Measurement of Proinsulin and C Peptide

Proinsulin is the precursor molecule for insulin and is found in the rough endoplasmic reticulum of the beta cells in the pancreatic islets. As shown in Figure 79-2, the proteolytic conversion of proinsulin results in the formation of equimo-lar amounts of insulin and its connecting peptide, C peptide. In the presence of an insulinoma, there is an elevation of both proinsulin and C peptide.1015 Furthermore, proinsulin levels, which are usually less than 20% of the total immunoreactive insulin in normal individuals, are elevated in the presence of an insulinoma. Levels higher than 50% are thought by some to be diagnostic of an islet cell carcinoma. Finally, should the diagnosis still be in doubt, measurement of circulating C peptide may be helpful. The normal C peptide level is less than 1.2 ng/dL.

There are two specific instances in which measurement of C peptide levels has been particularly helpful. The first is in patients with insulin-dependent diabetes mellitus. Such patients may have circulating antibodies to insulin that interfere with the measurement of insulin in the blood. Elevated levels of C peptide help confirm the diagnosis of insulinoma in such patients. The second situation in which the C peptide level is most useful is in patients who are surreptitiously injecting insulin. Commercial insulin has no C peptide; thus, these patients have low levels of C peptide in the setting of a high insulin level and hypoglycemia.

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