We examined whether
tolbutamide has any acute or short-term effects on
insulin action in Type 1 (
insulin-dependent) diabetes. A euglycaemic
glucose clamp was performed in seven Type 1 diabetic patients without clinical
insulin resistance by infusing
glucose at a constant rate of 0.01 mmol X kg-1 X min-1 for 3h together with a simultaneous
insulin infusion using an '
artificial pancreas'. The
insulin infusion rate required to maintain
blood glucose at 6.7 mmol/l at a set low
glucose infusion rate provides an index of
insulin action in vivo. The euglycaemic clamp was performed on 3 separate days in the same patient: (1) in the basal state; (2) during simultaneous intravenous
tolbutamide infusion of 0.5 g/h, and (3)
after treatment with 2.5 g
tolbutamide/day for 6 days in addition to
insulin. The
insulin infusion rate needed to maintain the set
blood glucose level did not differ significantly between the three experimental conditions (1.2 +/- 0.2 versus 1.3 +/- 0.3 versus 1.2 +/- 0.3 U/h). Plasma
glucagon,
growth hormone, non-
esterified fatty acid and
glycerol levels did not differ between control or sulphonylurea treatment studies. The results suggest that
tolbutamide does not exert any acute or short-term effects on
insulin action in vivo in
Type 1 diabetes. Our results do not provide support for the idea that this agent is a clinically useful adjunct to
insulin in such patients.