title: Glucose counterregulation in advanced type 2 diabetes: effect of β-adrenergic blockade.
abstract: OBJECTIVE
  To examine counterregulatory glucose kinetics and test the hypothesis that β-adrenergic blockade impairs these in patients with type 2 diabetes mellitus (T2DM) and advanced β-failure.
  
  
  METHODS
  Nine insulin-requiring T2DM subjects and six matched nondiabetic control subjects were studied. β-Cell function was assessed by the C-peptide response to arginine stimulation. Counterregulatory hormonal responses and glucose kinetics were assessed by hyperinsulinemic euglycemic-hypoglycemic clamps with [3-(3)H]glucose infusion. T2DM subjects underwent two clamp experiments in a randomized crossover fashion: once with infusion of the β-adrenergic antagonist propranolol and once with infusion of normal saline.
  
  
  RESULTS
  Compared with the control subjects, T2DM subjects had threefold reduced C-peptide responses to arginine stimulation. During the hypoglycemic clamp, glucagon responses were markedly diminished (16.0 ± 4.2 vs. 48.6 ± 6.0 ng/L, P < 0.05), but other hormonal responses and the decrement in the required exogenous glucose infusion rate (GIR) from the euglycemic clamp were normal (-10.4 ± 1.1 vs. -7.8 ± 1.9 µmol · kg(-1) · min(-1) in control subjects); however, endogenous glucose production (EGP) did not increase (-0.8 ± 1.0 vs. 2.2 ± 0.7 µmol · kg(-1) · min(-1) in control subjects, P < 0.05), whereas systemic glucose disposal decreased normally. β-Adrenergic blockade in the T2DM subjects increased GIR ∼20% during the euglycemic clamp (P < 0.01), but neither increased GIR during the hypoglycemic clamp or decreased its decrement from the euglycemic clamp to the hypoglycemic clamp.
  
  
  CONCLUSIONS
  Overall glucose counterregulation is preserved in advanced T2DM, but the contribution of EGP is diminished. β-Adrenergic blockade may increase insulin sensitivity at normoglycemia but does not impair glucose counterregulation in T2DM patients, even those with advanced β-cell failure.
authors.affiliation: Phoenix VA Medical Center, Phoenix, AZ.
authors.forename: Syed
authors.initials: S
authors.lastname: Bokhari
authors.affiliation: Phoenix VA Medical Center, Phoenix, AZ.
authors.forename: Elena
authors.initials: E
authors.lastname: Plummer
authors.affiliation: Phoenix VA Medical Center, Phoenix, AZ.
authors.forename: Peter
authors.initials: P
authors.lastname: Emmerson
authors.affiliation: Phoenix VA Medical Center, Phoenix, AZ.
authors.forename: Anchal
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Phoenix VA Medical Center, Phoenix, AZ christian.meyer@flhosp.org.
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D002096:C-Peptide / Q000378:metabolism; D016022:Case-Control Studies; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method
chemical_list: D000319:Adrenergic beta-Antagonists; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D005934:Glucagon; D005947:Glucose