A patient with Type 2 diabetes mellitus has elevated fasting glucose despite detectable C-peptide. C-peptide measurement (rather than insulin) is used to assess endogenous insulin secretion because:

• A C-peptide is co-secreted with insulin in equimolar amounts but has a longer half-life (~35 min vs. ~5 min for insulin) and is not cleared by the liver, making it a more reliable index of beta-cell secretion ✓
• B C-peptide is the active hormone that stimulates peripheral glucose uptake, and measuring it directly reflects insulin action
• C C-peptide is elevated in exogenous insulin use, allowing differentiation from beta-cell hypersecretion
• D C-peptide measurement avoids cross-reactivity with proinsulin in ELISA assays, which overestimate insulin levels

Explanation

Proinsulin is cleaved in the beta-cell secretory granule into insulin and C-peptide in equimolar amounts; both are released into the portal circulation with each secretory event. C-peptide has several advantages as a marker of endogenous insulin secretion: (1) unlike insulin, it is not extracted by the liver (only ~50% first-pass hepatic insulin clearance vs. essentially no hepatic C-peptide clearance), so peripheral C-peptide levels better reflect total secretory output; (2) C-peptide has a longer plasma half-life (~35 min) than insulin (~5 min), providing a more stable index; and (3) exogenous insulin preparations contain no C-peptide, so a low C-peptide in the presence of hypoglycaemia distinguishes exogenous insulin administration from endogenous hypersecretion (insulinoma). Option C has the logic reversed — exogenous insulin suppresses C-peptide. Option B is incorrect; C-peptide has minimal metabolic activity.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.