Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis.

BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans. METHODS: Randomized crossover single-blind study in 17 healthy volunteers receiving GIP (2 or 5 pmol kg(-1) min(-1), n = 8), GLP-1 (0.75 pmol kg(-1) min(-1), n = 9) or NaCl for 180 min with a radionuclide-labeled omelette and fruit punch (370 kcal). Outcome measures were gastric emptying rate, insulinogenic index, hunger, satiety, desire to eat, and prospective food consumption. Blood was analyzed for GIP, GLP-1, glucagon, C-peptide, peptide YY (PYY) and ghrelin. KEY RESULTS: Glucose-dependent insulinotropic polypeptide 2 and 5 pmol kg(-1) min(-1) decreased gastric half-emptying time from 128.5 ± 34.0 min in controls to 93.3 ± 6.3 and 85.2 ± 11.0 min (P < 0.05). Glucose-dependent insulinotropic polypeptide 5 pmol kg(-1) min(-1) decreased postprandial glucose (P < 0.001) and insulin (P < 0.05) with increased insulinogenic index. Glucose-dependent insulinotropic polypeptide had no effects on hunger, desire to eat, satiety or prospective consumption. Glucagon-like peptide-1 0.75 pmol kg(-1) min(-1) increased half-emptying time from 76.6 ± 7.6 min to 329.4 ± 71.6 (P < 0.01). Glucagon-like peptide-1 decreased plasma glucose and insulin (both P < 0.05-0.001), and increased insulinogenic index markedly. Hunger, desire to eat and prospective consumption were decreased (P < 0.05), and satiety borderline increased (P < 0.06). CONCLUSION & INFERENCES: The incretin effect of GIP and GLP-1 differs as GLP-1 exerts a strong glucoregulatory incretin through inhibition of gastric emptying, which GIP does not. Thus, GLP-1 as incretin mimetic may offer unique benefits in terms of weight loss in treatment of type 2 diabetes.

Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans.

BACKGROUND: Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6-h infusion in humans. METHODS: Ghrelin (15 pmol kg(-1) min(-1)) or saline was infused intravenously for 360 min after intake of radio-opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon-like peptide-1 (GLP-1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed. KEY RESULTS: The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half-emptying time (50.3 +/- 3.9 vs 59.9 +/- 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP-1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin. CONCLUSIONS & INFERENCES: The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders.

Differential effect of PYY1-36 and PYY3-36 on gastric emptying in man.

Peptide tyrosine-tyrosine (PYY) is a prandially controlled hormone in endocrine ileal and colonic mucosa cells. In plasma, PYY appears as full-length PYY1-36 and truncated PYY3-36. Both have different pharmacological profile, and PYY3-36 seems to inhibit food intake. We aimed at investigating the effect of intravenously administered PYY1-36 and PYY3-36 on gastric emptying and short-term metabolic control. Eight healthy adults were studied in single-blinded, randomized design. At separate occasions, intravenous infusion of saline, PYY1-36 or PYY3-36 (0.8 pmol kg(-1) min(-1)) and a radio-labelled omelette were given. Gastric emptying (scintigraphy), appetite ratings (VAS), and plasma concentrations of insulin, glucose, GLP-1 and PYY were measured. PYY3-36 and PYY1-36 both inhibited gastric emptying, PYY3-36 most effectively. Half-emptying time was prolonged from 63.1+/-5.2 (saline) to 87.0+/-11.5 min (PYY3-36), whereas retention at 120 min was 2.5+/-1.4% for saline, 10.7+/-4.4 for PYY1-36 and 15.8+/-4.4 for PYY3-36. Neither form influenced glucose or GLP-1 concentrations, but both decreased the postprandial rise in insulin. PYY3-36 induced nausea (VAS increase 47.5+/-22.6 mm) and decreased prospective consumption (VAS change 39.5+/-7.7 mm). In conclusion, PYY3-36's reducing effect upon food intake might be mediated by a decreased gastric emptying rate.

Ghrelin stimulates gastric emptying and hunger in normal-weight humans.

CONTEXT: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. MAIN OBJECTIVE: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion in normal volunteers. DESIGN: This was a randomized, double-blind, crossover study. SUBJECTS: Subjects included normal human volunteers and patients with GH deficiency. INTERVENTION: Intervention included saline or ghrelin (10 pmol/kg.min) infusion for 180 min after intake of a radioactively labeled omelette (310 kcal) or GH substitution in GH-deficient patients. MAIN OUTCOME MEASURES: Measures consisted of gastric empty-ing parameters and postprandial plasma levels of ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY, and motilin. RESULTS: The emptying rate was significantly faster for ghrelin (1.26 +/- 0.1% per minute), compared with saline (0.83% per minute) (P < 0.001). The lag phase (16.2 +/- 2.2 and 26.5 +/- 3.8 min) and half-emptying time (49.4 +/- 3.9 and 75.6 +/- 4.9 min) of solid gastric emptying were shorter during ghrelin infusion, compared with infusion of saline (P < 0.001). The postprandial peak in plasma concentration for cholecystokinin and glucagon-like peptide-1 occurred earlier and was higher during ghrelin infusion. There was no significant effect of ghrelin on plasma motilin or peptide YY. There was no difference in gastric emptying before and after GH substitution. CONCLUSION: Our results demonstrate that ghrelin increases the gastric emptying rate in normal humans. The effect does not seem to be mediated via GH or motilin but may be mediated by the vagal nerve or directly on ghrelin receptors in the stomach. Ghrelin receptor agonists may have a role as prokinetic agents.

A role for pancreatic polypeptide in the regulation of gastric emptying and short-term metabolic control.

CONTEXT: Previous studies using pancreatic polypeptide (PP) infusions in humans have failed to show an effect on gastric emptying, glucose metabolism, and insulin secretion. This might be due to the use of nonhuman sequences of the peptide. OBJECTIVE: The objective of this study was to use synthetic human PP to study gastric emptying rates of a solid meal and postprandial hormone secretion and glucose disposal as well as the gastric emptying rate of water. DESIGN: This was a single-blind study. SETTING: The study was performed at a university hospital. PARTICIPANTS: Fourteen healthy adult subjects were studied. INTERVENTIONS: Infusion of saline or PP at 0.75 or 2.25 pmol/kg.min was given to eight subjects (gastric emptying of solid food), and infusion of saline or PP at 2.25 pmol/kg.min was given to six subjects (gastric emptying of water). MAIN OUTCOME MEASURES: The main outcome measures were gastric emptying of solids (scintigraphy), hunger ratings (visual analog scale), and plasma concentrations of PP, insulin, glucagon, somatostatin, glucagon-like peptide 1, glucose, and gastric emptying of plain water (scintigraphy). RESULTS: PP prolonged the lag phase and the half-time of emptying of the solid meal. The change in hunger rating, satiety, desire to eat after the meal, or prospective consumption was not affected. The postprandial rise in plasma glucose was prolonged by PP. The postprandial rise in insulin was also delayed by PP. PP had no significant effect on the emptying of water. CONCLUSIONS: PP inhibits gastric emptying of solid food and delays the postprandial rise in plasma glucose and insulin. PP is suggested to have a physiological role in the pancreatic postprandial counterregulation of gastric emptying and insulin secretion.

Inhibitory effect of exogenous orexin a on gastric emptying, plasma leptin, and the distribution of orexin and orexin receptors in the gut and pancreas in man.

Orexin A (OXA) is a novel peptide that appears to play a role in the regulation of food intake, arousal, and energy balance. The aim of this study was to study the effect of iv infusion of OXA on gastric emptying, appetite, leptin, ghrelin, and glucose metabolism in man (six normal men) and the localization of OXA and orexin receptors (OXRs) 1 and 2 in the human gut. Gastric emptying was studied scintigraphically after ingestion of a 99mTc-labeled omelet and iv infusion of OXA (10 pmol/kg.min). Appetite ratings and blood samples were obtained at regular intervals. The immunohistochemical distribution of OXA and OXRs was examined using antibodies recognizing OXA, OX1R, and OX2R in human gastrointestinal tissue. OXA had no effect on lag phase or gastric half-emptying time. However, the gastric emptying rate was significantly slower without affecting appetite ratings. Plasma concentrations of insulin were increased by OXA, whereas plasma leptin decreased and ghrelin was unchanged. OXA immunoreactivity was observed in a subset of neurons and varicose nerve fibers in the mucosa, ganglia, and circular muscle layer and mucosal endocrine cells in the stomach and small intestine. OXA-immunoreactive cells in the islets of Langerhans contained insulin with a subset expressing OX2R. In conclusion, peripheral OXA seems to slightly affect the regulation of gastric emptying in humans without affecting appetite ratings. OXA decreased plasma levels of leptin, suggesting a possible interaction between leptin and OXA in the regulation of energy homeostasis.

Peripheral administration of GLP-2 to humans has no effect on gastric emptying or satiety.

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted in parallel to the circulation after a meal. Intravenous (IV) GLP-1 has an inhibitory effect on gastric emptying, hunger and food intake in man. In rodents, central administration of GLP-2 increases satiety similar to GLP-1. The aim of the present study was to assess the effect of IV administered GLP-2 on gastric emptying and feelings of hunger in human volunteers. In eight (five men) healthy subjects (age 31.1+/-2.9 years and BMI 24.1+/-1.0 kg m(-2)), scintigraphic solid gastric emptying, hunger ratings (VAS) and plasma concentrations of GLP-2 were studied during infusion of saline or GLP-2 (0.75 and 2.25 pmol kg(-1) min(-1)) for a total of 180 min. Concentrations of GLP-2 were elevated to a maximum of 50 and 110 pmol l(-1) for 0.75 and 2.25 pmol kg(-1) min(-1) infusion of GLP-2, respectively. There was no effect of GLP-2 on either the lag phase (29.5+/-4.4, 26.0+/-5.2 and 21.2+/-3.6 min for saline, GLP-2 0.75 or 2.25 pmol kg(-1) min(-1), respectively) or the half emptying time (84.5+/-6.1, 89.5+/-17.8 and 85.0+/-7.0 min for saline, GLP-2 0.75 or 2.25 pmol kg(-1) min(-1), respectively). The change in hunger rating after the meal to 180 min was also unaffected by infusion of GLP-2. GLP-2 does not seem to mediate the ileal brake mechanism.

Gastric emptying and duodeno-gastro-oesophageal reflux in gastro-oesophageal reflux disease.

BACKGROUND: Previous studies present conflicting results regarding relationship between gastric emptying and gastro-oesophageal reflux disease. Reflux of duodenal content to oesophagus is generally considered to be associated with more severe disease. AIM: To assess presence of a gastric emptying disorder in persons with reflux of duodenal contents to oesophagus and to identify any correlation with gastric emptying and oesophageal motility. METHODOLOGY: A total of 15 subjects with (B+) and 15 subjects without (B-) bile reflux to oesophagus determined by 24-hour bilirubin monitoring were studied with scintigraphic solid gastric emptying and 24-hour oesophageal manometry. RESULTS: There was no difference in lag phase [median 23.7 (range 10.8-44.0) vs 24.6 (8.1-40.1) min], half emptying time [74.6 (48.0-93.6) vs 82.8 (54.4-153.9) min] or emptying rate [0.89 (0.59-1.34) vs 0.83 (0.36-1. 15)%/min] for B- and B+ subjects, respectively. In addition, there was no difference in emptying rate of gastric fundus between B- and B+ subjects. Subjects with bile reflux had less effective oesophageal contractions of oesophageal body [9.4(3.3-37)%] compared to subjects without bile reflux [32(19-47)%, p = 0.002]. However, there was no correlation between oesophageal motility and gastric emptying. CONCLUSION: Results suggest that a gastric emptying disorder is a less likely contributing cause of bile reflux to the oesophagus, but bile reflux is associated with less effective oesophageal motility.

GLP-1 inhibits gastric emptying of water but does not influence plasma.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) has been shown to inhibit gastric emptying of a caloric load but the effect on a non-caloric load is unknown. METHODS: Seven healthy men were studied after an over-night fast. Thirty min before the intake of 330 ml radioactively labeled water either GLP-1 (0.75 pmol/kg/min) or saline was administered intravenously and continued for 75 min. Scintigraphic gastric emptying was performed for 45 min and plasma samples were obtained for analysis of vasopressin, sodium, osmolality, GLP-1, insulin, and glucose. In addition, electric field stimulation of human gastric muscle strips was done. RESULTS: The median (range) percent water retained in the stomach, 45 min after intake of water, was 96% (68%-98%) and 12% (2%-42%) (P = 0.02) during infusion of GLP-1 and saline, respectively. Additionally, GLP-1 did not affect basal tone or contractile response of gastric muscle strips to electric field stimulation or acetylcholine (ACh). There was no change in plasma concentrations of vasopressin, sodium, or plasma osmolality during GLP-1 compared to saline infusion. CONCLUSION: GLP-1 has a profound inhibitory effect on the gastric emptying of water in man, but no short-term effect on water homeostasis. No effect was seen on contractility of gastric muscle strips suggesting an indirect action on gastric emptying.

Nationwide standardisation and evaluation of scintigraphic gastric emptying: reference values and comparisons between subgroups in a multicentre trial.

By means of a standardised procedure, reference values for scintigraphic gastric emptying were established. The influence of gender, age, menstrual cycle, body mass index (BMI) and smoking habits was also evaluated. Eight centres recruited 20 healthy subjects each. The meal consisted of a technetium-99m labelled omelet (1,300 kJ) and of 150 ml unlabelled soft drink. Geometric means of frontal and dorsal acquisitions were utilised in a linear fit model for determination of the linear emptying rate, and by using the intercepts of the regression line with the 90% and 50% levels, the lag phase and half-emptying time, respectively, were defined. All individuals showed an initial lag phase and subsequent linear emptying. Because of a longer lag phase and a slower linear emptying rate, premenopausal women had a slower gastric emptying than postmenopausal women and men of all ages. The gastric emptying rate increased with age in the women, mainly due to a shortened lag phase, while the emptying rate remained almost unchanged with age in the males. There were no significant differences in results between the centres. The menstrual cycle, BMI and smoking habits did not affect emptying. In conclusion, the fact that the results showed a slower gastric emptying rate in younger women compared with older women and men indicates that it is necessary to use separate reference values for fertile females.

Gastric emptying: comparison of scintigraphic, polyethylene glycol dilution, and paracetamol tracer assessment techniques.

BACKGROUND: The method of choice for studying gastric emptying is dependent on several factors. The aim of the present study was to assess the concordance between solid gastric emptying, using a scintigraphic technique as gold standard, and gastric emptying as measured with parcetamol tracer and polyethylene glycol (PEG) dilution. METHODS: Two groups of seven male volunteers with similar ages and weights were studied, one for scintigraphic (310-kcal omelette with 12-15 MBq 99mTc-labeled macroaggregated albumin) and paracetamol (1.5 g dissolved in water and administered concomitantly with the omelette) and one for the marker dilution study (PEG 4000 dissolved in a 310-kcal meal). RESULTS: The gastric half-emptying time (T50) was shorter in the PEG study than in the scintigraphic test (47.5 (37.5-62) versus 68.1 (43.6-89.4), median (range) (P < 0.05), respectively), whereas there was no significant difference between the T50 for gastric emptying as assessed with the scintigraphic and paracetamol tracer methods. No difference in gastric emptying rate using PEG dilution or paracetamol tracer was obtained. CONCLUSIONS: In summary, this study shows that scintigraphic, paracetamol tracer, and PEG dilution methods can all be used to assess gastric emptying. The use of the paracetamol tracer technique offers a relatively inexpensive technique that yields a good approximation of gastric emptying as verified by the scintigraphic emptying of a solid meal.

[Examination of gastric emptying with gamma camera. Clinically useful, uniform method now established]. / Undersökning av ventrikeltömning med gammakamera. Kliniskt användbar, enhetlig metod nu fastställd.

Although more than 30 years have passed since the introduction of scintigraphic testing of gastric emptying there has been no well-defined standard. Eight Swedish hospitals have established a nationally standardized method for scintigraphic testing of gastric emptying of solids. 160 healthy subjects participated. The meal consisted of a 99mTc-labeled omelet (1300 kJ) and 150 ml unlabeled soft drink (290 kJ). There were no differences in calculated variables between the centers. Premenopausal women showed slower emptying than postmenopausals and men of any age, making separate reference values for younger women necessary.

What is the message of a meeting? Analysis and comparison of the 2458 abstracts of the EANM/WCNMB congress in Berlin and the SNM meeting in Toronto in 1998. European Association of Nuclear Medicine/World Federation of Nuclear Medicine and Biology, and the Society of Nuclear Medicine.

The abstracts of the joint congress of EANM/WCNMB in Berlin 1998 and of the 45th Annual Meeting of the Society of Nuclear Medicine in Toronto 1998 have been analysed and compared in terms of comprehensibility, composition, questions at issue, methods, patient/subject number, type of conclusion and duplication of information between the meetings. All 1362 and 1096 abstracts, respectively, were analysed from the abstract books with regard to ten "hard" and four "soft" variables. The dominant topics were new radiopharmaceuticals, methods of synthesis, examination methods, evaluation of examinations, investigation algorithms, technical devices and novel use of radiopharmaceuticals. In addition to these topics, there were numerous reports about established radiopharmaceuticals and techniques, often without a specific merit mentioned. There were also many abstracts with questions outside nuclear medicine, but using such techniques. Few papers reported negative findings or dealt with quality assurance, dosimetry, and cost-effectiveness. Many of the conclusions contained hyperbole. Some abstracts were very extensive and detailed. Sixty-seven contributions conveyed identical information at both meetings. Structured and/or paragraphed abstracts promote clarity and reduce the number of lines that need to be read in order to comprehend the background and aim of the abstract. Such contributions were more frequent at the EANM/WCNMB congress while the SNM meeting covered a wider field with a greater representation of radiophysics, instrumentation, and computer evaluations.

GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans.

The aim of the present study was to assess the effect of glucagon-like peptide-1 (GLP-1) on solid gastric emptying and the subsequent release of pancreatic and intestinal hormones. In eight men [age 33.6 +/- 2.5 yr, body mass index 24.1 +/- 0.9 (means +/- SE)], scintigraphic solid gastric emptying during infusion of GLP-1 (0.75 pmol. kg(-1). min(-1)) or saline was studied for 180 min. Concomitantly, plasma concentrations of C- and N-terminal GLP-1, glucose, insulin, C-peptide, glucagon, and peptide YY (PYY) were assessed. Infusion of GLP-1 resulted in a profound inhibition of both the lag phase (GLP-1: 91.5, range 73.3-103.6 min vs. saline: 19. 5, range 10.2-43.4 min) and emptying rate (GLP-1: 0.34, range 0.06-0. 56 %/min vs. saline: 0.84, range 0.54-1.33 %/min; P < 0.01 for both) of solid gastric emptying. Concentrations of both intact and total GLP-1 were elevated to supraphysiological levels. Plasma glucose and glucagon concentrations were below baseline during infusion of GLP-1 in contrast to saline infusion, where concentrations were elevated above baseline (both P < 0.001). The insulin and C-peptide responses were lower during infusion with GLP-1 than with saline (P < 0.004 and P < 0.001, respectively). Plasma PYY concentrations decreased below baseline during GLP-1 infusion in contrast to saline, where concentrations were elevated above baseline (P = 0.04). Infusion of GLP-1 inhibits solid gastric emptying with secondary effects on the release of insulin, C-peptide, and glucagon, resulting in lower plasma glucose concentrations. In addition, the release of PYY into the circulation is inhibited by GLP-1 infusion, suggesting a negative feedback of GLP-1 on the function of the L-cell.

Gastric emptying and electrogastrography in patients on CAPD.

OBJECTIVE: To evaluate if impaired gastric emptying of digestible solids can explain the disturbed eating behavior in continuous ambulatory peritoneal dialysis (CAPD) patients, and if predialytic and dialytic (CAPD and hemodialysis) patients with impaired gastric emptying have a higher prevalence of electrogastrographic (EGG) abnormalities. DESIGN: Cross-sectional study. After ingestion of a 99mTc-labeled test meal, anterior and posterior 1-minute scintigraphic acquisitions were collected every 5 minutes during the first 50 minutes and thereafter every 10 minutes until 2 hours had elapsed. Simultaneously, cutaneous EGG recorded gastric myoelectric activity. SETTING: The Division of Nephrology and the Department of Nuclear Medicine at the same academic teaching hospital. PARTICIPANTS: Thirty outpatients participated in both the gastric emptying and the EGG studies. Dialysis patients should have been on dialysis for more than 3 months. For comparison, 160 healthy control subjects participated in the gastric emptying study. MAIN OUTCOME MEASURES: The following parameters were used to describe gastric emptying: lag phase 90%, half-emptying time (T50), gastric retention at 90 and 120 minutes (Ret 90/120) and gastric emptying rate (GER, %/min). Electrogastrographic measurements were expressed as percentages of normal slow waves [2.4-3.6 cycles/min (cpm)], bradygastria (1.5-2.4 cpm), and tachygastria (3.6-10 cpm). RESULTS: T50 was prolonged, Ret 90 and Ret 120 were higher, and GER was slower in male CAPD patients compared to male controls. No significant differences were found in postprandial EGG. CONCLUSION: Gastric emptying is impaired in male non-diabetic CAPD patients. However, abnormalities in postprandial EGG cannot explain this finding.

Distal small bowel hormones: correlation with fasting antroduodenal motility and gastric emptying.

The aim of the present study was to study the interdigestive motor complex (MMC), distal small intestinal hormones, and gastric emptying in normal-weight and obese subjects before and after jejunoileal bypass (JIB). Therefore, fasting antroduodenal motility, gastric emptying, and RIA for motilin (MOT), neurotensin (NT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) was performed in nine obese subjects before (BMI 42 +/- 4 kg/m2) and nine months after (BMI 31 +/- 4) JIB, and in two groups of nine age- and sex-matched controls (BMI 23 +/- 1 and 21 +/- 1). The rate of gastric emptying was faster in obese subjects and GLP-1 lower compared to normal-weight controls. After JIB, fewer phase III of the MMC were observed; fasting levels of PYY were elevated during the MMC; postprandial levels of NT, PYY, and GLP-1 were elevated; and gastric emptying was delayed. Our results suggest that there may be an association between an impaired GLP-1 response after food intake and obesity, and after JIB, PYY seems to regulate interdigestive motility while GLP-1 may regulate early gastric emptying.

Reduced food intake after jejunoileal bypass: a possible association with prolonged gastric emptying and altered gut hormone patterns.

The object of this study was to examine whether eating behavior, food preference, gastric emptying, and gut hormone patterns are altered after jejunoileal bypass (JIB) in patients with severe obesity. Eight obese [mean (+/- SD) body mass index (BMI; in kg/m2) 42.9 +/- 4] subjects were studied prospectively before and 9 mo after JIB with eight age- and sex-matched normal-weight control subjects. Total energy intake, data from the universal eating monitor (VIKTOR), eating motivation measured by visual analog scales, a food-preference checklist, a forced-choice list, solid-phase gastric emptying, and postprandial concentrations of cholecystokinin, motilin, and neurotensin were studied. BMI was reduced by 29% after JIB. Compared with normal subjects, the JIB patients showed a reduced desire to eat, decreased hunger, and reduced prospective consumption before a test meal. After surgery, obese subjects selected fewer food items and showed a reduced preference for high-carbohydrate and high-fat items before a test meal. There was a trend from an accelerated toward a decelerated eating pattern in obese subjects after JIB. After JIB, gastric emptying of obese subjects was slowed and similar to that in control subjects. Obese subjects had lower postprandial cholecystokinin concentrations that were lower than those of control subjects both before and after JIB. Postprandial concentrations of neurotensin were higher after JIB. We conclude that after JIB, the desire to eat and preference for high-carbohydrate and high-fat items is reduced, resulting in decreased energy intake. That gastric emptying is prolonged and gut hormone patterns are altered with low postprandial plasma cholecystokinin and high neurotensin plasma concentrations may at least partly account for these observations.

Gastrointestinal hormones and gastric emptying 20 years after jejunoileal bypass for massive obesity.

OBJECTIVE: Some studies have shown a more rapid gastric emptying in obese subjects. Six to twelve months after jejunoileal bypass (JIB) neurotensin (NT) and enteroglucagon have been shown to be elevated after food intake. These hormones, together with peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) have been implicated in the reduction of upper gastrointestinal motility seen after infusion of nutrients into the ileum. AIM: To study if the postprandial gut hormone pattern and gastric emptying is altered 20 y after JIB. SUBJECTS: Seven subjects operated with JIB a mean (s.d.) 20 +/- 3 y ago, with a BMI of 44 +/- 4 kg/m2 at the time of surgery and 31 +/- 4 at present. For comparison seven sex-matched non-operated obese controls (BMI 43 +/- 3) were studied. METHODS: Serial blood samples were obtained every 10 min after intake of a 280 kcal meal. Radioimmunoassays for motilin, cholecystokinin (CCK), NT, PYY and GLP-1 were performed. Gastric emptying of a solid meal was studied using a radioactively labelled omelette (of 310 kcal) for 120 min). RESULTS: After JIB postprandial motilin, CCK, NT, PYY and GLP-1 were elevated compared to non-operated obese subjects. Similarly, basal levels of CCK, motilin, GLP-1 and PYY were elevated in the operated group. No difference was observed in the rate of gastric emptying between the two groups. CONCLUSION: Both fasting and postprandial gut hormone levels are elevated 20 y after JIB. The impact of long-term rapid stimulation of the ileum and subsequent raised gut hormone levels on gastric emptying is not clear.

Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender.

It has been suggested that obesity is associated with an altered rate of gastric emptying, and that there are also sex differences in gastric emptying. The results of earlier studies examining gastric emptying rates in obesity and in males and females have proved inconsistent. The aim of this study was to investigate the influence of obesity and gender on gastric emptying, by extending conventional evaluation methods with Kaplan-Meier plots, in order to assess whether these factors have to be accounted for when interpreting results of scintigraphic gastric emptying tests. Twenty-one normal-weight volunteers and nine obese subjects were fed a standardised technetium-99m labelled albumin omelette. Imaging data were acquired at 5- and 10-min intervals in both posterior and anterior projections with the subjects in the sitting position. The half-emptying time, analysed by Kaplan-Meier plot (log-rank test), were shorter in obese subjects compared to normal-weight subjects and later in females compared to males. Also, the lag-phase and half-emptying time were shorter in obese females than in normal females. This study shows an association between different gastric emptying rates and obesity and gender. Therefore, body mass index and gender have to be accounted for when interpreting results of scintigraphic gastric emptying studies.