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      The clinical utility of C-peptide measurement in the care of patients with diabetes

      review-article
      1 , 2 , 1 , 2
      Diabetic Medicine
      Blackwell Publishing Ltd

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          Abstract

          C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes. Measurement of insulin secretion using C-peptide can be helpful in clinical practice: differences in insulin secretion are fundamental to the different treatment requirements of Type 1 and Type 2 diabetes. This article reviews the use of C-peptide measurement in the clinical management of patients with diabetes, including the interpretation and choice of C-peptide test and its use to assist diabetes classification and choice of treatment. We provide recommendations for where C-peptide should be used, choice of test and interpretation of results. With the rising incidence of Type 2 diabetes in younger patients, the discovery of monogenic diabetes and development of new therapies aimed at preserving insulin secretion, the direct measurement of insulin secretion may be increasingly important. Advances in assays have made C-peptide measurement both more reliable and inexpensive. In addition, recent work has demonstrated that C-peptide is more stable in blood than previously suggested or can be reliably measured on a spot urine sample (urine C-peptide:creatinine ratio), facilitating measurement in routine clinical practice. The key current clinical role of C-peptide is to assist classification and management of insulin-treated patients. Utility is greatest after 3–5 years from diagnosis when persistence of substantial insulin secretion suggests Type 2 or monogenic diabetes. Absent C-peptide at any time confirms absolute insulin requirement and the appropriateness of Type 1 diabetes management strategies regardless of apparent aetiology.

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          Most cited references126

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          Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.

          Patients with permanent neonatal diabetes usually present within the first three months of life and require insulin treatment. In most, the cause is unknown. Because ATP-sensitive potassium (K(ATP)) channels mediate glucose-stimulated insulin secretion from the pancreatic beta cells, we hypothesized that activating mutations in the gene encoding the Kir6.2 subunit of this channel (KCNJ11) cause neonatal diabetes. We sequenced the KCNJ11 gene in 29 patients with permanent neonatal diabetes. The insulin secretory response to intravenous glucagon, glucose, and the sulfonylurea tolbutamide was assessed in patients who had mutations in the gene. Six novel, heterozygous missense mutations were identified in 10 of the 29 patients. In two patients the diabetes was familial, and in eight it arose from a spontaneous mutation. Their neonatal diabetes was characterized by ketoacidosis or marked hyperglycemia and was treated with insulin. Patients did not secrete insulin in response to glucose or glucagon but did secrete insulin in response to tolbutamide. Four of the patients also had severe developmental delay and muscle weakness; three of them also had epilepsy and mild dysmorphic features. When the most common mutation in Kir6.2 was coexpressed with sulfonylurea receptor 1 in Xenopus laevis oocytes, the ability of ATP to block mutant K(ATP) channels was greatly reduced. Heterozygous activating mutations in the gene encoding Kir6.2 cause permanent neonatal diabetes and may also be associated with developmental delay, muscle weakness, and epilepsy. Identification of the genetic cause of permanent neonatal diabetes may facilitate the treatment of this disease with sulfonylureas. Copyright 2004 Massachusetts Medical Society
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            Improvement in Outcomes of Clinical Islet Transplantation: 1999–2010

            OBJECTIVE To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010. RESEARCH DESIGN AND METHODS A total of 677 islet transplant-alone or islet-after-kidney recipients with type 1 diabetes in the CITR were analyzed for five primary efficacy outcomes and overall safety to identify any differences by early (1999–2002), mid (2003–2006), or recent (2007–2010) transplant era based on annual follow-up to 5 years. RESULTS Insulin independence at 3 years after transplant improved from 27% in the early era (1999–2002, n = 214) to 37% in the mid (2003–2006, n = 255) and to 44% in the most recent era (2007–2010, n = 208; P = 0.006 for years-by-era; P = 0.01 for era alone). C-peptide ≥0.3 ng/mL, indicative of islet graft function, was retained longer in the most recent era (P < 0.001). Reduction of HbA1c and resolution of severe hypoglycemia exhibited enduring long-term effects. Fasting blood glucose stabilization also showed improvements in the most recent era. There were also modest reductions in the occurrence of adverse events. The islet reinfusion rate was lower: 48% by 1 year in 2007–2010 vs. 60–65% in 1999–2006 (P < 0.01). Recipients that ever achieved insulin-independence experienced longer duration of islet graft function (P < 0.001). CONCLUSIONS The CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007–2010 compared with those in 1999–2006, with fewer islet infusions and adverse events per recipient.
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              Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial.

              In patients with type 1 diabetes, measurement of connecting peptide (C-peptide), cosecreted with insulin from the islets of Langerhans, permits estimation of remaining beta-cell secretion of insulin. In this retrospective analysis to distinguish the incremental benefits of residual beta-cell activity in type 1 diabetes, stimulated (90 min following ingestion of a mixed meal) C-peptide levels at entry in the Diabetes Control and Complications Trial (DCCT) were related to measures of diabetic retinopathy and nephropathy and to incidents of severe hypoglycemia. Based on the analytical sensitivity of the assay (0.03 nmol/l) and study entry criteria, the DCCT subjects were divided into four groups of stimulated C-peptide responses: 40 mg/24 h once and repeated at the next annual visit). There were also differences in severe hypoglycemia across C-peptide levels in both treatment groups. In the intensively treated cohort there were essentially identical prevalences of severe hypoglycemia ( approximately 65% of participants) in the first three groups; however, those subjects with mixed-meal stimulated C-peptide level >0.20 nmol/l for at least baseline and the first annual visit in the DCCT experienced a reduced prevalence of approximately 30%. Therefore, even modest levels of beta-cell activity at entry in the DCCT were associated with reduced incidences of retinopathy and nephropathy. Also, continuing C-peptide (insulin) secretion is important in avoiding hypoglycemia (the major complication of intensive diabetic therapy).

                Author and article information

                Journal
                Diabet Med
                Diabet. Med
                dme
                Diabetic Medicine
                Blackwell Publishing Ltd
                0742-3071
                1464-5491
                July 2013
                23 June 2013
                : 30
                : 7
                : 803-817
                Affiliations
                [1 ]NIHR Exeter Clinical Research Facility, University of Exeter Medical School Exeter, UK
                [2 ]Diabetes and Endocrinology, Royal Devon and Exeter NHS Foundation Trust Exeter, UK
                Author notes
                Correspondence to: Angus Jones. E-mail: angus.jones@ 123456pms.ac.uk
                Article
                10.1111/dme.12159
                3748788
                23413806
                fa553e8e-97c9-4605-9f5e-b2d16601772f
                © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 14 February 2013
                Categories
                Review Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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