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Ann Intern Med. 2012 Dec 4;157(11):767-75. doi: 10.7326/0003-4819-157-11-201212040-00004.

Diagnostic accuracy of an "amended" insulin-glucose ratio for the biochemical diagnosis of insulinomas.

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Diabeteszentrum Bad Lauterberg, Kirchberg 21, D-37431 Bad Lauterberg im Harz, Germany.



Recent biochemical diagnostic guidelines for insulinomas require demonstration of hypoglycemia with inappropriately elevated (nonsuppressed) insulin, C-peptide, or proinsulin, but these criteria may overlap with those in patients without insulinomas. Use of an "amended" insulin-glucose ratio that accounts for the normal variation in insulin secretion according to prevailing glycemia may improve diagnostic accuracy.


To compare the diagnostic accuracy of current diagnostic guideline criteria with the amended insulin-glucose ratio in patients with a suspected insulinoma.


Retrospective cohort study.


2 specialized university departments in Germany.


114 patients with suspected hypoglycemia over 10 years having diagnostic prolonged fasts.


Glucose, insulin, C-peptide, and the amended insulin-glucose ratio were measured during and at discontinuation of prolonged fasts.


Of 114 patients who were evaluated, 49 had surgical resection of histologically confirmed insulinomas. Insulinoma was excluded in 65 patients; follow-up for a mean of 10 years (range, 0 to 16 years) showed no progressively severe hypoglycemic events or diagnoses of insulinoma. Patients with insulinoma had lower glucose levels and higher insulin and C-peptide levels overall than did control patients at the end of prolonged fasts, but there was considerable overlap. The amended insulin-glucose ratio correctly identified 48 of 49 patients with insulinoma and excluded the diagnosis in 64 of 65 control patients, resulting in positive and negative predictive values of 0.98 (95% CI, 0.89 to 1.00) and 0.99 (CI, 0.92 to 1.00), respectively, compared with 0.75 (CI, 0.63 to 0.85) and 0.98 (CI, 0.89 to 1.00), respectively, for glucose, insulin, and C-peptide concentration criteria.


The study had a retrospective design, no proinsulin concentrations were available, and a nonspecific insulin immunoassay (crossreactive with proinsulin) was used.


The amended insulin-glucose ratio showed improved diagnostic accuracy over established criteria that use glucose, insulin, and C-peptide concentrations.



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