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. RESEARCH DESIGN AND 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.
RCT Entities:
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. RESEARCH DESIGN AND 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: Sathish Babu Vasamsetti; Jonathan Florentin; Emilie Coppin; Lotte C A Stiekema; Kang H Zheng; Muhammad Umer Nisar; John Sembrat; David J Levinthal; Mauricio Rojas; Erik S G Stroes; Kang Kim; Partha Dutta Journal: Immunity Date: 2018-06-26 Impact factor: 31.745