Prevention of type 2 diabetes.

The importance of type 2 diabetes is due to its high prevalence, the difficulties in achieving optimal glucose control (financial, time, quality of life) and the high frequency of chronic microvascular and macrovascular complications that add very significantly to the morbidity, mortality and overall cost of the disease. Numerous risk factors have been identified that predict the future onset of type 2 diabetes in individuals and an early stage of the disease (impaired glucose tolerance) can often be identified. Insulin resistance is central to the pathogenesis and is initially compensated by an increased insulin secretion. Over time, insulin secretion progressively fails and diabetes appears. Several approaches have been proposed for the prevention of diabetes. Lifestyle changes (nutritional therapy and physical activity) have been shown to reduce the frequency of diabetes in small studies and are being assessed in the NIH-funded Diabetes Prevention Trial. Metformin, which reduces insulin resistance and hyperinsulinaemia, is being assessed in this same trial. Acarbose, which has been shown to reduce post-prandial insulin secretion and improve insulin resistance, is being assessed in the STOP-NIDDM trial. The ACE inhibitor ramipril has been shown in the HOPE study to reduce the appearance of diabetes by one third when given to patients with vascular disorders and this class of agents has been shown to improve insulin resistance. Another very promising approach is the use of thiazolidinediones (rosiglitazone, pioglitazone) to improve the insulin resistance and possibly preserve the beta cells by reducing the need for increased insulin secretion. These lifestyle changes and medications have been shown to be safe in the treatment of type 2 diabetes. There is a high probability that one of these approaches will be effective in delaying or preventing type 2 diabetes, and prevention may become a clinical reality in the near future.