Browsing by Author "Vergotine, Zelda"

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    High 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.
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    Molecular investigation of genetic factors associated with insulin resistance and obesity in a South African population
    (Stellenbosch : Stellenbosh University, 2015-12) Vergotine, Zelda; Erasmus, Rajiv T.; Matsha, Tandi E.; Pillay, Tahir S.; Kotze, Maritha J.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology: Chemical Pathology.
    ENGLISH ABSTRACT: Background: The aetiopathogenesis of type 2 diabetes and the associated insulin resistance have been shown to have a strong genetic basis. Several genetic variants of the peroxisome proliferatoractivated receptor gamma (PPARG) and the insulin receptor substrate (IRS) 1 genes have been associated with the metabolic states of obesity, insulin resistance and type 2 diabetes in Caucasian populations. Furthermore, insulin resistance is strongly associated with diabetes and subsequent cardiovascular disease. These are increasingly common in low- to middle -income countries, including South Africa. Limited information is currently available regarding genetic associations with insulin resistance in African populations. Objectives: (1) To identify subjects with insulin resistance and determine the frequencies of the single nucleotide polymorphisms in the PPARG and IRS1 genes and examine the associated risk of insulin resistance and type 2 diabetes mellitus in a mixed-ancestry South African population. (2) To investigate the relationship between indices of insulin resistance and carotid intima media thickness, a marker of subclinical cardiovascular disease/atherosclerosis. Methods: A total of 856 (235 males) mixed-ancestry adults drawn from an urban community of Bellville South, Cape Town were genotyped for PPARG Pro12Ala (rs1801282, G>C), Pro115Gln (rs1800571, G>T), Val290Met (rs72551362, G>A), Pheu388Leu (rs72551363, T>A), Arg397Cys (rs72551364, C>T), His449His (rs3856806, C>T) and IRS1 Gly972Arg (rs 1801278, G>A). The oral glucose tolerance test was performed and cardiometabolic risk factors measured. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance, the homeostasis model assessment of functional beta-cells, the quantitative insulin-sensitivity check index, the fasting insulin resistance index and the glucose/insulin ratio. Carotid intima media thickness was measured in longitudinal section at the far wall of the distal common carotid arteries, 2 cm from the bifurcation, at three consecutive end-points, 5-10 mm apart. Results: The genotype frequencies of PPARG Pro12Ala, IRS1 Gly972Arg and PPARG His449His were 10,4%, 7,7% and 23,8% respectively. No mutations were found for PPARG Pro115Gln, Val290Met, Pheu388Leu and Arg379Cys. In a model containing both PPARG Pro12Ala and IRS1 Gly972Arg alleles and their interaction term, the presence of the PPARG Pro12 resulted in a 64% risk of prevalent type 2 diabetes mellitus and was associated with higher 2 hour post-OGTT insulin levels in subjects with normoglycaemia. The PPARG Pro12 was associated with insulin resistance and interacted with IRS1 Gly972Arg, increasing the risk of type 2 diabetes mellitus. The PPARG His449His allele T frequency was about 14% and in an additive genetic model significantly reduced the risk of diabetes by 44%. After adjustment for age, gender, body mass index and diabetes status, the fasting plasma glucose (β=0,087;p=0,042) and glucose/insulin ratio (β=0,026; p=0,026) were associated with carotid intima media thickness. However, the effect on the overall model performance was marginal, R2<29,7%. Conclusion: The PPARG Pro12 was associated with insulin resistance and showed a gene-gene interaction with the unfavorable polymorphism IRS1 Gly972Arg, leading to an increased risk of type 2 diabetes mellitus. In contrast, the PPARG His449His T allele showed a protective effect against the risk of developing diabetes. Furthermore, indices of insulin resistance such as homeostatis model assessment of insulin resistance, quantitative insulin-sensitivity check index, fasting insulin resistance index and the glucose/insulin ratio were weakly associated with carotid intima media thickness in the risk stratification of cardiovascular disease in this population.
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    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
    (BioMed Central, 2014-01) Vergotine, Zelda; Yako, Yandiswa Y.; Kengne, Andre P.; Erasmus, Rajiv T.; Matsha, Tandi E.
    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.