title: Cyclosporine delays but does not prevent clinical onset in glucose intolerant pre-type 1 diabetic children.
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.
authors.affiliation: INSERM U342 and Pediatric Endocrinology, Saint Vincent de Paul Hospital, René Descartes University, Paris, France. jccarel@infobiogen.fr
authors.forename: J C
authors.initials: JC
authors.lastname: Carel
authors.forename: C
authors.initials: C
authors.lastname: Boitard
authors.forename: G
authors.initials: G
authors.lastname: Eisenbarth
authors.forename: J F
authors.initials: JF
authors.lastname: Bach
authors.forename: P F
authors.initials: PF
authors.lastname: Bougnères
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004361:Drug Tolerance; D005260:Female; D018149:Glucose Intolerance; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007330:Insulin Antibodies / Q000097:blood; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D011236:Prediabetic State / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D007166:Immunosuppressive Agents; D007328:Insulin; D007330:Insulin Antibodies; C024211:islet cell antibody; D016572:Cyclosporine; D003404:Creatinine