What is the significance of urine C-peptide (Connecting Peptide) levels?

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Last updated: May 26, 2025View editorial policy

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From the Guidelines

Urine C-peptide is a valuable diagnostic test for distinguishing between type 1 and type 2 diabetes, assessing residual beta cell function, and investigating suspected cases of insulinoma or factitious hypoglycemia, as recommended by the most recent guidelines 1. The test measures the amount of C-peptide excreted in urine, providing insight into the body's insulin production. C-peptide is produced in equal amounts to insulin when proinsulin is cleaved in the pancreas, making it an excellent marker for endogenous insulin secretion.

Key Points to Consider

  • The test is particularly useful in ambiguous cases, such as individuals who have a type 2 phenotype but present in ketoacidosis 1.
  • For collection, a 24-hour urine sample is typically required, though some protocols may use shorter collection periods or spot samples with creatinine correction.
  • Normal values generally range from 20-120 μg/day, though reference ranges vary by laboratory 1.
  • Lower levels suggest decreased insulin production as seen in type 1 diabetes, while normal or elevated levels in a diabetic patient typically indicate type 2 diabetes with insulin resistance.
  • The test offers advantages over serum C-peptide measurement, including being less invasive, reflecting insulin production over time rather than at a single moment, and being unaffected by exogenous insulin administration.
  • However, results can be affected by kidney function since C-peptide is primarily excreted renally.

Clinical Applications

  • Distinguishing between type 1 and type 2 diabetes: C-peptide measurements may help distinguish type 1 from type 2 diabetes in ambiguous cases 1.
  • Assessing residual beta cell function: The test can help assess residual beta cell function in patients with diabetes.
  • Investigating suspected cases of insulinoma or factitious hypoglycemia: C-peptide measurements can aid in the diagnosis of insulinoma or factitious hypoglycemia 1.

From the Research

Urine C-peptide Measurement

  • Urine C-peptide measurement is a non-invasive alternative to blood measures of beta-cell function 2, 3
  • The urine C-peptide creatinine ratio is a stable and reproducible measure of endogenous C-peptide 4, 5
  • This measurement can be used to assess insulin secretion and classify diabetes subtype 2, 6

Clinical Utility

  • Urine C-peptide measurement can assist in the clinical management of patients with diabetes, particularly in distinguishing between Type 1 and Type 2 diabetes 2, 6
  • The measurement can also be used to assess the potential for insulin deficiency and guide treatment choices 4, 6
  • A stimulated urine C-peptide creatinine ratio cut-off of 0.3 nmol/mmol can identify subjects without clinically significant endogenous insulin secretion 4

Comparison to Serum C-peptide

  • Urine C-peptide creatinine ratio is well correlated with serum C-peptide 4, 5
  • The correlation between urine and serum C-peptide is similar in patients with and without moderate renal impairment 5
  • Urine C-peptide creatinine ratio may be a more practical alternative to serum C-peptide measurement due to its stability and ease of collection 3, 4

Potential Uses

  • Urine C-peptide measurement may be used to guide diabetes diagnosis and management 6
  • The measurement may also be used to assess the likelihood of response to individual therapies and predict microvascular and macrovascular complications 6

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

Detection of C-Peptide in Urine as a Measure of Ongoing Beta Cell Function.

Methods in molecular biology (Clifton, N.J.), 2016

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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