Metabolic and hormonal studies in South African women of Indian and African origin

PhD (Chemical Pathology),Faculty of Health Sciences, University of the Witwatersrand, 2009Introduction: The data published by the Medical Research Council of South Africa demonstrated that cardiovascular disease and diabetes mellitus are the second and tenth leading causes of death in South Africa, respectively (Bradshaw et al.,2003). The prevalence of obesity is higher in the African than Indian population (Puoane et al., 2002), whereas cardiovascular diseases (CVD) and diabetes are more common in the latter population (Omar et al., 1994, Joffe et al., 1994). Diabetes and hypertension has been related with abdominal obesity in a number of studies conducted in the African and mixed-ancestry communities of the Western Cape (Steyn et al., 1996, Levitt et al., 1993). The reason for the high prevalence of obesity in the African population is not known however it is known that the aetiology of obesity involves both environmental and genetic factors (Grundy, 2004). Objective: The main aim of this project was to ascertain the role of metabolic, hormonal, anthropometric and environmental factors in the pathogenesis of obesity-related disorders in two South African ethnic groups namely Indian and African women. These populations were chosen because of the wide differences in risk factors for the development of CVD and diabetes reported in these groups. Subjects and methods: Plasma and serum samples were taken during a 5-hour OGTT from 20 lean, 20 obese, 20 obese type 2 diabetic patients, and 10 overweight women of African and Indian origin, i.e. 140 subjects in total. All participants were recruited from an urban population of women residing in the Greater Johannesburg area. Serum insulin, C-peptide, proinsulin and adipokines were measured using ELISA kits. Fasting plasma glucose, serum cholesterol, HDL-cholesterol and triglycerides levels were measured on the ROCHE MODULAR System. Insulin resistance was calculated using HOMA. Visceral and subcutaneous fat areas were measured using a 5-level CT-scan. Nutrient intake was assessed using a validated quantified food frequency questionnaire. Socio-economic status was estimated from the level of education and the number of selected household amenities. The data collected from the project was analysed by using SAS System for Windows Release 8.02 SAS Institute Inc., Cary, NC, USA 1999-2001. V Results: Results from the study presented in the table below indicate that Indian females were more insulin resistant and had a worse atherogenic lipid profile than African females (statistically higher LDL and triglycerides levels). The greater visceral fat mass in the Indian subjects appears to be associated with triglycerides and correlated with insulin resistance (r=0.554, p<0.05). This effect was not observed in Africans. African females had a higher proportion of their energy intake as carbohydrates than Indians (49.3% and. 45.2%, respectively, p<0.05), whereas Indians had a higher proportion of their total energy intake as fat than Africans (34.0% and 29.9%, respectively, p<0.05). The level of educational attainment and possession of household amenities was lower in the African than Indian group, but this did not significantly influence any of the anthropometric variables. Conclusions: Visceral fat accumulation was greater in diabetic and lean Indian subjects than in diabetic and lean African groups, which may explain their higher risk for obesity-related disorders at lower BMI. Significantly higher HOMA levels in obese Indians and significantly lower proinsulin/insulin ratio in lean and obese Indian women compared to lean and obese African women suggests that lean and obese Indians have better beta-cell proinsulinprocessing efficiency than Africans, probably due to the higher secretory load imposed on beta cells by the higher level of insulin resistance in the Indian subjects. Triglycerides, one of the major components in the diagnostic criteria of metabolic syndrome, were significantly different in the obese group (higher in Indians) and this may lead to the higher prevalence of CVD in the Indian population. Interethnic differences for leptin levels were observed in the lean group of women with higher levels in the Indian subjects. When all non-diabetic subjects were combined serum leptin levels were significantly higher in Indian than African subjects. This is an intriguing result, since obesity is more common in the African than Indian populations of South Africa. Caloric intake was higher in lean African than Indian females. However, the hypothesis that lower leptin levels in lean African females may lead to higher dietary intake and thus an increased prevalence of obesity in this group must be evaluated in a longitudinal study of leptin levels and weight gain. The impact of lower socio-economic status in African than Indian population is not clear; however data from the literature does demonstrate a negative correlation of obesity prevalence with education and incom

Association between HIV replication and serum leptin levels: an observational study of a cohort of HIV-1-infected South African women

<p>Abstract</p> <p>Background</p> <p>Advanced HIV infection can result in lipoatrophy and wasting, even in the absence of ongoing opportunistic infections, suggesting that HIV may directly affect adipose tissue amount and distribution.</p> <p>Methods</p> <p>We assessed the relationship of fat (measured using anthropometry, DEXA, MRI scans) or markers related to glucose and lipid metabolism with viral load in a cross-sectional sample of 83 antiretroviral-naïve HIV-1-infected South African women. A multivariable linear model was fitted to log₁₀VL to assess the combined effect of these variables.</p> <p>Results</p> <p>In addition to higher T cell activation, women with viral load greater than the population median had lower waist circumference, body mass index and subcutaneous abdominal fat, as well as lower serum leptin. We demonstrate that leptin serum levels are inversely associated with viral replication, independent of the amount of adipose tissue. This association is maintained after adjusting for multiple variables associated with disease progression (i.e., cellular activation and innate immunity effector levels).</p> <p>Conclusions</p> <p>Our results demonstrate that serum leptin levels are inversely associated with viral replication, independent of disease progression: we postulate that leptin may affect viral replication.</p

Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells

Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl2 and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl2 concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis