What is C-peptide (Connecting peptide)?

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Last updated: April 4, 2025View editorial policy

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From the Guidelines

C-peptide is a protein fragment produced during insulin production in the pancreas, and measuring it in the blood provides valuable information about how much insulin a person's pancreas is producing naturally, which is crucial for distinguishing between type 1 and type 2 diabetes, evaluating insulin production in diabetic patients, and determining if high insulin levels are due to excessive pancreatic production or external insulin administration 1.

Key Points

  • C-peptide is a byproduct of insulin production, released into the bloodstream in equal amounts to insulin.
  • Measuring C-peptide levels helps determine the pancreas's natural insulin production, which is essential for diagnosing and managing diabetes.
  • C-peptide testing is particularly useful in ambiguous cases, such as distinguishing between type 1 and type 2 diabetes, especially when clinical presentation and subsequent course are unclear 1.
  • Normal C-peptide levels indicate proper insulin production, while low levels may suggest type 1 diabetes, and high levels can indicate insulin resistance as seen in type 2 diabetes.

Clinical Applications

  • C-peptide measurement can aid in diagnosing type 1 diabetes, especially in adults with suspected type 1 diabetes, as outlined in the flowchart for investigation of suspected type 1 diabetes in newly diagnosed adults 1.
  • C-peptide testing is recommended in people receiving insulin treatment, with a random sample or formal C-peptide stimulation test, to determine the level of insulin production and guide treatment decisions 1.
  • C-peptide levels can also help evaluate insulin production in diabetic patients and determine if high insulin levels are due to excessive pancreatic production or external insulin administration.

Evidence-Based Recommendations

  • The most recent and highest-quality study recommends using C-peptide measurements to distinguish between type 1 and type 2 diabetes in ambiguous cases, with a level of evidence rated as moderate 1.
  • The American Diabetes Association recommends measuring C-peptide levels in people with suspected type 1 diabetes, especially in adults, to guide diagnosis and treatment decisions 1.

From the Research

Definition and Function of C-Peptide

  • C-peptide is a protein that joins insulin's α and B chains in the proinsulin molecule 2.
  • It is cleaved from proinsulin and secreted in an equimolar concentration to insulin from the β cells 2.
  • C-peptide may be used as a marker of endogenous insulin production and a reflection of β-cell function 2.

Biological Properties and Effects

  • C-peptide has important biological properties and displays beneficial effects in many tissues affected by diabetic complications 3.
  • It has been shown to increase peripheral blood flow and protect from renal damage 3.
  • C-peptide interacts with cellular membranes at unidentified sites distinctive of the insulin family of receptors, and signals to multiple targets known to play a role in diabetes and diabetic complications 3.

Clinical Applications and Utility

  • C-peptide may lend itself to clinical applications, particularly in the management of type 1 and type 2 diabetes 3, 4, 5.
  • Measurement of endogenous insulin secretion using fasting C-peptide is recommended as a diagnostic criterion for type 1 diabetes 5.
  • C-peptide levels may be used to predict future outcomes in type 2 diabetes and to indicate the need for insulin therapy 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Exploring the potential role of C-peptide in type 2 diabetes management.

Diabetic medicine : a journal of the British Diabetic Association, 2025

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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