Meal In Healthy Subjects Research Articles

Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are both incretin hormones regulating postprandial insulin secretion. Their relative importance in this respect under normal physiological conditions is unclear, however, and the aim of the present investigation was to evaluate this. Eight healthy male volunteers (mean age: 23 (range 20–25) years; mean body mass index: 22.2 (range 19.3–25.4) kg/m 2) participated in studies involving stepwise glucose clamping at fasting plasma glucose levels and at 6 and 7 mmol/l. Physiological amounts of either GIP (1.5 pmol/kg/min), GLP-1(7–36)amide (0.33 pmol/kg/min) or saline were infused for three periods of 30 min at each glucose level, with 1 h “washout” between the infusions. On a separate day, a standard meal test (566 kcal) was performed. During the meal test, peak insulin concentrations were observed after 30 min and amounted to 223±27 pmol/l. Glucose+saline infusions induced only minor increases in insulin concentrations. GLP-1 and GIP infusions induced significant and similar increases at fasting glucose levels and at 6 mmol/l. At 7 mmol/l, further increases were seen, with GLP-1 effects exceeding those of GIP. Insulin concentrations at the end of the three infusion periods (60, 150 and 240 min) during the GIP clamp amounted to 53±5, 79±8 and 113±15 pmol/l, respectively. Corresponding results were 47±7, 95±10 and 171±21 pmol/l, respectively, during the GLP-1 clamp. C-peptide responses were similar. Total and intact incretin hormone concentrations during the clamp studies were higher compared to the meal test, but within physiological limits. Glucose infusion alone significantly inhibited glucagon secretion, which was further inhibited by GLP-1 but not by GIP infusion. We conclude that during normal physiological plasma glucose levels, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide contribute nearly equally to the incretin effect in humans, because their differences in concentration and potency outweigh each other.

Effect of dietary antioxidants on postprandial endothelial dysfunction induced by a high-fat meal in healthy subjects

Persons following current dietary guidelines have a lower risk of mortality from coronary heart disease. The objective was to compare the short-term effect of a high-fat meal and a high-carbohydrate meal, with and without dietary antioxidants, on vasomotor, antiplatelet, and hemostatic functions of the endothelium in healthy subjects. In an observer-blinded, randomized crossover study, 25 (13 men and 12 women) healthy subjects were given each of 3 meals in random order at 1-wk intervals: a high-fat meal (760 kcal), an isoenergetic high-carbohydrate meal, and a high-fat meal with dietary antioxidants from vegetables (865 kcal). Endothelial functions, as assessed by hemodynamic and rheologic responses to L-arginine--the natural precursor of nitric oxide--were evaluated before and 4 h after each meal. Unlike the high-carbohydrate meal, the high-fat meal increased the plasma concentrations of triacylglycerol (P < 0.01); both meals activated hemostasis. The high-carbohydrate meal did not modify blood pressure, and platelet aggregation decreased in response to the L-arginine load (-7.1 +/- 2.3 mm Hg and -8.5 +/- 4.5%, respectively). After the high-fat meal, the decrease in blood pressure in response to L-arginine was reduced (-1 +/- 0.8 mm Hg), and platelet aggregation showed a paradoxical increase (4.1 +/- 2.1%; P < 0.01 compared with the high-carbohydrate meal). The high-fat meal with antioxidants partially restored the vascular response to L-arginine. Compared with a high-carbohydrate meal, a high-fat meal can modify endothelial functions toward a more atherogenetic profile, which is partially prevented by dietary antioxidants.

Oral clarithromycin enhances gallbladder emptying induced by a mixed meal in healthy subjects

Background: In humans, erythromycin has been demonstrated to accelerate gallbladder emptying due to its motilin-like effects on the gastrointestinal tract. Recently, it was shown that clarithromycin, another macrolide, used for the eradication of Helicobacter pylori infection, also stimulated gastrointestinal motility in the fasting state. We conducted a comparative study on the effects of a single oral dose of clarithromycin and of erythromycin on gallbladder emptying in healthy subjects. Methods: Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were measured by ultrasound in 21 healthy subjects (11 males, 10 females, mean age 42.5±10.6 years). A test meal (14 g fat, 425 kcal) was ingested 30 min after a single oral dose (500 mg) of either clarithromycin or erythromycin, and the measurements were repeated the following day with the other drug (cross-over double-blind study). A control group consisting of 12 subjects (seven males, five females, mean age 50.7±8.2 years) was used to evaluate gallbladder emptying following the same test meal without drug administration. Differences between groups were analyzed using two-tailed Student’s t-test for unpaired observations. Results: Gallbladder emptying at 60, 75, and 90 min was greater after erythromycin ( P<0.05 at 90 min) and clarithromycin than it was in controls. The ejection fraction was significantly greater after clarithromycin (76.5%) and erythromycin (79.7%) than it was in controls. Gallbladder refilling occurred earlier after clarithromycin than after erythromycin. Conclusions: The prokinetic effect of clarithromycin on the gallbladder appears to be of similar amplitude but of shorter duration than that of erythromycin.

Vagal Tone and Meal-Induced Abdominal Symptoms in Healthy Subjects

Background/Aims: Patients with functional dyspepsia often have meal-induced dyspeptic symptoms and low vagal tone. We examined whether these variables are related in healthy subjects. Methodology: In 40 healthy subjects vagal tone and abdominal symptoms were recorded before and after a 500-ml soup meal ingested in 1 and 4 min on separate visits. Vagal tone was indexed by respiratory sinus arrhythmia (RSA). Results: Scores for nausea and discomfort were higher when the soup was ingested in 1 min as compared with 4 min (nausea: p = 0.02; discomfort: p = 0.04). There was no difference in fullness or abdominal pain. RSA was unrelated to meal-induced symptom scores. RSA varied with respiration and body position: It was highest while breathing deeply in the sitting position (24.0 beats/min). With normal breathing RSA was highest in the supine position (9.0 beats/min), lower while sitting (7.0 beats/min) and lowest while standing (6.2 beats/min). Conclusions: Epigastric discomfort in response to rapid ingestion of a test meal in healthy subjects was not related to vagal tone as indexed by RSA. Vagal tone varied with breathing pattern and body position. It is possible that increasing vagal tone by such measures can be beneficial in the treatment of patients with functional dyspepsia.

Simultaneous measurement of gastric emptying of a solid meal by ultrasound and by scintigraphy

OBJECTIVE: Although ultrasonic imaging may represent a valid alternative to scintigraphy for measurement of gastric emptying, most studies comparing the two methods have been carried out with liquid meals. The aim of this study was to compare scintigraphic and ultrasonographic measurements of gastric emptying of a solid meal in healthy subjects and in patients with possible delay in emptying. METHODS: Nineteen subjects were studied: five controls, six patients with gastroesophageal reflux, and eight patients with dysmotility-like dyspepsia. Gastric emptying was measured by both scintigraphy and ultrasonography after ingestion of an 800-calorie solid, realistic meal containing 99mTc-labeled chicken liver. Scintigraphic measurements were made every 15 min for 6 h, and ultrasonic imaging of antral sections was undertaken every 15 min for the first 1 h and every 30 min thereafter. Total emptying times were calculated independently using the two methods, and the emptying patterns recorded by the two methods were compared. RESULTS: Maximal antral dilation occurred 30 min (range 0–90 min) after the end of the meal and persisted until 96 ± 42 min, by which time gastric radioactivity had decreased from its maximum by 43% ± 23%. From this time on, the antral cross-sectional area returned toward the basal value, declining faster than the gastric counts recorded by scintigraphy. Total emptying times measured by ultrasound and by scintigraphy were in good agreement in all subjects, with a mean difference of only 4.5 min (limits of agreement, −17.1 to 21.6 min). CONCLUSIONS: Ultrasonographic measurement of antral cross-sectional area provides a valid alternative to scintigraphy for the measurement of total gastric emptying of a solid meal. It is less reliable if other parameters of gastric emptying such as T 1/2 are required.

Effect of cream cheese consumption on the glycaemic response to the meal in healthy subjects

The effects of the ingestion of 20% fat-cream cheese with a breakfast on glycaemic and insulinaemic responses of male healthy volunteers have been studied in two experiments with 12 subjects each. The results indicate that as few as 100 g cream cheese significantly decrease the maximal glycaemic value and the area under the glucose curve, when compared with a standard french breakfast. Increasing the ingested amount of cream cheese has no further effect on the responses. The possible mechanisms are evoked.

Effect of loxiglumide on lower esophageal sphincter motor events and gastric relaxation induced by duodenal infusion of a liquid meal in healthy subjects

Effect of loxiglumide on lower esophageal sphincter motor events and gastric relaxation induced by duodenal infusion of a liquid meal in healthy subjects

Flow across the Human Pylorus Soon after Ingestion of Food, Studied with Duplex Sonography: Effect of Glyceryl Trinitrate

Background: By means of duplex sonography, gastric emptying can be related to antral motor activity. The aim of this study was to examine gastric emptying in relation to antral contractions during and immediately after ingestion of a liquid meal in healthy subjects and to study the effect of glyceryl trinitrate (GTN) on this early phase of gastric emptying. Methods: Ten healthy, non-smoking men (median age, 36 years; range, 29-41 years) were studied twice on separate days, once without drug administration and once after taking a 0.5-mg sublingual GTN tablet 3 min before ingesting 500 ml of a meat soup (20 kcal; Toro). The subjects were investigated during 3 min of fasting, during 3 min of drinking the soup, and during the first 10 min postprandially. Results: Transpyloric forward flow commenced on average 80 sec and 95 sec after the start of drinking the soup without and with GTN, respectively (P = NS). Non-contractile, pulsatile transpyloric flow (that is, pendulating, transpyloric flow not associated with antral contractions) occurred during episodes of concurrent relaxation of the terminal antrum, the pylorus, and the duodenal bulb. This type of flow occurred mainly just before the start of contractile, pulsatile transpyloric flow (associated with propulsive antral contractions). Initial non-contractile, pulsatile transpyloric flow before commencement of contractile, pulsatile transpyloric flow lasted longer with GTN (188 sec) than without GTN (25 sec) (P < 0.05). Consequently, contractile, pulsatile transpyloric flow commenced later with GTN (302 sec) than without (102 sec) (P < 0.05). Conclusions: Non-contractile transpyloric flow seems to be a physiologic phenomenon during the early phase of gastric emptying. GTN prolongs the initial phase of non-contractile, and delays the onset of contractile, pulsatile transpyloric flow.

Gastric relaxation in response to a soup meal in healthy subjects. A study using a barostat in the proximal stomach.

Meal-induced relaxation of the proximal stomach can be investigated by means of a barostat. Using a standard liquid meat soup that elicits symptoms and a wide antrum in patients with functional dyspepsia, we aimed at finding the best meal size and fat load for studying gastric relaxation. In the first trial 200 ml and 500 ml meat soup (1 g fat/200 ml) was given to six healthy individuals. In the second trial a constant volume of soup (200 ml) containing graded amounts of fat (1, 10, and 20 g/200 ml) was given to seven healthy individuals. Gastric relaxation was investigated for 1 h after consumption of the soup. A sagittal cross-sectional antral was assessed ultrasonographically every 10 min, and abdominal discomfort was scored. Overall, a positive response (volume increase of 30 ml or more within 5 min after consumption of the meal) was found in 26 of 30 (87%) investigations. Individual maximal responses ranged from 38 to 482 ml (mean, 180 ml +/- 128). Area under the time-volume curve (AUC) was similar after 200 and 500 ml soup (mean, 100 ml/30 min and 107 ml/30 min, respectively). AUC increased with increasing fat content, with a significant difference between the low-fat and high-fat meal (p < 0.05). The barostat bag induced fed-state antral contractions in most individuals (p < 0.001). There was a negative correlation between AUC and postprandial abdominal discomfort (p = 0.04). The barostat is a sensitive technique for detecting gastric relaxation, also in response to our standard meat soup meal. The postprandial relaxation response in healthy individuals in dependent on the fat content of the meal. The barostat bag may alter gastric motor activity. Abdominal discomfort after soup ingestion may be related to poor gastric relaxation.

Gall bladder emptying patterns in response to a normal meal in healthy subjects and patients with gall stones: ultrasound study.

In this study gall bladder emptying patterns in response to a solid meal were studied using ultrasound. A similar triphasic pattern was seen in eight healthy control subjects and eight patients with gall stones, with 'early' and 'late' net emptying phases separated by a period of net refilling with peak postprandial gall bladder volumes occurring at (mean (SD)) 33.1 (17.9) minutes and 27.4 (18.8) minutes in control subjects and patients, respectively. A phase of slower net emptying followed, which was complete at 146 (33) minutes in control subjects and 125 (33) minutes in the gall stone patients (not significant). Superimposed upon this overall triphasic pattern, postprandial gall bladder emptying was punctuated by repeated short lived episodes of filling and emptying. The mean (SD) estimated postprandial bile outputs were 0.83 (0.34) ml/min in four control subjects and 1.2 (1.1) ml/min in seven patients with gall stones. We propose a 'washout' model to reconcile this large turnover of bile with the concentrating and storage functions of the gall bladder and predict that the extent rather than the rate of gall bladder emptying is important in determining stasis of bile in the gall bladder.

Diminished meal‐induced thermogenesis in elderly man

The purpose of this study was to examine the possible influence of age on thermogenic response to a mixed meal in healthy subjects. Twenty-five healthy male subjects participated in the study and they were divided into three groups, comprising 10 young subjects with an average age of 27 years (22-35 years), seven middle-aged individuals (51 years, 42-60 years) and eight elderly men (70 years, 67-74 years). They were all studied with continuous indirect calorimetry in the basal state and for 3 h after the ingestion of a mixed meal in liquid form. The size of the meal corresponded to 60% of the individually computed 24-h basal energy expenditure. Resting energy expenditure was lower in the elderly men than in the young ones when expressed in absolute values (P less than 0.001) as well as in relation to body weight (P less than 0.01) and body surface area (P less than 0.01). After the meal energy expenditure increased rapidly and reached a relatively constant level after 60 min in all groups; the average increase above the basal level during the whole postprandial period was less in the elderly (21.1 +/- 2.5%, P less than 0.01) and the middle-aged (24.2 +/- 1.7%, P less than 0.05) than in the young (28.6 +/- 1.6%) men. It is concluded that the thermogenic response during the first 3 h following a mixed meal decreases with age and that this diminished meal-induced thermogenesis may contribute to lower nutrient requirements in old age.

Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases.

Plasma secretin concentrations were determined in healthy subjects and patients with duodenal ulcer, achlorhydria, and celiac sprue. Mean fasting plasma secretin concentrations in 26 healthy subjects and 26 duodenal ulcer patients were 6.7 +/- 0.5 and 10.2 +/- 1.2 pg/ml, respectively, and were significantly different (P less than 0.02). After ingestion of a standard meat meal, pyloric pH decreased to less than 4.5 within 15 min and plasma secretin concentrations significantly increased in all 52 subjects. In 14 subjects (seven healthy subjects and seven patients with duodenal ulcer), no significant rise in plasma secretin concentration occurred when pyloric pH was maintained at greater than 5.0 by intravenous cimetidine (600 mg) and intragastric antacid. In 10 achlorhydric patients, intragastric pH remained greater than 5.0 after the meal and plasma secretin concentrations did not change. However, plasma secretin concentrations increased significantly when 0.1 N HCl was infused in the stomach (25 mEq/hr) during the postprandial period. In all eight adult patients with celiac disease (seven untreated, one partially treated), pyloric pH remained less than 4.0 after a meal. Postprandial secretin concentrations did not increase significantly in six and showed a transient rise in two. These studies show that (1) plasma secretin concentration increases significantly after meals in healthy subjects and patients with duodenal ulcer; (2) neutralization of gastric acid and the achlorhydric state show no significant postprandial rise in plasma secretin concentration; (3) achlorhydric patients do not have a defect in secretin release in response to acid; and (4) failure of postprandial rise in plasma secretin in patients with celiac disease is attributed to impaired release of secretin and in achlorhydric patients it is attributed to lack of acid secretion.

Fasting motor activity occurs during a day of normal meals in healthy subjects.

Using a radiotelemetric technique of pressure recording which did not interfere with normal feeding, jejunal motor activity was recorded in seven healthy human subjects, who were given three hospital meals during the course of a day, and allowed ad libitum supplementary snacks. Fasting motor activity was detected during the day in five subjects, and, although its occurrence was very variable, tended to occur shortly before the next meal.

Peripheral plasma somatostatin-like immunoreactive responses to insulin hypoglycemia and a mixed meal in healthy subjects and in noninsulin-dependent maturity-onset diabetics.

We have measured peripheral plasma immunoreactive somatostatin (SRIF-LI) in 10 healthy subjects and 10 noninsulin-dependent maturity-onset diabetics (NIDDM). The mean (+/-SE) basal level of SRIF-LI in NIDDMs of 185 +/- 27 was similar to that of 174 +/- 23.5 pg/ml in age-, weight-, and sex-matched healthy subjects. Insulin hypoglycemia of equivalent magnitude induced a 113 +/- 15.8 pg/ml increase in SRIF-LI 40 min after injection in healthy subjects and no significant change in the NIDDMs. Ingestion of a mixed meal induced a biphasic rise with a mean peak of 75 +/- 30 pg/ml above basal at 15 min and a later peak of 130 +/- 35 pg/ml above basal at 120 min in healthy subjects. In NIDDM, there was no significant rise above basal, and the differences were significant at 15 and 120 min. Our findings are compatible with deficient SRIF release in these NIDDM in whom the deficient SRIF secretion may contribute to the hyperglycemia.

The XYY Male

<h3>Introduction</h3> In clinical practice colonic manometry is recommended to exclude colonic inertia (no response to meal and to drug stimulation, i.e. bisacodyl) in patients with slow transit laxative-refractory constipation (Bharucha 2013). As to date, this has not been assessed by colonic HRM in adults, our <i>aim</i>was to evaluate the sensations and colonic motor response to a meal and to bisacodyl in patients with slow-transit laxative-refractory constipation. <h3>Methods</h3> Consecutive patients with slow-transit and laxative-refractory Rome III constipation were enrolled. During colonoscopy, an HRM catheter (40 sensors, 2.5 cm spaced) and an infusion tube were advanced as far as possible (caecum) and clipped to the mucosa. Colonic pressures were recorded for three hours before and two after a standardised meal, and for one hour after intra-colonic bisacodyl (10 mg). Abdominal discomfort, abdominal gas, desire to evacuate gas, desire to defecate and urgency to defecate were evaluated by means of 100 mm visual analogue scale (VAS) every 15 minutes. Number of pan-colonic pressurizations (PCPs, Corsetti 2015) and of low-amplitude (LAPSs, Dinning 2014) and high-amplitude propagating sequences (HAPSs, De Schryver 2002) were evaluated. A normal response to bisacodyl was identified by the occurrence of at least one HAPS. Data (mean±SD) were compared with those obtained in 10 healthy subjects (HS) (30±11 years, 5 females). <h3>Results</h3> A total of 24 refractory slow-transit constipation patients (43±13 years, 22 females) were studied; 15 of these also referred pain or discomfort. As compared to HS, the total number of PCPs and of LAPSs was significantly lower in patients without pain (respectively, 19±21 vs 89±40 and 6±10 vs 52±39, all p &lt; 0.01), while it did not differ in patients with pain (respectively, 60±41 and 38±46). PCPs significantly increased after a meal in HS and in patients with (p &lt; 0.01) but not in those without pain (p = 0.20). Retrograde LAPSs increased significantly after the meal in HS (p = 0.01) but not in patients, regardless of the presence of pain (all p &gt; 0.25). The response to bisacodyl was normal in all patients with pain and in 2/8 (25%) of those without pain (p = 0.01). VAS scores for discomfort differed significantly between patients with pain as compared to both patients without pain and healthy subjects (P = 0.006). <h3>Conclusion</h3> Compared to slow transit patients without pain, patients with pain have a partially preserved response to meal (increased PCPs but not LAPSs), a higher prevalence of a normal response to bisacodyl and report higher score for discomfort during manometry. <h3>Disclosure of Interest</h3> None Declared