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

Description

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 it is packed into secretory granules. During maturation of these 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, studies suggest that it 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 to 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)

A study by Freese et al indicated that in children with new-onset type 1 diabetes, progressive stress on beta-cell endoplasmic reticula as well as aberrant proinsulin processing are demonstrated by rising ratios of proinsulin to C-peptide. The investigators also found a correlation between younger age at diagnosis and greater proinsulin/C-peptide ratio.^[6]