Background and aims: The rate of gastric emptying (GE) of carbohydrate is a major determinant of postprandial glycaemia. ‘Marked’ hypoglycaemia (~2.6mmol/L) accelerates GE substantially in both health and Type 1 diabetes and is likely to represent an important counter-regulatory mechanism by increasing the rate of carbohydrate absorption. There is no information about the effect of ‘mild’ hypoglycaemia (between 3.0-3.9mmol/L) on GE, which is more common in clinical practice. We have evaluated the effects of two levels of insulin-induced, hypoglycaemia i.e. ‘mild’ (blood glucose ~3.6mmol/L) and ‘marked’ (blood glucose ~2.6mmol/L) when compared to ‘euglycaemia’ (6mmol/L) on GE in health. Materials and methods: Nine healthy males (mean age: 33.9 ± 1.0 yrs; BMI 23.4 ± 1.3 kg/m2; HbA1c: 5.3 ± 0.6%) underwent concurrent measurements of GE of a solid meal (100g minced beef radio-labelled with 99mTc) by scintigraphy and arterialised venous blood glucose by glucose-oxidase analyser, on 3 separate occasions during ‘mild’ and ‘marked’ hypoglycaemia, and ‘euglycaemia’, in random order. Hypoglycaemia (~2.6mmol/L or ~3.6mmol/L) was established using a glucose-insulin clamp 15min before (t=-15min), and maintained for a further 60min (t=60 min) after, meal consumption. At t=60min, blood glucose was returned to 6mmol/L and maintained from t=60-120 min. On the ‘euglycaemia’ study day, blood glucose was clamped at ~6mmol/L and maintained at that level for the duration of the study. GE was measured for 120min after meal ingestion and expressed as % retention over time. Data are shown as mean ± SEM (Figure). A maximumlikelihood mixed effects model was used to estimate the difference in area under the curve (AUC) for gastric retention between glycaemic treatments with Bonferroni-adjusted pairwise comparisons of the estimated marginal means. A P-value <0.05 was considered significant. Results: There was an overall effect of glycaemia on gastric retention such that gastric emptying was accelerated during both ‘mild’ and ‘marked’ hypoglycaemia compared to euglycaemia as reflected by the AUC0-120min (P<0.001). Pairwise comparisons showed significant differences in the AUC0-120 between euglycaemia and ‘mild’ hypoglycaemia (P=0.02) and between euglycaemia and ‘marked’ hypoglycaemia (P=0.001), with a trend (P=0.06) for GE to be faster during ‘marked’ compared to ‘mild’, hypoglycaemia. Conclusion: The effect of hypoglycaemia to accelerate GE is dependent on the degree of hypoglycaemia in health. While both ‘mild’ and ‘marked’ hypoglycaemia accelerate gastric emptying substantially, the effect of ‘marked’ hypoglycaemia is greater.