Implementation of treatment protocols in the Diabetes Control and Complications Trial.

To describe the methods used to implement intensive and conventional therapies in the Diabetes Control and Complications Trial (DCCT) and the metabolic results that occurred with the different treatment regimens. The DCCT was a controlled clinical trial that demonstrated the beneficial effect of intensive therapy on the long-term complications of insulin-dependent diabetes mellitus (IDDM). A total of 1,441 volunteers with IDDM, aged 13-39, from 29 centers in the U.S. and Canada, were randomly assigned to conventional or intensive diabetes therapy. Intensive therapy, which used multiple daily injections (MDI) of insulin ( > or = 3 injections/day) or continuous subcutaneous insulin infusion (CSII), was implemented by a team that included diabetes nurses, dietitians, behavioral experts, and diabetologists. Volunteers in the intensive treatment group could use MDI or CSII, based on patient and clinic preference, and could switch between therapies over the course of the study. The volunteers were followed for a mean of 6.5 years (range 3-9 years). A detailed analysis of implementation of the two treatments indicates that intensive and conventional treatment subjects adhered to their respective insulin injection regimens > 97% of the time. Adherence to other elements of intensive treatment was similarly high and resulted in median HbA1c values between 6.7 and 7.2, compared with 8.7-9.2 with conventional therapy, over the course of the study. Severe hypoglycemia occurred three times more often in intensively treated subjects. Although subjects on intensive treatment were not randomly assigned to MDI or CSII, we compared those subjects who used either of these methods for > or = 90% of the study time. CSII-treated patients maintained a mean HbA1c of 6.8 vs. 7.0 in MDI-treated subjects during the trial (P < 0.05). The frequency of hypoglycemia with coma and seizure and diabetic ketoacidosis was modestly higher with CSII than with MDI. Intensive therapy was implemented successfully in the DCCT. The detailed description herein will serve to facilitate translation of the DCCT results to the clinical setting.