Diabetes, Vol 45, Issue 1 101-104, Copyright © 1996 by American Diabetes Association
Long-term results of early cyclosporin therapy in juvenile IDDM
G De Filippo, JC Carel, C Boitard and PF Bougneres
U342 Institut National de la Sante et de la Recherche Medicale (INSERM), Saint Vincent de Paul Hospital, Rene Descartes University, Paris, France.
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.