Summary
Several studies have demonstrated the efficacy of cyclosporin A in modifying the initial course of Type 1 (insulin-dependent) diabetes mellitus in older children and adults but none have reported the effects in very young children. We treated 14 newly-diagnosed Type 1 diabetic patients aged 22 months to 95 months with cyclosporin A. Mean insulin dose at entry was 0.7±0.07 IU · kg−1 · day−1. Initial cyclosporin A dose was 10 mg · kg−1 · day−1. Insulin dose reached a nadir of 0.13 IU · kg−1 · day−1 by 180 days. Mean glucagon-stimulated connecting peptide levels were maximal at 6 months (0.75 nmol/l) and were maintained while on cyclosporin A. Insulin was discontinued in four patients for 4,12,15 and 30 months respectively. In five other patients the insulin dose was less than 0.15 IU · kg−1 · day−1 for at least 3 months. Glycated haemoglobin levels for all patients were within the normal range. Side effects included anorexia, stomach pains, poor weight gain, hypertrichosis, gum hyperplasia, mild anaemia and elevated creatinine. All patients have now discontinued cyclosporin A and all but one have been followed for 5 years after discontinuation. Reasons for discontinuing cyclosporin A included exposure to chicken pox (varicella), non-resolving otitis media, incomplete or no response and relapse. All side effects have resolved since the treatment was discontinued. Following discontinuation of cyclosporin A insulin requirements and glycated hemoglobin levels increased while glucagon-stimulated connecting peptide levels declined dramatically. In summary, a small number of very young patients treated with cyclosporin A achieved non-insulin requiring remissions while partial remissions occurred in several other patients and endogenous insulin production was maintained. Side effects to the drug occurred although there have been no long-term consequences.
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Feutren G, Papoz L, Assan R, Vialettes et al. (1986) Cyclosporin increases the rate and length of remission in insulin-dependent diabetes of recent onset. Lancet II: 119–124
Canadian-European randomized control trial group (1988) Cyclosporine-induced remission of IDDM after early intervention. Association of one year of cyclosporine with enhanced insulin secretion. Diabetes 37: 1574–1582
Stiller CR, Dupré J, Gent M et al. (1987) Effects of cyclosporine in recent-onset juvenile Type 1 diabetes: impact of age and duration of disease. J Pediatr 111: 1069–1072
Bougneres PF, Carel JC, Castano L et al. (1988) Factors determining early remission of Type 1 diabetes in children treated with cyclosporin A. N Engl J Med 38: 663–670
Bach JF (1987) Cyclosporine in insulin-dependent diabetes mellitus. J Pediatr 111: 1073–1074
Feutren G (1988) Functional consequences and risk factors of chronic cyclosporin A nephrotoxicity in Type 1 diabetes trials. Transplant Proc 20: 356–366
Stiller CR, Dupré J, Gent M et al. (1984) Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset. Science 223: 1362–1367
Laupacis A, Stiller CR, Gardell C et al. (1983) Cyclosporin prevents diabetes in BB Wistar rats. Lancet I: 10–12
Assan R, Sachs MD, Laborie C et al. (1985) Metabolic and immunologic effect of cyclosporine in recently diagnosed Type 1 diabetes mellitus. Lancet I: 67–71
Dupré J, Stiller CR, Gent M et al. (1988) Effects of immunosuppression with cyclosporine in insulin dependent diabetes mellitus of recent onset: the Canadian open study of 44 months. Transplant Proc 20: 184–192
Stiller CR, Keown PA (1984) Cyclosporine therapy in perspective: In Morris PJ, Tilney NL (eds) Progress in transplantation. Churchill Livingstone, Edinburgh, pp 11–45
Bougnères PF, Landais P, Boisson C et al. (1990) Limited duration of remission of insulin dependency in children with recent overt type 1 diabetes treated with low-dose cyclosporin. Diabetes 39: 1264–1272
Finegood D, Hramiak IM, Dupré J (1990) Relationship between stimulated C-peptide responses and insulin sensitivity in insulin-dependent diabetics treated with cyclosporin. Diabetologia 33 [Suppl]: A208 (Abstract)
Bach JF (1988) The risk/benefit ratio in immunointervention for autoimmune diseases. J Autoimmun 1: 711–720
Bach JF (1992) Immunointervention in autoimmune diseases from cellular selectivity to autoantigen specificity. J Autoimmun 5 [Suppl]: A3–10
Editorial (1984) Lymphoma in organ transplant recipients. Lancet I: 601–603
Hanto DW, Frizzera G, Gajl-Peczalska KJ, Simmons RL (1985) Epstein-Barr virus, immunodeficiency and B cell lymphoproliferation. Transplantation 39: 461–472
Ho M, Jaffe R, Miller G et al. (1988) The frequency of EpsteinBarr virus infection and associated lymphoproliferative syndrome after transplantation and its manifestations in children. Transplantation 45: 719–727
Ettenger RB, Rosenthal JT, Marik J et al. (1991) Long-term results with cyclosporine immune suppression in pediatric cadaver renal transplantation. Transplant Proc 23: 1011–1012
Klore B, Strom TM, Hahn H et al. (1991) Remarkable long-term prognosis and excellent growth in kidney-transplant children under cyclosporine monotherapy. Transplant Proc 23: 1013–1017
Elliott RB, Chase HP (1991) Prevention of delay of Type 1 (insulin dependent) diabetes mellitus in children using nicotinamide. Diabetologia 34: 362–365
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Jenner, M., Bradish, G., Stiller, C. et al. Cyclosporin A treatment of young children with newly-diagnosed Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35, 884–888 (1992). https://doi.org/10.1007/BF00399937
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DOI: https://doi.org/10.1007/BF00399937