The effect of acebutolol and propranolol on the hypoglycaemic action of glibenclamide.

1 The effect of acebutolol, a relatively selective beta-adrenoceptor blocking drug and propranolol, a non-selective one, on the hypoglycaemic action of glibenclamide after an oral glucose load has been investigated in a group of maturity-onset diabetic patients. 2 Glibenclamide significantly reduced the blood glucose levels and both acebutolol and propranolol, at therapeutic doses, were found to modify this action significantly. 3 The effect of acebutolol was slightly less than that of propranolol. The difference was not statistically significant. 4 The modes of action of sulphonylureas are reviewed and it is suggested that beta-adrenoceptor blockers may modify their effect on insulin release. This appears to be a drug interaction rather than an effect of beta-adrenoceptor blockade on glucose tolerance.

The reproducibility of serial meal and oral glucose tolerance tests in normal subjects.

Five normal volunteer subjects within 10% of their ideal body weight received four isocaloric meals per day during two separate study periods. Each study period consisted of two consecutive days one week apart. The plasma glucose and insulin response was determined half-hourly throughout the second day of each of the two study periods. Good reproducibility of the glucose and insulin response to the standardised meals on the two comparative profile days was observed. Only at three points during the day was the plasma glucose significantly different between the profile days while no differences existed for plasma insulin. In addition, a separate group of four healthy normal volunteer subjects within 10% of their ideal body weight received four 50 g oral glucose tolerance tests on each of four days, ie on two consecutive days one week apart. During the second day of each study period half-hourly plasma glucose and insulin concentrations were determined. The within subject reproducibility of the plasma glucose and insulin response to the serial glucose loads was excellent. At one time point only was the mean plasma glucose for the group significantly different between the two study days. No statistically significant difference however was observed for the plasma insulin response between the two days. As the day progressed during both test procedures a small decrease in carbohydrate tolerance was observed. The amplitude of glycaemic excursions in response to the oral glucose tolerance tests was greater than that observed in response to the meal tolerance tests.

The effect of glibenclamide on the glucose and insulin profile in maturity onset diabetics following both acute and long term treatment.

Glibenclamide was administered to five non insulin dependent diabetic (NIDD) patients, whose hyperglycaemia was not controlled by diet alone. The plasma glucose and insulin porfile was determined under strictly standardised conditions before, after the first administration and after 6 months of treatment with glibenclamide. A rapid and satisfactory lowering of plasma glucose was observed in all patients after the first administered dose and a very similar response was seen after 6 months of therapy, when glibenclamide was administered once a day. Despite a consistent plasma glucose lowering effect a very variable plasma insulin response was evident between the patients. This difference may be of relevance in the long term prognosis of these patients with respect to atherogenesis. For the period of the study weight gain was minimal, no episodes of hypoglycaemia or alcohol induced flushing were recorded.

Repeated blood glucose and plasma insulin levels in normal volunteer subjects receiving isocaloric meals, before and after chlorpropamide and glibenclamide.

The blood glucose and plasma insulin response to the two hypoglycaemic agents, chlorpropamide (Diabenese) and glibenclamide (Daonil) was determined in normal subjects under strict metabolic control in a double blind study. The subjects were admitted to hospital for the period of the study, during which time they received four isocaloric meals per day and their physical exercise was standardised. Chlorpropamide had a prolonged hypoglycaemic effect compared with the short lived response after glibenclamide. Thy hypoglycaemic characteristics of the two preparations could not be explained simply on the insulin responses. Chlorpropamide was capable of lowering blood glucose without raising plasma insulin levels, whereas glibenclamide produced a prolonged and marked increase in plasma insulin levels only to be associated with a short-lived hypoglycaemic response. The latter suggested that a degree of insulin resistance had been produced secondary to the early profound lowering of the blood glucose following glibenclamide. The data indicate therefore the need for caution in extrapolating to diabetic subjects the hypoglycaemic characteristics of an agent such as glibenclamide derived from studies in normal subjects.