Hypoglycemia-Dependent β<sub>2</sub>-Adrenoceptor Downregulation: A Contributing Factor to Hypoglycemia Unawareness in Patients with Type-1 Diabetes?

Vol. 62, No. 3, 2004

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Original Paper

Hypoglycemia-Dependent ₂-Adrenoceptor Downregulation: A Contributing Factor to Hypoglycemia Unawareness in Patients with Type-1 Diabetes?
K.O. Schwab^a,b, U. Menche^a, G. Schmeisl^c, M.J. Lohse^a

^aDepartment of Pharmacology and Toxicology, University of Würzburg,
^bDepartment of Pediatrics, University of Freiburg, and
^cDiabetes-Reha-Klinik Fürstenhof, Bad Kissingen, Germany

Address of Corresponding Author

Horm Res 2004;62:137-141 (DOI: 10.1159/000080064)

Key Words

Hypoglycemia unawareness
Insulin-dependent diabetes mellitus
₂-Adrenoceptor density
Lymphocytes

Abstract

To evaluate the influence of the incidence and unawareness of hypoglycemia on lymphocyte beta ₂-adrenoceptor densities, we measured beta ₂-adrenoceptor density using [¹²⁵I]-iodocyanopindolol and CGP 12177 before and after 1 week of treatment optimization in 33 adults with type-1 diabetes mellitus. Diabetes treatment of all patients was modified to improve their glycemic control. During this week, all patients had to complete a protocol with 7 daily glucose measurements, one of which was at night. The subjective symptoms were evaluated in case of hypoglycemia. A significant correlation between a hypoglycemia incidence below (but not above) the threshold of 2.75 mmol/l (50 mg/dl) and beta ₂-adrenoceptor densities on lymphocytes was found after the study week (r = -0.72, p < 0.00001). Nine patients suffering from hypoglycemia unawareness had a significantly higher incidence of hypoglycemia (p < 0.002) and lower beta ₂-adrenoceptor densities on lymphocytes compared to 24 patients who recognized all of their hypoglycemic episodes (p < 0.004). We conclude that downregulation of beta ₂-adrenoceptor densities on lymphocytes occurs as a result of recurrent hypoglycemia defined as glucose levels of <2.75 mmol/l. beta ₂-Adrenoceptor densities are decreased in patients with subjective hypoglycemia unawareness and might contribute to the reduced beta -adrenergic sensitivity in this subgroup of patients.

Author Contacts

K. Otfried Schwab, MD
Department of Pediatrics, University of Freiburg
Mathildenstrasse 1, DE-79106 Freiburg/Breisgau (Germany)
Tel. +49 761 270 4482/4300, Fax +49 761 270 4414
E-Mail schwab@kikli.ukl.uni-freiburg.de

Article Information

Received: January 14, 2004
Accepted after revision: June 3, 2004
Published online: August 3, 2004
Number of Print Pages : 5
Number of Figures : 2, Number of Tables : 1, Number of References : 37

Medline Abstract (ID 15297801)

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