The delay in gastric emptying which is evident in about 30±50 % of outpatients with longstanding Type I (insulin-dependent) or Type II (non-insulindependent) diabetes mellitus has been attributed to irreversible autonomic neuropathy [1±5]. It is now recognised, however, that acute changes in the blood glucose concentration have a major effect on gastric emptying as well as motor function in other regions of the gastrointestinal tract [1, 6±14]. The effects of acute hyperglycaemia on gastrointestinal motor function appear to be related directly to the blood glucose concentration [1, 15±19]. Hyperglycaemia slows gastric emptying markedly in patients with Type I and Type II diabetes [1,7,8] and healthy subjects [6]. The mechanisms mediating this effect are uncertain but hyperinsulinaemia might be an important factor. In normal subjects, hyperinsulinaemia, under euglycaemic conditions, slows emptying of Diabetologia (1999) Summary Hyperglycaemia slows gastric emptying in both normal subjects and patients with diabetes mellitus. The mechanisms mediating this effect, particularly the potential role of insulin, are uncertain. Hyperinsulinaemia has been reported to slow gastric emptying in normal subjects during euglycaemia. The purpose of this study was to evaluate the effect of euglycaemic hyperinsulinaemia on gastric emptying in Type I (insulin-dependent) and Type II (noninsulin-dependent) diabetes mellitus. In six patients with uncomplicated Type I and eight patients with uncomplicated Type II diabetes mellitus, measurements of gastric emptying were done on 2 separate days. No patients had gastrointestinal symptoms or cardiovascular autonomic neuropathy. The insulin infusion rate was 40 mU × m ±2 × min ±1 on one day and 80 mU × m ±2 × min ±1 on the other. Gastric emptying and intragastric meal distribution were measured using a scintigraphic technique for 3 h after ingestion of a mixed solid/liquid meal and results compared with a range established in normal volunteers. In both Type I and Type II patients the serum insulin concentration had no effect on gastric emptying or intragastric meal distribution of solids or liquids. When gastric emptying during insulin infusion rates of 40 mU × m ±2 × min ±1 and 80 mU × m ±2 × min ±1 were compared the solid T 50 was 137.8 ± 24.6 min vs 128.7 ± 24.3 min and liquid T 50 was 36.7 ± 19.4 min vs 40.4 ± 15.7 min in the Type I patients; the solid T 50 was 94.9 ± 19.1 vs 86.1 ± 10.7 min and liquid T 50 was 21.8 ± 6.9 min vs 21.8 ± 5.9 min in the Type II patients. We conclude that hyperinsulinaemia during euglycaemia has no notable effect on gastric emptying in patients with uncomplicated Type I and Type II diabetes; any effect of insulin on gastric emptying in patients with diabetes is likely to be minimal. [Diabetologia (1999) Corresponding author: Prof. I. A. Macdonald, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK Abbreviations: CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; RoIs, regions of interest; ALP, amylin and a...