What is the role of C-peptide (Connecting peptide) in diagnosing diabetes?

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From the Guidelines

C-peptide testing is a valuable tool for distinguishing between type 1 and type 2 diabetes, particularly in cases where the diagnosis is unclear, as stated in the most recent guidelines 1.

Key Points to Consider

  • The test measures endogenous insulin production, which is essential for determining the type of diabetes and guiding treatment decisions.
  • Normal C-peptide levels typically range from 0.5-2.0 ng/mL, with low levels indicating type 1 diabetes and normal to high levels suggesting type 2 diabetes.
  • C-peptide testing is particularly useful when evaluating for insulin resistance or monitoring beta cell function over time.
  • The test requires a blood sample and may be combined with glucose testing, with results interpreted in the context of other clinical information, such as kidney function, medications, and other factors.
  • According to the latest guidelines, a C-peptide test is only indicated in people receiving insulin treatment, and a random sample with concurrent glucose can replace a formal C-peptide stimulation test in the context of classification 1.

Clinical Application

  • C-peptide levels can help guide treatment selection, as patients with very low C-peptide may require insulin therapy, while those with adequate levels might respond to oral medications.
  • In cases where the diagnosis is unclear, C-peptide testing can aid in differentiating between type 1 and type 2 diabetes, as recommended by the guidelines 1.
  • Healthcare providers should consider C-peptide testing as part of a comprehensive diagnostic approach, taking into account clinical presentation, medical history, and other relevant factors.
  • The latest guidelines emphasize the importance of careful monitoring and education for individuals with possible type 1 diabetes who are not treated with insulin, to rapidly initiate insulin therapy in the event of glycemic deterioration 1.

From the Research

C-peptide Measurement in Diabetes

  • C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes 2, 3, 4, 5, 6
  • Measurement of insulin secretion using C-peptide can be helpful in clinical practice, particularly in differentiating between type 1 and type 2 diabetes 2, 3, 4, 5, 6

Clinical Utility of C-peptide Measurement

  • C-peptide measurement can assist in the classification and management of insulin-treated patients, with utility greatest after 3-5 years from diagnosis 2
  • A low basal C-peptide level can be considered a criterion for transferring patients initially diagnosed with type 2 diabetes to the type 1 diabetes group 3
  • C-peptide level may be a good predictor of clinical partial remission during the first year of type 1 diabetes 3
  • C-peptide measurement can also be used to assist in patient selection for islet cell transplantation and post-transplant monitoring 3

Methods of C-peptide Estimation

  • Methods of estimation include urinary and unstimulated and stimulated serum sampling 4
  • Modern assays detect levels of C-peptide that can be used to guide diabetes diagnosis and management 4
  • Glucagon stimulation C-peptide testing is recommended due to its balance of sensitivity and practicality 4

C-peptide Levels and Diabetes Type

  • A C-peptide level of less than 0.2 nmol/l is associated with a diagnosis of type 1 diabetes mellitus (T1DM) 4
  • C-peptide level may correlate with microvascular and macrovascular complications and future use of insulin therapy, as well as likely response to other individual therapies 4
  • C-peptide measurement can help reclassify diabetes types and provide more appropriate disease management 6

Limitations and Future Research

  • The lack of robust evidence about the clinical utility of C-peptide measurement in type 2 diabetes limits its use in such cases 5
  • Problems remain in the standardization of the assay for C-peptide, raising concerns about comparability of measurements between different laboratories 5
  • Future research is needed to address current limitations and areas of uncertainties in the use of C-peptide measurement in diabetes management 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

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

Diabetic medicine : a journal of the British Diabetic Association, 2013

Research

[The clinical utility of C-peptide measurement in diabetology].

Pediatric endocrinology, diabetes, and metabolism, 2015

Research

A Practical Review of C-Peptide Testing in Diabetes.

Diabetes therapy : research, treatment and education of diabetes and related disorders, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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