Preserved sensitivity to beta2-adrenergic receptor agonists in patients with type 1 diabetes mellitus and hypoglycemia unawareness.
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 mug(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.
De Galan
Bastiaan E
BE
Department of General Internal Medicine 463, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. b.degalan@aig.umcn.nl
De Mol
Pieter
P
Wennekes
Lianne
L
Schouwenberg
Bas J J
BJ
Smits
Paul
P
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol; D001364:Awareness / Q000187:drug effects* / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005542:Forearm / Q000098:blood supply; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D014664:Vasodilation / Q000187:drug effects
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000420:Albuterol; D006442:Glycated Hemoglobin; D007328:Insulin