ABSTRACT
OBJECTIVE: Hypoglycemia is one of the major factors limiting implementation of tight glycemic control in patients with type 1 diabetes and is associated with increased morbidity and mortality during intensive insulin treatment. ß-2 Adrenergic receptor (AR) agonists have been reported to diminish nocturnal hypoglycemia; however, whether long-acting inhaled ß-2 AR agonists could potentially be used to treat or prevent hypoglycemia has not been established. RESEARCH DESIGN AND METHODS: Seven patients with type 1 diabetes and seven healthy control subjects received inhaled formoterol (48 µg), a highly specific ß-2 AR agonist, or a placebo during a hyperinsulinemic-hypoglycemic clamp study to evaluate its capacity to antagonize the effect of insulin. In a second set of studies, five subjects with type 1 diabetes received inhaled formoterol to assess its effect as a preventive therapy for insulin-induced hypoglycemia. RESULTS: During a hyperinsulinemic-hypoglycemic clamp, compared with placebo, inhaled formoterol decreased the glucose infusion rate required to maintain plasma glucose at a target level by 45-50% (P < 0.05). There was no significant effect on glucagon, epinephrine, cortisol, or growth hormone release (P = NS). Furthermore, in volunteers with type 1 diabetes 1 h after increasing basal insulin delivery twofold, glucose levels dropped to 58 ± 5 mg/dL, whereas hypoglycemia was prevented by inhaled formoterol (P < 0.001). CONCLUSIONS: Inhalation of the ß-2 AR-specific agonist formoterol may be useful in the prevention or treatment of acute hypoglycemia and thus may help patients with type 1 diabetes achieve optimal glucose control more safely.
