Effect of cisapride on gastric emptying of indigestible solids in patients with gastroparesis diabeticorum. A comparison with metoclopramide and placebo

Cisapride is a prokinetic agent believed to facilitate acetylcholine release from the myenteric plexus of the gut. The effect of cisapride on gastric emptying of solids was studied in 9 diabetic patients, all of whom had delayed gastric emptying of indigestible solids (gastroparesis). Six patients had chronic nausea and vomiting, and 3 had no symptoms. Cisapride (5 mg) was given intravenously 15 min before ingestion of a 400-kcal test meal and 10 indigestible solid radiopaque markers. On separate days and in random order each patient also received intravenous metoclopramide (10 mg) or placebo 15 min before ingestion of the meal and markers. Mean gastric emptying of radiopaque markers, assessed by serial radiographs of the gastric region, was accelerated by metoclopramide and cisapride, but the difference reached significance only with cisapride (p less than 0.05). There was considerable intersubject variability in gastric emptying responses to cisapride and metoclopramide. No side effects occurred with either drug. This study indicates that acute, intravenous administration of cisapride accelerates gastric emptying of indigestible solids in patients with diabetic gastroparesis.     

Metoclopramide therapy in patients with delayed gastric emptying

Twenty-eight patients with delayed gastric emptying as measured by an abnormal barium burger were treated with metoclopramide in a randomized, double-blind fashion. Five had diabetic gastroparesis, four had undergone vagotomy and pyloroplasty, and 19 were idiopathic. Patients received either metoclopramide or placebo for a three-week period and symptoms were scored prestudy, at weekly intervals, and at termination of the study. Ten of 14 patients on metoclopramide and four of 14 on placebo decreased their symptom score to a level below entry criteria, indicating a significant metoclopramide effect when compared to placebo. The mean total symptom score for the metoclopramide group was 18.4 prestudy and 7.2 poststudy while for placebo was 19.1 prestudy and 12.9 poststudy. Although improvement on placebo was significant, these patients were still symptomatic. The improvement on metoclopramide was significantly greater than the improvement on placebo. Metoclopramide is an effective agent in treating the symptom complex of delayed gastric emptying.     

Objective and subjective results of a randomized,double-blind,placebo-controlled trial using cisapride to treat gastroparesis

Cisapride, a relatively new gastrointestinal prokinetic agent, has been reported to increase gastric emptying and improve symptoms of gastroparesis. We investigated these effects of cisapride in patients with severe idiopathic and diabetic gastroparesis during an eight-week trial. The study design was a two-week single-blind placebo run in period to exclude placebo responders, followed by a six-week randomized, double-blind, placebo-controlled treatment phase. Delayed gastric emptying of solids on radionuclide scan and a minimum symptom intensity score were inclusion criteria. Forty-three patients were entered: four placebo responders and one other patient were excluded, leaving 19 patients randomized to cisapride (20 mg per os three times a day before meals), and 19 patients to placebo. Seven individual symptoms of gastroparesis were scored in a daily diary and reviewed at two-week visits. Sixteen patients in the cisapride group were able to complete the trial compared to 12 on placebo. The gastric emptying study was repeated at the end of treatment or at the time of withdrawal for those who dropped out. Cisapride significantly increased solid gastric emptying relative to baseline (P=0.005) whereas placebo did not (P>0.10). Cisapride did not significantly improve any symptom of gastroparesis relative to baseline or to placebo. We conclude that in a population of severe, refractory gastroparetic patients cisapride significantly accelerates gastric emptying of a solid meal without significantly reducing symptoms during a short-term treatment trial compared to placebo. Further trials of cisapride in less advanced and end-stage gastroparetics than studied here or combining cisapride with other prokinetic agents or antiemetics, are warranted.Financial support was provided by Janssen Pharmaceutica. This study took place in the General Clinical Research Center of the University of Virginia Medical Center and was supported by NIH grant M01-RR 00847.     

Metoclopramide in Gastroesophageal Reflux Disease: Rationale for its Use and Results of a Double-Blind Trial

We investigated the acute effect of metoclopramide on lower esophageal sphincter pressure, esophageal contraction amplitude, and gastric emptying and compared metoclopramide, 10 mg four times a day, to placebo in improving the symptoms and objective parameters of reflux esophagitis in 19 patients in a randomized, double-blind 4-wk outpatient trial. Orally administered metoclopramide, 10 mg, significantly accelerated gastric emptying of a semisolid meal in patients in whom it was delayed; lower esophageal sphincter pressure was significantly increased for up to 90 min, but there were no changes in esophageal contraction amplitude. During the treatment trial, metoclopramide resulted in an overall improvement in heartburn and regurgitation of 60%, significantly better than 32% improvement after placebo (p less than 0.05). Compared to baseline symptoms scores, metoclopramide significantly improved both daytime and nighttime heartburn and regurgitation. Compared to placebo-treated patients, the metoclopramide group had significantly fewer episodes of daytime heartburn and regurgitation (p less than 0.05), while nighttime symptoms significantly improved with both treatments. Mean antacid consumption was significantly reduced by metoclopramide, 61%, compared to placebo-treated patients, 21% (p less than 0.05), who were ingesting a mean of 1.9 oz of antacid daily. Endoscopic and histological improvement were similar in both groups, although histological healing occurred in three patients after metoclopramide compared with none in the placebo group. Our data suggest that: 1) gastric emptying and lower esophageal sphincter pressure were significantly improved by acute administration of oral metoclopramide; 2) metoclopramide therapy for 4 wk is significantly more effective than placebo (medium dose antacid therapy) in relieving the symptoms of gastroesophageal reflux without significantly altering objective parameters of esophagitis; 3) metoclopramide effectively addresses the diffuse upper gastrointestinal motor disturbances present in reflux esophagitis patients.     

Effects of metoclopramide and bethanechol on delayed gastric emptying present in gastroesophageal reflux patients

Gastric emptying has been reported to be delayed in a significant percentage of patients with gastroesophageal reflux. The rationale for the use of metoclopramide and bethanechol in gastroesophageal reflux has been based on their ability to stimulate lower esophageal sphincter pressure and enhance acid clearance mechanisms. In this study, we investigated the comparative efficacies of metoclopramide and bethanchol in improving the rate of gastric emptying in gastroesophageal reflux patients in whom delayed emptying was present. Gastric emptying studies used an isotope-labeled mixed solid-liquid meal. Thirteen reflux patients with delayed gastric emptying received metoclopramide, 10 mg intramuscularly, and subcutaneous bethanechol, 0.07 mg/kg, in a randomized single-blind fashion. Eleven additional reflux patients with delayed gastric emptying received oral metoclopramide, 10 mg, in an open-labeled fashion. After parenteral metoclopramide, gastric emptying was significantly (p less than 0.05) faster compared with both the initial basal day and the bethanechol treatment day. Compared with the normal gastric emptying rate established in 26 control subjects, metoclopramide accelerated gastric emptying into the normal range. Bethanechol did not increase gastric emptying. Metoclopramide orally also significantly improved gastric emptying. Our study indicates that metoclopramide, both parenterally and orally, increased the rate of gastric emptying in those reflux esophagitis patients in whom it was delayed, while bethanechol did not improve the degree of gastric retention in the same patients. Our results extend the rationale for the therapeutic efficacy of metoclopramide in gastroesophageal reflux disease.     

Gastric emptying response to variable oral erythromycin dosing in diabetic gastroparesis

Intravenous erythromycin has been shown to improve gastric emptying in diabetic gastroparesis. Oral erythromycin also accelerates gastric emptying, but to a lesser degree. To determine if this is a dose-dependent phenomenon, gastric emptying was measured in 10 insulin-requiring diabetic patients with gastroparesis after administration of either 250 mg or 1000 mg of erythromycin or placebo. The drugs were orally administered in a randomized, double-blind fashion 30 min prior to ingestion of a meal containing [^99mTc]-sulfur colloid-labeled beef stew and [¹¹¹In]DTPA-labeled orange juice. Anterior and posterior gastric images were recorded for 3 hr at 15-min intervals using an externally positioned gamma camera. The results demonstrated that both doses of oral erythromycin significantly improved solid-phase gastric emptying. The mean half-emptying time of solids was decreased from 151±40 min with placebo to 58±10 min and 40±9 min with 250 mg and 1000 mg of erythromycin, respectively. However, a dose-dependent relationship was not demonstrated with the two doses of erythromycin employed. These results suggest that for most patients with diabetic gastroparesis, a single 250-mg dose of erythromycin will significantly improve gastric emptying. It is possible that a dose-dependent relationship will be demonstrated with doses of erythromycin less than 250 mg.     

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.     

Effect of metoclopramide on normal and delayed gastric emptying in gastroesophageal reflux patients

Gastric emptying has an important role in the pathophysiology of gastroesophageal reflux disease. We investigated the effect of metoclopramide, a gastric prokinetic agent, in gastroesophageal reflux patients with normal as well as delayed emptying. Twenty-six patients with subjective and objective evidence of gastroesophageal reflux ingested an egg salad sandwich meal labeled with 99mtechnetium-DTPA for a baseline study, and then again on a separate day after receiving oral metoclopramide, 10 mg, 30 min prior to the test meal. The mean percent isotope remaining in the stomach after 90 min improved significantly (P less than 0.001) from 70.3 +/- 3.9% (SEM) to 55.2 +/- 4.2% after metoclopramide. Fourteen (54%) had a basal emptying in the normal range of 34-69% retention of isotope at 90 min, (means +/- 2 SD), while it was slow in 12 (46%). For those with delayed basal gastric emptying, the mean retention of 88.9 +/- 2.9% at 90 min was significantly (P less than 0.005) decreased by metoclopramide to 68.6 +/- 6.1%. In those patients with a normal basal gastric emptying and a mean retention of 54.4 +/- 2.3% at 90 min, there was also significant improvement (P less than 0.025) to 43.6 +/- 3.6% after metoclopramide. These data indicate that metoclopramide increased gastric emptying in gastroesophageal reflux patients with normal as well as delayed gastric emptying. Therefore on a patient management level a trial of metoclopramide is warranted in patients with gastroesophageal reflux disease and is not limited by the gastric emptying status of the patient.     

Domperidone, metoclopramide, and placebo. All give symptomatic improvement in gastroesophageal reflux

A double-blind crossover study was conducted of two gastric prokinetic drugs in 23 patients with gastroesophageal reflux. Patients were divided into two groups on the basis of a dual-isotope mixed-meal study of their gastric emptying (GE). Group I had normal GE and group II delayed GE. Nine gastrointestinal symptoms were assessed for frequency and severity before treatment. The trial had three 1-month treatment periods using metoclopramide 10 mg q.i.d., domperidone 20 mg q.i.d., or placebo on a random basis. Symptoms were reassessed at the end of each month. Taken as a whole, the group showed a significant symptomatic response in all three treatment periods (p less than 0.0001), but patients with delayed or normal GE did not differ significantly in their symptomatic response. Eleven patients complained of side effects with metoclopramide and three stopped therapy before the 1-month course was completed. Two patients described side effects with domperidone, including one woman with galactorrhea after 36 h of treatment. Three patients on placebo also complained of important side effects. We conclude that a significant placebo effect is present in the treatment of gastroesophageal reflux. No significant difference was demonstrated in symptomatic improvement between placebo, domperidone, and metoclopramide in this study.     

Botulinum toxin A for the treatment of delayed gastric emptying

BACKGROUND: Observational data suggest that intrapyloric injection of botulinum toxin A (BoTN/A) reduces symptoms and accelerates gastric emptying in idiopathic and diabetic gastroparesis. Our purpose was to determine whether botulinum toxin improves symptoms to a significantly greater extent than placebo. An additional objective was to determine whether there is an acceleration of gastric emptying after injection. METHODS: A single-institution, randomized, double-blind, placebo-controlled trial* was done. Eligible patients had a Gastroparesis Cardinal Symptom Index score > or = 27 with randomization to intrapyloric botulinum toxin, 200 U (units), or saline placebo. Reassessment of symptoms and repeat gastric emptying scan at 1-month follow-up were done. RESULTS: Thirty-two patients were randomized to botulinum toxin (N = 16) and placebo (N = 16). At 1-month follow-up, 37.5% randomized to botulinum toxin and 56.3% randomized to placebo achieved improvement as defined by this study. There were no identifiable clinical predictors of response. The botulinum toxin group demonstrated improvement in gastric emptying; however, this was not superior to placebo. No serious adverse events were attributable to botulinum toxin. CONCLUSIONS: Intrapyloric injection of botulinum toxin improves gastric emptying in patients with gastroparesis, although this benefit was not superior to placebo at 1 month. Also, in comparison to placebo, symptoms do not improve significantly by 1 month after injection. Overall, we are unable to recommend botulinum toxin therapy for widespread use in the treatment of delayed gastric emptying until more data are available.     

Correlation between echographic gastric emptying and appetite: influence of psyllium.

The correlation between ultrasonographic gastric emptying and appetite was studied. Echographic evaluation of gastric emptying by measurement of the antral vertical diameter and assessment of sensations of hunger and satiety using analogue visual scales were performed simultaneously in 12 healthy volunteers. Measurements were carried out after the intake of 10.8 g psyllium or placebo in a randomised, crossover, double blind trial. The correlation between echographic gastric emptying and sensations of hunger and satiety was excellent (p < 0.001) after the intake of either psyllium or placebo. Psyllium significantly delayed gastric emptying from the third hour after a meal. It increased the sensation of satiety and decreased hunger at the sixth hour after the meal. The association between echographic measurement and visual scales is a simple method of evaluating the relationship between the stomach and appetite. The pharmacodynamic effect of psyllium should be confirmed by longterm therapeutic trials.     

Effect of altering gastric emptying on postprandial plasma glucose concentrations following a physiologic meal in type-II diabetic patients

The purpose of this study was to determine the effects of altering gastric emptying on postprandial plasma glucose concentration after a physiologic meal in patients with type II diabetes mellitus (T II DM). Nine T II DM patients underwent a double-blind, randomized, three-way crossover study, receiving erythromycin 200 mg, morphine 8 mg, or normal saline (placebo) intravenously prior to ingestion of a radiolabeled, dual-isotope, solid–liquid meal. Gastric emptying of solids and liquids and serial plasma glucose, glucagon, and serum insulin concentrations were measured at baseline and for 5 hr after meal ingestion. Erythromycin accelerated and morphine delayed solid- and liquid-phase gastric emptying compared to placebo (P < 0.05). During the first hour, the postprandial plasma glucose concentrations were higher after erythromycin (P < 0.05) and lower after morphine (P < 0.05) compared to placebo. The peak postprandial plasma glucose concentration was higher after erythromycin (P = 0.05) and lower after morphine (P < 0.05) compared to placebo. In conclusion, pharmacologic acceleration of gastric emptying resulted in higher postprandial glucose concentrations, while delaying gastric emptying resulted in lower postprandial glucose concentrations after a physiologic meal in T II DM. These results suggest that administration of opiate analgesics or prokinetic agents to diabetic patients may alter glucose control. Modifying gastric emptying may be helpful in achieving glucose control in T II DM.     

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 motilin on gastric emptying in patients with diabetic gastroparesis.

Erythromycin markedly accelerates gastric emptying, possibly because it acts as a motilin agonist. In the present study, the effect of an equipotent dose of motilin was tested. In six patients with severe diabetic gastroparesis, gastric emptying of liquids and solids was examined scintigraphically after motilin or placebo in a double-blind crossover study. Motilin (10 pmol.kg-1.min-1) or saline was infused over a 90-minute period starting 5 minutes before breakfast. Motilin markedly accelerated emptying. For liquids, the half-emptying time was reduced from 51 +/- 6 to 22 +/- 11 minutes (P less than 0.01) and for solids from 111 +/- 4 to 51 +/- 12 minutes (P less than 0.01). The mean increase in plasma motilin levels was 1315 +/- 342 pg/mL, corresponding to an effective infusion rate of about 4 pmol.kg-1.min-1. In the control experiments, basal motilin levels (173 +/- 17 pg/mL) were within the normal range but increased steadily postprandially, reaching 321 +/- 25 pg/mL at the end of the study period, probably reflecting gastric distension. The postprandial increase in pancreatic polypeptide level was blunted compared with accepted normal values but was more pronounced during motilin infusion, i.e., 650 +/- 217 vs. 279 +/- 66 pg/mL (P less than 0.01), probably because of the improved emptying. Our data show that motilin accelerates gastric emptying in diabetic gastroparesis and support the hypothesis that erythromycin's effect is mediated through motilin receptors.     

The Treatment of Idiopathic and Diabetic Gastroparesis with Acute Intravenous and Chronic Oral Erythromycin

The objective of this study was to investigate the effects of intravenous erythromycin and chronic oral dosing of erythromycin on gastric emptying in patients with idiopathic or diabetic gastroparesis. Symptoms were assessed on oral dosing and during long-term follow-up in an ambulatory setting at a University referral center. Fourteen patients (10 idiopathic and four diabetic gastroparesis) were studied. Four patients left during the 4-wk study; two due to rash, one with cramps and vomiting on erythromycin, and one due to other medical problems. Ten patients completed the 4-wk study and commenced long-term therapy. Five of these patients experienced enough symptomatic relief to continue oral erythromycin long-term, being followed for an average period of 8.4 months. After initial documentation of delayed gastric emptying, patients received 6 mg/kg intravenous erythromycin lactobionate before a second gastric emptying study. Erythromycin base was then given orally at a dose of 500 mg tid-ac and qhs, with a final gastric emptying study performed after 4 wk. During long-term follow-up, erythromycin dosage was adjusted to minimize symptoms. Radionuclide-labeled gastric emptying of a solid meal was studied at baseline, following intravenous erythromycin, and after 4 wk of oral treatment with erythromycin. Symptom scores were assessed at baseline, at 4 wk, and then at 8-wk intervals. The percentage of the solid meal retained in the stomach at 2 h decreased from 85%±11% (SD) at baseline to 20%± 29% following intravenous erythromycin ( p < 0.001), and to 48%± 21% after 4 wk of oral therapy ( p < 0.01 vs. baseline). There was a reduction in total symptom scores and a significant reduction in global assessment scores ( p = 0.03). We conclude that erythromycin bas a strong gastric prokinetic effect in both idiopathic and diabetic gastroparesis, and may represent a useful new therapeutic approach to this problem.     

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.     

Management of Diabetic Gastroparesis

Symptoms suggestive of gastroparesis occur in 5% to 12% of patients with diabetes. Such a complication can affect both prognosis and management of the diabetes; therefore, practicing clinicians are challenged by the complex management of such cases. Gastroparesis is a disorder characterized by a delay in gastric emptying after a meal in the absence of a mechanical gastric outlet obstruction. This article is an evidence-based overview of current management strategies for diabetic gastroparesis. The cardinal symptoms of diabetic gastroparesis are nausea and vomiting. Gastroesophageal scintiscanning at 15-minute intervals for 4 hours after food intake is considered the gold standard for measuring gastric emptying. Retention of more than 10% of the meal after 4 hours is considered an abnormal result, for which a multidisciplinary management approach is required. Treatment should be tailored according to the severity of gastroparesis, and 25% to 68% of symptoms are controlled by prokinetic agents. Commonly prescribed prokinetics include metoclopramide, domperidone, and erythromycin. In addition, gastric electrical stimulation has been shown to improve symptoms, reduce hospitalizations, reduce the need for nutritional support, and improve quality of life in several open-label studies.     

Postprandial Plasma Glucose Response and Gastrointestinal Symptom Severity in Patients With Diabetic Gastroparesis

Background:Gastroparesis is a well-known diabetic complication. The pathogenesis is not fully understood. However, it is important to early diagnose these patients.Method:This study evaluated the plasma glucose response after a test meal, and gastrointestinal (GI) symptom severity in patients with clinical suspicion of diabetic gastroparesis, and assessed its usefulness to predict gastroparesis. In all, 83 subjects with insulin-treated diabetes mellitus (DM) type 1 and 2 were included; 53 subjects had gastroparesis and 30 had normal gastric emptying determined by gastric scintigraphy. GI symptom severity during the preceding 2 weeks was evaluated with a validated questionnaire. The test meal consisted of 100 g meat, 40 g pasta, 150 g carrot, and 5 g oil. The subjects ingested the meal under fasting conditions, and plasma glucose was followed during 180 minutes.Results:Patients with gastroparesis demonstrated a blunted plasma glucose response after a test meal versus patients with normal gastric emptying (P < .005), reflected by lower maximum increase in plasma glucose response and incremental area under the curve of the plasma glucose, but a similar time to the maximum plasma glucose level. All GI symptoms were more severe in patients with gastroparesis. GI symptom severity had the best discriminative value to identify patients with gastroparesis with an area under the receiver operating curve of 0.83 (optimal cutoff: sensitivity 87%, specificity 80%).Conclusions:Patients with diabetic gastroparesis have a blunted postprandial plasma glucose response. Combining this information with the presence of GI symptoms can help clinicians identify diabetic patients with gastroparesis.     

Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis.

BACKGROUND: Erythromycin has recently been found to be a gastrointestinal prokinetic agent in humans. Acute hyperglycaemia has been associated with delayed gastric emptying in both healthy controls and diabetic patients. Our aim was to investigate in gastroparetic patients (diabetics and idiopathics) whether hyperglycaemia, per se, reduces gastric motility during erythromycin-induced acceleration of gastric emptying of solids. METHODS: In 12 gastroparetic patients, 6 diabetics and 6 idiopathics, gastric emptying of solids was measured scintigraphically after giving placebo in normoglycaemia (5-8.9 mmol/l glucose) or 200 mg erythromycin lactobionate intravenously in normo- or hyperglycaemia (16-19 mmol/l glucose) induced by intravenous glucose infusion in random order on separate days. RESULTS: Erythromycin in normoglycaemia accelerated solids gastric emptying compared with placebo in all patients by abolishing the lag-phase duration and by decreasing the retained percentage of a meal in the stomach at 120 and 150 min (14.5% +/- 5.3% versus 88.4% +/- 10.6% and 3.5% +/- 2.1% versus 70.1% +/- 15.4%, respectively) (P < 0.001). The retained isotopic percentage in the stomach after erythromycin in induced hyperglycaemia compared with erythromycin in normoglycaemia, at 120 and 150 min, was increased (51.9% +/- 9.8% versus 14.5% +/- 5.3%, and 24.5% +/- 5.9% versus 3.5% +/- 2.1%, respectively) (P < 0.001) but was decreased in comparison with placebo (P < 0.001). A significantly increased percentage of isotope was retained in the stomach of the diabetic patients at 120 and 150 min, compared with the idiopathics, only after giving erythromycin in the hyperglycaemic condition (57.6% +/- 8.7% versus 46.1% +/- 7.6% (P = 0.036) and 27.8% +/- 5.7% versus 21.1 +/- 4.4% (P = 0.040), respectively). CONCLUSIONS: Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis and increases the retained isotopic meal in the stomach. Hyperglycaemia reduces gastric motility more in the diabetic patients with gastroparesis than in idiopathic patients.