Diabetes mellitus: current concepts of the hormonal and metabolic defects

In the last 50 years our conception of diabetes has changed considerably. It is no longer just a failure of the pancreas to release insulin. It may be a resistance to insulin, so that amounts which would ordinarily be normal are no longer adequate for the body. The relative deficiency of insulin may also represent the release of what would otherwise be normal amounts of insulin at the wrong time. Indeed diabetes may not only be insulin deficiency, but also glucagon excess. The consequences of this complex hormonal imbalance are not simply failure to metabolize glucose, but also excessive production of glucose and alteration of the body's capacity to handle the other nutrients - amino acids and fatty acids. Not only may these two hormones, insulin and glucagon, regulate the metabolism of more than glucose alone but they are, in turn, regulated by more than glucose. Furthermore, one consequence of inability to burn glucose along normal pathways may be that it is converted to substances such as sorbitol and glycoproteins and this conversion may give rise to many of the complications of diabetes.