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Effect of Intensive Therapy on Residual β-Cell Function in Patients with Type 1 Diabetes in the Diabetes Control and Complications Trial: A Randomized, Controlled Trial

[+] Article and Author Information

The Diabetes Control and Complications Trial Research Group. A complete listing of the DCCT Research Group is available in Archives of Ophthalmology, 1995; 113:49-51. Grant Support: In part by the Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, through cooperative agreements and a research contract. Additional support was given by the National Heart, Lung and Blood Institute; the National Eye Institute; and the National Center for Research Resources. Requests for Reprints: The DCCT Research Group, Box NDIC/DCCT, Bethesda, MD 20892.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1998;128(7):517-523. doi:10.7326/0003-4819-128-7-199804010-00001
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Background: Although insulin secretion is severely decreased in most patients with type 1 diabetes, levels of residual insulin secretion often vary early in the disease. The significance of residual insulin secretion with regard to metabolic control and to long-term complications and ways to preserve such secretion are not well understood.

Objective: To compare the effects of intensive and conventional therapy on residual insulin secretion in Diabetes Control and Complications Trial (DCCT) participants.

Design: Multicenter, randomized, controlled clinical trial.

Setting: 29 DCCT clinical centers.

Patients: 855 of the 1441 DCCT participants had had type 1 diabetes for 1 to 5 years at baseline. Of these 855 patients, 303 were C-peptide responders (C-peptide level, 0.20 to 0.50 pmol/mL after ingestion of a standardized, mixed meal); 138 of these patients were randomly assigned to intensive therapy, and 165 were assigned to conventional therapy. Five hundred fifty-two patients were nonresponders (stimulated C-peptide level < 0.2 pmol/mL); 274 of these patients were assigned to intensive therapy, and 278 were assigned to conventional therapy.

Interventions: 1] Intensive therapy with 3 or more insulin injections daily or continuous subcutaneous infusion of insulin, guided by 4 or more glucose tests per day or 2) conventional therapy with 1 or 2 insulin injections daily.

Measurements: Stimulated C-peptide level was measured annually in responders. Development of retinopathy and microalbuminuria was assessed annually, hemoglobin A1c levels were measured quarterly, and episodes of hypoglycemia were ascertained quarterly.

Results: Responders receiving intensive therapy maintained a higher stimulated C-peptide level and a lower likelihood of becoming nonresponders than did responders receiving conventional therapy (risk reduction, 57% [95% CI, 39% to 71%]; P < 0.001). As in the entire DCCT cohort, intensively treated responders had a reduced risk for retinopathy progression and development of microalbuminuria and a higher risk for severe hypoglycemia compared with conventionally treated responders. Among intensively treated patients, responders had a lower hemoglobin A1c value (P < 0.01), a 50% (95% CI, 12% to 72%) reduced risk for retinopathy progression, and a lower risk for severe hypoglycemia (risk reduction, 65% [CI, 53% to 74%]; P < 0.001) compared with nonresponders.

Conclusions: Intensive therapy for type 1 diabetes helps sustain endogenous insulin secretion, which, in turn, is associated with better metabolic control and lower risk for hypoglycemia and chronic complications. These observations underscore the importance of initiating intensive diabetic management as early as safely possible after type 1 diabetes is diagnosed.

Figures

Grahic Jump Location
Figure 1.
Distribution of stimulated C-peptide levels by treatment group over 6 years of the study among patients who were C-peptide responders at baseline.PPPPPPPP

Box plots present the annual distributions for each treatment group. The ends of each box correspond to the lower and upper quartiles. Brackets represent the 5% and 95% points of the distribution. The horizontal line in each plot represents the median, and the asterisk in each plot represents the mean. > 0.2 for eligibility period, > 0.2 at baseline, = 0.003 at year 1, = 0.01 at year 2, = 0.006 at year 3, = 0.001 at year 4, = 0.124 at year 5, and > 0.2 at year 6. Striped bars = intensive therapy group; white bars = conventional therapy group.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Probability of maintaining C-peptide secretion (stimulated C-peptide level ≥ 0.dotted lineP

20 pmol/mL) with intensive therapy (solid line) compared with conventional therapy ( ) ( < 0.001).

Grahic Jump Location

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