Independent external validation and comparison of prevalent diabetes risk prediction models in a mixed-ancestry population of South Africa

BACKGROUND: Guidelines increasingly encourage the use of multivariable risk models to predict the presence of prevalent undiagnosed type 2 diabetes mellitus worldwide. However, no single model can perform well in all settings and available models must be tested before implementation in new populations. We assessed and compared the performance of five prevalent diabetes risk models in mixed-ancestry South Africans. METHODS: Data from the Cape Town Bellville-South cohort were used for this study. Models were identified via recent systematic reviews. Discrimination was assessed and compared using C-statistic and non-parametric methods. Calibration was assessed via calibration plots, before and after recalibration through intercept adjustment. RESULTS: Seven hundred thirty-seven participants (27% male), mean age, 52.2years, were included, among whom 130 (17.6%) had prevalent undiagnosed diabetes. The highest c-statistic for the five prediction models was recorded with the Kuwaiti model [C-statistic 0.68: 95% confidence: 0.63-0.73] and the lowest with the Rotterdam model [0. 64 (0.59-0.69)]; with no significant statistical differences when the models were compared with each other (Cambridge, Omani and the simplified Finnish models). Calibration ranged from acceptable to good, however over- and underestimation was prevalent. The Rotterdam and the Finnish models showed significant improvement following intercept adjustment. CONCLUSIONS: The wide range of performances of different models in our sample highlights the challenges of selecting an appropriate model for prevalent diabetes risk prediction in different settings

Effects of Isixhosa and English versions of GeoGebra on geometry achievement

The purpose of this study was to investigate the effects of using GeoGebra in different linguistic situations, namely isiXhosa and English, in township schools in Port Elizabeth. The objectives were to design an isiXhosa version of GeoGebra and investigate whether or not using it in first and second languages would offer any different results with regard to achievement in, and visuospatial ability of, geometry. Learners and teachers’ perceptions of the GeoGebra software were investigated within the framework of these variables. A pre-post-test, mixed method, concurrent, embedded triangulation research design was used with qualitative aspects playing a more prominent role than the quantitative data. Data collection strategies included baseline assessment to determine teachers’ perceptions of their ability to work with GeoGebra, focus group interviews with learners, semi-structured interviews with teachers, classroom observation and learners’ geometry tests. The study used Vygotsky’s socio-cultural model as a philosophical framework, while the explanatory framework of this study was situated within Baddeley’s revised model of working memory. The translation of GeoGebra from English to isiXhosa proved to be successful in terms of user responses and the fact that it is the first official African language of this dynamic software to be published, offered and made available online. Pre-post geometry testing revealed that for all the groups, the section on riders displayed the largest mean increase. Performance on the riders, which were aligned to the Curriculum Assessment Policy Statement (CAPS) grade 10 examination papers, can be viewed as an indicator of visuospatial ability. Importantly, the mean scores of the learners using the isiXhosa version of GeoGebra improved more in terms of practical significance (effect size = 0,78 for Riders) than the improvement in scores of learners who used the English version (Effect size = 0,61 for Riders). The total effect sizes of the isiXhosa and English groups were 0,69 and 0,36 respectively. This finding seems to resonate with the findings that language proficiency is an indicator of mathematical achievement. This is so in spite of the small size of the sample because the main purpose of the study was to obtain a brief impression (snapshot) of the situation regarding language issues involved when learning mathematics via the software GeoGebra

Proliferator-activated receptor gamma Pro12Ala interacts with the insulin receptor substrate 1 Gly972Arg and increase the risk of insulin resistance and diabetes in the mixed ancestry population from South Africa

BACKGROUND: The peroxisome proliferator-activated receptor gamma (PPARG), Pro12Ala and the insulin receptor substrate (IRS1), Gly972Arg confer opposite effects on insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the independent and joint effects of PPARG Pro12Ala and IRS1 Gly972Arg on markers of insulin resistance and T2DM in an African population with elevated risk of T2DM. In all 787 (176 men) mixed-ancestry adults from the Bellville-South community in Cape Town were genotyped for PPARG Pro12Ala and IRS1 Gly972Arg by two independent laboratories. Glucose tolerance status and insulin resistance/sensitivity were assessed. RESULTS: Genotype frequencies were 10.4% (PPARG Pro12Ala) and 7.7% (IRS1 Gly972Arg). Alone, none of the polymorphisms predicted prevalent T2DM, but in regression models containing both alleles and their interaction term, PPARG Pro12 conferred a 64% higher risk of T2DM. Furthermore PPARG Pro12 was positively associated in adjusted linear regressions with increased 2-hour post-load insulin in non-diabetic but not in diabetic participants. CONCLUSION: The PPARG Pro12 is associated with insulin resistance and this polymorphism interacts with IRS1 Gly972Arg, to increase the risk of T2DM in the mixed-ancestry population of South Africa. Our findings require replication in a larger study before any generalisation and possible application for risk stratification

Validation of two prediction models of undiagnosed chronic kidney disease in mixed-ancestry South Africans

BACKGROUND: Chronic kidney disease (CKD) is a global challenge. Risk models to predict prevalent undiagnosed CKD have been published. However, none was developed or validated in an African population. We validated the Korean and Thai CKD prediction model in mixed-ancestry South Africans. METHODS: Discrimination and calibration were assessed overall and by major subgroups. CKD was defined as 'estimated glomerular filtration rate (eGFR) <60ml/min/1.73m 2 ' or 'any nephropathy'. eGFR was based on the 4-variable Modification of Diet in Renal Disease (MDRD) formula. RESULTS: In all 902 participants (mean age 55years) included, 259 (28.7%) had prevalent undiagnosed CKD. C-statistics were 0.76 (95 % CI: 0.73-0.79) for 'eGFR <60ml/min/1.73m 2 ' and 0.81 (0.78-0.84) for 'any nephropathy' for the Korean model; corresponding values for the Thai model were 0.80 (0.77-0.83) and 0.77 (0.74-0.81). Discrimination was better in men, older and normal weight individuals. The model underestimated CKD risk by 10% to 13% for the Thai and 9% to 93% for the Korean model. Intercept adjustment significantly improved the calibration with an expected/observed risk of 'eGFR <60ml/min/1.73m 2 ' and 'any nephropathy' respectively of 0.98 (0.87-1.10) and 0.97 (0.86-1.09) for the Thai model; but resulted in an underestimation by 24% with the Korean model. Results were broadly similar for CKD derived from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. CONCLUSION: Asian prevalent CKD risk models had acceptable performances in mixed-ancestry South Africans. This highlights the potential importance of using existing models for risk CKD screening in developing countries

Metabolic Syndrome in People Living with Human Immunodeficiency Virus: An Assessment of the Prevalence and the Agreement between Diagnostic Criteria

Objectives. We determined metabolic syndrome (MetS) prevalence and assessed the agreement between different diagnostic criteria in HIV-infected South Africans. Method. A random sample included 748 HIV-infected adult patients (79% women) across 17 HIV healthcare facilities in the Western Cape Province. MetS was defined using the Joint Interim Statement (JIS 2009), International Diabetes Federation (IDF 2005), and Adult Treatment Panel III (ATPIII 2005) criteria. Results. Median values were 38 years (age), 5 years (diagnosed HIV duration), and 392 cells/mm3 (CD4 count), and 93% of the participants were on antiretroviral therapy (ART). MetS prevalence was 28.2% (95%CI: 25–31.4), 26.5% (23.3–29.6), and 24.1% (21–27.1) by the JIS, IDF, and ATPIII 2005 criteria, respectively. Prevalence was always higher in women than in men (all ), in participants with longer duration of diagnosed HIV (all ), and in ART users not receiving 1st-line regimens (all ). The agreement among the three criteria was very good overall and in most subgroups (all ). Conclusions. The three most popular diagnostic criteria yielded similarly high MetS prevalence in this relatively young population receiving care for HIV infection. Very good levels of agreement between criteria are unaffected by some HIV-specific features highlighting the likely comparable diagnostic utility of those criteria in routine HIV care settings

Paraoxonase1 Genetic Polymorphisms in a Mixed Ancestry African Population

Paraoxonase 1 (PON1) activity is markedly influenced by coding polymorphisms, Q/R at position 192 and M/L at position 55 of the PON1 gene. We investigated the frequencies of these polymorphisms and their effects on PON1 and antioxidant activities in 844 South African mixed ancestry individuals. Genotyping was done using allele-specific TaqMan technology, PON1 activities were measured using paraoxon and phenylacetate, oxidative status was determined by measuring the antioxidant activities of ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers included malondialdehyde and oxidized LDL. The frequencies of Q192R and L55M were 47.6% and 28.8%, respectively, and the most common corresponding alleles were 192R (60.4%) and 55M (82.6%). The Q192 was significantly associated with 5.8 units’ increase in PON1 concentration and 15.4 units’ decrease in PONase activity after adjustment for age, sex, BMI, and diabetes, with suggestion of differential effects by diabetes status. The PON1 L55 variant was associated with none of the measured indices. In conclusion, we have shown that the Q192R polymorphism is a determinant of both PON1 concentration and activity and this association appeared to be enhanced in subjects with diabetes

Rare Mutations of Peroxisome Proliferator-Activated Receptor Gamma: Frequencies and Relationship with Insulin Resistance and Diabetes Risk in the Mixed Ancestry Population from South Africa

Background. Genetic variants in the nuclear transcription receptor, PPARG, are associated with cardiometabolic traits, but reports remain conflicting. We determined the frequency and the clinical relevance of PPARG SNPs in an African mixed ancestry population. Methods. In a cross-sectional study, 820 participants were genotyped for rs1800571, rs72551362, rs72551363, rs72551364, and rs3856806, using allele-specific TaqMan technology. The homeostatic model assessment of insulin (HOMA-IR), β-cells function (HOMA-B%), fasting insulin resistance index (FIRI), and the quantitative insulin-sensitivity check index (QUICKI) were calculated. Results. No sequence variants were found except for the rs3856806. The frequency of the PPARG-His447His variant was 23.8% in the overall population group, with no difference by diabetes status (). The His447His allele T was associated with none of the markers of insulin resistance overall and by diabetes status. In models adjusted for 2-hour insulin, the T allele was associated with lower prevalent diabetes risk (odds ratio 0.56 (95% CI 0.31–0.95)). Conclusion. Our study confirms the almost zero occurrences of known rare PPARG SNPs and has shown for the first time in an African population that one of the common SNPs, His447His, may be protective against type 2 diabetes

Genome-wide DNA methylation in mixed ancestry individuals with diabetes and prediabetes from South Africa

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

Tooth loss in relation to serum cotinine levels - A cross-sectional study from the Belville South area in South Africa

Tooth loss constitutes a major public health challenge, sharing common risk factors with non-communicable diseases. To report the relationship between tooth loss and serum cotinine levels in a population sample of mixed ethnic heritage from the Belville South area in South Africa. Cross-sectional epidemiological study.Subjects were invited from 2014 to 2016 according to a consecutive sampling technique and all those who met the inclusion criteria were included. In all, 1876 individuals were included, being 1416 females (75.5%), with a combined average age of 49.5 ± 15.3 years. In total 46.7% of the sample was edentulous, with females presenting a higher proportion than males (50.7% vs. 34.1%, p &lt; 0.001). The relative risk (RR) of being edentulous was higher for females (RR=1.8, 95% CI=1.35-2.41, p&lt;0.001) and for participants with cotinine levels 15-299 ng/ml (RR = 1.37, 95% CI=1.02=1.83, p=0.04) and ≥300 ng/ml (RR=1.51, 95% CI=1.09-2.08, p=0.01). Maxillary incisors and mandibular molars were the most prevalent missing teeth. The burden of tooth loss is high in the studied population sample, as well their unmet needs for dental care. Female gender, tobacco exposure, and aging were associated with partial and total edentulism

High prevalence of diabetes mellitus and metabolic syndrome in a South African coloured population: Baseline data of a study in Bellville, Cape Town

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