Persistent C-peptide: what does it mean?

Abstract

Purpose of review: The assumption that patients with an extended duration of type 1 diabetes mellitus (T1D) do not retain residual functional β cells and endogenous insulin production has recently been challenged. The purpose to this review is to highlight some of the key emerging evidence supporting residual insulin and C-peptide secretion in long-standing T1D.

Recent findings: Recent investigations conducted in a group of type 1 diabetics of long-term duration, characterized clinically and histologically, provided solid evidence to suggest that pancreatic β cells are still present even after 50 years in a majority of these individuals. These residual β cells can secrete insulin in a physiologically regulated manner. Several published reports showed promising effects of glucagon-like peptide 1 (GLP-1) agonists on the glycemic control and residual C-peptide production in long-term T1D, although prospective studies are needed to rule out the potential long-term adverse effects of these drugs.

Summary: C-peptide is no longer considered an irrelevant by-product of insulin biosynthesis. In-depth basic and translational investigations aimed at understanding the molecular immunology and the pathophysiology are needed to elucidate the mechanisms underlying the residual insulin and C-peptide production in long-term T1D. This may shed light on to the regenerative capacity of β cells, the genetic susceptibility of the mechanisms of resistance to β-cell destruction, and possibly identifying new therapeutic strategies for T1D. Studies evaluating the long-term effects of insulin secretogogue agents along with immune intervention hold promise for their use in future clinical trials for long-term T1D.