Determinants of type 2 diabetes mellitus risk in middle-aged black South African men and women

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Background: Globally, T2D is estimated to account for 5.1 million deaths, or 8.4% of all-cause deaths in adults. While the prevalence of diabetes in sub-Saharan Africa (SSA) is relatively low (5.7%), the projected rate of increase over the next 20 years exceeds that of other regions, with the prevalence in SSA expected to double by 2035. Black Africans with T2D have higher rates of associated co-morbidities, referred to as multi-morbidity, and are 2-3 times more likely to die from these diseases than their white counterparts. Within South Africa (SA), there is a high prevalence of T2D, particularly in black African urban-dwelling populations, which has increased significantly over the past 20 years, most likely driven by the increasing prevalence of obesity, particularly in black SA women (39.9%). Indeed, a high BMI accounted for 93.8% of deaths in SA women due to diabetes in 2000. Notably, SA also has an additional challenge of a high burden of infectious diseases, with a national HIV prevalence of 12.2%. Aim: The aim of the study is to examine the changes in sex hormone levels over the menopausal transition in women, and in men of the same age, and explore the effects on body fat distribution and insulin sensitivity and secretion, dissecting the specific roles of glucocorticoids and inflammatory mediators, in the context of HIV. Methods: Baseline data was collected on 1007 black women (age: 49.1±5.7 years; BMI: 33.3±7.3 kg/m2) from 2011-2014 and 962 black men (age: 49.3±12.6 years; BMI: 25.1±5.9 kg/m2); between 2014 and 2015, as part of the SWEET (Study of Women Entering and in Endocrine Transition) and AWI-Gen (Africa Wits-INDEPTH partnership for Genomics Studies on body composition and cardiometabolic disease risk – www.h3africa.org) studies. The proposed study will consist of two parts. Part 1: Using a longitudinal design, follow up data will be collected to measure changes in sex hormones, circulating cortisol and inflammatory markers, to assess their role in mediating changes in body fat distribution and insulin sensitivity, and to examine the influence of HIV status on this relationship. Part 2: Using a cross-sectional design, differences in adipose tissue oestrogen receptors, glucocorticoid metabolism and inflammation will be examined in black South African pre- and post-menopausal women, with and without HIV, and the association with body fat distribution and insulin sensitivity will be explored.