Global DNA methylation profiling in peripheral blood cells of South African women with gestational diabetes mellitus.

Background/Objective: Recently, several studies have reported that DNA methylation changes in tissue are reflected in blood, sparking interest in the potential use of global DNA methylation as a biomarker for gestational diabetes mellitus (GDM). This study investigated whether global DNA methylation is associated with GDM in South African women. Methods: Global DNA methylation was quantified in peripheral blood cells of women with (n = 63) or without (n = 138) GDM using the MDQ1 Imprint® DNA Quantification Kit. Results: Global DNA methylation levels were not different between women with or without GDM and were not associated with fasting glucose or insulin concentrations. However, levels were 18% (p = 0.012) higher in obese compared to non-obese pregnant women and inversely correlated with serum adiponectin concentrations (p = 0.005). Discussion: Contrary to our hypothesis, global DNA methylation was not associated with GDM in our population. These preliminary findings suggest that despite being a robust marker of overall genomic methylation that offers opportunities as a biomarker, global DNA methylation profiling may not offer the resolution required to detect methylation differences in the peripheral blood cells of women with GDM. Moreover, global DNA methylation in peripheral blood cells may not reflect changes in placental tissue. Further studies in a larger sample are required to explore the candidacy of a more targeted approach using gene-specific methylation as a biomarker for GDM in our population.

Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus.

Increasing evidence implicate altered DNA methylation in the pathophysiology of gestational diabetes mellitus (GDM). This exploratory study probed the association between GDM and peripheral blood DNA methylation patterns in South African women. Genome-wide DNA methylation profiling was conducted in women with (n = 12) or without (n = 12) GDM using the Illumina Infinium HumanMethylationEPIC BeadChip array. Functional analysis of differentially methylated genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 1046 CpG sites (associated with 939 genes) were differentially methylated between GDM and non-GDM groups. Enriched pathways included GDM-related pathways such as insulin resistance, glucose metabolism and inflammation. DNA methylation of the top five CpG loci showed distinct methylation patterns in GDM and non-GDM groups and was correlated with glucose concentrations. Of these, one CpG site mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which have been shown to regulate insulin production and secretion and may offer potential as an epigenetic biomarker in our population. Further validation using pyrosequencing and conducting longitudinal studies in large sample sizes and in different populations are required to investigate their candidacy as biomarkers of GDM.

Association between gestational diabetes and biomarkers: a role in diagnosis.

BACKGROUND: We investigated the association between markers of insulin resistance, chronic inflammation, and adipokines and GDM. METHODS: In our case-cohort study in Johannesburg we included women with GDM and controls. We tested the ability of biomarkers to identify women at high risk of GDM. RESULTS: Of the 262 pregnant women, 83 (31.7%) had GDM. Women with GDM were heavier (p = 0.04) and had more clinical risk factors (p = 0.008). We found a significant difference in fasting insulin (p < 0.001), adiponectin (p = 0.046), HOMA (p < 0.001) and QUICKI (p < 0.001). HOMA (AUROC = 0.82) or QUICKI (AUROC = 0.82) improved the ability of risk factors to identify women at high risk of GDM. CONCLUSIONS: Insulin sensitivity markers are promising tools to identify women at high risk of GDM.

Molecular Biomarkers for Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a growing public health problem worldwide. The condition is associated with perinatal complications and an increased risk for future metabolic disease in both mothers and their offspring. In recent years, molecular biomarkers received considerable interest as screening tools for GDM. The purpose of this review is to provide an overview of the current status of single-nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs as biomarkers for GDM. PubMed, Scopus, and Web of Science were searched for articles published between January 1990 and August 2018. The search terms included "gestational diabetes mellitus", "blood", "single-nucleotide polymorphism (SNP)", "DNA methylation", and "microRNAs", including corresponding synonyms and associated terms for each word. This review updates current knowledge of the candidacy of these molecular biomarkers for GDM with recommendations for future research avenues.

Effect of a nutrition education programme on clinical status and dietary behaviours of adults with type 2 diabetes in a resource-limited setting in South Africa: a randomised controlled trial.

OBJECTIVE: To evaluate the effect of a participant-customised nutrition education programme on glycated Hb (HbA(1c)), blood lipids, blood pressure, BMI and dietary behaviours in patients with type 2 diabetes mellitus. DESIGN: A randomised controlled trial. The control group (n 41) received education materials. The intervention group (n 41) received the same education materials and participated in eight weekly (2-2·5 h) group nutrition education sessions and follow-up sessions. Outcomes were assessed at 6 and 12 months. An intention-to-treat analysis was conducted. ANCOVA compared the groups (adjustments for baseline values, age, sex and clinic). SETTING: Two community health centres, Moretele sub-district (North West Province), South Africa. SUBJECTS: Adults (aged 40-70 years) with type 2 diabetes, HbA(1c) ≥8 %. RESULTS: Differences in HbA(1c) (primary outcome) were -0·64 % (P=0·15) at 6 months and -0·63 % (P=0·16) at 12 months in favour of the intervention group. Starchy-food intake was significantly lower in the intervention group, 9·3 v. 10·8 servings/d (P=0·005) at 6 months and 9·9 v. 11·9 servings/d (P=0·017) at 12 months. Median energy intake was significantly lower in the intervention group at 12 months (5988 v. 6946 kJ/d, P=0·017). No significant group differences in BMI, lipid profile, blood pressure and intakes of macronutrients, vegetables and fruits were observed. CONCLUSIONS: Nutrition education was not efficacious on HbA(1c); however, it improved specific dietary behaviours. Group education and hands-on activities appeared to contribute to the improvement. Optimal goal setting and self-efficacy training/assessment could benefit future nutrition education programmes for people with type 2 diabetes mellitus in resource-limited settings.

Screening in Primary Care for Diabetic Retinopathy, Maculopathy and Visual Loss in South Africa.

OBJECTIVE: The aim of the study was to determine the prevalence of diabetic retinopathy, maculopathy and visual loss in primary care patients and to identify associated risk factors. RESEARCH DESIGN AND METHODS: We conducted a cluster randomised trial at primary care clinics in the Tshwane district in South Africa. Grades of retinopathy and maculopathy (with fundus camera) and visual acuity (Snellen chart) were assessed and, using mobile screening and teleophthalmology, clinical and biochemical testing was conducted to obtain information about glycaemic control and microvascular complications. RESULTS: The prevalence rates for any retinopathy, preproliferative retinopathy and proliferative retinopathy were 24.9, 19.5 and 5.5%, respectively. The prevalence rates of diabetic maculopathy, observable maculopathy and referable maculopathy were 20.8, 11.8 and 9.0%, respectively. The presence of retinopathy was associated with high body mass index, systolic blood pressure, being on insulin treatment, high HbA1c and the presence of neuropathy. High systolic blood pressure, being on insulin treatment, high HbA1c level and high low-density lipoprotein cholesterol level as well as the presence of albuminuria were significant in predicting any diabetic maculopathy. Laser photocoagulation was given to 8.3% of patients from the mobile unit and 12% of patients were referred to the nearest hospital with an outpatient eye clinic for follow-up treatment of various other eye conditions. Using the WHO categories, the study found that 78.1% of diabetes patients had normal vision, 19.3% were visually impaired and 2.2% were severely impaired or blind. CONCLUSION: High prevalence rates for diabetic retinopathy, maculopathy and visual loss were found and associations were identified.

Screening for dietary fat intake of grade six children: self-assessment vs. maternal assessment.

As part of justifiable nutrition promotion, this study aimed to determine internal consistency of a dietary fat screener and to compare self-assessment to maternal assessment of fat intake of grade six (about 12 years old) learners in a South African public primary school. The children completed in school a pictorial, quantitative food frequency-type screener consisting of 10 high-fat food categories; mothers individually completed a text version. Internal consistency was measured with item-total correlations, Cronbach's alpha and the split-half method. Child-mother comparison was based on kappa (κ) statistics, McNemar's tests, Wilcoxon signed-rank test and the Bland-Altman method. In total, 101 (93.5%) children and 78 (72.2%) mothers responded. The screener was internally consistent, regardless of data source and statistical technique. For portion sizes and frequency of intake, children consistently reported higher intake than mothers. This resulted in systematic error, also evidenced by a significant difference from zero for the difference between child's and mother's final test scores for the whole group, and for boys and girls separately (always P < 0.001). In 76% of the pairs, classification into high fat or prudent intake was identical, yet the chance-corrected agreement was poor (κ = 0.16) and non-agreement was non-symmetrical (P = 0.001). Children and mothers reported high fat intakes (93% and 75%, respectively). It was concluded that the dietary fat screener was internally consistent, yet children and mothers did not agree in their assessment. The high fat intakes reported by children and mothers warrant measurement refinement and implementation of primary prevention programmes.

Implementation research: a protocol for two three-arm pragmatic randomised controlled trials on continuous glucose monitoring devices in people with type 1 diabetes in South Africa and Kenya.

BACKGROUND: Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. METHODS: This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). DISCUSSION: This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. TRIAL REGISTRATION: NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023.

Introduction of the AmpliChip CYP450 Test to a South African cohort: a platform comparative prospective cohort study.

BACKGROUND: Adverse drug reactions and lack of therapeutic efficacy associated with currently prescribed pharmacotherapeutics may be attributed, in part, to inter-individual variability in drug metabolism. Studies on the pharmacogenetics of Cytochrome P450 (CYP) enzymes offer insight into this variability. The objective of this study was to compare the AmpliChip CYP450 Test® (AmpliChip) to alternative genotyping platforms for phenotype prediction of CYP2C19 and CYP2D6 in a representative cohort of the South African population. METHODS: AmpliChip was used to screen for thirty-three CYP2D6 and three CYP2C19 alleles in two different cohorts. As a comparison cohort 2 was then genotyped using a CYP2D6 specific long range PCR with sequencing (CYP2D6 XL-PCR + Sequencing) platform and a PCR-RFLP platform for seven CYP2C19 alleles. RESULTS: Even though there was a low success rate for the AmpliChip, allele frequencies for both CYP2D6 and CYP2C19 were very similar between the two different cohorts. The CYP2D6 XL-PCR + Sequencing platform detected CYP2D6*5 more reliably and could correctly distinguish between CYP2D6*2 and *41 in the Black African individuals. Alleles not covered by the AmpliChip were identified and four novel CYP2D6 alleles were also detected. CYP2C19 PCR-RFLP identified CYP2C19*9,*15, *17 and *27 in the Black African individuals, with *2, *17 and *27 being relatively frequent in the cohort. Eliminating mismatches and identifying additional alleles will contribute to improving phenotype prediction for both enzymes. Phenotype prediction differed between platforms for both genes. CONCLUSION: Comprehensive genotyping of CYP2D6 and CYP2C19 with the platforms used in this study, would be more appropriate than AmpliChip for phenotypic prediction in the South African population. Pharmacogenetically important novel alleles may remain undiscovered when using assays that are designed according to Caucasian specific variation, unless alternate strategies are utilised.

Association of hemodynamic response during dipyridamole stress testing with 99mTc-MIBI SPET myocardial perfusion image findings.

The aim of this study was to assess whether there is an association between changes in the heart rate and blood pressure after dipyridamole stress and abnormal scan findings detected with gated technetium-99m methoxy isobutylisonitrile (99mTc-MIBI) myocardial perfusion imaging (MPI). A total of 200 consecutive patients with known or suspected coronary artery disease underwent MPI using a 2 days stress/rest protocol. Heart rate (HR), blood pressure and electrocardiogram were monitored during the stress study. Dipyridamole-induced increase in HR ratio (peak HR/baseline HR) of more than 1.20 and decrease in systolic blood pressure (SBP) of 10 mmHg or more were defined as a normal response. Low ejection fraction (EF) was defined as EF less than 45%. Semi-quantitative measures used include summed stress score (SSS), summed difference score (SDS), end systolic volume (ESV) and left ventricular ejection fraction (LVEF). Chi-square-and regression analysis was used to assess associations between the various hemodynamic parameters and MPI abnormalities. Our results showed that 75% of patients had abnormal scans. Statistically significant associations were observed between each of the following factors and abnormal scan findings: abnormal SBP response to dipyridamole (P=0.011), increased SSS (P=0.040) and low LVEF (P=0.012). A significant association was also observed between decreased HR response and low LVEF (P=0.012). In conclusion, this study demonstrated that an abnormal hemodynamic response during dipyridamole stress test was associated with abnormal myocardial perfusion imaging scan findings, low LVEF and SSS.

The impact of diabetes during pregnancy on neonatal outcomes among the Aboriginal population in Western Australia: a whole-population study.

BACKGROUND: Aboriginal and Torres Strait Islander (hereafter Aboriginal) women have a high prevalence of diabetes in pregnancy (DIP), which includes pre-gestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM). We aimed to characterize the impact of DIP in babies born to Aboriginal mothers. METHODS: A retrospective cohort study, using routinely collected linked health data that included all singleton births (N = 510 761) in Western Australia between 1998 and 2015. Stratified by Aboriginal status, generalized linear mixed models quantified the impact of DIP on neonatal outcomes, estimating relative risks (RRs) with 95% CIs. Ratio of RRs (RRRs) examined whether RRs differed between Aboriginal and non-Aboriginal populations. RESULTS: Exposure to DIP increased the risk of adverse outcomes to a greater extent in Aboriginal babies. PGDM heightened the risk of large for gestational age (LGA) (RR: 4.10, 95% CI: 3.56-4.72; RRR: 1.25, 95% CI: 1.09-1.43), macrosomia (RR: 2.03, 95% CI: 1.67-2.48; RRR: 1.39, 95% CI: 1.14-1.69), shoulder dystocia (RR: 4.51, 95% CI: 3.14-6.49; RRR: 2.19, 95% CI: 1.44-3.33) and major congenital anomalies (RR: 2.14, 95% CI: 1.68-2.74; RRR: 1.62, 95% CI: 1.24-2.10). GDM increased the risk of LGA (RR: 2.63, 95% CI: 2.36-2.94; RRR: 2.00, 95% CI: 1.80-2.22), macrosomia (RR: 1.95, 95% CI: 1.72-2.21; RRR: 2.27, 95% CI: 2.01-2.56) and shoulder dystocia (RR: 2.78, 95% CI: 2.12-3.63; RRR: 2.11, 95% CI: 1.61-2.77). Birthweight mediated about half of the DIP effect on shoulder dystocia only in the Aboriginal babies. CONCLUSIONS: DIP differentially increased the risks of fetal overgrowth, shoulder dystocia and congenital anomalies in Aboriginal babies. Improving care for Aboriginal women with diabetes and further research on preventing shoulder dystocia among these women can reduce the disparities.

COVID-19 severity and in-hospital mortality in an area with high HIV prevalence.

Background: HIV infection causes immune dysregulation affecting T-cell and monocyte function, which may alter coronavirus disease 2019 (COVID-19) pathophysiology. Objectives: We investigated the associations among clinical phenotypes, laboratory biomarkers, and hospitalisation outcomes in a cohort of people hospitalised with COVID-19 in a high HIV prevalence area. Method: We conducted a prospective observational cohort study in Tshwane, South Africa. Respiratory disease severity was quantified using the respiratory oxygenation score. Analysed biomarkers included inflammatory and coagulation biomarkers, CD4 T-cell counts, and HIV-1 viral loads (HIVVL). Results: The analysis included 558 patients, of whom 21.7% died during admission. The mean age was 54 years. A total of 82 participants were HIV-positive. People living with HIV (PLWH) were younger (mean age 46 years) than HIV-negative people; most were on antiretroviral treatment with a suppressed HIVVL (72%) and the median CD4 count was 159 (interquartile range: 66-397) cells/µL. After adjusting for age, HIV was not associated with increased risk of mortality during hospitalisation (age-adjusted hazard ratio = 1.1, 95% confidence interval: 0.6-2.0). Inflammatory biomarker levels were similar in PLWH and HIV-negative patients. Detectable HIVVL was associated with less severe respiratory disease. In PLWH, mortality was associated with higher levels of inflammatory biomarkers. Opportunistic infections, and other risk factors for severe COVID-19, were common in PLWH who died. Conclusion: PLWH were not at increased risk of mortality and those with detectable HIVVL had less severe respiratory disease than those with suppressed HIVVL. What this study adds: This study advances our understanding of severe COVID-19 in PLWH.

Assessing barriers to insulin therapy among people with type 2 diabetes in South Africa using the Insulin Treatment Appraisal Scale: A cross-sectional survey.

AIMS: To assess barriers to insulin therapy among people with type 2 diabetes after adapting the Insulin Treatment Appraisal Scale (ITAS) to the South African context. METHODS: A panel of experts reviewed the original ITAS for clarity and relevance to the South African context. The ITAS was administered to 253 adults with type 2 diabetes attending diabetes outpatient clinics in the Tshwane Metropolitan Municipality. Internal consistency (Cronbach's alpha) was tested and construct validity was examined using exploratory factor analysis (EFA). PIR was appraised in insulin users and non-users. RESULTS: The EFA revealed that the adapted ITAS had a two-factor structure, similar to the original scale, with acceptable internal consistency (α = 0.85). Insulin-using participants had significantly less negative attitudes to insulin therapy than non-users (40.7 ± 7.1 vs. 51.5 ± 11.2, p < 0.001). Compared to participants who used insulin, participants who did not use insulin were afraid of injecting themselves with a needle (71% vs. 11%, p < 0.001) and saw insulin treatment as a sign of worsening diabetes (63% vs. 29%, p < 0.001). CONCLUSIONS: Consistent with previous studies, participants who were not using insulin had more negative beliefs and attitudes towards insulin treatment than those who were already using insulin. South African clinicians should use the ITAS to assess positive and negative perceptions regarding insulin therapy in both insulin-naïve and insulin-treated people, to evaluate interventions to reduce PIR and improve treatment outcomes.

Factors affecting the implementation of a complex health intervention to improve insulin management in primary care: A SWOT analysis.

BACKGROUND:  In South Africa, initiating and managing insulin in primary care for people living with type 2 diabetes (PLWD) is a major challenge. To address these challenges, a multidisciplinary team from the University of Pretoria (South Africa) developed the Tshwane Insulin project (TIP) intervention. AIM:  To determine internal and external factors, either facilitators or barriers, that could influence the implementation of the TIP intervention and propose strategies to ensure sustainability. SETTING:  Tshwane District, Gauteng province, South Africa. METHODS:  We used the SWOT framework to qualitatively analyse the strengths, weaknesses, opportunities, and threats influencing the implementation of the TIP intervention. Four field researchers and three managers from the TIP team participated in an online group discussion. We also conducted semi-structured interviews with healthcare providers (HCPs) (seven nurses, five doctors) and patients with type 2 diabetes (n = 13). RESULTS:  Regardless of the identified weaknesses, the TIP intervention was accepted by PLWD and HCPs. Participants identified strengths including app-enabled insulin initiation and titration, pro-active patient follow-up, patient empowerment and provision of glucose monitoring devices. Participants viewed insulin resistance and the attitudes of HCPs as potential threats. Participants suggested that weaknesses and threats could be mitigated by translating education material into local languages and using the lived experiences of insulin-treated patients to address insulin resistance. The procurement of glucose monitoring devices by national authorities would promote the sustainability of the intervention. CONCLUSION:  Our findings may help decision-makers and health researchers to improve insulin management for PLWD in resource-constrained settings by using telehealth interventions.

Effectiveness of an adapted diabetes nutrition education program on clinical status, dietary behaviors and behavior mediators in adults with type 2 diabetes: a randomized controlled trial.

PURPOSE: This study evaluated the effectiveness of an adapted social-cognitive theory underpinned diabetes nutrition education program (NEP) on: clinical (HbA1c, BMI, blood lipids, blood pressure) and selected dietary behaviors (starchy foods and energy intake, vegetables and fruit intake) and behavior mediators (knowledge and diabetes management self-efficacy) in patients with type 2 diabetes mellitus (T2DM). METHODS: A tertiary hospital outpatient adults (40-70 years) with poorly controlled (HbA1c ≥ 8 %) T2DM were randomized to either intervention group (n = 39: NEP, 7-monthly group education sessions, bi-monthly follow-up sessions, 15-minute individual session, workbook + education materials) or control group (n = 38: education materials only). NEP aimed to improve clinical status through improved dietary behaviors and behavior mediators. Outcomes and changes in diabetes medication were assessed at six and 12 months. Intention-to-treat analysis was conducted. ANCOVA compared the groups (baseline values, age, sex adjustments). RESULTS: Forty-eight (62.3 %) participants completed the study. Intervention group compared to the control group had lower (-0.53 %), clinically meaningful HbA1c (primary outcome) at 6 months, albeit not sustained at 12 months. Compared to the control group, the intervention group had significantly lower: (i) systolic blood pressure at six and 12 months (ii) diastolic pressure at 12 months, (iii) energy intake at six-months, (iv) up-titration of insulin at six and 12 months and higher diabetes knowledge scores at six months. CONCLUSIONS: NEP had limited effects on HbA1c, targeted dietary behaviors and behavior mediators but showed positive effects on blood pressure. The NEP health cost savings potential supports the need for improving program participation. TRIAL REGISTRATION: ClinicalTrials.gov. number NCT03334773; 7 November 2017 retrospectively registered.

Suboptimal control for patients with type 2 diabetes in the Central Chronic Medicine Dispensing programme in South Africa.

BACKGROUND: In South Africa, the Central Chronic Medicine Dispensing and Distribution (CCMDD) programme allows stable patients with non-communicable diseases, including type 2 diabetes mellitus (T2DM), to collect their medication from a pick-up location near their home, thus avoiding long waiting times and travel expenses. The CCMDD programme aims at improving patient retention and adherence through better access to medicines, resulting in better health outcomes. AIM: We assessed whether patients with T2DM enrolled in CCMDD achieved the recommended targets for glycaemic, blood pressure (BP) and lipid control. SETTING: City of Tshwane, South Africa. METHODS: We reviewed the records of 198 T2DM patients enrolled in CCMDD and assessed their control of haemoglobin A1c (HbA1c), BP and lipids. RESULTS: Most of the records reviewed belonged to women (64.7%), African (89.9%), hypertensive (82.7%) and to patients exclusively on oral antidiabetic agents (98.5%). Patients were, on average, 57.7 (s.d. = 12.1) years old and had participated in the CCMDD programme for, on average, 2 years. The mean HbA1c was 8% (s.d. = 2). Glycaemic control was achieved by only 29.2% of patients, and 49% of patients had HbA1c between 7% and 9%. Ninety-three patients (66%) had achieved the total cholesterol target, 57.4% achieved BP targets and 6.9% had achieved the low-density lipoprotein cholesterol target. CONCLUSION: A small group of patients achieved the targets for glycaemic, BP and lipid control. Despite improved accessibility to medication, the CCMDD is not synonymous of improved clinical outcomes. Future research should ascertain the factors associated with suboptimal control for these patients.

No Association Between ADIPOQ or MTHFR Polymorphisms and Gestational Diabetes Mellitus in South African Women.

PURPOSE: Gestational diabetes mellitus (GDM) is a growing public health concern. GDM affects approximately 14% of pregnancies globally, and without effective treatment, is associated with short- and long-term complications in mother and child. Lower serum adiponectin (ADIPOQ) concentrations and aberrant DNA methylation have been reported during GDM. The aim of this study was to investigate the association between the ADIPOQ -11377C>G and -11391G>A, and methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphisms and GDM in a population of black South African women. MATERIALS AND METHODS: DNA was isolated from the peripheral blood of 447 pregnant women with (n=116) or without (n=331) GDM, where after ADIPOQ (rs266729 and rs17300539) and MTHFR (rs1801133) polymorphisms were genotyped using TaqMan Quantitative Real-Time PCR analysis. RESULTS: Women with GDM had a higher body mass index (p=0.012), were more insulin resistant (p<0.001) and had lower adiponectin levels (p=0.013) compared to pregnant women with normoglycemia. Genotypic, dominant and recessive genetic models showed no association between ADIPOQ rs266729 and rs17300539 and MTHFR rs1801133 polymorphisms and GDM. Intriguingly, the risk G allele of ADIPOQ rs266729 was associated with higher fasting glucose and insulin concentrations, while the T allele in MTHFR rs1801133 was associated with higher fasting insulin concentrations only. CONCLUSION: ADIPOQ rs266729 and rs17300539 and MTHFR rs1801133 polymorphisms are not associated with GDM in a population of black South African women. These findings suggest that these single nucleotide polymorphisms (SNPs) do not individually increase GDM risk in the African population. However, the role of these SNPs in possible gene-gene or gene-environment interactions remain to be established.

Adiponectin DNA methylation in South African women with gestational diabetes mellitus: Effects of HIV infection.

DNA methylation is increasingly recognized as a potential biomarker of metabolic disease. However, there is limited information on the impact of human immunodeficiency virus (HIV) infection on the candidacy of DNA methylation to serve as molecular biomarkers. This study investigated the effect of HIV infection on DNA methylation patterns in the peripheral blood of South African women with (n = 95) or without (n = 191) gestational diabetes mellitus (GDM). DNA methylation levels at eight CpG sites in the adiponectin gene (ADIPOQ) promoter were measured using bisulfite conversion and pyrosequencing. Differences between HIV negative (-) and positive (+) women were observed. In HIV- women, methylation at CpG -3400 was lower in GDM+ women compared to those with normoglycemia (8.5-fold; p = 0.004), and was associated with higher fasting glucose (ß-co-efficient = 0.973; p = 0.006) and lower adiponectin (ß-co-efficient = -0.057; p = 0.014) concentrations. These associations were not observed in HIV+ women. In silico analysis showed that Transcription Factor AP2-alpha is able to bind to the altered CpG site, suggesting that CpG -3400 may play a functional role in the regulation of ADIPOQ expression. Our findings show that DNA methylation differs by HIV status, suggesting that HIV infection needs to be taken into consideration in studies exploring DNA methylation as a biomarker of GDM in high HIV prevalence settings.

Attitudes and beliefs of South African primary healthcare practitioners on initiating insulin in people with type 2 diabetes: Findings from the Tshwane Insulin Project (TIP).

AIMS: To investigate the attitudes and beliefs of primary healthcare practitioners (HCPs) towards initiating insulin therapy for people with type 2 diabetes (T2D) in South Africa. METHODS: A cross-sectional survey was conducted amongst HCPs from 23 clinics. The nurses' questionnaire was administered by research nurses while doctors completed an online version about their attitudes, beliefs and perceived barriers to initiating insulin. RESULTS: Of the 73 HCPs surveyed, 68% were nurses and 84% were women. Only 24% of HCPs believed that most patients would eventually need to initiate insulin regardless of their adherence to treatment regimens and 86% preferred to delay insulin therapy. Doctors were reluctant to initiate insulin, citing patient-related reasons such as low socio-economic level (41%), inability to refrigerate insulin (77%) and inability to self-monitor blood glucose (55%). Doctors mentioned that patient behaviour including not adhering to treatment regimen and appointments (91%) and reluctance to start insulin therapy (82%) influenced their prescription practices. Doctors mentioned that health system factors, including the pressure to see patients quickly (68%) and lack of continuity of care (64%) were barriers to initiating insulin. CONCLUSIONS: Optimising insulin therapy in primary care requires health system changes including promoting person-centred care and continuing training for HCPs.

Designing an integrated, nurse-driven and home-based digital intervention to improve insulin management in under-resourced settings.

BACKGROUND: In South Africa, initiating insulin for people with type 2 diabetes and subsequent titration is a major challenge for the resource-constrained healthcare system. Inadequate support systems in primary care, including not being able to access blood glucose monitors and test strips for self-monitoring of blood glucose, results in patients with type 2 diabetes being referred to higher levels of care. In primary care, initiation of insulin may be delayed due to a shortage of healthcare workers. The delayed initiation of insulin is also exacerbated by the reported resistance of both healthcare providers and people with type 2 diabetes to start insulin. In South Africa, telehealth provides an opportunity to overcome these challenges and manage insulin therapy in primary care. METHODS: We describe the development of a digital health intervention including the framework used, the theoretical approach and subsequent implementation strategies. RESULTS: This intervention is an innovative, nurse-driven and app-enabled intervention called 'the Tshwane Insulin Project intervention'. The Tshwane Insulin Project intervention was designed and evaluated using the framework recommended by the Medical Research Council for complex interventions. The Tshwane Insulin Project intervention was developed in four sequential phases: planning, design, implementation and evaluation. The Tshwane Insulin Project intervention followed the Integrated Chronic Disease Management framework to facilitate implementation and acceptability. The Tshwane Insulin Project comprises a facility-level intervention, where nurses evaluate patients and initiate insulin, an individual-level intervention where community healthcare workers visit patients at their homes to follow-up and provide educational information, while using telehealth to enable physician-directed insulin titration if needed, and a community-level intervention aimed at empowering community healthcare workers to support people living with diabetes and raise awareness of diabetes. CONCLUSION: The technological advancements in digital health and telemedicine present an opportunity to improve diabetes care in resource-limited countries. This work can inform those intending to develop and implement complex interventions in primary healthcare in developing countries.