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

    loading  Checking for direct PDF access through Ovid

Abstract

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.

Related Topics

    loading  Loading Related Articles