Limited Duration of Remission of Insulin Dependency in Children With Recent Overt Type I Diabetes Treated With Low-Dose Cyclosporin

Abstract

Preliminary data from our group indicated that cyclosporin A induced frequent remissions of insulin dependency in a group of 40 insulin-dependent (type I) diabetic children if given at the onset of clinical manifestations of diabetes. We report a 2-yr analysis of the response to cyclosporin A in the group of 81 patients included in the initial study. As observed before, a remission could be obtained in most of the patients (65%) in association with a shorter duration of symptoms, less severe hyperglycemia, lower incidence of ketoacidosis, and higher plasma C-peptide concentrations. All remissions ended during the follow-up period after a mean ± SE duration of 316 ± 21 days (range 31–850 days). Two parameters were linked to the duration of remissions: the mean circulating level of cyclosporin during the first 3 mo and the duration of prediagnostic polyuria. We were unable to relate the end of a remission to variations in the cyclosporin regimen, titer of autoantibodies, or progression of β-cell failure. The euglycemic clamp technique revealed that insulin sensitivity decreases with time in patients not taking insulin. At 24 mo, the patients who had a remission of insulin dependency had better glycemic control, lower insulin dosages, and C-peptide levels two- to threefold higher than the nonremission patients and four- to sixfold higher than the historical control subjects. The cyclosporin regimen was well tolerated over the observed period: more specifically, serum creatinine remained unchanged, and kidney biopsies performed at 18–24 mo of treatment were within normal limits. We conclude that this immunosuppressive regimen given to patients with overt type I diabetes maintains a residual insulin secretion, which, however, does not allow >2-yr remissions of insulin dependency. It remains to be studied whether some preservation of β-cell function will thereafter be retained and whether this can improve the management and prognosis of the disease. It will also be necessary to test whether earlier diagnosis can ameliorate and prolong our results.