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Urine C-peptide is measured when a continuous assessment of β-cell function is desired or frequent blood sampling is not practical (eg, in children).1 C-peptide excretion in urine has been used to assess pancreatic function in gestational diabetes and in patients with unstable glycemic control in insulin-dependent diabetes mellitus (IDDM).2,3
C-peptide is a single-chain 31-amino acid (AA 33-63) connecting (C) polypeptide with a molecular weight of approximately 3021 daltons.1,5 In the process of biosynthesis of insulin, the C-peptide is formed as a byproduct together with insulin by the proteolytic cleavage of the precursor molecule proinsulin, stored in secretory granules in the Golgi complex of the pancreatic β-cells. Proinsulin, in turn, was cleaved from preproinsulin.1,6
C-peptide fulfills an important function in the assembly of the two-chain insulin (α- and β-chain) structure and the formation of the two disulfide bonds within the proinsulin molecule. Insulin and C-peptide are secreted in equimolar amounts and released into circulation via the portal vein.2 As half of the insulin, but almost none of the C-peptide, is extracted in the liver, C-peptide has a longer half-life (about 35 minutes) than insulin; 5 to 10 times higher concentration of C-peptide persists in the peripheral circulation, and these levels fluctuate less than insulin.1,2,6
The liver does not extract C-peptide, which is removed from the circulation by the kidneys and degraded, with a fraction excreted unchanged in the urine. The concentration in urine is about 20- to 50-fold higher than in serum. C-peptide concentrations are, therefore, elevated in renal disease.1,5,6
1. Sacks DB. Carbohydrates. In: Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. 3rd ed. Philadelphia, Pa: WB Saunders Co;1999: 750-808.
2. Lunell NO, Persson B, Devarajan LV, et al. Urinary C-peptide in the neonate correlates both to maternal glucose tolerance and to fetal size at birth. Am J Perinatol. 1988 Apr; 5(2):144-145. PubMed 3348860
3. Cha T, Tahara Y, Ikegami H, et al. Urinary C-peptide as an index of unstable glycemic control in insulin-dependent diabetes mellitus (IDDM). Diabetes Res Clin Pract. 1991 Sep; 13(3):181-187. PubMed 1959481
4. C-Peptide on Elecsys 1010/2010 and Modular Analytics E170, [package insert ] 2007-06, V4. Indianapolis, Ind: Roche Diagnostics; 2007.
5. Clark PM. Assays for insulin, proinsulin(s) and C-peptide. Ann Clin Biochem. 1999; 36(Pt 5):541-564. PubMed 10505204
6. Thomas L. Insulin, C-peptide, proinsulin. Clinical Laboratory Diagnostics. 1st ed. Washington, DC: AACC Press;1998:149-150.
