Preserved Sensitivity to β2-Adrenergic Receptor Agonists in Patients with Type 1 Diabetes Mellitus and Hypoglycemia Unawareness

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Abstract

Background and Objective:

Use of β2-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 β2-adrenergic sensitivity. Therefore, in vivo sensitivity to β2-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. β2-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 β2-adrenergic receptor agonist stimulation is preserved in type 1 diabetic patients with hypoglycemia unawareness.

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