The outcome of recent studies has led to redefinition of concepts relating to the prevalence, pathogenesis and clinical significance of disordered gastric emptying in patients with diabetes mellitus. The use of scintigraphic techniques has established that gastric emptying is abnormally slow in approx. 30-50% of outpatients with long-standing Type 1 or Type 2 diabetes, although the magnitude of this delay is modest in many cases. Upper gastrointestinal symptoms occur frequently and affect quality of life adversely in patients with diabetes, although the relationship between symptoms and the rate of gastric emptying is weak. Acute changes in blood glucose concentration affect both gastric motor function and upper gastrointestinal symptoms. Gastric emptying is slower during hyperglycaemia when compared with euglycaemia and accelerated during hypoglycaemia. The blood glucose concentration may influence the response to prokinetic drugs. Conversely, the rate of gastric emptying is a major determinant of post-prandial glycaemic excursions in healthy subjects, as well as in Type 1 and Type 2 patients. A number of therapies currently in development are designed to improve post-prandial glycaemic control by modulating the rate of delivery of nutrients to the small intestine.

The presence of nutrients in the small intestine slows gastric emptying and suppresses appetite and food intake; these effects are partly mediated by the release of gut hormones, including CCK. We investigated the hypothesis that the modulation of antropyloroduodenal motility, suppression of appetite, and stimulation of CCK and glucagon-like peptide-1 secretion by intraduodenal fat are dependent on triglyceride hydrolysis by lipase. Sixteen healthy, young, lean men were studied twice in double-blind, randomized, crossover fashion. Ratings for appetite-related sensations, antropyloroduodenal motility, and plasma CCK and glucagon-like peptide-1 concentrations were measured during a 120-min duodenal infusion of a triglyceride emulsion (2.8 kcal/min) on one day with, on the other day without, 120 mg tetrahydrolipstatin, a potent lipase inhibitor. Immediately after the duodenal fat infusion, food intake at a buffet lunch was quantified. Lipase inhibition with tetrahydrolipstatin was associated with reductions in tonic and phasic pyloric pressures, increased numbers of isolated antral and duodenal pressure waves, and stimulation of antropyloroduodenal pressure-wave sequences (all P < 0.05). Scores for prospective consumption and food intake at lunch were greater, and nausea scores were slightly less, and the rises in plasma CCK and glucagon-like peptide-1 were abolished (all P < 0.05). In conclusion, lipase inhibition attenuates the effects of duodenal fat on antropyloroduodenal motility, appetite, and CCK and glucagon-like peptide-1 secretion.

Postprandial hypotension occurs frequently in older people and may lead to syncope and falls. Some recent studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate of gastric emptying. The aim of this study was, therefore, to determine whether the fall in blood pressure induced by intraduodenal glucose is influenced by the rate of nutrient delivery into the small intestine, bypassing the effects of gastric emptying. Eight healthy elderly subjects (four male and four female, age 70.3 ± 3.4 years) were studied on two separate days, in double‐blind, randomised order. Glucose was infused intraduodenally at a rate of either 1 or 3 kcal min−1, for 60 min, (0–60 min) followed by 0.9 % saline for a further 60 min (60–120 min). Blood pressure and heart rate were recorded at baseline and every 3 min during the study. Blood glucose and plasma insulin were also determined. Only the 3 kcal min−1 infusion caused a significant fall in systolic (P < 0.001) and diastolic (P < 0.0001) blood pressure and an increase in the heart rate (P < 0.0001). The rises in blood glucose (P < 0.01) and plasma insulin (P < 0.05) concentrations were greater during the 3 kcal min−1 infusion. We conclude that in healthy older subjects, the magnitude of the fall in blood pressure and increase in heart rate induced by intraduodenal glucose infusion is dependent on the rate of nutrient delivery into the small intestine. These results may have relevance to the treatment of postprandial hypotension.

There is evidence that gastrointestinal function adapts in response to a high-fat (HF) diet. This study investigated the hypothesis that an HF diet modifies the acute effects of duodenal lipid on appetite, antropyloroduodenal pressures, plasma CCK and plasma glucagon-like peptide-1 (GLP-1) levels in humans. Twelve healthy men were studied twice in randomized, crossover fashion. The effects of a 90-min duodenal lipid infusion (6.3 kJ/min) on the above parameters were assessed immediately following 14-day periods on either an HF or a low-fat (LF) diet. After the HF diet, pyloric tonic and phasic pressures were attenuated, and the number of antropyloroduodenal pressure-wave sequences was increased when compared with the LF diet. Plasma CCK and GLP-1 levels did not differ between the two diets. Hunger was greater during the lipid infusion following the HF diet, but there was no difference in food intake. Therefore, exposure to an HF diet for 14 days attenuates the effects of duodenal lipid on antropyloroduodenal pressures and hunger without affecting food intake or plasma hormone levels.