Challenges in optimal metabolic control of diabetes.

The results of the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) showed that tight glycemic control with any of several therapeutic regiments has the potential to significantly reduce the risks for long-term microvascular complications of type 1 or type 2 diabetes. The results of these large-scale long-term studies also demonstrated that there is no threshold for the relationship between blood glucose [i.e. glycosylated hemoglobin (HbA(1c))] and reduced risk. This means that 'optimal' glycemic control in a patient with type 1 or type 2 diabetes is a blood glucose level as close as possible to the level in an individual without diabetes. Limitations of most available therapies for type 1 and 2 diabetes have hampered achievement of this goal. Most available insulin preparations used to treat patients with type 1 disease can achieve approximately normal basal insulin levels only when used with a pump or a complex treatment regimen requiring a large number of daily injections. Pumps are limited by high expense, and complex injection protocols increase the potential for patient errors and non-compliance. The development of new insulins such as aspart insulin and lispro insulin, both short-acting, and insulin glargine, a long-acting insulin analogue suitable for once-daily administration, may help overcome these challenges. In patients with type 2 diabetes, achieving optimal glycemic control is complicated by the progressive nature of the disease and the loss of efficacy of oral agents (e.g. sulfonylureas, metformin, and thiazolidinediones) over time. Moreover, neither oral therapy nor insulin alone is likely to achieve optimal glycemic control in most of these patients in the long term. The availability of new insulin preparations that mimic the normal mealtime bursts of insulin, and another that provides a sustained insulin supply similar to basal insulin secretion in an individual without diabetes has the potential to significantly improve long-term control over blood glucose in patients with type 2 diabetes.