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.

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.

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.

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.

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.

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.

Tuberculosis, Human Immunodeficiency Virus, and the Association With Transient Hyperglycemia in Periurban South Africa.

BACKGROUND: Diabetes mellitus (DM) increases tuberculosis (TB) risk. We assessed the prevalence of hyperglycemia (DM and impaired glucose regulation [IGR]) in persons with TB and the association between hyperglycemia and TB at enrollment and 3 months after TB treatment in the context of human immunodeficiency virus (HIV) infection. METHODS: Adults presenting at a Cape Town TB clinic were enrolled. TB cases were defined by South African guidelines, while non-TB participants were those who presented with respiratory symptoms, negative TB tests, and resolution of symptoms 3 months later without TB treatment. HIV status was ascertained through medical records or HIV testing. All participants were screened for DM using glycated hemoglobin and fasting plasma glucose at TB treatment and after 3 months. The association between TB and DM was assessed. RESULTS: Overall DM prevalence was 11.9% (95% confidence interval [CI], 9.1%-15.4%) at enrollment and 9.3% (95% CI, 6.4%-13%) at follow-up; IGR prevalence was 46.9% (95% CI, 42.2%-51.8%) and 21.5% (95% CI, 16.9%-26.3%) at enrollment and follow-up. TB/DM association was significant at enrollment (odds ratio [OR], 2.41 [95% CI, 1.3-4.3]) and follow-up (OR, 3.3 [95% CI, 1.5-7.3]), whereas TB/IGR association was only positive at enrollment (OR, 2.3 [95% CI, 1.6-3.3]). The TB/DM association was significant at enrollment in both new and preexisting DM, but only persisted at follow-up in preexisting DM in patients with HIV-1 infection. CONCLUSIONS: Our study demonstrated high prevalence of transient hyperglycemia and a significant TB/DM and TB/IGR association at enrollment in newly diagnosed DM, but persistent hyperglycemia and TB/DM association in patients with HIV-1 infection and preexisting DM, despite TB therapy.

Food purchasing behaviour of shoppers from different South African socio-economic communities: results from grocery receipts, intercept surveys and in-supermarkets audits.

OBJECTIVE: To identify factors associated with food purchasing decisions and expenditure of South African supermarket shoppers across income levels. DESIGN: Intercept surveys were conducted, grocery receipts collated and expenditure coded into categories, with each category calculated as percentage of the total expenditure. In-supermarket food quality audit and shelf space measurements of foods such as fruits and vegetables (F&V) (healthy foods), snacks and sugar-sweetened beverages (SSB) (unhealthy foods) were also assessed. Shoppers and supermarkets were classified by high-, middle- and low-income socio-economic areas (SEA) of residential area and location, respectively. Shoppers were also classified as "out-shoppers" (persons shopping outside their residential SEA) and "in-shoppers" (persons shopping in their residential SEA). Data were analysed using descriptive analysis and ANOVA. SETTING: Supermarkets located in different SEA in urban Cape Town. PARTICIPANTS: Three hundred ninety-five shoppers from eleven purposively selected supermarkets. RESULTS: Shelf space ratio of total healthy foods v. unhealthy foods in all the supermarkets was low, with supermarkets located in high SEA having the lowest ratio but better quality of fresh F&V. The share expenditure on SSB and snacks was higher than F&V in all SEA. Food secure shoppers spent more on food, but food items purchased frequently did not differ from the food insecure shoppers. Socio-economic status and food security were associated with greater expenditure on food items in supermarkets but not with overall healthier food purchases. CONCLUSION: Urban supermarket shoppers in South Africa spent substantially more on unhealthy food items, which were also allocated greater shelf space, compared with healthier foods.

Progression to type 2 diabetes mellitus and associated risk factors after hyperglycemia first detected in pregnancy: A cross-sectional study in Cape Town, South Africa.

BACKGROUND: Global data indicate that women with a history of hyperglycemia first detected in pregnancy (HFDP) are at up to 7 times risk of progressing to type 2 diabetes mellitus (T2DM) compared with their counterparts who have pregnancies that are not complicated by hyperglycemia. However, there are no data from the sub-Saharan African region, which has the highest projected rise in diabetes prevalence globally. The aim of this study was to determine the proportion of women who progress to T2DM and associated risk factors 5 to 6 years after HFDP in Cape Town, South Africa. METHODS AND FINDINGS: All women with HFDP, at a major referral hospital in Cape Town, were followed up 5 to 6 years later using a cross-sectional study. Each participant had a 75 g oral glucose tolerance test; anthropometric measurements and a survey were administered. A total of 220 participants were followed up. At this time, their mean age was 37.2 years (SD 6.0). Forty-eight percent (95% CI 41.2-54.4) progressed to T2DM, 5.5% (95% CI 3.1-9.4) had impaired fasting glucose, and 10.5% (95% CI 7.0-15.3) had impaired glucose tolerance. Of the participants who progressed to T2DM, 47% were unaware of their diabetes status. When HFDP was categorized post hoc according to WHO 2013 guidelines, progression in the diabetes in pregnancy (DIP) group was 81% (95% CI 70.2-89.0) and 31.3% (95% CI 24.4-39.3) in the gestational diabetes mellitus (GDM) category. Factors associated with risk of progression to T2DM were; at follow-up: waist circumference (odds ratios [OR] 1.1, 95% CI 1.0-1.1, p = 0.007), hip circumference (OR 0.9, 95% CI 0.8-1.0, p = 0.001), and BMI (OR 1.1, 95% CI 1.0-1.3, p = 0.001), and at baseline: insulin (OR 25.8, 95% CI 3.9-171.4, p = 0.001) and oral hypoglycaemic treatment during HFDP (OR 4.1, 95% CI 1.3-12.9, p = 0.018), fasting (OR 2.7, 95% CI 1.5-4.8, p = 0.001), and oral glucose tolerance test 2-hour glucose concentration at HFDP diagnosis (OR 4.3, 95% CI 2.4-7.7, p < 0.001). Our findings have limitations in that we did not include a control group of women without a history of HFDP. CONCLUSIONS: The progression to T2DM in women with previous HFDP found in this study highlights the need for interventions to delay or prevent progression to T2DM after HFDP. In addition, interventions to prevent HFDP may also contribute to reducing the risk of T2DM.

Factors that influence patient empowerment in inpatient chronic care: early thoughts on a diabetes care intervention in South Africa.

BACKGROUND: The burden of non-communicable diseases is growing rapidly in low- and middle-income countries. Research suggests that health interventions that aim to improve patient self-management and empower patients to care actively for their disease will improve health outcomes over the long-term. There is, however, a gap in the literature about the potential role of the inpatient setting in supporting chronic care. This is particularly important in low-and-middle income countries where hospitals may be a rare prolonged point of contact between patient and health provider. The aim of this small scale, exploratory study was to understand what factors within the inpatient setting may affect patients' feelings of empowerment in relation to their chronic disease care and provides recommendations for future inpatient-based interventions to support self-management of disease. METHODS: This study was based in a public, academic hospital in South Africa. Eighteen qualitative, semi-structured interviews were conducted with multiple participants with experience of diabetes care: inpatients and health professionals such as nurses, endocrinologists, and dieticians. Findings were analysed using a broad, exploratory, thematic approach, guided by self-management and chronic care literature. RESULTS: Interviews with both patients and providers suggest that patients living in low socio-economic contexts are likely to struggle to access appropriate healthcare information and services, and may often have financial and emotional priorities that take precedence over their chronic illness. Younger people may also be more dependent on their family and community, giving them less ability to take control of their disease care and lifestyle. In addition, hospital care remains bound by an acute care model; and the inpatient setting of focus is characterised by perceived staff shortages and ineffective communication that undermine the implementation of patient empowerment-focused interventions. CONCLUSIONS: Patient and provider contexts are likely to make supporting patient engagement in long-term chronic care difficult in lower income settings. However, knowledge of these factors can be harnessed to improve chronic care interventions in South Africa and other similar countries.

Evolution of sensory neuropathy after initiation of antiretroviral therapy.

INTRODUCTION: We studied the evolution of sensory neuropathy after antiretroviral therapy (ART) in human immunodeficiency virus-infected South Africans. METHODS: Enrolment commenced before ART with 6-monthly follow-ups for 24 months. Symptomatic distal sensory polyneuropathy (SDSP) was defined as one symptom and sign. Symptom/sign scores were compared between visits. RESULTS: We enrolled 184 participants. Pre-ART, 16% had SDSP. After 18 months of ART, pain prevalence decreased in those with pre-ART SDSP (odds ratio [OR], 0.09; 95% confidence interval [95%CI], 0.03-0.29). Symptoms improved in 50% ever experiencing pain (mean improvement = 4.5 on 11-point scale). Participants SDSP-free pre-ART developed SDSP at a rate of 18 per 100 person-years. After 24 months (n = 102), 18% had SDSP. Stavudine (60% of cohort) did not predict incident SDSP, but associated with increased prevalence of reduced/absent reflexes at 18 months (OR, 2.24; 95% CI, 1.08-4.65). DISCUSSION: Painful symptoms improved during ART. Evolving sensory neuropathy was due to increasing small and large fiber dysfunction. Muscle Nerve 57: 371-379, 2018.

Trilateral overlap of tuberculosis, diabetes and HIV-1 in a high-burden African setting: implications for TB control.

The diabetes mellitus burden is growing in countries where tuberculosis (TB) and HIV-1 remain major challenges, threatening TB control efforts. This study determined the association between TB and diabetes/impaired glucose regulation in the context of HIV-1.A cross-sectional study was conducted at a TB clinic in Cape Town (South Africa). Participants were screened for diabetes and impaired glucose regulation using fasting plasma glucose, oral glucose tolerance test and glycated haemoglobin (HbA1c).414 TB and 438 non-TB participants were enrolled. In multivariable analysis, diabetes was associated with TB (OR 2.4, 95% CI 1.3-4.3; p=0.005), with 14% population-attributable risk fraction; however, this association varied by diagnostic test (driven by HbA1c). The association remained significant in HIV-1-infected individuals (OR 2.4, 95% CI 1.1-5.2; p=0.030). A high prevalence of impaired glucose regulation (65.2% among TB cases) and a significant association with TB (OR 2.3, 95% CI 1.6-3.3; p<0.001) was also found.Diabetes and impaired glucose regulation prevalence was high and associated with TB, particularly in HIV-1-infected individuals, highlighting the importance of diabetes screening. The variation in findings by diagnostic test highlights the need for better glycaemia markers to inform screening in the context of TB and HIV-1.

Educational Outreach with an Integrated Clinical Tool for Nurse-Led Non-communicable Chronic Disease Management in Primary Care in South Africa: A Pragmatic Cluster Randomised Controlled Trial.

BACKGROUND: In many low-income countries, care for patients with non-communicable diseases (NCDs) and mental health conditions is provided by nurses. The benefits of nurse substitution and supplementation in NCD care in high-income settings are well recognised, but evidence from low- and middle-income countries is limited. Primary Care 101 (PC101) is a programme designed to support and expand nurses' role in NCD care, comprising educational outreach to nurses and a clinical management tool with enhanced prescribing provisions. We evaluated the effect of the programme on primary care nurses' capacity to manage NCDs. METHODS AND FINDINGS: In a cluster randomised controlled trial design, 38 public sector primary care clinics in the Western Cape Province, South Africa, were randomised. Nurses in the intervention clinics were trained to use the PC101 management tool during educational outreach sessions delivered by health department trainers and were authorised to prescribe an expanded range of drugs for several NCDs. Control clinics continued use of the Practical Approach to Lung Health and HIV/AIDS in South Africa (PALSA PLUS) management tool and usual training. Patients attending these clinics with one or more of hypertension (3,227), diabetes (1,842), chronic respiratory disease (1,157) or who screened positive for depression (2,466), totalling 4,393 patients, were enrolled between 28 March 2011 and 10 November 2011. Primary outcomes were treatment intensification in the hypertension, diabetes, and chronic respiratory disease cohorts, defined as the proportion of patients in whom treatment was escalated during follow-up over 14 mo, and case detection in the depression cohort. Primary outcome data were analysed for 2,110 (97%) intervention and 2,170 (97%) control group patients. Treatment intensification rates in intervention clinics were not superior to those in the control clinics (hypertension: 44% in the intervention group versus 40% in the control group, risk ratio [RR] 1.08 [95% CI 0.94 to 1.24; p = 0.252]; diabetes: 57% versus 50%, RR 1.10 [0.97 to 1.24; p = 0.126]; chronic respiratory disease: 14% versus 12%, RR 1.08 [0.75 to 1.55; p = 0.674]), nor was case detection of depression (18% versus 24%, RR 0.76 [0.53 to 1.10; p = 0.142]). No adverse effects of the nurses' expanded scope of practice were observed. Limitations of the study include dependence on self-reported diagnoses for inclusion in the patient cohorts, limited data on uptake of PC101 by users, reliance on process outcomes, and insufficient resources to measure important health outcomes, such as HbA1c, at follow-up. CONCLUSIONS: Educational outreach to primary care nurses to train them in the use of a management tool involving an expanded role in managing NCDs was feasible and safe but was not associated with treatment intensification or improved case detection for index diseases. This notwithstanding, the intervention, with adjustments to improve its effectiveness, has been adopted for implementation in primary care clinics throughout South Africa. TRIAL REGISTRATION: The trial is registered with Current Controlled Trials (ISRCTN20283604).

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

AIMS/HYPOTHESIS: There is evidence to suggest that ectopic fat deposition in liver and skeletal muscle may differ between black and white women resulting in organ-specific differences in insulin sensitivity. Accordingly, the aim of the study was to examine ethnic differences in hepatic and peripheral insulin sensitivity, and the association with hepatic and skeletal muscle lipid content, and skeletal muscle gene expression. METHODS: In a cross-sectional study including 30 obese premenopausal black and white women, body composition (dual energy x-ray absorptiometry), liver fat and skeletal muscle (soleus and tibialis anterior) fat accumulation (proton-magnetic resonance spectroscopy), skeletal muscle gene expression, insulin sensitivity (two-step isotope labelled, hyperinsulinaemic-euglycaemic clamp with 10 mU m(-2) min(-1) and 40 mU m(-2) min(-1) insulin infusions), and serum adipokines were measured. RESULTS: We found that, although whole-body insulin sensitivity was not different, obese white women presented with lower hepatic insulin sensitivity than black women (% suppression of endogenous glucose production [% supp EGP], median [interquartile range (IQR)]: 17 [5-51] vs 56 [29-100] %, p = 0.002). While liver fat tended to be lower (p = 0.065) and skeletal muscle fat deposition tended to be higher (p = 0.074) in black compared with white women, associations with insulin sensitivity were only observed in black women (% supp EGP vs liver fat: r = -0.57, p < 0.05 and % supp EGP vs soleus fat: r = -0.56, p < 0.05). CONCLUSIONS/INTERPRETATION: These findings may suggest that black women are more sensitive to the effects of ectopic lipid deposition than white women.

Pharmacogenetics of plasma efavirenz exposure in HIV-infected adults and children in South Africa.

AIMS: Genetic factors, notably CYP2B6 516G→T [rs3745274] and 983T→C [rs28399499], explain much of the interindividual variability in efavirenz pharmacokinetics, but data from Africa are limited. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations in HIV-infected Black South African adults and children. METHODS: Steady-state mid-dosing interval efavirenz concentrations were measured. We genotyped 241 polymorphisms in genes potentially relevant to efavirenz metabolism and transport, including ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3. RESULTS: Among 113 participants (59 adults and 54 children), minor allele frequencies for CYP2B6 516G→T, 983T→C, and 15582C→T [rs4803419] were 0.36, 0.07, and 0.09, respectively. Based on composite CYP2B6 15582/516/983 genotype, there were 33 extensive metabolizer, 62 intermediate metabolizer and 18 slow metabolizer genotypes. Median (IQR) mid-dose efavirenz concentrations were 1.44 (1.21-1.93) µg ml(-1), 2.08 (1.68-2.94) µg ml(-1) and 7.26 (4.82-8.34) µg ml(-1) for extensive, intermediate and slow metabolizers, respectively. In univariate analyses, a model that included composite genotype best predicted efavirenz concentrations (ß = 0.28, 95% CI 0.21, 0.35, P = 2.4 × 10(-11)). Among individual CYP2B6 polymorphisms, 516G→T best predicted efavirenz concentrations (ß = 0.22, 95% CI 0.13, 0.30, P = 1.27 × 10(-6)). There was also associations with 983T→C (ß = 0.27, 95% CI 0.10, 0.44, P = 0.002) and 15582C→T (ß = 0.11, 95% CI 0.01, 0.22, P = 0.04). Associations were consistent in adults and children. No other polymorphisms were independently associated with efavirenz concentrations. CONCLUSIONS: Composite CYP2B6 genotype based on CYP2B6 516G→T, 983T→C, and 15582C→T best described efavirenz exposure in HIV-infected Black South African adults and children.

Patterns of HIV, TB, and non-communicable disease multi-morbidity in peri-urban South Africa- a cross sectional study.

BACKGROUND: Many low and middle-income countries are experiencing colliding epidemics of chronic infectious (ID) and non-communicable diseases (NCD). As a result, the prevalence of multiple morbidities (MM) is rising. METHODS: We conducted a study to describe the epidemiology of MM in a primary care clinic in Khayelitsha. Adults with at least one of HIV, tuberculosis (TB), diabetes (DM), and hypertension (HPT) were identified between Sept 2012-May 2013 on electronic databases. Using unique patient identifiers, drugs prescribed across all facilities in the province were linked to each patient and each drug class assigned a condition. RESULTS: These 4 diseases accounted for 45% of all prescription visits. Among 14364 chronic disease patients, HPT was the most common morbidity (65%). 22.6% of patients had MM, with an increasing prevalence with age; and a high prevalence among younger antiretroviral therapy (ART) patients (26% and 30% in 18-35 yr and 36-45 year age groups respectively). Among these younger ART patients with MM, HPT and DM prevalence was higher than in those not on ART. CONCLUSIONS: We highlight the co-existence of multiple ID and NCD. This presents both challenges (increasing complexity and the impact on health services, providers and patients), and opportunities for chronic diseases screening in a population linked to care. It also necessitates re-thinking of models of health care delivery and requires policy interventions to integrate and coordinate management of co-morbid chronic diseases.

Changes in blood pressure, glucose levels, insulin secretion and anthropometry after long term exposure to antiretroviral therapy in South African women.

BACKGROUND: A number of metabolic abnormalities, such as dysglycaemia, insulin resistance, lipodystrophy and dyslipidaemia, are associated with the use of antiretroviral drugs. We aimed to assess the effects of long-term antiretroviral exposure on blood pressure, glycaemia, insulin secretion and anthropometric measures in black South African women. METHODS: A convenience sample of HIV-infected women on first-line ART for a median of 16 months at baseline, had the following evaluations twice, at baseline and after approximately 5 years: anthropometry, including skin fold thicknesses, blood pressure, oral glucose test, and insulin. Insulin sensitivity and secretion (HOMA-IR, IGI and DIo) were estimated. RESULTS: At baseline more than half the 103 women were using stavudine and efavirenz. The median interval between baseline and follow-up evaluation was 66 months. Weight, waist circumference, and waist-hip ratio increased over time, while limb skinfold thickness decreased over time. Systolic and diastolic blood pressure increased significantly and the proportion of participants with hypertension increased from 3.9 to 15.5% (p < 0.001). There were increases from baseline in plasma glucose concentrations at 30 and 120 min; insulin concentrations at 0 and 30 min; and IGI and DIo. The proportion of participants with diabetes increased from 1 to 7.5% (p = 0.070). CONCLUSION: In black South African women with long-term exposure to ART, increases in hypertension and possibly diabetes were observed. Participants experienced an increase in central fat and a decrease in peripheral fat distribution. Early identification and management of these metabolic changes are important, especially in a region with the highest HIV-infected population in the world.

Socioeconomic predictors and consequences of depression among primary care attenders with non-communicable diseases in the Western Cape, South Africa: cohort study within a randomised trial.

BACKGROUND: Socioeconomic predictors and consequences of depression and its treatment were investigated in 4393 adults with specified non-communicable diseases attending 38 public sector primary care clinics in the Eden and Overberg districts of the Western Cape, South Africa. METHODS: Participants were interviewed at baseline in 2011 and 14 months later, as part of a randomised controlled trial of a guideline-based intervention to improve diagnosis and management of chronic diseases. The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) was used to assess depression symptoms, with higher scores representing more depressed mood. RESULTS: Higher CESD-10 scores at baseline were independently associated with being less educated (p = 0.004) and having lower income (p = 0.003). CESD-10 scores at follow-up were higher in participants with less education (p = 0.010) or receiving welfare grants (p = 0.007) independent of their baseline scores. Participants with CESD-10 scores of ten or more at baseline (56 % of all participants) had 25 % higher odds of being unemployed at follow-up (p = 0.016), independently of baseline CESD-10 score and treatment status. Among participants with baseline CESD-10 scores of ten or more, antidepressant medication at baseline was independently more likely in participants who had more education (p = 0.002), higher income (p < 0.001), or were unemployed (p = 0.001). Antidepressant medication at follow up was independently more likely in participants with higher income (p = 0.023), and in clinics with better access to pharmacists (p = 0.053) and off-site drug delivery (p = 0.013). CONCLUSIONS: Socioeconomic disadvantage appears to be both a cause and consequence of depression, and may also be a barrier to treatment. There are opportunities for improving the prevention, diagnosis and treatment of depression in primary care in inequitable middle income countries like South Africa. TRIAL REGISTRATION: The trial is registered with Current Controlled Trials ( ISRCTN20283604 ).