Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial,☆☆,,★★

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Abstract

The Diabetes Control and Complications Trial has demonstrated that intensive diabetes treatment delays the onset and slows the progression of diabetic complications in subjects with insulin-dependent diabetes mellitus from 13 to 39 years of age. We examined whether the effects of such treatment also occurred in the subset of young diabetic subjects (13 to 17 years of age at entry) in the Diabetes Control and Complications Trial. One hundred twenty-five adolescent subjects with insulin-dependent diabetes mellitus but with no retinopathy at baseline (primary prevention cohort) and 70 adolescent subjects with mild retinopathy (secondary intervention cohort) were randomly assigned to receive either (1) intensive therapy with an external insulin pump or at least three daily insulin injections, together with frequent daily blood-glucose monitoring, or (2) conventional therapy with one or two daily insulin injections and once-daily monitoring. Subjects were followed for a mean of 7.4 years (4 to 9 years). In the primary prevention cohort, intensive therapy decreased the risk of having retinopathy by 53% (95% confidence interval: 1% to 78%; p = 0.048) in comparison with conventional therapy. In the secondary intervention cohort, intensive therapy decreased the risk of retinopathy progression by 70% (95% confidence interval: 25% to 88%; p = 0.010) and the occurrence of microalbuminuria by 55% (95% confidence interval: 3% to 79%; p = 0.042). Motor and sensory nerve conduction velocities were faster in intensively treated subjects. The major adverse event with intensive therapy was a nearly threefold increase of severe hypoglycemia. We conclude that intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy and nephropathy when initiated in adolescent subjects; the benefits outweigh the increased risk of hypoglycemia that accompanies such treatment. (J PEDIATR 1994;125:177-88)

Section snippets

Subjects

A total of 195 adolescent subjects (125 primary prevention and 70 secondary intervention cohort) were recruited by 29 clinical centers from 1983 to 1989.2 At the time of study termination, in June 1993, the adolescent subjects had been studied for an average of 7.4 years (range, 4 to 9 years). The results reported here include the outcomes in the subjects who were adolescents at the time of study entry, independent of whether they were adolescents during the entire study. The subjects in this

Adherence and metabolic control achieved

One hundred ninety-five adolescent subjects were followed for a mean of 7.4 years (range, 4 to 9 years), for a total of more than 1448 patient-years. None of the adolescent subjects voluntarily withdrew from the study, and more than 95% of all scheduled examinations were completed. Two subjects died and two were assigned to inactive status for some time because of unavailability or the investigator's decision that continuation would be hazardous. Overall, the average percentage of time spent in

DISCUSSION

We undertook an analysis of outcome in adolescent subjects with IDDM because none of the previous randomized clinical trials of intensive therapy included young subjects, even though the majority of subjects with IDDM have their onset before age 20 years. Thus the demonstration that intensive therapy with the goal of lowering plasma glucose concentrations delays the onset and slows the progression of early diabetic retinopathy (the principal study outcome) in adolescents with IDDM is especially

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  • Cited by (0)

    Supported by the Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, through cooperative agreements and a research contract. Additional support provided by the National Heart, Lung, and Blood Institute, the National Eye Institute, and the National Center for Research Resources.

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    Reprint requests: Diabetes Control and Complications Trial Research Group, Box NDIC/DCCT, Bethesda, MD 20892.

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    See commentary, Reviewing the Diabetes Control and Complications Trial: One member of the "control panel" speaks

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