C-peptide Testing Should Be Performed in a Fasting State
C-peptide measurements should be performed in a fasting state when used to distinguish between diabetes types or assess residual beta cell function. 1, 2
Rationale for Fasting C-peptide Testing
The American Diabetes Association (ADA) guidelines specifically mention that when C-peptide testing is required for coverage of insulin pump therapy, it should be measured in a fasting state when the simultaneous fasting plasma glucose is <220 mg/dL 1. This recommendation is based on the need for standardized conditions to accurately assess endogenous insulin secretion.
Fasting conditions provide several important advantages:
- Standardized measurement conditions - Eliminates variability from recent food intake
- Better correlation with beta cell function - Provides baseline assessment of insulin secretory capacity
- More reliable comparison to reference ranges - Reference ranges are typically established using fasting samples
Clinical Applications of C-peptide Testing
C-peptide testing has several important clinical applications:
- Differentiating diabetes types - Particularly useful in ambiguous cases, such as individuals with type 2 phenotype who present with ketoacidosis 1, 2
- Assessing residual beta cell function - Most useful when measured 3-5 years after diagnosis 2, 3
- Determining insulin requirements - Low levels suggest absolute insulin dependence 2
Interpretation of C-peptide Results
The American Diabetes Association suggests the following interpretation framework 2:
| C-peptide level | Suggested diagnosis |
|---|---|
| <0.6 ng/mL (<200 pmol/L) | Type 1 diabetes, requiring insulin therapy |
| 0.6-1.8 ng/mL (200-600 pmol/L) | Indeterminate, may require additional testing |
| >1.8 ng/mL (>600 pmol/L) | Type 2 diabetes, consider non-insulin or combination therapies |
Important Considerations and Caveats
- Timing matters - C-peptide should not be measured within 2 weeks after a hyperglycemic emergency 2
- Concurrent glucose measurement - Always measure glucose simultaneously with C-peptide 2, 4
- Limitations - There is a range of C-peptide concentrations (0.13-0.36 nmol/L) that may not clearly discriminate between type 1 and type 2 diabetes 4
- Alternative approaches - While fasting C-peptide is standard, some research suggests that postprandial C-peptide to glucose ratio may better reflect maximum beta cell secretory capacity in certain situations 5, 6
When to Order C-peptide Testing
C-peptide testing is most useful in:
- Atypical diabetes presentations
- Adults with suspected late-onset type 1 diabetes
- Evaluating possible monogenic diabetes (MODY)
- When required by payers for coverage of insulin pump therapy
The ADA does not recommend routine testing of insulin or C-peptide in most people with diabetes, as these assays are primarily useful for research purposes 1.