We investigate how nutrition in early life alters the risk of children and young people developing obesity, diabetes, metabolic and cardiovascular diseases and how these effects are mediated by hormones.
Our research falls into three broad areas, each focused on particular periods during the lifespan.
Conception through to adolescence
We want to know how altered nutrition during this time impacts on adult health and the mechanisms that mediate these effects. This knowledge gives us the ability to manipulate nutrition (for example, the balance of micronutrients) to improve the health of at-risk individuals and reduce their chances of hypertension, diabetes, heart disease and stroke in later life.
We investigate the long term effects of the early life nutritional environments experienced by children who were:
- conceived through in vitro fertilisation (IVF)
- conceived through ovulation induction
- born small for gestational age (SGA)
- born preterm
- born post-term
- born to older mothers
- first born compared with later born children (effects of birth order)
We also look at factors that may influence later childhood and adult outcomes including maternal and paternal age, parental diets and exercise before conception and during pregnancy.
Our studies aim to discover the molecular and epigenetic mechanisms that drive these changes so we can develop targeted interventions to prevent or minimise any adverse effects on health in later life.
There are many claims made about health supplements but little scientific evidence. We are designing robust trials to examine the impact of micronutrients on metabolism, body composition and cardiovascular status in adults. These include polyphenols such as olive leaf extract, dietary fibre and omega-3-fatty acids. In addition we are investigating the mechanisms through which these micronutrients affect metabolism.
Epigenetic regulation of key metabolic genes in preterm and post-term babies
We have shown that children born preterm have an abnormality in the way the hormone insulin regulates glucose metabolism. This condition, known as insulin resistance is a major risk factor for type 2 diabetes. The incidence of preterm birth is increasing rapidly and its association with chronic adult conditions such as diabetes and cardiovascular diseases poses a significant public health concern worldwide.
In the early neonatal period preterm babies experience a nutritional environment that is different from that of babies born at term. This may make them more vulnerable to metabolic changes which lead to diabetes and related adult diseases. We want to see if we can prevent this occurring by manipulating their early nutrition.
Altered conception and in vitro fertilisation (IVF)
We have found that IVF offspring are different from normally conceived children. IVF children are taller, slimmer and have a healthier blood fat profile. We are investigating factors related to altered conception and older maternal age which may affect the development and long term health of children through a range of clinical studies that include:
- pharmacologic induction of ovulation
- the impact of older maternal age
- the impact of early embryo development on long term growth and metabolism
- how a mother’s diet affects the success of her becoming pregnant through IVF
- epigenetic changes in genes that regulate growth and metabolism in IVF offspring.
Diabetes and obesity
We are investigating ways to improve the health of children and teenagers who are at risk of obesity and diabetes. Our studies aim to determine
- the effects of micronutrients (dietary fibre and anti-oxidants) on the development of insulin resistance in at-risk teenagers and middle aged adults
- the effect of exercise on heart function and the success of exercise as a means of improving heart function in diabetic and obese teenagers
- the value of exercise during pregnancy as a means of reducing fat accrual during fetal life and reducing the programmed risk of later obesity observed in infants. and cardiovascular function in mothers and infants.
Key concepts used in this research
- Insulin resistance
- Body composition
- Ambulatory blood pressure
- Cardiovascular status
Approaches, methodologies used in this research
- Formal assessment of insulin action/sensitivity through Bergman minimal modelling and euglycaemic and hyperglycaemic clamps. We have an international reputation in the assessment of insulin action in children and adolescents.
- 24 hour ambulatory blood pressure.
- Body composition studies through DEXA and bioelectrical impedance.
- Assessment of bone density through DEXA and peripheral qCT.
- Assessment of carotid artery intimal thickness and blood flow through ultrasound.
- Exercise capacity studies including basal metabolic rate and VO2 max.
- A dedicated clinical research unit in which complex dynamic metabolic studies can be performed on children and adults.
- Cardiac MRI scans
- Ultrasound assessment of carotid intimal thickness and assessments of periferal vascular function using flow-mediated vasodilation
- Endocrine assays
- Quantitative assessment of DNA methylation through Sequenom.