Puberty is normally associated with a decline in tissue sensitivity to insulin. However, normal glucose homoeostasis is maintained by compensatory increases in glucose-stimulated insulin secretion. Here we describe studies performed in healthy children which have determined the site of insulin resistance (hepatic vs. peripheral) and whether this resistance extends to other substrates such as amino acid and free fatty acid metabolism. The changes in insulin action and secretion that are normally seen during puberty lead us to question the role of insulin resistance in other childhood conditions that are complicated by the later development of type I or type II diabetes, namely thalassaemia major and Turner's syndrome. These studies showed that in patients with thalassaemia and Turner's syndrome, insulin resistance and increased insulin secretion are very early metabolic defects that appear before the development of diabetes.