural patterns linked to the Pan-African philosophy of Ubuntu, which promotes solidarity through humanness and human dignity. We explore the mediating role Ubuntu plays in people's ability to self-manage HIV/NCD multimorbidity in underprivileged settings in urban and rural South Africa. METHODS: We conducted semi-structured interviews with 30 patients living with HIV/NCD multimorbidity between February-April 2022. Patients attended public health clinics in Gugulethu, Cape Town and Bulungula, Eastern Cape. We analysed interviews using framework analysis, using the Cumulative Complexity Model (CuCoM) and Burden of Treatment Theory (BoTT) as frameworks through which to conceptualise the data. RESULTS: Despite facing economic hardship, people with multimorbidity in South Africa were able to cope with their workload. They actively used and mobilized family relations and external networks that supported them financially, practically, and emotionally, allowing them to better self-manage their chronic conditions. Embedded in their everyday life, patients, often unconsciously, embraced Ubuntu and its core values, including togetherness, solidarity, and receiving Imbeko (respect) from health workers. This enabled participants to share their treatment workload and increase self-management capacity. CONCLUSION: Ubuntu is an important mediator for people living with multimorbidity in South Africa, as it allows them to navigate their treatment workload and increase their social capital and structural resilience, which is key to self-management capacity. Incorporating Ubuntu and linked African support theories into current treatment burden models will enable better understandings of patients' collective support and can inform the development of context-specific social health interventions that fit the needs of people living with chronic conditions in African settings.

Using the COM-B model and Behaviour Change Wheel to develop a theory and evidence-based intervention for women with gestational diabetes (IINDIAGO).

BACKGROUND: In South Africa, the prevalence of gestational diabetes (GDM) is growing, concomitant with the dramatically increasing prevalence of overweight/obesity among women. There is an urgent need to develop tailored interventions to support women with GDM to mitigate pregnancy risks and to prevent progression to type 2 diabetes post-partum. The IINDIAGO study aims to develop and evaluate an intervention for disadvantaged GDM women attending three large, public-sector hospitals for antenatal care in Cape Town and Soweto, SA. This paper offers a detailed description of the development of a theory-based behaviour change intervention, prior to its preliminary testing for feasibility and efficacy in the health system. METHODS: The Behaviour Change Wheel (BCW) and the COM-B model of behaviour change were used to guide the development of the IINDIAGO intervention. This framework provides a systematic, step-by-step process, starting with a behavioural analysis of the problem and making a diagnosis of what needs to change, and then linking this to intervention functions and behaviour change techniques to bring about the desired result. Findings from primary formative research with women with GDM and healthcare providers were a key source of information for this process. RESULTS: Key objectives of our planned intervention were 1) to address women's evident need for information and psychosocial support by positioning peer counsellors and a diabetes nurse in the GDM antenatal clinic, and 2) to offer accessible and convenient post-partum screening and counselling for sustained behaviour change among women with GDM by integrating follow-up into the routine immunisation programme at the Well Baby clinic. The peer counsellors and the diabetes nurse were trained in patient-centred, motivational counselling methods. CONCLUSIONS: This paper offers a rich description and analysis of designing a complex intervention tailored to the challenging contexts of urban South Africa. The BCW was a valuable tool to use in designing our intervention and tailoring its content and format to our target population and local setting. It provided a robust and transparent theoretical foundation on which to develop our intervention, assisted us in making the hypothesised pathways for behaviour change explicit and enabled us to describe the intervention in standardised, precisely defined terms. Using such tools can contribute to improving rigour in the design of behavioural change interventions. TRIAL REGISTRATION: First registered on 20/04/2018, Pan African Clinical Trials Registry (PACTR): PACTR201805003336174.

Cost-effectiveness of Lifestyle Africa: an adaptation of the diabetes prevention programme for delivery by community health workers in urban South Africa.

BACKGROUND: Lifestyle Africa is an adapted version of the Diabetes Prevention Program designed for delivery by community health workers to socioeconomically disadvantaged populations in low- and middle-income countries (LMICs). Results from the Lifestyle Africa trial conducted in an under-resourced community in South Africa indicated that the programme had a significant effect on reducing haemoglobin A1c (HbA1c). OBJECTIVE: To estimate the cost of implementation and the cost-effectiveness (in cost per point reduction in HbA1c) of the Lifestyle Africa programme to inform decision-makers of the resources required and the value of this intervention. METHODS: Interviews were held with project administrators to identify the activities and resources required to implement the intervention. A direct-measure micro-costing approach was used to determine the number of units and unit cost for each resource. The incremental cost per one point improvement in HbA1c was calculated. RESULTS: The intervention equated to 71 United States dollars (USD) in implementation costs per participant and a 0.26 improvement in HbA1c per participant. CONCLUSIONS: Lifestyle Africa reduced HbA1c for relatively little cost and holds promise for addressing chronic disease in LMIC. Decision-makers should consider the comparative clinical effectiveness and cost-effectiveness of this intervention when making resource allocation decisions. TRIAL REGISTRATION: Trial registration is at ClinicalTrials.gov (NCT03342274).

Using qualitative study designs to understand treatment burden and capacity for self-care among patients with HIV/NCD multimorbidity in South Africa: A methods paper.

Background: Low- and middle-income countries (LMICs), including South Africa, are currently experiencing multiple epidemics: HIV and the rising burden of non-communicable diseases (NCDs), leading to different patterns of multimorbidity (the occurrence of two or more chronic conditions) than experienced in high income settings. These adversely affect health outcomes, increase patients' perceived burden of treatment, and impact the workload of self-management. This paper outlines the methods used in a qualitative study exploring burden of treatment among people living with HIV/NCD multimorbidity in South Africa. Methods: We undertook a comparative qualitative study to examine the interaction between individuals' treatment burden (self-management workload) and their capacity to take on this workload, using the dual lenses of Burden of Treatment Theory (BoTT) and Cumulative Complexity Model (CuCoM) to aid conceptualisation of the data. We interviewed 30 people with multimorbidity and 16 carers in rural Eastern Cape and urban Cape Town between February-April 2021. Data was analysed through framework analysis. Findings: This paper discusses the methodological procedures considered when conducting qualitative research among people with multimorbidity in low-income settings in South Africa. We highlight the decisions made when developing the research design, recruiting participants, and selecting field-sites. We also explore data analysis processes and reflect on the positionality of the research project and researchers. Conclusion: This paper illustrates the decision-making processes conducting this qualitative research and may be helpful in informing future research aiming to qualitatively investigate treatment burden among patients in LMICs.

Effectiveness of self-financing patient-led support groups in the management of hypertension and diabetes in low- and middle-income countries: Systematic review.

OBJECTIVE: There is insufficient evidence on the role of self-financing patient support groups in the control of blood pressure (BP) and/or diabetes in low- and middle-income countries (LMICs). We conducted a systematic review to investigate the effectiveness of these groups in BP and glycaemic control. METHODS: We searched PubMed, Embase, SCOPUS, Web of Science, Global Health, African Journals Online, CINAHL and African Index Medicus for published peer-reviewed articles from inception up to November 2021. Grey literature was obtained from OpenGrey. Studies on patient support groups for hypertension and/or diabetes with a component of pooling financial resources, conducted in LMICs, were included. Narrative reviews, commentaries, editorials and articles published in languages other than English and French were excluded. Study quality and risk of bias were assessed using the National Institutes of Health Quality assessment tool and the revised Cochrane risk-of-bias tool. Results are reported according to PRISMA guidelines. RESULTS: Of 724 records screened, three studies met the criteria: two trials conducted in Kenya and a retrospective cohort study conducted in Cambodia. All studies reported improvement in BP control after 12 months follow-up with reductions in systolic BP of 23, 14.8, and 16.9 mmHg, respectively. Two studies reported diabetes parameters. The first reported improvement in HbA1c (reduction from baseline 10.8%, to 10.6% at 6 months) and random blood sugar (baseline 8.9 mmol/L, to 8.5 mmol/L at 6 months) but these changes did not achieve statistical significance. The second reported a reduction in fasting blood glucose (baseline-216 mg/dl, 12 months-159 mg/dl) in diabetic patients on medication. CONCLUSION: Self-financing patient support groups for diabetes and hypertension are potentially effective in the control of BP and diabetes in LMICs. More studies are needed to add to the scarce evidence base on the role of self-financing patient support groups.

Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development. METHODS: We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries. FINDINGS: During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pinteraction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; pinteraction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteraction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; pinteraction <0·0001), but not of cardiovascular diseases or mortality. INTERPRETATION: The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Multimorbidity of communicable and non-communicable diseases in low- and middle-income countries: A systematic review.

Objective: The aim of this systematic review is to analyse existing evidence on prevalence, patterns, determinants, and healthcare challenges of communicable and non-communicable disease multimorbidity in low- and middle-income countries (LMICs). Methods: PubMed, Cochrane, and Embase databases were searched from 1st January 2000 to 31st July 2020. The National Institute of Health (NIH) quality assessment tool was used to critically appraise studies. Findings were summarized in a narrative synthesis. The review was registered with PROSPERO (CRD42019133453). Results: Of 3718 articles screened, 79 articles underwent a full text review of which 11 were included for narrative synthesis. Studies reported on 4 to 20 chronic communicable and non-communicable diseases; prevalence of multimorbidity ranged from 13% in a study conducted among 242,952 participants from 48 LMICS to 87% in a study conducted among 491 participants in South Africa. Multimorbidity was positively associated with older age, female sex, unemployment, and physical inactivity. Significantly higher odds of multimorbidity were noted among obese participants (OR 2.33; 95% CI: 2.19-2.48) and those who consumed alcohol (OR 1.44; 95% CI: 1.25-1.66). The most frequently occurring dyads and triads were HIV and hypertension (23.3%) and HIV, hypertension, and diabetes (63%), respectively. Women and participants from low wealth quintiles reported higher utilization of public healthcare facilities. Conclusion: The identification and prevention of risk factors and addressing evidence gaps in multimorbidity clustering is crucial to address the increasing communicable and non-communicable disease multimorbidity in LMICs. To identify communicable and non-communicable diseases trends over time and identify causal relationships, longitudinal studies are warranted.

Evaluation of an adapted version of the Diabetes Prevention Program for low- and middle-income countries: A cluster randomized trial to evaluate "Lifestyle Africa" in South Africa.

BACKGROUND: Low- and middle-income countries (LMICs) are experiencing major increases in diabetes and cardiovascular conditions linked to overweight and obesity. Lifestyle interventions such as the United States National Diabetes Prevention Program (DPP) developed in high-income countries require adaptation and cultural tailoring for LMICs. The objective of this study was to evaluate the efficacy of "Lifestyle Africa," an adapted version of the DPP tailored for an underresourced community in South Africa compared to usual care. METHODS AND FINDINGS: Participants were residents of a predominantly Xhosa-speaking urban township of Cape Town, South Africa characterized by high rates of poverty. Participants with body mass index (BMI) ≥ 25 kg/m2 who were members of existing social support groups or "clubs" receiving health services from local nongovernmental organizations (NGOs) were enrolled in a cluster randomized controlled trial that compared Lifestyle Africa (the intervention condition) to usual care (the control condition). The Lifestyle Africa intervention consisted of 17 video-based group sessions delivered by trained community health workers (CHWs). Clusters were randomized using a numbered list of the CHWs and their assigned clubs based on a computer-based random allocation scheme. CHWs, participants, and research team members could not be blinded to condition. Percentage weight loss (primary outcome), hemoglobin A1c (HbA1c), blood pressure, triglycerides, and low-density lipoprotein (LDL) cholesterol were assessed 7 to 9 months after enrollment. An individual-level intention-to-treat analysis was conducted adjusting for clustering within clubs and baseline values. Trial registration is at ClinicalTrials.gov (NCT03342274). Between February 2018 and May 2019, 782 individuals were screened, and 494 were enrolled. Participants were predominantly retired (57% were receiving a pension) and female (89%) with a mean age of 68 years. Participants from 28 clusters were allocated to Lifestyle Africa (15, n = 240) or usual care (13, n = 254). Fidelity assessments indicated that the intervention was generally delivered as intended. The modal number of sessions held across all clubs was 17, and the mean attendance of participants across all sessions was 61%. Outcome assessment was completed by 215 (90%) intervention and 223 (88%) control participants. Intent-to-treat analyses utilizing multilevel modeling included all randomized participants. Mean weight change (primary outcome) was -0.61% (95% confidence interval (CI) = -1.22, -0.01) in Lifestyle Africa and -0.44% (95% CI = -1.06, 0.18) in control with no significant difference (group difference = -0.17%; 95% CI = -1.04, 0.71; p = 0.71). However, HbA1c was significantly lower at follow-up in Lifestyle Africa compared to the usual care group (mean difference = -0.24, 95% CI = -0.39, -0.09, p = 0.001). None of the other secondary outcomes differed at follow-up: systolic blood pressure (group difference = -1.36; 95% CI = -6.92, 4.21; p = 0.63), diastolic blood pressure (group difference = -0.39; 95% CI = -3.25, 2.30; p = 0.78), LDL (group difference = -0.07; 95% CI = -0.19, 0.05; p = 0.26), triglycerides (group difference = -0.02; 95% CI = -0.20, 0.16; p = 0.80). There were no unanticipated problems and serious adverse events were rare, unrelated to the intervention, and similar across groups (11 in Lifestyle Africa versus 13 in usual care). Limitations of the study include the lack of a rigorous dietary intake measure and the high representation of older women. CONCLUSIONS: In this study, we found that Lifestyle Africa was feasible for CHWs to deliver and, although it had no effect on the primary outcome of weight loss or secondary outcomes of blood pressure or triglycerides, it had an apparent small significant effect on HbA1c. The study demonstrates the potential feasibility of CHWs to deliver a program without expert involvement by utilizing video-based sessions. The intervention may hold promise for addressing cardiovascular disease (CVD) and diabetes at scale in LMICs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03342274.

Cardiometabolic outcomes of women exposed to hyperglycaemia first detected in pregnancy at 3-6 years post-partum in an urban South African setting.

BACKGROUND: Hyperglycaemia first detected during pregnancy(HFDP) has far-reaching maternal consequences beyond the pregnancy. Our study evaluated the cardiometabolic outcomes in women with prior HFDP versus women without HFDP 3-6 years post-partum in urban South Africa. DESIGN AND METHODS: A prospective cohort study was performed of 103 black African women with prior HFDP and 101 without HFDP, 3-6 years post-partum at Chris Hani Baragwanath Academic Hospital, Soweto. Index pregnancy data was obtained from medical records. Post-partum, participants were re-evaluated for anthropometric measurements, body composition utilizing dual energy X-ray absorptiometry(DXA) and biochemical analysis (two-hour 75gm OGTT fasting insulin, lipids, creatinine levels and glucose levels). Cardiovascular risk was assessed by Framingham risk score(FRS). Carotid intima media thickness(cIMT) was used as a surrogate marker for subclinical atherosclerosis. Factors associated with progression to cardiometabolic outcomes were assessed using multivariable logistic and linear regression models. RESULTS: Forty-six(45.1%) HFDP women progressed to diabetes compared to 5(4.9%) in non HFDP group(p<0.001); only 20(43.4%) were aware of their diabetic status in the whole group. The odds(OR, 95% confidence interval(CI)) of progressing to type 2 diabetes(T2DM) and metabolic syndrome(MetS) after correcting for confounders in the HFDP group was 10.5(95% CI 3.7-29.5) and 6.3(95%CI 2.2-18.1), respectively. All visceral fat indices were found to be significantly higher in the HFDP group after adjusting for baseline body mass index. Ten-year estimated cardiovascular risk(FRS) and mean cIMT was statistically higher in the HFDP group(8.46 IQR 4.9-14.4; 0.48 mm IQR 0.44-0.53 respectively) compared to the non-HFDP group(3.48 IQR 2.1-5.7; 0.46mm IQR 0.42-0.50) respectively and this remained significant for FRS but was attenuated for cIMT after correcting for confounders. HIV did not play a role in progression to any of these outcomes. CONCLUSION: Women with a history of HFDP have a higher risk of cardiometabolic conditions within 6 years post-partum in an urban sub-Saharan African setting.

Implementing and Evaluating Community Health Worker-Led Cardiovascular Disease Risk Screening Intervention in Sub-Saharan Africa Communities: A Participatory Implementation Research Protocol.

The increasing burden of non-communicable diseases (NCDs), particularly cardiovascular diseases (CVD) in low- and middle-income countries (LMICs) poses a considerable threat to public health. Community-driven CVD risk screening, referral and follow-up of those at high CVDs risk is essential to supporting early identification, treatment and secondary prevention of cardiovascular events such as stroke and myocardial infarction. This protocol describes a multi-country study that aims to implement and evaluate a community health worker (CHW)-led CVD risk screening programme to enhance referral linkages within the local primary care systems in sub-Saharan Africa (SSA), using a participatory implementation science approach. The study builds upon a prior community-driven multicentre study conducted by the Collaboration for Evidence-based Health Care and Public Health in Africa (CEBHA+). This is a participatory implementation research. The study will leverage on the CVD risk citizen science pilot studies conducted in the four selected CEBHA+ project countries (viz. Ethiopia, Rwanda, Malawi, and South Africa). Through planned engagements with communities and health system stakeholders, CHWs and lay health worker volunteers will be recruited and trained to screen and identify persons that are at high risk of CVD, provide referral services, and follow-up at designated community health clinics. In each country, we will use a multi-stage random sampling to select and then screen 1000 study participants aged 35-70 years from two communities (one rural and one urban). Screening will be done using a simple validated non-laboratory-based CVD risk assessment mobile application. The RE-AIM model will be used in evaluating the project implementation outcomes, including reach, fidelity, adoption and perceived effectiveness. Developing the capacities of CHWs and lay health worker volunteers in SSA to support population-based, non-invasive population-based CVD risk prevention has the potential to impact on early identification, treatment and secondary prevention of CVDs in often under-resourced communities. Using a participatory research approach to implementing mobile phone-based CHW-led CVD risk screening, referral and follow-up in SSA will provide the evidence needed to determine the effectiveness of CVD risk screening and the potential for scaling up in the wider region.

Kisspeptins and Glucose Homeostasis in Pregnancy: Implications for Gestational Diabetes Mellitus-a Review Article.

Gestational diabetes mellitus (GDM) is becoming an increasingly common complication of pregnancy with the global rise of obesity. The precise pathophysiological mechanisms underpinning GDM are yet to be fully elucidated. Kisspeptin, a peptide encoded by the KISS1 gene, is mainly expressed by placental syncytiotrophoblasts during pregnancy. It is an essential ligand for kisspeptin 1 receptor (KISS1R), which is expressed by both the villous and invasive extravillous cytotrophoblast cells. Circulatory kisspeptins rise dramatically in the second and third trimester of pregnancy coinciding with the period of peak insulin resistance. Kisspeptins stimulate glucose-dependent insulin secretion and decreased plasma levels inversely correlate with markers of insulin resistance. Additionally, kisspeptins play a critical role in the regulation of appetite, energy utilisation and glucose homeostasis. GDM pregnancies have been associated with low circulatory kisspeptins, despite higher placental kisspeptin and KISS1R expression. This review evaluates the role of kisspeptin in insulin secretion, resistance and regulation of appetite as well as its implications in GDM.

IDF Diabetes Atlas: The prevalence of pre-existing diabetes in pregnancy - A systematic reviewand meta-analysis of studies published during 2010-2020.

OBJECTIVES: To estimate the prevalence of pre-existing diabetes in pregnancy from studies published during 2010-2020. METHODS: We searched PubMed, CINAHL, Scopus and other sources for relevant data sources. The prevalence of overall pre-existing, type 1 and type 2 diabetes, by country, region and period of study was synthesised from included studies using the inverse-variance heterogeneity model and the Freeman-Tukey transformation. Heterogeneity was assessed using the I2 statistic and publication bias using funnel plots. RESULTS: We identified 2479 records, of which 42 data sources with a total of 78 943 376 women, met the eligibility criteria. The included studies were from 17 countries in North America, Europe, the Middle East and North Africa, Australasia, Asia and Africa. The lowest prevalence was in Europe (0.5%, 95 %CI 0.4-0.7) and the highest in the Middle East and North Africa (2.4%, 95 %CI 1.5-3.1). The prevalence of pre-existing diabetes doubled from 0.5% (95 %CI 0.1-1.0) to 1.0% (95 %CI 0.6-1.5) during the period 1990-2020. The pooled prevalences of pre-existing type 1 and type 2 diabetes were 0.3% (95 %CI 0.2-0.4) and 0.2% (95 %CI 0.0-0.9) respectively. CONCLUSION: While the prevalence of pre-existing diabetes in pregnancy is low, it has doubled from 1990 to 2020.

The influence of maternal blood glucose during pregnancy on weight outcomes at birth and preschool age in offspring exposed to hyperglycemia first detected during pregnancy, in a South African cohort.

INTRODUCTION: Little is known about the influence of hyperglycemia first detected in pregnancy (HFDP) on weight outcomes in exposed offspring in Africa. We investigated the influence of maternal blood glucose concentrations during pregnancy on offspring weight outcomes at birth and preschool age, in offspring exposed to HFDP, in South Africa. RESEARCH DESIGN AND METHODS: Women diagnosed with HFDP had data routinely collected during the pregnancy and at delivery, at a referral hospital, and the offspring followed up at preschool age. Maternal fasting, oral glucose tolerance test 1 and 2-hour blood glucose were measured at diagnosis of HFDP and 2-hour postprandial blood glucose during the third trimester. Offspring were classified as either those exposed to diabetes first recognized in pregnancy (DIP) or gestational diabetes (GDM). At birth, neonates were classified into macrosomia, low birth weight (LBW), large for gestational age (LGA), appropriate (AGA) and small for gestational age (SGA)groups. At preschool age, offspring had height and weight measured and Z-scores for weight, height and BMI calculated. RESULTS: Four hundred and forty-three neonates were included in the study at birth, with 165 exposed to DIP and 278 exposed to GDM. At birth, the prevalence of LGA, macrosomia and LBW were 29.6%, 12.2% and 7.5%, respectively, with a higher prevalence of LGA and macrosomia in neonates exposed to DIP. At pre-school age, the combined prevalence of overweight and obesity was 26.5%. Maternal third trimester 2-hour postprandial blood glucose was significantly associated with z-scores for weight at birth and preschool age, and both SGA and LGA at birth. CONCLUSION: In offspring exposed to HFDP, there is a high prevalence of LGA and macrosomia at birth, and overweight and obesity at preschool age, with higher prevalence in those exposed to DIP, compared to GDM. Maternal blood glucose control during the pregnancy influences offspring weight at birth and preschool age.

Erratum: Demographic and socio-economic predictors of physical activity among people living with HIV of low socio-economic status.

[This corrects the article DOI: 10.4102/hsag.v24i0.1127.].

Risk factors for COVID-19 hospitalisation and death in people living with diabetes: A virtual cohort study from the Western Cape Province, South Africa.

BACKGROUND: COVID-19 outcomes and risk factors, including comorbidities and medication regimens, in people living with diabetes (PLWD) are poorly defined for low- and middle-income countries. METHODS: The Provincial Health Data Centre (Western Cape, South Africa) is a health information exchange collating patient-level routine health data for approximately 4 million public sector health care seekers. Data from COVID-19 patients diagnosed between March and July 2020, including PLWD, were analysed to describe risk factors, including dispensed diabetes medications and comorbidities, and their association with COVID-19 outcomes in this population. FINDINGS: There were 64,476 COVID-19 patients diagnosed. Of 9305 PLWD, 44.9% were hospitalised, 4.0% admitted to ICU, 0.6% received ventilation and 15.4% died. In contrast, proportions of COVID-19 patients without diabetes were: 12.2% hospitalised, 1.0% admitted, 0.1% ventilated and 4.6% died. PLWD were significantly more likely to be admitted (OR:3.73, 95 %CI: 3.53, 3.94) and to die (OR:3.01, 95 %CI: 2.76,3.28). Significant hospitalised risk factors included HIV infection, chronic kidney disease, current TB, male sex and increasing age. Significant risk factors for mortality were CKD, male sex, HIV infection, previous TB and increasing age. Pre-infection use of insulin was associated with a significant increased risk for hospitalisation (OR:1·39, 95 %CI:1·24,1·57) and mortality (OR1·49, 95 %CI:1·27; 1·74) and metformin was associated with a reduced risk for hospitalisation (OR:0·62,95 %CI:0·55, 0·71) and mortality (OR 0·77, 95 %CI:0·64; 0·92). INTERPRETATION: Using routine health data from this large virtual cohort, we have described the association of infectious and noncommunicable comorbidities as well as pre-infection diabetes medications with COVID-19 outcomes in PLWD in the Western Cape, South Africa. FUNDING: This research was funded in part, by the Wellcome Trust 203135/Z/16/Z, through support of NT. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The Wellcome Centre for Infectious Diseases Research in Africa is supported by core funding from the Wellcome Trust [203135/Z/16/Z]. NT receives funding from the CIDRI-Africa Wellcome Trust grant (203135/Z/16/Z), and NT and TT receive funding from the NIH H3ABioNET award (U24HG006941). NT receives funding from the UKRI/MRC (MC_PC_MR/T037733/1).

Obesity and adiposity of 3- to 6-year-old children born to mothers with hyperglycaemia first detected in pregnancy in an urban South African setting.

BACKGROUND: Understanding the association between maternal metabolic conditions in pregnancy and the risk of childhood overweight, a growing concern in sub-Saharan Africa (SSA), helps to identify opportunities for childhood obesity prevention. AIM: To assess the association between hyperglycaemia first detected in pregnancy (HFDP) (gestational diabetes mellitus [GDM] and diabetes in pregnancy [DIP]) and child obesity and adiposity in pre-school-aged children in South Africa, independently of maternal BMI. SUBJECTS AND METHODS: Measurement of anthropometry and fat mass index (FMI) by the deuterium dilution method was done for 102 3-6-year-old children born to mothers with HFDP and 102 HFDP-unexposed children. Hierarchical regression analysis and generalised structural equation modelling (GSEM) were performed. RESULTS: The prevalence of overweight/obesity was 10.5% and 11.1% in children exposed to GDM and DIP, respectively, and 3.9% in the HFDP-unexposed group. Log-transformed FMI was significantly higher in the DIP-exposed group (ß = 0.166, 95% CI = 0.014-0.217 p= .026), but not when adjusting for maternal pregnancy BMI (ß = 0.226, 95% CI = 0.003-0.015, p = .004). GSEM showed significant total effects of maternal BMI and birth weight on FMI/BMI. CONCLUSIONS: Maternal pregnancy BMI seems to play a greater role in the development of childhood adiposity than maternal hyperglycaemia, requiring further research and identifying maternal BMI as a relevant prevention target in our setting.