C-peptide

C-peptide is the 31-amino-acid chain excised from proinsulin in pancreatic beta cells. One molecule is co-secreted per insulin molecule, so fasting C-peptide directly reflects endogenous insulin secretion. Negligible hepatic extraction gives it a half-life of ~30 min versus insulin's 3–5 min, keeping it measurable under exogenous insulin therapy. Fasting C-peptide serves two roles: as a marker of beta-cell reserve (low values signal secretory loss in type 1 and late-stage type 2 diabetes) and as an index of chronic hyperinsulinaemia (elevated values indicate insulin resistance and compensatory hypersecretion). An NHANES cohort (Patel et al. 2012; n = 5,153 non-diabetic adults) found fasting C-peptide outperformed fasting insulin and resistance indices in predicting cardiovascular and all-cause death. A meta-analysis of 23 studies (Ahmadirad et al. 2023) confirmed a 22% higher all-cause mortality risk (HR 1.22; 95% CI 1.12–1.32) and 38% higher cardiovascular mortality (HR 1.38; 95% CI 1.08–1.77). In type 1 diabetes, residual secretion is protective; in insulin-resistant individuals, elevation signals metabolic burden. Interpretation requires clinical context (fasting glucose, HbA1c, diabetes status); C-peptide is most informative alongside fasting insulin and glucose.