What enzymes are used to check for diabetes, specifically C-peptide (Connecting Peptide)?

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From the Guidelines

C-peptide testing is a crucial tool for assessing pancreatic beta cell function in diabetes management, and it requires specific enzymes like carboxypeptidase H and prohormone convertases (PC1/3 and PC2) to accurately measure C-peptide levels, as recommended by the most recent guidelines 1.

Importance of C-peptide Testing

C-peptide testing is a valuable tool for assessing pancreatic beta cell function in diabetes management. This blood test measures the amount of C-peptide, a protein fragment released when proinsulin is converted to insulin in the pancreas.

Enzymes Involved in C-peptide Measurement

The test requires specific enzymes like carboxypeptidase H and prohormone convertases (PC1/3 and PC2) to accurately measure C-peptide levels.

Clinical Application of C-peptide Testing

For diabetes evaluation, C-peptide testing is typically ordered alongside fasting glucose and hemoglobin A1c tests. Normal fasting C-peptide levels range from 0.5 to 2.0 ng/mL, with lower levels suggesting insufficient insulin production (common in type 1 diabetes) and higher levels potentially indicating insulin resistance (often seen in type 2 diabetes) 1.

Key Considerations

  • C-peptide measurement is particularly useful because, unlike insulin, it's not affected by injected insulin and provides a more accurate picture of the body's natural insulin production capacity.
  • The test requires fasting for 8-12 hours beforehand, and results are usually available within a few days.
  • C-peptide testing helps differentiate between diabetes types, assess residual beta cell function, and guide treatment decisions regarding insulin therapy, as outlined in the latest guidelines 1.

Guidelines and Recommendations

According to the most recent guidelines, a C-peptide test is only indicated in people receiving insulin treatment, and the results should be interpreted in the context of clinical presentation and other diagnostic tests 1. Some key points to consider 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, particularly in people with normal or low BMI or after long duration.
  • Results showing very low levels (e.g., <80 pmol/L [<0.24 ng/mL]) do not need to be repeated.
  • Where a person is insulin treated, C-peptide must be measured prior to insulin discontinuation to exclude severe insulin deficiency.
  • Do not test C-peptide within 2 weeks of a hyperglycemic emergency, as recommended by the guidelines 1.

From the Research

Enzymes Used to Check for Diabetes

  • C-peptide (Connecting Peptide) is co-secreted with insulin and is used to assess functional β-cell mass 2
  • C-peptide levels can be measured using various assays, including enzyme-linked immunosorbent assay (ELISA) and immunoradiometric assay (IRMA) 3

C-Peptide Measurement

  • C-peptide measurement can be helpful in clinical practice to differentiate between type 1 and type 2 diabetes 4, 5
  • C-peptide levels can be used to identify individuals at risk for or with type 1 diabetes with residual β-cell function 2
  • C-peptide measurement can also be used to distinguish type 2 diabetes from Latent Autoimmune Diabetes in Adults and late-onset type 1 diabetes 2, 4

Assays Used for C-Peptide Measurement

  • Ultrasensitive Mercodia enzyme-linked immunosorbent C-peptide assay (ELISA) 3
  • Beckman immunoradiometric assay (IRMA) for C-peptide 3
  • Time-resolved fluoroimmunoassay 6
  • High-sensitivity commercial ELISA assay 2

Clinical Utility of C-Peptide Measurement

  • C-peptide measurement can be used to assess endogenous insulin secretion in patients with diabetes 4, 5
  • C-peptide levels can be used to predict clinical partial remission during the first year of type 1 diabetes 4
  • C-peptide measurement can be used to assist in patient selection for islet cell transplantation and post-transplant monitoring 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Rapid Point-of-Care Test for Determination of C-Peptide Levels.

Journal of diabetes science and technology, 2022

Research

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

Pediatric endocrinology, diabetes, and metabolism, 2015

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

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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