C-peptide (revision 6)

C-peptide is the connecting peptide excised from proinsulin during processing and secreted from the beta cell in equimolar quantity with insulin. Because it is not appreciably extracted by the liver, its peripheral concentration reflects secretion more faithfully than insulin does.^[1]

Insulin undergoes variable first-pass hepatic extraction of 40–80%, so peripheral insulin understates secretion by an amount that differs between people and with pulsatility. C-peptide avoids this and is the analyte used in any rigorous assessment of beta-cell function.^[1]

Its principal limitation is renal: C-peptide is cleared by the kidney, so concentrations rise in renal impairment independently of secretion, and interpretation in that setting requires care.^[2]

Deconvolution of a peripheral C-peptide profile using known kinetics yields a secretion rate, which is the reference approach for quantifying insulin secretion.^[3] It requires timed sampling and modelling and is a research technique.^[1]

Simpler indices are used clinically. A fasting C-peptide with a simultaneous glucose distinguishes states of insulin deficiency from insulin resistance; a stimulated C-peptide after a mixed meal or glucagon assesses residual secretory capacity.

The most common clinical use is classification: a very low C-peptide with hyperglycaemia indicates insulin deficiency, while a normal or high value with hyperglycaemia indicates resistance with preserved secretion. The thresholds are assay- and context-dependent.^[1]