| Summary: | 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. === Thesis (Ph.D. (Biochemistry))--North-West University, Potchefstroom Campus, 2010.
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