Type 2 diabetes and heart disease (cardiometabolic disease) affect increasing numbers of relatively young people in low- and middle-income countries (LMICs). Current approaches to preventing cardiometabolic disease mainly target lifestyle risk factors in high-risk adults. Programme 4 takes a ‘developmental origins’ approach, investigating pre-conceptional, prenatal and childhood influences on cardiometabolic risk and the potential of early life interventions to prevent it. We aim to identify interventions that improve fetal and infant development, including the development of metabolic tissues such as the pancreas and skeletal muscle, and thus reduce later-life vulnerability to disease. Such interventions also have the potential to enhance human capital (physical and cognitive development) and the fetal development (and lifelong health) of the next generation.
Our research is based mainly upon a long-standing close network of research groups and birth cohort studies in India covering a variety of settings (rural and urban) and a range of ages and socio-economic circumstances.
These studies have shown that maternal undernutrition and low birthweight are associated with an increased risk of insulin resistance, type 2 diabetes, and hypertension in later life. Risk is increased further by rapid weight gain (upward crossing on centiles) from mid-childhood onwards. In females the combination of low weight at birth but high adult weight increases the risk of gestational diabetes (diabetes in pregnancy). Gestational diabetes exposes the fetus to excess glucose and other ‘fuels’ leading to a large baby, who also has a high risk of developing obesity and diabetes as an adult.
These findings have led to us to establish intervention studies among mothers before and during pregnancy, aimed at improving fetal development and lifelong health in the next generation. These have involved nutritional supplementation, and more recently, studies in which the intervention targets multiple adverse maternal exposures all at one (e.g. to improve nutrition, prevent exposure to infection and environmental toxins, support mental health and increase parenting skills). We are following up/will follow up the children born in these studies, to assess the impact of the maternal intervention on cardiometabolic and other outcomes.
The programme has several major collaborations in LMICs other than India. One of our interventions studies in India (EINSTEIN) is linked to other similar studies in China, S. Africa and Canada as part of HeLTI (Healthy Life Trajectories Initiative, www.cihr-irsc.gc.ca/e/49510.html). We belong to the COHORTS group, a consortium of 5 birth cohorts in Brazil, Guatemala, India, South Africa and the Philippines, studying cardiometabolic and human capital outcomes in relation to early life factors, including socio-economic status, size at birth and childhood growth. We contribute data to the NCD-RisC collaboration (www.ncdrisc.org) which analyses non-communicable disease (NCD) trends among >19 million people in >180 countries. In the EMPHASIS study (www.emphasisstudy.org), we are investigating epigenetic mechanisms linking peri-conceptional nutrition and later life health outcomes in collaboration with the MRC unit in The Gambia. In the TALENT consortium (Transforming Adolescent Lives through Nutrition, http://generic.wordpress.soton.ac.uk/adolescentnutrition/ ) we are investigating diet and physical activity among adolescents in South Africa, The Gambia, Ivory Coast, Ethiopia, Kenya and India. In the INPReP study, we are collaborating with researchers in Burkina Faso, Ghana and S. Africa to develop interventions for mothers that are feasible within existing African health systems.
Programme 4’s objectives are to:
- test in humans the concept that maternal nutrition and metabolism before and during pregnancy have important effects on the lifelong body composition, cardiometabolic health and neurocognitive ability of the next generation
- develop interventions in transitioning populations that improve maternal nutrition and health, and the fetal development and lifelong health and human capital of the children
- characterise aspects of childhood and adolescent growth, diet, physical activity and socio-economic circumstances that are associated with adverse health outcomes in later life, to identify additional windows and targets for intervention
- identify mechanisms by which early life exposures influence adult health and disease
- build capacity, in India, other LMICs and the UK, in epidemiology, statistics, nutrition, and cohort and interventional research