The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

Avoidance of Hypoglycemia Restores Hypoglycemia Awareness by Increasing β-Adrenergic Sensitivity in Type 1 Diabetes

Andreas Fritsche, MD; Norbert Stefan, MD; Hans Häring, MD; John Gerich, MD; and Michael Stumvoll, MD
[+] Article, Author, and Disclosure Information

From Medizinische Universitätsklinik Tübingen, Tübingen, Germany; and University of Rochester School of Medicine, Rochester, New York.

Acknowledgments: The authors thank Anna Teigeler, Elke Hardt, and Dr. Walter Renn for assistance.

Grant Support: In part by grants 5M01-RR 00044, NIDDK-20411, and 20579 from the National Institute of Health/Division of Research Resources/General Clinical Research Center (Dr. Gerich) and grant DFG #Stu 192-2/1 from Deutsche Forschungsgemeinschaft (Dr. Stumvoll).

Requests for Single Reprints: Michael Stumvoll, MD, Medizinische Universitätsklinik Tübingen, Otfried-Müller-Straβe 10, 72076 Tübingen, Germany.

Current Author Addresses: Drs. Fritsche, Stefan, and Häring: Medizinische Universitätsklinik Tübingen, Otfried-Müller-Straβe 10, 72076 Tübingen, Germany.

Dr. Gerich: University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642.

Author Contributions: Conception and design: A. Fritsche, J. Gerich, M. Stumvoll.

Analysis and interpretation of the data: A. Fritsche, N. Stefan, J. Gerich, M. Stumvoll.

Drafting of the article: A. Fritsche, J. Gerich, M. Stumvoll.

Critical revision of the article for important intellectual content: A. Fritsche, H. Häring, J. Gerich, M. Stumvoll.

Final approval of the article: A. Fritsche, N. Stefan, H. Häring, J. Gerich, M. Stumvoll.

Provision of study materials or patients: A. Fritsche, N. Stefan, M. Stumvoll.

Statistical expertise: A. Fritsche, M. Stumvoll.

Obtaining of funding: J. Gerich, M. Stumvoll.

Administrative, technical, or logistic support: H. Häring, M. Stumvoll.

Collection and assembly of data: A. Fritsche, M. Stumvoll.

Ann Intern Med. 2001;134(9_Part_1):729-736. doi:10.7326/0003-4819-134-9_Part_1-200105010-00009
Text Size: A A A

Hypoglycemia unawareness is a major limiting factor in the management of type 1 diabetes (1). This common problem, reported to occur in about 25% of patients with type 1 diabetes (2), is characterized by loss of autonomic warning symptoms before development of neuroglycopenia (2). Hypoglycemia unawareness is associated with a sevenfold increase in the frequency of severe hypoglycemia (3), which may be accompanied by seizure and coma. In the past decade, several risk factors for hypoglycemia unawareness have been identified, including long duration of diabetes, tight glycemic control (low hemoglobin A1c values), and repeated episodes of hypoglycemia (12, 47). It has been thought that reduced counterregulatory hormone responses to hypoglycemia (45) are primarily responsible for hypoglycemia unawareness. However, recent studies suggest that impaired β-adrenergic sensitivity (810) may also be involved.

First Page Preview

View Large
First page PDF preview


Grahic Jump Location
Figure 1. The value refers to the comparison of the mean autonomic symptom score during the clamp (30 to 180 minutes) before and after avoidance of hypoglycemia. Bars represent SEs. To convert glucose values in mmol/L to mg/dL, divided by 0.0555.
Mean blood glucose level, autonomic symptom score, and plasma epinephrine level during hypoglycemic clamp before (white squares) and after (black squares) 4 months of avoidance of hypoglycemia.P
Grahic Jump Location
Grahic Jump Location
Figure 2. Continuous lines denote the linear regression line for the data points. The sum of the increases in heart rate is significantly greater than values obtained at baseline and after 2 months of avoidance of hypoglycemia (  < 0.001, multivariate analysis of variance). Bars represent SEs.
Mean increase in heart rate during isoproterenol testing before (white squares) and at 2 (black diamonds) and 4 (black squares) months after avoidance of hypoglycemia.P
Grahic Jump Location




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Submit a Comment/Letter

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.