Background and objective: Use of 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 ₂-adrenergic sensitivity. Therefore, in vivo sensitivity to ₂-adrenergic receptor agonist stimulation was compared between type 1 diabetic patients with and without hypoglycemia unawareness and nondiabetic controls.

Methods: 10 type 1 diabetic patients with hypoglycemia unawareness, 12 type 1 diabetic patients with intact hypoglycemic awareness and 11 healthy controls were enrolled. ₂-adrenergic sensitivity was determined by measuring the forearm vasodilator response to intra-arterial infusion of salbutamol. Salbutamol was infused in 6 increasing doses ranging from 0.003 to 1.0 µg•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•min^-1•dL^-1 in controls, 2.3 ± 0.4 mL•min^-1•dL^-1 in patients with intact awareness, and 1.4 ± 0.1 mL•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.

Conclusion: Sensitivity to ₂-adrenergic receptor agonist stimulation is preserved in type 1 diabetic patients with hypoglycemia unawareness.