Results of the Diabetes Control and Complications Trial have demonstrated that glycemic control of insulin-dependent diabetes mellitus matters. Lower glycosylated hemoglobin values in intensively treated versus conventionally treated patients reduce the risks of microvascular complications. Applying DCCT recommendations to the treatment of children and adolescents with IDDM requires a team approach, use of unconventional treatment regimens, and efforts to reduce the risks for hypoglycemia. In patients who are successful, the improvement in long-term prognosis justifies the investment in time, effort, and resources.

Continuous subcutaneous insulin infusion (CSII) was initiated in a young female adolescent with severe insulin resistance, decreased growth velocity, and poor metabolic control. The patient's insulin dose had been 3 u/kg/day, and it was hypothesized that her insulin requirements would be much less when only regular insulin was used. Because of the potential risk of severe hypoglycemia from giving regular insulin in amounts equivalent to her injection total daily dose as a constant subcutaneous infusion, the patient was hospitalized to begin pump therapy. Hourly glucose levels were collected for 24 hours to determine insulin requirements with this therapy. The patient subsequently required a significantly reduced dose of insulin (1.2 u/kg/day) with CSII, and her growth velocity improved. Metabolic control based on glycosylated hemoglobin levels also improved. Insulin pump treatment proved to be a viable solution for this young adolescent who required large doses of insulin to maintain reasonable control. Challenges of using this type of therapy in young patients are discussed.

OBJECTIVE - 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.RESEARCH DESIGN AND METHODS - 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 (greater than or equal to 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).RESULTS - 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 HbA(1c) 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 greater than or equal to 90% of the study time. CSII-treated patients maintained a mean HbA(1c) 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.CONCLUSIONS - 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.

Objective: To determine the magnitude of the decrease in the risk of retinopathy progression observed with intensive treatment and its relationship to baseline retinopathy severity and duration of follow-up.Design: Randomized clinical trial, with 3 to 9 years of follow-up.Setting and Patients: Between 1983 and 1989, 29 centers enrolled 1441 patients with insulin-dependent diabetes mellitus aged 13 to 39 years, including 726 patients with no retinopathy and a duration of diabetes of 1 to 5 years (primary prevention cohort) and 715 patients with very mild to moderate nonproliferative diabetic retinopathy and a duration of diabetes of 1 to 15 years (secondary intervention cohort). Ninety-five percent of all scheduled examinations were completed.Interventions: Intensive treatment consisted of the administration of insulin at least three times a day by injection or pump, with doses adjusted based on self-blood glucose monitoring and with the goal of normoglycemia. Conventional treatment consisted of one or two daily insulin injections.Outcome Measures: Change between baseline and follow-up visits on the Early Treatment Diabetic Retinopathy Study retinopathy severity scale, assessed with masked gradings of stereoscopic color fundus photographs obtained every 6 months.Results: Cumulative 8.5-year rates of retinopathy progression by three or more steps at two consecutive visits were 54.1% with conventional treatment and 11.5% with intensive treatment in the primary prevention cohort and 49.2% and 17.1% in the secondary intervention cohort. At the 6- and 12-month visits, a small adverse effect of intensive treatment was noted (''early worsening''), followed by a beneficial effect that increased in magnitude with time. Beyond 3.5 years of follow-up, the risk of progression was five or more times lower with intensive treatment than With conventional treatment. Once progression occurred, subsequent recovery was at lease two times more likely with intensive treatment than with conventional treatment. Treatment effects were similar in all baseline retinopathy severity subgroups.Conclusion: The results of the Diabetes Control and Complications Trial strongly support the recommendation that most patients with insulin-dependent diabetes mellitus use intensive treatment, aiming for levels of glycemia as close to the nondiabetic range as is safely possible.

The Diabetes Control and Complications Trial (DCCT) is a multicenter, randomized clinical trial studying the effects of two different diabetes regimens on the development and progression of early vascular complications in persons with insulin-dependent diabetes mellitus (IDDM). All of the centers have a Trial Coordinator. We administered a self-report questionnaire to each center to document the different activities for which the Trial Coordinator assumed responsibility in successfully orchestrating the trial. All Trial Coordinators were responsible primarily for recruitment, screening, medical management, education and training, and adherence and administration. Although documentation indicated that the Trial Coordinator was responsible for all of the above activities, the original applications reflected that very few of the Principal Investigators anticipated such a wide variety of duties. A Trial Coordinator was named in only 13 of the 21 applications and of these, only 6 actually assumed the position. This study points out the need to develop a means to define characteristics, background, and training appropriate for candidates for a Trial Coordinator position in future studies.

Recent studies indicate that glucose control may be improved in adult diabetics with intensive insulin (II) Rx (using either infusion pumps or multiple injections) and home blood glucose monitoring. To examine the efficacy of these Rx strategies in children, we examined whether near normal glucose levels could be achieved in 8 young (age 10-15 yrs) diabetics given II Rx (6 pump, 2 multiple injections) for 2-6 mos. Control was assessed by HbA1 (nl 5-8%) and glucose measurements of blood samples mailed from home (HG). Glycemic excursions (MAGE) were determined from inpatient glucose profiles (IG). Effect of II Rx on glucose levels (mg/dl) is shown below (¶ p < 0.01). HbA1 levels fell significantly after 2 wks (12.7±1.0 to 9.3±0.7%) and was further reduced by 4-8 wks.(7.6±0.1%, p<0.005). Glycosuria was virtually eliminated (81±20 vs 3±1 gm/day). Insulin dose increased by 50% with II Rx (to 1.4 U/kg/day). However, hypoglycemia symptoms were mild and none required IV glucose. Conclusions: Near normal glucose control can be achieved in the outpatient management of children and adolescents with diabetes. The comparative efficacy of insulin pump vs multiple injections needs to be determined.