title: Inhaled Formoterol Diminishes Insulin-Induced Hypoglycemia in Type 1 Diabetes.
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. β-2 Adrenergic receptor (AR) agonists have been reported to diminish nocturnal hypoglycemia; however, whether long-acting inhaled β-2 AR agonists could potentially be used to treat or prevent hypoglycemia has not been established.
  
  
  METHODS
  Seven patients with type 1 diabetes and seven healthy control subjects received inhaled formoterol (48 μg), a highly specific β-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 β-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.
authors.affiliation: Department of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, CT.
authors.forename: Renata D
authors.initials: RD
authors.lastname: Belfort-DeAguiar
authors.affiliation: Department of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, CT.
authors.forename: Sarita
authors.initials: S
authors.lastname: Naik
authors.affiliation: Department of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, CT.
authors.forename: Janice
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, CT.
authors.forename: Barbara
authors.initials: B
authors.lastname: Szepietowska
authors.affiliation: Department of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, CT robert.sherwin@yale.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D000068759:Formoterol Fumarate / Q000008:administration & dosage*; D015309:Glucose Clamp Technique; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000009:adverse effects; D007328:Insulin / Q000009:adverse effects; D008297:Male; D008875:Middle Aged
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013006:Growth Hormone; D000068759:Formoterol Fumarate