The Clinical Significance of C-peptide Measurement in Diabetes
C-peptide measurement is essential for distinguishing between diabetes types in ambiguous cases, assessing residual beta cell function, and guiding appropriate treatment decisions in patients with diabetes. 1
What is C-peptide?
- C-peptide is produced in equimolar amounts to insulin and reflects endogenous insulin secretion more accurately than insulin measurement since it is not extracted by the liver 2
- It serves as a reliable marker of pancreatic beta cell function and insulin production capacity 3
Key Clinical Applications of C-peptide Testing
Diabetes Classification
- C-peptide helps differentiate between type 1 and type 2 diabetes in ambiguous cases, such as individuals with type 2 phenotype presenting with ketoacidosis 4, 1
- Very low C-peptide values (<200 pmol/L) are consistent with type 1 diabetes 1
- C-peptide values between 200-600 pmol/L may indicate type 1 diabetes, maturity-onset diabetes of the young (MODY), or insulin-treated type 2 diabetes 1
- C-peptide values >600 pmol/L suggest type 2 diabetes 1
Identifying Insulin Deficiency
- Low C-peptide (<0.4 nmol/L) indicates absolute insulin deficiency, as seen in checkpoint inhibitor-associated diabetes mellitus (CIADM) 4
- Patients with absolute insulin deficiency require insulin therapy for survival 1
- C-peptide can identify patients with latent autoimmune diabetes in adults (LADA), who initially present as type 2 diabetes but have positive pancreatic autoantibodies and lower C-peptide levels 5
Treatment Guidance
- C-peptide levels guide treatment decisions - patients with robust C-peptide levels may respond to oral agents, while those with low levels require insulin therapy 4
- In type 3c diabetes (pancreatogenic), management varies based on C-peptide levels - robust levels suggest oral agents may be effective, while low levels indicate insulin therapy is necessary 4
- C-peptide measurement is sometimes required by insurance payers for coverage of insulin pump therapy 4
Optimal Testing Methods
- A random C-peptide sample within 5 hours of eating can replace formal stimulation tests for diabetes classification 1
- For insurance coverage of insulin pump therapy, fasting C-peptide should be measured when simultaneous fasting plasma glucose is ≤220 mg/dL 4
- C-peptide testing should not be performed within 2 weeks of a hyperglycemic emergency 1
- For insulin-treated patients, C-peptide should be measured prior to insulin discontinuation to exclude severe insulin deficiency 1
Additional Clinical Applications
- C-peptide is essential in investigating nondiabetic hypoglycemia to rule out hypoglycemia due to surreptitious insulin administration 4
- The postprandial C-peptide to glucose ratio better reflects maximum beta cell secretory capacity compared to fasting measurements 2
- C-peptide can assist in patient selection for islet cell transplantation and post-transplant monitoring 5
- Point-of-care C-peptide testing is now available, allowing for rapid assessment with fingerstick samples 6
Clinical Pitfalls and Considerations
- C-peptide results should be interpreted in context with glucose levels - if glucose is <4 mmol/L (<70 mg/dL), consider repeating the test 1
- C-peptide measurement may not be clinically necessary in all cases, as response to drug therapy can provide useful information 4
- High uncorrected fasting C-peptide in the presence of hyperglycemia may suggest insulin resistance 5
- C-peptide utility is greatest 3-5 years from diagnosis when persistence of substantial insulin secretion suggests type 2 or monogenic diabetes 7