Skip to main content
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes Care

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
e-Letters: Observations

GLP-1 Provoked Severe Hypoglycemia in an Individual With Type 2 Diabetes and a Benign Insulinoma

  1. Ronald J. Ruby1,
  2. John P. Armato1,
  3. Charles Pyke2 and
  4. Anne L. Peters3⇑
  1. 1Pacific Coast Medical Group, Manhattan Beach, CA
  2. 2Histology and Imaging, Novo Nordisk A/S, Bagsvaerd, Denmark
  3. 3Division of Endocrinology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
  1. Corresponding author: Anne L. Peters, momofmax{at}mac.com.
Diabetes Care 2014 Aug; 37(8): e177-e178. https://doi.org/10.2337/dc14-0514
PreviousNext
  • Article
  • Figures & Tables
  • Info & Metrics
  • PDF
Loading

This is a case of a severe hypoglycemia caused by an excess of GLP-1 receptors on a benign insulinoma in an individual with type 2 diabetes. The hypoglycemia was likely induced by a GLP-1 receptor agonist. The patient is a 54-year-old Caucasian female evaluated for “reactive” hypoglycemia that had worsened over the past 10 years. She had gained 20 pounds and reported intermittent episodes of “lightheadedness and shakiness,” which she treated with carbohydrates. One morning after a breakfast of pancakes and syrup, her husband described an episode that required him to feed her “a lot of orange juice to keep her awake.”

She had no pertinent past medical history and a normal physical exam. Diabetes was diagnosed based on an oral glucose tolerance test with a fasting plasma glucose of 7.05 mmol/L, a 120-min value of 11.71 mmol/L, and a HbA1c of 5.1% (32 mmol/mol). At diagnosis, therapy with pioglitazone/metformin (15 mg/850 mg/day) and liraglutide 0.6 mg/day was started based on the protocol at the center where she was treated (1). Following the second dose of liraglutide 0.6 mg, she experienced confusion. In the emergency department, her blood glucose level was 1.38 mmol/L. It was difficult to raise and sustain her glucose levels and she required hospitalization on intravenous dextrose for 6 days. Her glucose levels were 2.22–3.0 mmol/L with insulin levels that ranged from 240 to 5,778 pmol/L. During this hospitalization she was found to have a pancreatic mass. A partial pancreatectomy was performed and histopathological examination confirmed a benign insulinoma.

The patient’s tumor underwent standard histological evaluation, revealing strongly positive staining for immunoreactive insulin. Due to the hypoglycemia following administration of a GLP-1 receptor agonist, immunohistochemistry for GLP-1 receptors (2) as well as insulin, glucagon, pancreatic polypeptide, somatostatin, and cytokeratin-19 was performed. Normal-appearing pancreatic tissue adjacent to the insulinoma served as internal positive control. The insulinoma cells were consistently immunopositive for GLP-1 receptors and insulin. Normal-appearing islets demonstrated a normal distribution of endocrine cells with GLP-1 receptor expression only seen in β-cells. No other compartments in the pancreas, including ductal epithelium, as identified by cytokeratin-19 staining, contained GLP-1 receptor immunoreactive cells (Fig. 1).

Figure 1
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1

Double labeling fluorescence immunohistochemistry for GLP-1 receptor (green) and cytokeratin-19 (red). A is from area with insulinoma. B is from adjacent normal part of pancreas with normal-appearing islet and ducts. The insulinoma area consists of trabecular structures with densely packed tumor cells arranged in microlobuli (asterisks in A). Note absence of GLP-1 receptor immunoreactivity within ductal structures in both A and B (arrows).

In this case, a patient with an insulinoma and type 2 diabetes diagnosed with an oral glucose tolerance test was started on a triple-drug regimen to slow disease progression. This produced a prolonged episode of hypoglycemia that led to the diagnosis of a benign insulinoma. In vitro and in vivo studies have revealed that benign insulinomas overexpress GLP-1 receptors, although less common in malignant insulinomas (3). The presence of GLP-1 receptors on β-cells is consistent with their mechanism of action resulting in increased insulin secretion. Thus, should a patient develop severe hypoglycemia on a GLP-1 receptor agonist an insulinoma should be considered.

Article Information

Acknowledgments. The authors are grateful to Drs. Lotte Bjerre Knudsen and Alan Moses at Novo Nordisk for their guidance and editorial assistance.

Duality of Interest. A.L.P. has been on the speaker’s bureau and served as a consultant for Novo Nordisk, Bristol-Myers Squibb, and AstraZeneca. C.P. is an employee of Novo Nordisk. No other potential conflicts of interest relevant to this article were reported.

Author Contributions. R.J.R. and J.P.A. treated the patient and obtained all of the clinical data and identified this as a novel case. They also reviewed and edited the manuscript and contributed to the discussion. C.P. performed and analyzed the immunohistochemistry, reviewed and edited the manuscript, and contributed to the discussion. A.L.P. wrote the manuscript and reviewed the data. A.L.P. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

References

  1. ↵
    1. Armato J,
    2. DeFronzo RA,
    3. Abdul-Ghani M,
    4. Ruby R
    . Successful treatment of prediabetes in clinical practice: targeting insulin resistance and β-cell dysfunction. Endocr Pract 2012;18:342–350
    OpenUrlCrossRefPubMed
  2. ↵
    1. Pyke C,
    2. Knudsen LB
    . The glucagon-like peptide-1 receptor—or not? Endocrinology 2013;154:4–8
    OpenUrlCrossRefPubMedWeb of Science
  3. ↵
    1. Wild D,
    2. Christ E,
    3. Caplin ME,
    4. et al
    . GLP-1 versus somatostatin receptor targeting reveals 2 distinct forms of malignant insulinomas. J Nucl Med 2011;52:1073–1078
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
Diabetes Care: 37 (8)

In this Issue

August 2014, 37(8)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by Author
  • Podcast
  • Masthead (PDF)
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes Care.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
GLP-1 Provoked Severe Hypoglycemia in an Individual With Type 2 Diabetes and a Benign Insulinoma
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
GLP-1 Provoked Severe Hypoglycemia in an Individual With Type 2 Diabetes and a Benign Insulinoma
Ronald J. Ruby, John P. Armato, Charles Pyke, Anne L. Peters
Diabetes Care Aug 2014, 37 (8) e177-e178; DOI: 10.2337/dc14-0514

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

GLP-1 Provoked Severe Hypoglycemia in an Individual With Type 2 Diabetes and a Benign Insulinoma
Ronald J. Ruby, John P. Armato, Charles Pyke, Anne L. Peters
Diabetes Care Aug 2014, 37 (8) e177-e178; DOI: 10.2337/dc14-0514
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Article Information
    • References
  • Figures & Tables
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Is Shelter-in-Place Policy Related to Mail Order Pharmacy Use and Racial/Ethnic Disparities for Patients With Diabetes?
  • Trends in Nontraumatic Lower-Extremity Amputation Among Privately Insured Adults With Diabetes in the U.S., 2004–2018
  • Lower-Extremity Amputation Trends Among People With Diabetes in a Large Urban Environment
Show more e-Letters: Observations

Similar Articles

Navigate

  • Current Issue
  • Standards of Care Guidelines
  • Online Ahead of Print
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.