What is the normal fasting C‑peptide range in individuals with type 1 diabetes mellitus?

C-Peptide Levels in Type 1 Diabetes

In individuals with type 1 diabetes, C-peptide levels are typically <200 pmol/L (<0.6 ng/mL), with very low levels <80 pmol/L (<0.24 ng/mL) indicating absolute insulin deficiency and severe beta-cell destruction. 1, 2

Diagnostic Thresholds for Type 1 Diabetes

The American Diabetes Association provides clear cutoff values for interpreting C-peptide in the context of diabetes classification:

• C-peptide <200 pmol/L (<0.6 ng/mL) is consistent with type 1 diabetes 1, 2
• C-peptide <80 pmol/L (<0.24 ng/mL) strongly indicates absolute insulin deficiency and is diagnostic of type 1 diabetes, requiring insulin therapy for survival 1
• C-peptide 200-600 pmol/L (0.6-1.8 ng/mL) may indicate type 1 diabetes, MODY, or insulin-treated type 2 diabetes of long duration 1, 2

Clinical Context and Interpretation

There is no "normal range" for C-peptide in established type 1 diabetes—the levels are abnormally low or absent, reflecting progressive beta-cell destruction. The degree of C-peptide preservation has important clinical implications:

• Very low levels (<0.2 nmol/L or <0.24 ng/mL) definitively indicate severe insulin deficiency and do not require repeat testing 1, 3
• Approximately 5-10% of adults with type 1 diabetes are antibody-negative, making C-peptide measurement essential for classification in this subset 2
• Residual C-peptide may persist for years after diagnosis in some patients, though levels remain well below those seen in type 2 diabetes 4

Testing Considerations

When measuring C-peptide in patients with suspected or established type 1 diabetes:

• Do not test within 2 weeks of a hyperglycemic emergency (diabetic ketoacidosis), as results will be unreliable 1
• A random C-peptide sample within 5 hours of eating can replace formal stimulation testing for diabetes classification 1
• For fasting C-peptide measurement, ensure simultaneous fasting plasma glucose is ≤220 mg/dL (≤12.2 mmol/L) 1
• If concurrent glucose is <70 mg/dL (<4 mmol/L) when C-peptide is measured, consider repeating the test 1

Clinical Significance of Residual C-Peptide

While most patients with established type 1 diabetes have very low or undetectable C-peptide:

• Higher residual C-peptide levels (even within the low range) are associated with better glycemic control and more time in target glucose range 4
• Beta-cell responsiveness to hyperglycemia and alpha-cell responsiveness to hypoglycemia are only observed at relatively higher levels of residual C-peptide 4
• Younger age at diagnosis, lower BMI, and more severe presentation (such as diabetic ketoacidosis) predict more rapid decline in C-peptide levels over time 5

Common Pitfalls to Avoid

• Misdiagnosis occurs in 40% of adults with new type 1 diabetes, often misclassified as type 2 diabetes 2
• C-peptide concentrations of 0.13-0.36 nmol/L (130-360 pmol/L) fall in an intermediate zone that may not clearly discriminate between diabetes types 6
• Different C-peptide assays yield inconsistent results, especially at low concentrations—assay specifications should be documented 7
• In insulin-treated patients, C-peptide must be measured prior to insulin discontinuation to exclude severe insulin deficiency 1