March 8, 1993

The Molar Ratio of Insulin to C-PeptideAn Aid to the Diagnosis of Hypoglycemia due to Surreptitious (or Inadvertent) Insulin Administration

Author Affiliations

From the Department of Medicine, State University of New York Health Science Center at Syracuse. Dr Blumenthal is now with the Department of Medicine, Christ Hospital and Medical Center, Oak Lawn, Ill.

Arch Intern Med. 1993;153(5):650-655. doi:10.1001/archinte.1993.00410050082011

After β-cell stimulation by carbohydrate or other secretagogues, insulin and C-peptide are secreted into the portal vein in a 1:1 molar ratio. A large fraction of endogenous insulin is cleared by the liver, whereas C-peptide, which is cleared primarily by the kidney and has a lower metabolic clearance rate than insulin, traverses the liver with essentially no extraction by hepatocytes. Hence, the molar ratio of insulin to C-peptide in peripheral venous blood (ICPR) should be less than 1.0 during fasting and feeding, unless exogenous insulin is introduced into the systemic circulation. Consequently, an ICPR in excess of 1.0 in a hypoglycemic patient argues persuasively for surreptitious or inadvertent insulin administration and against insulinoma (or sulfonylurea ingestion) as the cause of the hypoglycemia. This conclusion is supported by personal experience and by the literature.

(Arch Intern Med. 1993;153:650-655)