Why measure C-peptide (Connecting Peptide) levels?

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Last updated: March 29, 2025View editorial policy

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From the Guidelines

C-peptide should be pulled to assess insulin production by the pancreas, helping to distinguish between type 1 and type 2 diabetes, especially in ambiguous cases or when the clinical presentation is unclear 1.

Importance of C-peptide Testing

C-peptide testing is crucial in determining the type of diabetes, as it helps to differentiate between type 1 and type 2 diabetes.

  • Low C-peptide levels indicate decreased insulin production, typical in type 1 diabetes where autoimmune destruction of beta cells occurs.
  • Normal or high levels suggest insulin resistance as seen in type 2 diabetes, where the body produces insulin but cannot use it effectively.

Clinical Applications

C-peptide testing has several clinical applications, including:

  • Diagnosing insulinoma (insulin-producing tumors)
  • Monitoring beta cell function after pancreas transplantation
  • Evaluating hypoglycemia causes

Testing Procedure

When testing C-peptide, blood is drawn after fasting or following a meal stimulus.

  • A random sample (with concurrent glucose) within 5 h of eating can replace a formal C-peptide stimulation test in the context of classification.
  • If the result is >600 pmol/L (>1.8 ng/mL), the circumstances of testing do not matter.
  • If the result is <600 pmol/L (<1.8 ng/mL) and the concurrent glucose is <4 mmol/L (<70 mg/dL) or the person may have been fasting, consider repeating the test.

Reliability of C-peptide

C-peptide is a more reliable marker of endogenous insulin production, especially in patients taking insulin medications, as it is not significantly affected by liver metabolism 1.

Recent Guidelines

According to the latest guidelines, C-peptide testing is recommended in people receiving insulin treatment, and it should be measured prior to insulin discontinuation to exclude severe insulin deficiency 1.

Key Considerations

Key considerations when interpreting C-peptide results include:

  • C-peptide values 200-600 pmol/L (0.6-1.8 ng/mL) are usually consistent with type 1 diabetes or maturity-onset diabetes of the young but may occur in insulin-treated type 2 diabetes.
  • Results showing very low levels (e.g., <80 pmol/L [<0.24 ng/mL]) do not need to be repeated.

From the Research

Importance of C-Peptide Measurement

  • C-peptide is a valuable measure of pancreatic beta cell function, produced in equimolar amounts to endogenous insulin but excreted at a more constant rate over a longer time 2.
  • Measuring C-peptide levels can help guide diabetes diagnosis and management, as well as predict the likelihood of microvascular and macrovascular complications and future use of insulin therapy 2, 3.

Clinical Applications of C-Peptide Measurement

  • C-peptide levels can be used to classify diabetes type, with a level of less than 0.2 nmol/l associated with a diagnosis of type 1 diabetes mellitus (T1DM) 2, 4.
  • In children and adolescents, a random C-peptide measurement at diagnosis can help classify diabetes, with higher levels associated with type 2 diabetes (T2D) and maturity onset diabetes of the young (MODY) 4.
  • C-peptide measurement can also be used to evaluate beta-cell function in patients with insulin-treated type 2 diabetes, with lower levels associated with longer disease duration and higher fasting glucose levels 5.

Methods of C-Peptide Measurement

  • C-peptide levels can be measured using urinary and unstimulated and stimulated serum sampling, as well as modern assays that detect levels of C-peptide 2.
  • Dried blood spots (DBS) collected at home can also be used to measure C-peptide levels, with strong correlation between DBS and plasma C-peptide levels 6.
  • Frequent monitoring of C-peptide levels using DBS can provide valuable information on beta-cell function and glucose responsiveness over time 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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