3. Metabolic Surgery and Control of Type 2 Diabetes

Transcription

1 3. Metabolic Surgery and Control of Type 2 Diabetes Philip R. Schauer, MD Shai M. Eldar, MD Helen M. Heneghan, MD Stacy A. Brethauer, MD The rising prevalence of obesity, coupled with disappointing results of nonoperative weight reduction programs, has led to the prosperity of bariatric surgery ( 1 3 ). The development of minimally invasive surgery techniques over the last 2 decades has further enhanced the safety profile and appeal of surgically induced weight loss approaches. It was recently estimated that close to bariatric operations were performed worldwide in 2008 ( 4 ). While the primary indication for these procedures is to achieve significant and durable weight loss, their remarkable metabolic effects merit equal attention. Improvement or resolution of the metabolic syndrome components, diabetes, hypertension, and dyslipidemia, form only a partial list of the obesity-related comorbidities positively affected by bariatric surgery ( 5 ). In fact, the term metabolic surgery has been coined to reflect the whole spectrum of effects induced by bariatric procedures. In particular, the dramatic and prompt remission of type 2 diabetes (T2DM) postoperatively has stimulated researchers to investigate the exact mechanisms responsible for this phenomenon. Disease remission or improvement usually occurs before any significant weight loss has occurred, implying that other mechanisms are responsible for the improvement in glucose homeostasis seen, particularly after the Roux-en Y gastric bypass (RYGB) procedure ( 6, 7 ). Currently, National Institutes of Health guidelines recommend bariatric surgery for patients with a body mass index (BMI) 40 kg/m 2, or a BMI 35 kg/m 2 with obesity-related comorbidities. The US Food and Drug Administration recently expanded these criteria, approving gastric banding for patients who have a BMI 30 kg/m 2 with obesity-related comorbidities. As the safety profile of bariatric procedures has greatly improved, growing numbers of clinicians believe this threshold could be lowered even further to offer surgical intervention to Translational Endocrinology & Metabolism, Volume 3, Number 2,

2 slightly overweight patients with poorly controlled diabetes despite maximal medical therapy. The weight loss-independent effect of metabolic surgery, addressed by Rubino and Cummings in other sections of this volume, may potentially open the door for surgery in nonobese patients with T2DM. Metabolic Surgery Procedures RYGB, laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), and biliopancreatic diversion (BPD) are the most commonly performed bariatric procedures at present. While gastric banding and the sleeve gastrectomy are purely restrictive in their mechanism of action, RYGB and BPD have a malabsorptive component in addition to restrictive properties. Each procedure s mechanism of action results in unique outcomes and also contributes to a constellation of procedurespecific risks, merits, and limitations. Although regional variations exist with regard to preferences for individual procedures, the gastric bypass remains the most popular weight loss surgery in the United States and is gaining popularity rapidly in Asia, Europe, and Australia ( 4 ). Gastric Banding In this procedure ( Figure 3-1 ), an adjustable silicone ring is wrapped around the proximal stomach and connected to a port placed subcutaneously. This band creates a small proximal pouch with a narrowed outflow lumen. The creation of a small pouch restricts food intake and leads to early satiety. By serially inflating the band through the connected port, higher degrees of restriction can be achieved for better weight loss. Deflation of the band may be indicated in cases of partial or complete gastric outlet obstruction, secondary to malpositioning or overfilling of the band. While this procedure is considered the least challenging technically, with the lowest perioperative morbidity and mortality rates of all bariatric operations, its long-term complications and high reoperation rates have led to a decrease in its popularity. The average excess weight loss (EWL) attainable with a band is reported to be 46% ( 8 ). Sleeve Gastrectomy This procedure ( Figure 3-2 ) involves resection of the greater curvature of the stomach, resulting in a tubular, sleeve-shaped remnant stomach. Similar to gastric banding, this is also a restrictive procedure but yields greater EWL than a band, with an average EWL of >55% ( 9 ). This is partially 50 Translational Endocrinology & Metabolism: Metabolic Surgery Update

3 FIG 3-1. Adjustable gastric banding. An adjustable band is placed around the upper stomach to create a ml gastric pouch above the band. The band diameter can be adjusted in the outpatient clinic setting to optimize weight loss. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography All Rights Reserved. attributed to the fact that the majority of the stomach is removed, which results in alterations of gut hormonal levels, with consequent effects on glucose metabolism ( 10 ). Until recently, this procedure was usually performed as the first of a multistage procedure in severely obese high-risk patients in order to minimize their operative risk. It is now accepted as a stand-alone procedure with very good short-term and medium-term results. Sleeve gastrectomy is among the most rapidly growing procedures internationally. Gastric Bypass The RYGB ( Figure 3-3 ) is the most commonly performed bariatric procedure worldwide, and achieves its effects through 2 mechanisms; restriction is created by the formation of a small (10 20 ml) gastric pouch, and malabsorption occurs by rerouting the proximal bowel so that the distal Metabolic Surgery and Control of Type 2 Diabetes 51

4 FIG 3-2. Sleeve gastrectomy. The stomach is stapled vertically to remove most of the body and fundus to achieve 75% gastric volume reduction. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography All Rights Reserved. stomach, duodenum, and proximal small bowel are excluded. The combination of these 2 mechanisms results in greater EWL (>65% on average) compared to purely restrictive operations ( 8 ). Although the RYGB is considered the most technically challenging of the aforementioned operations and is usually performed by experienced laparoscopic surgeons, it has a favorable safety profile and few adverse long-term consequences. Biliopancreatic Diversion While the BPD ( Figure 3-4 ) has a restrictive component, it is primarily a malabsorptive operation, due to exclusion of the duodenum and proximal small bowel. Although EWL is greatest with the BPD (75% on average), this must be considered alongside the higher complication rate associated 52 Translational Endocrinology & Metabolism: Metabolic Surgery Update

5 FIG 3-3. Roux-en-Y gastric bypass. The stomach is stapled to create a ml gastric pouch isolated from the remaining stomach. The jejunum is divided just beyond the ligament of Treitz and connected to the gastric pouch. The biliopancreatic limb, which carries bile and digestive enzymes, is reconnected to the jejunum at the jejuno-jejunostomy. The gastric bypass involves both gastric volume reduction (95%) and a short bypass of the remaining stomach and duodenum. Most of the small bowel involved in absorption (>95%) remains intact, so there is minimal risk of malnutrition (<1%). Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography All Rights Reserved. with this procedure, specifically the risk of severe malabsorption and nutritional deficiencies ( 8 ). Perioperative Morbidity and Mortality The majority of bariatric cases can now be performed laparoscopically. This has greatly decreased the operative morbidity and mortality previously associated with bariatric surgery ( 11 ). Conversion rates to open Metabolic Surgery and Control of Type 2 Diabetes 53

6 FIG 3-4. Biliopancreatic diversion. The stomach is stapled to create an approximately 250 ml gastric pouch, and the remaining stomach is removed. The ileum is divided 250 mm from the cecum and connected to the gastric pouch. The biliopancreatic limb, which carries bile and digestive enzymes, is reconnected to the ileum at enter-enterostomy. The biliopancreatic diversion involves both gastric volume reduction (50%) and a long bypass of most of the jejunum and ileum. Because most of the small bowel involved is bypassed, there is significant reduction in calorie absorption, causing significant weight loss but also a greater risk of malnutrition (5%). Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography All Rights Reserved. surgery are in the range of 0% to 5.7%, with the highest rates observed in revisional cases and for complex malabsorptive procedures ( 12, 13 ). In general, the less complex and technically challenging the procedure, the lower the morbidity and mortality. With greater experience and advancement in laparoscopic techniques, morbidity and mortality rates have decreased over the last decade and are now comparable to other common surgical procedures. Complication rates following bariatric surgery are quite acceptable; the Longitudinal Assessment of Bariatric Surgery study reported a 4.3% incidence of major adverse events in the 54 Translational Endocrinology & Metabolism: Metabolic Surgery Update

7 early postoperative period ( 14 ). Buchwald et al reported low early and late mortality rates after bariatric procedures, 0.28% and 0.35% respectively ( 15 ). Diabetes Control after Metabolic Surgery in Severely Obese Patients (BMI >35 kg/m 2 ) Multiple observational studies demonstrate significant, sustained improvements in T2DM among patients with severe obesity (BMI 35 kg/m 2 ) after vertical banded gastroplasty (VBG), LAGB, RYGB, and BPD ( 5 10 ). Direct comparisons among these studies are difficult, however, because of inconsistent reporting of preoperative BMI, age, duration/severity of T2DM, and glycemic measures. Furthermore, terms such as resolution and remission of diabetes have been defined with great variation utilizing HbA1c values ranging from <6.0% to <7.0%. More recently, Buse et al have attempted to standardize definitions of remission, but most studies were published prior to these consensus definitions ( 16 ). In a meta-analysis involving 136 studies (mostly observational) and patients, with T2DM resolution defined as persistent normoglycemia off of diabetes medications, Buchwald et al reported an overall 77% remission of T2DM Observational studies with after bariatric surgery ( 8 ). Most of these intermediate or long-term studies, however, were ret rospective, with follow-up (4-8 years) suggest follow-up of typically only 1 to 3 years. Nevertheless, the mean procedure-specific reso- may occur in some patients that while diabetes recurrence lution (remission) of T2DM was, impressively, who had initial remission, most 48%, 68%, 84%, and 98% for LAGB, VBG, remain in remission or under RYGB, and BPD, respectively ( Table 3-1 ). good control (HbA1c <7.0%). Observational studies with intermediate or long-term follow-up (4-8 years) suggest that while diabetes recurrence may occur in some patients who had initial remission, most remain in remission or under good control (HbA1c <7.0%) ( 6, 7 ). The multicenter Swedish Obese Subjects (SOS) study is a prospective, controlled study evaluating the long-term effects of bariatric surgery compared to nonsurgical weight management of severely obese patients (BMI >34 kg/m 2 ) in a community setting ( 17 ). Although only 13% of patients had T2DM, most were insulin resistant or prediabetic. Bariatric surgery (gastric banding n=156, VBG n=451, RYGB n=34) caused an average 16.1% weight loss at 10 years, compared to a small weight gain in controls. Mean weight loss was greater after RYGB ( 25.0 kg) than after LAGB ( 13.2 kg) or VBG ( 16.5 kg). Mean fasting blood glucose Metabolic Surgery and Control of Type 2 Diabetes 55

8 TABLE 3-1. EBWL and diabetes resolution/remission outcomes after bariatric surgery including gastric banding, gastroplasty, gastric bypass, and BPD. This meta-analysis included patients in 136 studies. The average resolution/remission rate was 77% for all procedures. Most studies included follow-up for <2 years. However, resolution/remission rates for those studies with >2-year follow-up were similar to those with <2 year follow-up. Total Gastric Banding Gastroplasty Gastric Bypass BDP % EBWL % Resolved overall % Resolved <2 y % Resolved 2 y [Adapted from Buchwald H et al. Am J Med. 2009;122( 3 ): ]. Weight and T2DM after bariatric surgery: systematic review and meta-analysis. tended to increase during the study in nonsurgical controls (+18.7% at 10 years), whereas a substantial decrease was seen in surgical patients at 2 years ( 13.6%) and 10 years ( 2.5%). The risk of developing diabetes was one-third as much for surgically treated patients at 10 years, while recovery rates from diabetes were 3 times greater for surgical patients. Twenty-year follow-up results of glycemic control are soon to be published. Until recently, randomized controlled comparisons of metabolic surgery with medical management of T2DM were very limited. In 2006, Dixon et al reported a randomized controlled trial (RCT) (n=60) comparing LAGB versus conventional T2DM management in subjects with BMI kg/m 2 who had early (<2 years duration) and relatively mild diabetes ( 18 ). LAGB produced significantly larger reductions in weight, fasting plasma glucose (FPG), HbA1c, and diabetes medication usage and achieved remission (HbA1c <6.3%) rates of 73% compared to only 13% for medical management ( p <0.05). In 2012, Schauer et al and Mingrone et al simultaneously reported RCTs comparing metabolic surgery with medical management of T2DM ( 19, 20 ). Mingrone et al compared conventional medical treatment (n=20) with RYGB (n=20) and BPD (n=20) in patients with BMI 35 kg/m 2 (mean BMI 45 kg/m 2 ) and advanced T2DM (mean HbA1c=8.6%). At 2 years, remission rates (HbA1c <6.5% without medication) were 0% (medical), 75% (RYGB), and 95% (BPD). HbA1c improved to 7.7% (medical), 6.4% (RYGB), and 5.0% (BPD) favoring both surgical procedures over conventional medical treatment ( p <0.001). Total body weight loss 56 Translational Endocrinology & Metabolism: Metabolic Surgery Update

9 was 33% for both surgical procedures, compared to only 5% for medical treatment. Schauer et al compared more intense medical treatment (n=50) with LSG (n=50) and RYGB (n=50) in patients with BMI kg/m 2 and advanced T2DM (mean HbA1c=8.9% to 9.5%). At 12 months, remission rates (HbA1c <6%) were 12% (medical), 37% (LSG), and 42% (RYGB) ( p < 0.001). HbA1c improved to 7.5% (medical), 6.6% (LSG), and 6.4% (RYGB), favoring both surgical procedures over intense medical treatment ( p <0.001). Total body weight loss was 29% and 25% for RYGB and LSG, respectively, compared to only 5% for intense medical therapy ( p <0.001). The surgical patients also significantly reduced dependency on diabetes medications, while medical patients increased dependency on diabetes medications. Both studies showed that surgery was well tolerated with few major complications and resulted in both superior glycemic control and greater improvements in cardiovascular risk factors compared to medical treatment. Long-Term Overall Reduction of Mortality and Cardiovascular Events after Bariatric Surgery Several retrospective investigations of bariatric operations in severely obese patients, including individuals with and without T2DM, reported better long-term survival after bariatric surgery compared to matched, nonoperated The prospective SOS study also controls, with mortality reductions of 33% showed a 24% nonadjusted to 89% ( ). Additionally, in a large decrease in all-cause mortality case-control study by Adams et al involving 7925 patients undergoing RYGB versus compared with superbly for the surgical group 7925 matched nonoperated individuals, at a matched controls, with mean follow-up of 8.4 years, surgery reduced decreases in cardiovascular all-cause mortality by 40%, cardiovascular and cancer deaths accounting mortality by 56%, cancer mortality by 60%, for most of this benefit. and, remarkably, diabetes-related mortality by 92% ( 27 ). The prospective SOS study also showed a 24% nonadjusted decrease in all-cause mortality for the surgical group compared with superbly matched controls, with decreases in cardiovascular and cancer deaths accounting for most of this benefit ( 28 ). More recently, the 20-year cardiovascular outcomes of the SOS study were reported. The surgical group (n=2010) had a significantly reduced rate of both fatal and nonfa tal cardiovascular events compared to the nonsurgical group (n=2037) ( p <0.001) ( 29 ). Metabolic Surgery and Control of Type 2 Diabetes 57

10 Bariatric Surgery and Other Gastrointestinal Operations in Patients with BMI<35 kg/m 2 The remarkable control of diabetes in severely obese patients suggests that surgery may be beneficial for moderately obese or nonobese patients with T2DM. A recent systematic review evaluated results of 18 studies involving 477 patients with T2DM and BMI <35 kg/m 2 who had metabolic surgery ( 30 ). The operations included conventional procedures such as RYGB, BPD, and LSG, but also investigational operations such as duodenal jejunal bypass. Composite results demonstrated that these procedures resulted in reduction in BMI from 30.4 kg/m 2 to 24.8 kg/m2, FPG from 203 mg/dl to Currently there are 3 RCTs mg/dl, and HbA1c from 9.0% to 6.3% supporting efficacy of ( p <0.05). Recently, Cohen et al reported on metabolic surgery for T2DM in 6-year follow-up of 66 patients witht2dm patients with BMI <35 kg/m 2. and BMI <35 kg/m2 who had RYGB ( 31 ). Overall remission rate at 6 years was 88% (HbA1c <6.5% without medications), and HbA1c fell from 9.7% to 5.9% ( p <0.001). No major complications occurred. Currently there are 3 RCTs supporting efficacy of metabolic surgery for T2DM in patients with BMI <35 kg/m 2. As previously noted, Dixon et al and Schauer et al showed that metabolic surgery was superior to medical treatment in patients with BMI as low as kg/m 2 ( 32 ). Lee et al compared gastric bypass with LSG (n=60) in patients with BMI kg/m 2 with T2DM. Both procedures were effective, yielding remission rates (HbA1c <6.5%) of 93% (gastric bypass) and 47% (LSG) at 12 months. HbA1c fell from 10% to 5.7% after gastric bypass and to 7.2% after LSG. Guidelines and Consensus for the Surgical Treatment of T2DM As the evidence to support metabolic surgery as a specific treatment of T2DM has increased, so too has the general consensus among scientists and clinicians who manage T2DM. Throughout the 1990s and the first decade of the new millennium, none of the major diabetes scientific professional societies mentioned any role for bariatric surgery in their diabetes guidelines. In 2007, for the first time in history, a diverse panel of more than 50 international experts, representing many medical specialties, including diabetology, surgery, gastroenterology, and cardiology, met in Rome to develop the first consensus statements regarding the role of gastrointestinal surgery to treat T2DM. This conference, known as the Diabetes Surgery Summit, resulted in the first published recommendations on 58 Translational Endocrinology & Metabolism: Metabolic Surgery Update

11 the use and study of diabetes surgery ( 33 ). Shortly thereafter, in 2009, the American Diabetes Association (ADA), became the first major national diabetes organization to recognize the role of surgery for treating diabetes, especially in patients with severe obesity (BMI 35 kg/m 2 ) ( 34 ). The ADA statement on bariatric surgery, however, was relatively brief, only 2 pages Key points of the IDF guidelines of a 200-page annual diabetes guideline. To document include the provide a more comprehensive and global importance of a perspective on the role of bariatric surgery for diabetes, the International Diabe- with emphasis on quality multidisciplinary team effort tes Federation completed a comprehensive surgical outcomes and consensus statement on the role of surgery long-term follow-up. treating T2DM ( 35 ). Key points of the document include the importance of a multidisciplinary team effort with emphasis on quality surgical outcomes and long-term follow-up. Furthermore, the document recommends that bariatric/metabolic surgery should be an accepted option in people who have T2DM and a BMI 35 kg/m 2. In addition, surgery should be considered as an alternative treatment option in persons with BMI kg/m 2 when diabetes cannot be adequately controlled by optimal medical regimen. Conclusion The evidence to support the safety and efficacy of bariatric/metabolic surgery for treating T2DM is stronger than ever. In addition to a large volume of very consistent observational data demonstrating efficacy of bariatric surgery, recent RCTs demonstrate superiority of surgery over both conventional and intensive medical therapy regimens in achieving glycemic control and reducing dependency of medications. Physicians who treat patients with T2DM and obesity should be aware that surgery can be a powerful treatment option that has significant potential to reduce longterm morbidity and mortality of this devastating disease. References 1. Catenacci VA, Hill JO, Wyatt HR. The obesity epidemic. Clin Chest Med. 2009; 30(3): Fisher BL, Schauer P. Medical and surgical options in the treatment of severe obesity. Am J Surg. 2002;184(6B):9S 16S 3. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, JAMA. 2010;303(3): Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide Obes Surg. 2009;19(12): Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14): Metabolic Surgery and Control of Type 2 Diabetes 59

12 6. Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238(4): , discussion Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222(3): , discussion Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122(3): Brethauer SA, Hammel JP, Schauer PR. Systematic review of sleeve gastrectomy as staging and primary bariatric procedure. Surg Obes Relat Dis. 2009;5(4): Peterli R, Wölnerhanssen B, Peters T, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009; 250(2): Agaba EA, Shamseddeen H, Gentles CV, Sasthakonar V, Gellman L, Gadaleta D. Laparoscopic vs open gastric bypass in the management of morbid obesity: a 7-year retrospective study of 1,364 patients from a single center. Obes Surg. 2008;18(11): Carelli AM, Youn HA, Kurian MS, Ren CJ, Fielding GA. Safety of the laparoscopic adjustable gastric band: 7-year data from a U.S. center of excellence. Surg Endosc. 2010;24(8): Maher JW, Martin Hawver L, Pucci A, Wolfe LG, Meador JG, Kellum JM. Four hundred fifty consecutive laparoscopic Roux-en-Y gastric bypasses with no mortality and declining leak rates and lengths of stay in a bariatric training program. J Am Coll Surg. 2008;206(5): , discussion Flum DR, Belle SH, King WC, et al; Longitudinal Assessment of Bariatric Surgery (LABS) Consortium. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med. 2009;361(5): Buchwald H, Estok R, Fahrbach K, Banel D, Sledge I. Trends in mortality in bariatric surgery: a systematic review and meta-analysis. Surgery. 2007;142(4): , discussion Buse JB, Caprio S, Cefalu WT, et al. How do we define cure of diabetes? Diabetes Care. 2009;32(11): Sjöström L, Lindroos AK, Peltonen M, et al; Swedish Obese Subjects Study Scientific Group. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004;351(26): Dixon JB, O Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA. 2008;299(3): Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17): Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17): MacDonald Jr KG, Long SD, Swanson MS, et al. The gastric bypass operation reduces the progression and mortality of non-insulin-dependent diabetes mellitus. J Gastrointest Surg. 1997;1(3): , discussion Flum DR, Dellinger EP. Impact of gastric bypass operation on survival: a populationbased analysis. J Am Coll Surg. 2004;199(4): Translational Endocrinology & Metabolism: Metabolic Surgery Update

13 23. Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg. 2004;240(3): , discussion Sowemimo OA, Yood SM, Courtney J, et al. Natural history of morbid obesity without surgical intervention. Surg Obes Relat Dis. 2007;3(1):73 77, discussion Peeters A, O Brien PE, Laurie C, et al. Substantial intentional weight loss and mortality in the severely obese. Ann Surg. 2007;246(6): Perry CD, Hutter MM, Smith DB, Newhouse JP, McNeil BJ. Survival and changes in comorbidities after bariatric surgery. Ann Surg. 2008;247(1): Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007;357(8): Sjöström L, Narbro K, Sjöström CD, et al; Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007; 357(8): Sjöström L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307(1): Shimizu H, Timratana P, Schauer PR, Rogula T. Review of metabolic surgery for type 2 diabetes in patients with a BMI <35 kg/m(2). J Obes. 2012;2012: Epub 2012 Jun Cohen RV, Pinheiro JC, Schiavon CA, Salles JE, Wajchenberg BL, Cummings DE. Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care. 2012;35(7): Lee WJ, Chong K, Ser KH, et al. Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial. Arch Surg. 2011;146(2): Rubino F, Kaplan LM, Schauer PR, Cummings DE; Diabetes Surgery Summit Delegates. The Diabetes Surgery Summit consensus conference: recommendations for the evaluation and use of gastrointestinal surgery to treat type 2 diabetes mellitus. Ann Surg. 2010;251(3): American Diabetes Association. Standards of medical care in diabetes Diabetes Care. 2009;32(Suppl 1):S13 S Dixon JB, Zimmet P, Alberti KG, Rubino F; International Diabetes Federation Taskforce on Epidemiology and Prevention. Bariatric surgery: an IDF statement for obese type 2 diabetes. Diabet Med. 2011;28(6): Metabolic Surgery and Control of Type 2 Diabetes 61