Changed integrated gastrointestinal response to a mixed meal in exocrine pancreatic insufficiency.

Using a multiple-marker dilution technique to quantitate flow volumes at a jejunal sampling site 70 cm from pylorus, propulsion and absorption of a 300-ml mixed liquid test meal were compared in seven patients with exocrine pancreatic insufficiency and in ten healthy subjects. In pancreatic insufficiency, outputs of lipase and amylase were 8% of control levels. Early gastric emptying rate was similar in both groups, but emptying was completed earlier, and less gastric acid was emptied in pancreatic insufficiency. In pancreatic insufficiency, initial biliary output was larger than in controls, and transit time through the test segment was twice that of controls. During the prolonged transit time, larger amounts of glucose (but less fat) were absorbed in pancreatic insufficiency. Forty minutes after the meal, almost a third of the fatty content of the meal was propelled to lower parts of the intestine. In conclusion, pancreatic insufficiency is associated with impaired inhibitory regulation of gastric and biliary outputs after a mixed meal. The impaired digestion of nutrients in pancreatic insufficiency is partially compensated for by slowing of intestinal transit, permitting more efficient absorption. Exposure of the gut to large quantities of fat is suggested to trigger the slowing of upper intestinal transit in pancreatic insufficiency.     

Effect of obesity and major weight reduction on gastric emptying

BACKGROUND: An enhanced gastric emptying rate might reduce the satiating effect of food and thereby promote obesity. Gastric emptying rate has previously been compared between obese and lean subjects with conflicting outcome. OBJECTIVE: Comparison of gastric emptying rate in lean and obese subjects before and after a major weight reduction. DESIGN: The study was designed as a case-control study comparing obese and lean subjects and a subsequent comparison of obese subjects before and after a dietary induced major weight reduction. METHOD: Gastric emptying rate following a solid test meal was estimated scintigraphically for 3 h using the left anterior oblique projection. SUBJECTS: Nineteen non-diabetic obese (mean BMI=38.7 kg/m2) and 12 lean (mean BMI=23.1 kg/m2) males matched for age and height. All obese subjects were re-examined after a mean weight loss of 18.8 kg (95% CI, 14.4-23.2) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. RESULTS: When comparing obese and lean subjects no differences were seen in overall 3 h emptying rate (30.3% per hour vs 30.5% per hour). However, a trend towards a higher percentage gastric emptying during the initial 30 min was seen in the obese when compared to lean subjects (24.0% vs 17.8% of the test meal; P=0.08). Weight loss was associated with a reduction in percentage gastric emptying during the initial 30 min (from 24.0% to 18.3% of the test-meal; P<0. 02), whereas the overall 3 h emptying rate was unaffected (30.3% vs 30.9% per hour). Neither initial or overall emptying rate differed between reduced-obese and lean subjects. CONCLUSION: Overall 3 h gastric emptying rate was similar in obese and normal weight males, and unaffected by a major weight loss. However, percentage gastric emptying during the initial 30 min for a solid meal appeared to be increased in obese males and was normalized after a major weight reduction.     

Gallbladder and gastric motility in obese newborns, pre-adolescents and adults

Background and Aim: Impaired gallbladder and gastric motility have been associated with obesity in adults. The timing of appearance of this dysfunction, however, is unclear. Methods: Lean and obese subjects from three different age groups were studied noninvasively: 50 newborns (1–12 months old, six obese), 18 pre‐adolescents (7–8 years old, seven obese), and 99 adults (22–80 years old, 32 obese) classified according to standard normal tables and body mass index. Changes of fasting/postprandial gallbladder and gastric motility were assessed simultaneously by functional ultrasonography in response to milk (newborns and pre‐adolescents) and to a liquid test meal (adults). Results: In newborns, fasting and postprandial gallbladder volumes and gastric emptying were similar between obese and lean subjects. In pre‐adolescents, obese subjects had a larger fasting gallbladder volume, with slower postprandial gastric emptying than lean subjects. In obese adults, the most evident dysfunction emerged, with larger fasting and postprandial residual gallbladder volume, and slower postprandial gastric emptying than lean subjects. Conclusions: Obese subjects display abnormal gallbladder and gastric motility patterns, which first appear in pre‐adolescents and deteriorate in adults. Such abnormalities are absent in obese newborns. Functional ultrasonography can detect altered cholecysto‐gastric motility at the earliest stage. Our findings suggest an age‐related decline of motility, probably secondary to excessive fat and insulin‐resistance.     

Relation between body weight and the gastric and intestinal handling of an oral caloric load.

The gastric and intestinal handling of a standard liquid 300-ml meal (0.89 kcal/ml) was examined in 10 healthy, non-obese subjects by a quantitative multiple-indicator dilution technique. Such a meal contains about one-tenth of the daily energy requirements. The heavier the subject the more energy was transferred from the stomach to the intestine during the first 80 minutes after taking the meal. A high body weight was also associated with a rapid transit through the proximal 70 cm of intestine and the passing of a substantial part of the meal calories to the lower intestine. These circumstances favour a fast incorporation of fed calories. In subjects with lower body weights eneryg was delivered more slowly from the stomach. The absorbed an equal amount of energy in the proximal intestine as did the heavier subjects, but during the longer transit times. The percentage absorption in the investigated segment was therefore higher.     

Gastric and oesophageal emptying in obesity

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

Gender differences in gut transit shown with a newly developed radiological procedure

BACKGROUND: Gut transit measurements are essential for understanding the pathophysiology of many gastrointestinal disorders. The ideal bowel transit test should be easy to perform, widely accessible, reproducible, non-invasive and inexpensive and the risks should be minimal. These requirements prompted us to develop a procedure for simultaneous measurement of gastric emptying, small-bowel transit and colonic transit at one visit. We assessed the influence of gender, body mass index, age, menopause and smoking on gastrointestinal transit in healthy subjects. METHODS: Eighty-three healthy subjects (43 women) were included. Colonic transit was based on 10 radiopaque rings given daily for 6 days with fluoroscopy on day 7. Then, the subjects had a test meal containing 20 radiopaque markers. Using fluoroscopy, gastric emptying and small-bowel transit of the markers were followed until they reached the colon. RESULTS: Gastric emptying, small-bowel transit and colonic transit were significantly slower in female healthy subjects compared to males (2.9 (1.6-4.9) h, median and percentile 10-90, versus 2.4 (0.7-3.7) h, P=0.005; 4.4 (2.1-11.1) h versus 3.2 (1.5-6.0) h, P=0.001; 1.5 (1.0-3.7) days versus 1.3 (0.8-1.9) days P=0.002), respectively. Small-bowel transit was significantly faster in women with overweight and in postmenopausal women compared to lean and premenopausal women, respectively. CONCLUSION: This procedure meets most of the requirements of the ideal bowel transit test and is easily performed at one visit. Small-bowel transit as well as gastric emptying and colonic transit were significantly slower for women.     

The effect of chilli on gastrointestinal transit

The effects of chilli on gastrointestinal transit (gastric emptying, orocaecal transit, whole gut transit) were evaluated in eight healthy volunteers. In each subject, gastrointestinal transit of a standard test meal was measured on two separate days. On one of these occasions, 20 g of chilli powder was added to the meal. Gastric emptying was quantified with a radioisotopic technique, orocaecal transit by measurement of breath hydrogen concentrations and whole gut transit by counting the number of radio-opaque markers in the stool. The rate of gastric emptying was slower (P less than 0.05) and whole gut transit was faster (P less than 0.02) after the meal containing chilli, compared with the other meal. There was no significant difference in orocaecal transit. These results show that ingestion of chilli is associated with significant effects on gastric emptying and intestinal transit.     

Gastric inhibitory polypeptide (GIP) hypersecretion in obesity depends on meal size and is not related to hyperinsulinemia

Summary The response of immunoreactive gastric inhibitory polypeptide (IR-GIP), immunoreactive insulin (IRI) and immunoreactive C-peptide (IR-C-peptide) to the ingestion of mixed liquid test meals containing 1031 kcal (550 ml) and 422 kcal was studied in 17 obese and 17 normal weight control subjects. When the 422 kcal load was ingested in a volume of 550 ml, the plasma IR-GIP response was significantly greater than in a volume of 225 ml at 15 and 30 min in lean and obese subjects, but the total integrated IR-GIP response was not significantly different between the obese and lean group. Also intraduodenal infusion of 150 ml (280 kcal) of the test meal elicited identical plasma IR-GIP concentrations in lean and obese subjects. An exaggerated IR-GIP response in obese subjects was seen only following the 1031 kcal load (integrated IR-GIP response: 23.6±1.9 in lean subjectsvs 50.3±3.8 nmol/1/180 min in obese subjects; p<0.01). The IRI response was always significantly greater in obese than in lean subjects and not related to the GIP response. Fasting plasma IR-C-peptide levels were significantly elevated in obese subjects (lean: 0.52±0.04; obese: 1.42±0.12 nmol/l; p<0.005), but the postprandial integrated IR-C-peptide responses in the obese and lean group were identical, indicating decreased hepatic insulin extraction in obesity. It is concluded that an exaggerated IR-GIP response in obesity occurs only after ingestion of a high calorie meal probably as consequence of an increased gastric emptying rate and that the hyperinsulinemic response of obese subjects is not attributable to GIP hypersecretion.     

The role of postprandial releases of insulin and incretin hormones in meal-induced satiety--effect of obesity and weight reduction

BACKGROUND: Previous studies have indicated that the secretion of the intestinal satiety hormone glucagon-like peptide-1 (GLP-1) is attenuated in obese subjects. OBJECTIVE: To compare meal-induced response of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in obese and lean male subjects, to investigate the effect of a major weight reduction in the obese subjects, and to look for an association between these hormones and ad libitum food intake. METHOD: Plasma concentrations of intestinal hormones and appetite sensations were measured prior to, and every 30 min for 180 min after, ingestion of a 2.5 MJ solid test meal. Gastric emptying was estimated scintigraphically. An ad libitum lunch was served 3 h after the test meal. SUBJECTS: Nineteen non-diabetic obese (body mass index (BMI) 34.1--43.8 kg/m(2)) and 12 lean (BMI 20.4--24.7 kg/m(2)) males. All obese subjects were re-examined after a mean stabilised weight loss of 18.8 kg (95% CI 14.4--23.2). RESULTS: Total area under the GLP-1 response curve (AUC(total, GLP-1)) was lower in obese before and after the weight loss compared to lean subjects (P<0.05), although weight loss improved the response from 80 to 88% of that of the lean subjects (P=0.003). The GIP response was similar in obese and lean subjects. However, after the weight loss both AUC(total, GIP) and AUC(incremental, GIP) were lowered (P<0.05). An inverse correlation was observed between AUC(incremental, GIP) and energy intake at the subsequent ad libitum meal in all groups. In lean subjects ad libitum energy intake was largely predicted by the insulin response to the preceding meal (r(2)=0.67, P=0.001). CONCLUSION: Our study confirmed previous findings of a reduced postprandial GLP-1 response in severely obese subjects. Following weight reduction, GLP-1 response in the obese subjects apparently rose to a level between that of obese and lean subjects. The data suggests that postprandial insulin and GIP responses are key players in short-term appetite regulation.     

Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people

BACKGROUND & AIMS: Peptide YY (PYY) levels are reported to be decreased in obesity. The relation between gastric functions, satiation, and gut hormones in obesity is incompletely understood. The aim of this study was to compare gastric volumes, emptying, maximum tolerated volumes, postchallenge symptoms, and selected gut hormones in normal, overweight, or obese healthy volunteers. METHODS: In 73 nonbulimic normal, overweight, or obese participants weighing less than 137 kg, we measured gastric emptying of solids and liquids by scintigraphy (gastric emptying half-time [GE t(1/2)]); gastric volumes by single-photon emission computed tomography; maximum tolerated volumes and symptoms by satiation test; and plasma leptin, ghrelin, insulin, glucagon-like peptide 1, and PYY levels. Groups were compared using 1-way analysis of covariance adjusted for sex. Univariate associations among measured responses were assessed using Spearman correlations. Multiple linear regression models, adjusting for weight and sex, assessed the independent ability of gastric functions and hormones to predict satiation volume. RESULTS: Obese and overweight subjects had significantly lower postprandial gastric volumes, higher fasting and postprandial insulin and leptin levels, and lower fasting ghrelin and lower postprandial reduction in ghrelin levels. PYY levels were not different in obese or overweight subjects compared with controls. The GE t(1/2) was correlated inversely with postprandial PYY; increased body weight was associated with faster GE t(1/2) of solids (r(s) = 0.33, P = .005) and liquids (r(s) = 0.24, P = .04). Postprandial changes in gastric volume and PYY were independent predictors of satiation (both P = .01). CONCLUSIONS: Overweight or obesity are associated with lower postprandial gastric volumes and normal PYY levels. Gastric emptying influences postprandial PYY levels. Postprandial PYY and gastric volume independently predict satiation volume in nonbulimic people across a wide body mass index range.     

Is the transit time of a meal through the small intestine related to the rate at which it leaves the stomach?

Using non-invasive techniques, we investigated how varying the size or composition of a meal altered the rate at which it passed through the stomach and small intestine in normal volunteers. Increasing the size of the meal by doubling the absorbable components delayed gastric emptying, did not significantly influence the time taken for the head of the meal to reach the caecum, but retarded the entry of the bulk of the meal residues into the caecum. Incorporating fat in the meal slowed gastric emptying, but did not significantly affect small bowel transit time. The addition of the unabsorbable disaccharide lactulose (in place of an equivalent amount of sucrose) accelerated small bowel transit time, but did not significantly influence gastric emptying. Thus, our results indicated that changes in small bowel transit time could occur independently of changes in gastric emptying in normal healthy subjects.     

Effect of lidamidine hydrochloride and loperamide on gastric emptying and transit of the small intestine. A double-blind study

We performed a double-blind randomized study in 24 healthy volunteers, to evaluate the effects of two doses of lidamidine hydrochloride, loperamide, and placebo on transit of the small intestine and gastric emptying. Transit time of the small intestine was determined by measuring the rise in breath hydrogen excretion after ingestion of lactulose. Although there was a trend for prolonged intestinal transit time in both lidamidine groups, this difference was not significant compared with that in the placebo group. Loperamide significantly slowed transit when compared with placebo or lidamidine (p less than 0.001). Gastric emptying was assessed by using a solid-phase radiolabeled meal. Three parameters of gastric emptying were analyzed: half-emptying time, area under the gastric emptying curve, and beta. Although there was a trend for a longer half-emptying time in the group that received 12 mg of lidamidine, this difference approached, but did not reach, statistical significance (p = 0.06) compared with placebo. The area under the gastric emptying curve, a potentially more sensitive parameter for measuring gastric emptying, was significantly increased in the group receiving 12 and 18 mg of lidamidine (p less than 0.05) compared with the group receiving loperamide or placebo. In summary, lidamidine significantly delayed gastric emptying but had no significant effect on small bowel transit. These data suggest that the antidiarrheal properties of lidamidine are the result of enhanced absorption or inhibition of secretion of fluid and electrolytes.     

Delayed gastric emptying in the obese: an assessment using the non-invasive (13)C-octanoic acid breath test

AIM: Much of the controversy surrounding the correlation between obesity and gastric emptying lies in the inconsistency of methodology and analysis. This study was designed to overcome some of the discrepancies encountered in previous studies and to test the hypothesis that obese individuals have altered gastric emptying compared to lean individuals. METHODS: Gastric emptying was measured using the (13)C-octanoic acid breath test in 16 lean and 16 obese women pair-matched for age. Following an overnight fast, subjects were given a standard 2 MJ egg meal labelled with 100 microl of [1-(13)C]-octanoic acid. Breath samples were collected at regular intervals over a 6-h period. (13)C-isotopic enrichment in the breath was analysed using isotope ratio mass spectrometry and the data fitted to the established gastric emptying model. The lag times (t(lag)), half excretion times (t(1/2)), latency phase (t(lat)) and ascension times (t(asc)) were calculated. RESULTS: The mean t(1/2)-values (+/-standard error of the mean) were 3.67 +/- 0.14 h and 4.23 +/- 0.18 h for lean and obese respectively, indicating significantly delayed gastric emptying in the obese (p = 0.019). The obese group also showed a significantly slower lag time (t(lag), p = 0.005) and latency phase (t(lat), p = 0.005), but no significant difference was found in the ascension time (t(asc), p = 0.154). Within groups, no correlation was found between half excretion times and body weight or half excretion times and body mass index. CONCLUSIONS: The present study demonstrated a prolonged lag phase and delayed gastric emptying in obese women when compared to lean women. This delay may be as a consequence of high-fat diets, a sedentary lifestyle and increased gastric distension associated with obesity, or a contributing factor in the pathogenesis of obesity resulting from the inactivation of gastrointestinal satiety signals and in an increase in food intake.     

Gallbladder volume and emptying in diabetics: the role of neuropathy and obesity.

Gallbladder (GB) volume was monitored by real-time sonography in diabetics (n = 21) and healthy volunteers (n = 55) after a test meal. Seventeen controls and seven diabetics were obese; six patients had both autonomous and somatic neuropathy, and four had somatic neuropathy. Fasting GB volume was similar in controls and diabetics with and without autonomic neuropathy; it was correlated with body mass index (controls, r = 0.43, P less than 0.002; diabetics, r = 0.46, P less than 0.04), and was increased in obese subjects. Post-prandial GB emptying was decreased in diabetics. Those with autonomous neuropathy exhibited larger residual volumes than controls (P less than 0.03). Post-prandial GB emptying was slower and less complete in (non-diabetic) obese subjects and deteriorated further in diabetic obese subjects. GB fasting tone was normal, but GB kinetics were impaired in diabetics; obesity and autonomous neuropathy were correlated with GB hypomotility.     

Gastrointestinal transit disorders in patients with insulin-treated diabetes mellitus

Gastric emptying, mouth-to-cecum transit and whole gut transit of a solid-liquid meal were measured in 43 insulin-treated diabetics and in 30 control subjects by using scintigraphic techniques, the hydrogen breath test and stool markers. In the diabetics various parameters including duration of diabetes, gastrointestinal symptoms and complications such as autonomic neuropathy, peripheral neuropathy and proteinuria were determined and related to gastrointestinal transit times. Gastric emptying was significantly prolonged in diabetics as compared to the control group (p less than 0.05) with 35% of the diabetics disclosing abnormally delayed gastric emptying, whereas no significant overall differences were observed between diabetics and controls concerning mouth-to-cecum transit and whole gut transit time. However, abnormally prolonged mouth-to-cecum transit was detected in 23% and delayed whole gut transit in 26% of the diabetics (p less than 0.02 as compared to the control group). There was a significant correlation of dyspeptic symptoms and diarrhea with prolonged gastric emptying (p less than 0.001). Gastric emptying, but not mouth-to-cecum transit or whole gut transit was significantly related to autonomic nerve dysfunction (p less than 0.001) and peripheral neuropathy (p less than 0.02). Furthermore, gastric emptying and WGT were significantly correlated to proteinuria (p less than 0.03). Using a linear regression model, autonomic neuropathy, diarrhea and dyspeptic symptoms were the major parameters in predicting delayed gastric emptying. It is concluded that in diabetics different compartments of the gut are affected by gastrointestinal motor abnormalities and that these segments are probably regulated by independent or different control mechanisms.     

Human migrating myoelectric complex in relation to gastrointestinal transit of a meal.

Feeding interrupts the migrating myoelectric complex in most mammals. This study aimed to assess whether resumption of the migrating myoelectric complex in the human duodenum after eating was related to the gastrointestinal transit of the meal. Five healthy subjects participated in the study. After eating a radiolabelled test meal consisting of mixed liquid and solids, duodenal myoelectric activity and gastrointestinal transit of the meal were determined simultaneously. In spite of considerable variation in entire gastric emptying time between subjects (range 2.5-5.0 hours), significant correlation was found between the completion of gastric emptying and the resumption of duodenal phase III activity within subjects (p less than 0.01). A new technique for recording the duodenal myoelectric activity was used.     

Gastrointestinal motility in obesity

Abstract. Gastrointestinal motility is closely linked to the rate at which nutrients become systemically available. Regulation of gastric emptying represents the most important brake against delivery of nutrients to the intestine in excess of digestive and absorptive capacity. In man, gastric emptying is slowed in proportion to the energy density of the meal, which will level out the rate of energy delivery to the duodenum. Studies suggest a more rapid gastric emptying in obesity, although the opposite has been reported in some experimental settings. Moreover, gastric volume is larger in obese individuals and appropriate satiety signals are not triggered in response to gastric distension. Postprandial intestinal transit time in obesity is similar to that in normal-weight subjects, however, despite this fact, intestinal absorption of nutrients is more efficient in obesity. Several regulatory mechanisms for gastrointestinal motility, such as the autonomous and enteric nervous systems and gastrointestinal regulatory peptides, are also of importance for feeding behaviour and metabolism. Dysfunction of the autonomous nervous system has been observed, the sensitivity to cholecystokinin is decreased in obesity, and plasma concentrations of somatostatin and neurotensin are lower than in normal-weight subjects. These changes in regulatory mechanisms favour rapid gastrointestinal transit of ingested nutrients and promote rapid intestinal absorption in obesity and decreased satiety in response to ingested food. It is presently not known whether the observed changes in gastrointestinal motility in obesity represent a primary feature linked to the pathogenesis of such disease.     

Gastrointestinal transit through esophagus,stomach, small and large intestine in patients with progressive systemic sclerosis

Liquid esophageal transit and gastric emptying, mouth-to-cecum transit, and whole gut transit of a solid-liquid meal were measured in 14 patients with PSS, 16 control subjects (esophageal transit), and 20 control subjects (gastrointestinal transit), respectively, by using scintigraphic techniques, the hydrogen breath test, and stool markers. In patients with PSS, the glucose hydrogen breath test for detection of small intestinal overgrowth was performed and various gastrointestinal symptoms were determined. Esophageal transit and gastric emptying were significantly prolonged in PSS patients with 11 of 14 PSS patients (79%) disclosing delayed esophageal transit and eight of 14 PSS patients (57%) disclosing delayed gastric emptying. All PSS patients with prolonged gastric emptying also had delayed esophageal transit and there was a significant positive correlation between esophageal transit and gastric emptying (r=0.696,P<0.01). No significant differences between PSS patients and controls were detected concerning mouth-to-cecum transit and whole gut transit, but abnormally delayed mouth-to-cecum transit was found in four of 10 PSS patients (40%) and abnormally prolonged whole gut transit was detected in three of 13 PSS patients (23%). Small bacterial overgrowth was diagnosed in three of 14 PSS patients (21%). Delayed esophageal transit and gastric emptying were associated with dysphagia, retrosternal pain, and epigastric fullness, while prolonged whole gut transit was associated with constipation. It is concluded that delayed gastric emptying is frequently associated with esophageal transit disorders in PSS patients and may be one important factor for the development of gastroesophageal reflux disease in these patients.     

Effect of cisapride on the gastrointestinal transit of a solid meal in normal human subjects.

The effect of cisapride, a new gastrointestinal prokinetic agent, on the transit of a standard meal through the stomach, small intestine and colon was studied in 10 normal subjects. Cisapride had no significant effect on gastric emptying but decreased mouth to caecum transit time (p less than 0.01). Stool weight and frequency were not significantly increased but the time for the first appearance of stool markers and the arrival of 20% and 50% of stool markers was decreased after cisapride (p less than 0.05).     

Increased volume and decreased emptying of the gallbladder in large (morbidly obese, tall normal, and muscular normal) people

Impaired gallbladder emptying has been suggested as a possible factor in the pathogenesis of gallstones. Obese people have an increased incidence of gallstones, but there is no evidence of this in nonobese large people. This study was undertaken to determine if abnormal gallbladder motility is present in obese people. Fasting gallbladder volumes were determined using real-time ultrasound in 18 morbidly obese subjects whose weights were in a steady state [45 kg (100 lb) over ideal weight or twice expected weight for age and height; 9 males, 9 females], 18 age- and sex-matched volunteers of average size, and 18 nonobese large normal males (9 tall, 9 muscular). Gallbladder emptying studies with 99mtechnetium-diisopropyliminodiacetic acid were performed using 200 ml of 10% cream as a stimulus. The small-volume liquid fatty meal contained 113indium-diethylenetriaminepentaacetic acid to control for differences in gastric emptying in obesity. The gallbladder emptying rate in large people, both obese and nonobese, was less than that in normals of average size (p = 0.05). Fasting gallbladder volumes in large people were: obese, 41 ml (37-66 ml) (median; 95% confidence limits); nonobese large normal, 40 ml (27-43 ml). These values were greater than in normals of average size [17 ml (14-21 ml) (p = 0.03)]. Postprandial gallbladder volumes were also greater in large people: obese, 15 ml (8-23 ml); nonobese large normal, 20 ml (13-23 ml) compared with 2 ml (1-5 ml) in normals of average size (p less than 0.05). There were no differences between obese and nonobese large people. There were no differences in gastric emptying rates or in cholecystokinin, gastrin, motilin, and secretin release between obese and normal subjects. Gallbladder volume is crudely proportional to body size. Although fasting and postprandial volumes are greater in obesity, this is also present in nonobese, relatively size-matched controls. These data do not support a role for impaired gallbladder emptying in gallstone formation in obese patients whose weights are in a steady state.