Effect of calcitonin on gastric emptying and on postprandial gastrin and insulin release in patients with type I gastric ulcer

In a double-blind placebo-controlled study, the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in six patients with type I gastric ulcer. Synthetic salmon calcitonin 415 pmol i.v. was given as a bolus followed by a 90-min infusion to reach an overall dose of 62.25 pmol.kg-1. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin suppressed gastric emptying in all patients examined. The mean gastric transit time, MTT90, increased from 38.1 +/- 0.4 min after placebo to 43.1 +/- 0.6 min after calcitonin (P less than 0.001). Calcitonin significantly blunted the postprandial gastrin release: AUC0-90 10,398 +/- 2886 ng. l-1 min (placebo) and 8238 +/- 2573 ng. l-1 min (calcitonin), P less than 0.05, and abolished the postprandial insulin release--AUC0-90 2244 +/- 230 mU.l-1 min (placebo) vs. 638 +/- 198 mU.l-1 min (calcitonin), P less than 0.01. A steady increase in the serum glucose during calcitonin infusion, reaching up to 5.6 +/- 0.31 mmol.l-1 at the end of the infusion, was observed. Calcitonin did not significantly affect serum calcium or phosphorus concentrations. The authors conclude that a delayed gastric emptying is to be expected in patients undergoing calcitonin treatment.     

Effect of calcitonin on gastric emptying and on serum insulin and gastrin concentrations after ingestion of a mixed solid-liquid meal in humans

In a double-blind placebo-controlled study, we examined the effect of calcitonin on gastric emptying, and on serum concentrations of gastrin, insulin, glucose, calcium, and phosphorus after a mixed solid-liquid meal in 11 healthy men. Synthetic salmon calcitonin was administered as a 415 pmol i.v. bolus injection followed by a 90-min infusion to reach an overall dose of 62.25 pmol/kg body mass. Gastric emptying of a radiolabeled meal was surveyed by means of a gamma camera. A pronounced inhibition of gastric emptying with calcitonin was observed in all subjects (median gastric half emptying time 60.3 min after placebo versus 197.6 min after calcitonin; p less than 0.001). Calcitonin did not effect the postprandial gastrin release, nor did it change significantly the serum calcium or phosphorus concentrations. A decreased postprandial insulin release by calcitonin (mean +/- SEM area under the insulin curve 2,124.6 +/- 382.0 min mU L-1 after placebo versus 640.9 +/- 124.0 min mU L-1 after calcitonin; p less than 0.002) was accompanied by a different pattern of serum glucose concentrations during the infusion of the hormone when compared to the situation with a placebo. We discuss potential mechanisms and clinical relevance of our findings.     

Effect of calcitonin on gastric emptying in patients with an active duodenal ulcer.

In a double blind placebo controlled study the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in eight patients with duodenal ulcer. Synthetic salmon calcitonin 415 pmol iv was given as a bolus followed by a 90 minute infusion to reach an overall dose of 62.25 pmol/kg. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin markedly delayed gastric emptying in all patients examined. The emptying index (Ix) decreased from 2.979 (0.397)/min after placebo to 0.896 (0.317)/min after calcitonin (p less than 0.001). Calcitonin did not affect significantly postprandial gastrin release: AUC0-90, 8768 (880) pg/l min (placebo) and 7807 (619) pg/l min (calcitonin). Postprandial insulin release was abolished by calcitonin -Auc0-90, 2258 (242) mU/l min (placebo) v 736 (131) mU/l min (calcitonin), p less than 0.001. Parallel to the suppression of insulin release was a steady increase in the serum glucose during calcitonin infusion, with the highest glucose concentration of 5.8 (0.53) mmol/l at the end of infusion of the hormone. Calcitonin did not change significantly serum calcium or phosphorus concentrations. A combination of a delaying effect on gastric emptying with the inhibition of gastric acid secretion elicited by calcitonin warrants further studies of calcinonin in the treatment of duodenal ulcer.     

Effect of cisapride on gastric emptying and ileal transit time of balanced liquid meal in healthy subjects

Cisapride is a new prokinetic gastrointestinal agent which has been shown to be able to increase gastric emptying and intestinal transit time in experimental animals and in patients with preexisting motility alterations. Up to now, however, clinical research evaluating the activity of the drug in healthy subjects is very limited. We have therefore undertaken a placebo-controlled study to simultaneously investigate the effect of cisapride (20 mg p.o.) on gastric emptying and intestinal transit time of a balanced liquid meal in 9 healthy volunteers. Median gastric half-time was 60 min after cisapride, as compared to 73 min after placebo (p less than 0.05). Intestinal transit time was similar after cisapride (75 min) or after placebo (105 min). These data confirm that cisapride significantly increases the speed of gastric emptying also in normal subjects. The lack of effect on intestinal transit could be explained by the interindividual variation observed in our experiments.     

Prolongation of gastric emptying by aerosolized atropine

Aerosolized atropine causes anticholinergic side effects. We evaluated gastroparesis, a previously unreported side effect of inhaled atropine, in a double-blind, placebo-controlled, crossover study. Six young asthmatics received atropine (0.05 mg/kg) or placebo at 4-h intervals for 3 dosages, on 2 separate days at least 1 wk apart. Subjective complaints, pulse, visual accommodation, and citric-acid-stimulated salivary flow were recorded 30 min after each dose on each study day. A radionuclide (99mTc) study of gastric emptying time was done 30 min after the final dose on each study day. Atropine prolonged mean gastric half emptying time (112 +/- 59 min) compared with placebo (65 +/- 34 min) (p less than 0.05). However, gastric emptying after atropine was in the abnormal range in only 2 patients. Stimulated salivary flow decreased after atropine (1.97 +/- 1.7 g saliva) compared with flow after placebo (4.1 +/- 1.2 g) (p less than 0.05). No changes in visual accommodation or pulse rate were seen. Dry mouth and decreased salivation correlated with delayed gastric emptying (r = 0.76, p less than 0.05). Anticholinergic side effects of aerosolized atropine include prolonged gastric emptying in some patients. Gastroparesis after inhaled atropine is suggested by the symptom of dry mouth.     

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.     

Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study

BACKGROUND: Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In animals, ghrelin increases gastric emptying and reverses postoperative ileus. We present the results of a double blind, placebo controlled, crossover study of ghrelin in gastric emptying in patients with diabetic gastroparesis. METHODS: Ten insulin requiring diabetic patients (five men, six type I) referred with symptoms indicative of gastroparesis received a two hour infusion of either ghrelin (5 pmol/kg/min) or saline on two occasions. Blood glucose was controlled by euglycaemic clamp. Gastric emptying rate (GER) was calculated by real time ultrasound following a test meal. Blood was sampled for ghrelin, growth hormone (GH), and pancreatic polypeptide (PP) levels. Cardiovagal neuropathy was assessed using the Mayo Clinic composite autonomic severity score (range 0 (normal)-3). RESULTS: Baseline ghrelin levels were mean 445 (SEM 36) pmol/l. Ghrelin infusion achieved a peak plasma level of 2786 (188) pmol/l at 90 minutes, corresponding to a peak GH of 70.9 (19.8) pmol/l. Ghrelin increased gastric emptying in seven of 10 patients (30 (6)% to 43 (5)%; p = 0.04). Impaired cardiovagal tone correlated inversely with peak postprandial PP values (p < 0.05) but did not correlate with GER. CONCLUSIONS: Ghrelin increases gastric emptying in patients with diabetic gastroparesis. This is independent of vagal tone. We propose that analogues of ghrelin may represent a new class of prokinetic agents.     

Effect of calcitonin on gall-bladder volume in man

The effect of increasing intravenous doses of synthetic salmon calcitonin (0.0044, 0.0088, 0.0175, and 0.0350 iu/kg per min) versus placebo on the fasted gall-bladder volume was assessed in seven normal subjects according to a double-blind study protocol. In addition, the action of calcitonin on meal-induced gall-bladder emptying was examined. Gall-bladder volumes were measured by means of real-time ultrasonography. Calcitonin evoked a dose-dependent relaxation of the fasted gall-bladder. A statistically significant increase of the fasted gall-bladder volume was observed with 0.0175 (23.4 +/- 5.5 cm3 placebo versus 33.9 +/- 7.7 cm3 calcitonin, P less than 0.001) and 0.0350 (21.4 +/- 4.6 cm3 placebo versus 36.1 +/- 8.4 cm3 calcitonin, P less than 0.01) iu/kg per min calcitonin, whereas a mean increase of the gall-bladder volume amounted to 32.1% and 46.5%, respectively. A significant delay of the gall-bladder emptying after calcitonin was reflected by a decrease of the ejection fraction: 23.2 +/- 8.3% calcitonin versus 57.8 +/- 6.9% placebo (P less than 0.02) at 20 min, and 40.5 +/- 8.8% calcitonin versus 67.2 +/- 3.8% placebo (P less than 0.02) at 30 min after the test meal. Calcitonin is concluded to have a potent relaxing effect on the human gall-bladder.     

Gastric neuropeptides and gastric motor abnormality in streptozotocin-induced diabetic rats: observation for four weeks after streptozotocin

Alterations of gastric calcitonin gene-related peptide and substance P content and gastric emptying in early stages of streptozotocin-induced diabetic rats were investigated. Diabetes was induced by intravenous injection of streptozotocin (50 mg/kg) in male Wistar rats. Gastric emptying of phenol red solution and calcitonin gene-related peptide and substance P content of gastric walls, measured by radioimmunoassay, was assessed two and four weeks after streptozotocin injection. Gastric emptying two weeks after streptozotocin was delayed (32 ± 9%) and that four weeks after was enhanced (73 ± 2%) compared with nondiabetic control rats (50 ± 3%). Calcitonin gene-related peptide content of the gastric antrum and corpus was increased two weeks after and decreased four weeks after streptozotocin, while gastric substance P content was not changed at any time in diabetic rats. Insulin treatment reversed alterations of gastric emptying and calcitonin gene-related peptide content. The delayed gastric emptying in two-week diabetic rats was reversed by CGRP antagonist and the enhanced gastric emptying in four-week diabetic rats was reversed by CGRP pretreatment. These results suggest a possible relationship between gastric calcitonin gene-related peptide and abnormal gastric motility in diabetic state.     

Relationship between the effects of cisapride on gastric emptying and plasma glucose concentrations in diabetic gastroparesis

BACKGROUND/AIMS: The effect of erythromycin on gastric emptying is attenuated during hyperglycaemia. The aim of this study was to determine in patients with diabetic gastroparesis whether the effect of cisapride on gastric emptying of solids and liquids is influenced by the plasma glucose concentration. METHODS: Nineteen patients with type 1 diabetes mellitus, who had delayed gastric emptying of solids and/or liquids, were studied. On 2 separate days, each patient received cisapride (20 mg) or placebo orally 60 min before scintigraphic measurement of gastric emptying of a mixed solid (ground beef) and liquid (dextrose) meal. The plasma glucose concentrations were measured at -5, 30, 60, 90, and 120 min during each gastric emptying measurement. RESULTS: Cisapride accelerated both solid (retention at 100 min 43 +/- 4 vs. 69 +/- 4%, p < 0.001) and liquid (T50 27 +/- 2 vs. 39 +/- 2 min, p < 0.001) gastric emptying. The mean plasma glucose level was not significantly different after placebo when compared with cisapride (19.5 +/- 1.1 vs. 18.2 +/- 1.0 mmol/l). The change in the 50% emptying time (T50) for liquid, but not solid, emptying was related (r = 0.55, p = 0.01) to the change in the plasma glucose AUC from 0 to 30 min between the placebo and cisapride tests, i.e., the acceleration was greater if the plasma glucose concentration was relatively less during the gastric emptying test performed on cisapride. CONCLUSION: The effect of cisapride on gastric emptying, at least that of liquids, in patients with diabetic gastroparesis appears to be dependent on the plasma glucose concentration.     

Effect of erythromycin on gastric emptying in healthy individuals assessed by radio-opaque markers and plasma acetaminophen levels

We simultaneously recorded gastric emptying of radio-opaque markers (ROMs) and monitored serial changes in plasma acetaminophen (AAP) levels to demonstrate the relationship between the ROM and the AAP methods, and we investigated the effect of a single intravenous dose of erythromycin (EM) on gastric emptying in healthy human subjects. After an overnight fast, subjects were randomized to receive either placebo or EM lactobionate (Abbott, North Chicago, IL, USA) 250 mg intravenously in a single dose, given immediately before a standard meal. Subjects ingested 1.5 g of AAP and ROMs with the test meal. A supine plain abdominal radiograph was taken 1, 2, 3, and 6h after ingestion of the test meal. Peripheral blood samples were obtained 0, 0.5, 1, 1,5, 2, 3, and 6 h after ingestion of the test meal. EM significantly accelerated gastric emptying of ROMs. By 6 h, no markers remained in the stomach in any of the subjects in the placebo or EM groups. By 120 min, half of the ROMs had passed into the duodenum in 12.5% of subjects after placebo, whereas EM injection resulted in gastric emptying of half of the ROMs in all subjects. There was no difference in plasma AAP concentration between the placebo and EM groups. There were significant correlations between maximum plasma AAP concentration and gastric emptying of ROMs 120 min after ingestion (r=0.546;P=0.019), and between time of maximum plasma AAP concentration and gastric emptying of ROMs 120 min after ingestion (r=−0.568;P=0.014). The time taken to reach the peak concentrations ranged from 30 to 90 min after ingestion, whereas most ROMs were emptied 120 min after ingestion. We conclude that the gastric emptying assessed by ROMs and by serial changes in plasma AAP level are good, non-invasive, clinically applicable tests, with a significant correlation between the two tests. A single intravenous dose of EM had a prokinetic effect on gastric emptying, assessed by ROMs, in healthy human subjects.     

Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes

The effects of different i.v. doses of glucagon-like peptide 1 (GLP-1) on glucose homeostasis and gastric emptying were compared in patients with type 2 diabetes. Twelve patients with type 2 diabetes received three different infusion rates of GLP-1 (0.4, 0.8, and 1.2 pmol/kg x min) or placebo in the fasting state and after a solid test meal (containing [(13)C]octanoic acid). Blood was drawn for glucose, insulin, C-peptide, glucagon, and GLP-1 determinations. The gastric emptying rate was calculated from the (13)CO(2) excretion rates in breath samples. Statistics were determined using repeated measures ANOVA and Duncan's post hoc test. Plasma glucose concentrations were equally normalized with all GLP-1 doses (P < 0.001). Insulin and C-peptide concentrations dose-dependently rose during GLP-1 infusion in the fasting state (P < 0.05), but were dose-dependently reduced by GLP-1 after meal ingestion (P = 0.0031 and 0.0074, respectively). Glucagon secretion was suppressed with GLP-1. Gastric emptying was decelerated by GLP-1 in a dose-dependent fashion (P < 0.001). Despite a dose-dependent stimulation of insulin secretion, glucose normalization can be achieved even with 0.4 pmol GLP-1/kg x min. Due to the dose-dependent inhibition of gastric emptying, lower GLP-1 doses than previously used may be as suitable for glucose control in patients with type 2 diabetes.     

A synthetic prostaglandin E2 analogue, enprostil, hastens gastric emptying of solids in patients with an active duodenal ulcer

The effect of gastric emptying of two doses (35 and 70 micrograms) of enprostil given orally was evaluated in eight patients with endoscopically confirmed duodenal ulcer. Gastric emptying of a radiolabelled solid meal was assessed with the use of a gamma camera. Enprostil dose-dependently accelerated gastric emptying of solids; the gastric emptying index, Ix, increased from 1.62 +/- 0.38 min-1.10(-2) after placebo to 2.77 +/- 0.56 min-1.10(-2) after 35 micrograms enprostil (p less than 0.05 versus placebo) and to 3.65 +/- 0.64 min-1.10(-2) after 70 micrograms enprostil (p less than 0.005 versus placebo). The fraction of the radiolabelled food retained in the stomach at the end of the gastric emptying examination (that is, after 90 min) amounted to 50.5 +/- 6.9% after placebo, 35.2 +/- 7.4% after 35 micrograms enprostil, and 24.1 +/- 8.4% after 70 micrograms enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.     

Induced-hyperglycemia attenuates erythromycin-induced acceleration of hypertonic liquid-phase gastric emptying in type-I diabetic patients

BACKGROUND: Erythromycin has been found to be a gastrointestinal prokinetic agent of hypertonic liquids, while acute hyperglycemia has been associated with delayed gastric emptying in diabetic patients. AIM: To investigate whether hyperglycemia, per se, reduces gastric motility during erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients. METHODS: In 12 type-I diabetic patients following a hypertonic radiolabeled liquid meal, gastric emptying was measured scintigraphically during normoglycemia (5-8.9 mmol/l glucose) or hyperglycemia induced by intravenous (16-19 mmol/l) glucose infusion. The tests were performed on 4 separate days in random order after administering either placebo or 200 mg i.v. erythromycin. RESULTS: In the hyperglycemic state compared to normoglycemia, the gastric emptying of the hypertonic liquid was reduced after placebo or erythromycin administration. The lag-phase duration (17.8+/-5.5 and 7.8+/-4.5 vs. 10.8+/-3.4 and 3.7+/-2.5 min, respectively, p<0.001), the overall gastric emptying time of the half meal (52.8+/-13 and 24.9+/-5.5 vs. 42.5+/-10.5 min and 16.6+/-6 min, respectively, p<0.001) and the retained percentage of liquid meal in the stomach at 60 and 100 min postprandially (p<0.001) were significantly increased. CONCLUSIONS: The erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients is related to the plasma glucose level. The induced hyperglycemia reduces the erythromycin-induced acceleration of liquid-phase gastric emptying, decreasing the overall gastric emptying rate. In spite of the inhibitory effect of induced hyperglycemia on the gastric emptying of hypertonic liquids, erythromycin is still able to accelerate the emptying rate and could prove to be a useful prokinetic agent under hyperglycemic conditions.     

Effect of metoclopramide in chronic gastric retention after gastric surgery.

The effect of metoclopramide, a stimulant of gastric motility, on gastric emptying was tested in 6 patients with chronic gastric retention after vagotomy and gastric resection, unexplained by mechanical obstruction or stomal ulceration. Gastric emptying was measured using a gamma camera technique and a solid meal labeled with 99mtechnetium-labeled diethylenetriaminepentaacetic acid. Metoclopramide produced a 2.6-fold increase in gastric emptying in the first 90 min after eating the meal, compared to placebo (P less than 0.01). Metoclopramide did not alter gastric emptying in 8 normal volunteers. These data indicate that metoclopramide may be useful in treatment of patients with chronically impaired gastric emptying after gastric surgery.     

Gastric emptying and subjective symptoms of nausea: lack of effects of a 5-hydroxytryptamine-3 antagonist ondansetron on gastric emptying in patients with gastric stasis syndrome

Thirty-seven consecutive patients referred to a regional gastroenterology outpatient clinic with complaints of persistent nausea had a double isotopic scintigraphic evaluation of solid and liquid gastric emptying. Gastric emptying of both forms followed an exponential model. Marked day to day variation of gastric emptying was noted with a coefficient of variation of approximately 0.20 for both phases. Only 9 of 37 patients had delayed gastric emptying rate of the solid component (greater than 180 min) and no correlation between gastric stasis syndrome and nausea was established. Among these patients the median time for the stomach to empty 50% of the solid component was 261 min and 50% of the liquid component was 66 min. Treatment of these 9 patients shown to have gastric stasis syndrome and further 3 patients with diabetic gastroparesis with ondansetron, a highly selective antagonist of 5-hydroxytryptamine-3-receptors, resulted in a gastric emptying rate which was not statistically faster than after placebo (p = 0.11).     

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease

OBJECTIVE: A delay in gastric emptying has been reported in patients with gastro-oesophageal reflux disease (GORD), but its role in increasing the number of reflux episodes is still debated. The aim of this study was to assess the relationship between acceleration of gastric emptying and gastro-oesophageal reflux in patients with endoscopy-negative GORD and pathological oesophageal acid exposure. MATERIAL AND METHODS: Twelve patients (7 M, age range 24-65 years) underwent 6-h postprandial (2.1 MJ meal) combined gastric emptying by real-time ultrasonography and intra-oesophageal pH monitoring after cisapride (20 mg b.i.d.) and placebo for 3 days, on two separate occasions at least 7 days apart in double-blind randomized order. Gastric emptying after placebo was also measured in 12 healthy volunteers (7 M, age range 25-54 years). RESULTS: In the patients' group, the area under the emptying time curve was greater (p<0.01), and half and total emptying times prolonged (p<0.01) compared to the healthy subjects, 115 min (mean)+/-6 (SEM) versus 86+/-6 and 232 min+/-16 versus 160+/-7, respectively. Cisapride accelerated both half- and total gastric emptying (p<0.02): -22 min (mean); -10 to -34 (95% CI) and -48 min; -10 to -85, respectively, decreased both percentage of time at pH < 4 (p<0.01) and number of reflux episodes (p<0.05). However, no relationship was found between changes in gastric emptying and in the reflux variables by linear regression analysis (R2<0.005). CONCLUSION: The emptying rate of the whole stomach is not a major determinant of gastro-oesophageal reflux.     

Hyperglycemia Attenuates Erythromycin-Induced Acceleration of Liquid-Phase Gastric Emptying of Hypertonic Liquids in Healthy Subjects

Acute hyperglycemia has been associated with delayed gastric emptying in healthy controls. Erythromycin has recently been found to be a gastrointestinal prokinetic agent in both solids and hypertonic liquids. Our aim was to examine whether the acute steady-state hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of hypertonic liquids after a fasted state of the stomach in healthy subjects. In 12 healthy subjects scintigraphic measurement of gastric emptying of a hypertonic radiolabeled liquid meal, during normoglycemia (5–8.9 mmol/l glucose) or induced hyperglycemia (16–19 mmol/liter glucose) by intravenous glucose infusion after giving either placebo or 200 mg intravenous erythromycin, was performed on four separate days in random order. In the hyperglycemic state compared with normoglycemia, either after placebo administration or erythromycin, the gastric emptying of the hypertonic liquid was reduced. The lag-phase duration was significantly increased (17.5 ± 5.5 min, and 7.2 ± 4.5 min vs 10.5 ± 3.4 min, and 3.5 ± 2.5 min, respectively, P < 0.0001) as were the overall T1/2 (gastric emptying time of the half meal) (52.5 ± 13 min and 24.5 ± 5.5 min vs 42 ± 10.5 min, and 16 ± 6 min, respectively, P < 0.0001) and the percentage of liquid meal retained in the stomach at 60 and 100 min postprandially (P < 0.001). In conclusion, hyperglycaemia attenuates the acceleration effect of erythromycin and decreases the overall gastric emptying rate of hypertonic liquids in healthy subjects.     

Glucose control is not improved by accelerating gastric emptying in patients with type 1 diabetes mellitus and gastroparesis. a pilot study with cisapride as a model drug.

The present pilot study investigated whether acceleration of gastric emptying in patients with type 1 diabetes and delayed gastric emptying (a possible cause of poorly controlled diabetes) improves long-term glucose control. Eight outpatients with diabetes (age 28-63 years, mean diabetes duration 24.6+/-6.0 years) and delayed gastric emptying of radio-opaque markers were randomised and treated, for three months each, with a prokinetic drug (cisapride 20 mg twice daily) and placebo. Mean capillary glucose, glucose variability (M-values, MAGE), fructosamine, and HbA1c were assessed. Gastric emptying of a solid standard meal was measured by scintigraphy after each treatment period. Chronic administration of a prokinetic drug resulted in improved solid gastric emptying (percentage residual) at 120 min (p=0.025). The percentage residual was 43.6+/-9.6 % during prokinetic treatment and 59.7+/-9.9 % during placebo (standard error of paired differences 5.7 %). The mean gastric emptying time (t/2) of solids was 88 min during prokinetic treatment compared to 113 min in the placebo arm (SE of paired differences 14 min; p=0.09). Mean blood glucose values (9.0+/-3.8 vs. 8.8+/-3.7 mmol/l), daily glucose variability (MAGE 6.8+/-1.3 vs. 6.3+/-1.6 mmol/l; M-value 15.2+/-2.5 vs. 13.9+/-4.5), and HbA1c at 3 months (7.8+/-1.1 % vs. 7.6+/-1.0 %) were not statistically different between prokinetic drug and placebo treatment. Similarly, the frequency of hypoglycaemic episodes (< or = 3 mmol/l) was not different in both groups (78 vs. 68). Our pilot study showed that long-term acceleration of gastric emptying had no effect on overall glycaemic control, the magnitude of glucose excursions, and hypoglycaemic episodes in patients with diabetic gastroparesis. We do not recommend, therefore, acceleration of gastric emptying as treatment strategy for "brittle diabetes" in patients with type 1 diabetes.     

The effect of omeprazole on gastric acidity and the absorption of liver cobalamins

The effect of gastric anacidity on the absorption of food-bound cobalamins is uncertain. Omeprazole, an inhibitor of the enzyme H-K-ATPase in the parietal cell, is the most potent inhibitor of gastric acidity known so far. In 17 healthy male volunteers the absorption of liver-bound cobalamins was assessed after a single intravenous dose of omeprazole (80 mg) or placebo in a double-blind, crossover manner. The effect of omeprazole on pH, gastric acidity, and intrinsic factor (IF) concentration was measured in aspirates of gastric juice 5 min before and 30 and 60 min after the administration of liver homogenate containing 0.74 nmol of 57Co-labelled cobalamins. Omeprazole treatment resulted in anacidity (pH values above 6.0) in 14 individuals 30 min after the liver dose and in 15 individuals after 60 min. The IF concentration was unchanged in the omeprazole experiment as compared with the placebo experiment. The absorption of liver-bound cobalamins was 310 pmol (189-501 pmol) in the omeprazole experiment as compared with 415 pmol (150-549 pmol) in the placebo experiment (median values and range, p = 0.5228). We suggest that anacidity induced by omeprazole does not reduce the absorption of liver-bound cobalamins.