Effects of different missing data imputation techniques on the performance of undiagnosed diabetes risk prediction models in a mixed-ancestry population of South Africa

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

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

APOL1 genetic variants, chronic kidney diseases and hypertension in mixed ancestry South Africans

BackgroundThe frequencies of apolipoprotein L1 (APOL1) variants and their associations with chronic kidney disease (CKD) vary substantially in populations from Africa. Moreover, available studies have used very small sample sizes to provide reliable estimates of the frequencies of these variants in the general population. We determined the frequency of the two APOL1 risk alleles (G1 and G2) and investigated their association with renal traits in a relatively large sample of mixed-ancestry South Africans. APOL1 risk variants (G1: rs60910145 and rs73885319; G2: rs71785313) were genotyped in 859 African mixed ancestry individuals using allele-specific TaqMan technology. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.ResultsThe frequencies of rs73885319, rs60910145 and rs71785313 risk alleles were respectively, 3.6%, 3.4%, and 5.8%, resulting in a 1.01% frequency of the APOL1 two-risk allele (G1:G1 or G1:G2 or G2:G2). The presence of the two-risk allele increased serum creatinine with a corresponding reduction in eGFR (either MDRD or CKD-EPI based). In dominant and log-additive genetic models, significant associations were found between rs71785313 and systolic blood pressure (both p ≤ 0.025), with a significant statistical interaction by diabetes status, p = 0.022, reflecting a negative non-significant effect in nondiabetics and a positive effect in diabetics.ConclusionsAlthough the APOL1 variants are not common in the mixed ancestry population of South Africa, the study does provide an indication that APOL1 variants may play a role in conferring an increased risk for renal and cardiovascular risk in this population

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

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

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

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

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

Association between dental and periodontal conditions with chronic kidney disease: A cross-sectional analysis of urban South Africans

Oral diseases are preventable causes of poor health outcomes in people with chronic kidney disease (CKD). Investigate the association between dental and periodontal conditions with kidney function and determine whether inflammation mediate the association between periodontitis and CKD. Cross-sectional analysis of 1551 South African adults of mixed ancestry. CKD was classified as estimated glomerular filtration rate (eGFR) &lt;60mL/min/1.73m2. Oral profile was captured by decayed, missing, filled teeth index (DMFTi), bleeding on probing (BOP), pocket depth (PD), clinical attachment loss (CAL), and periodontitis classified as PD ≥4 mm.Overall, 6% had CKD, with 93% and 66% of participants with and without CKD, respectively having a high DMFTi (p&lt;0.0001). Further, 84% (CKD) and 43% (without CKD) were edentulous (p&lt;0.0001). A great proportion of the dentate sub-sample (n=846) had periodontitis, however, BOP, PD ≥4mm and CAL ≥4mm were similar between the groups. DMFTi was associated with eGFR and prevalent CKD (p&lt;0.023), with this association driven by the Missing component. Periodontitis was not associated with eGFR nor CKD (p&gt;0.282). In routine care of people with CKD, attention should be given to oral health

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

Background: Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations. Objectives: To assess the association of these genes with T2DM risk in a South African mixed-ancestry population. Methods: Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits. Results: In logistic regression models adjusted for age, sex, body mass index (BMI) and insulin resistance, minor allele of rs997509 was associated with a higher risk of prevalent T2DM under a recessive model [odd ratio 4.60 (95% confidence interval: 1.07 to 19.86); p = 0.040].Under additive model, the rs7903146 [1.43 (1.00 to 2.04); p= 0.053] and rs9941349 [1.43 (1.00 to 2.04); p = 0.052] minor alleles showed marginally significant associations with a high risk of T2DM. However, only the rs7903146 alleles (p=0.011) and genotypes (p=0.025) distributions were statistically significantly different between diabetic and non-diabetic individuals. Conclusion: Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry population