Factors Associated with Early Remission of Type I Diabetes in Children Treated with Cyclosporine

• Published in: The New England journal of medicine Vol. 318; no. 11; pp. 663 - 670
• Main Authors: Bougneres, P.F, Carel, J.C, Castano, L, Boitard, C, Gardin, J.P, Landais, P, Hors, J, Mihatsch, M.J, Paillard, M, Chaussain, J.L, Bach, J.F
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 17.03.1988
• Subjects: Adolescent; Age Factors; Antigens; Autoantibodies; Biological and medical sciences; Biopsy; Blood glucose; Blood Glucose - analysis; Body Weight; Body weight loss; C-Peptide - analysis; Child; Children; Clinical trials; Cyclosporins; Cyclosporins - adverse effects; Cyclosporins - therapeutic use; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - drug therapy; Diabetic ketoacidosis; Diabetic Ketoacidosis - complications; Drug dosages; Female; Glucagon; Glucose; Glycated Hemoglobin A - analysis; Hemoglobin; Histocompatibility antigen HLA; Hormones. Endocrine system; Humans; Immunosuppression; Insulin; Insulin - administration & dosage; Intravenous administration; Ketoacidosis; Male; Medical sciences; Peptides; Pharmacology. Drug treatments; Pilot Projects; Remission; Remission (Medicine); Remission Induction; Sex Factors; Time Factors; Toxicity; Human; Endocrinopathy; Chemotherapy; Treatment; Insulin dependent diabetes; Autoimmune disease; Remission; Early stage; Child
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198803173181103

To improve criteria for entry into future trials of immunosuppression, we enrolled 40 children with recent-onset Type I insulin-dependent diabetes in a pilot trial of cyclosporine. Twenty-seven patients were able to discontinue insulin therapy 48±5 days after the start of immunosuppression. At four months, their fasting and postprandial blood glucose concentrations averaged 110 and 160 mg per deciliter (6.1 and 8.9 mmol per liter) with a mean hemoglobin A 1c level of 6.15 percent. Seventy-five percent of these patients with early remission still did not need insulin at 12 months, and their glycemic control was similar to that at 4 months. The major differences between the 27 patients with remission and the 13 without remission were the duration of symptoms before diagnosis (26.8 vs. 48.0 days, P<0.01), the degree of weight loss (3.2 vs. 10 percent of body weight, P<0.001), the initial hemoglobin A 1c level (10.7 vs. 13.2 percent, P<0.001), and the frequency of ketoacidosis (11 vs. 61.5 percent, P<0.001). The lesser degree of weight loss was the strongest independent predictor of remission. The response of C-peptide to intravenous glucagon (0.50 vs. 0.17 pmol per milliliter, P<0.05) was also an independent predictor. No differences were observed between the two groups of patients in age, sex, HLA phenotype, autoantibodies to insulin or islet-cell antigens, or doses or trough levels of cyclosporine. Only minimal manifestations of toxicity were detected over the period of observation. We conclude that early treatment with cyclosporine in children with recent-onset Type I diabetes can induce remission from insulin dependence, with half the patients not requiring insulin after a full year. (N Engl J Med 1988; 318:663–70.) THERE is a large body of evidence that Type I insulin-dependent diabetes mellitus (IDDM) is of autoimmune origin. 1 Consequently, recent therapeutic efforts have been directed toward intervention with various immunosuppressive agents. The results of preliminary attempts using steroids, anti-lymphocyte serum, azathioprine, or plasmapheresis were inconclusive. 2 3 4 5 Two open pilot studies in which cyclosporine was given to adults with diabetes provided encouraging data, 6 , 7 but their interpretation was complicated by the possibility of interference with the spontaneous remissions observed in diabetic adults during the first months of insulin treatment. 8 , 9 Convincing evidence of favorable short-term effects of cyclosporine on Type I IDDM came from . . .