FETAL AND POSTNATAL GROWTH AND THE ORIGINS OF ADULT DIABETES

Julie Owens, Department of Physiology, Research Centre for the Physiology of Early Development, University of Adelaide, Adelaide, SA, 5005.

Numerous epidemiological and case control studies in many communities around the world have now shown that small size at birth, in terms of reduced weight or length and increased thinness, is associated with insulin resistance and hyperinsulinaemia and subsequent development of glucose intolerance and diabetes in adult life. In addition, small size at birth and clinical intrauterine growth restriction are characterised by insulin resistance of peripheral tissues, skeletal muscle and adipose tissue, in young and aged adult males, as occurs in insulin resistance and type 2 diabetes more generally. Much of the variation in size at birth can be accounted for by perturbations in maternal and placental delivery of essential substrates to the fetus. It is therefore suggested that inadequate substrate supply in utero alters the functional development of the insulin axis and the key glucoregulatory tissues involved, permanently impairing peripheral insulin action and glucose homeostasis in the adult. This is supported by observations in the guinea pig, where fetal growth restriction, arising spontaneously or due to mild or moderate maternal feed restriction, causes whole body and skeletal muscle insulin resistance of glucose utilisation and glucose storage and compensatory hyperinsulinaemia in the young adult and subsequent diabetes in aged adults. Recently, accelerated postnatal growth in the first year of life (catch-up) has been shown to independently predict adult glucose intolerance and diabetes in humans, suggesting that it may also influence insulin action. Consistent with this, neonatal catch-up independently predicts impaired whole body and peripheral insulin action, while weanling catch-up predicts increased circulating free fatty acids (known to impair insulin action and secretion), in the young adult guinea pig. Whether altered fetal and postnatal growth directly affect adult insulin action and its determinants and the nature of the mechanisms responsible for this are the focus of future studies.