Andreas Fritsche, MD; Norbert Stefan, MD; Hans Häring, MD; John Gerich, MD; Michael Stumvoll, MD
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.
Fritsche A, Stefan N, Häring H, Gerich J, Stumvoll M. Avoidance of Hypoglycemia Restores Hypoglycemia Awareness by Increasing β-Adrenergic Sensitivity in Type 1 Diabetes. Ann Intern Med. 2001;134:729-736. doi: 10.7326/0003-4819-134-9_Part_1-200105010-00009
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Published: Ann Intern Med. 2001;134(9_Part_1):729-736.
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 (1, 2, 4-7). It has been thought that reduced counterregulatory hormone responses to hypoglycemia (4-5) are primarily responsible for hypoglycemia unawareness. However, recent studies suggest that impaired β-adrenergic sensitivity (8-10) may also be involved.
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Cardiology, Endocrine and Metabolism, Diabetes, Coronary Risk Factors.
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