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Duodenal and ileal glucose infusions differentially alter gastrointestinal peptides, appetite response, and food intake: a tube feeding study.
Poppitt, SD, Shin, HS, McGill, AT, Budgett, SC, Lo, K, Pahl, M, Duxfield, J, Lane, M, Ingram, JR
The American journal of clinical nutrition. 2017;(3):725-735
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Abstract
Background: Activation of the ileal brake through the delivery of nutrients into the distal small intestine to promote satiety and suppress food intake provides a new target for weight loss. Evidence is limited, with support from naso-ileal lipid infusion studies.Objective: The objective of the study was to investigate whether glucose infused into the duodenum and ileum differentially alters appetite response, food intake, and secretion of satiety-related gastrointestinal peptides.Design: Fourteen healthy male participants were randomly assigned to a blinded 4-treatment crossover, with each treatment of single-day duration. On the day before the intervention (day 0), a 380-cm multilumen tube (1.75-mm diameter) with independent port access to the duodenum and ileum was inserted, and position was confirmed by X-ray. Subsequently (days 1-4), a standardized breakfast meal was followed midmorning by a 90-min infusion of isotonic glucose (15 g, 235 kJ) or saline to the duodenum or ileum. Appetite ratings were assessed with the use of visual analog scales (VASs), blood samples collected, and ad libitum energy intake (EI) measured at lunch, afternoon snack, and dinner.Results: Thirteen participants completed the 4 infusion days. There was a significant effect of nutrient infused and site (treatment × time, P < 0.05) such that glucose-to-ileum altered VAS-rated fullness, satisfaction, and thoughts of food compared with saline-to-ileum (Tukey's post hoc, P < 0.05); decreased ad libitum EI at lunch compared with glucose-to-duodenum [-22%, -988 ± 379 kJ (mean ± SEM), Tukey's post hoc, P < 0.05]; and increased glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) compared with all other treatments (Tukey's post hoc, P < 0.05).Conclusions: Macronutrient delivery to the proximal and distal small intestine elicits different outcomes. Glucose infusion to the ileum increased GLP-1 and PYY secretion, suppressed aspects of VAS-rated appetite, and decreased ad libitum EI at a subsequent meal. Although glucose to the duodenum also suppressed appetite ratings, eating behavior was not altered. This trial was registered at www.anzctr.org.au as ACTRN12612000429853.
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Crohn's disease activity index does not correlate with endoscopic recurrence one year after ileocolonic resection.
Regueiro, M, Kip, KE, Schraut, W, Baidoo, L, Sepulveda, AR, Pesci, M, El-Hachem, S, Harrison, J, Binion, D
Inflammatory bowel diseases. 2011;(1):118-26
Abstract
BACKGROUND Crohn's disease clinical trials utilize the Crohn's Disease Activity Index (CDAI) to measure primary endpoint assessments of clinical recurrence and remission. We evaluated the extent of agreement between clinical recurrence/remission as defined by the CDAI and endoscopic recurrence 1 year after intestinal resection for Crohn's disease (CD). METHODS Twenty-four CD patients who had been randomly assigned to a postoperative clinical trial had 1 year clinical, endoscopic, and histological assessment for disease recurrence. The primary endpoint was the extent of agreement between endoscopic recurrence and clinical recurrence 1 year after intestinal resection for CD. Secondary endpoints were extent of agreement between endoscopic recurrence and the surrogate markers of CD activity, i.e., histological activity, sedimentation rate, and C-reactive protein (CRP). RESULTS Twelve of the 24 patients (50%) were in endoscopic remission (i0, i1) and 12 (50%) had endoscopic recurrence (i2, i3, or i4). There was good agreement between endoscopy and histological activity scores (intraclass correlation coefficient = 0.53, kappa coefficient = 0.58). In contrast, there was little to no relationship between endoscopy and CDAI scores; median CDAI scores for endoscopy scores of i0/i1, i2, i3, and i4 were 118, 76, 156, and 78, respectively (P for trend = 0.88). The kappa coefficient (of agreement) between endoscopy score ± 2 and CDAI score ± 150 was 0.12 (exact P = 0.68), indicating poor agreement. Similarly, there was no consistent association observed between endoscopy scores and mean CRP and ESR values at week 54. CONCLUSIONS The CDAI shows poor agreement with endoscopic recurrence 1 year after intestinal resection. Endoscopic recurrence should be the primary endpoint of future postoperative studies and ileocolonoscopy the gold standard test to detect postoperative recurrence.
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Prospective randomized controlled trial comparing 2 versions of laparoscopic ileal interposition associated with sleeve gastrectomy for patients with type 2 diabetes with BMI 21-34 kg/m(2).
De Paula, AL, Stival, AR, Macedo, A, Ribamar, J, Mancini, M, Halpern, A, Vencio, S
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2010;(3):296-304
Abstract
BACKGROUND The objective of the present study was to prospectively evaluate the results of 2 versions of laparoscopic ileal interposition (II) and sleeve gastrectomy (SG) for the treatment of patients with type 2 diabetes mellitus and body mass index of 21-34 kg/m(2). METHODS The laparoscopic procedures were prospectively and randomly performed in 38 patients. Of the 38 patients, 18 underwent the first version (II-SG) and 20 underwent the second version in which a diversion of the second portion of the duodenum was applied (II-DSG) and a segment of ileum was interposed into the proximal duodenum. The groups were comparable regarding age (56 and 50 years); gender (13 men and 5 women and 14 men and 6 women); weight (78 and 86 kg); mean BMI (27 and 29 kg/m(2)); duration of type 2 diabetes mellitus (10.1 and 9.2 years); the presence of dyslipidemia (12 and 8 patients), micro- and macroalbuminuria (9 and 9 patients), hypertension (8 and 15 patients), and retinopathy (5 and 8 patients); and the use of antidiabetic medications and the hemoglobin A1c level (8.6% and 8.4%). All patients were followed up for >or=2 years. RESULTS The mean hospital stay was 3.4 days for the II-SG and 3.5 days for the II-DSG group. No patient required reoperation. All patients in both groups achieved lower levels of hemoglobin A1c. In the II-SG group, the mean hemoglobin A1c level was 6.35% (range 4.9-8.1). In the II-DSG group, the mean hemoglobin A1c level was 5.39% (range 4.2-6.5%). The mean BMI decreased in both groups to 22.2 kg/m(2) in the II-SG group and 22.7 kg/m(2) in the II-DSG group. Normal cholesterol levels (<200 mg/dL) were observed in 95% of the II-SG group and 100% of the II-DSG group. The triglycerides were lower than 150 mg/dL in 73% of the II-SG group and 90% of the II-DSG group after 24 months. CONCLUSION Laparoscopic II-SG and II-DSG were safe and effective operations for controlling type 2 diabetes mellitus in a nonobese (BMI 21-34 kg/m(2)) population.
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Effect of fat saturation on satiety, hormone release, and food intake.
Maljaars, J, Romeyn, EA, Haddeman, E, Peters, HP, Masclee, AA
The American journal of clinical nutrition. 2009;(4):1019-24
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Abstract
BACKGROUND Ileal delivery of fat reduces hunger and food intake through activation of the ileal brake. Physicochemical properties of fat have been shown to affect satiety and food intake. OBJECTIVE The objective of this study was to assess the effect of ileal fat emulsions with differing degrees of fatty acid saturation on satiety, food intake, and gut peptides (cholecystokinin and peptide YY). We hypothesized that long-chain triacylglycerols with diunsaturated fatty acids would increase satiety and reduce energy intake compared with long-chain triacylglycerols with monounsaturated or saturated fatty acids. DESIGN We performed a double-blind, randomized, crossover study in which 15 healthy subjects [mean age: 24 y; mean body mass index (in kg/m(2)): 22] were intubated with a naso-ileal catheter and participated in 4 experiments performed in random order on 4 consecutive days. After consumption of a liquid meal, subjects received a fat or control infusion in the ileum. Fat emulsions consisted of 6 g of 18:0 (shea oil; mainly 18:0), 18:1 (canola oil; mainly 18:1), or 18:2 (safflower oil; mainly 18:2) oils. Food intake was measured during an ad libitum lunch. Satiety questionnaires (visual analog scale) and blood samples were collected at regular intervals. RESULTS Compared with the control, only 18:2 and 18:1 significantly increased fullness and reduced hunger. No effect on food intake was observed. 18:1 and 18:2 increased cholecystokinin secretion significantly compared with the control. Fatty acid saturation did not affect peptide YY secretion. CONCLUSIONS When infused into the ileum, triacylglycerols with unsaturated fatty acids increase satiety, whereas triacylglycerols with saturated fatty acids does not. This trial was registered with the Dutch Trial Register as: ISRCTN51742545.
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Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers.
Maljaars, PW, Symersky, T, Kee, BC, Haddeman, E, Peters, HP, Masclee, AA
International journal of obesity (2005). 2008;(11):1633-9
Abstract
OBJECTIVE The ileal brake is a feedback mechanism activated by nutrients, especially fat, with marked effects on satiety. The effects of low doses of ileal fat on satiety are largely unknown. We therefore studied the effect of ileal vs oral delivery of low doses of fat on satiety and gut peptide secretion. DESIGN Randomized, single-blind crossover design. SUBJECTS Sixteen healthy, normal-weight volunteers (6 male; mean age 26 years, mean body mass index 22.4). INTERVENTION Participants were intubated with a 290-cm-long nasoileal tube and consumed, on 3 consecutive days, either a liquid breakfast with 3 g fat followed by an ileal placebo infusion at t=105-150 min (treatment C) or a fat-free liquid breakfast followed by an ileal infusion of either an emulsion of 3 g (treatment 13 g) or 9 g (treatment 19 g) fat (safflower oil). MEASUREMENTS Satiety parameters by visual analog scales and plasma concentrations of CCK and PYY. RESULTS C significantly increased satiety and CCK secretion compared with the fat-free breakfast. Ileal fat perfusion of both 3 and 9 g 13 g and 19 g) significantly increased satiety during and after fat perfusion, without differences in satiety between 13 g and 19 g. During ileal fat infusion, CCK increased dose dependently, whereas PYY concentrations increased significantly only after 9 g of fat. Secretion of CCK but not of PYY correlated to satiety levels. CONCLUSION Postprandial satiety following a liquid breakfast can be effectively and significantly increased by small amounts (as little as 3 g) of fat perfused into the ileum. Ileal fat dose-dependently increased CCK but not PYY secretion. The satiating effect of ileal fat may be partly mediated by CCK.
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Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after lleo-caecal resection.
Van Gossum, A, Dewit, O, Louis, E, de Hertogh, G, Baert, F, Fontaine, F, DeVos, M, Enslen, M, Paintin, M, Franchimont, D
Inflammatory bowel diseases. 2007;(2):135-42
Abstract
BACKGROUND Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within 1 year after ileo-caecal surgery. Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LAl on early post-operative endoscopic recurrence of CD. METHODS Seventy patients with CD were enrolled prior to elective ileo-caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestle (1010 colony-forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LAl on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization. RESULTS Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention-to-treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32 versus 1.22+/-1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LAl and placebo groups, respectively (P = 0.33). Using a per-protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LAl versus placebo groups: 1.44 +/-1.31 versus 1.05 +/- 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LAl and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LAl and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank test: P = 0.79). CONCLUSION Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection.
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Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation.
Cragg, RA, Phillips, SR, Piper, JM, Varma, JS, Campbell, FC, Mathers, JC, Ford, D
Gut. 2005;(4):469-78
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Abstract
BACKGROUND The role of intestinal transporter regulation in optimising nutrient absorption has been studied extensively in rodent and cell line models but not in human subjects. AIMS The aim of the present study was to investigate the response in vivo of zinc transporters in the human enterocyte to dietary zinc supplementation. SUBJECTS Eighteen patients who had previously undergone ileostomy, all free of any symptoms of inflammatory bowel disease. METHODS Subjects took a daily zinc supplement of 25 mg for 14 days in a double blind, placebo controlled, crossover trial. The effect of the supplement on expression in ileal biopsies of the zinc transporters SLC30A1, SLC30A4, SLC30A5, SLC39A1, SLC39A4, and metallothionein was measured by reverse transcription-polymerase chain reaction RT-PCR. Expression of SLC30A1, SLC30A5, and SLC39A4 was also examined by immunoblotting. RESULTS The zinc supplement reduced SLC30A1 mRNA (1.4-fold) together with SLC30A1, SLC30A5, and SLC39A4 protein (1.8-fold, 3.7-fold, and to undetectable levels, respectively) in ileal mucosa and increased metallothionein mRNA (1.7-fold). The supplement had no effect on expression of SLC30A4 or SLC39A1 mRNA. Localisation of SLC30A5 at the apical human enterocyte/colonocyte membrane and also at the apical membrane of Caco-2 cells was demonstrated by immunohistochemistry. Commensurate with these observations in zinc supplemented human subjects, SLC30A1, SLC30A5, and SLC39A4 mRNA and protein were reduced in Caco-2 cells cultured at 200 muM compared with 100 muM zinc. CONCLUSIONS These observations indicate that, in response to variations in dietary zinc intakes, regulated expression of plasma membrane zinc transporters in the human intestine contributes to maintenance of zinc status.
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Dietary peptides increase endogenous amino acid losses from the gut in adults.
Moughan, PJ, Butts, CA, Rowan, AM, Deglaire, A
The American journal of clinical nutrition. 2005;(6):1359-65
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BACKGROUND Accurate estimates of endogenous ileal total nitrogen and amino acid flows are necessary to ascertain true dietary amino acid digestibility coefficients and for the factorial estimation of dietary amino acid requirements. OBJECTIVE The objective was to ascertain endogenous amino acid losses from the small bowel in human subjects consuming a protein-free diet or a diet with enzyme-hydrolyzed casein (EHC; MW <5000) as the sole source of nitrogen. DESIGN The subjects were 8 men and women with terminal ileum ileostomies after ulcerative colitis who consumed the protein-free and EHC-based diets in a crossover design. Each subject received each test diet in single meals followed by 2 consecutive 9-h total collections of digesta. Digesta samples for the EHC treatment were centrifuged and ultrafiltered (10 000 MW cutoff), with the precipitate-plus-retentate fraction (>10 000 MW) providing a measurement of endogenous ileal amino acids. RESULTS The mean endogenous flows for most of the amino acids and nitrogen were significantly (P < 0.05) higher when determined with the EHC-based diet than with the protein-free diet. Mean (n = 8) endogenous ileal nitrogen flows were 2061 and 4233 mug/g dry matter intake for the protein-free and EHC-based diets, respectively. CONCLUSION The traditional protein-free method underestimates endogenous ileal amino acid loss in adults.
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Effects of meal frequency and high-fibre rye-bread diet on glucose and lipid metabolism and ileal excretion of energy and sterols in ileostomy subjects.
Lundin, EA, Zhang, JX, Lairon, D, Tidehag, P, Aman, P, Adlercreutz, H, Hallmans, G
European journal of clinical nutrition. 2004;(10):1410-9
Abstract
OBJECTIVE To investigate the effect of a rye, high-fibre diet (HFD) vs a wheat, low-fibre diet (LFD), meal frequency, nibbling (Nib, seven times a day) or ordinary (Ord, three times a day), and their combined effects on blood glucose, insulin, lipids, urinary C-peptide and ileal excretion of energy, cholesterol and bile acids in humans. DESIGN LFD period with Nib or Ord meal frequency followed by an HFD diet with Nib or Ord meal frequency in randomized, crossover design. SETTING Outpatients of ileostomy volunteers were called for an investigation in research word. SUBJECTS A total of 10 subjects (two female subjects, age 34 and 51 y; eight males, mean age 54.4 y, range 43-65 y) participated in the experiment. All subjects were proctocolectomized for ulcerative colitis (mean 16.0 y, range 8-29 y before the study). INTERVENTION In total, 10 ileostomy subjects started with LFD for 2 weeks, the first week on either Nib (five subjects) or Ord (five subjects) and the second week on the other meal frequencies, in a crossover design, followed by a wash-out week, and continued with HFD period for 2 weeks in the same meal frequency manner. All foods consumed in both Nib or Ord regimens were identical and a high-fibre rye bread was used in the HFD period and a low-fibre wheat bread in the LFD period. MAIN OUTCOME MEASURES Day-profiles of blood glucose, insulin and lipids, blood lipids before and after dietary intervention, and excretion of steroids in the effluents and C-peptide in the urine. RESULTS During the Nib regimen, plasma glucose and insulin peaks were lower at the end of the day with HFD compared with LFD. Urinary C-peptide excretion was significantly higher in the day-time on LFD compared with HFD (LFD-Ord vs HFD-Ord, P < 0.01; LFD-Nib vs HFD-Nib, P < 0.01). Plasma free-cholesterol, total cholesterol, triglycerides and phospholipids were significantly higher (P < 0.05) after LFD than after HFD with the Nib regimen. A higher excretion of energy (P < 0.05) and chenodeoxycholic acid (P < 0.05) were observed with HFD compared with LFD regardless of meal frequency. A higher daily excretion of cholic acid, total bile acids, cholesterol, net cholesterol and net sterols (P < 0.05) was observed on HFD compared with LFD with the Nib regimen. CONCLUSIONS An HFD decreased insulin secretion measured as a decreased excretion of C-peptide in urine and as decreased plasma insulin peaks at the end of the day during a Nib regimen. The smoother glycaemic responses at the end of the day during a Nib regimen may be a consequence of a second meal phenomenon, possibly related to the nature of dietary fibre complex.
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Ileal losses of nitrogen and amino acids in humans and their importance to the assessment of amino acid requirements.
Gaudichon, C, Bos, C, Morens, C, Petzke, KJ, Mariotti, F, Everwand, J, Benamouzig, R, Daré, S, Tomé, D, Metges, CC
Gastroenterology. 2002;(1):50-9
Abstract
BACKGROUND & AIMS Irreversible amino acid losses at the human ileum are not taken into account when tracer-derived amino acid requirements are calculated because the data available are scarce. We have investigated amino acid losses at the ileal level in humans after ingestion of a protein meal. METHODS Thirteen volunteers ingested a single meal of 15N milk or soy proteins. The appearance of 15N and 15N amino acids in the ileal effluents collected using an ileal tube was monitored for 8 hours. RESULTS In the soy group, higher losses of endogenous nitrogen, especially originating from amino acids, were observed, as well as a higher flow rate of dietary non-amino acid nitrogen. With soy protein, the digestibilities of valine, threonine, histidine, tyrosine, alanine, and proline were significantly lower than with milk. Ileal losses of leucine, valine, and isoleucine amounted to 12, 10, and 7 mg x kg(-1) x day(-1), respectively. Threonine ileal loss (9-12 mg x kg(-1) x day(-1)) was particularly high compared with the current amino acid requirement. CONCLUSIONS Amino acid losses at the human terminal ileum are substantial and depend on the type of dietary protein ingested. Although it remains unclear whether intact amino acids are absorbed in the colon, we suggest that ileal losses should be considered an important component of amino acid requirements.