Determinants of Type 2 Diabetes Risk in Middle-aged Black South African Men and Women

The study will be performed in two parts:

Part 1 - Using a longitudinal design, a sample of 500 black women at different stages of the menopausal transition, and 500 middle-aged men living in Soweto Johannesburg, South Africa, who were included in previous studies between 2011 and 2014, will be recruited. Socio-demographics, health and menopausal status will be assessed using questionnaires; physical activity and sedentary behaviour will be measured using accelerometry; dietary intake will be estimated using a food frequency questionnaire; body composition and body fat distribution will be assessed using dual energy x-ray absorptiometry (DXA); fasting blood samples will be drawn for the determination of cardio-metabolic risk (glucose, insulin, lipids), cluster of differentiation 4 (CD4) count, as well as sex hormones, inflammatory markers and cortisol concentrations. An oral glucose tolerance test will be performed to measure insulin sensitivity and secretion. Statistical analyses will include multilevel mediation modelling.

Part 2 - Using a cross-sectional design, a sub-sample of 100 women from Part 1 will be selected and divided into four groups including 25 pre-menopausal HIV-negative women and 25 age-matched pre-menopausal HIV-positive women (ARV-Naïve); 25 post-menopausal HIV-negative and 25 age-matched post-menopausal HIV-positive women (ARV-Naïve). The women will undergo a frequently sampled intravenous glucose tolerance test to measure insulin sensitivity and secretion, and adipose tissue biopsies will be taken from the gluteal and abdominal SAT depots for the analysis of gene and protein expression relating to inflammation, sex hormones, glucocorticoid metabolism and adipogenesis. Statistical analyses will include multilevel mediation modelling.

Inclusion criteria

Part 1:

• Women on whom baseline data was collected between 2011 and 2014 as part of the Study of Women Entering and in Endocrine Transition.
• Men on whom baseline data was collected in 2014 as part of a larger African genomics study (www.h3Africa.org).

Part 2: A sub-sample of women from Part 1 of the study:

• Pre-menopausal women age-matched within the age range 35-45 years;
• Post-menopausal women age-matched within the age range 55-65 years;
• All women: BMI 25-40 kg/m2

Exclusion criteria

Part 1:

• Failed to consent to participate in the study.

Part 2:

• Diabetes, thyroid dysfunction, inflammatory, hepatic and renal diseases;
• Use of hormone replacement therapy; hormonal contraceptives, oral cortisone, anti-inflammatory drugs or antiretroviral therapy;
• Peri-menopausal;
• Currently pregnant or lactating;
• Tobacco use.