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C Peptide

Insulin is initially synthesized as preproinsulin in the islet cells of the pancreas and is then cleaved to proinsulin, which is packaged into secretory granules. Proinsulin is enzymatically cleaved into equimolar amounts of insulin and C-peptide in these granules. An increase in blood glucose concentration is the primary stimulus for insulin secretion. Insulin secretion involves fusion of the secretory granules with the cell membrane and exocytosis of insulin, C-peptide, and proinsulin.

C-peptide (connecting peptide) is the 31-amino-acid polypeptide in the middle of the proinsulin molecule. C-peptide is cleared from the circulation by the kidneys. It has a circulating half-life of 30 minutes, which is longer than the 5 to10 minute half life for insulin. Because of the differences in half-lives, the molar ratio of circulating insulin to C-peptide is usually <1, despite equimolar secretion.

C peptide and insulin are both elevated in patients with elevated insulin secretion such as insulinoma and in insulin resistance associated with early type 2 diabetes, obesity and glucose intolerance. Both are also elevated in renal failure. C peptide and insulin are both decreased in patients with type 1 diabetes and longstanding type 2 diabetes.

Discordant serum insulin and serum C-peptide occur in patients with anti-insulin autoantibodies and in patients with factitious hypoglycemia due to self-administration of hypoglycemic agents Historically, the presence of anti-insulin antibodies in nondiabetic patients or patients with diabetes who had never been treated with insulin was taken as evidence favoring the surreptitious use of insulin. However, the more recent realization that insulin autoantibodies may precede the development of type 1 diabetes by many years has complicated this interpretation. In patients with insulin antibodies, insulin levels are increased because of the prolonged half-life of insulin bound to autoantibody.

The diagnosis of factitious hypoglycemia can usually be established by documenting the presence of hypoglycemia and by simultaneously measuring plasma insulin, C-peptide, proinsulin, and insulin secretagogues such as sulfonylurea and meglitinides. Factitious hypoglycemia due to surreptitious insulin administration results in elevated serum insulin levels and low or undetectable C-peptide levels.

Reference range is usually 1 – 4.0 ng/mL

Specimen requirement is a red top tube of blood collected from a fasting patient.

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