Preserved Sensitivity to  2-Adrenergic Receptor Agonists in Patients with Type 1 Diabetes Mellitus and Hypoglycemia Unawareness

Background and Objective: Use of beta(2)-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 beta(2)-adrenergic sensitivity. Therefore, in vivo sensitivity to beta(2)-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. beta(2)-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 mu g(1).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 ml(1.)min(-1.)dl(-1) in controls, 2.3 +/- 0.4 ml(1.)min(-1.)dl(-1) in patients with intact awareness, and 1.4 +/- 0.1 ml(1.)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 beta(2)-adrenergic receptor agonist stimulation is preserved in type 1 diabetic patients with hypoglycemia unawareness.