Probing the Meaning of Persistent Propeptide Release in Type 1 Diabetes.

Abstract

Type 1 diabetes is well recognized to be immune mediated, resulting in destruction of β-cells. That this eradication is not always complete was evident in an early report from the Diabetes Control and Complications Trial (DCCT) showing that 11% of adult participants with type 1 diabetes for more than 5 years had measurable C-peptide in the fasting state and following mixed-meal stimulation, while no adolescents had evidence of such (1). Further, in participants with measurable C-peptide responses, C-peptide declined in all after a year of randomized therapy, with this decline being less in those who received intensive insulin therapy. Subsequently, it was shown in adolescents that 2 weeks of intensive insulin therapy, compared with conventional therapy, resulted in improved β-cell function a year later along with superior glucose control (2). In addition to C-peptide, proinsulin has also been shown to be circulating in individuals with type 1 diabetes at the time of diagnosis and to be still measurable 30 months later (3,4). Thus, there is long-standing evidence that at the time of diagnosis and subsequently, individuals with type 1 diabetes have β-cells still capable of synthesizing proinsulin, and many can process it to C-peptide and insulin. In the current issue of Diabetes Care , Sims et al. (5) report longitudinal findings on proinsulin secretion in type 1 diabetes using a large number of samples from the T1D Exchange. They divided their subjects into three groups based on stimulated C-peptide responses to a mixed meal. We have categorized these groups as having absent, intermediate, and high C-peptide responses, although the latter are a great deal lower than what is observed in healthy people. Individuals in the absent group had C-peptide responses that were below the reliable lower detection limit of the assay, and they were not studied further. These …