Browsing by Author "Erasmus, Rajiv T."
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- ItemThe agreement between fasting glucose and markers of chronic glycaemic exposure in individuals with and without chronic kidney disease : a cross-sectional study(BMC (part of Springer Nature), 2020-01-30) George, Cindy; Matsha, Tandi E.; Korf, Marizna; Zemlin, Annalise E.; Erasmus, Rajiv T.; Kengne, Andre P.Background: To assess whether the agreement between fasting glucose and glycated proteins is affected by chronic kidney disease (CKD) in a community-based sample of 1621 mixed-ancestry South Africans. Methods: CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2. Fasting plasma glucose and haemoglobin A1c (HbA1c) concentrations were measured by enzymatic hexokinase method and highperformance liquid chromatography, respectively, with fructosamine and glycated albumin measured by immunoturbidimetry and enzymatic method, respectively. Results: Of those with CKD (n = 96), 79, 16 and 5% where in stages 3, 4 and 5, respectively. Those with CKD had higher levels of HbA1c (6.2 vs. 5.7%; p < 0.0001), glycated albumin (15.0 vs. 13.0%; p < 0.0001) and fructosamine levels (269.7 vs. 236.4 μmol/l; p < 0.0001), compared to those without CKD. Higher fasting glucose levels were associated with higher HbA1c, glycated albumin and fructosamine, independent of age, gender, and CKD. However, the association with HbA1c and glycated albumin differed by CKD status, at the upper concentrations of the respective markers (interaction term for both: p ≤ 0.095). Conclusion: Our results suggest that although HbA1c and glycated albumin perform acceptably under conditions of normoglycaemia, these markers correlate less well with blood glucose levels in people with CKD who are not on dialysis.
- ItemAssessing clustering of metabolic syndrome components available at primary care for Bantu Africans using factor analysis in the general population(BioMed Central, 2013-06) Nasila Sungwacha, John; Tyler, Joanne; Longo-Mbenza, Benjamin; Lasi On'Kin, Jean Bosco Kasiam; Gombet, Thierry; Erasmus, Rajiv T.ABSTRACT: To provide a step-by-step description of the application of factor analysis and interpretation of the results based on anthropometric parameters(body mass index or BMI and waist circumferenceor WC), blood pressure(BP), lipid-lipoprotein(triglycerides and HDL-C) and glucose among Bantu Africans with different numbers and cutoffs of components of metabolic syndrome(MS). This study was a cross-sectional, comparative, and correlational survey conducted between January and April 2005, in Kinshasa Hinterland, DRC. The clustering of cardiovascular risk factors was defined in all, MS group according to IDF(WC, BP, triglycerides, HDL-C, glucose), absence and presence of cardiometabolic risk(CDM) group(BMI,WC, BP, fasting glucose, and post-load glucose). RESULTS:Out of 977 participants, 17.4%( n = 170), 11%( n = 107), and 7.7%(n = 75) had type 2 diabetes mellitus(T2DM), MS, and CDM, respectively. Gender did not influence on all variables. Except BMI, levels of the rest variables were significantly higher in presence of T2DM than non-diabetics. There was a negative correlation between glucose types and BP in absence of CDM. In factor analysis for all, BP(factor 1) and triglycerides-HDL(factor 2) explained 55.4% of the total variance. In factor analysis for MS group, triglycerides-HDL-C(factor 1), BP(factor 2), and abdominal obesity-dysglycemia(factor 3) explained 75.1% of the total variance. In absence of CDM, glucose (factor 1) and obesity(factor 2) explained 48.1% of the total variance. In presence of CDM, 3 factors (factor 1 = glucose, factor 2 = BP, and factor 3 = obesity) explained 73.4% of the total variance. CONCLUSION: The MS pathogenesis may be more glucose-centered than abdominal obesity-centered in not considering lipid-lipoprotein , while BP and triglycerides-HDL-C could be the most strong predictors of MS in the general population. It should be specifically defined by ethnic cut-offs of waist circumference among Bantu Africans.
- ItemAssessment of the association of plant- based diets with cardiovascular disease risk profile in Africa: a systematic review and meta-analysis protocol(BMJ Publishing, 2020-06) Lopes, Tatum; Zemlin, Annalise E.; Erasmus, Rajiv T.; Faber, Mieke; Kengne, Andre P.Introduction Cardiovascular disease (CVD) is currently the leading cause of death worldwide. In Africa where infectious diseases are still the leading cause of death, the contribution of non-communicable diseases led by CVDs has significantly increased in recent years. The rise of CVDs in Africa is attributed at least in part to the adoption of sedentary behaviours and unhealthy eating habits, which are linked with urbanisation and westernisation of cultures. Dietary attributes associated with CVD risk have been less investigated in Africa. However, evidence from developed nations has reported a protective effect of healthy dietary patterns such as plant-based diets (PBDs) on cardiometabolic health. The current protocol is for a review aiming to assess existing evidence on the association of PBDs with CVD risk profile in African populations. Methods and analysis This protocol was developed following the 2015 guidelines of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. We will conduct a comprehensive search of the literature for published studies on PBDs in relation to CVD risk profile in African populations. Observational studies published between January 1990 and December 2019 will be screened. A search strategy using keywords and medical subject headings terms will be applied across multiple scientific databases including PubMed-Medline, Scopus and EBSCOhost and the African Journals Online platform. Manual searches of reference lists from relevant articles will be performed. Citations will be traced using the ISI Web of Science to further identify eligible studies. Grey literature will also be screened for relevant abstracts from conference proceedings, and experts in the field will be contacted where appropriate. Two investigators will independently screen all the titles and abstracts to determine which records are eligible for full-text review. Subsequently, two investigators will review the eligible full text using the selection criteria. A third investigator will be consulted to resolve any discrepancies. Data will be extracted from studies that are eligible for the review. Meta-analysis will be performed for studies with similar or comparable methods and reported outcome measures. This will be performed overall, and by major study-level characteristics. Heterogeneity in the estimates across studies will be assessed and quantified with the use of Cochrane Q and I2 statistics, respectively. Publication biases will be investigated through funnel plots and Egger test of bias. Relevant sensitivity analyses will be performed to confirm the robustness of the findings
- ItemAn audit of 24-hour creatinine clearance measurements at Tygerberg Hospital and comparison with prediction equations(Health and Medical Publishing Group (HMPG), 2007-10) Le Riche, Mia; Zemlin, Annalise E.; Erasmus, Rajiv T.; Davids, MRBACKGROUND: Internationally, clinical guidelines recommend the use of creatinine-based equations to estimate glomerular filtration rate (GFR) for assessment and follow-up of kidney disease. The routine use of 24-hour creatinine clearances (CrCl) is no longer advocated. Objectives. To examine the indications for requesting CrCl at Tygerberg Hospital, identify problems associated with the procedure, and evaluate the utility of the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations with different levels of renal dysfunction in the ethnic groups of the Western Cape. Methods. A clinical audit of CrCl was performed. The estimated GFR as predicted by the modified CG and MDRD formulae was compared with CrCl in 252 patients, representing three local ethnic groups. MDRD formulae with and without the correction factor for black ethnic group (MDRD-B) were evaluated. Results. Problems with urine collection or data supplied were identified in one-third of CrCl requests, leading to unreliable results. The CG correlated best with CrCl in the group as a whole. The average absolute and percentage differences from CrCl in the different ethnic groups were as follows: coloured (mixed ethnicity) (N = 186) - CG 13.4 ml/min/1.73 m2 (18%), MDRD 16.8 ml/min/1.73 m2 (23%) and MDRD-B 27.9 ml/mim/1.73 m2 (37%); black (N = 21) - CG 14.8 ml/min/1.73 m2 (19%), MDRD 12.9 ml/min/1.73 m2 (17%) and MDRD-B 25.1 ml/min/1.73 m2 (33%); white (N = 45) CG 13.5 ml/min/1.73 m2 (19%), MDRD 15.3 ml/min/1.73 m2 (21%) and MDRD-B 24.8 ml/min/1.73 m2 (35%). Throughout the renal function levels (chronic kidney disease stages 1 - 5) CG correlated better with CrCl than MDRD. Conclusions. Possible reasons for poor correlations include a high prevalence of obesity, underweight and normal GFR in the study population. There is a need for further research, using a gold standard, into the accuracy of these prediction equations in our unique patient populations before firm recommendations can be made regarding their use. Until then CrCl will continue to be widely used. Greater efforts at patient and health care worker education are required to ensure proper collections.
- ItemCase report : an index of suspicion in hyponatraemia(Hrvatsko društvo za medicinsku biokemiju, 2019) Barkhuizen, Marizna; Hoffmann, Mariza; Zöllner, Ekkehard W. A.; Erasmus, Rajiv T.; Zemlin, Annalise E.Serum indices can give valuable information and should be interpreted as a result. Lipaemia can influence results through different mechanisms, an important one being the electrolyte exclusion effect. A case of pseudohyponatraemia due to this is reported. A 15-year-old female with type 2 diabetes was seen for follow-up. Her biochemistry results revealed severe hyponatraemia of 118 mmol/L. Her capillary glucose concentration was 13.7 mmol/L with a corrected sodium of 122 mmol/L. A lipaemic index of 3+ (absolute value 1320) was noted, which was not flagged by the laboratory information system, as it was below the critical lipaemia limit for sodium determination. Repeated analysis of the same sample using a direct ion selective electrode method, the serum sodium concentration was 134 mmol/L (sodium corrected for glucose = 138 mmol/L). A triglyceride concentration was requested, which was severely raised (100.1 mmol/L). The electrolyte exclusion effect is an analytical phenomenon that causes falsely low electrolyte concentrations in the presence of severe lipaemia or hyperproteinaemia when using indirect analytical methods. These methods are used on many modern-day automated chemistry analysers and should be considered in a patient with asymptomatic hyponatraemia.
- ItemChronic kidney diseases in mixed ancestry South African populations : prevalence, determinants and concordance between kidney function estimators(BioMed Central, 2013-04) Matsha, Tandi E.; Yako, Yandiswa Y.; Van Rensburg, Megan; Hassan, Mogamat S.; Kengne, Andre P.; Erasmus, Rajiv T.Background: Population-based data on the burden of chronic kidney disease (CKD) in sub-Saharan Africa is still very limited. We assessed the prevalence and determinants of CKD, and evaluated the concordance of commonly advocated estimators of glomerular filtration rate (eGFR) in a mixed ancestry population from South Africa. Methods: Participants were a population-based sample of adults selected from the Bellville-South community in the metropolitan city of Cape Town. eGFR was based on the Cockroft-Gault (CG), Modification of Diet in Kidney Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) equations (with and without adjustment for ethnicity). Kidney function staging used the Kidney Disease Outcome Quality Initiative (KDOQI) classification. Logistic regressions and kappa statistic were used to investigate determinants of CKD and assess the agreement between different estimators. Results: The crude prevalence of CKD stage 3–5 was 14.8% for Cockcroft-Gault, 7.6% and 23.9% respectively for the MDRD with and without ethnicity correction, and 7.4% and 17.3% for the CKD-EPI equations with and without ethnicity correction. The highest agreement between GFR estimators was between MDRD and CKD-EPI equations, both with ethnicity correction, Kappa 0.91 (95% CI: 0.86-0.95), correlation coefficient 0.95 (95% CI: 0.94-0.96). In multivariable logistic regression models, sex, age and known hypertension were consistently associated with CKD stage 3–5 across the 5 estimators Conclusions: The prevalence of CKD stages greater than 3 is the highest reported in Africa. This study provides evidence for support of the CKD-EPI equation for eGFR reporting and CKD classification.
- ItemChronic kidney diseases in mixed ancestry South African populations : prevalence, determinants and concordance between kidney function estimators(BioMed Central, 2013-04) Matsha, Tandi E.; Yako, Yandiswa Y.; Rensburg, Megan A.; Hassan, Mogamat S.; Kengne, Andre P.; Erasmus, Rajiv T.ABSTRACT: Population-based data on the burden of chronic kidney disease (CKD) in sub-Saharan Africa is still very limited. We assessed the prevalence and determinants of CKD, and evaluated the concordance of commonly advocated estimators of glomerular filtration rate (eGFR) in a mixed ancestry population from South Africa. Methods Participants were a population-based sample of adults selected from the Bellville-South community in the metropolitan city of Cape Town. eGFR was based on the Cockroft-Gault (CG), Modification of Diet in Kidney Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) equations (with and without adjustment for ethnicity). Kidney function staging used the Kidney Disease Outcome Quality Initiative (KDOQI) classification. Logistic regressions and kappa statistic were used to investigate determinants of CKD and assess the agreement between different estimators. Results The crude prevalence of CKD stage 3–5 was 14.8% for Cockcroft-Gault, 7.6% and 23.9% respectively for the MDRD with and without ethnicity correction, and 7.4% and 17.3% for the CKD-EPI equations with and without ethnicity correction. The highest agreement between GFR estimators was between MDRD and CKD-EPI equations, both with ethnicity correction, Kappa 0.91 (95% CI: 0.86-0.95), correlation coefficient 0.95 (95% CI: 0.94-0.96). In multivariable logistic regression models, sex, age and known hypertension were consistently associated with CKD stage 3–5 across the 5 estimators. Conclusions The prevalence of CKD stages greater than 3 is the highest reported in Africa. This study provides evidence for support of the CKD-EPI equation for eGFR reporting and CKD classification.
- ItemCirculating miR-30a-5p and miR-182-5p in prediabetes and screen-detected diabetes mellitus(Dove Press, 2020-12) Weale, Cecil Jack; Matshazi, Don M.; Davids, Saarah F. G.; Raghubeer, Shanel; Erasmus, Rajiv T.; Kengne, Andre Pascal; Davison, Glenda Mary; Matsha, Tandi E.Background: microRNAs (miRNAs) have been touted as potential diagnostic and prognostic biomarkers for various diseases. The aim of the present study was to evaluate the diagnostic value of miR-30a-5p and miR-182-5p for prediabetes and screen-detected type 2 diabetes mellitus (T2DM). Methods: The study included 1270 participants (207 prediabetes, 94 screen-detected diabetes and 969 normotolerant) from the Vascular and Metabolic Health (VMH) study. Whole blood levels of miR-30a-5p and miR-182-5p were quantitated by RT-qPCR. Multivariable logistic regressions were used to relate miRNAs with prediabetes or T2DM and receiver operating characteristic (ROC) curves were used to evaluate the ability of each miRNA to diagnose these conditions. Results: Both miRNAs were significantly highly expressed in individuals with prediabetes or T2DM (both ≥3.2-fold, and p<0.001). We also observed significant under-expression in T2DM relative to prediabetes for miR-182-5p (0.49-fold, p=0.001). Age, sex and BMI-adjusted partial correlation coefficient analysis revealed a significant correlation between the two miRNAs across glucose tolerance statuses (r≥0.932, p<0.001). In normotolerant individuals, both miRNAs showed a negative correlation with waist circumference and positive correlation with HDL-cholesterol whilst in T2DM they correlated positively with hip circumference, 2-hour insulin, HDL- and LDL-cholesterol. Multivariable logistic regressions revealed both miRNAs to be consistently and continuously associated with prediabetes or T2DM (OR≥1.18, 95% 95% CI: 1.10-1.28, p<0.001), while only miR-182-5p associated with a reduced prevalence of T2DM relative to prediabetes (OR: 0.89, 95% CI: 0.83-0.96, p=0.003). In ROC analyses, miR-182-5p almost outperformed HbA1c in diagnosing prediabetes; area under the curve 0.74 vs 0.69. Conclusion: Our findings demonstrate that miR-30a-5p and miR-182-5p are associated with dysglycaemia and could potentially predict prediabetes, particularly miR-182-5p.
- ItemDifferential prevalence and associations of overweight and obesity by gender and population group among school learners in South Africa : a cross-sectional study(BioMed Central, 2017-07-17) Negash, Sarah; Agyemang, Charles; Matsha, Tandi E.; Peer, Nasheeta; Erasmus, Rajiv T.; Kengne, Andre P.Background: Factors influencing the increasing prevalence of overweight/obesity among children and adolescents in sub-Saharan Africa remain unclear. We assessed the prevalence and determinants of overweight and obesity and effects on cardio-metabolic profile in school learners in the Western Cape, South Africa. Methods: Cross-sectional data were collected from 7 to 18-year-old South African school learners attending 14 schools, randomly selected from 107 government schools in the areas. The learners were selected through stratified random sampling techniques. Logistic regressions were used to assess the determinants of overweight/obesity and its association with cardio-metabolic profile. Results: Among the 1559 participants, the overall prevalence of overweight/obesity was 22.9%. Being a girl (Odds ratio 2.51, 95% CI: 1.92–3.29), or Black African (1.35, 1.04–.75) was associated with increased odds of being overweight/obese. The identified health consequences among the overweight/obese learners differed between the ethnic groups. Overweight/obese coloured (mixed ancestry) learners were more likely to have hypertension (3.27, 1.18–9.08), hypertriglyceridemia (1.94, 0.99–3.78) and low high-density lipoprotein cholesterol (HDL-C) (3.65, 2.33–5.72), overweight/obese Black African learners had higher odds for hypertension (3.62, 1.31–10.04) and low HDL-C (1.56, 1.01–2.40) and overweight/obese White learners were prone to low HDL-C (5.04, 1.35–18.80). Conclusions: Overweight/obesity is highly prevalent among school learners in Western Cape (South Africa), with being female or Black African increasing the odds. That overweight/obesity is also associated with adverse cardio-metabolic risk profile aggravates the problem and suggests worse cardiovascular outcomes in South African young adults in the future.
- ItemThe discriminatory power of visceral adipose tissue area vs anthropometric measures as a diagnostic marker for metabolic syndrome in South African women(BMC (part of Springer Nature), 2019-11-08) Davidson, Florence E.; Matsha, Tandi E.; Erasmus, Rajiv T.; Kengne, Andre P.; Goedecke, Julia H.Background: A number of studies have shown central adiposity, in particular visceral adipose tissue (VAT) accumulation to be a hallmark of metabolic syndrome (MetS). In clinical practice, waist circumference (WC) is used as a proxy for VAT. Aim: To compare the ability of dual energy x-ray absorptiometry (DXA)-derived VAT area and anthropometric measures of adiposity for diagnosing MetS in a sample of high risk South African women. Methods: MetS was quantified using the Joint Interim Statement (JIS) criteria. Fasting glucose, insulin and lipid profile were measured in 204 post-menopausal women. Anthropometry measures included body mass index (BMI), WC, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and a body shape index (ABSI). The area under the curve (AUC) was used to assess their performance in detecting any two components of MetS (excluding WC). Optimal WC and VAT area cut-points were derived to compare their performance for diagnosing MetS and to compare to internationally recognised cut-points. Results: The highest AUC for the prediction of MetS was recorded for VAT, followed by WHtR and WC (AUC, 0.767, 0.747 and 0.738 respectively), but these did not differ significantly (all p ≥ 0.192). In contrast, VAT was significantly better than BMI (p = 0.028), hip (p = 0.0004) and ABSI (p < 0.0001). The optimal WC (94.4 cm) and VAT area (174 cm2 based on the Youden’s index method and 175.50 cm2 based on the CTL approach) cut-points performed similarly in detecting MetS. Conclusion: DXA-derived VAT and WC had the same overall performance in discriminating the presence of any 2 MetS components in high risk South African women. These findings support the current recommendations of using WC rather than VAT for MetS risk screening, as it is cheap, accessible and easy to measure.
- ItemDistribution and association of hs-CRP with cardiovascular risk variables of metabolic syndrome in adolescent learners(AOSIS Publishing, 2012-06) Rensburg, Megan A.; Matsha, Tandi; Hoffman, Mariza; Hassan, Mogamat S.; Erasmus, Rajiv T.Objective: Metabolic syndrome (MetS) and its associated cardiovascular risk are on the increase in children. High-sensitivity C-reactive protein (hs-CRP) has emerged as a useful marker for inflammation associated with atherosclerosis and cardiovascular disease. Our aim was to determine the distribution of hs-CRP in an effort to identify the MetS variable that is critical in modulating plasma CRP levels in a population of South African adolescents. Design: A cross-sectional analytical study design was used for this investigation, where the dependent and independent variables were measured simultaneously. Methods: Anthropometric variables, blood pressure, fasting blood glucose and lipids were performed on 324 consenting learners aged 15–18 years from three different ethnic groups (Black, White and Coloured). The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) for ages 15–18 year olds was used to define MetS. Results: The prevalence of MetS and obesity was 3.7% and 7.1%, respectively. The hs-CRP levels were significantly higher in subjects with a waist-circumference greater than the 90th percentile (p < 0.01) and in obese learners with MetS, but was lower in adolescents with normal weight and MetS. Median hs-CRP levels increased with an increasing number of metabolic abnormalities and exceeded 3 mg/L in 19% of adolescents. Gender and ethnic differences were observed. Conclusion: Our findings suggest that obesity and waist circumference appear to be major mediators of hs-CRP levels in South African adolescents.
- ItemEffect of model updating strategies on the performance of prevalent diabetes risk prediction models in a mixed-ancestry population of South Africa(Public Library of Science, 2019-02-07) Masconi, Katya L.; Matsha, Tandi E.; Erasmus, Rajiv T.; Kengne, Andre P.Background: Prediction model updating methods are aimed at improving the prediction performance of a model in a new setting. This study sought to critically assess the impact of updating techniques when applying existent prevalent diabetes prediction models to a population different to the one in which they were developed, evaluating the performance in the mixed-ancestry population of South Africa. Methods: The study sample consisted of 1256 mixed-ancestry individuals from the Cape Town Bellville-South cohort, of which 173 were excluded due to previously diagnosed diabetes and 162 individuals had undiagnosed diabetes. The primary outcome, undiagnosed diabetes, was based on an oral glucose tolerance test. Model updating techniques and prediction models were identified via recent systematic reviews. Model performance was assessed using the C-statistic and expected/observed (E/O) events rates ratio. Results: Intercept adjustment and logistic calibration improved calibration across all five models (Cambridge, Kuwaiti, Omani, Rotterdam and Simplified Finnish diabetes risk models). This was improved further by model revision, where likelihood ratio tests showed that the effect of body mass index, waist circumference and family history of diabetes required additional adjustment (Omani, Rotterdam and Finnish models). However, discrimination was poor following internal validation of these models. Re-estimation of the regression coefficients did not increase performance, while the addition of new variables resulted in the highest discriminatory and calibration performance combination for the models it was undertaken in. Conclusions: While the discriminatory performance of the original existent models during external validation were higher, calibration was poor. The highest performing models, based on discrimination and calibration, were the Omani diabetes model following model revision, and the Cambridge diabetes risk model following the addition of waist circumference as a predictor. However, while more extensive methods incorporating development population information were superior over simpler methods, the increase in model performance was not great enough for recommendation.
- ItemEffects of different missing data imputation techniques on the performance of undiagnosed diabetes risk prediction models in a mixed-ancestry population of South Africa(Public Library of Science, 2016) Masconi, Katya L.; Matsha, Tandi E.; Erasmus, Rajiv T.; Kengne, Andre P.Background: Imputation techniques used to handle missing data are based on the principle of replacement. It is widely advocated that multiple imputation is superior to other imputation methods, however studies have suggested that simple methods for filling missing data can be just as accurate as complex methods. The objective of this study was to implement a number of simple and more complex imputation methods, and assess the effect of these techniques on the performance of undiagnosed diabetes risk prediction models during external validation. Methods: Data from the Cape Town Bellville-South cohort served as the basis for this study. Imputation methods and models were identified via recent systematic reviews. Models’ discrimination was assessed and compared using C-statistic and non-parametric methods, before and after recalibration through simple intercept adjustment. Results: The study sample consisted of 1256 individuals, of whom 173 were excluded due to previously diagnosed diabetes. Of the final 1083 individuals, 329 (30.4%) had missing data. Family history had the highest proportion of missing data (25%). Imputation of the outcome, undiagnosed diabetes, was highest in stochastic regression imputation (163 individuals). Overall, deletion resulted in the lowest model performances while simple imputation yielded the highest C-statistic for the Cambridge Diabetes Risk model, Kuwaiti Risk model, Omani Diabetes Risk model and Rotterdam Predictive model. Multiple imputation only yielded the highest C-statistic for the Rotterdam Predictive model, which were matched by simpler imputation methods. Conclusions: Deletion was confirmed as a poor technique for handling missing data. However, despite the emphasized disadvantages of simpler imputation methods, this study showed that implementing these methods results in similar predictive utility for undiagnosed diabetes when compared to multiple imputation.
- ItemGenome-wide DNA methylation in mixed ancestry individuals with diabetes and prediabetes from South Africa(Hindawi Publishing Corporation, 2016) Matsha, Tandi E.; Pheiffer, Carmen; Humphries, Stephen E.; Gamieldien, Junaid; Erasmus, Rajiv T.; Kengne, Andre P.Aims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation analysis in 3 individuals with screen detected diabetes, 3 individuals with prediabetes, and 3 individuals with normoglycaemia from the Bellville South Community, Cape Town, South Africa, who were age-, gender-, body mass index-, and duration of residency-matched. Methylated DNA immunoprecipitation (MeDIP) was performed by Arraystar Inc. (Rockville, MD, USA). Results. Hypermethylated DMRs were 1160 (81.97%) and 124 (43.20%), respectively, in individuals with diabetes and prediabetes when both were compared to subjects with normoglycaemia. Our data shows that genes related to the immune system, signal transduction, glucose transport, and pancreas development have altered DNA methylation in subjects with prediabetes and diabetes. Pathway analysis based on the functional analysis mapping of genes to KEGG pathways suggested that the linoleic acid metabolism and arachidonic acid metabolism pathways are hypomethylated in prediabetes and diabetes. Conclusions. Our study suggests that epigenetic changes are likely to be an early process that occurs before the onset of overt diabetes. Detailed analysis of DMRs that shows gradual methylation differences from control versus prediabetes to prediabetes versus diabetes in a larger sample size is required to confirm these findings.
- ItemGlucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals(Hindawi, 2016-08-14) Matsha, Tandi E.; Pheiffer, Carmen; Mutize, Tinashe; Erasmus, Rajiv T.; Kengne, Andre P.ENGLISH ABSTRACT: The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both ) and in screen-detected diabetes compared to known diabetes on treatment (). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control.
- ItemHaematological profile of chronic kidney disease in a mixed-ancestry South African population : a crosssectional study(BMJ Publishing Group, 2018-11) George, Cindy; Matsha, Tandi E.; Erasmus, Rajiv T.; Kengne, Andre P.Objectives The objectives were to characterise the haematological profile of screen-detected chronic kidney disease (CKD) participants and to correlate the complete blood count measures with the commonly advocated kidney function estimators. Methods The current cross-sectional study used data, collected between February 2015 and November 2016, of 1564 adults of mixed-ancestry, who participated in the Cape Town Vascular and Metabolic Health study. Kidney function was estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and anaemia as haemoglobin level <13.5 g/dL (men) and <12 g/dL (women). Results Based on the MDRD and CKD-EPI equations, the crude prevalence of CKD was 6% and 3%. Irrespective of the equation used, median red blood cell (RBC) indices were consistently lower in those with CKD compared with those without CKD (all p<0.0001). Despite not showing any significant difference in total white blood cell (WBC) count between the two groups, the number of lymphocytes were lower (p=0.0001 and p<0.0001 for MDRD and CKDEPI, respectively) and neutrophil count (both p<0.0297) and the ratio of lymphocytes to neutrophil (both p<0.0001) higher in the CKD group compared with those without CKD; with the remaining WBC indices similar in the two groups. The platelet count was similar in both groups. Of the screen-detected CKD participants, 45.5% (MDRD) and 57.8% (CKD-EPI) were anaemic, with the prevalence increasing with increasing severity of CKD, from 37.2% (stage 3) to 82.4% (stages 4–5). Furthermore, CKD-EPIestimated kidney function, but not MDRD, was positively associated with RBC indices. Conclusion Though it remains unclear whether common kidney function estimators provide accurate estimates of CKD in Africans, the correlation of their estimates with deteriorating RBC profile, suggests that advocated estimators, to some extent approximate kidney function in African populations.
- ItemHbA1c of 6.5% to diagnose Diabetes Mellitus—Does it work for Us?—The Bellville South Africa study(Public Library of Science (PLOS), 2011-08) Zemlin, Annalise E.; Matsha, Tandi E.; Hassan, Mogamat S.; Erasmus, Rajiv T.Background: HbA1c has been the gold standard for glycaemic control follow-up for decades. In 2009, a level of 6.5% (48 mmol/mol) was proposed as diagnostic for diabetes. We test this cut-off in our community. Methods: Participants (946) from a community-based study were screened for diabetes using either a fasting blood glucose or oral glucose tolerance test (OFTT). The HbA1c cut-off of 6.5% was tested for each group. A receiver operator characteristic (ROC) curve for both groups was generated to establish an optimal cut-off. Results: Our study included 224 (23.7%) males and 722 (76.3%) females. Using fasting blood glucose alone, 117 (14%) were diagnosed with diabetes 250% had an HbA1c value of $6.5% (48 mmol/mol). Using an OGTT, 147 (18%) were diagnosed with diabetes 246% had an HbA1c value of $6.5% (48 mmol/mol). ROC curves found a level of 6.1% (43 mmol/mol) to be optimal in both groups (AUC 0.85 and 0.82 respectively). The sensitivities were 80% and 75% and the specificities 77% and 78% respectively. Conclusions: A cut off of 6.5% (48 mmol/mol) is a good diagnostic tool with its high specificity; however the low sensitivity limits its use. We found a level of 6.1% (43 mmol/mol) to be optimal. This emphasizes the need for evidenced based values to be established in various population groups.
- ItemHigh molecular weight adiponectin levels are neither influenced by adiponectin polymorphisms nor associated with insulin resistance in mixed-ancestry hyperglycemic subjects from South Africa(De Gruyter Open, 2016) Zemlin, Annalise E.; Matsha, Tandi E.; Kengne, Andre P.; Hon, Gloudina; Erasmus, Rajiv T.Background: High molecular weight (HMW) adiponectin has antiatherogenic, antiinflammatory and antidiabetic properties and these effects have been linked to its effect on high density lipoprotein cholesterol (HDL-c). Single nucleotide polymorphisms (SNPs) in the adiponectin gene influence adiponectin levels. We examined the relationship between HMW-adiponectin levels and cardiometabolic traits in normo- and hyperglycemic mixed ancestry South Africans and correlated these levels to two common polymorphisms. Methods: HMW-adiponectin was determined in 101 subjects from the Cape Town Bellville South community-based study on a mixed ancestry population. Comparisons were made between individuals with normo- and hyperglycemia. Two common SNPs, ADIPOQ SNPs rs17300539 and rs266729, known to affect adiponectin levels were also tested for. Levels of HMW-adiponectin were then correlated with cardiometabolic traits in all groups. Results: Levels of HMW-adiponectin were not significantly different in the normo- and hyperglycemic groups (median 11.6 vs. 10.5 μg/mL, p=0.3060) and in men and women (8.44 vs. 11.34 μg/mL, p=0.67). ADIPOQ SNPs rs17300539 and rs266729 did not influence levels of HMW-adiponectin. Robust correlation analyses revealed a significant positive correlation between HMW-adiponectin and HDL-c (r=0.45; 95%CI: 0.27–0.59), similarly in normo- and hyperglycemic participants (p>0.99). This association was substantially attenuated in robust linear regressions adjusted for age, gender and adiposity. Conclusions: Adiponectin levels in this population were not determined by the commonest SNPs of the adiponectin gene, were unaffected by glycemic status; but were significantly correlated with HDL-c levels. Previous studies have attributed some of the beneficial effects of adiponectin to its effect on HDL-c.
- ItemHigh prevalence of diabetes mellitus and metabolic syndrome in a South African coloured population : baseline data of a study in Bellville, Cape Town(HMPG, 2012-11) Erasmus, Rajiv T.; Soita, Rajiv T.; Hassan, Mogamat S.; Blanco-Blanco, Ernesto; Vergotine, Zelda; Kengne, Andre P.; Matsha, Tandi E.Objective. The coloured population has the second-highest prevalence of diabetes in South Africa. However, the data were based on a study conducted almost 20 years ago in a peri-urban coloured population of the Western Cape. We aimed to determine the prevalence of diabetes mellitus and metabolic syndrome in an urban coloured population in South Africa. Design. In a cross-sectional survey, 642 participants aged ≥31 years were drawn from an urban community of Bellville South, Cape Town, from mid-January 2008 to March 2009. Type 2 diabetes was assessed according to the WHO criteria, and metabolic syndrome was based on the International Diabetes Federation (IDF), ATP III and 2009 Joint Interim Statement (JIS) definition. Results. The crude prevalence of 28.2% (age-adjusted 26.3%, 95% confidence interval (CI) 22.0 - 30.3) for type 2 diabetes was: 4.4% (age-adjusted 3.2%, 95% CI 1.6 - 4.9) for impaired fasting glycaemia, and 15.3% (age-adjusted 15.0%, 95% CI 11.4 - 18.6) for impaired glucose tolerance. Undiagnosed type 2 diabetes was present in 18.1% (age-adjusted 16.8%, 95% CI 13.3 - 20.4). The crude prevalence of metabolic syndrome was higher with the JIS definition (62.0%) than the IDF (60.6%), and the National Cholesterol Education Program (NCEP) ATP III (55.4%). There was good overall agreement between the MetS criteria, k=0.89 (95% CI 0.85 - 0.92). Conclusion. The prevalence of diabetes has increased hugely in the coloured community, and the high prevalence of undiagnosed diabetes portends that cardiovascular diseases might grow to epidemic proportions in the near future in South Africa.