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Long-term results of early cyclosporin therapy in juvenile IDDM
G De Filippo1, J C Carel, C Boitard
1U342 Institut National de la Sante et de la Recherche Medicale (INSERM), Saint Vincent de Paul Hospital, René Descartes University, Paris, France.
Insights
Low-dose cyclosporin A in juvenile diabetes (IDDM) patients showed prolonged benefits in beta-cell function and reduced insulin needs, but the effects were not significant long-term.
Area of Science:
- Immunology
- Endocrinology
- Pediatrics
Background:
- Juvenile diabetes mellitus (IDDM) treatment often involves managing insulin dependency.
- Cyclosporin A has shown potential for partial beta-cell function recovery and transient remission in IDDM patients.
- Long-term effects of cyclosporin A in pediatric IDDM have not been extensively studied.
Purpose of the Study:
- To evaluate the long-term efficacy and impact of low-dose cyclosporin A on beta-cell function in juvenile IDDM patients.
- To assess the duration of therapeutic benefits beyond the interruption of cyclosporin A treatment.
Main Methods:
- A cohort of 130 juvenile IDDM patients was analyzed.
- 83 patients received cyclosporin A, with doses adjusted and treatment interrupted based on response (6-62 months).
- 47 diabetic children served as a control group for comparison over 4 years.
Main Results:
- Cyclosporin A group maintained approximately double the plasma C-peptide levels compared to controls (P < 0.02).
- Time to undetectable glucagon-stimulated C-peptide secretion was significantly longer in the cyclosporin group (5.8 years vs. 3.2 years, P < 0.02).
- Treated patients required lower insulin doses and had improved glycated hemoglobin (HbA1c) and reduced hypoglycemia (P < 0.05).
Conclusions:
- Low-dose cyclosporin A demonstrates prolonged positive effects on beta-cell function and metabolic control in recently diagnosed juvenile IDDM patients, extending beyond drug cessation.
- Despite observed benefits, the magnitude and duration of these effects were insufficient to warrant widespread clinical use of cyclosporin A for this indication.
- No significant secondary side effects of cyclosporin A were noted in the study cohort.
Abstract:
In juvenile IDDM patients, immunosuppression with cyclosporin A allows partial beta-cell function recovery and transient remissions of insulin dependency. The effects of this therapeutic approach, however, have not been evaluated in the long-term, since no reported trial exceeded 1 year. Here we analyze 130 diabetic children followed at our institution during the first years of their disease. Cyclosporin was given to 83 of them at an initial dose of 7.2 +/- 0.1 mg.kg-1.day-1, which was decreased stepwise then interrupted after 6-62 months, depending on the response to therapy. A total of 47 diabetic children, who served as control subjects in two trials, were pooled for comparison. Over 4 years, the cyclosporin-treated group kept plasma C-peptide approximately twice as high as the control group (P < 0.02). It took 5.8 +/- 0.6 years for C-peptide secretion stimulated by glucagon to become undetectable in the cyclosporin group versus 3.2 +/- 0.6 years in the control group (P < 0.02). Average insulin dose remained lower by 0.2-0.4 U.kg-1.day-1 and glycated hemoglobin by approximately 1% in cyclosporin-treated patients (P < 0.02), who also had less hypoglycemia than the diabetic control subjects (P < 0.05). After 4 years, differences between the groups became nonsignificant. We observed no significant secondary effects of cyclosporin. In conclusion, positive effects of low-dose cyclosporin in recently diagnosed clinical IDDM patients are prolonged beyond interruption of the drug. The magnitude and duration of the benefit, however, do not appear sufficient to justify this immunosuppressive treatment in clinical practice.