Glucose counterregulation in advanced type 2 diabetes: effect of β-adrenergic blockade.

Abstract

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. 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. 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. 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.