Influence of the degree of control of diabetes on the prevention, postponement and amelioration of late complications.

The relationship between hyperglycaemia and the chronic complications of diabetes has been disputed for many years. Some physicians believe that the evidence that hyperglycaemia is the primary determinant of the chronic complications is convincing; others believe the question remains unsettled. Several types of study provide information. In vitro and in vivo studies demonstrate biochemical alterations induced by hyperglycaemia which could lead to structural changes and diabetic complications. Animal models demonstrate that the complications develop with induction of hyperglycaemia and are ameliorated when blood glucose is returned toward normal. Many uncontrolled clinical studies demonstrate an association between diabetes control and complications but cannot prove causality. Controlled clinical trials have sometimes, but not always, shown functional changes suggestive of amelioration of complications with control of hyperglycaemia. A definitive clinical trial has not yet been completed. Pancreas transplantation has the potential of completely normalising blood glucose, but studies to date have been limited by small numbers of patients, the advanced state of complications, and the lack of adequate controls. On balance, the evidence is highly suggestive that hyperglycaemia is a major determinant of the chronic complications of diabetes. Even if the relationship is established, the risk involved in treatment programmes to achieve near normoglycaemia must be better defined so that potential risk versus benefit can be evaluated in the individual patient when making treatment decisions.