Source of C-peptide

{{Infobox concept | name = C-peptide | subtitle = Laboratory medicine | Origin = Connecting peptide of proinsulin | Secretion = Equimolar with insulin | Hepatic extraction = Negligible | Clearance = Renal }} '''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.{{r|jones2013}} 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|beta-cell function]].{{r|jones2013}} 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.{{r|ada2024}} == Use in assessment == Deconvolution of a peripheral C-peptide profile using known kinetics yields a secretion rate, which is the reference approach for quantifying [[Insulin secretion|insulin secretion]].{{r|rorsman2013}} It requires timed sampling and modelling and is a research technique.{{r|jones2013}} 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.{{r|jones2013}} == Interpretation caveats == | Situation | Effect on C-peptide | |---|---| | Renal impairment | Raised, independent of secretion | | Fasting versus stimulated | Different questions; not interchangeable | | Exogenous insulin | Suppresses endogenous secretion, lowering C-peptide | | Assay differences | Between-method variation is substantial | The exogenous insulin row is the basis of one of the analyte's forensic uses: insulin administered from outside raises insulin while suppressing C-peptide, a pattern that endogenous hypersecretion does not produce.{{r|jones2013}} Assay standardisation has improved but between-method differences remain, so a value should be interpreted against the reporting laboratory's reference interval rather than a remembered number.{{r|ada2024}} == Relevance to incretin therapy == Incretin agonists amplify secretion while present, so a C-peptide measured during treatment reflects the drug as well as the beta cell. Assessments of underlying secretory capacity are therefore made off treatment where the question requires it.{{r|drucker2018}} Improvements in C-peptide-derived indices during treatment are frequently reported and are frequently over-interpreted: an improved index under continuing treatment is not evidence of a durable change in the beta cell. See [[Beta cell function]].{{r|jones2013}} C-peptide appears on some baseline laboratory panels discussed in this field; see [[Baseline laboratory panel]]. Nothing on this wiki is medical advice.{{r|ada2024}} == References == {{reflist}} <ref name="jones2013">Jones AG, Hattersley AT. "The clinical utility of C-peptide measurement in the care of patients with diabetes." ''Diabetic Medicine'' 30(7):803–817 (2013). DOI:10.1111/dme.12159. PMID 23413806.</ref> <ref name="ada2024">American Diabetes Association. "Standards of Care in Diabetes." ''Diabetes Care'' 47(Suppl 1) (2024).</ref> <ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). PMID 29617641.</ref> <ref name="rorsman2013">Rorsman P, Braun M. "Regulation of insulin secretion in human pancreatic islets." ''Annual Review of Physiology'' 75:155–179 (2013). PMID 22974438.</ref> == See also == * [[Insulin secretion]] * [[Beta cell function]] * [[Fasting insulin]] * [[HOMA-IR]] * [[Baseline laboratory panel]] {{DEFAULTSORT:C-peptide}} [[Category:Metabolic biomarkers]] [[Category:Laboratory medicine]] [[Category:Clinical practice]]