Plasma C-Peptide Levels and Clinical Remissions in Recent-Onset Type I Diabetic Patients Treated With Cyclosporin A and Insulin

Abstract

Remission from insulin dependency in insulin-treated recent-onset type I (insulin-dependent) diabetic patients can result from a partial recovery of insulin secretion, an improvement in tissue sensitivity to insulin, or both. The same hypothesis must be analyzed when remission occurs in cyclosporin A (CsA)-treated patients. In this study, plasma C-peptide levels were serially measured in the basal state and after stimulation in 219 recent-onset type I diabetic patients; 129 received CsA, and all patients were similarly monitored and insulin treated. The results were analyzed in view of the occurrence of remission. Remission was defined as good metabolic control in the absence of hypoglycemic treatment for ≥1 mo. Remission occurred in 44% of the CsA-treated group and lasted for mean ± SE 10.0 ± 0.9 mo vs. 21.6% in the non-CsA-treated group with a duration of 4.4 ± 0.8 mo. Plasma C-peptide levels were initially dramatically lower than normal in both groups in the basal and stimulated states. C-peptide levels increased significantly later, at 3 and 6 mo, in both groups. C-peptide values were proportional to the rates of remission in both groups. In the non-CsA-treated group, C-peptide levels later decreased, and these patients inexorably relapsed to insulin dependency. In contrast, in the CsA-treated group, the initial recovery in insulin secretory capacity was maintained over the 18–24 mo of the study. Furthermore, higher remission rates and longer-lasting remission were obtained in patients who reached higher C-peptide levels at the 3rd mo of treatment. Conversely, a progressive decrease in C-peptide values followed interuption of CsA treatment in some patients who had previously maintained some C-peptide secretory capacity. Our results support the hypothesis of an efficient suspension by CsA of the progressive deterioration of islets. The maintenance of β-cell secretory capacity by CsA plus insulin was better than by insulin alone. However, C-peptide concentrations remained lower than normal in patients in remission. An improvement in sensitivity to insulin may have also contributed to the development of remission.