Judith M. Wishart

Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects

SummaryThe relationships between gastric emptying and intragastric distribution of glucose and oral glucose tolerance were evaluated in 16 healthy volunteers. While sitting in front of a gamma camera the subjects drank 350 ml water containing 75 g glucose and 20 MBq 99mTc-sulphur colloid. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide were obtained at — 2, 2, 5, 10, 15, 30, 45, 60, 75, 90, 105, 120 and 150 min. Gastric emptying approximated a linear pattern after a short lag phase (3.3±0.8 min). The 50% emptying time was inversely related to the proximal stomach 50% emptying time (r=−0.55, p<0.05) and directly related to the retention in the distal stomach at 120 min (r=0.72, p<0.01). Peak plasma glucose was related to the amount emptied at 5 min (r=0.58, p<0.05) and the area under the blood glucose curve between 0 and 30 min was related to the amount emptied at 30 min (r=0.58, p<0.05). In contrast, plasma glucose at 120 min was inversely related to gastric emptying (r=−0.56, p<0.05) and plasma insulin at 30 min (r=−0.53, p<0.05). Plasma insulin at 120 min was inversely related (r=−0.65, p<0.01) to gastric emptying. The increase in plasma gastric inhibitory polypeptide at 5 min was related directly to gastric emptying (r=0.53, p<0.05). These results indicate in normal subjects that (i) gastric emptying accounts for about 34 % of the variance in peak plasma glucose after a 75-g oral glucose load (ii) plasma glucose levels at 120 min are inversely, rather than directly, related to gastric emptying (iii) the distal stomach influences gastric emptying of glucose.

Gastric and oesophageal emptying in patients with Type 2 (non-insulin-dependent) diabetes mellitus

SummaryGastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 20 randomly selected Type 2 (non-insulin-dependent) diabetic patients receiving oral hypoglycaemic therapy and 20 control subjects. In the diabetic patients, the relationships between oesophageal emptying, gastric emptying, gastrointestinal symptoms, autonomic nerve function and glycaemic control were examined. The percentage of the solid meal remaining in the stomach at 100 min (p<0.001), the 50% gastric emptying time for the liquid meal (p<0.05) and oesophageal emptying (p<0.05) were slower in the diabetic patients compared to the control subjects. Scores for upper gastrointestinal symptoms and autonomic nerve dysfunction did not correlate significantly (p>0.05) with oesophageal, or gastric emptying. The 50% gastric emptying time for the liquid meal was positively related (r=0.58, p<0.01) to the plasma glucose concentration at the time of the performance of the gastric emptying test and the lag period, before any solid food emptied from the stomach, was longer (p<0.05) in subjects with plasma glucose concentrations during the gastric emptying measurement greater than the median, compared to those with glucose concentrations below the median. These results indicate that delayed gastric and oesophageal emptying occur frequently in Type 2 diabetes mellitus and that delayed gastric emptying relates, at least in part, to plasma glucose concentrations.

Relationships between oesophageal transit and solid and liquid gastric emptying in diabetes mellitus

In 87 randomly selected diabetic patients (67 type 1, 20 type 2) and 25 control subjects, gastric emptying of digestible solid and liquid meals and oesophageal transit of a solid bolus were measured with scintigraphic techniques. Gastrointestinal symptoms, autonomic nerve function and glycaemic control were evaluated in the diabetic patients. Gastric emptying and oesophageal transit were slower (P < 0.001) in the diabetic patients compared with the control subjects, and each was delayed in about 40% of them. There was a relatively weak (r=0.32; P<0.01) relationship between solid and liquid gastric emptying, and no significant correlation (r=0.11, NS) between oesophageal transit and gastric emptying of the solid meal. Scores for upper gastrointestinal symptoms and autonomic nerve function correlated weakly (r=0.21; P < 0.05) with both oesophageal transit and gastric emptying. Gastric emptying of the liquid meal was slower (P < 0.05) in patients with blood glucose concentrations > 15 mmol/1. These results indicate that gastric emptying in patients with diabetes mellitus should be assessed by liquid as well as by solid test meals and that oesophageal transit should not be used as a predictor of generalised diabetic gastroenteropathy.

Effects of a Protein Preload on Gastric Emptying, Glycemia, and Gut Hormones After a Carbohydrate Meal in Diet-Controlled Type 2 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.

Effect of cisapride on gastric and esophageal emptying in insulin-dependent diabetes mellitus*

The effects of cisapride on gastric emptying, esophageal emptying, gastrointestinal symptoms, and glycemic control were evaluated in 20 insulin-dependent diabetics who had delayed gastric emptying of the solid or liquid component of a meal, or both. A double-isotope technique was used to measure gastric emptying, and esophageal emptying was measured as the time for a bolus of the solid meal to enter the stomach. On 2 days each patient received cisapride (20 mg) or placebo orally, 60 min before an esophageal and gastric emptying test. A third gastric and esophageal emptying test was performed after each patient had orally taken 10 mg of cisapride or placebo q.i.d. for 4 wk. Single-dose cisapride increased esophageal emptying (p less than 0.01) and both solid and liquid gastric emptying (p less than 0.001). The response to cisapride was most marked in patients with the greatest delay in esophageal and gastric emptying (p less than 0.05). After administration of cisapride for 4 wk, gastric emptying of solid and liquid were faster (p less than 0.001), but esophageal emptying was not significantly different from the placebo test. Upper gastrointestinal symptoms were less after cisapride (p less than 0.05), whereas there was no change on placebo (p greater than 0.2). Plasma glucose and glycosylated hemoglobin concentrations were not different after cisapride compared with placebo. These results indicate that single-dose cisapride increases esophageal emptying in insulin-dependent diabetics and that chronic administration of cisapride is effective in the treatment of diabetic gastroparesis.

Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects

The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in glucose homeostasis in both health and diabetes. In mice, sucralose, an artificial sweetener, stimulates GLP-1 release via sweet taste receptors on enteroendocrine cells. We studied blood glucose, plasma levels of insulin, GLP-1, and GIP, and gastric emptying (by a breath test) in 7 healthy humans after intragastric infusions of 1) 50 g sucrose in water to a total volume of 500 ml (approximately 290 mosmol/l), 2) 80 mg sucralose in 500 ml normal saline (approximately 300 mosmol/l, 0.4 mM sucralose), 3) 800 mg sucralose in 500 ml normal saline (approximately 300 mosmol/l, 4 mM sucralose), and 4) 500 ml normal saline (approximately 300 mosmol/l), all labeled with 150 mg 13C-acetate. Blood glucose increased only in response to sucrose (P<0.05). GLP-1, GIP, and insulin also increased after sucrose (P=0.0001) but not after either load of sucralose or saline. Gastric emptying of sucrose was slower than that of saline (t50: 87.4+/-4.1 min vs. 74.7+/-3.2 min, P<0.005), whereas there were no differences in t50 between sucralose 0.4 mM (73.7+/-3.1 min) or 4 mM (76.7+/-3.1 min) and saline. We conclude that sucralose, delivered by intragastric infusion, does not stimulate insulin, GLP-1, or GIP release or slow gastric emptying in healthy humans.

Effect of age on bone density and bone turnover in men

OBJECTIVE Little Is known about the pattern of age‐related bone loss in men, and although androgens are required for optimum bone mass it Is not clear whether the fall in bone mass with age in men is related to failing androgens.

Gastric and oesophageal emptying in insulin-dependent diabetes mellitus

Abstract Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 45 randomly selected insulin‐dependent diabetics and in 22 control subjects. In the diabetics, the relationships between oesophageal emptying, gastric emptying, age, duration of diabetes mellitus, upper gastrointestinal symptoms, glycaemic control and the complications, autonomic neuropathy, peripheral neuropathy and retinopathy were examined. The lag period before solid food left the stomach was not significantly different in diabetics compared with control subjects, but the percentage retention of solid food at 100 min was greater (P < 0.001) in the diabetic subjects. Both the early phase (percentage retention at 10 min) and the 50% emptying time for liquid gastric emptying were delayed (P < 0.001) in the diabetic subjects. Of the diabetics, 58% had delayed gastric emptying of either the solid and/or the liquid meal; oesophageal emptying was delayed in 42%. Upper gastrointestinal symptoms correlated poorly with both gastric and oesophageal emptying. Oesophageal emptying, solid gastric emptying and the liquid 50% emptying time correlated with the severity of autonomic nerve dysfunction (P < 0.05). The early phase of liquid emptying (retention at 10 min) was significantly slower (P < 0.05) in patients with mean plasma glucose concentrations of > 15 mmol/l during the gastric emptying test and the lag period for solid emptying correlated with both the glycosylated haemoglobin and mean plasma glucose concentrations.

Gastric and Oesophageal Emptying in Obesity

Gastric and oesophageal emptying were evaluated in 31 obese patients and 31 control subjects. A double-isotope technique was used to measure gastric emptying of a mixed solid/liquid meal, and oesophageal emptying was measured as the time taken for a bolus of the solid meal to enter the stomach. Gastric emptying of the solid (p less than 0.001) and the liquid (p less than 0.02) meal and oesophageal emptying (p less than 0.001) were delayed in the obese patients compared with the control subjects. There were no significant relationships among gastric emptying, oesophageal emptying, and upper gastrointestinal symptoms in the obese patients alone, but in the total group of 62 subjects there were significant correlations between body mass index and both gastric (r = 0.44, p less than 0.01) and oesophageal (r = 0.45, p less than 0.001) emptying. These results indicate that delayed gastric and oesophageal emptying occurs frequently in obesity and that these abnormalities relate to body weight.

The effects of miglitol on glucagon‐like peptide‐1 secretion and appetite sensations in obese type 2 diabetics

Background: Previous studies reported that administration of first generation α‐glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon‐like peptide‐1 (GLP‐1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP‐1 after AGI therapy in diabetics. GLP‐1 plays a role to mediate satiety. Any agent that substantially elevates GLP‐1 levels may theoretically reduce hunger, increase satiation and limit food intake.