C-Peptide to Insulin Molar Ratio Calculator
C-Peptide to Insulin Molar Ratio Calculator
Molar C-peptide divided by molar insulin, both in pmol/L. The pancreas secretes them in equal amounts, so a ratio near 1 means the insulin did not come from the pancreas.
C-peptide : insulin molar ratio
Molar ratio, both pmol/LC-peptide 650 pmol/L with insulin 65 pmol/L, from the same fasting sample
Formula
- both in pmol/L
- the ratio is only molar if both are molar. Multiply a ng/mL C-peptide by 331 and a µIU/mL insulin by 6 first
- equimolar secretion
- proinsulin is cleaved into one molecule of insulin and one of C-peptide, so the beta cell releases exactly equal numbers of each
- why the ratio exceeds 1
- insulin is largely removed on its first pass through the liver and has a half-life of four to six minutes; C-peptide escapes hepatic extraction and lasts about thirty, so it accumulates relative to insulin
- not the mass ratio
- the familiar 'insulin over C-peptide above 1' rule uses insulin in µIU/mL against C-peptide in ng/mL — a mixed-unit ratio, not this one, and the two cannot be compared
Worked example
C-peptide 650 pmol/L with insulin 65 pmol/L, from the same fasting sample
650 ÷ 65 = 10.0
Both figures are molar, so the ratio is dimensionless
In the older units that is about 1.96 ng/mL C-peptide and 10.8 µIU/mL insulin
Within the usual fasting range of roughly 5 to 15
Reading the ratio
| Molar ratio | Suggests | Next step |
|---|---|---|
| < 1 | Insulin exceeding C-peptide — not possible from endogenous secretion alone | Confirm the absolute values on a sample drawn during hypoglycaemia; discuss with endocrinology |
| 1 – 5 | Lower than expected | Check the sample was fasting and consider insulin antibody interference |
| 5 – 15 | The usual fasting range in healthy people | Interpret the absolute C-peptide and insulin against the simultaneous glucose |
| > 15 | C-peptide accumulating relative to insulin | Consider renal impairment, haemolysis, or an analogue the insulin assay does not see |
Why the ratio can mislead
| Situation | Effect on the ratio | Why |
|---|---|---|
| Chronic kidney disease | Raised | C-peptide is cleared by the kidney and insulin is not, so C-peptide accumulates |
| Haemolysed sample | Raised | Red cells release insulin-degrading enzyme, destroying insulin in the tube |
| Modern insulin analogues | Normal or raised | Many immunoassays detect them poorly, so the insulin reads low despite the patient having taken it |
| Insulin antibodies | Lowered | Antibody interference can raise the measured insulin without any extra hormone being present |
| Sulfonylurea or glinide | Preserved, 5 – 15 | These drugs stimulate the beta cell, so both hormones rise together — a drug screen, not this ratio, identifies them |
| Sample not taken during hypoglycaemia | Uninterpretable | Insulin and C-peptide are only informative when measured while the glucose is genuinely low |
Why the ratio is normally well above 1
Proinsulin is cleaved into one molecule of insulin and one of C-peptide, so the beta cell releases exactly equal numbers of each. What happens afterwards is not equal. Insulin is largely extracted on its first pass through the liver and has a half-life of four to six minutes; C-peptide escapes that extraction, is cleared by the kidney, and lasts around thirty. C-peptide therefore accumulates relative to insulin, and in a healthy fasting person the molar ratio settles somewhere around 5 to 15. Expressed the other way round, the peripheral insulin to C-peptide molar ratio is roughly 0.15.
Both numbers must be molar for this to hold, and that is the commonest place the calculation goes wrong. The widely repeated rule that an insulin to C-peptide ratio above 1 indicates exogenous insulin uses insulin in µIU/mL against C-peptide in ng/mL — a mixed-unit ratio that happens to sit near 1 in health for arithmetic reasons rather than physiological ones. It is not the molar ratio and the two cannot be compared. Enter pmol/L for both above: multiply a ng/mL C-peptide by 331 and a µIU/mL insulin by 6.
The clinical setting where this matters is unexplained hypoglycaemia in someone without diabetes, or hypoglycaemia in someone with diabetes that does not fit their treatment. Insulin from outside the body suppresses the beta cell, so C-peptide falls while measured insulin stays high, and the ratio collapses towards or below 1 — a pattern endogenous secretion cannot produce. Insulinoma and sulfonylurea poisoning both drive the beta cell instead, so insulin and C-peptide rise together and the ratio is preserved; a sulfonylurea screen, not this ratio, separates those two.
Two caveats keep the ratio in its place. A sample is only interpretable if it was drawn while the plasma glucose was genuinely low, and the Endocrine Society approach rests on the absolute values at that moment — a measurable insulin with a C-peptide suppressed below about 200 pmol/L points to exogenous insulin, while both being raised points to endogenous secretion. And several modern insulin analogues are poorly detected by insulin immunoassays, so a patient who has taken one can show a low insulin, a suppressed C-peptide and a perfectly normal ratio. The suppressed C-peptide is then the finding that carries the information. This calculation supports a clinician’s assessment; it does not substitute for one.
Frequently asked questions
What is a normal C-peptide to insulin molar ratio?
Roughly 5 to 15 in a healthy fasting person, with both values in pmol/L. The two hormones are secreted in equal amounts, but insulin is largely removed on its first pass through the liver and has a much shorter half-life, so C-peptide accumulates relative to it.
Why must both values be in pmol/L?
Because a ratio is only molar if both of its terms are. The familiar rule about an insulin to C-peptide ratio above 1 uses insulin in µIU/mL against C-peptide in ng/mL, which is a mixed-unit ratio and a different quantity. Multiply a ng/mL C-peptide by 331 and a µIU/mL insulin by 6.
What does a low ratio mean?
Insulin high relative to C-peptide, which endogenous secretion cannot produce, since the pancreas releases them in equal amounts. In a sample drawn during documented hypoglycaemia this raises the question of insulin from outside the body. It is not a diagnosis and needs the absolute values and a clinician.
Can a normal ratio exclude exogenous insulin?
No. Several modern insulin analogues are poorly detected by insulin immunoassays, so someone who has taken one can show a low measured insulin, a suppressed C-peptide and a normal or even high ratio. The suppressed C-peptide during hypoglycaemia is the finding that matters.
Does this distinguish an insulinoma from a sulfonylurea?
No. Both stimulate the beta cell, so insulin and C-peptide rise together and the molar ratio stays in the usual range in each. A sulfonylurea and glinide screen on the hypoglycaemic sample is what separates them, alongside imaging and the clinical history.
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References
- Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94(3):709–728.
- Polonsky KS, Rubenstein AH. C-peptide as a measure of the secretion and hepatic extraction of insulin: pros and cons. Diabetes. 1984;33(5):486–494.
- Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013;30(7):803–817.