Lack of effect of propranolol and metoprolol on glucose tolerance in maturity-onset diabetics.

Lack of effect of propranolol and metoprolol on glucose tolerance in maturity-onset diabetics Although the effect of beta-blocking drugs on the response to hypo-glycaemia has been extensively studied, less attention has been paid to the possibility that they might cause deterioration of glucose tolerance. Release of insulin is stimulated by beta-agonists, and two studies have shown that infusion of propranolol reduces insulin response to a glucose load in normal subjects.1 2 A group of maturity-onset diabetics tended to have higher blood sugars during chronic treatment with propranolol or the beta-selective agent metoprolol than when receiving placebo.3 We report here a controlled study of the effects of these two drugs at two dosage levels on the oral glucose tolerance and insulin response of a group of maturity-onset diabetics. The patients were six hypertensive diabetics (mid-afternoon blood sugar >10 mmol/l (180 mg/100 ml), phase IV diastolic blood pressure >95 mm Hg on three occasions). None had previously received beta-blockers and all were in good general health. Four were receiving oral hypoglycaemic agents (metformin, tolazamide, tolbutamide, or chlorpropamide) and two diet alone. On five occasions at least one week apart each subject attended at 9 am after fasting and omitting any hypoglycaemic drugs for 12 hours beforehand. For two days before the study each received one of the following twice daily: placebo; metoprolol 100 mg; metoprolol 200 mg; propranolol 80 mg; propranolol 160 mg. Treatments were randomised between the five visits of each subject according to a double-blind cross-over protocol. On the morning of the study the final (fifth) dose was given with 100 ml water, and one hour later 50 g glucose was given in 250 ml water. Serial samples were taken for assay of plasma glucose, plasma potassium, and serum insulin concentrations. Neither beta-blocker had a significant effect on fasting plasma glucose, glucose tolerance, or insulin response (figure). There was no suggestion of a dose-related trend falling short of statistical significance or of a consistent difference between propranolol and metoprolol. Potassium concentrations were consistently 0-2-0-3 mmol (mEq)/l higher during beta-blockade than with placebo (p<0-001 by paired t test), regardless of selectivity, and fell significantly during the three hours after glucose administration (p <0 001) on all treatments, including placebo.