Effects of lipase inhibition on gastric emptying of, and on the glycaemic, insulin and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetes

• Published in: Diabetologia 2004-12, Vol.47 (12), p.2208-2214
• Main Authors: ODONOVAN, D, HOROWITZ, M, RUSSO, A, FEINLE-BISSET, C, MUROLO, N, GENTILCORE, D, WISHART, J. M, MORRIS, H. A, JONES, K. L
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Blood pressure; Blood Pressure - drug effects; Carbohydrates; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Dietary Carbohydrates - pharmacology; Dietary Fats - pharmacology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme Inhibitors - pharmacology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gastric Emptying - drug effects; Gastric Emptying - physiology; Glucagon; Glucagon - blood; Glucagon-Like Peptide 1; Glucose; Heart rate; Heart Rate - drug effects; Hemoglobin; Humans; Insulin; Insulin - blood; Insulin - metabolism; Insulin Secretion; Lactones - pharmacology; Lipase - antagonists & inhibitors; Male; Medical sciences; Middle Aged; Orlistat; Peptide Fragments - blood; Plasma; Polypeptides; Protein Precursors - blood
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-004-1591-4

We examined the effects of lipase inhibition with orlistat on (i) gastric emptying of, and (ii) the glycaemic, glucagon-like peptide-1 (GLP-1) and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetic patients. Eight type 2 diabetic patients, who were aged 62 years (median range: 49-68 years) and managed by diet alone, consumed a meal containing 65 g powdered potato, 20 g glucose reconstituted with 200 ml water (labelled with 20 MBq (99m)Tc-sulphur-colloid) and 45 g margarine. They did this on two separate occasions, with and without 120 mg orlistat, and while in the seated position with their back against a gamma camera. Venous blood samples for measurement of blood glucose, plasma insulin and GLP-1 were obtained immediately before the meal and at regular intervals afterwards. Blood pressure (systolic and diastolic) and heart rate were measured using an automated device. Gastric emptying of the meal was faster after orlistat than without orlistat (50% emptying time [mean +/- SEM], 61+/-8 min vs 98+/-5 min; p=0.0001). In the first 60 min after the meal blood glucose (p=0.001) and plasma insulin (p=0.01) concentrations were higher in patients who had taken orlistat; between 60 and 180 min plasma GLP-1 (p=0.02) concentrations were lower after orlistat than without orlistat. Between 0 and 30 min systolic blood pressure (p=0.003) was lower, and heart rate (p=0.03) greater in subjects who had taken orlistat than in those who had not. Inhibition of fat digestion by orlistat may-as a result of more rapid gastric emptying-exacerbate postprandial glycaemia and the postprandial fall in blood pressure in patients with type 2 diabetes after ingestion of meals containing fat and carbohydrate.