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Blocking carbohydrate absorption and weight loss

Altern Ther Health Med. 2007 Jul-Aug;13(4):32-7.

Blocking carbohydrate absorption and weight loss: a clinical trial using a proprietary fractionated white bean extract.

Udani JSingh BB.

Source

University of California, Los Angeles School of Medicine, USA.

Abstract

BACKGROUND:

A proprietary fractionated white bean extract of Phaseolus vulgaris has been shown in vitro to inhibit the digestive enzyme alpha-amylase. This may prevent or delay the digestion of complex carbohydrates, potentially resulting in weight loss.

METHODS:

A 4-week randomized, double-blind, placebo-controlled study of 25 healthy subjects consuming 1000 mg of a proprietary fractioned white bean extract or an identical placebo twice a day before meals in conjunction with a multi-component weight-loss program, including diet, exercise, and behavioral intervention, was conducted.

RESULTS:

Both groups reduced their weight and waist size significantly from baseline. The active group lost 6.0 lbs (P=.0002) and 2.2 in (P=.0050), and the placebo group lost 4.7 lbs (P=.0016) and 2.1 in (P=.0001). The differences between groups were not significant (weight P=.4235, waist size P=.8654). Through subsequent exploratory analysis to investigate group findings further, subjects were stratified by total dietary carbohydrate intake. This probative analysis revealed that the tertile of subjects who had consumed the most carbohydrates demonstrated significant reductions in both weight (8.7 lbs vs 1.7 lbs, P=.0412) and waist size (3.3 in vs 1.3 in P=.0100) compared with placebo subjects in the same tertile of carbohydrate intake.

CONCLUSION:

Subjects who adhere to a program including dietary modification, exercise, and behavioral intervention can significantly reduce their weight and waist size in a short period of time. In an exploratory analysis of data, the tertile of subjects who ate the most carbohydrates experienced a significant reduction in both weight and waist size with the addition of the white bean extract compared to the placebo group of the same tertile of carbohydrate consumption. Longer studies with a larger pool of subjects are required to validate these findings.

  • I. First International Consensus Conference on the Mini-Bypass / One Anastomosis Bypass II. “Conference Program” and Invitation to Present and Participate / Confirmation III. Online Tickets/Registration ******************************************************************* I. First International Consensus Conference on the Mini-Bypass / One Anastomosis Bypass Now over 100 surgeons have expressed interest in participating in the First International Consensus Conference on the Mini-Bypass / One Anastomosis Bypass. The tentative plan will be to hold the meeting in Paris at Marriott Charles de Gaulle Thursday 18.10.2012 - Meeting room from 09:00- 18:00 Friday 19.10.2012 - Meeting room from 09:00-18:00 The Paris Charles de Gaulle Airport Marriott hotel is located 2 kilometers away from Paris France Charles de Gaulle International Airport The plan for the conference will be to have two days of presentations from you and other experts from around the world and following the structure ot the Sleeve Gastrectomy Consensus Conferences. We will perform a survey and voting of the presenters and participants and will plan to publish our findings. Later in this email (and Online) you will see the tentative schedule of presenters for the conference. Please review your planned presentation and confirm your interest to present or not ******************************************************************* II. Conference Program and Invitation to Present and Participate / Confirmation MGB/OAB Consensus Conference (Preliminary List) Presenter Name, Address, City/Town, State/Province,  ZIP/Postal Code,  Country,  Topic 1. Mario Neves, CUF Infante Santo Hospital,  Lisbon, Portugal,  What should be the best operation  Financial issues of Bariatric surgery, marioneves1@gmail.com 2. Ganesh Ramalingam,  Khoo teck puat hospital, Singapore,  Singapore  Asian experience  changing trends in type of bariatric surgery, rganesh16@hotmail.com 3. K S Kular, Kular College & Hospital,  Bija , Ludhiana, Punjab, India, Tips an tricks of MGB, drkskular@yahoo.com 4. Mario Musella,  Federico II University - Medical School, Naples      NA, Italy The increasing number of MGB Italian surgeons despite of this intervention is not officially recognized by the Italian Society for Bariatric Surgery (SICOB). New numbers and results. mario.musella@unina.it 5. Dr. Karl RHEINWALT, Dept. of Bariatric and Metabolic Surgery, Cologne, Nordrhine-Westfalia, Germany, The current and future role of MGB in the German Bariatric Set-up  or  Indications for MGB in a German Center of Obesity Surgery, karl-peter.rheinwalt@st-franziskus-koeln.de 6. Cesare Peraglie, CLOS, Celebration, Fl, USA, Technique, post-op care, complications or whatever is needed. DrP@clos.net 7. Craig Taylor,  Concord General Hospital,  Sydney, New South Wales, Australia, Sleeve Gastrectomy,  Gastric Banding, taylor_c@mac.com 8. Roberto Tacchino, Catholic University, Rome RM, Italy; Single incision MGB, roberto.tacchino@yahoo.it 9. Andrés Sánchez-Pernaute, Hospital Clínico San Carlos, Madrid, Madrid, Spain;  Single Anastomosis Duodeno Ileal bypass with Sleeve gastrectomy, which is basically the malabsorptive version of mini-bypass, asanchezp.hcsc@salud.madrid.org; pernaute@yahoo.com 10. Halit Eren Taskin, Istanbul University Cerrahpasa Medical School, Istanbul, Istanbul, Turkey; SILS bariatric surgery, Is SILS MGB possible what would be the advantage? taskinh@ccf.org 11. Michel Suter, Hôpital du Chablais, Aigle, Vaud, Switzerland; Risks associated with biliary reflux in the stomach and esophagus, michelsuter@netplus.ch 12. Dr. Raymond Arnoux, Clinique du Tondu, Bordeaux, 33000, France, RGBP vs MGBP in France: BAROS score At 3 years, in 1000 cases. raymond.arnoux@wanadoo;fr 13. Dr. Manuel Garcia-Caballero,  University Malaga, Malaga,  Spain; One Anastomosis Gastric Bypass for obesity and diabetes surgery, gcaballe@uma.es 14. Juan Carlos Del Castillo, Clinica Remedios,  Cali, Valle Del Cauca, Colombia;  Omega bypass in patients at High risk, lobesidad@gmail.com 15. Emilio Manno, Cardarelli Hospital, Naples, Italy, Obesity Surgery Decision making, emilio.manno@aocardarelli.it 16. Dr Ahsan Badar MS, FRCS, FICS, FMAS, Diploma in Laparoscopic Surgery (France), has Graduated and Post Graduated from Government Medical college, Nagpur, during 1982-86 and 1987-90 respectively, Nagpur, Maharashtra, India; My experience with Mini Gastric Bypass,  drabadar@gmail.com 17. Dr Arun Prasad, Apollo Hospital, New Delhi, Delhi, India;  My experience of MGB, surgerytimes@gmail.com 18. Maurizio Grillo, Naples Area, Italy Hospital & Health Care, Doctor at AORN Cardarelli Neaples, Medical doctor at Vannini Hospital Rome, Mini-gastric bypass, maurizio@dottorgrillo.com 19. Surendra Ugale, Kirloskar Hospital at Basheerbagh India;  MGB is great for Poor Responders after Sleeve Gastrectomy, surenugale@gmail.com 20. Michal Cierny, Breclav Hospital, Breclav,  South Moravia,  Czech Republic, MGB Czech experience - preliminary data from comparative study RYGB - MGB, michal@cierny.cz 21. Cacio Wietzycoski, Hospital Unimed Vale do Cai,  Montenegro RS, Brasil, Metabolic Surgery, Wietzycoski@hotmail.com 22. Wei-Jei Lee, Min-Sheng General Hospital, Taipei, Taiwan, Taiwan, Long-term result of MGB and RYGB: a comparison, wjlee_obessurg_tw@yahoo.com.tw 23. Weiner Rudolf, KH Sachsenhausen,  Frankfurt am main, Hessen, Germany,  Long-term results in Germany, rweiner@khs-ffm.de 24. M.Yasser Kayyal,  Tawam Hospital in affiliation with Johns Hopkins; Al Ain, Abu dhabi, UAE;  Indications for MGB, mkayal@tawamhospital.ae 25. Rui Ribeiro, Centro Hospitalar de Lisboa Central,  Lisboa, Estremadura,  Portugal;  Experience with MGBP - advantages and tips, ruijsribeiro@gmail.com 26. Mohamed Yasser Minofia University MD Ain Shams University, Cairo Egypt, Heliopolis, Egypt;  Efficiency of RYGPB, Myasser_201@hotmail.com 27. Monica Vera Z., Centro Medico Foianini, Santa Cruz, Bolivia, Complications of Bariatric Surgery, Cirugiadeobesidad-bolivia@hotmail.com 28. Maurizio De Luca Department of Surgery  Regional Hospital of Vicenza, Vicenza, Italia;  Complication and Long term results, maurizio@dottorgrillo.com 29. Randeep Wadhawan;  FORTIS Hospital, Vasant Kunj,New Delhi -110070, New Delhi- 110070, India;  Comparison of Laparoscopic Sleeve Gastrectomy and MGB - Diabetes resolution, randeepwadhawan@yahoo.com 30. Dr. Matthias Raggi,  Klinikum Stuttgart,  Stuttgart, B.-W. Germany;  Bile reflux in MGB, mail@dr-Raggi.de 31. Patrice H. Lointier Md Ph D, Clermont - Ferrand ,PUY De Dome, France;  An Overview Of Obesity-Related Surgery Claims In France, lointier.patrice@wanadoo.fr 32. Miguel Angel Carbajo, Centro De Excelencia De Cirugía De La Obesidad, Valladolid, Id, Spain;   10-Years Follow-Up Roux-En-Y Gastric Bypass (477 Cases) Vs. 10 Years Experience Over One Anastomosis Gastric Bypass (2020 Cases), doctorcarbajo@obesos.info 33. Prof. Jean-Marc Chevallier Hôpital Européen Georges Pompidou 20 rue Leblanc 75908 Paris Cedex 15, FRANCE Email jean-marc.chevallier@egp.aphp.fr:  The MGB in France 34. Jean Mouiel, M.D., Department of Surgery,. Hopital Saint-Roch, B.P. 319, F-06006 Nice C6dex, France; tel.: 93 133258, telex: 970082 France;  Obesity Surgery in France, PR.MOUIEL@wanadoo.fr 35. Abdouh E El Banna, University Professor of Surgery. The department of Surgery, Al-azhar University, Cairo,Egypt.;  How I Do It: Mini-Gastric Bypass; Starting an MGB Program, abduhelbanna@hotmail.com 36. Philip Jose Koleski Medical | Digestive Surgeon, Surgeon General Digestive Tract Surgery, General Surgery, Bradesco Saúde, SANTA CATARINA, Blumenau, Garcia Street Armando Odebrecht:  Expected Outcomes; MGB vs. Other Bariatric Procedures, felipe.koleski@hotmail.com 37. Dr. Jean Cady. Clinique Geoffroy Saint-Hilaire, 59 rue Geffroy Saint Hilaire 75005 PARIS;  MGB in France: Outcomes and Tips, jeancady@wanadoo.fr 38. Safwan A Taha; MD, FACS., Member:  SAGES, ASMBS, IFSO, EDS, EATS, ELSA., Professor of Surgery, Consultant Laparoscopic & Bariatric Surgeon. Medical Director \ Chief Surgeon, Director of the Laparoscopic & Obesity Surgery Center, Al-Noor Hospital, Airport Road, Abu Dhabi; UAE., Tel. +971 50 1453062 (Mobile), P.O.Box 48481, Abu Dhabi; UAE., Small Bowel Obstruction following the RNY/MGB, safwanat@yahoo.com 39. Mr Michael Van den Bossche MD, FRCS, FICS, Spire Southampton Hospital, Obesity Surgery, Gastrointestinal surgery, Weight loss surgery (Obesity), Consultant general surgeon, Princess Elisabeth Hospital, Guernsey, Fellow, Royal College of Surgeons   Experience MGB In United Kingdom, michaelvdb@cwgsy.net 40. Jacques Himpens, MD, The European School of Laparoscopic Surgery, Department of Gastrointestinal Surgery, Saint Pierre University Hospital, Brussels, Belgium.,  Reflux Prevention, Conversion of Mgb to Rny & Vice Versa, jacques_himpens@hotmail.com ******************************************************************* III. Online Tickets/Registration Mini Gastric Bypass - One Anastomosis Consensus Conference  Thursday, October 18, 2012 at 8:00 AM - Friday, October 19, 2012 at 12:00 PM (PDT) Roissy-en-France, France Thank you sincerely Dr Rutledge
  • Int J Obes (Lond). 2008 Feb;32(2):322-8. Epub 2007 Oct 2.Peanut digestion and energy balance.Traoret CJLokko PCruz ACOliveira CGCosta NMBressan JAlfenas RCMattes RD.SourceDepartment of Foods and Nutrition, Purdue University, West Lafayette, IN 47907-2059, USA.AbstractOBJECTIVE:To explore the effects of peanut consumption on fecal energy excretion with a balanced, non-vegetarian diet.DESIGN:Four arm parallel group design (that is, whole peanut (P), peanut butter (PB), peanut oil (PO) or peanut flour (PF) consumption) with one crossover (control and intervention).SUBJECTS:In total 63 healthy men and women from Ghana, Brazil and USA (N=15-16 per group) with an average body mass index of 21.8 kg m(-2).MEASUREMENTS:Percent fat of fecal wet weight daily energy excretion during the control and the treatment periods.RESULTS:Compared to control, the percentage of fat in the feces increased significantly for the P group (5.22+/-0.29%) relative to the other three groups ((PO=3.07+/-0.36%, PB=3.11+/-0.31% (P=0.001), and PF=3.75+/-0.40% (P=0.019)). The same findings held for kJ g(-1) of feces excreted. During the P supplementation period, the energy excretion was 21.4+/-1.0 kJ g(-1) versus 18.7+/-1.0 kJ g(-1) for PO (P=0.034), 18.8+/-0.7 kJ g(-1) for PB (P=0.042) and 18.5+/-0.8 kJ g(-1) for PF (P=0.028).CONCLUSION:Fecal fat and energy loss is greater with consumption of whole peanuts compared to peanut butter, oil or flour. This may contribute to the less than predicted change of body weight observed with peanut consumption. There were no cultural differences.  
  • Obesity and Bariatrics for the EndoscopistNew TechniquesBarham K. Abu Dayyeh; Christopher C. ThompsonAuthors and DisclosuresPosted: 11/21/2011; Ther Adv Gastroenterol. 2011;4(6):433-442. © 2011 Sage Publications, Inc.  Print This Email this    Abstract and IntroductionThe Role of Endoscopy in the Management of Post-RYGB Surgery ComplicationsThe Role of Endoscopy in the Primary Management of Obesity and Metabolic DiseaseConclusionReferencesAbstract and IntroductionAbstractObesity and its associated conditions, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions. Gastrointestinal weight loss surgery (GIWLS) shows the most promise in achieving significant and sustained weight loss and diabetes resolution. However, a large mismatch exists between the magnitude of the obesity epidemic and the number of surgical procedures performed to produce a significant shift in the distribution of obesity on a population level. This mismatch is fueled by high surgical costs, morbidity and mortality associated with surgical interventions, and the fact that the greatest public health burden of obesity comes from those around the center of the population body mass index distribution with mild to moderate obesity, rather than those at the distribution tail with severe obesity that GIWLS targets. New endoscopic methods, capitalizing on advances in our understanding of the physiological mechanisms by which GIWLS works, are developing to provide viable alternatives in the treatment of bariatric surgical complications, and for the primary treatment of obesity. These methods may have the added advantage of reduced invasiveness, reversibility, cost-effectiveness, and applicability to a larger segment of the population with moderate obesity.IntroductionObesity and its associated conditions, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions. According to the National Health and Nutrition Survey (NHANES), about one third of the adult US population has obesity, and the prevalence of metabolic syndrome and diabetes in this population is 39.2% and 14.2%, respectively [Flegal et al. 2010; Nguyen et al. 2008].Of the many therapeutic approaches for the treatment of obesity and its complications, gastrointestinal weight loss surgery (GIWLS) shows the most promise in achieving significant and sustained weight loss and diabetes resolution when compared with medications or dietary and behavioral modifications [Sjostrom et al. 2007]. Laparoscopic Roux-en-Y gastric bypass (RYGB), open RYGB, and adjustable gastric band comprise approximately 98% of all GIWLS, with vertical banded gastroplasty, duodenal switch, gastric sleeve and biliopancrea-tic diversion contributing the remaining 2%.RYGB is currently the GIWLS of choice according to a meta-analysis of 136 studies including 22,094 subjects. The average excess body weight loss with RYGB is 62% with 84% full diabetes resolution, 68% full hypertension resolution, 97% hyperlipidemia improvement, and 81% complete resolution of obstructive sleep apnea. The 30 days operative mortality rate of the RYGB is 0.5% [Buchwald et al. 2009, 2004; Tice etal. 2008].The proven efficacy of GIWLS coupled with an improved surgical safety profile afforded by the introduction of laparoscopic surgical techniques have led to a surge in the number of bariatric surgery procedures performed in the USA and worldwide, with an estimated 220,000 bariatric operations performed in the USA and Canada in 2008 [Buchwald and Oien, 2009; Kohn et al. 2009].Despite this increase, a large mismatch exists between the magnitude of the obesity epidemic and the number of GIWLS performed to produce a significant shift in the distribution of obesity on a population level. This mismatch is fueled by high surgical costs, morbidity and mortality associated with surgical interventions, and the fact that the greatest public health burden of obesity comes from those around the center of the population body mass index distribution, with mild to moderate obesity, rather than those at the high distribution tail with severe obesity that GIWLS targets. Thus, minimally invasive and effective interventions that replicate some of the anatomical manipulations of GIWLS endoscopically are greatly needed.Recently, our understanding of the mechanism by which RYGB surgery works has evolved from that of mechanical restriction and malab-sorption [Fisher and Schauer. 2002], to that of anatomical surgical manipulations resulting in physiological alterations in the gut neuroendo-crine signaling to the brain, pancreas, liver, adipose tissue, and muscles to regulate food intake through enhanced satiety, increased energy expenditure, and improved glucose homeostasis [Bueter et al. 2010; Stylopoulos et al. 2009; Vetter et al. 2009; Wang et al. 2008]. This coupled with rapidly evolving new endoscopic techniques and technologies have enabled endoscopy to not only assume a pivotal role in the effective management of post-RYGB complications, but also in the primary management of obesity.In this review, we will discuss the advances in endoscopic techniques and technologies that have enabled the modern endoscopist to manage effectively the majority of post-RYGB surgery complications. We will also discuss the evolution of endoscopically placed devices that have the potential to replicate the physiological effects of the RYGB surgery in an effective and minimally invasive manner to allow their application to a larger subset of the population with moderate obesity. The Role of Endoscopy in the Management of Post-RYGB Surgery ComplicationsRYGB surgery is associated with a number of early and late complications that are associated with increased morbidity and mortality, and can result in re-operation or revision surgery [Kellogg et al. 2009; Almahmeed et al. 2007]. Early complications with their associated incidence are as follow: nausea, vomiting, and dehydration 5%, anastomotic leaks 4%, thromboembolic events 3.5%, bowel obstruction 2%, gastrointestinal hemorrhage 2%, wound complications 2%, and death 0.5% [Kellogg et al. 2009; Almahmeedet al. 2007; Gonzalez et al. 2006; Podnos et al. 2003]. Late complications include: marginal ulcers 27–52%, weight regain 30%, anastomotic stenosis 4–27%, incisional hernia 8%, gastrogastric fistula 1–2%, and biliary and nutritional complications [Lee et al. 2009; Diniz Mde et al. 2008; Carrodeguas et al. 2005; Podnos et al. 2003].Marginal ulcers are the most frequently encountered post-RYGB complication that is usually diagnosed with an upper endoscopy. A thorough endoscopic examination for gastrogastric fistula and foreign material removal from the ulcer site by endoscopic scissors are important as this may aid in ulcer resolution [Frezza et al. 2007]. Further management of marginal ulcers consists of evaluating the pouch pH, testing and treating Helicobacter pylori,soluble proton-pump inhibitor therapy, liquid sucralfate, elimination of nonsteroidal anti-inflammatory drugs, smoking cessation, and optimizing diabetes control. Marginal ulcers that present with acute upper gastrointestinal bleeding are managed endoscopically with mechanical hemoclipping in a similar fashion to bleeding peptic ulcers [Guo et al. 2009], and those ulcers that re-bleed will often require surgical revisions.Anastomotic strictures can result from tension on the anastomotic site and ischemia, or secondary to nonabsorbable suture material at the gastroje-junostomy site. Two options for the management of anastomotic strictures exist, that is, balloon dilation with a through the scope method, or Savary-Gilliard bougies. Both techniques are very effective and safe, with most patients responding to dilation after an average of two sessions [Fernandez-Esparrach et al. 2008; Ukleja et al. 2008]. Strictures refractory to dilation can be managed with endoscopic covered stents, such as Polyflex or Alveous, to avoid the high complication rate associated with re-operation. Although the short-term success rates of these stents is high at about 84%, the incidence of complications such as stent migration is also high, and data about their long-term benefit and risk profile are lacking [Eubanks et al. 2008].Staple-line disruption and anastomotic leaks are devastating complications of RYGB surgery with high morbidity and mortality in the acute setting, and chronically may lead to fistula formations, such as gastrogastric fistulas that lead to weight regain. The incidence of staple-line disruption following RYGB surgery is highly dependent on the surgical technique utilized, with much higher rates reported when the pouch and bypassed stomach are stapled in continuity versus transected completely [Capella and Capella, 1996]. Although in continuity staple-line disruptions more commonly result in chronic gastrogastric fistula not leaks. Given the high morbidity and mortality associated with the operative management of staple-line complications, alternative endoscopic approaches have been explored. Covered stents are one method that has been developed as a means of primary endoscopic closure. In a meta-analysis of seven studies involving 77 subjects, in whom self-expanding stents were utilized for management of postbariatric surgery leaks, the pooled proportion of successful leak closure was 84.5%, with a successful stent removal after leak closure of 90%. Stent migration rate was 26%. Most migrations were minimal with no associated mortality reported [Puli et al. 2010]. Other means of primary closure have also been reported. Multiple case series demonstrated the feasibility of utilizing a variety of endoscopic techniques, such as fibrin glue, hemoclips, endoscopic suturing devices, sclerotherapy, Surgisis (an acellular matrix biomaterial derived from the porcine small intestine submucosa that stimulates proliferation of fibroblasts), and argon plasma coagulation for the repair of chronic fistula resulting from anastomotic leaks or in combination with covered self-expandable metallic stents for refractory fistulas cases [Fernandez-Esparrach et al. 2010; Toussaint et al. 2009; Papavramidis et al. 2008; Merrifield et al. 2006]. Although the above techniques appear feasible and promising, long-term data about their efficacy and durability are lacking.Much of the focus on endoscopic revision of the RYGB has been on the gastrojejunal stoma and gastric pouch, as dilation of the gastrojejunal stoma, and/or enlargement of the gastric pouch, are thought to be risk factors for suboptimal weight loss and weight regain after the procedure. Although, the mechanisms and postsurgical physiology remain unclear, this has led to the development of a variety of less invasive endoscopic techniques and devices aimed at the reduction of the gastrojejunal stoma diameter and gastric pouch size. These include sclerotherapy techniques [Loewen and Barba, 2008; Catalano et al. 2007; Spaulding et al. 2007], endoluminal suturing devices [Ryou et al. 2009; Herron et al. 2008; Tang et al. 2008; Thompson et al. 2006], and tissue plication platforms [Mikami et al. 2010].The Randomized Evaluation of Endoscopic Suturing Transorally for Anastomotic Outlet Reduction (RESTORe) trial; a multicenter, prospective, double-blinded, sham-controlled trial, tested the use of the EndoCinch device (Bard, Murray Hill, NJ, USA) for treatment of weight regain after RYGB secondary to dilated gastrojejunal stoma. The RESTORe trial evaluated the 6 months absolute percentage weight loss outcome and safety of gastrojejunal anastomosis reduction with the EndoCinch device. On per-protocol completers analysis, the absolute weight loss in the intervention group was 4.7 ± 5.7% (n = 43), compared with 1.9 ± 5.2% (n = 26) in the sham group (p = 0.041). Using a last observation carried forward intent-to-treat analysis, the mean 6-month weight loss was 4.2 ± 5.4% (n = 50) and 1.9 ± 5.2% (n = 27) (p = 0.066). Technical success of reducing the gastrojejunal anastomosis to less than 10 mm was achieved in 89% of subjects. The percentage of adverse events were similar in both groups [Thompsonet al. 2010].Finally, rapid weight loss post-RYGB increases the risk of biliary complication, such as choledocholithiasis through increased risk of stone formation resulting from the weight loss. The RYGB anatomy, however, poses a particular challenge for the endoscopist to gain retrograde access to the biliary tree through the biliopan-creatic limb utilizing endoscopic retrograde cholangiopancreatography (ERCP) to deal with these complications. Therefore, multiple endoscopic techniques and technologies have been developed to gain ERCP access. These can be divided into two categories: access through the RYGB anatomic route, or access through a gastrostomy or jejunostomy tract created in the gastric remnant or the small bowel.Techniques that gain access to the biliopancreatic limb through the RYGB anatomic route either utilize a forward viewing pediatric colonoscope, balloon-assisted enteroscopy, or rotational over-tube enteroscopy. A recent multicenter retrospective data collection from eight sites including 129 subjects, of which 64 had RYGB, reported an enteroscopy success rate of 88%, ERCP success rate of 79%, and successful native papilla cannulation in 46 out of 73 subjects. All techniques (i.e. single balloon, double balloon, and rotational overtube enteroscopy) achieved similar results [Shah et al. 2010].Gastrostomy or jejunostomy access to the bilio-pancreatic limb can be gained endoscopically with the aid of balloon-assisted enteroscopy to create a retrograde percutaneous endoscopic gastrostomy (PEG) in the gastric remnant. The PEG tract can be dilated after maturation to allow access for the duodenoscope [Baron et al. 2008; Martinez et al. 2006]. Alternatively, laparoscopy-assisted ERCP may be performed in the operating room to gain immediate gastrostomy or jejunostomy access that can accommodate a sterilized duodenoscope [Lopes and Wilcox, 2010]. The Role of Endoscopy in the Primary Management of Obesity and Metabolic DiseaseIn discussing endoscopic replication of RYGB anatomic manipulations, it is useful to divide the surgery into separate distinct components: (a) gastric volume restriction; (b) exclusion of the distal stomach from alimentary flow; (c) exclusion of the proximal intestine; (d) exposure of the jejunum to partially digested nutrients.Gastric InterventionsEndoscopically placed intragastric balloons (IGBs) for the treatment of obesity by reduction of gastric volume were first introduced to the US market in the mid 1880s with the Garren—Edwards gastric bubble (GEGB). The GEGB had multiple complications, mainly small bowel obstruction due to balloon deflation requiring endoscopic or surgical retrieval, and it failed to demonstrate efficacy in a prospective, double-blind, sham-operated, randomized trial of 59 obese patients with a 9-month follow-up period [Hogan et al.1989; Benjamin, 1988]. Subsequently, newer generation IGBs with better safety profiles were developed. The BioEnterics (Allergan, Irvine, CA, USA) intragastric balloon (BIB) was introduced in the early 1990s, and the Heliosphere (Heliscopie, Vienne, France) balloon (Heliosphere BAG) in 2004. The BIB is an elastic spherical balloon made from silicone and filled with about 500 ml of saline; whereas, the Heliosphere is a double-layered polymer balloon covered with silicone, and filled with about 650–750 ml of air. Newer IGBs with more sophisticated migration-hindering and deployment/retrieval mechanisms, which also allow for endoscopic balloon volume adjustments, are now available. Data from a recent meta-analysis of 15 articles showed a mean weight loss of about 14.7 kg (12.2% of initial weight, and 32.1% of excess weight) at balloon removal with the BIB. This balloon was well tolerated with early removal rate of 4.2%. The long-term follow up of 50 subjects who had the BIB balloon for an average of 7 months, showed that 16 out of the 50 maintained a weight loss of ≥ 10% after about 5 years of removal [Ercan et al. 2010]. Similar experience was reported with the Heliosphere balloon with no long-term efficacy data available [Imaz et al. 2008; Trande et al. 2008].Several endoscopic devices have been developed for the primary treatment of obesity by creating multiple tissue plications to reduce gastric volume. Fogel and colleagues first described the use of the EndoCinch device for the creation of an endoluminal vertical gastroplasty as a primary treatment of obesity in 64 subjects (Figure 1). This study was a single-center, uncontrolled study with a 1-year follow up. The procedure was performed in roughly 60min under general anesthesia. The percentage of excess weight lost (EWL) reported was 58.1 +/– 19.9% with a favorable safety profile [Fogel et al. 2008]. However, the durability of the tissue plications was not adequately assessed in this study, and randomized, sham-controlled trials are needed to validate these results. (Enlarge Image)Figure 1.Endoscopic vertical gastroplasty technique using the EndoCinch endoscopic suturing device: (a) the EndoCinch device; (b) endoscopic suturing pattern for the creation of a vertical gastroplasty by the EndoCinch device; (c) and (d) endoscopic views before and after the creation of the endoscopic vertical gastroplasty. (Reprinted with permission from Fogel et al. [2008].) A transoral endoscopically guided stapling system (TOGA system) (Satiety Inc., Palo Alto, CA, USA) has been used to create an endoluminal vertical gastroplasty in two separate, prospective, uncontrolled pilot human trials (Figure 2). The procedure takes about 131 min to perform under general anesthesia. The mean percentage EWL reported in these two trials was 24% and 46% at 6 months. An intact staple line at 6 months was documented by endoscopy in most subjects [Deviere et al. 2008; Moreno et al. 2008]. A multicenter, randomized, sham-controlled trial of this technique is currently underway. (Enlarge Image)Figure 2.Transoral endoscopically guided stapling system (TOGA) for the creation of an endoscopic vertical gastroplasty, (a) The TOGA sleeve stapler that is used to create a gastric sleeve with a luminal diameter of approximately 20 mm parallel to the lesser curvature of the stomach, and the TOGA restrictor used to staple gastric folds together and restrict the distal end of the sleeve to approximately 12 mm. (b) The TOGA sleeve stapler with the extendable wire fully deployed for optimal alignment of the stapler, and a diagram showing the TOGA restrictor in place. (c) Radiographic and endoscopic views of the vertical gastroplasty created by the TOGA system. (Reprinted with permission from Deviere et al. [2008].) A new transoral endoscopic restrictive system (TERIS) (BaroSense, Redwood, CA, USA) that endoscopically places a restrictive silicone device with a 10 mm orifice anchored by five silicone anchors through five transmural plications at the gastric side of the gastroesophageal junction to replicate the effects of a laparoscopic gastric band has been developed (Figure 3). De Jong and colleagues have recently reported their experience in 13 subjects followed for 3 months. The median procedure time was 142 min under general anesthesia. Serious complications were reported in three subjects (two pneumoperitoneum requiring percutaneous intervention, and one gastric perforation). The safety profile of the procedure improved after adjusting the stapling device and performing the procedure with carbon dioxide insufflation. The median reported EWL at 3 months was 28% [De Jong et al. 2010]. (Enlarge Image)Figure 3.TERIS showing an endoscopically placed restrictive silicone device with a 10 mm orifice anchored by five silicone anchors through five transmural plications at the gastric side of the gastroesophageal junction. (Reprinted with permission from De Jong et al. [2010].) TERIS, transoral endoscopic restrictive system. Small Bowel InterventionsEndoBarrier (GI Dynamics, Lexington, MA, USA), a new duodenal-jejunal bypass sleeve (DJBS) made from a endoscopically to the duodenal bulb, shows promise and efficacy in the management of obesity and associated diabetes (Figure 4). When deployed, the DJBS mimics the mechanical manipulation of RYGB surgery by creating a mechanical barrier that allows food to bypass the duodenum and proximal jejunum without mixing with bile and pancreatic enzymes until later in the gut, thus potentially manipulating the enteroinsular system. In rats with diet-induced diabetes, this device showed a 20% weight reduction compared with sham-operated rats with no malabsorption and substantial improvement in insulin resistance [Aguirre et al. 2008]. (Enlarge Image)Figure 4.A duodenal-jejunal bypass sleeve (EndoBarrier) made from a Teflon liner and delivered endoscopically to the duodenal bulb. (Reprinted with permission from Cote and Edmundowicz [2009].) Results from two recent multicenter, prospective, randomized, open-label, sham-controlled trials enrolling 21 DJBS subjects and 26 sham controls in one, and 30 DJBS subjects with 11 diet controls in the other were recently reported [Gersin et al. 2010; Schouten et al. 2010]. Percentage EWL at 12 weeks was 11.9% versus 2.0% in the sham controls in one, and 19% versus 6.9% in the diet controls in the other. Eight DJBS subjects required early termination in one trial and four in the other. Reasons for the early termination included device migration, obstruction, bleeding, epigastric pain, nausea, and vomiting. Average implantation time was 35min [range 12–102], and average explantation time was 17min [range 5–99]. No acute procedural complications were reported. Diabetic subjects had an impressive 3.4 point improvement in their HbA1c within the 12-week study period, compared with 0.7 point in the diet-controlled diabetic group [Schouten et al. 2010].Natural Orifice Transluminal Endoscopic SurgeryAlthough in its infancy, the field of endoscopic surgery shows promise in reproducing different components of bariatric surgical procedures endoscopically. Recently, a hybrid natural orifice transluminal endoscopic surgery (NOTES) transvaginal approach was used to create a sleeve gastrectomy in obese women in Brazil [Ramos et al.2008]. Furthermore, work to create a gastrojejunal anastomosis through a NOTES approach is underway.OthersOther endoscopically delivered devices, endoscopic techniques, and endoscopic suturing and endoplication platforms that can be utilized in the primary treatment of obesity are at different stages of development. ConclusionNew endoscopic methods are being developed to provide viable alternatives in the treatment of bariatric surgical complications. In addition, understanding the physiological effects of the different gastrointestinal mechanical manipulations produced by RYGB surgery may enable modern endoscopy to replicate different components of this surgery, with the potential added advantages of reduced invasiveness, reversibility, and cost effectiveness. Additionally, these features may allow endoscopic procedures to be applied to the larger segment of the population with moderate obesity. Although, it is unlikely for a single endoscopic approach to be as effective as traditional surgery for severe obesity, the application of a combination of such devices in tandem or in sequence, potentially with new selective drugs, will likely enable the treatment of a range of patients with varying severity of disease.
  • Bariatric Surgery and the Role of the Clinical Endocrinologist2011 UpdateJeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNUAuthors and DisclosuresPosted: 11/08/2011; Endocrine Practice. 2011;17(5):788-797. © 2011 American Association of Clinical Endocrinologists  Print This Email this    Abstract and IntroductionSetting the Stage: Seminal Events Since 2008Clinical Problems in Bariatric SurgeryCase Studies in Bariatric SurgerySynthesisReferencesAbstract and IntroductionAbstractObjective: To discuss the emerging roles of bariatric surgery and clinical endocrinology within the context of obesity and diabetes mellitus comprehensive care plans and cost-effective strategies.Methods: Relevant literature is reviewed and clinical cases are presented.Results: The global obesity epidemic poses many challenges to clinical endocrinologists and has fomented a coordinated effort among specialists to revolutionize management paradigms. Technologic innovation drives the need for accelerated learning and research efforts in bariatric surgery. The national shortage of physicians with expertise in nutritional medicine compounds the management problems for this expanding patient population. Certain issues merit continued attention and research, such as gastric banding for mild obesity, surgery for treatment of diabetes, sleeve gastrectomy, and nutritional and metabolic consequences.Conclusion: Clinical endocrinologists should have a central role in the perioperative decision-making for patients undergoing bariatric surgery.IntroductionThe global obesity epidemic has incited innovation and technology to advance at such a great pace that many subspecialties have had to reengineer and reprioritize their efforts in metabolic medicine. Perhaps the best example is that of bariatric surgery and the role of the clinical endocrinologist in perioperative care. In 2008, the American Association of Clinical Endocrinologists (AACE), The Obesity Society, and the American Society for Metabolic and Bariatric Surgery published evidence-based clinical practice guidelines (CPG) on the perioperative nutritional, metabolic, and nonsurgical support of patients undergoing bariatric surgery.[1] Within these CPG, also endorsed by the American Society of Parenteral and Enteral Nutrition, are 164 specific recommendations providing a comprehensive and collaborative effort to support clinical decision-making. Even though this resource was a welcomed addition to the armamentarium for bariatric surgery perioperative care, it also identified a potential weakness: that many patients undergoing bariatric surgery were not receiving expert medical nutrition care and that the number of available physicians with expertise in nutritional medicine was probably insufficient to care for the expected number of patients. Because clinical endocrinologists receive formal training in metabolic disorders and some training in clinical nutrition, AACE has incorporated plenary sessions, workshops, and "Meet The Experts" sessions on bariatric surgery since 2007 at their annual meetings. This article will review contemporary trends in bariatric surgery and then present 4 controversial aspects that have emerged since the 2008-published CPG. The discussions will focus on recent publications, most in the past 1 to 2 years, and have particular applicability to the role of the clinical endocrinologist in perioperative decision-making.  Setting the Stage: Seminal Events Since 2008Various white papers have been published since 2008 spanning the breadth of interest related to bariatric surgery (Table 1). Even though the utility of these authoritative documents has been called into question lately based on differences in methodology and final recommendations, they have succeeded in drawing attention to 3 important trends that will frame current controversies.First, the increased trend in obesity prevalence rates across ages, social classes, and cultures leads to greater cardiovascular disease (CVD), economic burden, and all-cause mortality.[15] Type 2 diabetes mellitus (T2DM) and obesity are inexorably intertwined. The T2DM prevalence is now 9.6% in the United States[16] and increases with higher body mass index (BMI) weight classes.[17] There is also an increased prevalence of obesity with T2DM—now 49.1% in the United States compared with 32.2% to 35.5% in patients without T2DM.[17,18] The natural extrapolation of this relationship is that interventions to prevent and treat the state of being overweight or obese can have salutary effects on the epidemiology of T2DM.Bariatric surgery appears to be safe and effective,[19] but may be prohibitively expensive for application to a clinical problem with this global magnitude.[20] However, strategies can be developed for the algorithmic implementation of bariatric surgery based on an improved understanding of the pathophysiology and the social environment, rather than on media-based claims and attitudes.[20] For instance, the impact of environment can be clarified by analyzing dietary patterns. Consuming a diet rich in fruits, vegetables, whole grains, and reduced-fat dairy products protects against the development of T2DM.[21] It has therefore been suggested that the medical community must develop an integrative delivery network or metabolic service line;[22] that is, to continue to pursue comprehensive preventive strategies to address the dysmetabolism epidemic across all risk strata while continuing to incorporate focused guidelines for the appropriate use of aggressive disease management paradigms, such as bariatric surgery.Second, the trend toward more rigorous governmental scrutiny of new antiobesity drugs, particularly with respect to CVD risks, has resulted in more limited therapeutic options for obese patients. The frustrations with intensive lifestyle intervention, coupled with the paucity of antiobesity drugs with proven long-term safety and effectiveness, has engendered an innovative, technology-driven setting (Table 2). Unfortunately, accelerating the pace of innovation, acceptance, and incorporation into white paper materials produces unexpected downstream clinical problems and ethical dilemmas.[13] This raises the question of where on the learning curve is the "sweet-spot" for widespread implementation? In other words, where do the concerns about inexperience (early on learning curve) intersect with best practice (late on the learning curve)? Furthermore, which patients are most appropriate candidates for these procedures and which procedures are most appropriate for your patient?Third, because there are an increasing number of patients undergoing bariatric surgery who have varying degrees of preoperative and postoperative nutritional and metabolic disorders,[1,32–36] there is a greater societal need for physicians specializing in nutritional medicine. The shortage in physician nutrition experts has been addressed and will require a concerted effort among stakeholders, including clinical endocrinologists, at educational and clinical practice levels.[37,38] Thus, clinical endocrinologists should become aware of the contemporary challenges in the surgical management of obesity, and to that end, 4 clinical problems will be presented.Clinical Problems in Bariatric SurgeryProblem 1: Should Patients With Only Mild Obesity be Referred for Laparoscopic Adjustable Gastric Banding? Is There a Role forPrevention of Severe Obesity?In the 2008 AACE/The Obesity Society/American Society for Metabolic and Bariatric Surgery CPG on bariatric surgery, recommendations R1 through R4 provide the criteria for patient eligibility.[1] This is summarized in recommendations R1 and R2 as patients with a BMI greater than 40 kg/m2 (or 35 kg/m2 with an obesity-related comorbidity) in whom surgery would not be associated with excessive risk.[1] In recommendation R3, it is stated that "insufficient data are available to recommend bariatric surgery for patients with a BMI < 35 kg/m2".[1] However, in subsequent years, sufficient data[39–44] were presented to the US Food and Drug Administration that led to the approval of more relaxed criteria (BMI of at least 30 kg/m2 with an obesity-related comorbidity; mild obesity) for laparoscopic adjustable gastric banding (LAGB). Varela and Frey[45] demonstrated comparable safety and effectiveness of LAGB between mildly obese and more severely obese patients. However, the question remains: even though patients are now eligible for LAGB at lower BMI levels, at what BMI would you actually recommend LAGB? The approach to this question is framed by considerations of the patient's behavior toward intensive lifestyle intervention and likelihood of progress; severity of the patient's metabolic profile; risk for obesity-related comorbidities, CVD, and mortality; and safety and effectiveness of the resources available for that patient. At this point, many physicians have bought-in to this concept of prevention of severe obesity based on certain weight gain, while others remain on the sideline awaiting further data, especially with long-term results.Problem 2: Is There a Role for Surgery to Specifically Treat T2DM?Over many years, both medical and surgical specialists have observed that clinical and biochemical markers of T2DM improve after bariatric surgery.[41,46–51] Moreover, bariatric surgery is cost-effective over a lifetime in reducing mortality and diabetes complications in obese patients.[47,52,53] Also, there are fascinating direct and indirect effects of surgical perturbations on the enteroinsular axis with important downstream effects on incretins, glycemic control, appetite, and other metabolic pathways.[54–56] Nevertheless, some obese patients who have had bariatric surgery do not show improvement in their T2DM or experience a recurrence of T2DM after a presumed remission. This has been attributed to inadequate weight loss (the most important mechanism), disordered eating with overconsumption of energy-dense foods, severe insulin resistance and/or β-cell defect, misdiagnosis of latent autoimmune diabetes in adults, and/or surgical factors.[57]This information has fomented a paradigm shift in bariatric surgery from interventions primarily directed to obesity, to the broader category of metabolic disorders, namely T2DM. The Diabetes Surgery Summit was held in Rome, Italy, in 2007 at which time preliminary data were presented and sentiments regarding diabetes surgery were polled and reported. In 2008, the first World Congress for Interventional Therapies for Diabetes was convened in New York where controversies were systematically explored and further research was advocated.[58] In 2011, the second World Congress for Interventional Therapies for Diabetes was held with an apparent consensus that, in fact, surgery may have a role in select patients with T2DM.[59] The International Diabetes Federation articulated the role of bariatric surgical procedures for the management of T2DM in a position statement.[2] In short, they stated that in response to a significant global problem, and based on the proven long-term safety and effectiveness of these procedures, bariatric surgery should be a treatment option for patients with T2DM and a BMI of 35 kg/m2 or greater without comorbidities, or a BMI of 30 kg/m2 or greater with comorbidities, in whom intensive lifestyle intervention and pharmacotherapy are unable to achieve treatment targets.[2] This position has also been expressed in the recently published 2011 AACE CPG for a diabetes comprehensive care plan. In this document, recommendation R11 states that for patients with T2DM, LAGB may be considered in those with a BMI greater than 30 kg/m2 and Roux-en-Y gastric bypass (RGB) may be considered in those with a BMI greater than 35 kg/m2 to achieve at least short-term weight loss.[60]There are 2 broad categories of surgical interventions for T2DM: those that are already approved for use for obesity (purely restrictive: LAGB and laparoscopic sleeve gastrectomy [LSG]; combined restrictive and malabsorptive: laparoscopic gastric banding (LGB) and biliopancreatic diversion with duodenal switch [BPD-DS]) and those that are investigational and designed specifically for the management of T2DM (eg, ileal transposition [61] and duodeno-jejunal bypass [55,62]). How do we frame the problem regarding diabetes surgery? First, the timing of surgery must be based on clinical trials with intent-to-treat analyses for diabetes endpoints, demonstration of long-term safety and effectiveness, and appropriate comparator groups. Should the procedure be recommended early in the course of T2DM when patients are at low risk and prevention of complications is desired? Should the procedure be recommended late in the course of T2DM when CVD complications may not be preventable, as suggested by the recent ACCORD (Action to Control Cardiovascular Risk in Diabetes)[63] and SCOUT (Sibutramine Cardiovascular Outcome Trial)[64] trials? Or, should an intermediate timing be considered? Second, the selection of the optimal surgical procedure must still be formalized. For instance, even though gastric banding procedures may be safer, the glycemic control benefits are primarily related to weight loss. More aggressive procedures that bypass the proximal and/or distal intestine may create a favorable incretin milieu for longer-term benefits. Investigational procedures can be technologically less invasive and have antidiabetic effects without bariatric effects. Unfortunately, very few prospective studies[41] have an intent-to-treat design for T2DM in which both control (nonsurgical therapy) and treatment (surgical therapy) patients are selected based on the presence of T2DM. Also, there are essentially no head-to-head studies comparing different bariatric surgery studies for the treatment of T2DM. Third, better follow-up strategies must be formulated with diabetes surgery. One of the major apprehensions for a broader indication for bariatric surgery is the appearance of nutritional and metabolic complications that overwhelm a medical system already suffering from a shortage of physician experts in nutritional medicine.Problem 3: The Sleeve GastrectomySleeve gastrectomy is the restrictive component of the BPD-DS. The greater curvature of the stomach is resected, creating a narrow tubular passageway that results in a gastric volume of approximately 100 cc. In recent years, the LSG has been performed as a single definitive bariatric surgical procedure, part of an intended hybridized (with LGB or vertical banded gastroplasty) or staged (very high initial BMI; followed by LGB or BPD-DS) procedure, or as a revisional option after a failed bariatric procedure (LAGB, vertical band gastroplasty, or previous LSG).[65,66] The LSG also has significant antidiabetic benefits[47] that are comparable to those of LGB.[67,68] Complications include stapler-line leakage, gastrointestinal reflux, intra-abdominal or intraluminal bleeding, trocar site hernia, pulmonary embolism, and strictures.[69,70] Although the procedure is safe and effective for weight loss, there can be weight regain after 5 years or insufficient weight loss due to neurohormonal factors or a physiologically dilated remnant stomach.[71] A second staged bariatric procedure to incorporate a malabsorptive component, or a Silastic ring to prevent lower gastric sleeve dilatation, may be considered to assist with weight loss.[72] The decision of whether to recommend LAGB, LGB, or LSG remains difficult without a clear evidence base to generically support one procedure over another. Ultimately, the choice is based in the context of specific metabolic goals, specific patient risk factors, and specific performance attributes of the surgeon and medical center. Shi et al[73] still view the LSG procedure as investigational because of insufficient demonstration of a long-term beneficial operational impact in the management of obesity.Problem 4: Nutritional and Metabolic Follow-up of the Patient Undergoing Bariatric SurgeryPerhaps the most relevant shortcoming for clinical endocrinologists in the care of patients undergoing bariatric surgery is the perioperative nutritional and metabolic management ( Table 3 ). Whether this has resulted from a critical shortage in physician nutrition experts and teachers and mentors in nutritional medicine, or from a culture where clinical endocrinologists are not routinely involved in the perioperative care of the bariatric surgery patient, more diligent monitoring of these nutritional and metabolic disorders in this patient population is desperately needed.Preoperatively, it is vital to recognize that obese patients are not only at risk for nutritional deficiencies, but actually manifest them biochemically and/or clinically (eg, iron deficiency in 44% of patients, thiamine deficiency in 29%, and vitamin D deficiency in 68% [74]), and these nutrients should be replenished. Postoperatively, the distribution and severity of specific nutrient deficiencies depend on the bariatric procedure performed and the functional gastrointestinal anatomy disrupted. For example, restrictive procedures (such as LAGB and LSG) that affect gastric anatomy will also potentially compromise intrinsic factor production and bioavailability of iron, thus affecting vitamin B12 and iron status, respectively.[75] Malabsorptive procedures that bypass portions of the proximal small intestine (such as RGB and BPD-DS) will affect absorption of water-soluble vitamins, such as folate, thiamine, and niacin.[75,76] More extensive bypass of the small intestine, as with distal RGB gastric bypass or BPD-DS, can result in clinically significant protein deficiency (7.7% to 11.9%, compared with less than 1% to 4.7% with gastric bypass) and fat malabsorption with the potential for deficiencies in essential fatty acids and the fat-soluble vitamins.[1,77]In addition to the relatively straightforward problems of single-nutrient deficiencies are the more complex nutrient-metabolism interactions that produce postoperative complications. For instance, the metabolic bone disease observed in patients who have undergone bariatric surgery may be related to more than just vitamin D deficiency or negative calcium balance. There are complex physiological mechanisms related to changes in body composition, intestinal health, and the leptin-hypothalamic-osteoblast-enterocyte-pancreatic β-cell network.[78] Moreover, patients who have undergone bariatric surgery and have dumping syndrome, nutritional anemia, neuropathy, or kidney stones may also find their way to an endocrinologist's office. SynthesisThe role of bariatric surgery is evolving and now takes the form ofmetabolic surgery, which targets specific elements: adiposity, T2DM, dyslipidemia, hypertension, and CVD. The role of the clinical endocrinologist is similarly evolving and must keep pace with technologic innovations and an expanding evidence base in obesity and T2DM management. The controversies discussed above emphasize the need for specialized care that can be provided by a clinical endocrinologist. What will the future hold?Undoubtedly, clinical endocrinologists will need to hone their skills for collaboration in the care of the patient who is overweight or obese and has T2DM. This includes familiarization with the standard, as well as investigational, bariatric surgical procedures, particularly with respect to their long-term safety, efficacy and effectiveness, and mechanisms of action. A concerted effort by endocrine fellowship programs to provide dedicated training in the broad area of nutritional medicine should be advocated. There will be a continued emergence of white papers that, hopefully, will represent a collaborative spirit among professional societies and demonstrate areas of agreement while transparently describing areas of contention. These documents will serve to guide clinical decision-making, but will not supplant humanism that incorporates subjective and idiosyncratic factors for individual patients. Ultimately, bariatric surgical procedures are expected to be used more widely, finding their niche in CPG and algorithms for obesity and T2DM.
  • Med Sci Sports Exerc. 2012 Mar 26. [Epub ahead of print]Development of a Neuromuscular Electrical Stimulation Protocol for Sprint Training.Russ DWClark BCKrause JHagerman FC.Source1Laboratory for Integrative Muscle Biology, Division of Physical Therapy, Ohio University, Athens, OH USA 2Ohio Musculoskeletal & Neurological Institute (OMNI), Ohio University, Athens, OH USA 3Department of Biomedical Sciences, Ohio University Heritage College of Osteopathic Medicine, Athens, OH USA † Professor Emeritus.AbstractPURPOSE:Sprint training is associated with several beneficial adaptations in skeletal muscle, including an enhancement of sarcoplasmic reticulum (SR) Ca release. Unfortunately, several patient populations (e.g., the elderly, those with cardiac dysfunction) that might derive great benefit from sprint exercise are unlikely to tolerate it. The purpose of this report is to describe the development of a tolerable neuromuscular electrical stimulation(NMES) protocol that induces skeletal muscle adaptations similar to those observed with sprint training.METHODS:Our NMES protocol was modeled after a published sprint exercise protocol and utilized a novel electrode configuration and stimulation sequence to provide adequate training stimulus while maintaining subject tolerance. Nine young, healthy subjects (4 men) began and completed the training protocol of the knee extensormuscles.RESULTS:All subjects completed the protocol, with ratings of discomfort far less than those reported in studies of traditional NMES. Training induced significant increases in SR Ca2+ release and citrate synthase activity (∼16 and 32%, respectively), but SR Ca2+ uptake did not change. The percentage of MHC IIx isoform was decreased significantly after training. At the whole muscle level, neither central activation nor maximum voluntary isometric contraction force were significantly altered, although isometric force did exhibit a trend toward an increase (∼3%, P = 0.055). Surprisingly, the NMES training produced a significant increase in muscle cross-sectional area (∼3%, P = 0.04).CONCLUSION:It appears that an appropriately-designed NMES protocol can mimic many of the benefits of sprint exercise training, with a low overall time commitment and training volume. These findings suggest that NMES has the potential to bring the benefits of sprint exercise to individuals who are unable to tolerate traditional sprint training.
  • Chest. 2012 Mar;141(3):716-25. Epub 2011 Nov 23.Functional and Muscular Effects of Neuromuscular Electrical Stimulation in Patients With Severe COPD: A Randomized Clinical Trial.Vivodtzev IDebigaré RGagnon PMainguy VSaey DDubé AParé MÈBélanger MMaltais F.SourceCentre de Recherche, Institut Universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC, G1V 4G5, Canada. Francois.Maltais@med.ulaval.ca.AbstractBACKGROUND:The mechanisms through which neuromuscular electrical stimulation (NMES) training may improve limb muscle function and exercise tolerance in COPD are poorly understood. We investigated the functional and muscular effects of NMES in advanced COPD.METHODS:Twenty of 22 patients with COPD were randomly assigned to NMES (n = 12) or sham (n = 8) training in a double-blind controlled study. NMES was performed on quadriceps and calf muscles, at home, 5 days per week for 6 weeks. Quadriceps and calf muscle cross-sectional area (CSA), quadriceps force and endurance, and the shuttle-walking distance with cardiorespiratory measurements were assessed before and after training. Quadriceps biopsy specimens were obtained to explore the insulin-like growth factor-1/AKT signaling pathway (70-kDa ribosomal S6 kinase [p70S6K] , atrogin-1).RESULTS:NMES training improved muscle CSA (P < .05), force, and endurance (P < .03) when compared with sham training. Phosphorylated p70S6K levels (anabolism) were increased after NMES as compared with sham (P = .03), whereas atrogin-1 levels (catabolism) were reduced (P = .01). Changes in quadriceps strength and ventilation during walking contributed independently to variations in walking distance after training (r = 0.77, P < .001). Gains in walking distance were related to the ability to tolerate increasing current intensities during training (r = 0.95, P < .001).CONCLUSIONS:In patients with severe COPD, NMES improved muscle CSA. This was associated with a more favorable muscle anabolic to catabolic balance. Improvement in walking distance after NMES training was associated with gains in muscle strength, reduced ventilation during walking, and the ability to tolerate higher stimulation intensity. Trial registry: ClinicalTrials.gov; No.: NCT00874965; URL: www.clinicaltrials.gov.  
  • Wien Klin Wochenschr. 2003 Oct 31;115(19-20):710-4.Safety of a combined strength and endurance training using neuromuscular electrical stimulation of thigh muscles in patients with heart failure and bipolar sensing cardiac pacemakers.Crevenna RMayr WKeilani MPleiner JNuhr MQuittan MPacher RFialka-Moser VWolzt M.SourceUniversitätsklinik für Physikalische Medizin und Rehabilitation, Universität Wien, Vienna, Austria. richard.crevenna@univie.ac.atAbstractNeuromuscular electrical stimulation (NMES) is an effective and non-strenuous therapy to enhance the strength and endurance capacity of the skeletal muscles in patients with severe chronic heart failure. NMES in patients with pacemakers is controversial because potential electromagnetic interference may result in pacemaker malfunction. Therefore, such patients are in general excluded from NMES. The aim of this pilot study was to evaluate the safety of a combined NMES protocol to increase strength and endurance capacity of the skeletal muscles in patients with heart failure and implanted pacemakers. Seven patients with chronic heart failure and implanted cardiac pacemakers with bipolar sensing leads received NMES treatment of thigh muscles, using a combined protocol comprising biphasic, symmetric, rectangular constant current impulses at different frequencies (8-50 Hz), pulse width up to 60 s (8 Hz), 4 s (15 Hz), 4 s (30 Hz), and 6 s (50 Hz), and amplitudes up to +/- 100 mA (all frequencies) applied to both knee extensor and flexor muscles via surface electrodes (8 x 13 cm each). Acute electromagnetic interference during a safety procedure (telemetric monitoring) before therapeutic NMES application was not observed in any of the patients. The 7 patients received during 20 therapeutic NMES sessions a total of 23,380 on-phases, comprising 2194.08 x 10(3) biphasic electrical pulses, without adverse events. Heart rate monitoring during stimulation and pacemaker interrogation revealed no abnormalities. NMES treatment of thigh muscles using a combined NMES protocol to enhance strength and endurance capacity appears to be safe in patients with heart failure and implanted pacemakers with bipolar sensing, as far as the described electrode configuration and parameter range is applied.  
  • Am J Phys Med Rehabil. 2002 Jun;81(6):446-51.MRI quantification of muscle activity after volitional exercise and neuromuscular electrical stimulation.Ogino MShiba NMaeda TIwasa KTagawa YMatsuo SNishimura HYamamoto TNagata KBasford JR.SourceRehabilitation Center, Kurume University, Kurume City, Japan.AbstractOBJECTIVE:The efficacy, and even the depth, of muscle stimulation during surface electrode neuromuscular electrical stimulation (NMES) is a matter of debate. This study addresses these issues by assessing the utility of a magnetic resonance imaging (MRI) technique in localizing and quantitating changes in the nature of MRI signals in the quadriceps muscle after volitional exercise and NMES.DESIGN:Volitional isometric and NMES-evoked quadriceps muscle activity was evaluated in two controlled trials. In the first, isometric quadriceps strength was determined during NMES and maximal volitional isometric exercise in six healthy men. In the second, changes in the ratio of MRI T2 signal intensities before and after volitional isometric exercise and NMES were used to quantitate MRI signal changes associated with muscle activation in 12 additional healthy men.RESULTS:MRI clearly detected quadriceps muscle tissue activation after both volitional and stimulated contractions, even though the NMES knee extension torque was only 23.5% that of maximal volitional isometric exercise. In particular, the T2 intensity ratios increased 26.5% +/- 17.3% (mean +/- standard deviation) after volitional exercise and 12.9% +/- 12.8% after NMES. This pattern of volitional isometric exercise, producing larger T2 intensity ratio values than NMES, was present in both deep and superficial layers and throughout the quadriceps muscle.CONCLUSIONS:Although volitional muscle contractions were several times stronger than those induced by NMES in this study, our findings support the idea that MRI can provide a noninvasive way to quantitate and localize volitional and electrically stimulated muscle activation.  
  • J Rheumatol. 2003 Jul;30(7):1571-8.A home-based protocol of electrical muscle stimulation for quadriceps muscle strength in older adults with osteoarthritis of the knee.Talbot LAGaines JMLing SMMetter EJ.SourceThe Johns Hopkins University, School of Nursing, Baltimore, Maryland 21205-2110, USA. ltalbot@son.jhmi.eduAbstractOBJECTIVE:To determine whether home-based neuromuscular electrical stimulation (NMES) applied to the quadriceps femoris (QF) muscle increases strength, physical activity, and physical performance in older adults with knee osteoarthritis (OA).METHODS:Thirty-four adults (> 60 yrs) with radiographically confirmed symptomatic knee OA were randomized to NMES plus education or education only (EDU). The primary outcome was isometric QF peak torque (PTIso), with secondary outcomes of daily step counts, total activity vector magnitude, 100-foot walk-turn-walk, timed stair climb, chair rise, and pain. The NMES group used a portable electrical muscle stimulator 3 days a week for unilateral QF training with incremental increases in the intensity of isometric contraction to 30-40% of maximum over 12 weeks. Both groups received the 12-week Arthritis Self-Management course and were followed an additional 12 weeks.RESULTS:The stimulated knee-extensor showed a 9.1% increase in 120 degrees PTIso compared to a 7% loss in the EDU group (time x group interaction for 120 degrees PTIso; p = 0.04). The chair rise time decreased by 11% in the NMES group, whereas the EDU group saw a 7% reduction (p = 0.01, time; p = 0.9, group). Similarly, both groups improved their walk time by approximately 7% (p = 0.02, time; p = 0.61 group). Severity of pain reported following intervention did not differ between groups.CONCLUSION:In older adults with knee OA, a home-based NMES protocol appears to be a promising therapy for increasing QF strength in adults with knee OA without exacerbating painful symptoms.  
  • J Strength Cond Res. 2011 Feb;25(2):520-6.Effects of combined electromyostimulation and gymnastics training in prepubertal girls.Deley GCometti CFatnassi APaizis CBabault N.SourcePerformance Expertise Center Gilles Cometti, Faculty of Sports Sciences, University of Burgundy, Dijon, France. gaelle.deley@u-bourgogne.frAbstractThis study investigated the effects of a 6-week combined electromyostimulation (EMS) and gymnastic training program on muscle strength and vertical jump performance of prepubertal gymnasts. Sixteen young women gymnasts (age 12.4 ± 1.2 yrs) participated in this study, with 8 in the EMS group and the remaining 8 as controls. EMS was conducted on knee extensor muscles for 20 minutes 3 times a week during the first 3 weeks and once a week during the last 3 weeks. Gymnasts from both groups underwent similar gymnastics training 5-6 times a week. Isokinetic torque of the knee extensors was determined at different eccentric and concentric angular velocities ranging from -60 to +240° per second. Jumping ability was evaluated using squat jump (SJ), counter movement jump (CMJ), reactivity test, and 3 gymnastic-specific jumps. After the first 3 weeks of EMS, maximal voluntary torque was increased (+40.0 ± 10.0%, +35.3 ± 11.8%, and +50.6 ± 7.7% for -60, +60, and +240°s⁻¹, respectively; p < 0.05), as well as SJ, reactivity test and specific jump performances (+20.9 ± 8.3%, +20.4 ± 26.2% and +14.9 ± 17.2% respectively; p < 0.05). Six weeks of EMS were necessary to improve the CMJ (+10.1 ± 10.0%, p < 0.05). Improvements in jump ability were still maintained 1 month after the end of the EMS training program. To conclude, these results first demonstrate that in prepubertal gymnasts, a 6-week EMS program, combined with the daily gymnastic training, induced significant increases both in knee extensor muscle strength and nonspecific and some specific jump performances.
  • J Strength Cond Res. 2011 Nov 5. [Epub ahead of print]Electromyostimulation - A Systematic Review of the Effects of Different EMS Methods on Selected Strength Parameters in Trained and Elite Athletes.Filipovic AKleinöder HDörmann UMester J.SourceMuscle Function Laboratory, Institute of Sport Science and Sport Informatics, German Sport University, Cologne, Germany.AbstractThis is the first part of two studies that systematically review the current state of research and structure the results of selected Electromyostimulation (EMS) studies in a way that makes accurate comparisons possible.This part will focus on the effects of EMS on strength enhancement. On the basis of these results part two will deal with the influence of the training regimen and stimulation parameters on EMS training effectiveness in order to make recommendations for training control.Out of about 200 studies, 89 trials were selected according to pre-defined criteria: subject age (<35), subject health (unimpaired), EMS type (percutaneus stimulation), and study duration (>7days). To evaluate these trials, we first defined appropriate categories according to the type of EMS (local or whole-body) and type of muscle contraction (isometric, dynamic, isokinetic). Then we established the most relevant strength parameters for high-performance sports: maximal strength, speed strength, power, jumping and sprinting ability. Unlike former reviews, this study differentiates between three categories of subjects based on their level of fitness (untrained subjects, trained subjects and elite athletes) and on the types of EMS methods used (local, whole-body, combination). Special focus was on trained and elite athletes. Untrained athletes were investigated for comparison purposes.This scientific analysis revealed that EMS is effective for developing physical performance. After a stimulation period of 3-6 weeks, significant gains (p<0.05) were shown in maximal strength (isometric Fmax +58.8%; dynamic Fmax +79.5%), speed strength (eccentric isokinetic Mmax +37.1%; concentric isokinetic Mmax +41.3%; Rate of Force Development (RFD) +74%; force impulse +29%; vmax +19%), and power (+67%). Developing these parameters increases vertical jump height by up to +25% (Squat Jump (SJ) +21.4%, Counter Movement Jump (CMJ) +19.2%, Drop Jump (DJ) +12%) and improves sprint times by as much as -4.8% in trained and elite athletes. With regard to the level of fitness, the analysis shows that trained and elite athletes, despite their already high level of fitness, are able to significantly enhance their level of strength to same extent as is possible with untrained subjects.EMS offers a promising alternative to traditional strength training for enhancing the strength parameters and motor abilities described above. Because of the clear-cut advantages in time management, especially when whole-body EMS is used, we can expect this method to see increasing use in high-performance sports.  
  • J Strength Cond Res. 2011 Nov;25(11):3218-38.Electromyostimulation--a systematic review of the influence of training regimens and stimulation parameters on effectiveness in electromyostimulation training of selected strength parameters.Filipovic AKleinöder HDörmann UMester J.SourceMuscle Function Laboratory, Institute of Sport Science and Sport Informatics, German Sport University, Cologne, Germany. andre.filipovic@gmx.netAbstractOur first review from our 2-part series investigated the effects of percutaneous electromyostimulation (EMS) on maximal strength, speed strength, jumping and sprinting ability, and power, revealing the effectiveness of different EMS methods for the enhancement of strength parameters. On the basis of these results, this second study systematically reviews training regimens and stimulation parameters to determine their influence on the effectiveness of strength training with EMS. Out of about 200 studies, 89 trials were selected according to predefined criteria: subject age (<35 years), subject health (unimpaired), EMS type (percutaneus stimulation), and study duration (>7 days). To evaluate these trials, we first defined appropriate categories according to the type of EMS (local or whole-body) and type of muscle contraction (isometric, dynamic, isokinetic). Unlike former reviews, this study differentiates between 3 categories of subjects based on their level of fitness (untrained subjects, trained subjects, and elite athletes) and on the types of EMS methods used (local, whole-body, combination). Special focus was on trained and elite athletes. Untrained subjects were investigated for comparison purposes. The primary purpose of this study was to point out the preconditions for producing a stimulus above the training threshold with EMS that activates strength adaptations to give guidelines for implementing EMS effectively in strength training especially in high-performance sports. As a result, the analysis reveals a significant relationship (p < 0.05) between a stimulation intensity of ≥50% maximum voluntary contraction (MVC; 63.2 ± 19.8%) and significant strength gains. To generate this level of MVC, it was possible to identify guidelines for effectively combining training regimens (4.4 ± 1.5 weeks, 3.2 ± 0.9 sessions per week, 17.7 ± 10.9 minutes per session, 6.0 ± 2.4 seconds per contraction with 20.3 ± 9.0% duty cycle) with relevant stimulation parameters (impulse width 306.9 ± 105.1 microseconds, impulse frequency 76.4 ± 20.9 Hz, impulse intensity 63.7 ± 15.9 mA) to optimize training for systematically developing strength abilities (maximal strength, speed strength, jumping and sprinting ability, power).  
  • Sports Med. 2008;38(2):161-77.Combined application of neuromuscular electrical stimulation and voluntary muscular contractions.Paillard T.SourceLaboratoire d'Analyse de la Performance Sportive, Département STAPS, Université de Pau et des Pays de l'Adour, Tarbes, France. thierry.paillard@univ-pau.frAbstractElectromyostimulation (EMS) and voluntary muscle contraction (VC) constitute different modes of muscle activation and induce different acute physiological effects on the neuromuscular system. Long-term application of each mode of muscle activation can produce different muscle adaptations. It seems theoretically possible to completely or partially cumulate the muscle adaptations induced by each mode of muscle activation applied separately. This work consisted of examining the literature concerning the muscle adaptations induced by long-term application of the combined technique (CT) [i.e. EMS is combined with VC - non-simultaneously] compared with VC and/or EMS alone in healthy subjects and/or athletes and in post-operative knee-injured subjects. In general, CT induced greater muscular adaptations than VC whether in sports training or rehabilitation. This efficiency would be due to the fact that CT can facilitate cumulative effects of training completely or partially induced by VC and EMS practiced alone. CT also provides a greater improvement of the performance of complex dynamic movements than VC. However, EMS cannot improve coordination between different agonistic and antagonistic muscles and thus does not facilitate learning the specific coordination of complex movements. Hence, EMS should be combined with specific sport training to generate neuromuscular adaptations, but also allow the adjustment of motor control during a voluntary movement. Likewise, in a therapeutic context, CT was particularly efficient to accelerate recovery of muscle contractility during a rehabilitation programme. Strength loss and atrophy inherent in a traumatism and/or a surgical operation would be more efficiently compensated with CT than with VC. Furthermore, CT also restored more functional abilities than VC. Finally, in a rehabilitation context, EMS is complementary to voluntary exercise because in the early phase of rehabilitation it elicits a strength increase, which is necessary to perform voluntary training during the later rehabilitation sessions.
  • Sports Med. 1992 Aug;14(2):100-13.Neuromuscular electrical stimulation and voluntary exercise.Hainaut KDuchateau J.SourceLaboratory of Biology, Université Libre de Bruxelles, Belgium.AbstractNeuromuscular electrical stimulation (NMES) has been in practice since the eighteenth century for the treatment of paralysed patients and the prevention and/or restoration of muscle function after injuries, before patients are capable of voluntary exercise training. More recently NMES has been used as a modality of strengthening in healthy subjects and highly trained athletes, but it is not clear whether NMES is a substitute for, or a complement to, voluntary exercise training. Moreover the discussion of the mechanisms which underly the specific effects of NMES appears rather complex at least in part because of the disparity in training protocols, electrical stimulation regimens and testing procedures that are used in the various studies. It appears from this review of the literature that in physical therapy, NMES effectively retards muscle wasting during denervation or immobilisation and optimises recovery of muscle strength during rehabilitation. It is also effective in athletes with injured, painful limbs, since NMES contributes to a shortened rehabilitation time and aids a safe return to competition. In healthy muscles, NMES appears to be a complement to voluntary training because it specifically induces the activity of large motor units which are more difficult to activate during voluntary contraction. However, there is a consensus that the force increases induced by NMES are similar to, but not greater than, those induced by voluntary training. The rationale for the complementarity between NMES and voluntary exercise is that in voluntary contractions motor units are recruited in order, from smaller fatigue resistant (type I) units to larger quickly fatiguable (type II) units, whereas in NMES the sequence appears to be reversed. As a training modality NMES is, in nonextreme situations such as muscle denervation, not a substitute for, but a complement of, voluntary exercise of disused and healthy muscles.
  • Sports Med. 1992 May;13(5):320-36.Neuromuscular electrical stimulation. An overview and its application in the treatment of sports injuries.Lake DA.SourceDepartment of Physical Therapy, Northeastern University, Boston, Massachusetts.AbstractIn sports medicine, neuromuscular electrical stimulation (NMES) has been used for muscle strengthening, maintenance of muscle mass and strength during prolonged periods of immobilisation, selective muscle retraining, and the control of oedema. A wide variety of stimulators, including the burst-modulated alternating current ('Russian stimulator'), twin-spiked monophasic pulsed current and biphasic pulsed current stimulators, have been used to produce these effects. Several investigators have reported increased isometric muscle strength in both NMES-stimulated and exercise-trained healthy, young adults when compared to unexercised controls, and also no significant differences between the NMES and voluntary exercise groups. It appears that when NMES and voluntary exercise are combined there is no significant difference in muscle strength after training when compared to either NMES or voluntary exercise alone. There is also evidence that NMES can improve functional performance in a variety of strength tasks. Two mechanisms have been suggested to explain the training effects seen with NMES. The first mechanism proposes that augmentation of muscle strength with NMES occurs in a similar manner to augmentation of muscle strength with voluntary exercise. This mechanism would require NMES strengthening protocols to follow standard strengthening protocols which call for a low number of repetitions with high external loads and a high intensity of muscle contraction. The second mechanism proposes that the muscle strengthening seen following NMES training results from a reversal of voluntary recruitment order with a selective augmentation of type II muscle fibres. Because type II fibres have a higher specific force than type I fibres, selective augmentation of type II muscle fibres will increase the overall strength of the muscle. The use of neuromuscular electrical stimulation to prevent muscle atrophy associated with prolonged knee immobilisation following ligament reconstruction surgery or injury has been extensively studied. NMES has been shown to be effective in preventing the decreases in muscle strength, muscle mass and the oxidative capacity of thigh muscles following knee immobilisation. In all but one of the studies, NMES was shown to be superior in preventing the atrophic changes of knee immobilisation when compared to no exercise, isometric exercise of the quadriceps femoris muscle group, isometric co-contraction of both the hamstrings and quadriceps femoris muscle groups, and combined NMES-isometric exercise. It has also been reported that NMES applied to the thigh musculature during knee immobilisation improves the performance on functional tasks.(ABSTRACT TRUNCATED AT 400 WORDS)
  • American Journal of Clinical Nutrition, Vol 55, 552S-555S, Copyright © 1992 by The American Society for Clinical Nutrition, Inc REVIEW ARTICLES Overview of surgical techniques for treating obesityJG Kral State University of New York Health Science Center, Brooklyn 11203.Nonsurgical methods fail to maintain clinically significant weight loss greater than or equal to 5 y in severely obese patients. Vertical banded gastroplasty and Roux-Y gastric bypass are the main operations for obesity. Modifications of intestinal bypass reserved for special cases require particular expertise in long-term management. Operations function by inducing satiety, nimiety, or aversion. Optimal weight loss or goal weights have not been defined and outcome predictors are inadequate. Results depend more on motivation and behavior than on metabolic, gastrointestinal, or technical factors. New approaches such as adding vagotomy or using inflatable cuffs to adjust outlet size in gastroplasty or modifying outlets or segment lengths in gastric bypass might improve long-term results. A staged approach to surgical treatment of obesity is proposed. Surgery will persist as a viable treatment alternative for severe obesity until effective preventive measures are taken to reduce the prevalence of this serious disease.
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