The effects of oral acetylsalicylic acid (ASA) 3.2 g a day for 5 days on glucose and glucose regulatory hormones were examined in 4 normal subjects, and in 14 insulin requiring diabetic subjects, 9 of whom had significant residual Beta cell function as assessed by C-peptide secretion and 5 of whom did not. In all subjects plasma samples were assayed for glucose, C-peptide, glucagon, growth hormone, and cortisol during sequential intravenous glucose and arginine infusions while the subject was receiving ASA or placebo. The plasma samples from the normal subjects were assayed for insulin.

ASA significantly increased early insulin release (p < 0.02) and decreased plasma glucose (p < 0.02) in response to intravenous glucose in the normal subjects. ASA had no effect on glucose or hormone responses to intravenous arginine.

The C-peptide positive diabetics had a significantly lower basal plasma glucose while receiving ASA, and this difference persisted throughout the test (p < 0.02). C-peptide levels were similar to control during ASA ingestion. ASA had no significant effect on plasma glucose in the C-peptide negative diabetics.

ASA significantly increased fasting plasma glucagon in the normal subjects (p < 0.05) and C-peptide negative diabetics (p < 0.05). There was a significant positive correlation between the changes in plasma glucose and plasma glucagon both basally and 10 min after the commencement of the glucose infusion for the C-peptide negative diabetics but not for the C-peptide positive diabetics or the normal subjects. ASA had no effect on plasma growth hormone or cortisol levels.

The reduction of plasma glucose by ASA in man is dependent on continuing β cell function. In the absence of β cell function the stimulatory effect of ASA on glucagon production becomes the major determinant of ASA's effect on plasma glucose. The effects of ASA on pancreatic islet function appears to be the major determinant of its effect on glucose handling.