Research Project
6640690
DESCRIPTION (provided by applicant): Epidemiological studies have shown that low birthweight in combination with adult obesity is associated with a marked increase in the prevalence of the metabolic or insulin resistance syndrome (insulin resistance, hypertension, dyslipidaemia and glucose intolerance). This syndrome is in turn associated with an increased risk of both type 2 diabetes and atherosclerotic vascular disease. These observations have led to the hypothesis that adaptations made by the fetus in response to undernutrition give rise to persisting changes in metabolism which lead to insulin resistance and the metabolic syndrome. Although the nature of these changes are not understood, animal studies and preliminary human observations made by the Principal Investigator have led to the hypothesis that in utero resetting of the hypothalamic-pituitary-adrenal (EPA) axis resulting in increased secretion of the adrenal stress hormone, cortisol, is an important change which may initiate the metabolic syndrome. The aim of the studies are to characterize the nature of the abnormality of the HPA axis in adults who were small at birth and the way in which this abnormality interacts with adult obesity to determine the prevalence of the metabolic syndrome or its components. It is expected that the information from these studies will form a first step towards the development of pharmacological strategies aimed at reducing the deleterious effects of low birthweight on adult health. It also has the potential to provide outcome measures in trials of maternal nutrition or other interventions to improve fetal growth and well-being, and by identifying affected individuals early in life may allow specific targeting of public health interventions (e.g. obesity reduction).
