C-Peptide/Connecting Peptide
TECHNICAL UPDATE

DESCRIPTION/BACKGROUND INFORMATION:

C-peptide is a 31 amino acid polypeptide with a molecular weight of 3,020 daltons. It has no known metabolic function. Pancreatic beta cells synthesize proinsulin, an inactive precursor to insulin, which is an 86 amino acid polypeptide made up of A and B chains joined by a connecting (C) peptide. Proinsulin is enzymatically cleaved to create insulin and C-peptide which are secreted into the portal circulation in equimolar amounts when insulin is required. This makes C-peptide a useful marker of insulin production and its measurement offers several advantages over insulin measurements.

C-peptide may be measured in either blood or urine. Its half-life in circulation is between two and five times longer than that of the more rapidly changing levels of insulin, and due to its relative metabolic inertness, it is a more stable indicator of beta cell function. C-peptide levels in peripheral blood are about five to six times greater than insulin levels. Quantitation of C-peptide has clinical importance because its only source is from pancreatic beta cells and therefore distinguishes between endogenous and exogenous insulin sources.

CLINICAL APPLICATION:

The primary indication for measurement of C-peptide is in the evaluation of fasting hypo-glycemia. C-peptide measurement is used to diagnose insulinomas and to detect factitious hypoglycemia. When hypoglycemia is due to surreptitious insulin injection, insulin concentrations are high, but C-peptide levels are low due to the fact that C-peptide is not found in commercial insulin preparations and exogenous insulin suppresses beta cell function. It is used in the follow-up of pancreatectomy and to evaluate the viability of islet cell transplants. These indications have recently been expanded to include evaluation of insulin dependence in mature onset of diabetes mellitus. In newly diagnosed Type I or Type II diabetes, C-peptide can be used to help determine how much insulin the patient's pancreas is still producing. Any insulin produced by the patient will be reflected in the C-peptide levels.

Low C-peptide levels are expected when insulin secretion is decreased as in insulin-dependent diabetes, or suppressed as a normal response to exogenous insulin. Other factors associated with decreased C-peptide levels are certain congenital metabolic disorders, suppression tests, thiazide diuretics and alcohol ingestion.

Elevated C-peptide levels may result from the increased beta cell activity seen in insulinomas, glucose intake, thyrotoxicosis, Cushing's Syndrome, hypokalemia, theophylline administration, pregnancy, acromegaly and renal failure.

C-peptide is free of some of the interferences encountered when measuring insulin directly. C-peptide doesn't measure exogenous insulin and doesn't cross react with insulin antibodies which interfere with insulin immunoassays. Insulin antibodies are commonly found in patients who have undergone insulin therapy making it impossible to measure their insulin levels to check on residual beta cell activity. C-peptide levels have been used as an alternative to yield information on the history of insulin-dependent diabetes and to indirectly monitor insulin secretion in the presence of insulin antibodies.

LIMITATIONS:

C-peptide metabolism differs from that of insulin so C-peptide levels are a semi-quantitative indicator of insulin secretion. The half-life of C-peptide has been estimated at approximately 30 minutes as opposed to five minutes for insulin, therefore, C-peptide levels are approximately five times that of insulin. The liver plays a major role in clearing insulin, while C-peptide is removed primarily by degradation and elimination through the kidneys. Elevated C-peptide levels are seen in renal failure. Hepatic and renal disorders will affect the ratio of C-peptide to insulin. Patients routinely exposed to animals or animal serums can develop heterophilic antibodies that can react with the immunoglobulins in the assay reagents causing anomalous results. These reagents, though, have been formulated to minimize the risk of this type of interference. Instances of insulinoma have been reported in which proinsulin was increased, but insulin and C-peptide weren't.

TEST NAME & NUMBER:

• 2064 C-Peptide

REFERENCES:

1. Burtis, Carl A. and Ashwood, Edward R., Eds., Tietz Fundamentals of Clinical Chemistry, 5th Ed., W.B. Saunders Co., Philadelphia, 2001.
2. C-Peptide, Lab Tests Online, http://www.labtestsonline.org.
3. C-Peptide, Serum, ARUP, http://www.aruplab.com.
4. Henry, John B., Clinical Diagnosis and Management by Laboratory Methods, 18th Ed., W.B. Saunders Co., Philadelphia, 1991.
5. Immulite 2000 C-Peptide Package Insert, Diagnostic Products Corporation, Los Angeles, January 21, 2002.