What is the expected C-peptide (connecting peptide) level in a patient with diabetes type 1?

Expected C-Peptide Levels in Type 1 Diabetes

In established type 1 diabetes, C-peptide levels are expected to be low or undetectable, typically <200 pmol/L (<0.6 ng/mL), with many patients having levels <80 pmol/L (<0.24 ng/mL), indicating severe insulin deficiency and absolute dependence on exogenous insulin. 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): Consistent with type 1 diabetes 1, 2
• C-peptide <80 pmol/L (<0.24 ng/mL): Indicates absolute insulin deficiency and definitively confirms severe beta cell loss; does not require repeat testing 1, 2
• C-peptide 200-600 pmol/L (0.6-1.8 ng/mL): May indicate type 1 diabetes, MODY, or long-standing insulin-treated type 2 diabetes 1, 2

Pathophysiology and Disease Progression

The rate of beta cell destruction in type 1 diabetes is variable, being rapid in children and slower in adults. 3

• In late-stage type 1 diabetes, there is little or no insulin secretion, manifested by low or undetectable plasma C-peptide levels 3
• C-peptide levels decline for decades after diagnosis, with the rate of decline significantly related to age of onset 4
• Even very low levels of persistent C-peptide (>10 pmol/l) can be detected in some patients years after diagnosis and may have clinical significance 4

Clinical Significance of Residual C-Peptide

While most patients with established type 1 diabetes have very low C-peptide, some retain minimal residual beta cell function:

• Patients with C-peptide >10 pmol/L show protection from diabetic complications including nephropathy, neuropathy, foot ulcers, and retinopathy 4
• Higher residual C-peptide (>400 pmol/L) is associated with lower rates of hypoglycemia, better glycemic control, and lower insulin requirements 5, 6
• The lowest C-peptide levels are associated with severe hypoglycemia compared to mild or moderate hypoglycemia 4

Testing Considerations and Timing

When measuring C-peptide to confirm type 1 diabetes diagnosis:

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

Integration with Autoantibody Testing

Plasma glucose rather than A1C should be used to diagnose acute onset of type 1 diabetes in individuals with symptoms of hyperglycemia. 3

• Autoimmune markers include islet cell autoantibodies, GAD65, insulin antibodies, IA-2, IA-2b, and ZnT8 3
• If antibody-positive, the diagnosis is type 1 diabetes regardless of C-peptide level, though C-peptide should still be low 1
• Approximately 5-10% of adults with type 1 diabetes are antibody-negative, making C-peptide measurement essential in this subset 1

Common Pitfalls to Avoid

• Misdiagnosis occurs in 40% of adults with new type 1 diabetes, often misclassified as type 2 diabetes 1
• C-peptide testing is only indicated in insulin-treated patients for classification purposes 1
• Very low C-peptide levels (<80 pmol/L) definitively indicate severe insulin deficiency and do not need repeat testing 1, 2
• In insulin-treated patients, C-peptide must be measured prior to insulin discontinuation to exclude severe insulin deficiency 2