Low levels of C-peptide may not be a sign of pancreatic β-cell death or apoptosis: New insight into pancreatic endocrine function and indications for metabolic surgery

Abstract

Type 2 diabetes mellitus (T2 DM) is characterized by a decline in insulin secretion and increased hepatic and peripheral insulin resistance, resulting in poor glycemic control and several long-term complications [1]. C-peptide fulfills an important function in the synthesis of insulin. After cleavage of proinsulin in pancreatic β-cells, the 31-aminoacid protein C-peptide is secreted into the portal circulation in equimolar concentrations with insulin. C-peptide has been used as a surrogate marker for β-cell function in patients with type 1 and 2 diabetes mellitus [2]. Indeed, recent studies aimed at the development of new T2 DM treatment modalities have monitored the levels of C-peptide and other markers [3] with the goal of identifying severe β-cell dysfunction. In addition, fasting C-peptide levels have been used as a criterion for determining inclusion or exclusion in several T2 DM treatment protocols [4–6]. Several clinical trials have arbitrarily adopted a C-peptide level of 1 ng/dL as the threshold for protocol inclusion [6–9]. Levels below this threshold were predicted to lead to poor outcomes in patients selected for surgical treatment. In clinical practice, fasting C-peptide levels have been used as a marker of β-cell function before bariatric/metabolic procedures in T2 DM patients, and also as a prognostic factor for predicting success after metabolic surgery. Higher levels of C-peptide have been shown to indicate better outcomes, leading to the suggestion that the selection of surgical technique should be based on fasting C-peptide levels [8,10]. Unlike latent autoimmune diabetes of adulthood, in which the diabetes results from a cellular-mediated autoimmune