Proinsulin/C-peptide ratio, glucagon and remission in new-onset Type 1 diabetes mellitus in young adults


Dr Anna Schölin, Clinical Research Department 2 (Lab. 16), Entrance 70, 3 str, Uppsala University Hospital, S-751 85 Uppsala, Sweden. E-mail:


Diabet. Med. 28, 156–161 (2011)


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. We explored if efficiency of proinsulin processing is 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 and after 3, 6, 9, 12, 18, 24, 30 and 36 months. We studied 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. Non-remission also tended to be associated with higher glucagon values. Patients entering remission were more often men, had higher BMI at diagnosis, but did not differ at baseline with respect to islet antibody titres compared with patients with no remission.

Conclusions  Remissions after diagnosis of Type 1 diabetes were associated with lower proinsulin/C-peptide ratios, 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.