The success ofsleeve gastrectomy in the managementofmetabolic syndrome and obesity

Asim Shabbir,Dallan Dargan

Department of Surgery,National University Hospital,NUHS Tower Block,Level 8,Singapore 119228.

The success ofsleeve gastrectomy in the managementofmetabolic syndrome and obesity

Asim Shabbir✉,Dallan Dargan

Department of Surgery,National University Hospital,NUHS Tower Block,Level 8,Singapore 119228.

The rapid reversalof diabetes,hypertension,hyperlipidaemia and obesity by surgical means has challenged accepted doctrines regarding the managementofmetabolic syndrome.Sleeve gastrectomy,which developed initially as a preparatory procedure for biliopancreatic diversion with duodenal switch,has seen an exponential rise in popularity as an effective lone laparoscopic bariatric procedure.Superior excess weightloss,a low complication rate, and excellentfood tolerance,combined with a shorthospitalstay,have made this the procedure of choice for patients and surgeons across the globe.High volume centres nurture the ongoing developmentof experienced and specialized teams,pathways and regimens.Optimum surgical outcomes allow minimization of metabolic syndrome,reducing cardiovascular and cerebrovascular risk.

metabolic surgery,sleeve gastrectomy,diabetes mellitus,obesity

Introduction

The most widely used definition of metabolic syndrome is thatof the Third Report of the American National Cholesterol Education Program[1].Three or more of the following risk factors,which are easily mesured,must be present for diagnosis:abdominal obesity(＞102 cm/40 in men,＞88 cm/35 in women), triglycerides≥150 mg/dL,low high density lipoprotein (HDL)cholesterol(＜40 mg/d L men,＜50 mg/dL women),high blood pressure≥130/≥85 mmHg and raised fasting glucose≥110 mg/dL.Risk ofmyocardial infarction is increased considerably by this cluster of variables.

Obesity alone may resultin sleep apnoea,congestive cardiac failure,spine and joint degenerative conditions, and depression.In South East Asia,obesity rates are among the lowest in the world,but are increasing quickly along with unprecedented economic growth. The Asian Consensus Meeting on Metabolic Surgery has outlined guidance formetabolic surgery in individuals of Asian ethnicity.Indications include obesity with a body mass index(BMI)of≥35 kg/m2,or≥32 kg/ m2with co-morbidities,or≥30 kg/m2with 2 ormore of:raised triglycerides,abdominal obesity(waist＞80 cm in females and＞90 cm in males),reduced HDL cholesterol,hypertension,and raised fasting plasma glucose levels[2].Between 2004 and 2009,a 449%increase in bariatric surgical procedures was noted among 11 Asian countries[3].

Weightcontrolvia dietary modificationsand increased physical activity remain the primary and mostcosteffective initialinterventions forobesity.Lipid lowering drugs have a central role in prevention of atherogenesis, coronary artery disease and cerebrovascular disease. However,for the majority of patients with moderate tosevere type II diabetes and obesity,intensive medical therapy including lifestyle changes does not provide sufficient reduction in the glycated haemoglobin level to effectively reverse diabetes(HbA1c＜6.0).Surgery has come to the fore in metabolic syndrome following the success of bariatric procedures.An improvement in type IIdiabetes,observed in addition to weightreduction, has been demonstrated.

The ongoing expansion from bariatric into metabolic surgery for sleeve gastrectomy reflects international recognition ofitsrole in the correction ofco-morbidities in the moderately obese,particularly insulin resistance diabetes.The inclusion of bariatric surgery in the algorithm of the International Diabetic Federation for type IIdiabetes[4]consolidates the evidence.

Mechanisms

Sleeve gastrectomy,which involves laparoscopic removalofapproximately 75%ofthe stomach,isregarded as a restrictive bariatric procedure,with a considerable calorie restriction effecton BMI.However,the metabolic effects are much greater than calorie restriction alone. Severalplausible hypotheses forthe metabolic effects of the surgery have been articulated.Alterations in the secretion ofhormones like ghrelin,peptide-YY(PYY), leptin,glucagon-like peptide 1(GLP-1),glucose dependentinsulinotropic peptide(GIP),decrease in insulin resistance,long-term weight loss and alterations in gutmicrobiota together contribute to optimalglucose homeostasis aftersurgery[5,6].

The role of incretins in the promotion of insulin production is frequently postulated as a mechanism for the success of metabolic surgery.Two main incretins, GLP-1 and GIP,are produced from the small intestine epithelium in response to intestinalglucose concentrations. Incretins enhance glucose-dependentinsulin production at the pancreaticβ-cells.Additionally,GLP-1 inhibits glucagon production.In diabetic individuals,the secretion of GLP-1 and response to GIP are blunted.

A comparative analysis of guthormones aftersleeve gastrectomy and gastric bypass found thatboth exerted influence on GLP-1,GIP,obestatin and leptin,and bypass had an additionalduodenaleffecton cholecystokinin[7]. Exaggerated GLP aftergastric bypasshasbeen associated with increased pancreatic beta cellfunction although causality remains uncertain[8].

Insulin secretion happens in two phases,the firstof which is restored considerably followin g sleev e gastrectomy.Basso et al.in their study reported a‘‘gastric hypothesis’’for this restoration of 1stphase insulin secretion,which improves glycaemic control. They proposed that a decrease in hydrochlo ric acid-stimulated,vagally-innervated,antral mucosa secretion of gastrin releasing peptide(GRP)in turn stimulated GLP-1 release[9].

Fastergastric emptying was demonstrated scintigraphically in 11 patients at 6 months from surgery,and then compared to pre-operative testing.The time from the end of mealuntilthe beginning of emptying into the duodenum was reduced from 19.2 to 9.5 minutes. Gastric emptying half-time decreased from 94.3 to 47.6 minutes,indicating a quicker transitthrough the stomach.Quickerentry offood to the distalsmallbowel directly stimulatesthe L-cellsforthe 2ndphase of GLP-1 peptide release[10,11].Another study by Tzovaras etal. supported thistheory when they demonstrated symptoms suggestive of dumping syndrome after provocation in patients post-sleeve,reinforcing the notion thatsleeve is nota purely restrictive procedure[12].

Ghrelin,an appetite stimulant,produces orexigenic effects via stimulation of neuropeptide Y from the hypothalamus.Ghrelin is mainly produced by the oxyntic cells of the stomach,and has been implicated in obesity and metabolic syndrome.Diet induced weight loss raises circulating ghrelin levels.Sleeve gastrectomy significantly lowers fasting ghrelin despite weight loss,with suppression of ghrelin after meals, compared with no change from baseline fasting or post-prandial ghrelin levels after gastric bypass[13]. The reduction in serum ghrelin levels persists at5 year follow-up of sleeve gastrectomy[14].Insulin inhibits release of ghrelin.

PYY is co-secreted with GLP 1 from the distal intestine after meals,and increases insulin sensitivity and also inhibits the hypothalamic production of neuropeptide Y.PYY levels are increased after either sleeve gastrectomy orgastric bypass[13].

Pharmacological GLP-1 agonists have been approved by the United States Food and Drug Administration (FDA),as have inhibitors of dipeptidyl peptidase 4 (DPP 4),a protease which degrades GLP-1 and GIP. While such medications may control hyperglycaemia in diabetes,and even produce slight weight loss and hypertension reduction,the effects are not comparable to metabolic surgery.

Metabolic outcomes of sleeve gastrectomy

The Fourth International Consensus Summit on Sleeve Gastrectomy in New York,2012 included a survey of 46,133 sleeve gastrectomy cases,among 130 surgeons,at an average of 5 years after surgery. Excess weightloss was 59%at1 year,gradually falling to 50%at 6 years.Low complication rates were noted:high leak 1.1%,haemorrhage 1.8%and stenosis 0.9%[15].

Asweightlossplaysa key role in metabolic syndrome outcomes after sleeve gastrectomy,for excess weight loss,increasing numbers of trials demonstrate its effectiveness.Himpens etal.reported the percentage excess weightloss(EWL)after sleeve gastrectomy as 77.5%and 57.3%at 3 and 6 years,respectively[16]. Among super obese patients,the reported mean EWL is 52%,43%and 46%at72,84 and 96 months follow up,respectively[17].

Although widely considered safe and effective,postoperative complications do remain a feature of this surgery,though fewerand earlierin comparison to other procedure,with leak rates of2.2%in a meta-analysis of 9,991 cases[18].

Directcomparison ofmedicalversusbariatric surgical managementof obesity and diabetes was performed in the STAMPEDE prospective randomised controlled trial atthe Cleveland Clinic[19].Gastric bypass(Roux En Y) or sleeve gastrectomy provided a mean of 29.4 kg and 25.1 kg EWL,respectively,versus 5.4 kg in the intensive medicalgroup.Regarding diabetes,the success rate for reduction in HbA1c to 6.0%at 12 months was over 3 times greater after sleeve gastrectomy or gastric bypass surgery(42%and 37%versus 12%, respectively)[20].As a result,lesser medications for diabetes,hypertension and hyperlipidaemia need composite improvementin allparameters of metabolic syndrome.Long-term follow up of sleeve gastrectomy patients at6-8 years showed a 77%improvementor remission ofdiabetes[17].

A systematic analysis of 33 studies comprising 3,997 patients demonstrated reduction in hypertension in 75%ofcases,with resolution in 58%,atan average follow up of16.9±9.8 months[21].Cardiac remodelling following sleeve gastrectomy has been shown on echocardiography.Reduced left ventricular mass, septum and posteriorwallthickness,were demonstrated in the study by Cavarretta etal.;thus,there isimprovement in cardiac function[22].Lipid profile improvement, specifically HDL and triglyceride levels,totalcholesterol/ HDL and triglyceride/HDL ratios at1 year follow-up have been reported withoutlowering oftotalcholesterol and LDL levels after sleeve gastrectomy[23].

The Asian population in generalis known to develop metabolic syndrome at lower BMIs in comparison to their Caucasian counterpartand hence,studies have reported outcomes from Asia in this cohort.In Asian populations with type II diabetes and non-morbid obesity(BMI,25-35 kg/m2),sleeve gastrectomy has demonstrated up to 50%resolution in diabetes at 1 year[24].The principalmechanism is thoughtto be related to calorie restriction and weight loss,and C-peptide levels returning to＞3 ng/mL appears to be the most reliable marker of resolution.

Why Sleeve Gastrectomy?

In subjects with moderate obesity(36+/-2 kg)and uncontrolled type II diabetes,an extension of the STAMPEDE trial has shown restoration of pancreatic β-cellfunction,in contrastto intensive medicaltherapy or sleeve gastrectomy[25].

However,in Asia,where expertiseregarding metabolic procedures and their long term management is limited, widespread promotion of a malabsorptive procedure without equipping the masses with the necessary knowledge may prove detrimentalforthis field and for patients.A procedure with risk and benefitbetween the gastric band and gastric bypass is appealing.Sleeve gastrectomy has been shown to have greater excess weightloss,and improvementin diabetes,than gastric band[26].Indeed,sleeve is a successfulrevision procedure following failure ofgastric band,with concomitantband removalatsleeve gastrectomy,and 53%excess weight loss atone year[27].Food tolerance and gastrointestinal quality of life after sleeve gastrectomy are comparable to pre-surgery controls.The food tolerance questionnaire and the GastrointestinalQuality ofLife index(GIQLI)at 2 and 4 years found sleeve gastrectomy superior to adjustable gastric band,and Roux-En-Y gastric bypass[28].At6 years from sleeve gastrectomy,95.2% reporttheirfood tolerance from acceptableto excellent[29]. Sleeve gastrectomy can be employed for obese patients with metabolic syndrome who are at high risk of developing complications after malabsorptive procedures,including chronic smokers and non-steroidalantiinflammatory drug users.It is a valuable option for patients who are elderly and those with inflammatory boweldisease[30].

The burden oftaking medications daily and regularly is noteasy to handle.The simple thoughtoftaking less medications orbeing free from taking them is a joy.A retrospective study of sleeve gastrectomy in morbidly obese individuals reported a mean excessive BMIloss of 79.9%after 2 years.After surgery,83.3%of patients with type IIdiabetes discontinued theirhypoglycaemic medication after 1 month.Antihypertensive drugs were discontinued by 6 months,and medications for hypertriglyceridemia after 3 months.A significant reduction in glucose,triglyceride levels,triglyceride/ HDL ratio and increased HDL levels were noted and these changes were maintained under normalranges for at least 2 years[31].

The future of laparoscopic sleeve gastrectomy

Alternative procedures including gastric band, laparoscopic Roux-En-Y gastric bypass and gastric balloon insertion may be performed.The relative technical simplicity of sleeve gastrectomy,low morbidity,endoscopic access to the gastrointestinal tract,absence of anastomoses,minimal nutritional deficiencies,excellent weight loss with control of associated comorbidities,and the possibility to convert to other procedures,place sleeve gastrectomy at an advantage over other bariatric procedures.

Gastric bypass has a long history and long-term results support its efficacy in treating obese patients with metabolic disorders.It is an established factthat there are mechanisms beyond weight loss that are responsible for the excellent metabolic outcomes of gastric bypass and thatthese are related to bypassing the foregut.To maximize the scope ofsleevegastrectomy as a metabolic procedure,innovative procedureswith the benefits of both sleeve gastrectomy and gastric bypass are being employed.The sleeve duodenojejunalbypass surgery(LSG/DJB),single-anastomosis duodenojejunal bypass with sleeve gastrectomy(SADJB-SG),sleeve gastrectomy with loop bipartition,and loop duodenojejunal bypass with sleeve gastrectomy,are alllargely based on manipulation offoregut.The shortterm outcomes have been promising;however,they are still considered experimentalas both intermediate and long term data are awaited.Loop duodenalbypass in combination with sleeve gastrectomy for type II diabetes in individuals with BMI 21-38 kg/m2has shown promising early results,with 91%achieving HbA1c of 7.0 g/dL at6 months from surgery[32].

Laparoscopic Roux-En-Y gastric bypass prohibits visualisation ofthe excluded stomach.For populations with a high risk of gastric cancer,including Japan, endoscopic visualisation isparamount.In obese individuals with risk factors such as Helicobacter pylori infection, atrophic gastric mucosa including intestinal metaplasia, or a family history of gastric cancer,Kasama et al. published a series of laparoscopic sleeve gastrectomy with duodenojejunalbypass[33].The procedure wasfound to be feasible,and safe,with similarEWLto Roux-En-Y gastric bypass.AdditionalEWL versus sleeve gastrectomy was attributed to the added malabsorptive effects ofthe duodenojejunalbypass.

Sleeve with ideal interposition is an example of sleeve with hindgut manipulation.Patients undergoing this procedure have demonstrated restoration ofinsulin sensitivity,with increased insulin output,and doubling ofβ-cell glucose sensitivity[34].The mechanism is postulated to be intestinal over-stimulation,with increased GLP 1 and incretin secretion.

Conclusion

Sleeve gastrectomy is a valuable weapon in the fight against metabolic syndrome and obesity.Excess weightloss,resolution ofdiabetes,hypertension,sleep apnoea and cardiac remodelling with reduction in cardiac risk profile,provide compelling arguments for expansion of metabolic surgery.The biomedical research potentialfrom distinct anatomicalchanges in the gut,occurring in a controlled manner during surgery,isinspiring.The collaboration between surgical and laboratory teams sheds new lighton pathogenesis of metabolic syndrome and diabetes,through the effectiveness ofgastrointestinalsurgery,and heralds in a new era spurred by the necessity to curb the epidemic.

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✉Corresponding author:Dr.Asim Shabbir,Department of Surgery, National University Hospital,1E Kent Ridge Road,NUHS Tower Block,Level 8,Singapore 119228.Tel/Fax:65-67724296/65-67778427,E-mail:cfsasim@nus.edu.sg.Received 18 July 2014,Revised 20 July 2014,Accepted 01 September 2014,Epub 04 October 2014

The authors reported no conflictof interests.

©2015 by the Journal of Biomedical Research.All rights reserved.

10.7555/JBR.28.20140107