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Test ID: CPR C-Peptide, Serum

Reporting Name

C-Peptide, S

Useful For

Diagnostic workup of hypoglycemia:

-Diagnosis of factitious hypoglycemia due to surreptitious administration of insulin

-Evaluation of possible insulinoma

-Surrogate measure for the absence or presence of physiological suppressibility of endogenous insulin secretion during diagnostic insulin-induced hypoglycemia (C-peptide suppression test)


Assessing insulin secretory reserve in selected diabetic patients (as listed below) who either have insulin autoantibodies or who are receiving insulin therapy:

-Assessing residual endogenous insulin secretory reserve

-Monitoring pancreatic and islet cell transplant function

-Monitoring immunomodulatory therapy aimed at slowing progression of preclinical, or very early stage type 1 diabetes mellitus

Clinical Information

C-peptide (connecting peptide), a 31-amino-acid polypeptide, represents the midportion of the proinsulin molecule. Proinsulin resembles a hairpin structure, with an N-terminal and C-terminal, which correspond to the A and B chains of the mature insulin molecule, oriented parallel to each other and linked by disulfide bonds. The looped portion of the hairpin between the A and B chains is called C-peptide. During insulin secretion, C-peptide is enzymatically cleaved off and cosecreted in equimolar proportion with mature insulin molecules.


Following secretion, insulin and C-peptide enter the portal circulation and are routed through the liver where at least 50% of the insulin binds to receptors, initiates specific hepatic actions (stimulation of hepatic glucose uptake and suppression of glycogenolysis, gluconeogenesis, and ketogenesis), and is subsequently degraded. Most of the insulin molecules that pass through the liver into the main circulation bind to peripheral insulin receptors, promoting glucose uptake, while the remaining molecules undergo renal elimination. Unlike insulin, C-peptide is subject to neither hepatic nor significant peripheral degradation but is mainly removed by the kidneys. As a result, C-peptide has a longer half-life than insulin (30-35 minutes versus 5-10 minutes), and the molar ratio of circulating insulin to circulating C-peptide is generally below 1, despite equimolar secretion. Until recently, C-peptide was thought to have no physiological function, but it now appears that there may be specific C-peptide cell-surface receptors (most likely belonging to the super-family of G-protein coupled receptors), which influence endothelial responsiveness and skeletal and renal blood flow.


In most disease conditions associated with abnormal serum insulin levels, the changes in serum C-peptide levels parallel insulin-related alterations (insulin to C-peptide molar ratio ≤1). Both serum C-peptide and serum insulin levels are elevated in renal failure and in disease states that lead to augmented primary endogenous insulin secretion (eg, insulinoma, sulfonylurea intoxication). Both also may be raised in any disease states that cause secondary increases in endogenous insulin secretion mediated through insulin resistance, primarily obesity, glucose intolerance, and early type 2 diabetes mellitus (DM), as well as endocrine disorders associated with hypersecretion of insulin-antagonistic hormones (eg, Cushing syndrome, acromegaly). Failing insulin secretion in type 1 DM and longstanding type 2 DM is associated with corresponding reductions in serum C-peptide levels.


Discordant serum insulin and serum C-peptide abnormalities are mainly observed in 2 situations: exogenous insulin administration and the presence of anti-insulin autoantibodies. Factitious hypoglycemia due to surreptitious insulin administration results in appropriate suppression of endogenous insulin and C-peptide secretion. At the same time, the peripherally administered insulin bypasses the hepatic first-pass metabolism. In these situations, insulin levels are elevated and C-peptide levels are decreased. In patients with insulin antibodies, insulin levels are increased because of the prolonged half-life of autoantibody-bound insulin. Some patients with anti-idiotypic anti-insulin autoantibodies experience episodic hypoglycemia caused by displacement of autoantibody-bound insulin.


To compare insulin and C-peptide concentrations (ie, insulin to C-peptide ratio):

-Convert insulin to pmol/L: insulin concentration in mcIU/mL x 6.945 = insulin concentration in pmol/L

-Convert C-peptide to pmol/L: C-peptide concentration in ng/mL x 331 = C-peptide concentration in pmol/L


Factitious hypoglycemia due to surreptitious insulin administration results in elevated serum insulin levels and low or undetectable C-peptide levels, with a clear reversal of the physiological molar insulin to C-peptide ratio (≤1) to an insulin to C-peptide ratio of greater than 1. By contrast, insulin and C-peptide levels are both elevated in insulinoma and the insulin to C-peptide molar ratio is 1 or less. Sulfonylurea ingestion also is associated with preservation of the insulin to C-peptide molar ratio of 1 or less.


In patients with insulin autoantibodies, the insulin to C-peptide ratio may be reversed to greater than 1, because of the prolonged half-life of autoantibody-bound insulin.


Dynamic testing may be necessary in the workup of hypoglycemia; the C-peptide suppression test is most commonly employed. C-peptide levels are measured following induction of hypoglycemia through exogenous insulin administration. The test relies on the demonstration of the lack of suppression of serum C-peptide levels within 2 hours following insulin-induced hypoglycemia in patients with insulinoma.


Reference intervals have not been formally verified in-house for pediatric patients. The published literature indicates that reference intervals for adult and pediatric patients are comparable.

Report Available

Same day/1 to 3 days

Day(s) Performed

Monday through Saturday

Clinical Reference

1. Service FJ, O'Brien PC, Kao PC, Young WF Jr: C-peptide suppression test: effects of gender, age, and body mass index; implications for the diagnosis of insulinoma. J Clin Endocrinol Metab. 1992;74:204-210

2. Lebowitz MR, Blumenthal SA: The molar ratio of insulin to C-peptide. An aid to the diagnosis of hypoglycemia due to surreptitious (or inadvertent) insulin administration. Arch Int Med. 1993 Mar 8;153(5):650-655

3. Leighton E, Sainsbury CA, Jones GC: A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017 Jun;8(3):475-487

4. Jones AG, Hattersley AT: The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet.Med. 2013 Jul;30(7):803-817. doi: 10.1111/dme.12159

5. Ahn CH, Kim LK, Lee JE, et al: Clinical implications of various criteria for the biochemical diagnosis of insulinoma. Endocrinol Metab (Seoul). 2014 Dec 29;29(4):498-504. doi: 10.3803/EnM.2014.29.4.498

6. Young DS, Huth EJ: SI Units for Clinical Measurement. American College of Physicians; 1998

Method Name

Electrochemiluminescence Immunoassay (ECLIA)

Specimen Type


Specimen Required

Patient Preparation:

1. Patient should fast for 8 hours.

2. For 12 hours before specimen collection do not take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.

Supplies: Aliquot Tube, 5 mL (T465)

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions: Centrifuge and aliquot serum into plastic vial within 2 hours of collection

Specimen Minimum Volume

0.75 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Frozen (preferred) 30 days
  Refrigerated  7 days

Reference Values

1.1-4.4 ng/mL

Reference intervals have not been formally verified in-house for pediatric patients. The published literature indicates that reference intervals for adult and pediatric patients are comparable.

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
CPR C-Peptide, S 13037-7


Result ID Test Result Name Result LOINC Value
CRPN C-Peptide, S 1986-9


If not ordering electronically, complete, print, and send a General Request (T239) with the specimen.

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