To improve criteria for entry into future trials of immunosuppression, we enrolled 40 children with recent-onset Type I
insulin-dependent diabetes in a pilot trial of
cyclosporine. Twenty-seven patients were able to discontinue
insulin therapy 48 +/- 5 days after the start of immunosuppression. At four months, their fasting and postprandial
blood glucose concentrations averaged 110 and 160 mg per deciliter (6.1 and 8.9 mmol per liter) with a mean
hemoglobin A1c level of 6.15 percent. Seventy-five percent of these patients with early remission still did not need
insulin at 12 months, and their
glycemic control was similar to that at 4 months. The major differences between the 27 patients with remission and the 13 without remission were the duration of symptoms before diagnosis (26.8 vs. 48.0 days, P less than 0.01), the degree of
weight loss (3.2 vs. 10 percent of
body weight, P less than 0.001), the initial
hemoglobin A1c level (10.7 vs. 13.2 percent, P less than 0.001), and the frequency of
ketoacidosis (11 vs. 61.5 percent, P less than 0.001). The lesser degree of
weight loss was the strongest independent predictor of remission. The response of
C-peptide to intravenous
glucagon (0.50 vs. 0.17 pmol per milliliter, P less than 0.05) was also an independent predictor. No differences were observed between the two groups of patients in age, sex, HLA phenotype,
autoantibodies to
insulin or islet-cell
antigens, or doses or trough levels of
cyclosporine. Only minimal manifestations of toxicity were detected over the period of observation. We conclude that early treatment with
cyclosporine in children with recent-onset Type I diabetes can induce remission from
insulin dependence, with half the patients not requiring
insulin after a full year.