Evaluation of specific genotypes in the context of the type 2 diabetes risk phenotype in the black South African population

Thesis (Ph.D. (Biochemistry))--North-West University, Potchefstroom Campus, 2010. Type 2 diabetes (T2D) is a complex disease that affects 4% of the general population and is expected to increase to 5.4% by the year 2025. A clear understanding of the aetiology of T2D susceptibility and pathogenesis will thus have a noticeable impact on global health. The black South African population is currently under increased risk for developing T2D due to the impact of urbanisation. Since the mechanisms of disease risk in this population differ to that of the so-called developed countries, it is necessary that the exact pathogenesis of this disease be elucidated in order to define suitable screening and therapeutic strategies for the black South African population. The purpose of this study was to initiate this process. Four genotypes were investigated, including alterations in the IRS-1, IRS-2, PPAR?2 and calpain 10 genes. This study was therefore the first to evaluate these specific genotypes in the context of the T2D risk phenotype in the black South African population, aiming towards a novel and population specific contribution towards current T2D research. The results of this study indicated that none of the screened genotypes were significant predictors of impaired glucose in the black South African population. A biphasic glucose curve shape (GCS) was associated with female gender, whereas a monophasic GCS, a high BMI, female gender as well as a high HbA1c level were linked to glucose intolerance. A high HbA1c level proved to be a significant predictor for glucose intolerance, although the four screened loci were not good predictors of the HbA1c level. The study also illustrated that it is not possible to simply adopt T2D screening strategies from those developed in other ethnic groups and that different genetic and environmental risk factors that play a role in the pathophysiology of T2D should be taken into account. The need for optimised and population specific T2D screening strategies is therefore emphasised. By further elucidating the complexities of T2D, a step towards providing more accurate screening strategies to the immediate population will be achieved. This will directly result in a significant decrease in the national burden of care, morbidity and mortality, paving the way to optimal health care strategies for this developing country. Doctoral