Implications of the United Kingdom Prospective Diabetes Study

Diabetes is a metabolic disorder primarily characterized by elevated blood glucose levels and by microvascular and cardiovascular complications that substantially increase the morbidity and mortality associated with the disease and reduce the quality of life. Type 1 diabetes is characterized by total reliance on exogenous insulin for survival and comprises ∼10% of all cases of diabetes. The more prevalent form of diabetes, called type 2, comprising 90% of all people with diabetes, is characterized by insulin deficiency and/or insulin resistance.

An association between the complications of diabetes and elevated blood glucose levels was postulated in the early part of this century. However, only in the last 3 decades has a substantial body of animal experimental studies and human observational studies and clinical trials directly linked hyperglycemia with the development of diabetic complications (1). Some of these studies have also demonstrated that treatment that lowers blood glucose reduces the risks of diabetic retinopathy, nephropathy, and neuropathy.

Notable are the results of the Diabetes Control and Complications Trial (DCCT) (2) and the similarly designed but smaller Stockholm Diabetes Intervention Study (3). These studies showed unequivocally in type 1 diabetes that lowering blood glucose delayed the onset and slowed the progression of microvascular complications. Risk reductions for various outcomes ranged from 35 to 75%. Secondary analyses in these studies showed strong relationships between the risks of developing these complications and glycemic exposure over time. Moreover, there was no discernable glucose threshold, i.e., there was a continuous reduction in complications as glycemic levels approached the normal range. Improved glycemic control was also associated with reduced cardiovascular events in the DCCT, but the difference was not statistically significant. Perhaps this was because the population studied was young adults and therefore the event rate was very low.

Many of the observational studies also support a correlation …