-
1.
Theobromine does not affect postprandial lipid metabolism and duodenal gene expression, but has unfavorable effects on postprandial glucose and insulin responses in humans.
Smolders, L, Mensink, RP, Boekschoten, MV, de Ridder, RJJ, Plat, J
Clinical nutrition (Edinburgh, Scotland). 2018;(2):719-727
Abstract
BACKGROUND & AIMS Chocolate consumption is associated with a decreased risk for CVD. Theobromine, a compound in cocoa, may explain these effects as it favorably affected fasting serum lipids. However, long-term effects of theobromine on postprandial metabolism as well as underlying mechanisms have never been studied. The objective was to evaluate the effects of 4-week theobromine consumption (500 mg/day) on fasting and postprandial lipid, lipoprotein and glucose metabolism, and duodenal gene expression. METHODS In a randomized, double-blind crossover study, 44 healthy men and women, with low baseline HDL-C concentrations consumed 500 mg theobromine or placebo daily. After 4-weeks, fasting blood was sampled and subjects participated in a 4-h postprandial test. Blood was sampled frequently for analysis of lipid and glucose metabolism. In a subgroup of 10 men, 5 h after meal consumption duodenal biopsies were taken for microarray analysis. RESULTS 4-weeks theobromine consumption lowered fasting LDL-C (-0.21 mmol/L; P = 0.006), and apoB100 (-0.04 g/L; P = 0.022), tended to increase HDL-C (0.03 mmol/L; P = 0.088) and increased hsCRP (1.2 mg/L; P = 0.017) concentrations. Fasting apoA-I, TAG, FFA, glucose and insulin concentrations were unchanged. In the postprandial phase, theobromine consumption increased glucose (P = 0.026), insulin (P = 0.011) and FFA (P = 0.003) concentrations, while lipids and (apo)lipoproteins were unchanged. In duodenal biopsies, microarray analysis showed no consistent changes in expression of genes, pathways or gene sets related to lipid, cholesterol or glucose metabolism. CONCLUSIONS It is not likely that the potential beneficial effects of cocoa on CVD can be ascribed to theobromine. Although theobromine lowers serum LDL-C concentrations, it did not change fasting HDL-C, apoA-I, or postprandial lipid concentrations and duodenal gene expression, and unfavorably affected postprandial glucose and insulin responses. This trial was registered on clinicaltrials.gov under study number NCT02209025.
-
2.
Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) as a revisional surgery.
Wu, A, Tian, J, Cao, L, Gong, F, Wu, A, Dong, G
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2018;(11):1686-1690
Abstract
BACKGROUND Few studies of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) as the revision surgery for laparoscopic adjustable gastric banding (LAGB) have been published. OBJECTIVES To explore the efficacy and safety of SADI-S as the revision surgery for LAGB. SETTING The research was completed by the University Hospital. METHODS From November 2013 to November 2015, a total of 22 weight-regain patients who previously underwent LAGB received SADI-S as the revision surgery at the People's Liberation Army General Hospital. Preoperative clinical characteristics as well as the data at 1, 3, 6, 12, 18, and 24 months after operation were collected and analyzed. RESULTS The operation time of SADI-S was 105 ± 12.2 minutes, and intraoperative blood loss was 27.3 ± 5.8 mL. The percentage of excess weight loss was 20.55 ± 9.10%, 40.1 ± 6.02%, 63.52 ± 10.43%, 70.72 ± 8.54%, 78.34 ± 9.25%, and 81.57 ± 11.12% at 1, 3, 6, 12, 18 and 24 months after surgery, respectively. The 2-year complete remission rate of type 2 diabetes was 17 of 18, and the partial remission rate was 1 of 18 after operation. The glycated hemoglobin was 8.7% ± 1.1%, 7.7% ± .9%, 6.2% ± .6%, 5.7% ± .5%, 5.5% ± .6%, 6.0% ± .9%, and 5.7% ± .8% preoperatively and at 1, 3, 6, 12, 18, and 24 months after the operation, respectively. One case presented incisional hernia and was repaired. There was no conversion to laparotomy. Vitamins and trace elements were administrated long term to these patients after the operation, and no patients experienced vitamin or trace element deficiencies. CONCLUSION SADI-S is safe and effective as a revision surgery for patients who experienced weight regain after LAGB. However, multicenter randomized controlled studies with larger sample sizes are needed to explore the long-term efficacy and safety of SADI-S.
-
3.
Case report on pathogenetic link between gluten and IgA nephropathy.
Costa, S, Currò, G, Pellegrino, S, Lucanto, MC, Tuccari, G, Ieni, A, Visalli, G, Magazzù, G, Santoro, D
BMC gastroenterology. 2018;(1):64
Abstract
BACKGROUND A relationship between IgA nephropathy (IgAN) and celiac disease (CD) has been reported. We show the pathogenetic link for the first time. CASE PRESENTATION A 39-year-old man with cystic fibrosis (CF) and CF-related diabetes started to present gross hematuria, back pain and headache. At admission, laboratory analysis showed increase in serum creatinine of 1.5 mg/dl, together with hematuria and mild proteinuria (1 g/24 h). He underwent a renal biopsy to investigate the cause of hematuria and renal failure. Biopsy was consistent with IgAN. In view of patient reported dyspepsia, an upper gastrointestinal endoscopy with duodenal biopsies was undertaken and was normal. We looked for mucosal deposits of tTG-2 in the duodenum and the renal mesangium. tTG-2 deposits were found both in the duodenum and in renal biopsies, where they topographically replicated mesangial IgA deposits. After one year on a continued gluten containing diet, the patient developed a Marsh 2 type duodenal pathology. CONCLUSIONS Our findings suggest a connection between CD and IgAN in terms of an immune-mediated gluten-induced pathogenesis even in the absence of villous atrophy and serum celiac autoantibodies.
-
4.
Comparative efficacy and safety of the duodenal-jejunal bypass liner in obese patients with type 2 diabetes mellitus: A case control study.
Laubner, K, Riedel, N, Fink, K, Holl, RW, Welp, R, Kempe, HP, Lautenbach, A, Schlensak, M, Stengel, R, Eberl, T, et al
Diabetes, obesity & metabolism. 2018;(8):1868-1877
Abstract
AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device mimicking surgical duodenal-jejunal bypass, and is indicated for the treatment of obesity-associated type 2 diabetes mellitus. This analysis was conducted to evaluate the efficacy and safety of the DJBL in comparison to lifestyle changes and antidiabetic drugs. MATERIALS AND METHODS To determine the efficacy and long-term safety of the DJBL, data concerning 235 obese patients with type 2 diabetes mellitus from the German DJBL registry were analysed. For comparison with standard treatment, propensity-score-matching with patients from the German DPV registry, including the matching parameters sex, age, diabetes duration, baseline BMI and baseline HbA1c, was applied. The final matched cohort consisted of 111 patients in the DJBL group and 222 matched control DPV patients. RESULTS Mean treatment time with the DJBL was 47.5 ± 12.2 weeks, mean BMI reduction was 5.0 kg/m2 (P < .001) and mean HbA1c reduction was 1.3% (11.9 mmol/mol) (P < .001). Reduction of antidiabetic medications and improvements in other metabolic and cardiovascular risk parameters was observed. In comparison to the matched control group, mean reductions in HbA1c (-1.37% vs -0.51% [12.6 vs 3.2 mmol/mol]; P < .0001) and BMI (-3.02 kg/m2 vs -0.39 kg/m2 ; P < .0001) were significantly higher. Total cholesterol, LDL cholesterol and blood pressure were also significantly better. CONCLUSION This study provides the largest, so far, hypothesis-generating evidence for a putative positive risk/benefit ratio for treatment of obese patients with type 2 diabetes mellitus with the DJBL as an alternative treatment option for this patient population.
-
5.
Intraepithelial lymphocytes, scores, mimickers and challenges in diagnosing gluten-sensitive enteropathy (celiac disease).
Sergi, C, Shen, F, Bouma, G
World journal of gastroenterology. 2017;(4):573-589
Abstract
The upper digestive tract is routinely scoped for several causes of malabsorption, and the number of duodenal biopsy specimens has increased notably in the last 10 years. Gluten-sensitive enteropathy (GSE) is an autoimmune disease, which shows an increasing prevalence worldwide and requires a joint clinico-pathological approach. The classical histopathology of GSE with partial or total villous blunting is well recognized, but the classification of GSE is not straightforward. Moreover, several mimickers of GSE with intraepithelial lymphocytosis have been identified in the last 20 years, with drug interactions and medical comorbidities adding to the conundrum. In this review, we report on the normal duodenal mucosa, the clinical presentation and laboratory diagnosis of GSE, the duodenal intraepithelial lymphocytes and immunophenotype of GSE-associated lymphocytes, the GSE mimickers, the differences "across oceans" among guidelines in diagnosing GSE, and the use of a synoptic report for reporting duodenal biopsies in both children and adults in the 21st century.
-
6.
The Impact of Biliopancreatic Diversion with Duodenal Switch (BPD/DS) Over 9 Years.
Strain, GW, Torghabeh, MH, Gagner, M, Ebel, F, Dakin, GF, Abelson, JS, Connolly, D, Pomp, A
Obesity surgery. 2017;(3):787-794
Abstract
BACKGROUND There is limited information on the multiple long-term effects of the biliopancreatic diversion with duodenal switch (BPD/DS). METHODS Patients who consented to a BPD/DS from 1999 to 2010 were evaluated for weight change, complications, comorbidity resolution, body composition, quality of life, and depressive symptoms during visits at 1, 3,5, 7, and 9 years. Descriptive statistics, analysis of variance, and pair-wise comparisons were calculated for each of the five follow-up cohorts vs. the baseline cohort. RESULTS Between 1999 and 2010, 284 patients received a BPD/DS; 275 patients (69.8 % women) age 42.7 years, BMI 53.4 kg/m2 qualified for baseline analysis. Two hundred seventy-five patients were available in year 1; 275 patients in year 3; 273 patients in year 5; 259 patients in year 7; and 228 patients in year 9. Gender distribution was not different. BMI was 30.1 at 1 year and 32.0 at 9 years. Body fat was reduced to 26 % after 2 years. Complications requiring surgery were significant. Nutritional problems developed in 29.8 % of patients over the course of observation. The baseline Beck Depression Index (BDI) was 13.9 and 7.2 in year 1. Year 1 through 9 remained unchanged. There were significant positive changes in quality of life between baseline and year 1 for most domains. These positive changes were maintained for the follow-up cohorts. After surgery the resolution of comorbidities continued for the 9 years. CONCLUSIONS Weight loss during the first year was well maintained, resolving comorbidities and improving quality of life. Rates of surgical complications resemble other bariatric procedures. Long-term nutrient deficiencies are of concern.
-
7.
Hydrothermal Duodenal Mucosal Resurfacing: Role in the Treatment of Metabolic Disease.
Cherrington, AD, Rajagopalan, H, Maggs, D, Devière, J
Gastrointestinal endoscopy clinics of North America. 2017;(2):299-311
-
-
Free full text
-
Abstract
The duodenum has become recognized as a metabolic signaling center that is involved in regulating insulin action and, therefore, insulin resistance states such as type 2 diabetes. Bariatric surgery and other manipulations of the upper intestine, in particular the duodenum, have shown that limiting nutrient exposure or contact in this key region exerts powerful metabolic effects. Early human clinical trial data suggest that endoscopic hydrothermal duodenal mucosal resurfacing is well tolerated in human subjects and has an acceptable safety profile. This article describes the rationale for this endoscopic approach and its early human use, including safety, tolerability, and early efficacy.
-
8.
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
-
-
Free full text
-
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.
-
9.
A randomised controlled trial of a duodenal-jejunal bypass sleeve device (EndoBarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes mellitus.
Glaysher, MA, Mohanaruban, A, Prechtl, CG, Goldstone, AP, Miras, AD, Lord, J, Chhina, N, Falaschetti, E, Johnson, NA, Al-Najim, W, et al
BMJ open. 2017;(11):e018598
Abstract
INTRODUCTION The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum. The non-surgical and reversible nature of these devices represents an attractive therapeutic option for patients with obesity and T2DM by potentially improving glycaemic control and reducing their weight. METHODS AND ANALYSIS In this multicentre, randomised, controlled, non-blinded trial, male and female patients aged 18-65 years with a body mass index 30-50 kg/m2 and inadequately controlled T2DM on oral antihyperglycaemic medications (glycosylated haemoglobin (HbA1c) 58-97 mmol/mol) will be randomised in a 1:1 ratio to receive either the EndoBarrier device (n=80) for 12 months or conventional medical therapy, diet and exercise (n=80). The primary outcome measure will be a reduction in HbA1c by 20% at 12 months. Secondary outcome measures will include percentage weight loss, change in cardiovascular risk factors and medications, quality of life, cost, quality-adjusted life years accrued and adverse events. Three additional subgroups will investigate the mechanisms behind the effect of the EndoBarrier device, looking at changes in gut hormones, metabolites, bile acids, microbiome, food hedonics and preferences, taste, brain reward system responses to food, eating and addictive behaviours, body fat content, insulin sensitivity, and intestinal tissue gene expression. TRIAL REGISTRATION NUMBER ISRCTN30845205, ClinicalTrials.gov Identifier NCT02459561.
-
10.
No Difference Between Latiglutenase and Placebo in Reducing Villous Atrophy or Improving Symptoms in Patients With Symptomatic Celiac Disease.
Murray, JA, Kelly, CP, Green, PHR, Marcantonio, A, Wu, TT, Mäki, M, Adelman, DC, ,
Gastroenterology. 2017;(4):787-798.e2
Abstract
BACKGROUND & AIMS Gluten ingestion leads to symptoms and small intestinal mucosal injury in patients with celiac disease. The only option is the strict lifelong exclusion of dietary gluten, which is difficult to accomplish. Many patients following a gluten-free diet continue to have symptoms and have small intestinal mucosal injury. Nondietary therapies are needed. We performed a phase 2 study of the ability of latiglutenase, an orally administered mixture of 2 recombinant gluten-targeting proteases, to reduce mucosal morphometric measures in biopsy specimens from patients with celiac disease. METHODS We performed a double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of latiglutenase in 494 patients with celiac disease (with moderate or severe symptoms) in North America and Europe, from August 2013 until December 2014. Participants reported following a gluten-free diet for at least 1 year before the study began. Patients with documented moderate or severe symptoms and villous atrophy (villous height:crypt depth ratio of ≤2.0) were assigned randomly to groups given placebo or 100, 300, 450, 600, or 900 mg latiglutenase daily for 12 or 24 weeks. Subjects completed the Celiac Disease Symptom Diary each day for 28 days and underwent an upper gastrointestinal endoscopy with duodenal biopsy of the distal duodenum at baseline and at weeks 12 and 24. The primary end point was a change in the villous height:crypt depth ratio. Secondary end points included numbers of intraepithelial lymphocytes, serology test results (for levels of antibodies against tissue transglutaminase-2 and deamidated gliadin peptide), symptom frequencies, and safety. RESULTS In a modified intent-to-treat population, there were no differences between latiglutenase and placebo groups in change from baseline in villous height:crypt depth ratio, numbers of intraepithelial lymphocytes, or serologic markers of celiac disease. All groups had significant improvements in histologic and symptom scores. CONCLUSIONS In a phase 2 study of patients with symptomatic celiac disease and histologic evidence of significant duodenal mucosal injury, latiglutenase did not improve histologic and symptom scores when compared with placebo. There were no significant differences in change from baseline between groups. ClinicalTrials.gov no: NCT01917630.