Michael A. Nauck, MD; Juris J. Meier, MD
Disclaimer: The authors take full responsibility for the content of the manuscript.
Acknowledgment: The authors thank Dr. Christiane Qualmann (Rotenburg [Wümme], Germany), Dr. M. Christiane Saddig (Insulinom- und GEP-Tumor-Zentrum Neuss-Düsseldorf, Germany), and Dr. Jochen Post (Nettetal, Germany) for their help in retrieving clinical and laboratory data from hospital charts; Professor Dr. Achim A.R. Starke (Insulinom- und GEP-Tumor-Zentrum Neuss-Düsseldorf) and the late Professor Dr. Michael Berger (Heinrich Heine University Düsseldorf, Düsseldorf, Germany) for contributing data from patients who were diagnosed and had surgery at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; and Professor Dr. Hans Jürgen Peiper (Department of Surgery, Georg-August University, Göttingen, Germany) and Professor Dr. Hans-Dietrich Röher (Department of Surgery, Heinrich Heine University Düsseldorf, Düsseldorf, Germany) for the surgical care of the patients with insulinoma described in this manuscript and for allowing access to respective clinical and histologic data.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-0539.
Reproducible Research Statement: Study protocol and statistical code: Not available. Data set: Available for collaborative analyses upon negotiation and agreement with Dr. Nauck (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Michael Nauck, MD, Diabeteszentrum Bad Lauterberg, Kirchberg 21, D-37431 Bad Lauterberg im Harz, Germany; e-mail, email@example.com.
Current Author Addresses: Dr. Nauck: Diabeteszentrum Bad Lauterberg, Kirchberg 21, D-37431 Bad Lauterberg im Harz, Germany.
Dr. Meier: Medizinische Klinik I, Abteilung für Diabetologie und Gasrointestinale Endokrinologie, St. Josef-Hospital, Klinikum der Ruhr-Universität, Gudrunstraße 56, 44891 Bochum, Germany.
Author Contributions: Conception and design: M.A. Nauck.
Analysis and interpretation of the data: M.A. Nauck, J.J. Meier.
Drafting of the article: M.A. Nauck, J.J. Meier.
Critical revision of the article for important intellectual content: M.A. Nauck, J.J. Meier.
Final approval of the article: M.A. Nauck, J.J. Meier.
Statistical expertise: M.A. Nauck, J.J. Meier.
Administrative, technical, or logistic support: J.J. Meier.
Collection and assembly of data: M.A. Nauck, J.J. Meier.
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.
Nauck MA, Meier JJ. Diagnostic Accuracy of an “Amended” Insulin–Glucose Ratio for the Biochemical Diagnosis of Insulinomas. Ann Intern Med. ;157:767–775. doi: 10.7326/0003-4819-157-11-201212040-00004
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Published: Ann Intern Med. 2012;157(11):767-775.
Endocrine and Metabolism, Gastroenterology/Hepatology, Gastrointestinal Cancer, Hematology/Oncology, Pancreatic Cancer.
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