Fetal and infant influences on non-insulin-dependent diabetes mellitus (NIDDM)

The 'thrifty phenotype' hypothesis states that impaired glucose tolerance (IGT) and noninsulin-dependent diabetes mellitus (NIDDM) are the result of adaptation to undernutrition in the fetal and infant environment. In adapting the fetus and infant have to be nutritionally 'thrifty'. If poor nutrition continues throughout life these adaptations are not detrimental. However, if adult nutrition is better, the ability of the pancreas to maintain homeostasis is exceeded, with resulting diabetes. The hypothesis has been tested by a series of longitudinal studies which relate early growth with IGT and NIDDM in adult life. The studies show that babies who are small at birth or during infancy have increased rates of IGT and NIDDM. These relations are independent of social class and are seen at all levels of current body mass. More detailed anthropometric measurements at birth show that the baby at risk of glucose intolerance is characterized by disproportionate fetal growth, particularly relative thinness. Direct measurements have shown that this is a function of insulin resistance rather than deficiency. Reduced fetal growth is also associated with higher levels of plasma glucose in children. The aetiology of IGT and NIDDM may lie in undernutrition in utero or during infancy. This has major implications for their prevention.