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

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

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

The agreement between fasting glucose and markers of chronic glycaemic exposure in individuals with and without chronic kidney disease: a cross-sectional study

Abstract 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 high-performance 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

Optimal waist-to-height ratio values for cardiometabolic risk screening in an ethnically diverse sample of South African urban and rural school boys and girls

BACKGROUND: The proposed waist-to-height ratio (WHtR) cut-off of 0.5 is less optimal for cardiometabolic risk screening in children in many settings. The purpose of this study was to determine the optimal WHtR for children from South Africa, and investigate variations by gender, ethnicity and residence in the achieved value. METHODS: Metabolic syndrome (MetS) components were measured in 1272 randomly selected learners, aged 10-16 years, comprising of 446 black Africans, 696 mixed-ancestry and 130 Caucasians. The Youden's index and the closest-top-left (CTL) point approaches were used to derive WHtR cut-offs for diagnosing any two MetS components, excluding the waist circumference. RESULTS: The two approaches yielded similar cut-off in girls, 0.465 (sensitivity 50.0, specificity 69.5), but two different values in boys, 0.455 (42.9, 88.4) and 0.425 (60.3, 67.7) based on the Youden's index and the CTL point, respectively. Furthermore, WHtR cut-off values derived differed substantially amongst the regions and ethnic groups investigated, whereby the highest cut-off was observed in semi-rural and white children, respectively, Youden's index0.505 (31.6, 87.1) and CTL point 0.475 (44.4, 75.9). CONCLUSION: The WHtR cut-off of 0.5 is less accurate for screening cardiovascular risk in South African children. The optimal value in this setting is likely gender and ethnicity-specific and sensitive to urbanization

Biomarkers as a predictor for diabetic retinopathy risk and management: A review

Background: The systemic and ocular manifestations of diabetes are an increasing burden on both private and public healthcare systems. The ability to accurately predict patient susceptibility and prognostic implications of the disease is essential to its optimal management and planning. Aim: The purpose of this paper was to review alternative biomarkers to those currently in use regarding the diagnosis and prognosis of diabetes and the ocular effects of the disease. Current biomarkers include Fasting Plasma Glucose (FPG), Oral Glucose Tolerance Test (OGTT) and Glycolated Haemoglobin (HbA1c). Methods: The research strategy comprised of a comprehensive literature review of articles from Mendeley, Cochrane and Elsevier with additional input from experts in the field serving as co-authors. Results: The review found that there are alternative biomarkers to those currently utilised. These include adiponectin, apolipoprotein B, C-reactive protein and ferritin. Fructosamine, while useful where whole blood is available, is unreliable as a diagnostic biomarker resulting in a 10% variation coefficient. Post-prandial glucose (PPG) measurement most closely predicted HbA1c. Conclusion: With prediction of risk for diabetes in individuals, a value combination, expressed as either a numerical score or a percentage, consisting of adiponectin, apolipoprotein B, C-reactive protein and ferritin, almost doubled the relative risk of contracting the disease. Eye care practitioners need to question diabetic patients about their FPG and HbA1c levels and encourage them to have the relevant tests regularly, including PPG. The importance of biomarkers should be emphasised and used as an educational tool to facilitate better diabetes management and treatment adherence