IA-2 Antibody-Negative Status Predicts Remission and Recovery of C-Peptide Levels in Type 1 Diabetic Patients Treated With Cyclosporin
- Michael R. Christie, PhD1,
- Jens Mølvig2,
- Charlotte J. Hawkes, PhD1,
- Bendix Carstensen2,
- Thomas Mandrup-Poulsen2 and
- the Canadian-European Randomised Control Trial Group
- 1Department of Medicine, Guy’s, King’s and St. Thomas’ School of Medicine, London, U.K.
- 2Steno Diabetes Centre, Gentofte, Denmark
Abstract
OBJECTIVE—The use of cyclosporin in recent-onset type 1 diabetes has demonstrated the potential for immune intervention in the treatment and prevention of the disease. However, a proportion of patients failed to respond to cyclosporin treatment. Indicators of resistance to immune intervention would be valuable for the most effective use of such therapies in disease prevention. The aim of this study was to determine whether presence of IA-2 antibodies is such a marker.
RESEARCH DESIGN AND METHODS—IA-2 antibodies were determined by radioligand binding assay in sera from patients recruited into the Canadian-European cyclosporin trial. Insulin dose requirements and glucagon-stimulated C-peptide secretion were analyzed in patients grouped according to IA-2 antibody status at entry.
RESULTS—Cyclosporin treatment had no significant effect on frequency of IA-2 antibodies during the 1 year of treatment. Cyclosporin caused significant reduction in insulin requirements and significant increases in C-peptide secretion mainly in patients negative for IA-2 antibodies. Analysis of GAD antibodies in combination with antibodies to IA-2 indicated that the group most resistant to cyclosporin were IA-2 antibody positive, GAD antibody negative.
CONCLUSIONS—The results demonstrate that IA-2 antibody analysis is valuable in identifying individuals for whom immunosuppressive treatment would be most effective.
- GADA, GAD antibody
- IA-2A, IA-2 antibody
- IAA, insulin autoantibody
- ICA, islet cell antibody
- RR, relative risk
Footnotes
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Address correspondence and reprint requests to Dr. Michael Christie, Department of Medicine, GKT School of Medicine, Bessemer Road, London SE5 9PJ, U.K. E-mail: michael.christie{at}kcl.ac.uk.
Received for publication 8 August 2001 and accepted in revised form 25 March 2002.
Thomas Mandrup-Poulsen is employed by Novo Nordisk A/S, Bagsværd, Denmark, as Chief Physician of Steno Diabetes Center and serves Novo Nordisk as a member of the Development Committee responsible for the clinical development portfolio. All clinical activities of this center are paid by the public health care system, but Novo Nordisk strongly subsidizes Steno Diabetes Center research activities. Novo Nordisk manufactures and markets pharmaceuticals related to the treatment of diabetes.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE
