Gastrointestinal metabolic surgery for the treatment of type 2 diabetes mellitus

Medical therapy for type 2 diabetes mellitus is ineffective in the long term due to the progressive nature of the disease, which requires increasing medication doses and polypharmacy. Conversely, bariatric surgery has emerged as a cost-effective strategy for obese diabetic individuals; it has low complication rates and results in durable weight loss, glycemic control and improvements in the quality of life, obesity-related co-morbidity and overall survival. The finding that glucose homeostasis can be achieved with a weight loss-independent mechanism immediately after bariatric surgery, especially gastric bypass, has led to the paradigm of metabolic surgery. However, the primary focus of metabolic surgery is the alteration of the physio-anatomy of the gastrointestinal tract to achieve glycemic control, metabolic control and cardio-metabolic risk reduction. To date, metabolic surgery is still not well defined, as it is used most frequently for less obese patients with poorly controlled diabetes. The mechanism of glycemic control is still incompletely understood. Published research findings on metabolic surgery are promising, but many aspects still need to be defined. This paper examines the proposed mechanism of diabetes remission, the efficacy of different types of metabolic procedures, the durability of glucose control, and the risks and complications associated with this procedure. We propose a tailored approach for the selection of the ideal metabolic procedure for different groups of patients, considering the indications and prognostic factors for diabetes remission.

Recent advances in bariatric/metabolic surgery:appraisal of clinical evidence

Obesity and associated type 2 diabetes mellitus（T2DM） are becoming a serious medical issue worldwide.Bariatric surgery has been shown to be the most effective and durable therapy for the treatment of morbid obese patients.Increasing data indicates bariatric surgery as metabolic surgery is an effective and novel therapy for not well controlled obese T2 DM patients.The review of recent developments in bariatric/metabolic surgery covers 4major fields.1） Improvement of safety：recent advances in laparoscopic/metabolic surgery has made this minimal invasive surgery more than ten times safer than a decade ago.The safety profile of laparoscopic/metabolic surgery is compatible with that of laparoscopic cholecystectomy now.2） New bariatric/metabolic surgery：laparoscopic sleeve gastrectomy（LSG） is becoming the leading bariatric surgery because of its simplicity and efficacy.Other new procedures,such as gastric plication,banded plication,single anastomosis（mini） gastric bypass and Duodeno-jejunal bypass with sleeve gastrectomy have all been accepted as treatment modalities for bariatric/metabolic surgery.3）Mechanism of bariatric/metabolic surgery：Restriction is the most important mechanism for bariatric surgery.Weight regain after bariatric surgery is usually associated with loss of restriction.Recent studies demonstrated that gut hormone,microbiota and bile acid changes after bariatric surgery may play an important role in durable weight loss as well as in T2 DM remission.However,weight loss is still the cornerstone of T2 DM remission after metabolic surgery.4） Patient selection：patients who may benefit most from bariatric surgery was found to be patients with insulin resistance.For Asian T2 DM patients,the indication of metabolic surgery has been set to those with not well2controlled（Hb A1 c.7.5%） disease and with their BMI.27.5 Kg/m.A novel diabetes surgical score,ABCD score,is a simple system for predicting the success of surgical therapy for T2 DM.

Which predictors could effect on remission of type 2 diabetes mellitus after the metabolic surgery:A general perspective of current studies?

BACKGROUND The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus(T2DM).Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individual obese patients with T2DM.There are randomized trials that justify the inclusion of metabolic surgery into the treatment algorithm for patients with T2DM,but remission rates of T2DM after metabolic surgery can display great variability.AIM To discuss the most commonly used surgical options including vertical sleeve gastrectomy,adjustable gastric banding,Roux-en-Y gastric bypass,and biliopancreatic diversion with duodenal switch.METHODS We also report from observational and randomized controlled studies on rate of remission of T2DM after the surgical procedures.RESULTS In light of the recent findings,metabolic surgery is a safe and effective treatment option for obese patient with T2DM,but further studies are needed to clarify better the rate of diabetes remission.CONCLUSION In light of the recent findings,metabolic surgery is a safe and effective treatment option for obese patients with T2DM,but further studies are needed to clarify better the rate of diabetes remission.

Expert opinion on the preoperative medical optimization of adults with diabetes undergoing metabolic surgery

Diabetes mellitus(DM)and obesity are interrelated in a complex manner,and their coexistence predisposes patients to a plethora of medical problems.Metabolic surgery has evolved as a promising therapeutic option for both conditions.It is recommended that patients,particularly those of Asian origin,maintain a lower body mass index threshold in the presence of uncontrolled DM.However,several comorbidities often accompany these chronic diseases and need to be addressed for successful surgical outcome.Laparoscopic Roux-en-Y gastric bypass(RYGB)and laparoscopic sleeve gastrectomy(LSG)are the most commonly used bariatric procedures worldwide.The bariatric benefits of RYGB and LSG are similar,but emerging evidence indicates that RYGB is more effective than LSG in improving glycemic control and induces higher rates of long-term DM remission.Several scoring systems have been formulated that are utilized to predict the chances of remission.A glycemic target of glycated hemoglobin<7%is a reasonable goal before surgery.Cardiovascular,pulmonary,gastrointestinal,hepatic,renal,endocrine,nutritional,and psychological optimization of surgical candidates improves perioperative and long-term outcomes.Various guidelines for preoperative care of individuals with obesity have been formulated,but very few specifically focus on the concerns arising from the presence of concomitant DM.It is hoped that this statement will lead to the standardization of presurgical management of individuals with DM undergoing metabolic surgery.

Metabolic surgery:present and future

Several articles in this issue of the Journal cover a broad range of the new concepts of metabolic surgery, the mechanisms that leads to sustained metabolic syndrome remission, the new surgical procedures, and the perspective of surgeons and endocrinologists.

Bariatric surgery and diabetes:Current challenges and perspectives

Diabetes mellitus(DM)and obesity have become public issues of global concern.Bariatric surgery for the treatment of obesity combined with type 2 DM has been shown to be a safe and effective approach;however,there are limited studies that have systematically addressed the challenges of surgical treatment of obesity combined with DM.In this review,we summarize and answer the most pressing questions in the field of surgical treatment of obesity-associated DM.I believe that our insights will be of great help to clinicians in their daily practice.

Hybrid Duodenal Transit Bipartition: An Endoscopic and Laparoscopic Metabolic Procedure

Obesity has been increasing significantly in Brazil and worldwide, becoming a major public health issue. Traditional prevention and treatment strategies, including behavioral interventions, nutritional modifications, physical activity, pharmacotherapy, and metabolic/bariatric procedures, have proven insufficient to reverse this trend. Bariatric surgery is recognized as the most effective treatment for obesity and its comorbidities, but it carries potential long-term risks. Hybrid Duodenal Transit Bipartition is proposed as a minimally invasive “endobariatric” procedure combining endoscopic sleeve gastroplasty (ESG) with laparoscopic duodenoileal or distal duodenojejunal anastomosis. The main objective of this study is to demonstrate the importance of the intestinal metabolic component of hybrid duodenal transit bipartition. This intestinal component is responsible for optimizing and attempting to maintain weight loss and control comorbidities from an ESG through the incretin stimulus generated by the early arrival of food in the ileum or distal jejunum (duodenoileal or distal duodenojejunal anastomosis). Additionally, it is a minimally invasive procedure that preserves the entire digestive system and does not involve gastrointestinal exclusion, allowing for endoscopic and nutritional access. To date, only one patient has undergone the hybrid duodenal bipartition procedure, with satisfactory early postoperative results at 60 days and weight loss exceeding the scientific literature on patients who underwent isolated endoscopic sleeve gastroplasty. Further studies are needed to validate these results and assess the long-term metabolic benefits of this new approach.

Sleeve Gastrectomy with Duodenal Transit Bipartition (S-DTB): Preliminary Results and Technical Aspects of Its Metabolic Structure

Obesity is a significant and escalating health issue both in Brazil and globally, with over 650 million overweight adults worldwide. The treatment of obesity can be performed clinically, endoscopically or surgically;surgical treatment proves to be safe and more effective in terms of weight loss and long-term maintenance. Objective: This study aimed to monitor the progress of weight loss and comorbidity control in patients undergoing sleeve gastrectomy with duodenal bipartition. Methods: This pilot project involved 8 patients divided into 2 arms. In the first arm, patients underwent sleeve gastrectomy with Roux-en-Y duodenoileal transit bipartition (S-RYDITB), while in the second arm, patients underwent sleeve gastrectomy with Roux-en-Y duodenojejunal transit bipartition (S-RYDJTB). Both procedures involved Roux-en-Y reconstruction without duodenal exclusion. In S-RYDITB, the duodenal-ileal anastomosis was performed 300 cm from the ileocecal valve (ICV), creating a 250 cm common channel and a 50 cm alimentary channel. In S-RYDJTB, a biliopancreatic loop was created 200 cm from the angle of Treitz, with a 1 m alimentary channel. Results: Five patients underwent the procedures, with one undergoing S-RYDITB and four undergoing S-RYDJTB. No adverse events such as hospitalizations, readmissions, reoperations, fistulas, bleeding, pulmonary embolism, diarrhea, dumping syndrome, or hypoglycemia occurred during the study period. The mean length of hospital stay was 2 days. The average BMI decreased from 37.27 kg/m2 preoperatively to 29.48 kg/m2 after 6 months. The significant percentage of weight loss was 21.22%, with excess weight loss of 63.6%. Ninety-five percent remission of comorbidities, including hypercholesterolemia, hypertriglyceridemia, diabetes, hypertension, steatosis, and pre-diabetes. Two patients underwent sleeve gastrectomy with duodenal bipartition using a single anastomosis. Conclusion: Duodenal switch surgery has gained worldwide recognition for its safety and efficacy in treating obesity and its associated comorbidities. In efforts to maintain the positive outcomes of the classic technique while minimizing adverse effects such as malnutrition and diarrhea, modifications to the original procedure have been proposed. Among these adaptations, Sleeve gastrectomy with bipartition of duodenal transit (S-DTB) emerges as a promising variant, offering alternative strategies to optimize patients’ nutritional safety while preserving endoscopic access to the duodenum. Initial results of S-DTB, whether performed in Roux-en-Y or single anastomosis (loop) configuration without intestinal exclusions, demonstrate the procedure’s safety and effectiveness in managing obesity and its comorbidities.

Metabolic surgery in China: present and future

Obesity and its related complications comprise a serious public health problem worldwide,and obesity is increasing in China.Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic complications.The pathogenesis of obesity is complex and not yet fully understood.Here,we review the current efficacy and safety of metabolic surgery,as well as recent progress in mechanistic studies and surgical procedures in China.The exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety.

Bile acids and metabolic surgery

The epidemic of obesity and its co-mortalities has reached an alarming level worldwide.Currently,metabolic surgeries,especially the Roux-en-Y gastric bypass and vertical sleeve gastrectomy,are the most effective and sustainable treatments for obesity,type 2 diabetes,non-alcoholic steatohepatitis,as well as other metabolic diseases.However,the invasive nature of the surgeries limits their broad ap-plications to the general public.Therefore,developing alternative non-invasive approaches to mimic metabolic surgery is an important direction of the field.Recent studies have identified several potential metabolic surgery-induced downstream endocrine mediators,among which bile acids are key candidate signaling molecules.Bile acids are profoundly altered by metabolic surgery,which contributes to the metabolic effects of the surgery.In this review,we focus on the most recent studies on the roles of bile acids and bile acid receptors farnesoid X receptor and Takeda G protein-coupled receptor 5 in mediating the metabolic effects of metabolic surgery.We conclude that targeting bile acid pathways may be a promising pharmacological approach to mimic the beneficial effects of metabolic surgery.

Comparative effectiveness of medical treatment vs.metabolic surgery for histologically proven non-alcoholic steatohepatitis and fibrosis:a matched network meta-analysis

Background:Non-alcoholic steatohepatitis(NASH)comprises a major healthcare problem affecting up to 30%of patients with obesity and the associated risk for cardiovascular and liver-related mortality.Several new drugs for NASH-treatment are currently investigated.No study thus far directly compared surgical and non-surgical therapies for NASH.This network meta-analysis compares for the first time the effectiveness of different therapies for NASH using a novel statistical approach.Methods:The study was conducted according to the PRISMA guidelines for network meta-analysis.PubMed,CENTRAL and Web of Science were searched without restriction of time or language using a validated search strategy.Studies investigating therapies for NASH in adults with liver biopsies at baseline and after at least 12 months were selected.Patients with liver cirrhosis were excluded.Risk of bias was assessed with ROB-2 and ROBINS-I-tools.A novel method for population-adjusted indirect comparison to include and compare single-arm trials was applied.Main outcomes were NASH-resolution and improvement of fibrosis.Results:Out of 7,913 studies,twelve randomized non-surgical studies and twelve non-randomized surgical trials were included.NASH-resolution after non-surgical intervention was 29%[95%confidence interval(CI):23-40%]and 79%(95%CI:72-88%)after surgery.The network meta-analysis showed that surgery had a higher chance of NASH-resolution than medication[odds ratio(OR)=2.68;95%CI:1.44-4.97]while drug treatment was superior to placebo(OR=2.24;95%CI:1.55-3.24).Surgery(OR=2.18;95%CI:1.34-3.56)and medication(OR=1.79;95%CI:1.39-2.31)were equally effective to treat fibrosis compared to placebo without difference between them.The results did not change when only new drugs specifically developed for the treatment of NASH were included.Conclusions:Metabolic surgery has a higher effectiveness for NASH-therapy than medical therapy while both were equally effective regarding improvement of fibrosis.Trials directly comparing surgery with medication must be urgently conducted.Patients with NASH should be informed about surgical treatment options.

Metabolic bariatric surgery and type 2 diabetes mellitus:an endocrinologist's perspective

Traditional treatment of T2 DM consisting of modification of diet,an exercise regimen,and pharmacotherapy has problems of poor lifestyle modifications and fail tend of treatment over time,now bariatric surgery is recommended for treatment of obese patients with T2 DM because its great improvements on weight loss and metabolic.In this article,effects of bariatric surgery on diabetes and diabetes-related complications are reviewed.

Weight loss maintenance after bariatric surgery

Metabolic and bariatric surgery(MBS)is an effective treatment for patients with morbid obesity and its comorbidities.However,many patients experience weight regain(WR)after achieving their nadir weight.Establishing the definition of WR is challenging as postoperative WR has various definitions.Risk factors for WR after MBS include anatomical,racial,hormonal,metabolic,behavioral,and psychological factors,and evaluating such factors preoperatively is necessary.Long-term regular follow-up and timely treatment by a multidisciplinary team are important because WR after surgery is multi-factorial.Although lifestyle interventions that focus on appropriate dietary education,physical activity education or interventions,and behavioral psychological interventions are suggested,more well-designed studies are needed because studies evaluating intervention methods and the effectiveness of WR prevention are lacking.Antiobesity drugs can be used to prevent and manage patients with WR after MBS;however,more research is needed to determine the timing,duration,and type of anti-obesity drugs used to prevent WR.

Surgical or medical treatment of obesity-associated type 2 diabetesan increasing clinical conundrum

In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2D)associated with obesity.Bariatric surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D,but information on newer GLP-1RAs in these groups is predictably limited.In older individuals(age>65 years),both bariatric surgery and GLP-1RA therapy improve cardiovascular outcomes.Baria-tric surgery is not infrequently associated with post-operative postprandial hypoglycemia,which is not the case with GLP-1RAs and,paradoxically,there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial hypoglycemia.Comparative trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.

Analysis of long-term outcome of modified gastric bypass for type 2 diabetes mellitus in Chinese patients

BACKGROUND Bariatric and metabolic surgery have been routinely performed following the rapid increase in obesity and metabolic diseases worldwide.Of all evolving procedures,Roux-en-Y gastric bypass(RYGB)is considered the gold standard for surgical treatment of patients with type 2 diabetes mellitus(T2DM)and obesity.RYGB was introduced in China nearly 20 years ago,but the number of RYGB surgeries only accounts for 3.1%of the total number of weight loss and metabolic surgeries in China,it’s effect on Chinese people still needs further study.AIM To investigate the effect and safety of a modified gastric bypass performed in Chinese patients with T2DM.METHODS Patients with obesity and T2DM who underwent modified gastric bypass,with>5-year follow-up data,were analyzed.RESULTS All 37 patients underwent uneventful laparoscopic surgery,no patient was switched to laparotomy during the surgery,and no severe complications were reported.Average weight and body mass index of the patients reduced from 84.6±17.3(60.0–140.0)kg and 30.9±5.0(24.7–46.2)kg/m2 to 67.1±12.2(24.7–46.2)kg and 24.6±3.9(17.7–36.5)kg/m2,respectively,and fasting plasma glucose and glycated hemoglobin decreased from 7.4±3.4 mmol/L and 8.2%±1.7%preoperatively to 6.5±1.3 mmol/L and 6.5%±0.9%5-years postoperatively,respectively.Only 29.7%(11/37)of the patients used hypoglycemic drugs 5-years postoperatively,and the complete remission rate of T2DM was 29.7%(11/37).Triglyceride level reduced significantly but high-density lipoprotein increased significantly(both P<0.05)compared with those during the preoperative period.Liver and renal function improved significantly postoperatively,and binary logistic regression analysis revealed that the patients’preoperative history of T2DM and fasting C-peptide were significant prognostic factors influencing complete T2DM remission after RYGB(P=0.006 and 0.012,respectively).CONCLUSION The modified gastric bypass is a safe and feasible procedure for Chinese patients with obesity and T2DM,exhibiting satisfactory amelioration of weight problems,hyperglycemia,and combination disease.

Five Year Follow up after Surgical Treatment of Type 2 Diabetes with Laparoscopic Sleeve Gastrectomy Associated with a Duodenal Ileal Interposition

Introduction: Type 2 diabetes mellitus (T2D) is a chronic disease, primarily caused by a combination of defective insulin secretion and the inability of insulin-sensitive tissues to respond to insulin. Laparoscopic sleeve gastrectomy associated with duodenal ileal interposition (SGDII) has been shown to be a feasible treatment option for patients with T2D, as it provides improvement and control of glycemia, dyslipidemia and arterial hypertension. The aim of this study was to evaluate the mid and long-term results of SGDII for the treatment of diabetic patients, considering diabetic remission, weight loss and postoperative complications. Materials and Methods: Retrospective study with 96 patients with T2D submitted to SGDII, between 2010 and 2016. The glycated hemoglobin (HbA1c) value Results: Sixty-one patients (62.8%) were male, and 36 patients (37.2%) were female. The average age was 50.9 years. Median BMI was 33.43 kg/m2. The incidence of major postoperative complications in the first 30 days was 2.1%, with no mortality. Dyslipidemia control was sustained, after five years, in 62% of the patients. The five years follow-up demonstrated that 80% of patients had T2D remission at one year, 74.5% at three years and 61.8% at five years. Univariate analysis demonstrated that preoperative values of HbA1c and BMI, preoperative use of insulin, gender, and 30-day complication were not predictors of remission at all study intervals. The average duration of the disease was nine years and the mean glycated hemoglobin before surgery was 8.95%. Conclusion: SGDII resulted in good glycemic control at 5-years follow-up and represents a valid alternative for the treatment of T2D.

The success of sleeve gastrectomy in the management of metabolic syndrome and obesity

The rapid reversal of diabetes,hypertension,hyperlipidaemia and obesity by surgical means has challenged accepted doctrines regarding the management of metabolic 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 weight loss,a low complication rate,and excellent food tolerance,combined with a short hospital stay,have made this the procedure of choice for patients and surgeons across the globe.High volume centres nurture the ongoing development of experienced and specialized teams,pathways and regimens.Optimum surgical outcomes allow minimization of metabolic syndrome,reducing cardiovascular and cerebrovascular risk.

Laparoscopic revolution in bariatric surgery

The history of bariatric surgery is investigational. Dedicated surgeons have continuously sought for an ideal procedure to relieve morbidly obese patients from their burden of comorbid conditions, reduced life expectancy and low quality of life. The ideal procedure must have low complication risk, both in short- and long term, as well as minimal impact on daily life. The revolution of laparoscopic techniques in bariatric surgery is described in this summary. Advances in minimal invasive techniques have contributed to reduced operative time, length of stay, and complications. The development in bariatric surgery has been exceptional, resulting in a dramatic increase of the number of procedures performed world wide during the last decades. Although, a complex bariatric procedure can be performed with operative mortality no greater than cholecystectomy, specific procedure-related complications and other drawbacks must be taken into account. The evolution of laparoscopy will be the legacy of the 21st century and at present, day-care surgery and further reduction of the operative trauma is in focus. The impressive effects on comorbid conditions have prompted the adoption of minimal invasive bariatric procedures into the field of metabolic surgery.

Bariatric surgery in old age:a comparative study of laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy in an Asia centre of excellence

Bariatric surgery has been proved to be the safest and efficient procedure in treating morbid obese patients,but data is still lacking in the elderly population.The aim of our study was to compare the safety and efficacy of laparoscopic Roux-en-Y gastric bypass（LRYGB） and sleeve gastrectomy（LSG） in patients aged more than 55 years.We performed2 a retrospective review of a prospectively collected database.All patients with body mass index（BMI） §32 kg/mand aged more than 55 years undergoing LRYGB or LSG in BMI Surgery Centre,E-Da Hospital between January 2008 and December 2011 with at least one year of follow up were included for the analysis.Demography,peri-operative data,weight loss and surgical complications were all recorded and analyzed.Mean age and BMI of these 68 patients22（22 males and 46 female） were 58.8 years（55-79 years） and 39.5 kg/m（32.00-60.40 kg/m）.LRYGB was performed in 44 patients and LSG in 24 patients.The two groups were comparable in their preoperative BMI,American Society of Anaesthesia（ASA） score and gender distribution.LSG patients were significantly older than patients receiving LRYGB.The proportion of type 2 diabetes preoperatively was significantly higher in LRYGB patients as compared to LSG patients（88.63% vs.50%; P,0.01）.The prevalence of other co-morbidities was similar and comparable2 between the groups.Mean BMI in the LRYGB and LSG groups at the end of 1 year were 28.8 kg/mand228.2 kg/m,respectively,and there was no statistically significant difference in mean percentage of excess weight loss（%EWL） at 1 year.The percentage of resolution of diabetes was significantly higher in LRYGB（69.2%） as compared to LSG（33.3%）.On the other hand,there was no statistical difference in the percentage of resolution of hypertension,hyperlipidemia and fatty liver hepatitis.The overall morbidity and re-operation rate was higher in LRYGB patients.In morbidly elderly patients,both surgeries achieved good weight loss and resolution of comorbidities.LRYGB is superior to LSG in terms of diabetes remission but carries higher complication rates even at high volume centres.

Remission of type 2 diabetes mellitus

The surge in type 2 diabetes mellitus(T2DM)is tightly linked to obesity,leading to ectopic fat accumulation in internal organs.Weight management has become a cornerstone of T2DM treatment,with evidence suggesting that significant weight loss can induce remission.Remission,defined as sustained hemoglobin(HbA1c)below 6.5% for at least 3 months without medication,can be achieved through various approaches,including lifestyle,medical,and surgical interventions.Metabolic bariatric surgery offers significant remission rates,particularly for patients with severe obesity.Intensive lifestyle modifications,including lowcalorie diets and exercise,have also demonstrated significant potential.Medications like incretin-based agents show robust results in improving beta-cell function,achieving glycemic control,and promoting weight loss.While complete remission without medication may not be attainable for everyone,especially those with severe insulin resistance or deficiency,early and aggressive glycemic control remains a crucial strategy.Maintaining HbA1c below 6.5%from the time of diagnosis reduces the risk of long-term complications and mortality.Moreover,considering a broader definition of remission,encompassing individuals with sustained control on medication,could offer a more comprehensive and inclusive approach to managing this chronic disease.