Acute changes in the blood glucose concentration have a major reversible effect on esophageal, gastric, intestinal, gallbladder, and anorectal motility in both healthy subjects and diabetic patients. For example, gastric emptying is slower during hyperglycemia than euglycemia and accelerated during hypoglycemia. Acute hyperglycemia also affects perceptions arising from the gastrointestinal tract and may, accordingly, be important in the etiology of gastrointestinal symptoms in diabetes. Elevations in blood glucose that are within the normal postprandial range also affect gastrointestinal motor and sensory function. Upper gastrointestinal motor function is a critical determinant of postprandial blood glucose concentrations by influencing the absorption of ingested nutrients. Interventions that reduce postprandial hyperglycemia, by modulating the rate of gastric emptying, have the potential to become mainstream therapies in the treatment of diabetes.

OBJECTIVE: We evaluated whether a whey preload could slow gastric emptying, stimulate incretin hormones, and attenuate postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: Eight type 2 diabetic patients ingested 350 ml beef soup 30 min before a potato meal; 55 g whey was added to either the soup (whey preload) or potato (whey in meal) or no whey was given. RESULTS: Gastric emptying was slowest after the whey preload (P < 0.0005). The incremental area under the blood glucose curve was less after the whey preload and whey in meal than after no whey (P < 0.005). Plasma glucose-dependent insulinotropic polypeptide, insulin, and cholecystokinin concentrations were higher on both whey days than after no whey, whereas glucagon-like peptide 1 was greatest after the whey preload (P < 0.05). CONCLUSIONS: Whey protein consumed before a carbohydrate meal can stimulate insulin and incretin hormone secretion and slow gastric emptying, leading to marked reduction in postprandial glycemia in type 2 diabetes.

The importance of achieving tight glycemic control, usually assessed by glycated hemoglobin (HbA1c), for both the prevention and delay in the progression of diabetes-related microvascular complications, is established, and the American Diabetes Association/European Association for the Study of Diabetes joint committee has recommended an HbA1c <7% as the goal in patients with type 2 diabetes (1). The relative contributions of pre- and postprandial glycemia to HbA1c have been clarified during the last decade following the seminal report by Monnier et al. (2) indicating that in type 2 diabetes, postprandial glycemic excursions account for about 70% of variability when HbA1c is <7.3%, while the contribution of “fasting” glycemia is greater in less well-controlled patients. Subsequent studies have confirmed the predominance of postprandial glycemia in determining overall glycemic control in “well-controlled” type 2 diabetic patients managed by oral hypoglycemic agents or basal insulin (3). The importance of postprandial glycemia to overall glycemic control is not surprising considering that 1 ) humans in modern societies spend only about 3 or 4 h before breakfast in a truly fasting state because in health, gastric emptying of meals occurs at an overall rate of 1–4 kcal/min (4), and 2 ) postprandial hyperglycemia occurs frequently in diabetes (1). The relevance of postprandial glycemia is further increased by the recognition that it may represent an independent risk factor for adverse cardiovascular outcomes in both diabetic and nondiabetic populations (5). The determinants of postprandial glycemia include preprandial glycemic levels, meal composition, gastric emptying, insulin secretion, small intestinal glucose absorption, and hepatic and peripheral glucose metabolism. Furthermore, the relative contribution of each of these factors may vary over time during the postprandial state. Nevertheless, both the rate of gastric emptying and the secretion and action of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide …

Context: Gastric emptying (GE) is a major determinant of postprandial glycemia. Because the presence of fat in the small intestine inhibits GE, ingestion of fat may attenuate the glycemic response to carbohydrate. Objective: The objective of this study was to evaluate the effect of patterns of fat consumption on GE and glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations after a carbohydrate meal in type 2 diabetes. Design: This was a randomized, cross-over study in which GE of a radioisotopically labeled potato meal was measured on 3 d. Setting: The study was performed at the Royal Adelaide Hospital. Patients: Six males with type 2 diabetes were studied. Intervention: Subjects ingested 1) 30 ml water 30 min before the mashed potato (water), 2) 30 ml olive oil 30 min before the mashed potato (oil), or 3) 30 ml water 30 min before the mashed potato meal that contained 30 ml olive oil (water and oil). Main Outcome Measures: GE, blood glucose, plasma insulin, GLP-1, and GIP concentrations were the main outcome measures. Results: GE was much slower with oil compared with both water (P < 0.0001) and water and oil (P < 0.05) and was slower after water and oil compared with water (P < 0.01). The postprandial rise in blood glucose was markedly delayed (P = 0.03), and peak glucose occurred later (P = 0.04) with oil compared with the two other meals. The rises in insulin and GIP were attenuated (P < 0.0001), whereas the GLP-1 response was greater (P = 0.0001), after oil. Conclusions: Ingestion of fat before a carbohydrate meal markedly slows GE and attenuates the postprandial rises in glucose, insulin, and GIP, but stimulates GLP-1, in type 2 diabetes.

OBJECTIVE—To define the predictors of the rate of gastric emptying in patients with diabetes. RESEARCH DESIGN AND METHODS—A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes). RESULTS—The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 ± 3.2 vs. 50.2 ± 3.6%, P < 0.005) and liquid (retention at 100 min 22.7 ± 1.7 vs. 16.0 ± 1.8%, P < 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting), only abdominal bloating/fullness was associated with slower gastric emptying (P < 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors of slower gastric emptying of both solids and liquids. CONCLUSIONS—We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.