title: Effect of hypoglycemia on beta-adrenergic sensitivity in normal and type 1 diabetic subjects.
abstract: OBJECTIVE
  The purpose of this study was to assess the potential role of reduced tissue sensitivity to catecholamines in the pathogenesis of hypoglycemia unawareness in patients with type 1 diabetes.
  
  
  METHODS
  The effect of a single episode of hypoglycemia on beta-adrenergic sensitivity was studied in 10 type 1 diabetic patients with apparently normal awareness of hypoglycemia (age 29 +/- 5 years, diabetes duration 13 +/- 8 years, HbA1c 7.3 +/- 0.9%) and 10 age-matched healthy control subjects. Beta-adrenergic sensitivity was measured with the isoproterenol test after a hyperinsulinemic euglycemic clamp and after a hyperinsulinemic hypoglycemic clamp. Beta-adrenergic sensitivity was expressed as the dose of intravenous isoproterenol that increased the heart rate by 25 beats/min (IC25).
  
  
  RESULTS
  During hypoglycemia, diabetic subjects had an impaired plasma epinephrine response compared with that of the control subjects (16.7 +/- 5.0 vs. 40.1 +/- 6.8 ng/ml, P = 0.02). In control subjects, the IC25 was lower after hypoglycemia than after euglycemia (0.83 +/- 0.22 vs. 1.13 +/- 0.21 microg, P = 0.02) indicating an increase in beta-adrenergic sensitivity. In diabetic subjects, on the other hand, the IC25 was greater after hypoglycemia than after euglycemia (1.00 +/- 0.26 vs. 0.65 +/- 0.14 microg, P = 0.04), indicating a decrease in beta-adrenergic sensitivity.
  
  
  CONCLUSIONS
  In normal subjects, a single episode of hypoglycemia increases beta-adrenergic sensitivity. In diabetic subjects, in contrast, hypoglycemia reduces beta-adrenergic sensitivity. These results provide evidence that in type 1 diabetic patients, some maladaptation of tissue sensitivity to catecholamines contributes to the development of hypoglycemia unawareness. A unifying hypothesis is presented for the pathogenesis of hypoglycemia unawareness in type 1 diabetic patients incorporating the concepts of both a reduced catecholamine response and reduced adrenergic sensitivity
authors.affiliation: Department IV of Internal Medicine, University of Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Fritsche
authors.forename: M
authors.initials: M
authors.lastname: Stumvoll
authors.forename: M
authors.initials: M
authors.lastname: Grüb
authors.forename: S
authors.initials: S
authors.lastname: Sieslack
authors.forename: W
authors.initials: W
authors.lastname: Renn
authors.forename: R M
authors.initials: RM
authors.lastname: Schmülling
authors.forename: H U
authors.initials: HU
authors.lastname: Häring
authors.forename: J E
authors.initials: JE
authors.lastname: Gerich
mesh_terms: D000318:Adrenergic beta-Agonists; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007545:Isoproterenol; D008297:Male; D010465:Perception; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D004837:Epinephrine