ABSTRACT
Type 1 diabetes is characterized by autoimmune destruction of the beta cells of the pancreas, with resulting insulin deficiency. Despite 77 years of research and clinical experience since the discovery of insulin at the University of Toronto in the summer of 1921, our ability to achieve physiological insulin replacement and thus glycemic normalization remains illusive. Indeed, the inadequacies of contemporary diabetes management is exemplified by the fact that diabetes is the leading cause of blindness in adults, accounts for 30% of all causes of end- stage renal disease, is the most common cause of nontraumatic amputation of the lower extremity, and is a major risk factor for cardiovascular, cerebrovascular, and peripheral vascular disease. The debate on the importance of glucose control in the development of the microvascular complications of diabetes has been definitively answered with the publication of the Diabetes Control and Complications Trial (DCCT) results in 1993. The DCCT was a multicenter, randomized, prospective trial sponsored by the National Institutes of Health involving 1441 patients with type 1 diabetes in Canada and the United States. The study took its lead from several smaller European studies and addressed whether the complications of diabetes could be prevented with intensive diabetes management in individuals who had short-duration diabetes (1-5 years) and no complications at randomization (primary prevention) as well as patients with type 1 diabetes who had longer- duration diabetes (1-15 years) and early complications. The DCCT was stopped 1 year early because the magnitude of the beneficial effect of intensive diabetes
