Measured Versus Calculated Small Dense LDL-Cholesterol and Cardiometabolic Traits in a South African Population.

Small-dense low density lipoprotein (sdLDL) is increasingly viewed as a marker for evaluating atherogenic risk, however its clinical uptake is hampered by the cumbersomeness of available methods. Consequently, a number of alternative methods for the estimation of sdLDL have been developed and none have been tested in a population from Africa. We evaluated an equation to estimate sdLDL-C from classic lipid parameters in South Africans. This is a cross-sectional study involving 1550 participants in which direct measurement of sdLDL in 237 participants was performed using a homogeneous enzymatic assay. Their mean age (standard deviation, SD) was 54.2 (14.7) years. 156 (65.8%) were normotolerant, 29 (12.2%) prediabetes, 17 (7.2%) screen detected diabetes and 35 (14.8%) known diabetes. Measured sdLDL values ranged from 0.17 to 3.39 versus-1.85 to 2.52 mmol/L calculated sdLDL. There was a significant positive correlation between the two measurements with a Pearson correlation coefficient of 0.659 (95%CI: 0.581-0.726). In a regression model, the adjusted R2 was 0.440 after adding age, 0.441 after further adding gender, then 0.443 with dysglycemia and lastly 0.447 upon adding body mass index. With the exception of HDL-cholesterol levels that decreased across increasing quintiles of calculated sdLDL, our data showed significant correlations between sdLDL and cardiometabolic risk factors, all p values < 0.0001. In conclusion, this study has shown that calculated sdLDL can be efficiently used to approximate population levels of sdLDL; however the modest correlation indicate that at the individual level, it will poorly approximate true sdLDL levels, with possible implications for risk stratification.

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.

Oral Microbiome Signatures in Diabetes Mellitus and Periodontal Disease.

Disturbances in the oral microbiome are associated with periodontal disease initiation and progression and diabetes mellitus (DM), but how this contributes to the cause-and-effect relationship between periodontal disease and DM is poorly understood. We examined the bacterial composition in plaque samples from 128 South Africans with periodontal disease across glycemic statuses using 16S rDNA sequencing of regions 2, 3, 4, 6-7, 8, and 9. Of the 9 phyla identified, Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, and Actinobacteria made up >98%. Fusobacteria and Actinobacteria were significantly more abundant in subjects with diabetes, while Proteobacteria were less abundant. However, in the presence of gingival bleeding and DM, as compared with DM without gingival bleeding, Actinobacteria were markedly reduced while Bacteroidetes were more abundant. In contrast, no differences in Actinobacteria or Bacteroidetes abundance were observed between DM with and without pocket depth (PD) ≥4 mm. At the genus level, similar changes in relative abundance were observed in the presence of DM and periodontal disease. Our findings remained in conditional logistic regression models adjusted for age, sex, waist circumference, and the 5 most dominant phyla. For example, Actinobacteria significantly increased the odds of diabetes by 10% in subjects with gingival bleeding, while Fusobacteria increased this odd by 14%; yet, among subjects with PD ≥4 mm, Fusobacteria decreased the odds of DM by 47%. Our findings have confirmed the alterations in the composition of the oral microbiota across glycemic statuses as well as different stages of periodontal disease. However, it is not clear whether these differences were the consequence of hyperglycemia or the presence of periodontal diseases. Therefore, we recommend further investigations in a longitudinal study design.

Increase in blood pressure over a 7-year period in a mixed-ancestry South African population.

BACKGROUND: An increase in the prevalence of high blood pressure (BP) has been reported globally and in the South African (SA) population. OBJECTIVES: To investigate temporal changes in absolute BP levels and hypertension prevalence in the mixed-ancestry South Africans. METHODS: Participants were from two independent cross-sectional surveys conducted during 2008/09 (N=928) and 2014/16 (N=1 969) in Bellville South, Cape Town, SA. Participants' eligibility was based on several criteria, including age >20 years and neither bedridden nor pregnant. Data were obtained by administered questionnaires, clinical measurements (BP and anthropometry) and biochemical assessments (oral glucose tolerance tests and cotinine levels). Known hypertension was based on a self-reported history of doctor-diagnosed hypertension and ongoing treatment. Comparison across years was based on the crude prevalence of hypertension as well as direct age-standardised prevalence, based on the SA 2011 mixed-ancestry population distribution, in 10-year age increments. RESULTS: In all, 708 participants (76.3%) in 2008/09 and 1 488 (75.6%) in 2014/16 were female. Between 2008/09 and 2014/16, mean systolic BP increased from 124 to 136 mmHg (absolute mean difference 15 mmHg) and mean diastolic BP from 75 to 85 mmHg (absolute mean difference 9 mmHg) in the overall sample. The prevalence of screen-detected hypertension increased from 11.6% to 24.8%, with a similar increase in males and females, while the prevalence of known cases remained stable. These changes remained significant after adjustment for age and gender. CONCLUSIONS: A rightward shift in absolute BP translated into a significant increase in the prevalence of hypertension over time in this population. The predominant increases in screen-detected hypertension suggest that the deteriorating profile was not matched by efforts to detect and manage individuals with higher-than-optimal BP levels.

Genetic association studies of obesity in Africa: a systematic review.

Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome-wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies.

The frequency, aetiology and outcome of severe hyponatraemia in adult hospitalised patients.

OBJECTIVE: To study the frequency, outcome and association with neurological signs and symptoms of severe hyponatraemia (< 120 mmol/l) in adult hospitalised patients. DESIGN: Retrospective study of severe hyponatraemia using laboratory data to identify patients. SETTING: 800 bed peri-urban hospital in the former homeland of Transkei. SUBJECTS: All adult inpatients from the medical and surgical wards with severe hyponatraemia during a 10 month period of which 18 cases records could not be traced and one was antefactual. MAIN OUTCOME MEASURES: Incidence of severe hyponatraemia, mortality, admission hyponatraemia, hospital acquired hyponatraemia, neurological symptoms and outcome. RESULTS: The overall incidence of severe hyponatraemia was 1.1%. Among the 58 patients (mean age 49.3 years), pulmonary tuberculosis (24%), Diabetes mellitus (19%) and renal failure (17.2%) were the principal aetiological conditions occurring in approximately 60% of hyponatraemic patients. A high mortality rate of 44.8% was observed which was probably associated with the severity of the underlying disease. 36.2% of patients had serum sodium levels of less than 115 mmol/l with a significantly (p < 0.05) higher mortality (62%) than those with values greater than 115 mmol/l (32%). Admission hyponatraemia (63.8%) was more frequent (p < 0.05) than hospital acquired hyponatraemia (36.2%); in the latter, hyponatraemia was more likely to normalise (p < 0.05). Neurological signs and symptoms developed in 17.2%, this being associated with a high mortality and lower mean serum sodium levels of 112 mmol/l respectively. Following therapy, serum sodium levels normalised in nearly half the patients. In three (5.2%) patients, the hyponatraemia worsened whilst another three became hypernatraemic. CONCLUSION: The incidence of severe hyponatraemia was lower than that observed in developed countries. It was associated with severe underlying disease and had a high mortality rate. Patients whose hyponatraemia did not normalise were more likely to have higher mortality.

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), ß-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 (P = 0.215). 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.

Indices of paraoxonase and oxidative status do not enhance the prediction of subclinical cardiovascular disease in mixed-ancestry South Africans.

We evaluated the association of indices of paraoxonase (PON1) and oxidative status with subclinical cardiovascular disease (CVD) in mixed-ancestry South Africans. Participants were 491 adults (126 men) who were stratified by diabetes status and body mass index (BMI). Carotid intima-media thickness (CIMT) was used as a measure of subclinical CVD. Indices of PON1 and oxidative status were determined by measuring levels and activities (paraoxonase and arylesterase) of PON1, antioxidant activity (ferric reducing antioxidant power and trolox equivalent antioxidant capacity), and lipid peroxidation markers (malondialdehyde and oxidized LDL). Diabetic subjects (28.9%) displayed a significant decrease in PON1 status and antioxidant activity as well as increase in oxidized LDL and malondialdehyde. A similar profile was apparent across increasing BMI categories. CIMT was higher in diabetic than nondiabetic subjects (P < 0.0001) but showed no variation across BMI categories. Overall, CIMT correlated negatively with indices of antioxidant activity and positively with measures of lipid oxidation. Sex, age, BMI, and diabetes altogether explained 29.2% of CIMT, with no further improvement from adding PON1 and/or antioxidant status indices. Though indices of PON1 and oxidative status correlate with CIMT, their measurements may not be useful for identifying subjects at high CVD risk in this population.

Three-year's changes in glucose tolerance status in the Bellville South cohort: rates and phenotypes associated with progression.

AIMS: To determine the phenotypes associated with progression to type 2 diabetes or worsening in glucose tolerance during a 3-year follow-up of a community-based cohort in Cape Town, South Africa. METHODS: A total of 198 eligible subjects (72.3% women) aged 55.2 years, from the Bellville-South community were followed-up between 2008 and 2011. Baseline and follow-up data collections included glucose tolerance status, anthropometric, blood pressure, lipids, insulin, γ-glutamyltransferase, cotinine, creatinine and HbA1c. Progression in glucose tolerance status at 3-year was the composite of new-onset diabetes and any worsening in glucose tolerance status. RESULTS: The cumulative incidence of progression in glucose tolerance status was: 16.2% (32 participants including 11 with new-onset diabetes), and increased in a stepwise fashion with the number of components of metabolic syndrome (MetS). In age and sex-adjusted logistic regression analyses, MetS [odd ratio: 3.08 (95% CI: 1.34-7.10)], HbA1c [5.26 (1.94-14.24)], HDL-cholesterol [0.05 (0.01-0.33)], γ-glutamyltransferase [1.99 (1.07-3.67)], triglycerides [1.71 (1.13-2.58)] and total/HDL-cholesterol [1.45 (1.08-1.93)] were significant predictors of progression, while borderline effects were observed for baseline glucose and diastolic blood pressure. Markers of adiposity were mostly stable or improved among non-progressors during follow-up, but deteriorated significantly among progressors, resulting in significant statistical interactions. CONCLUSIONS: High rates of deterioration of glucose status over time were found in our population, with nearly one-fifth of them acquiring a glucose tolerance worse status within a very short follow-up. Our study extends to this setting the well-known utility of phenotypes of MetS single or in combination, in predicting worsening in glucose tolerance status.

The 30-year cardiovascular risk profile of South Africans with diagnosed diabetes, undiagnosed diabetes, pre-diabetes or normoglycaemia: the Bellville, South Africa pilot study.

The aim of this pilot study was to assess the 30-year risk for cardiovascular disease (CVD) in the South Africa population of mixed-ancestry in individuals with non-diabetic hyperglycaemia, and undiagnosed and self-reported diabetes. Participants were drawn from an urban community of the Bellville South suburb of Cape Town. In total, 583 subjects without a history of CVD were eligible for lifetime CVD risk estimation. Gender-specific prediction for CVD risk was calculated using the 30-year CVD interactive risk calculator. High CVD risk (> 20%) was evident in normoglycaemic and younger subjects (under 35 years). The significant predictors of CVD were sibling history of diabetes, and triglyceride, low-density lipoprotein cholesterol and glycated haemoglobin levels (p < 0.001). The high lifetime risk in normoglycaemic and younger subjects may be considered a warning that CVD might take on epidemic proportions in the near future in this country. We recommend the inclusion of education on CVD in school and university curricula.

Association of cocaine- and amphetamine-related transcript, leptin and leptin receptor gene polymorphisms with anthropometric obesity phenotype indicators in South African learners.

BACKGROUND/AIMS: Obesity has increased rapidly in South African children and adolescents. Genes involved in appetite regulation have been extensively studied worldwide, but their role in the obesity phenotype in South African Black and mixed-ancestry school adolescents is unknown. METHODS: Seven common polymorphisms in LEP, GHRL, CART and LEPR were analysed for genotype and haplotype association with anthropometric obesity phenotype indicators in South African Black and mixed-ancestry adolescent school learners. RESULTS: The CART c.517A→G polymorphism was significantly associated with obesity susceptibility. The LEPR Lys(109)Arg G allele was associated with an average reduction of 2.36 kg/m(2) in body mass index (BMI), 5.66 cm in waist circumference (WC) and 1.61 cm in mid-upper-arm circumference (MUAC). This was confirmed by haplotype analysis. Additionally, a haplotype of the LEP polymorphisms significantly increased BMI, MUAC and hip circumference, while LEPR haplotypes were associated with differences in MUAC. CONCLUSION: Our findings suggest that c.517A→G and Lys(109)Arg contribute to the variation in anthropometric obesity phenotype indicators observed among Black African and mixed-ancestry South African learners. Furthermore, haplotypes of LEP, LEPR and GHRL polymorphisms were associated with varying measurements of weight, BMI and WC. Further studies are required to confirm our results in a larger and homogeneous study population group.