Early-Morning Hyperglycemia in IDDM: Acute Effects of Cholinergic Blockade

Growth hormone (GH) hypersecretion in insulindependent diabetes mellitus (IDDM) subjects has been shown to be causally related to early-morning hyperglycemia. We studied the effect of nocturnal GH suppression on acute glycemic control in six IDDM patients during a constant overnight insulin infusion (0.075 mU · kg⁻¹ · min⁻¹). In control experiments (infusion of insulin alone), plasma glucose increased from 5.6 ± 0.6 mM at 2400 to 11.1 ± 1.3 mM at 0900 (P = .0024). When in addition the cholinergic muscarinic antagonist pirenzepine wasgiven (100 mg at 2200 and again at 2400), plasma glucose increased from 5.6 ± 0.3 mM at 2400 to 8.4 ± 1.4 mM at 0900 (P > .05). The nocturnal surges of GH that were demonstrated in all patients during the control nights were suppressed during the treatment nights. There were no significant changes in insulin, cortisol, orepinephrine concentrations. Mean glucagon and norepinephrine concentrations were reduced from 127 ± 2.7 ng/L and 8.7 ± 0.5 nM to 101 ± 1.9 ng/L (P < .001) and 3.5 ± 0.2 nM (P < .001) on control and treatment nights, respectively. Neither glucagon nor norepinephrine concentrations changed significantly between 2400 and 0900 on either control or treatment nights. We conclude that nocturnal GH suppression by pirenzepine during a constant low-rate insulin infusion is associated with an attenuation of the early-morning plasma glucose rise.