C-Peptide 

Updated: Nov 20, 2019
Author: Georges Elhomsy, MD, ECNU, FACE; Chief Editor: Eric B Staros, MD 

Reference Range

C-peptide is a peptide composed of 31 amino acids. It is released from the pancreatic beta cells during cleavage of insulin from proinsulin. It is mainly excreted by the kidney, and its half-life is 3-4 times longer than that of insulin.

The reference ranges for C-peptide are as follows[1] :

  • Fasting: 0.78-1.89 ng/mL or 0.26-0.62 nmol/L (SI units)
  • 1 hour after glucose load: 5-12 ng/mL
 

Interpretation

C-peptide levels are elevated in the following:

  • Insulinoma

  • Sulfonylurea intoxication

  • Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS)

  • Insulin resistance state(eg,obesity,Cushing syndrome)

  • Chronic kidney disease

C-peptide levels are suppressed in the following:

  • Type 1 diabetes mellitus

  • Exogenous insulin injection (factitious)

  • Hypoglycemia due to insulin-like growth factor secreting tumor

  • Insulin-independent hypoglycemia

 

Collection and Panels

Collection details are as follows:

  • Patient instructions: Overnight fasting is indicated

  • Specimen type: Serum

  • Collection tube: Red-top tube or gel-barrier tube

  • Unacceptable conditions: Grossly hemolyzed specimens

  • Specimen preparation: Separate serum from cells and transfer to transport tube

  • Storage/transport temperature: Refrigerated

  • Stability: Refrigerated, 2 weeks; Frozen, 2 weeks

  • Panels: None

 

Background

Description

C-peptide is a peptide composed of 31 amino acids. It is released from the pancreatic beta cells during cleavage of insulin from proinsulin. It is mainly excreted by the kidney, and its half-life is 3-4 times longer than that of insulin.

The insulin precursor, preproinsulin, is produced in the rough endoplasmic reticulum of pancreatic beta cells and is later cleaved to proinsulin and transported to the Golgi apparatus, where is packed into secretory granules. During maturation of this granules, proinsulin is cleaved into 3 peptide chains—insulin (2 chains, A and B) and C-peptide.

Although, historically, C-peptide was considered to have no biologic activity; recent studies suggest that C-peptide may improve capillary blood flow in the feet, decrease urinary albumin excretion, and improve nerve function in individuals with type 1 diabetes.[2, 3] }[4, 5]

Indications/Applications

C-peptide should be measured in the combination of insulin and proinsulin as part of the workup for nondiabetic hypoglycemia to differentiate between insulin-dependent hypoglycemia (high C-peptide levels) versus insulin-independent hypoglycemia (low C-peptide levels). For appropriate interpretation of these tests, low serum blood glucose levels (< 55 mg/dL; preferably < 45 mg/dL) should be documented in the same blood sample.

In combination with serum and/or urine sulfonylurea screening, C-peptide testing can help differentiate between factitious hypoglycemia due to exogenous insulin use (low C-peptide level, high insulin level) and sulfonylurea intoxication (high C-peptide level, high insulin level).

C-peptide can also be used for the following:

  • To monitor pancreatic function after a pancreatic transplantation or pancreatectomy

  • To monitor beta-cell function in a patient with early-stage type 1 diabetes mellitus who is receiving immunomodulatory therapy to slow disease progression

  • To differentiate between type 2 diabetes mellitus and latent autoimmune diabetes of adults (LADA)