When is C-peptide (Connecting Peptide) ordered in diabetes?

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Last updated: May 20, 2025View editorial policy

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From the Guidelines

C-peptide testing is typically ordered in diabetes to distinguish between type 1 and type 2 diabetes, assess beta cell function, and evaluate for insulin resistance, particularly in cases where the diagnosis is unclear or when considering insulin therapy in type 2 diabetes, as recommended by the most recent guidelines 1.

Key Indications for C-peptide Testing

  • Distinguishing between type 1 and type 2 diabetes in adults with ambiguous presentation
  • Suspected latent autoimmune diabetes in adults (LADA)
  • Considering insulin therapy in type 2 diabetes
  • Evaluating suspected factitious hypoglycemia or insulin overdose

Interpretation of C-peptide Levels

  • Low C-peptide levels suggest type 1 diabetes or advanced type 2 diabetes with significant beta cell failure
  • Normal or high levels typically indicate type 2 diabetes with insulin resistance

Clinical Utility

  • C-peptide measurement can help monitor beta cell function over time in patients with type 2 diabetes to guide treatment decisions regarding insulin initiation
  • It is an excellent marker of endogenous insulin production, as it is produced in equal amounts to insulin when proinsulin is cleaved

Recent Guidelines

  • The 2024 guidelines for the diagnosis and classification of diabetes recommend C-peptide measurements to help distinguish type 1 from type 2 diabetes in ambiguous cases 1
  • The guidelines also suggest that C-peptide testing 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

From the Research

C-Peptide Testing in Diabetes

  • C-peptide is a measure of pancreatic beta cell function and is produced in equimolar amounts to endogenous insulin 2.
  • It is used to guide diabetes diagnosis and management, with levels associated with diabetes type and duration of disease 2.
  • A c-peptide level of less than 0.2 nmol/l is associated with a diagnosis of type 1 diabetes mellitus (T1DM) 2.

Clinical Utility of C-Peptide Measurement

  • C-peptide measurement has a potential role in type 2 diabetes management, with levels correlating with microvascular and macrovascular complications and future use of insulin therapy 3, 4.
  • Assessing C-peptide in patients with insulin-treated type 2 diabetes can help evaluate residual β-cell function and guide treatment decisions 4.
  • C-peptide levels can predict the adoption of a basal-bolus treatment in insulin-treated patients with type 2 diabetes 4.

Limitations and Areas of Uncertainty

  • 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.
  • Further research is needed to clarify the value of C-peptide testing in understanding and managing type 2 diabetes and to highlight areas where further research is needed 3, 5.

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

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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