The rationale for glucose control in diabetes mellitus.

After more than 60 years of active investigation, the role of intensive treatment regimens in preventing and ameliorating diabetes complications is close to being resolved. Currently available intensive regimens do not achieve normoglycemia and are associated with significant complications. Moreover, they are dependent on a high level of patient motivation and adherence and may not be widely applicable in the IDDM population. Given these limitations, it is critical that their benefit, if any, be documented before they are introduced widely into clinical therapy. If the glucose hypothesis proves to be true, the benefits of intensive therapy will outweigh all of its limitations. Although previous trials have failed to document benefits with regard to retinopathy (the decrease in the progression from incipient nephropathy to clinical proteinuria is of unknown clinical significance), the DCCT has adequate power to define the role of intensive therapy. If the DCCT demonstrates a salutary effect of intensive therapies, a rationale for such efforts finally will have been established. The goal for the next generation of clinical investigation will be to develop new means of intensive therapy that have less risk and are more accessible and acceptable to all persons with diabetes.