Programme highlights:
- Our work has contributed to the literature available on the menopausal transition in African women, particularly with regard to differences in body composition between the menopausal stages, and the association with cardiometabolic risk.
The prediction of cardiometabolic risk using longitudinal data and metabolomics analyses has shown that metabolite patterns can be useful in identifying and monitoring type 2 diabetes risk 10 years prior to disease onset and provide insight into the pathophysiology of type 2 diabetes in this high-risk, but under-studied, population.- Comparative work with other sub-Saharan African regions has shown that there is a marked variation
in the prevalence of obesity both regionally and between men and women, and the highest prevalence of obesity was observed in southern Africa (42.3–66.6% in women and 2.81–17.5% in men) compared to in east and west Africa. Preliminary findings have shown that multimorbidity is common and must be explored further.
We hypothesise that:
- There are individual factors, as well as distal factors such as social, economic and environmental factors, which influence not only health behaviours but also the interaction and clustering of different chronic diseases, which will negatively influence disease outcomes.
- Measurement of longitudinal metabolic and physiological determinants of disease outcomes will contribute to knowledge around biological mechanisms of disease in our populations.
- Identifying determinants of disease and biological disease mechanisms will ensure more effective ‘combination’ interventions to improve the quality of life and health outcomes for all people with multimorbidity.
Ongoing research activities:
Birth to Twenty Plus (Bt20+) cohort study
Principal Investigators Richter, Norris, Stein (Emory) & Stein (Oxford)
Bt20+ is part of a global network of five large long-running birth cohort studies in low- and middle-income countries that have contributed significantly to understanding the long-range impacts of exposures in early childhood on adult health and wellbeing (COHORTS – Consortium of Health Outcome Research in Transitioning Societies). Current research includes assessment of G1 at age 27-28 years to examine the origins of human health and productivity in early growth, personality characteristics and cognitive capacity, and the environmental circumstances that promote their full potential from infancy to adulthood, using the now unique 29-year Bt20+ cohort. The cohort has had substantial scientific and social impact in Soweto since it was started by a group including Professor Linda Richter in 1989. Professor Richter currently has a grant to document this influence in a published book.
Additionally, a series of studies are embedded in the Bt20+ longitudinal cohort.
Birth to Twenty Plus (Bt20+) caregivers’ longitudinal cohort
This is a cohort of over 1000 urban Black women (mothers/caregivers) who have been followed up regularly since 1990 making it the longest running study of women’s ageing and health in South Africa. These women have been followed up in various studies including:
METABO study
Principal Investigator Goedecke and Co-Investigator Micklesfield & colleagues from Umea University, Sweden
The aim of this sub-study of n=240 of the original Bt20 caregivers (who had a serum sample from 2002-2005 for metabolomics analyses) is to identify metabolites and metabolic pathways that predict impaired glucose metabolism.
SAMRC/GSK/Newton NCD study
Principal Investigators Naidoo & Fabian and Co-Investigator Norris
This longitudinal follow-up study was designed to measure the changes in sex hormone levels over the menopausal transition in women (n=500), and in men of the same age (n=500), and to explore the effects on body fat distribution and insulin sensitivity and secretion, and to investigate the specific roles of glucocorticoids and inflammatory mediators in the context of HIV.
African Research in Kidney Disease (ARK) study
Principal Investigators Naidoo & Fabian and Co-investigator Norris
There are two study sites, Soweto (DPHRU) and Wits-MRC Agincourt Rural Public Health and Health Transitions Unit which is a Population Health and Demographic Surveillance site. In Soweto, young adults (previously Bt20+ cohort, now 29 years old) and their birth mothers, are being screened for kidney disease to explore associated phenotypic, perinatal and intergenerational risk factors. Together, the two sites in SA, and their collaboration with researchers in Uganda and Malawi, create an unprecedented platform for renal research in sub-Saharan Africa.
Intergenerational transmission of vascular health in South Africans: Three Bt20+ Generations
Principal Investigator Ware and Co-Investigators Norris, Naidoo, Davies, Smith, Mpondo, Rochat & Kagura
This study aims to investigate the intergenerational transmission of blood pressure, arterial stiffness and vascular health (carotid intima media thickness, retinal vessel analysis, and assessment of left ventricular hypertrophy) across three generations of the Bt20+ cohort. With the high South African prevalence of adult hypertension and stroke alongside evidence that elevated blood pressure is already detectable in children, the findings of this study will inform early detection and prevention efforts to reduce intergenerational transmission of risk while controlling for a wide range of potential confounders.
Intergenerational effects of stress and trauma on mental health and HPA axis function
Principal Investigator Kim and Co-Investigator Norris
This doctoral study is assessing the effects of social and emotional stress (including depression, anxiety and
post-traumatic stress disorder) on the HPA axis function among index Bt20+ participants (now 29 years old) and their pre-pubescent children.
The South African Breast Cancer (SABC) case control study and South African Breast Cancer and HIV Outcomes cohort study (SABCHO) study
Principal Investigator Joffe
The SABC study was undertaken to investigate risk factors for breast cancer among women of African descent in Soweto. It also aims to determine multimorbidity impact on breast cancer treatments and outcomes. The SABCHO study involves five academic tertiary hospital centres in Johannesburg and KwaZulu-Natal, which have enrolled >3000 South African women with breast cancer. The study is currently assessing the impact of multimorbidity on treatment, adherence, tolerance, and survival outcomes.
The Human Heredity and Health in African (H3Africa) Consortium AWI-Gen Study (Africa Wits-INDEPTH partnership for Genomic studies) 1 and 2
Principal Investigator Ramsay and Soweto Principal Investigators Norris & Micklesfield
The AWI-Gen study was established to study genetic and environmental factors that influence the risk of disease, with a particular focus on cardiometabolic disease. There are six sites in four sub-Saharan African countries, with DPHRU collecting data in Soweto (n=1000 men and n=1000 women). Data collection for AWI-Gen 1 was completed in 2014 and started for AWI-Gen 2 in 2019. Various programmes of work have been nested within this larger study including:
AWI-Gen XHALE
Principal Investigator Micklesfield and Co-Investigator Tobin
This project is funded by a Global Challenges Research Fund (GCRF) networking grant to develop capacity and expertise in assessing respiratory health in the six AWI-Gen sites, and to establish a multi-disciplinary network of researchers in respiratory health.
Characterisation of gene-lifestyle interactions associated with obesity-related traits in African populations
Principal Investigator Chikowore (Wellcome Trust training fellowship) and Sponsors Micklesfield & Ramsay
This research is determining candidate gene-environment interacting (GEI) variants in obesity-related traits. Assessments of sensitivity and specificity will be used to determine the predictive value of these gene-lifestyle interactions and genetic risk scores. The transferability of the identified GEIs across populations in Africa and Europe will be evaluated. The proposed research may help elucidate relevant risk factors and/or identify obesity intervention targets.
Musculoskeletal research on aging adults
Principal Investigator Gregson and Co-Investigator Micklesfield
This work includes participation in the Sub-Saharan Africa Musculo-Skeletal Network (SAMSON) collaborative and the recently-funded study “Understanding the impact of HIV infection and its treatment on the effect menopause has on the musculoskeletal health of African women”. SAMSON is a research network across west, east and southern Africa which aims to build sustainable capacity in musculoskeletal health research by creating a collaborative research platform, sharing learning, informing health policy, and promoting training, research capacity development, knowledge transfer and public engagement.
Global Diet and Activity Research (GDAR)
Principal Investigators Wareham & Unwin (UK) and Norris & Micklesfield (Soweto, SA)
The goal of this project is to support sustainable development and the prevention of NCDs in LMICs by establishing a research network that will investigate the determinants of diet and physical activity, develop and evaluate interventions, and inform policy. Data on potential levers that influence diet and physical activity behaviour across socioecological domains (interpersonal, household and neighbourhood) is being collected on young adults (18-24 years) in Soweto.
The Soweto Syndemics Study
Principal Investigator Mendenhall and Co-Investigator Norris
This project is surveying 5000 people living in Soweto to address individuals’ social, economic, emotional, and medical lives via survey and by collecting biological and psychological data. In the second phase, 150 individuals will be interviewed about their experiences care-seeking for multiple syndemic conditions and the social, economic, religious, and emotional conditions that accompany them. This project is novel as it is the first to test syndemic theory; it is also practical in its goals to provide targeted information for integrated primary care that can inform the restructuring of the South African health system currently underway.