Article: Pathophysiology Proinsulin ⁄C-peptide ratio, glucagon and remission in new-onset Type 1 diabetes mellitus in young adults

Aims After initiation of treatment in Type 1 diabetes, a period with lower insulin requirement often follows, reflecting increased insulin sensitivity and improved insulin secretion. Weexploredif efficiency ofproinsulin processingis associated with the remission phenomenon. Methods Seventy-eight patients with new-onset Type 1 diabetes were followed prospectively for 3 years. Daily insulin dosage, HbA1c, plasma glucose, proinsulin, C-peptide, glucagon concentrations and islet antibodies were determined at diagnosis andafter 3, 6, 9, 12, 18, 24, 30 and 36 months. Westudied remission, defined as an insulin dose £ 0.3 U kg )1 24 h )1 and HbA1c within the normal range, in relation to the above-mentioned variables. Results A rise and subsequent decline in plasma proinsulin and C-peptide concentrations was observed. Forty-five per cent of the patients experienced remission at one or more times, characterized by higher proinsulin and C-peptide levels, and lower proinsulin ⁄C-peptide ratios, indicating more efficient proinsulin processing, compared with those not in remission. Nonremissionalsotendedtobeassociatedwithhigherglucagonvalues.Patientsenteringremissionweremoreoftenmen,hadhigher BMI at diagnosis, but did not differ at baseline with respect to islet antibody titres compared with patients with no remission. Conclusions RemissionsafterdiagnosisofType 1diabeteswereassociatedwithlowerproinsulin ⁄C-peptideratios,suggesting more efficient proinsulin processing, and tended to have lower glucagon release than non-remissions. This indicates that, in remission, the residual islets maintain a secretion of insulin and glucagon of benefit for control of hepatic glucose production.