Determinants of Clinical Remission in Recent-Onset IDDM

Abstract

Objective— To assess the relationship of SI and insulin secretion (C-peptide levels) to remission status in recent-onset IDDM. Research Design and Methods— We followed 22 newly diagnosed patients, of whom 16 received immunomodulatory treatment with low-dose (5 mg·kg−1·day−1) CsA and/or short-term (72 h) methylprednisolone and 6 received standard insulin treatment, at 3-mo intervals for 12 mo. Insulin secretion was assessed by C-peptide levels and AIRglu, which was determined as the area under the insulin response curve, above the fasting level, from 0–10 min after a 0.3 g·kg−1·i.v. glucose xbolus. SI was assessed by the minimal model technique applied to a frequently sampled IVGTT. Clinical remission was defined in those patients who maintained normal range GHb and capillary blood glucose levels <7.8 mM premeal without insulin therapy for a minimum of 14 days. Results— The rate of clinical remission was not different with immunomodulatory treatment; nor were the metabolic parameters of plasma C-peptide levels, AIRglu, and S1 different in the treatment groups. The mean plasma C-peptide level improved significantly at 3 mo and was maintained to 12 mo. AIRglu was grossly subnormal throughout, but a significant improvement was seen at 3 and 6 mo. Mean SI was normalized at 3 and 6 mo but not maintained beyond 9 mo. The maximum rate of clinical remission was seen at 6 mo. Conclusions— Clinical remission in recent-onset IDDM patients is associated with improvement in both insulin secretion and SI. Although the improvement in basal C-peptide persisted, AIRglu increased only transiently and declined as loss of remission occurred in most patients. Loss of remission to an insulin-requiring state is associated with a decrease in SI.