Effects of intraduodenal infusion of lauric acid and L-tryptophan, alone and combined, on glucoregulatory hormones, gastric emptying and glycaemia in healthy men.

BACKGROUND AND AIM: In healthy men, intraduodenal administration of the fatty acid, lauric acid ('C12') and the amino acid, L-tryptophan ('TRP'), at loads that individually do not affect energy intake, reduce energy intake substantially when combined. C12 and TRP may also stimulate cholecystokinin and glucagon-like peptide-1 (GLP-1), which both slow gastric emptying, a key determinant of postprandial blood glucose. Accordingly, combination of C12 and TRP has the potential to reduce post-meal glycaemia more than either nutrient alone. METHODS: Twelve healthy, lean men (age (mean ± SD): 28 ± 7 years) received, on 4 separate occasions, 45-min intraduodenal infusions of C12 (0.3 kcal/min), TRP (0.1 kcal/min), C12 + TRP (0.4 kcal/min), or 0.9% saline (control), in a randomised, double-blind fashion. 30 min after commencement of the infusion a mixed-nutrient drink was consumed and gastric emptying measured (13C breath-test) for 3 h. Blood samples were obtained at baseline, in response to treatments alone, and for 2 h post-drink for measurements of plasma glucose, cholecystokinin, GLP-1, C-peptide, insulin and glucagon. 'Early' (first 30 min) and 'overall' glycaemic and hormone responses were evaluated. RESULTS: C12 + TRP and C12 delayed the rise in, but did not affect the overall glycaemic response to the drink, compared with control and TRP (all P < 0.05). C12 + TRP slowed gastric emptying compared with control and TRP (both P < 0.005), and C12 non-significantly slowed gastric emptying compared with control (P = 0.090). C12 + TRP and C12 delayed the rise in C-peptide and insulin, and also stimulated CCK and glucagon, compared with control and TRP (all P < 0.05). Only C12 + TRP stimulated early and overall GLP-1 compared with control (P < 0.05). CONCLUSIONS: In healthy men, C12 + TRP and C12, in the loads administered, had comparable effects to delay the rise in glucose following a nutrient drink, probably primarily by slowing of gastric emptying, as a result of CCK and GLP-1 stimulation, while TRP had no effect.

Resveratrol supplementation significantly influences obesity measures: a systematic review and dose-response meta-analysis of randomized controlled trials.

This study aimed to summarize earlier randomized controlled trials on the effects of resveratrol supplementation on body weight (BW), body mass index (BMI), waist circumference (WC) and fat mass (FM). We searched PubMed, SCOPUS, Cochrane Library and Google Scholar from inception to April 2018 using relevant keywords. All clinical trials investigating the effects of resveratrol supplementation on BW, BMI, WC and FM in adults were included. Overall, 28 trials were included. Pooled effect sizes suggested a significant effect of resveratrol administration on weight (weighted mean differences [WMD]: -0.51 kg, 95% confidence interval [CI]: -0.94 to -0.09; I2  = 50.3%, P = 0.02), BMI (WMD: -0.17 kg m-2 , 95% CI: -0.32, -0.03; I2  = 49.6%, P = 0.02) and WC (WMD: -0.79 cm, 95% CI: -1.39, -0.2; I2  = 13.4%, P = 0.009), respectively. However, no significant effect of resveratrol supplementation on FM was found (WMD: -0.36%, 95% CI: -0.88, 0.15; I2  = 0.0%, P = 0.16). Findings from subgroup analysis revealed a significant reduction in BW and BMI in trials using resveratrol at the dosage of <500 mg d-1 , those with long-term interventions (≥3 month), and performed on people with obesity. Taken together, the data suggest that resveratrol supplementation has beneficial effects to reduce BW, BMI and WC, but not FM.

Upper Gastrointestinal Function in Morbidly Obese Adolescents Before and 6 Months After Gastric Banding.

BACKGROUND: The effects of laparoscopic adjustable gastric band (LAGB) placement on upper gastrointestinal tract function in obese adolescents are unknown. Therefore, our aim was to determine the short-term effects of LAGB on esophageal motility, gastroesophageal reflux, gastric emptying, appetite-regulatory hormones, and perceptions of post-prandial hunger and fullness. METHODS: This study was part of a prospective cohort study (March 2009-December 2015) in one tertiary referral hospital. The study included obese adolescents (14-18 years) with a body mass index (BMI) > 40 (or ≥ 35 with comorbidities). Gastric emptying was assessed by 13C-octanoic acid breath test, pharyngeal, and esophageal motor function by high-resolution manometry with impedance (HRIM), and appetite and other perceptions using 100-mm visual analogue scales. Dysphagia symptoms were scored using a Dakkak questionnaire. Data were compared pre- and post-LAGB placement and at a 6-month follow-up. RESULTS: Based upon analysis of 15 adolescents, at the 6-month follow-up, LAGB placement: (i) led to a significant reduction in weight and BMI; (ii) increased fullness and decreased hunger post-meal; (iii) increased symptoms of dysphagia after solid food; and, despite these effects, (iv) caused little or no changes to appetite hormones, while (v) effects on gastric emptying, esophageal motility, esophageal bolus transport, and esophageal emptying were not significant. CONCLUSION: In adolescents, LAGB improved BMI and altered the sensitivity to nutrients without significant effects on upper gastrointestinal tract physiology at the 6-month follow-up.

Dietary glycaemic index and glycaemic load and upper gastrointestinal disorders: results from the SEPAHAN study.

BACKGROUND: Little is known about the effects of carbohydrate, particularly any association between dietary glycaemic index or glycaemic load and uninvestigated heartburn or uninvestigated chronic dyspepsia in the community. The present study aimed to determine associations between dietary glycaemic index or glycaemic load and uninvestigated heartburn or uninvestigated chronic dyspepsia. METHODS: This cross-sectional study was conducted in 2987 adults. Dietary glycaemic index and glycaemic load were estimated using a validated food-frequency questionnaire. Uninvestigated heartburn and uninvestigated chronic dyspepsia were determined using a modified and validated version of the Rome III questionnaire. RESULTS: After controlling for various confounders, high glycaemic load was associated with an increased risk of uninvestigated heartburn [odds ration (OR) = 1.75; 95% confidence interval CI = 1.03, 2.97; P = 0.04] and uninvestigated chronic dyspepsia (OR = 2.14; 95% CI: 1.04, 4.37; P = 0.04) in men but not in women. In normal-weight individuals, high glycaemic index was related to an increased risk of uninvestigated heartburn (OR = 1.52; 95% CI: 1.07, 2.15; P = 0.02) and high glycaemic load to an increased risk of uninvestigated chronic dyspepsia (OR=1.78; 95% CI: 1.05, 3.01; P = 0.03). No significant associations were observed in subjects with excess body weight. CONCLUSIONS: Our data suggest that there are body mass index- and sex-specific associations between dietary carbohydrate quality with uninvestigated heartburn and uninvestigated chronic dyspepsia.

Effects of small intestinal glucose on glycaemia, insulinaemia and incretin hormone release are load-dependent in obese subjects.

BACKGROUND/OBJECTIVES: Studies concerning the glycaemic response to oral glucose, or meals in obesity have usually failed to account for gastric emptying. It has been suggested that the incretin effect may be diminished in obesity as a result of a reduction in glucagon-like peptide-1 (GLP-1) secretion. We sought to determine the effect of two different rates of intraduodenal glucose infusions on glycaemic, insulinaemic and incretin hormone responses in lean and obese subjects and compare the effects of oral and intraduodenal glucose in obese subjects. SUBJECTS/METHODS: Eleven obese subjects (age 37.5±4.1 years, body mass index (BMI) 35.7±1.4 kg m-2) and 12 controls (age 34.7±4.0 years, BMI 23.9±0.7 kg m-2) received intraduodenal infusions of glucose at 1 or 3 kcal min-1, or saline for 60 min (t=0-60 min), followed by intraduodenal saline (t=60-120 min). In obese subjects, an oral glucose tolerance test was performed. Blood glucose, serum insulin, plasma total GLP-1 and total gastric inhibitory polypeptide (GIP) were measured. RESULTS: In both the groups (P<0.001), the incremental areas under the curve (iAUC)0-60 min for glucose was greater with the 3 kcal min-1 than the 1 kcal min-1 infusion; the iAUC0-120 min for glucose during 3 kcal min-1 was greater (P<0.05), in the obese. Insulin responses to 1 kcal min-1 and, particularly, 3 kcal min-1 were greater (P<0.001) in the obese. Stimulation of GLP-1 and GIP were greater (P<0.001) in response to 3 kcal min-1, compared with 1 kcal min-1 and saline, without any difference between the groups. In the obese, glycaemic, insulinaemic and GIP, but not GLP-1, responses to oral and intraduodenal glucose were related (P<0.05). CONCLUSIONS: The rate of duodenal glucose delivery is a major determinant of glycaemia, insulinaemia and incretin hormone release in obese subjects. Obesity is not apparently associated with impaired GLP-1 secretion.

Lipid stimulation of fatty acid sensors in the human duodenum: relationship with gastrointestinal hormones, BMI and diet.

BACKGROUND AND AIMS: The small intestinal free fatty acid (FFA) sensors, FFA receptor 1 (FFAR1), FFAR4, G-protein receptor 119 (GPR119) and cluster of differentiation-36 (CD36), mediate the fat-induced release of gastrointestinal (GI) hormones. We investigated whether expression of duodenal FFA sensors in humans was (i) altered by intraduodenal (ID) lipid infusion, (ii) disordered in overweight or obese individuals, (iii) related to lipid-induced GI hormone secretion or (iv) affected by habitual dietary patterns. METHODS: Endoscopic duodenal biopsies were collected from 20 lean (body mass index (BMI): 22±1 kg m-2), 18 overweight (BMI: 27±1 kg m-2) and 19 obese (BMI: 35±1 kg m-2) participants at baseline, and following a 30 min ID Intralipid infusion (2 kcal min-1); FFA sensor expression was quantified by reverse transcription-PCR. On a separate day, participants underwent ID Intralipid infusion (2 kcal min-1) for 120 min, to assess GI hormone responses. Habitual diet was evaluated using food frequency questionnaires. RESULTS: Baseline FFAR1 and FFAR4 expression were lower, and CD36 was higher, in obese participants compared with lean participants. ID lipid increased GPR119 and FFAR1 expression equally across study groups, but did not alter FFAR4 or CD36 expression. Increased FFAR1 expression correlated positively with glucose-dependent insulinotropic polypeptide (GIP) secretion (r=0.3, P<0.05), whereas there was no relationship between habitual diet with the expression of FFA sensors. CONCLUSIONS: Obesity is associated with altered duodenal expression of FFAR1, FFAR4 and CD36, suggesting altered capacity for the sensing, absorption and metabolism, of dietary lipids. GPR119 and FFAR1 are early transcriptional responders to the presence of ID lipid, whereas FFAR1 may be an important trigger for lipid-induced GIP release in humans.

The duodenal glucose load impacts the oral disposition index in healthy subjects.

AIM: In healthy subjects, the oral disposition index (ratio of insulin response to insulin sensitivity) is predictive of the development of Type 2 diabetes. Gastric emptying, which exhibits a substantial interindividual variation, is a major determinant of postprandial glycaemia in health and diabetes. We sought to determine whether the rate of intraduodenal glucose delivery affects the disposition index in people without diabetes. METHODS: Nineteen Caucasian males received glucose infusions via an intraduodenal catheter at either 2 kcal/min (ID2) or 4 kcal/min (ID4) for 120 min, on two separate days with measurements of blood glucose (G) and plasma insulin (I) at frequent intervals. The insulin response was estimated by the ratio of the change in insulin to that of change in glucose at 30 min (∆I(0-30)/∆G(0-30)) and 60 min (∆I(0-60)/∆G(0-60)). Insulin sensitivity was estimated as 1/fasting insulin. The oral disposition index (DI) was calculated as ∆I(0-30)/∆G(0-30) × 1/fasting insulin and ∆I(0-60)/∆G(0-60) × 1/fasting insulin. RESULTS: The overall glycaemic response was comparable on both days, but the insulin response was much greater at ID4 when calculated at either 30 or 60 min (P < 0.05). DI was also greater (P < 0.05) in response to ID4 than ID2. CONCLUSIONS: The rate of duodenal glucose delivery has a major impact on insulin release and, thereby, DI. This suggests that the rate of gastric emptying, which determines duodenal glucose delivery, is a determinant of DI.

Patterns of diet-related practices and prevalence of gastro-esophageal reflux disease.

BACKGROUND: No studies have evaluated associations between patterns of diet-related practices as determined by latent class analysis (LCA) and gastro-esophageal reflux disease (GERD). We aimed to assess this relationship in a large sample of Iranian adults. METHODS: In a cross-sectional study in 4763 adults, diet-related practices were assessed in four domains, 'meal pattern', 'eating rate', 'intra-meal fluid intake', and 'meal-to-sleep interval', using a pretested questionnaire. LCA was applied to identify classes of diet-related practices. We defined GERD as the presence of heartburn sometimes, often or always. KEY RESULTS: The prevalence of GERD in the study population was 23.5% (n = 1120). We identified two distinct classes of meal patterns: 'regular' and 'irregular', three classes of eating rates: 'moderate', 'moderate-to-slow', and 'moderate-to-fast', two major classes of fluid ingestion with meals: 'moderate' and 'much intra-meal drinking', and two classes regarding the interval between meals and sleeping: 'short' and 'long meal-to-sleep' interval. After adjustment for potential confounders, subjects with 'irregular meal pattern' had higher odds of GERD compared with subjects with 'regular meal pattern' (OR: 1.21; 1.00-1.46). However, when taking into account BMI, the association disappeared. 'Long meal-to-sleep interval' was inversely associated with GERD compared with 'short meal-to-sleep interval' (OR: 0.73; 95% CI: 0.57-0.95). 'Eating rate' and 'intra-meal fluid intake' were not significantly associated with GERD. CONCLUSIONS & INFERENCES: Our data suggest certain associations between dietary patterns and GERD. These findings warrant evaluation in prospective studies to establish the potential value of modifications in dietary behaviors for the management of GERD.

Digestive physiology of the pig symposium: secretion of gastrointestinal hormones and eating control.

Nutrient ingestion triggers numerous changes in gastrointestinal (GI) peptide hormone secretion that affect appetite and eating. Evidence for these effects comes from research in laboratory animals, healthy humans, and, increasingly, obese patients after Roux-en-Y gastric bypass (RYGB) surgery, which has marked effects on GI hormone function and is currently the most effective therapy for morbid obesity. Increases in cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine (PYY) and decreases in ghrelin secretion after meals are triggered by changes in the nutrient content of the intestine. One apparent physiological function of each is to initiate a reflex-like feedback control of eating. Here we briefly review this function, with an emphasis on the controls of their secretion. Each is secreted from enteroendocrine cells that are directly or indirectly affected by caloric load, macronutrient composition, and other characteristics of ingested food such as fatty acid chain length. In addition, digestive hydrolysis is a critical mechanism that controls their secretion. Although there are relatively few data in agricultural animals, the generally consistent results across widely divergent mammals suggests that most of the processes described are also likely to be relevant to GI hormone functions and eating in agricultural animals.

Duodenal lipid-induced symptom generation in gastroesophageal reflux disease: role of apolipoprotein A-IV and cholecystokinin.

BACKGROUND: Duodenal lipid intensifies the perception of esophageal acid perfusion. Recently, we showed that genes implicated in lipid absorption were upregulated in the duodenum of fasting gastro-esophageal reflux disease (GERD) patients. This suggests that chylomicron production and secretion may be enhanced and, consequently, the release of apolipoprotein A-IV (apoA-IV), a chylomicron-derived signaling protein. ApoA-IV may stimulate release of cholecystokinin (CCK), an activator of vagal afferents. This study evaluated putative involvement of abnormal apoA-IV and CCK responses to lipid in GERD. METHODS: Ten GERD patients and 10 healthy volunteers (HV) underwent duodenal perfusion with Intralipid 20%, 2 kcal min(-1) , for 60 min. Symptoms were scored, blood samples collected every 15 min during lipid perfusion and 15 min after discontinuation when duodenal biopsies were taken. Plasma and mucosal concentrations of apoA-IV and CCK and transcript levels of 21 genes implicated in lipid absorption, differentially expressed under fasting conditions, were quantified. KEY RESULTS: Heartburn (P = 0.003), abdominal discomfort (P = 0.037) and nausea (P = 0.008) only increased significantly during lipid infusion in GERD patients. Following lipid infusion mean mucosal apoA-IV concentration was lower in GERD patients compared with HV (P = 0.023), whereas plasma concentration tended to be elevated (P = 0.068). Mean mucosal CCK concentration was also lower in GERD patients (P = 0.009). Two genes, HIBADH and JTB, were upregulated in GERD patients (P = 0.008 and P = 0.038, respectively). CONCLUSIONS & INFERENCES: Our results suggest excessive duodenal lipid-induced release of apoA-IV and CCK in GERD. We postulate that the resulting heightened activation of duodenal vagal afferents may underlie central sensitization, thereby increasing the perception of reflux events.

Effects of variations in duodenal glucose load on glycaemic, insulin, and incretin responses in type 2 diabetes.

AIMS: Postprandial glucagon-like peptide-1 (GLP-1) secretion and the 'incretin effect' have been reported to be deficient in Type 2 diabetes, but most studies have not controlled for variations in the rate of gastric emptying. We evaluated blood glucose, and plasma insulin, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) responses to intraduodenal glucose in Type 2 diabetes, and compared these with data from healthy controls. METHODS: Eight males with well-controlled Type 2 diabetes, managed by diet alone, were studied on four occasions in single-blind, randomized order. Blood glucose, and plasma insulin, GLP-1, and GIP were measured during 120-min intraduodenal glucose infusions at 1 kcal/min (G1), 2 kcal/min (G2) and 4 kcal/min (G4) or saline control. RESULTS: Type 2 patients had higher basal (P < 0.0005) and incremental (P < 0.0005) blood glucose responses to G2 and G4, when compared with healthy controls. In both groups, the stimulation of insulin and GLP-1 by increasing glucose loads was not linear; responses to G1 and G2 were minimal, whereas responses to G4 were much greater (P < 0.005 for each) (incremental area under the GLP-1 curve 224 ± 65, 756 ± 331 and 2807 ± 473 pmol/l.min, respectively, in Type 2 patients and 373 ± 231, 505 ± 161 and 1742 ± 456 pmol/l.min, respectively, in healthy controls). The GLP-1 responses appeared comparable in the two groups. In both groups there was a load-dependent increase in plasma GIP with no difference between them. CONCLUSIONS: In patients with well-controlled Type 2 diabetes, blood glucose, insulin and GLP-1 responses are critically dependent on the small intestinal glucose load, and GLP-1 responses are not deficient.

Effects of acute dietary restriction on gut motor, hormone and energy intake responses to duodenal fat in obese men.

BACKGROUND: Previous patterns of energy intake influence gastrointestinal function and appetite, probably reflecting changes in small-intestinal nutrient-mediated feedback. Obese individuals consume more fat and may be less sensitive to its gastrointestinal and appetite-suppressant effects than lean individuals. OBJECTIVE: To evaluate the hypothesis that, in obese individuals, the effects of duodenal fat on gastrointestinal motor and hormone function, and appetite would be enhanced by a short period on a very-low-calorie diet (VLCD). METHODS: Eight obese men (body mass index 34±0.6 kg m(-2)) were studied on two occasions, before (V1), and immediately after (V2), a 4-day VLCD. On both occasions, antropyloroduodenal motility, plasma cholecystokinin (CCK), peptide-YY (PYY) and ghrelin concentrations, and appetite perceptions were measured during a 120-min intraduodenal fat infusion (2.86 kcal min(-1)). Immediately afterwards, energy intake was quantified. RESULTS: During V2, basal pyloric pressure and the number and amplitude of isolated pyloric pressure waves (PWs) were greater, whereas the number of antral and duodenal PWs was less, compared with V1 (all P<0.05). Moreover, during V2, baseline ghrelin concentration was higher; the stimulation of PYY and suppression of ghrelin by lipid were greater, with no difference in CCK concentration; and hunger and energy intake (kJ; V1: 4378±691, V2: 3634±700) were less (all P<0.05), compared with V1. CONCLUSIONS: In obese males, the effects of small-intestinal lipid on gastrointestinal motility and some hormone responses and appetite are enhanced after a 4-day VLCD.

Gastrointestinal hormonal dysfunction in gastroparesis and functional dyspepsia.

BACKGROUND: Numerous hormones secreted by the gut, during both the fasted state and in response to a meal, influence gastrointestinal motor and/or sensory function, and appear to contribute to the pathogenesis of delayed gastric emptying associated with gastroparesis, functional dyspepsia (FD) and feed intolerance in critical illness. Gut hormones are, accordingly, potential targets for the management of these patients. PURPOSE: This article will discuss the hypersensitivity to enteral fat and endogenous (nutrient-stimulated) and exogenous cholecystokinin (CCK) in patients with FD, and the elevation in both fasting and postprandial CCK levels evident in this group. It will review the use of pharmacological agonists of motilin and ghrelin, which accelerate gastric emptying, in the management of gastroparesis and FD. The frequent finding of markedly delayed gastric emptying in the critically ill will be examined; this is associated with elevated plasma CCK and peptide YY in both the fasted and postprandial states, which may account for the increase in small intestinal nutrient inhibitory feedback on gastric motility in this group. The concepts that the rate of gastric emptying is a major determinant of postprandial glycemic excursions in diabetes, and that modulation of gastric emptying may improve glycemic control, will be addressed; in type 1 and insulin-treated type 2 diabetic patients, co-ordination of insulin administration with nutrient delivery and absorption should be optimized, while type 2 patients who are not on insulin are likely to respond to dietary and/or pharmacological interventions which slow gastric emptying.

Dietary factors in functional dyspepsia.

Functional dyspepsia (FD) is characterized by upper gastrointestinal symptoms, which are frequently exacerbated by meal ingestion. While subgroups of FD patients exhibit a range of disturbances in upper gastrointestinal motor function, including delayed gastric emptying and abnormal intragastric meal distribution, which may reflect impaired proximal gastric relaxation and/or antral dysmotility, the association between symptoms and abnormalities in motor function appears to be relatively weak. More recently, the concept of visceral hypersensitivity to mechanical and chemical/nutrient stimuli has been promoted as important in the aetiology of dyspeptic symptoms. Somewhat surprisingly, the role of 'dietary' factors, that is, those factors, related directly to food ingestion, including patterns of nutrient intake, potential intolerance to specific foods or macronutrients, as well as cognitive factors, have been largely ignored. Moreover, presently available treatments fail to take into account the fact that symptoms are frequently induced by eating. This review focuses on the relevance of 'dietary' factors to FD.

Role of cholecystokinin in appetite control and body weight regulation.

Summary Cholecystokinin (CCK), a peptide that is distributed widely throughout the gastrointestinal tract and the central nervous system, has a number of physiological effects including the stimulation of gallbladder contraction and pancreatic and gastric acid secretion, slowing of gastric emptying and suppression of energy intake. This review focuses on current knowledge relating to (i) the effects of CCK on energy intake; (ii) the role for CCK in the pathophysiology of obesity; and (iii) the therapeutic potential for strategies which modulate the action or secretion of CCK in the management of obesity. While CCK plays a role in the acute regulation of appetite and energy intake, there is little evidence to suggest that specific CCK receptor agonists, or modulation of the actions of endogenous CCK by dietary manipulation, have sustainable inhibitory effects on energy intake. Hence, it appears unlikely that manipulating the pathways by which CCK modulates energy intake will prove to be an effective strategy in the long term management of obesity.

Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes.

AIMS/HYPOTHESIS: Long-term trials in insulin-treated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA(1)c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide's effect on satiety and food intake in humans has not yet been assessed. METHODS: In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60+/-9 years, BMI 28.9+/-4.8 kg/m(2)) and 15 non-diabetic obese men (age 41+/-21 years, BMI 34.4+/-4.5 kg/m(2)) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 microg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time. RESULTS: Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Delta-202+/-64 kcal, -23+/-8%, p<0.01) and obese (Delta-170+/-68 kcal, -16+/-6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides. CONCLUSIONS/INTERPRETATION: The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.

Effects of lipase inhibition on gastric emptying of, and on the glycaemic, insulin and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetes.

AIMS/HYPOTHESES: We examined the effects of lipase inhibition with orlistat on (i) gastric emptying of, and (ii) the glycaemic, glucagon-like peptide-1 (GLP-1) and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetic patients. METHODS: Eight type 2 diabetic patients, who were aged 62 years (median range: 49-68 years) and managed by diet alone, consumed a meal containing 65 g powdered potato, 20 g glucose reconstituted with 200 ml water (labelled with 20 MBq (99m)Tc-sulphur-colloid) and 45 g margarine. They did this on two separate occasions, with and without 120 mg orlistat, and while in the seated position with their back against a gamma camera. Venous blood samples for measurement of blood glucose, plasma insulin and GLP-1 were obtained immediately before the meal and at regular intervals afterwards. Blood pressure (systolic and diastolic) and heart rate were measured using an automated device. RESULTS: Gastric emptying of the meal was faster after orlistat than without orlistat (50% emptying time [mean +/- SEM], 61+/-8 min vs 98+/-5 min; p=0.0001). In the first 60 min after the meal blood glucose (p=0.001) and plasma insulin (p=0.01) concentrations were higher in patients who had taken orlistat; between 60 and 180 min plasma GLP-1 (p=0.02) concentrations were lower after orlistat than without orlistat. Between 0 and 30 min systolic blood pressure (p=0.003) was lower, and heart rate (p=0.03) greater in subjects who had taken orlistat than in those who had not. CONCLUSIONS/INTERPRETATION: Inhibition of fat digestion by orlistat may-as a result of more rapid gastric emptying-exacerbate postprandial glycaemia and the postprandial fall in blood pressure in patients with type 2 diabetes after ingestion of meals containing fat and carbohydrate.

Role of cognitive factors in symptom induction following high and low fat meals in patients with functional dyspepsia.

BACKGROUND: and aims: Dietary fat plays a role in the pathophysiology of symptoms in functional dyspepsia (FD). In healthy subjects, cognitive factors enhance postprandial fullness; in FD patients, attention increases gut perception. We hypothesised that the information given to patients about the fat content of a meal would affect dyspeptic symptoms. METHODS: Fifteen FD patients were each studied on four occasions in a randomised double blind fashion. Over two days they ingested a high fat yoghurt (HF) and over the other two days a low fat yoghurt (LF). For each yoghurt, the patients received the correct information about its fat content on one day (HF-C, LF-C) and the opposite (wrong) information on the other day (HF-W, LF-W). Dyspeptic symptoms, plasma cholecystokinin (CCK) concentrations, and gastric volumes were evaluated. RESULTS: Both the fat content and information about the fat content affected fullness and bloating scores-both were higher after HF-C compared with LF-C, and LF-W compared with LF-C, with no differences between HF-C and HF-W. Nausea scores were higher after HF compared with LF, with no effect of the information about fat content. No differences between discomfort and pain scores were found between study conditions. Plasma CCK and gastric volumes were greater following HF compared with LF, with no effect of the information given to the patients. All differences are p<0.05. CONCLUSIONS: Cognitive factors contribute to symptom induction in FD. Low fat foods may also elicit symptoms if patients perceive foods as high in fat, while CCK and gastric volumes do not appear to be affected by cognitive factors.