Hyperglycemia attenuates the gastrokinetic effect of erythromycin and affects the perception of postprandial hunger in normal subjects.

OBJECTIVE: The major aims of this study were to determine in normal subjects whether the effects of erythromycin on gastric emptying, postprandial hunger, and fullness are modified by the blood glucose concentration. RESEARCH DESIGN AND METHODS: A total of 10 normal subjects (aged 20-39 years) underwent concurrent measurements of gastric emptying, blood glucose, hunger, and fullness on four separate occasions: twice during euglycemia (approximately 4 mmol/l) and twice during hyperglycemia (approximately 15 mmol/l). Either erythromycin (3 mg/kg) or saline (0.9%) was administered intravenously immediately before ingestion of a radioisotopically labeled solid meal. RESULTS: Gastric emptying was slower (P < 0.0001) during hyperglycemia when compared with euglycemia after both erythromycin and saline administration. During hyperglycemia, erythromycin reduced the lag phase (77.8 +/- 12.6 vs. 20.3 +/- 7.3 min; P < 0.05) but had no effect on the postlag emptying rate (0.32 +/- 0.077% per min vs. 0.24% per min). Hunger decreased (P < 0.001) and fullness increased (P < 0.001) after the meal. Postprandial hunger was less during hyperglycemia after saline infusion (P < 0.05) but not after erythromycin. Hunger was greater after erythromycin during both hyperglycemia and euglycemia (P < 0.05). CONCLUSIONS: At a blood glucose concentration of approximately 15 mmol/l, 1) gastric emptying of a solid meal is slower, when compared with euglycemia, even after administration of erythromycin; 2) the effect of erythromycin on gastric emptying of a solid meal is attenuated; and 3) the perception of postprandial hunger is reduced.     

A pharmacological dose of glucagon suppresses gastric emptying of a radiolabelled solid meal in humans

The effect of glucagon (143 nmol i.v. bolus followed by 430 nmol infused at a constant rate over 90 min) vs placebo (normal saline) on gastric emptying was examined in a blind randomized study in eight healthy males. The gastric emptying of a radiolabelled solid meal was measured with the use of a gamma camera. Glucagon elicited a pronounced delay in gastric emptying in all subjects examined--mean gastric transit time MTT90 glucagon 44.2 +/- 0.22 min vs placebo 38.6 +/- 0.74 min, p less than 0.001.     

Noninvasive breath tests can detect alterations in gastric emptying in the mouse

BACKGROUND: Noninvasive breath tests may have significant utility for the measurement of gastric emptying in mice, but the tests' sensitivity for detection of changes in gastric emptying has not been evaluated. MATERIALS AND METHODS: Hydroxypropyl methyl cellulose was incorporated into a liquid meal to delay gastric emptying, and mice were injected with erythromycin to accelerate emptying of a liquid or solid meal. All test meals were labelled with (13)C-acetic acid or (13)C-octanoic acid. Breath samples collected at intervals were analysed for (13)CO(2) content, and gastric emptying rates were calculated from the resultant (13)CO(2) excretion curves. RESULTS: As predicted, hydroxypropyl methyl cellulose slowed emptying compared with water (14.21 +/- 0.94 min vs. 9.17 +/- 0.47 min, P < 0.001), while erythromycin treatment accelerated emptying of liquids (10.96 +/- 0.78 min vs. 16.41 +/- 1.94 min, P < 0.05) and solids (108.81 +/- 18.06 vs. 157.95 +/- 12.01 min, P < 0.05) compared with the saline injected controls. CONCLUSIONS: These data indicate that in mice the breath test is sensitive enough to detect differences in gastric emptying induced by meal composition and pharmacological agents. Noninvasive measurement of gastric emptying in mice will be useful as a method to evaluate the effect of nutrients or drugs on the motility of the gastrointestinal tract.     

Prevalence of delayed gastric emptying in diabetic patients and relationship to dyspeptic symptoms: a prospective study in unselected diabetic patients

OBJECTIVE: Data on the prevalence of abnormal gastric emptying in diabetic patients are still lacking. The relation between gastric emptying and dyspeptic symptoms assessed during gastric emptying measurement has not yet been investigated. The aim was to investigate the prevalence of delayed gastric emptying in a large cohort of unselected diabetic patients and to investigate the relation between gastric emptying and gastrointestinal sensations experienced in the 2 weeks before and during the test meal, prospectively. RESEARCH DESIGN AND METHODS: Gastric emptying was evaluated in 186 patients (106 with type 1 diabetes, mean duration of diabetes 11.6 +/- 11.3 years) using 100 mg (13)C-enriched octanoic acid added to a solid meal. RESULTS: Gastric emptying was significantly slower in the diabetic subjects than in the healthy volunteers (T(50): 99.5 +/- 35.4 vs. 76.8 +/- 21.4 min, P < 0.003; Ret(120 min): 30.6 +/- 17.2 vs. 20.4 +/- 9.7%, P < 0.006). Delayed gastric emptying was observed in 51 (28%) diabetic subjects. The sensations experienced in the 2 weeks before the test were weakly correlated with the sensation scored during the gastric emptying test. Sensations assessed during the gastric emptying test did predict gastric emptying to some extent (r = 0.46, P < 0.0001), whereas sensations experienced in the previous 2 weeks did not. CONCLUSIONS: This prospective study shows that delayed gastric emptying can be observed in 28% of unselected patients with diabetes. Upper gastrointestinal sensations scored during the gastric emptying tests do predict the rate of gastric emptying to some extent and sensation experienced during daily life does not.     

Effect of a single oral dose of two erythromycin ethylsuccinate formulations on gastric emptying in healthy volunteers: A scintigraphic study

Summary— Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.     

Predictors of delayed gastric emptying in 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.     

Gastric emptying in myotonic dystrophy

BACKGROUND: Gastrointestinal symptoms are common and important for the quality of life in patients with myotonic dystrophy (MD). Gastric emptying was studied in patients with MD who suffered from symptoms suggesting slow gastric emptying and the effect of prokinetic treatment was evaluated. METHODS: Gastric emptying was studied in 10 patients with MD who were suffering from nausea, early satiety, bloating, regurgitation, vomiting, or abdominal pain using a (99)Tc-labelled test meal, and was compared with gastric emptying in a group of healthy controls. The patients were subsequently treated with erythromycin and their gastrointestinal symptoms were recorded and the gastric emptying test was repeated. RESULTS: Patients with MD had a significantly longer gastric lag phase (46.1 +/- 4.3 vs. 31.9 +/- 4.0 min, P = 0.03), a slower emptying phase (7.1 +/- 0.9 vs. 10.2 +/- 0.9 kJ min(-1), P = 0.02) and a longer half-emptying time, T50 (141.7 +/- 10.5 vs. 98.6 +/- 8.7 min, P = 0.01) than a matched control group. Erythromycin did not stimulate the gastric emptying rate. The effect on gastrointestinal symptoms was modest, except for a reduction of diarrhoea. CONCLUSIONS: Patients with MD suffering from nausea, vomiting and early satiety, displayed a slow gastric emptying. Treatment with erythromycin had only moderate effect on gastric emptying or gastric symptoms, but reduced diarrhoea in a majority of the patients.     

Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans.

It is known that the ingestion of glucose alone causes a greater increase in plasma glucose levels than ingestion of the same amount of glucose given with other nutrients. Since physiological plasma concentrations of cholecystokinin (CCK) prolong gastric emptying, it is proposed that after a meal, CCK may modify plasma glucose levels by delaying glucose delivery to the duodenum. To evaluate the effect of CCK on oral glucose tolerance, plasma CCK, insulin, and glucose levels and gastric emptying rates were measured in eight normal males before and after the ingestion of 60 g glucose with the simultaneous infusion of either saline or one of two doses of CCK-8 (12 or 24 pmol/kg per h). Gastric emptying rates were measured by gamma camera scintigraphy of technetium 99m sulfur colloid and plasma CCK levels were measured by a sensitive and specific bioassay. Basal CCK levels averaged 1.0 +/- 0.1 pM (mean +/- SEM, n = 8) and increased to 7.1 +/- 1.1 pM after a mixed liquid meal. After glucose ingestion, but without CCK infusion, CCK levels did not change from basal, and the gastric emptying t1/2 was 68 +/- 3 min. Plasma glucose levels increased from basal levels of 91 +/- 3.9 mg/dl to peak levels of 162 +/- 11 mg/dl and insulin levels increased from 10.7 +/- 1.8 microU/ml to peak levels of 58 +/- 11 microU/ml. After glucose ingestion, with CCK infused at 24 pmol/kg per h, plasma CCK levels increased to 8 pM and the gastric emptying t1/2 increased to 148 +/- 16 min. In concert with this delay in gastric emptying, peak glucose levels rose to only 129 +/- 17 mg% and peak insulin levels rose to only 24.2 +/- 4.2 microU/ml. With CCK at 12 pmol/kg per h, similar but less dramatic changes were seen. To demonstrate that endogenous CCK could modify the plasma glucose and insulin responses to oral glucose, oral glucose was given with 50 g of lipid containing long-chain triglycerides. This lipid increased peak CCK levels to 3.7 +/- 0.9 pM. Concomitant with this rise in CCK was a delay in gastric emptying and a lowering of plasma glucose and insulin values. To confirm that CCK reduced hyperglycemia by its effect on gastric motility, 36 g glucose was perfused directly into the duodenum through a nasal-duodenal feeding tube in four subjects. With duodenal perfusion of glucose, there was no change in plasma CCK levels, but plasma glucose levels increased from basal levels of 93+/-5 to 148+/-6 mg/dl and insulin levels rose from 10.6+/-3.5 to 29.5+/-5.2 microU/ml. When CCK was infused at 24 pmol/kg per h, neither the plasma glucose nor insulin responses to the duodenal administration of glucose were modified. Thus we conclude that CCK, in physiological concentrations, delays gastric emptying, slows the delivery of glucose to the duodenum, and reduces postprandial hyperglycemia. These data indicate, therefore, that CCK has a significant role in regulating glucose homeostasis in human.     

Control of postprandial hyperglycemia: optimal use of short-acting insulin secretagogues

OBJECTIVE: This study was designed to compare the efficacy of acute premeal administration of glipizide versus nateglinide in controlling postprandial hyperglycemia in subjects with non-insulin-requiring type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 20 subjects (10 female, 10 male) with non-insulin-requiring type 2 diabetes were admitted overnight to the General Clinical Research Center on four occasions. In random order, 10 mg glipizide (30 min premeal), 120 mg nateglinide (15 min premeal), 10 mg glipizide plus nateglinide (30 and 15 min premeal, respectively), or placebo pills (30 and 15 min premeal) were administered in a double-blind fashion before a standardized breakfast. Blood was drawn for analysis of glucose, insulin, and C-peptide at -0.05, 0, 0.5, 1, 2, 3, and 4 h relative to the meal. RESULTS: The subjects were aged 56 +/- 2 years and were moderately obese (BMI 31 +/- 1 kg/m(2)), with a mean HbA(1c) of 7.4 +/- 0.4%. The peak postprandial glucose excursion above baseline was higher with placebo (6.1 +/- 0.5 mmol/l) than glipizide (4.3 +/- 0.6 mmol/l, P = 0.002), nateglinide (4.2 +/- 0.4 mmol/l, P = 0.001), or glipizide plus nateglinide (4.1 +/- 0.5 mmol/l, P = 0.001). The area under the curve for the glucose excursion above baseline was also higher with placebo (14.1 +/- 1.8 mmol/h. l) compared with glipizide (6.9 +/- 2.4 mmol/h. l, P = 0.002), nateglinide (9.7 +/- 2 mmol/h. l, P = 0.004), or glipizide plus nateglinide (5.6 +/- 2.2 mmol/h. l, P < 0.001). Peak and integrated glucose excursions did not differ significantly between glipizide and nateglinide. However, by 4 h postmeal, plasma glucose levels were significantly higher with nateglinide (9 +/- 0.9 mmol/l) compared with the premeal baseline (7.8 +/- 0.6 mmol/l, P = 0.04) and compared with the 4-h postprandial glucose level after administration of glipizide (7.6 +/- 0.6 mmol/l, P = 0.02). Integrated postprandial insulin levels were higher with glipizide (1,556 +/- 349 pmol/h. l) than nateglinide (1,364 +/- 231 pmol/h. l; P = 0.03). Early insulin secretion, as measured by insulin levels at 30 min postmeal, did not differ between glipizide and nateglinide. CONCLUSIONS: Acute premeal administration of nateglinide or glipizide has equal efficacy in controlling postbreakfast hyperglycemia in type 2 diabetes when each drug is administered at the optimum time before the meal. Glipizide causes a more pronounced and sustained postmeal insulin secretory response compared with nateglinide. Glipizide facilitates the return to near-fasting glucose levels at 4 h postmeal, but with the possible risk of increased frequency of postmeal hypoglycemia in drug-naive patients. The clinical decision to use glipizide versus nateglinide should be based on factors other than the control of postprandial hyperglycemia in type 2 diabetes.     

Erythromycin improves gastric emptying in critically ill patients intolerant of nasogastric feeding

OBJECTIVE: To evaluate the effect of intravenous erythromycin on gastric emptying and the success of enteral feeding in mechanically ventilated, critically ill patients with large volume gastric aspirates. DESIGN: Prospective, double-blind, randomized, and placebo-controlled trial. SETTING: General intensive care unit in a university hospital. PATIENTS: Twenty critically ill, mechanically ventilated patients intolerant of nasogastric feeding (indicated by a residual gastric volume of > or =250 mL during feed administration at > or =40 mL/hr). INTERVENTIONS: After a gastric aspirate of > or =250 mL, which was discarded, the enteral feeding was continued at the previous rate for 3 hrs. Intravenous erythromycin (200 mg) or placebo was then administered over 20 mins. The residual gastric contents were again aspirated and the volume was recorded 1 hr after the infusion began. MEASUREMENTS AND MAIN RESULTS: Gastric emptying was calculated as volume of feed infused into the stomach over 4 hrs minus the residual volume aspirated. Mean gastric emptying was 139+/-37 (+/-SEM) mL after erythromycin and -2+/-46 mL after placebo (p = .027). Nasogastric feeding was successful in nine of ten patients treated with erythromycin and five of ten who received placebo 1 hr after infusion (chi-square p = .05). CONCLUSION: In critically ill patients who have large volumes of gastric aspirates indicating a failure to tolerate nasogastric feeding, a single small dose of intravenous erythromycin allows continuation of feed in the short term.     

Effect of sucralfate and an aluminum hydroxide gel on gastric emptying of solids and liquids

Our purpose was to investigate whether an aluminum-containing compound (sucralfate) and an aluminum-containing antacid (Amphojel; Wyeth Laboratories), both of which are commonly used in peptic ulcer disease, affect gastric emptying. Gastric emptying was studied in ten healthy subjects with the double isotope technique to assess simultaneous emptying rates of the solid and liquid components of a meal. 99mTechnetium sulfur colloid-labeled chicken liver served as the solid component and 111indium diethylenetriamine penta-acetic acid-labeled water was the liquid component. In a randomized, double-blind fashion, 1 gm sucralfate and 30 ml aluminum hydroxide gel were compared with placebo on separate days. Subjects ate the isotope-labeled test meal after dosing, and gastric emptying was monitored for 3 hours by a gamma-camera interfaced with a computer. There was no significant change in gastric emptying of either solids or liquids after sucralfate. The aluminum hydroxide gel slowed the gastric emptying rate for solids more than did the placebo, but this difference was significant only at the intervals of 165 and 180 minutes after the meal. We conclude that aluminum in the form of therapeutic doses of sucralfate does not delay gastric emptying of solids or liquids in normal subjects, while the larger amount of aluminum in therapeutic doses of the antacid gel has some slowing effect on gastric emptying of the solid components of a meal.     

Impaired Hyperglycemia-Induced Delay in Gastric Emptying in Patients With Type 1 Diabetes Deficient for Islet Amyloid Polypeptide

OBJECTIVE—Slowing of gastric emptying by hyperglycemia, a physiological response to minimize postprandial hyperglycemia, may be impaired in patients with type 1 diabetes. The causes and consequences on glucose homeostasis are unknown.RESEARCH DESIGN AND METHODS—Consequences of euglycemia- and hyperglycemia-induced changes in gastric emptying on postprandial glucose fluxes and excursions were studied in 10 healthy subjects and 15 type 1 diabetic subjects after ingestion of a mixed meal using the double isotope approach ([6,6-²H₂] and [1-¹³C]glucose) and scintigraphic measurements of gastric emptying.RESULTS—Gastric emptying was greater in type 1 diabetic subjects (90–120 min, P < 0.03), and 50% retention times were comparable in healthy subjects and type 1 diabetic subjects (167 ± 8 vs. 152 ± 10, P = 0.32). Hyperglycemia markedly delayed gastric emptying in healthy subjects but did not alter it in type 1 diabetic subjects (50% retention time 222 ± 18 vs. 167 ± 8 min, P = 0.003 and 148 ± 9 vs. 152 ± 10 min, P = 0.51). Plasma islet amyloid polypeptide (IAPP) increased approximately fourfold in healthy subjects (P < 0.001), whereas it was undetectable in type 1 diabetic subjects. IAPP replacement, using the analog pramlintide, in type 1 diabetic subjects slowed gastric emptying to a comparable extent, as did hyperglycemia in healthy subjects (P < 0.14), and greatly reduced postprandial hyperglycemia (P < 00.1). Meal-derived glucose appearance in plasma (10.7 ± 0.5 vs. 6.8 ± 0.7 μmol · kg⁻¹ · min⁻¹, P < 0.001) was reduced, and splanchnic glucose sequestration increased (14.0 ± 3.0 vs. 25.0 ± 6.0%, P = 0.04).CONCLUSIONS—In patients with type 1 diabetes the ability to delay gastric emptying in response to hyperglycemia is impaired. This impairment contributes to exaggerated rates of meal-derived glucose appearance and, ultimately, postprandial glucose excursions.The importance of insulin and glucagon in maintaining postprandial glycemic excursions within a narrow range is well established (1). However, alterations in gastric emptying, another potentially important factor (2), are not generally considered to be of clinical significance for postprandial hyperglycemia in diabetes unless diabetes late complications, such as gastroparesis, have emerged (3,4).Gastroparesis is a relatively rare diabetes late complication resulting from irreversible intestinal nerve damage (5) and has to be distinguished from the physiological inhibitory effects of acute hyperglycemia on gastric motility (6,7). The latter has been proposed as a defense mechanism to minimize postprandial hyperglycemia by reducing the rate of efflux of glucose into the circulation from the gut (8). This process may be of special importance for patients with type 1 diabetes because they have been reported to have a reduced ability to delay gastric emptying in response to hyperglycemia (9).The pancreatic β-cell hormone islet amyloid polypeptide (IAPP) is cosecreted with insulin in a fixed molar ratio (10) and reduces gastric emptying. Thus, patients with type 1 diabetes even without concomitant enteric neuropathy should have increased rather than delayed rates of gastric emptying, because they are IAPP deficient (11). Accordingly, the present studies were undertaken to test the hypothesis that impairment in hyperglycemia-induced delay in gastric emptying should result in greater meal-derived glucose appearance in the systemic circulation and thus should contribute to postprandial hyperglycemia in patients with type 1 diabetes.     

Effect of rectal distension on gallbladder emptying and circulating gut hormones

BACKGROUND: Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. MATERIALS AND METHODS: Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. RESULTS: Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. CONCLUSION: Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.     

Erythromycin and early enteral nutrition in mechanically ventilated patients

OBJECTIVE: To determine whether erythromycin facilitates early enteral nutrition in mechanically ventilated, critically ill patients. DESIGN: Prospective, randomized, placebo-controlled, single-blind trial. SETTING: General intensive care unit in a university-affiliated general hospital. PATIENTS: Forty consecutive critically ill patients receiving invasive mechanical ventilation and early nasogastric feeding. INTERVENTIONS: Patients were assigned randomly to intravenous erythromycin (250 mg/6 hrs; n = 20) or a placebo (intravenous 5% dextrose, 50 mL/6 hrs; n = 20) for 5 days. The first erythromycin or 5% dextrose injection was given at 8 am on the day after intubation. One hour later, a daily 18-hr enteral nutrition regimen via a 14-Fr gastric tube was started. Residual gastric volume was aspirated and measured every day at 9 am, 3 pm, 9 pm, and 3 am. Enteral nutrition was discontinued if residual gastric volume exceeded 250 mL or the patient vomited. MEASUREMENTS AND MAIN RESULTS: On the first day, residual gastric volume was smaller in the erythromycin than in the placebo group (3 pm, 15 +/- 7 mL vs. 52 +/- 14 mL, p <.05; 9 pm, 29 +/- 15 mL vs. 100 +/- 20 mL, p <.001; 3 am, 11 +/- 4 mL vs. 54 +/- 13 mL, p <.05). With erythromycin, residual gastric volume at 9 pm was smaller on the second day (33 +/- 11 mL vs. 83 +/- 19 mL, p <.01) and residual gastric volume at 3 pm was smaller on the third day (39 +/- 15 mL vs. 88 +/- 19 mL, p <.05) than with placebo. On the fourth and fifth days, the differences in residual gastric volume were not significant. Enteral nutrition was discontinued before the end of the 5-day period in seven of the 20 erythromycin patients and 14 of the 20 placebo patients (p <.001). CONCLUSION: In critically ill patients receiving invasive mechanical ventilation, erythromycin promotes gastric emptying and improves the chances of successful early enteral nutrition.     

Gastric emptying and release of incretin hormones after glucose ingestion in humans.

This study investigated in eight healthy male volunteers (a) the gastric emptying pattern of 50 and 100 grams of glucose; (b) its relation to the phase of interdigestive motility (phase I or II) existing when glucose was ingested; and (c) the interplay between gastric emptying or duodenal perfusion of glucose (1.1 and 2.2 kcal/min; identical total glucose loads as orally given) and release of glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1(7-36)amide (GLP-1), C-peptide, insulin, and plasma glucose. The phase of interdigestive motility existing at the time of glucose ingestion did not affect gastric emptying or any metabolic parameter. Gastric emptying of glucose displayed a power exponential pattern with a short initial lag period. Duodenal delivery of glucose was not constant but exponentially declined over time. Increasing the glucose load reduced the rate of gastric emptying by 27.5% (P < 0.05) but increased the fractional duodenal delivery of glucose. Both glucose loads induced a fed motor pattern which was terminated by an antral phase III when approximately 95% of the meal had emptied. Plasma GLP-1 rose from basal levels of approximately 1 pmol/liter of peaks of 3.2 +/- 0.6 pmol/liter with 50 grams of glucose and of 7.2 +/- 1.6 pmol/liter with 100 grams of glucose. These peaks occurred 20 min after glucose intake irrespective of the load. A duodenal delivery of glucose exceeding 1.4 kcal/min was required to maintain GLP-1 release in contrast to ongoing GIP release with negligibly low emptying of glucose. Oral administration of glucose yielded higher GLP-1 and insulin releases but an equal GIP release compared with the isocaloric duodenal perfusion. We conclude that (a) gastric emptying of glucose displays a power exponential pattern with duodenal delivery exponentially declining over time and (b) a threshold rate of gastric emptying of glucose must be exceeded to release GLP-1, whereas GIP release is not controlled by gastric emptying.     

The effect of sildenafil on gastric emptying in patients with end-stage renal failure and symptoms of gastroparesis

BACKGROUND: Delayed gastric emptying is a common disorder among patients with end-stage renal failure (ESRF). Pyloric relaxation, a major determinant of gastric emptying, is a nitric oxide (NO)-mediated process. NO-induced smooth muscle relaxation is mediated through its second messenger cyclic guanosine monophosphate, which is broken by tissue phosphodiesterases (PDEs). Thus the inhibition of cyclic guanosine monophosphate breakdown by PDE inhibitors can potentiate NO-mediated responses and facilitate pyloric relaxation. In an animal model of diabetes mellitus, treatment with sildenafil (a PDE-5 inhibitor) restored NO-mediated pyloric relaxation and improved gastric emptying. The aim of our study was to examine the hypothesis that sildenafil may improve gastric emptying in patients with ESRF and symptoms of gastric paresis. METHODS: We studied 12 patients with ESRF (6 men; age range, 54-80 years; 5 with diabetic nephropathy; 4 +/- 1 years receiving long-term renal replacement therapy) after either placebo or a 25-mg tablet of sildenafil (Viagra; Pfizer Inc). Gastric emptying of a solid meal (one medium-sized fried egg mixed with 37 MBq [1 mCi] technetium Tc 99m phytate plus 1 slice of bread and 150 mL of water at the end of the meal) was assessed 1 hour after dosing by use of a single-headed camera. Images were acquired every 30 seconds for 90 minutes immediately after patients ate. RESULTS: The gastric emptying rate was decreased at baseline (after placebo), to 33% +/- 6% (normal, > or =50%). Treatment with sildenafil had no effect on gastric emptying rates after 90 minutes (from 33% +/- 6% after placebo to 30% +/- 6% after sildenafil, P =.9). CONCLUSIONS: Sildenafil did not improve gastric emptying in patients with ESRF and gastric paresis. Sildenafil may have opposing effects on gastric peristalsis (causing gastric relaxation) compared with its effects on pyloric relaxation. Studies combining sildenafil with prokinetic drugs are of interest.     

Randomized dose ranging study of the reduction of fasting and postprandial glucose in type 2 diabetes by nateglinide (A-4166).

OBJECTIVE: This randomized crossover double-blind placebo-controlled study aimed to assess the efficacy of nateglinide (A-4166), a novel phenylalanine-derived insulin secretagogue, in type 2 diabetic subjects while fasting and 5 min before a standard meal. RESEARCH DESIGN AND METHODS: A single dose of nateglinide (60, 120, or 180 mg) or placebo was given to eight diet-treated overnight-fasted type 2 diabetic patients and to seven patients 5 min before a standard breakfast. Plasma glucose, radioimmunoassay insulin, and nateglinide were measured at baseline and for a further 180 min. RESULTS: The time-averaged 180-min postdose mean decrease in fasting plasma glucose concentration was greater after nateglinide (1.8 mmol/l; 95% CI 1.5-2.0) than after placebo (0.7 mmol/l; 95% CI 0.3-1.2) (P < 0.001). Hypoglycemia did not develop in any of the subjects. Insulin concentrations increased 1.5-, 1.8-, and 1.9-fold with the 60-, 120-, and 180-mg doses, respectively (P < 0.001), peaking approximately 30 min after the dose. Nateglinide concentrations peaked after approximately 30 min, decreasing to 21% of peak by 180 min. In the meal test, the mean increase (2.9 mmol/l, 2.3-3.6) in plasma glucose over 180 min after placebo was reduced by 1.8 mmol/l (P < 0.001) with the two higher doses of nateglinide. CONCLUSIONS: A single dose of nateglinide administered to diet-treated type 2 diabetic patients with fasting hyperglycemia increased insulin secretion and reduced fasting glucose without hypoglycemia. Administered 5 min before a meal, nateglinide reduced the postprandial glucose excursion by 64%. With its rapid onset and short duration of action, nateglinide is a promising oral prandial therapy in type 2 diabetes.     

Association between gastric emptying rate and nutritional status in patients treated with continuous ambulatory peritoneal dialysis.

OBJECTIVE: To estimate gastric emptying rate in continuous ambulatory peritoneal dialysis (CAPD) patients, with or without indwelling dialysate, and to evaluate if there is an association between gastric motility and nutritional status. DESIGN: Single-center cross-sectional study. SETTING: Peritoneal Dialysis Unit, Medical Faculty, Jagiellonian University Hospital, Krakow, Poland. PATIENTS AND METHODS: 20 end-stage renal disease patients [11 F, 9 M; mean age 50.1 +/- 11 years; treated with CAPD for median 13.5 (2-61) months] were studied. All patients were nondiabetic and had no comorbidity that might influence gastric motility; nor were they receiving any prokinetic drugs. Gastric emptying rate was estimated with dynamic abdominal scintigraphy, started immediately after complete ingestion of a standard 200-kcal solid meal injected with 99mTc-labeled colloid, activity 40 MBq. Scintigraphy was performed at the rate of 23 images in 4-minute intervals for 92 minutes. Two consecutive procedures--with and without PD fluid--were performed at weekly intervals. As nutritional parameters, protein catabolic rate (PCR) and lean body mass (LBM) (based on urea and creatinine kinetics, respectively), body mass Index (BMI), and serum albumin were measured. RESULTS: All analyzed gastric emptying parameters, measured with or without dialysis fluid, were markedly prolonged in patients compared to values accepted as normal in the local scintigraphy unit. Gastric emptying half-time (T(1/2)) and percent of initial activity in minute 46 and in minute 92 were 60.5 +/- 25.0 minutes, 57.19% +/- 17.5%, and 33.8% +/- 20.9% with a full peritoneal cavity, and 63.9 +/- 28.2 minutes, 59.1% +/- 23.9%, and 33.9% +/- 24.3% with an empty peritoneal cavity. The T(1/2) and percent of initial activity after 46 and 92 minutes for healthy subjects were 39 +/- 9 minutes, 45% +/- 11%, and 15% +/- 6%, respectively. T(1/2) without dialysis fluid revealed a negative correlation with LBM and BMI values (r = -0.5, p < 0.05, and r = -0.56, p < 0.01; respectively). Patients with dialysate-free T(1/2) > 40 minutes were characterized by significantly lower serum albumin level compared to subjects with T(1/2) < 40 minutes (39.2 +/- 2.9 vs 42.9 +/- 3.6 g/L, p < 0.05). The values of all gastric emptying parameters measured for an empty abdomen were prolonged in subjects with BMI < 25 kg/m2. No difference was found between patients with and without PD fluid. CONCLUSIONS: Gastric emptying is markedly impaired in CAPD patients compared to healthy subjects. However, the presence of dialysate does not influence it significantly. Gastric emptying rate was negatively associated with the nutritional status of treated subjects. This association can be demonstrated when gastric motility is measured with an empty peritoneal cavity.     

Effect of motilin on gastric emptying in patients with diabetic gastroparesis

OBJECTIVES: Because disturbances of gastric emptying are a serious complication in insulin-dependent diabetic subjects with regard to the maintenance of good metabolic control, we wanted to assess the effectiveness of motilin as a potential treatment for gastric emptying disturbances. RESEARCH DESIGN AND METHODS: The intestinal hormone motilin has been shown to accelerate gastric emptying in healthy subjects. Therefore, we examined the effect of intravenous motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9 insulin-dependent diabetic patients with diabetic gastroparesis. All patients had a significantly delayed gastric emptying rate compared with a group of 11 healthy control subjects. RESULTS: During the infusion of motilin, gastric emptying was accelerated, and it was no longer significantly different from control values. CONCLUSIONS: These data demonstrate that motilin and related compounds such as erythromycin derivatives could be useful for the treatment of disturbed gastric emptying in diabetic subjects.     

Effects of alpha-glucosidase inhibition on meal glucose tolerance and timing of insulin administration in patients with type I diabetes mellitus

OBJECTIVE: Miglitol, an alpha-glucosidase inhibitor, delays absorption of carbohydrates. This study was undertaken to determine the potential of this agent as an adjunct to insulin in the treatment of diabetes. RESEARCH DESIGN AND METHODS: Twelve nonobese patients with insulin-dependent (type I) diabetes mellitus were randomly selected from the outpatient diabetes clinic. The patients were made euglycemic with the Biostator, and postprandial hyperglycemia was determined under the following conditions: protocol 1, subcutaneous injection of insulin (13 +/- 1 U) given 60 min before the meal, with insulin dosages determined by the Biostator; protocols 2 and 3 same as protocol 1 but with insulin given at the time of meal ingestion; protocols 4 and 5 same as protocol 1 but with insulin given 30 min before the meal. Miglitol (100 mg) was administered in protocols 2 and 4 and placebo in protocols 3 and 5. RESULTS: When insulin was given 30 min before the meal with miglitol (protocol 4) or placebo (protocol 5), plasma glucose increased from 4.94 +/- 0.16 to 5.94 +/- 0.55 mM and from 5.11 +/- 0.22 to 8.22 +/- 0.72 mM, respectively (P less than 0.01). When insulin was given at the time of the meal with miglitol (protocol 2) or placebo (protocol 3), plasma glucose increased from 5.44 +/- 0.27 to 7.77 +/- 0.5 mM and from 5.72 +/- 0.22 to 10.83 +/- 0.77 mM, respectively (P less than 0.01). When insulin was given 60 min before the meal (protocol 1), plasma glucose initially decreased from 5.61 +/- 0.38 to 4.33 +/- 0.33 mM and then increased to 6.94 +/- 0.66 mM after the meal.(ABSTRACT TRUNCATED AT 250 WORDS)