Objective: To examine whether intensive therapy designed to achieve glycemic levels as close to normal as possible prevents or slows the progression of neuropathy when compared with conventional therapy in patients with insulin-dependent diabetes mellitus in the Diabetes Control and Complications Trial.
Design: Multicenter, randomized, controlled clinical trial.
Setting: 29 U.S. and Canadian clinical centers.
Participants: 1441 patients aged 13 to 39 years, of whom 726 had had insulin-dependent diabetes mellitus for 1 to 5 years and had no retinopathy at baseline (primary prevention cohort); 715 had had diabetes for 1 to 15 years and had minimal to moderate nonproliferative retinopathy at baseline (secondary intervention cohort).
Intervention: Intensive therapy with three or more daily insulin injections or continuous subcutaneous insulin infusion guided by four or more glucose tests per day compared with conventional therapy with one or two daily insulin injections.
Results: Intensive therapy reduced the development of confirmed clinical neuropathy (defined as a history or physical examination consistent with clinical neuropathy confirmed by either abnormal nerve conduction or autonomic nervous system testing) by 64% (95% CI, 45% to 76%) in the combined cohorts after 5 years of follow-up (5% of the intensive therapy group compared with 13% of the conventional therapy group). The prevalence of abnormal nerve conduction and abnormal autonomic nervous system function were reduced by 44% (CI, 34% to 53%) and 53% (CI, 24% to 70%), respectively (26% of the intensive treatment group developed abnormal nerve conduction compared with 46% of the conventional treatment group; 4% of the intensive treatment group had abnormal autonomic nervous system function compared with 9% of the conventional treatment group). Finally, nerve conduction velocities generally remained stable with intensive therapy but decreased significantly with conventional therapy.
Conclusion: Intensive diabetes therapy markedly delays or prevents the development of clinically manifest diabetic polyneuropathy as confirmed by objective nerve function testing in patients with insulin-dependent diabetes mellitus.