C-Peptide and Vascular Complications in Type 2 Diabetic Subjects

Corresponding author: Seok Man Son Department of Internal Medicine, Pusan National University School of Medicine, and Diabetes Center and Endocrine Clinic, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup,Yangsan 626-770, Korea E-mail: [email protected] C-peptide is a small peptide comprised of 31 amino acids, with a short half-life of approximately 30 minutes. It was first identified by Steiner et al. [1] as a by-product of proinsulin and its main role is in assisting in the arrangement of the correct structure of insulin. Proinsulin consists of an A chain, connecting peptide (C-peptide), and B chain. C-peptide has a central glycine-rich region that allows the correct positioning of the A and B chains for insulin to achieve its tertiary structure [1]. It is secreted into the bloodstream in equimolar amounts together with insulin in response to glucose stimulation. C-peptide has been long considered an inactive peptide; however, over the last two decades, numerous studies have revealed that Cpeptide displays a physiological role in different cell types [2,3]. The C-terminal pentapeptide of C-peptide obtains the full activity of intact C-peptide in stimulating Na/K-ATPase [4]. The amino acid sequence of C-peptide can vary by species, although it has several conserved sequences, such as its N-terminal acidic region, glycine-rich central segment, and C-terminal pentapeptide [5]. Moreover, evidence indicates that Cpeptide is not merely an inactive by-product of insulin biosynthesis but also a hormonally-active peptide itself [3,4]. The delta C-peptide value, which postprandial serum Cpeptide levels minus fasting serum C-peptide levels, correlates closely with glucagon-stimulated C-peptide concentrations and decreases progressively as diabetic duration increases [5,6]. Approximately 5% of pancreatic C-peptide is excreted in the urine [7]. Twenty-four-hour urine collections have been shown to correlate well with serum C-peptide measurements; however, they are cumbersome and prone to incomplete urine collection [8]. Post-meal urine C-peptide creatinine ratios have been shown to have similar sensitivity and specificity to glucagon-stimulated serum C-peptide values in classifying diabetes by insulin requirement, but have otherwise been studied little [9]. Urine C-peptide collected in boric acid has recently been shown to be stable for 72 hours at room temperature with no decline in C-peptide levels over this time [10]. The urine Cpeptide creatinine ratio may thus have the potential to provide a simple practical measurement of insulin secretion for use in routine clinical practice. The Diabetes Control and Complications Trial showed that the residual secretion of serum C-peptide decreased the incidence of diabetic retinopathy and nephropathy in subjects with type 1 diabetes [11]. In a recent cross sectional study, 471 type 1 diabetic patients were followed from 1994 to 2004 [12]. Those subjects with the lowest fasting C-peptide levels were found to have the highest rate of microvascular complications. No association was observed between C-peptide levels and macrovascular complications. There is increasing evidence that, in type 1 diabetic patients, the conservation of residual beta cell function slows microvascular complications, by improving blood glucose control and by the preservation of residual C-peptide secretion. The effects of C-peptide include a positive influence on longterm complications in type 1 diabetic patients. Some groups Editorial Complications