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Preserved Sensitivity to ß₂-Adrenergic Receptor Agonists in Patients with Type 1 Diabetes Mellitus and Hypoglycemia Unawareness

Departments of General Internal Medicine (B.E.D.G., B.J.J.S., P.S.) and Pharmacology-Toxicology (P.D.M., L.W., P.S.), Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands

Address all correspondence and requests for reprints to: Bastiaan E. De Galan, M.D., Ph.D., Department of General Internal Medicine 463, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. E-mail: b.degalan{at}aig.umcn.nl.

Background and Objective: Use of ß₂-adrenergic receptor agonists has been advocated for the treatment of hypoglycemia unawareness in type 1 diabetes. In vitro, however, hypoglycemia unawareness has been associated with reduced ß₂-adrenergic sensitivity. Therefore, in vivo sensitivity to ß₂-adrenergic receptor agonist stimulation was compared between type 1 diabetic patients with and without hypoglycemia unawareness and nondiabetic controls.

Methods: Ten type 1 diabetic patients with hypoglycemia unawareness, 12 type 1 diabetic patients with intact hypoglycemic awareness, and 11 healthy controls were enrolled. ß₂-Adrenergic sensitivity was determined by measuring the forearm vasodilator response to intraarterial infusion of salbutamol. Salbutamol was infused in six increasing doses ranging from 0.003 to 1.0 µg¹·min^–1·dl^–1. Forearm blood flow (FBF) was bilaterally measured by venous occlusion plethysmography. Diabetic patients received low-dose insulin before FBF measurements to ensure that experiments were carried out under normoglycemic conditions.

Results: At baseline, FBF was 1.9 ± 0.3 ml¹·min^–1·dl^–1 in controls, 2.3 ± 0.4 ml¹·min^–1·dl^–1 in patients with intact awareness, and 1.4 ± 0.1 ml¹·min^–1·dl^–1 in patients with hypoglycemia unawareness (P = 0.048 vs. aware patients). In response to salbutamol, FBF increased 9.1-fold in controls, 8.0-fold in patients with intact awareness, and 10.7-fold in patients with hypoglycemia unawareness (P = NS). Heart rate increased in all groups due to systemic spillover of salbutamol but appeared blunted, considering a greater fall in mean arterial pressure in patients with hypoglycemia unawareness.

Conclusions: Sensitivity to ß₂-adrenergic receptor agonist stimulation is preserved in type 1 diabetic patients with hypoglycemia unawareness.

This article has been cited by other articles:

				J. R. White Jr. The Contribution of Medications to Hypoglycemia Unawareness Diabetes Spectr, April 1, 2007; 20(2): 77 - 80. [Full Text] [PDF]