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Progressive pancreatic beta-cell function failure and insulin resistance are the key characteristics of type 2 diabetes mellitus (T2DM)
- C-peptide is secreted from pancreatic beta cells at an equimolar ratio to insulin
- once the excessive secretion of insulin can no longer compensate for the degree of insulin resistance, clinically significant hyperglycemia will happen
- insulin secreted from pancreatic beta-cells will be partially cleared in the liver before entering the peripheral circulation [1,2]
- C-peptide is not extracted by the liver and other organs, and the half life of C-peptide level in blood is longer than that of insulin (10-30 versus 4 min)
- C-peptide can be measured in serum or urine
- serum and urinary C-peptide levels reflect the absolute amount of endogenous insulin secretion
- C-peptide secreted with insulin in equimolar amounts is not cleared in the liver
- peripheral plasma C-peptide concentrations reflect endogenous insulin secretion more accurately than serum insulin 
- C-peptide is therefore used as a marker of beta cell function
- C-peptide is capable of assessing beta cell function even in patients under insulin therapy
The C-peptide index (CPI), a ratio of serum C-peptide to plasma glucose concentrations, is a readily measured index of beta-cell function 
- since glucose itself is a major stimulus of beta cells, insulin secretion is augmented by the higher glucose level seen in patients with diabetes
- to assess beta cell function, C-peptide level should be adjusted for glucose
- Polonsky KS, Licinio-Paixao J, Given BD, Pugh W, Rue P, Galloway J, Karrison T, Frank B. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. The Journal of clinical investigation. 1986; 77:98-105
- Van Cauter E, Mestrez F, Sturis J, Polonsky KS. Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes. 1992; 41:368-377
- Cersosimo E, Solis-Herrera C, Trautmann ME, Malloy J, Triplitt CL. Assessment of pancreatic beta-cell function: review of methods and clinical applications. Current diabetes reviews. 2014; 10:2-42.
- Saisho Y, Kou K, Tanaka K, Abe T, Kurosawa H, Shimada A, Meguro S, Kawai T, Itoh H. Postprandial serum C-peptide to plasma glucose ratio as a predictor of subsequent insulin treatment in patients with type 2 diabetes. Endocrine journal. 2011; 58:315-322.
Last edited 08/2020 and last reviewed 02/2021