DETERMINANTS OF CLINICAL REMISSION IN RECENT-ONSET IDDM

OBJECTIVE - To assess the relationship of S(I) 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 AlR(glu), 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 bolus. S(I) 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, AIR(glu), and S(I) different in the treatment groups. The mean plasma C-peptide level improved significantly at 3 mo and was maintained to 12 mo. AIR(glu) was grossly subnormal throughout, but a significant improvement was seen at 3 and 6 mo. Mean S, 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 S(I). Although the improvement in basal C-peptide persisted, AIR(glu) 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 S(I).