Cyclosporine delays but does not prevent clinical onset in glucose intolerant pre-type 1 diabetic children

J Autoimmun. 1996 Dec;9(6):739-45. doi: 10.1006/jaut.1996.0096.

Abstract

We conducted a pilot study of immunosuppression with low dose cyclosporine in first degree relatives of diabetic patients with immunologic and metabolic criteria for preclinical diabetes: islet cell antibodies (ICA) > or = 20 Juvenile Diabetes Foundation (JDF) units, first phase insulin response < 10th percentile and impaired glucose tolerance. Cyclosporine was given at an initial dose of 7.5 mg/kg*d and tapered after the end of the first year. Six cyclosporine-treated relatives were compared to nine historical controls followed at the same or at different centres. All untreated patients developed diabetes within 12 months (5.9 +/- 1.1 months). Four of the cyclosporine-treated subjects developed diabetes at 5, 24, 24 and 47 months while the other two are non diabetic 47 and 57 months after entry into the trial (time to diabetes > 34 +/- 8 months, P < 0.001 vs the control group; Mann-Whitney test). First phase insulin response increased to normal values in two patients. These results suggest that reversible functional impairment, in association with beta-cell destruction, contributes to the failure of insulin secretion in preclinical type 1 diabetes.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Autoantibodies / blood
  • Blood Glucose / metabolism
  • Child
  • Cohort Studies
  • Creatinine / blood
  • Cyclosporine / blood
  • Cyclosporine / pharmacology*
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Drug Tolerance
  • Female
  • Glucose Intolerance
  • Humans
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacology*
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Antibodies / blood
  • Insulin Secretion
  • Islets of Langerhans / immunology
  • Male
  • Prediabetic State / etiology
  • Prediabetic State / physiopathology
  • Prediabetic State / prevention & control*
  • Prospective Studies
  • Time Factors

Substances

  • Autoantibodies
  • Blood Glucose
  • Immunosuppressive Agents
  • Insulin
  • Insulin Antibodies
  • islet cell antibody
  • Cyclosporine
  • Creatinine