C-peptide
At a glance
Section titled “At a glance”- C-peptide is a marker for endogenous insulin production (exogenous insulin contains no C-peptide)
- Always interpret together with glucose, clinical picture, medication, and renal function
- More stable than insulin as a measure of beta-cell secretion
- With reduced kidney function, C-peptide may be falsely elevated
- Fasting measurement and tracking trends often works excellently in practice
Relationship with insulin
Section titled “Relationship with insulin”Beta cells secrete insulin and C-peptide in equal molar amounts (equimolar). Therefore, C-peptide is a marker for endogenous secretion — exogenous insulin contains no C-peptide.
| Characteristic | Insulin | C-peptide |
|---|---|---|
| Clearance | Variable (first-pass liver) | Mainly renal |
| Half-life | Short | Longer |
| Stability | More variable | More stable as measure of secretion |
Measurement
Section titled “Measurement”- Fasting C-peptide is useful as a baseline estimate of beta-cell function, provided always together with fasting glucose and explicit consideration of renal function
- For maximum diagnostic precision in type classification, a stimulated test may be useful, but consistent fasting measurement and tracking trends often works excellently in practice
Quick interpretation (adults)
Section titled “Quick interpretation (adults)”Guidelines; cut-offs vary by lab/assay. Conversion: 1000 pmol/L = 1.0 nmol/L.
| C-peptide | Interpretation |
|---|---|
| < 0.2 nmol/L | Severe insulin deficiency; often type 1 or end-stage beta-cell exhaustion. Usually insulin-dependent |
| 0.2-0.6 nmol/L | Intermediate; combine with autoantibodies and clinical picture; repeat if changes occur |
| > 0.6-0.7 nmol/L | Clear residual secretion; more often consistent with type 2 or slow autoimmune progression |
With suspected LADA
Section titled “With suspected LADA”| C-peptide | Management |
|---|---|
| < 0.3 nmol/L | Often managed as type 1 |
| 0.3-0.7 nmol/L | Gray area with monitoring |
| > 0.7 nmol/L | Often managed as type 2 with reassessment if worsening |
Renal function
Section titled “Renal function”C-peptide is largely cleared by the kidneys. With reduced kidney function, serum C-peptide may be elevated due to reduced clearance, without the pancreas producing more insulin. This can lead to overestimation of beta-cell function.
- Always include eGFR/creatinine
- With clearly lower eGFR: be cautious with absolute cut-offs; mainly use trends under comparable conditions
- With (very) low eGFR/dialysis: C-peptide is unsuitable for distinguishing type 1 vs type 2; rely more on clinical picture, antibodies, and treatment response
HOMA-IR based on C-peptide
Section titled “HOMA-IR based on C-peptide”For insulin resistance estimation, HOMA2 is more suitable than the original linear HOMA-IR, because the relationship between glucose and secretion is not linear. HOMA2 can, depending on implementation, also calculate with C-peptide (instead of insulin).
- Oxford HOMA2 (DTU) is the classic reference implementation
- HOMA is a fasting steady-state approach; with highly variable glucose or severe kidney dysfunction, interpretation is more vulnerable
Veelgestelde vragen
What is C-peptide?
C-peptide is a protein secreted by beta cells together with insulin, in equal molar amounts (equimolar). It's a marker for endogenous insulin production - exogenous insulin contains no C-peptide.
Why measure C-peptide instead of insulin?
Insulin is cleared variably (including first-pass through the liver), while C-peptide has a longer half-life and is more stable as a measure of secretion. When using insulin injections, C-peptide is the only way to measure your own production.
How do I interpret a C-peptide result?
Always together with glucose: with low glucose, low C-peptide can be physiological. With higher glucose, relatively low C-peptide indicates insufficient secretion. Also consider renal function - with reduced kidney function, C-peptide may be falsely elevated.
What does a low C-peptide mean?
Below 0.2 nmol/L indicates severe insulin deficiency, often type 1 or end-stage beta-cell exhaustion. Between 0.2-0.6 nmol/L is intermediate and requires combination with autoantibodies and clinical picture. Above 0.6-0.7 nmol/L there is clear residual secretion.
When is C-peptide unreliable?
Avoid interpretation shortly after DKA/HHS (temporary suppression) or immediately after hypoglycemia (rebound). With severely reduced kidney function or dialysis, C-peptide is unsuitable for type classification.
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