Published September 2012

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Preamble

The following position statement is issued by the American Society for Metabolic and Bariatric Surgery in response to numerous inquires made to the Society by patients, physicians, society members, hospitals, and others regarding the safety and efficacy of bariatric surgery for patients with Class 1 obesity. In this statement, available data are summarized and recommendations for treatment are made regarding bariatric surgery for patients with a body mass index (BMI) of 30-35 kg/m2 based on current knowledge, expert opinion, and published peer-reviewed scientific evidence available at this time. The statement is not intended as, and should not be construed as, stating or establishing a local, regional, or national standard of care. The statement may be revised in the future as additional evidence becomes available.

The Issue

Obesity is the major epidemic of our generation. The National Nutritional Examination Survey (NHANES) suggest that obesity affects women (35.8%), men (35.5%) and children (2-19 years of age, 16.9%).1, 2 Increasingly data is accumulating that many of the metabolic problems that accompany obesity begin at a BMI of 30 or even earlier and increase early mortality. 3, 4 Recently the Food and Drug Administration voted to extend the use of a medical device, the Lap BandTM, to people afflicted with Class I obesity with one or more co-morbidities and randomized prospective data from the STAMPEDE trial demonstrates the effectiveness of RYGP and Sleeve in patients with a BMI of 27 and greater in the treatment of Type 2 Diabetes.5 The current data support lowering the arbitrary BMI cutoff of 35 kg/m2 established in 1991 by offering surgical therapy to patients with Class 1 obesity. The primary purpose of this review is to evaluate the evidence regarding the benefits and risks of all bariatric procedures in patients with BMI > 30 kg/m2.

Class 1 Obesity as a health problem.

Obesity is defined as a disease in which fat has accumulated to the extent that health is impaired. In the absence of a simple direct method for measuring total body fat, the Body Mass Index (BMI) is the most common method for describing levels of obesity. For Western societies, the World Health Organization and the United States National Institutes of Health have defined a BMI of > 30 kg/m2 as being obese6, 7 based primarily on the associated mortality risk. In addition, the co-morbid conditions associated with obesity contributed substantially to the definition. Overweight and obesity can be divided into four levels of severity of co-morbidity and mortality risk (Table 1).

The morbidity and mortality risks of obesity have been subject to multiple systematic reviews. Some of these provide a global overview8 but others are focused on specific weight-related diseases such as diabetes9, cardiovascular disease10 and various cancers11-15. A recent comprehensive systematic review and meta-analysis of the possible co-morbidity risks for both overweight and the classes of obesity has brought together the data from 89 individual studies3 and the pooled relative risk for co-morbidities related to the severity of obesity was calculated. Significant associations were found between all classes of overweight/obesity and type 2 diabetes, coronary artery disease, hypertension, congestive heart failure, asthma, stroke, pulmonary embolism, gallbladder disease, nine common cancers, osteoarthritis and chronic back pain. Although Class I obesity was not identified separately from overweight or the more severely obese, the findings were present for both the overweight and all three classes of obesity confirming the effect of Class I obesity in the pathogenesis of these diseases.

The mortality risk of obesity is best examined by following large populations over many years. The Prospective Studies Collaboration is an international consortium of 61 large, prospective epidemiologic studies mainly from North America and Europe and based at the University of Oxford. They analyzed 57 of these studies involving nearly 900,000 adults for whom BMI was available.4 They excluded the data from the first five years of follow-up and tracked outcomes for a mean of 8 years. They related BMI to cause-specific mortality and showed that, from a BMI of 25kg/m2, mortality was approximately 30% greater for each additional 5 kg/m2. The risk status was largely independent of age. Also noted was an increased risk of stroke, myocardial infarction and diabetes. Overall, for Class 1 obesity, the lifespan was decreased by 3 years.

Similar findings had been derived from the Framingham database16 and the National Health and Nutrition Examination Survey (NHANES).17 In a Special Report in the New England Journal of Medicine18, Olshansky and colleagues argued that the increasing problems of obesity and its co-morbidities, particularly type 2 diabetes, will override the benefits of other health advances and a continued increase in life expectancy will not persist. From these data we conclude that Class 1 obesity is a health problem that leads to additional serious co-morbidities and a shortened life expectancy. Therefore, Class 1 obesity deserves effective treatment.

Historic Perspective for Treatment Recommendations.

The morbidity and mortality caused by the disease of obesity is well established and has long been recognized by all major advisory bodies. It was recognized by a National Institutes of Health consensus conference in 1985. A subsequent separate consensus conference, held in March 1991, considered the role of bariatric surgery for these patients19. A synthesis of the views of the opinion leaders present at that time recommended that bariatric surgery should be considered for those patients who have: BMI > 40, BMI > 35 in association with major co-morbidities such as severe sleep apnea, Pickwickian syndrome, obesity-related cardiomyopathy, or BMI>35 in association with obesity-induced physical problems with lifestyle, including joint disease or body size problems interfering with employment, family function, and ambulation.

Since the NIH consensus conference, new procedures have been introduced, the laparoscopic approach has largely replaced open surgery, and higher levels of scientific evidence are now available regarding the health hazards of obesity and the risks and benefits of bariatric surgery. Given the major changes that have occurred in this field, it is appropriate to review the data now available and, in the context bariatric surgery as it is currently practiced, consider modification of the arbitrary recommendations established 20 years ago.

Despite attempts to update the recommendations of the original guidelines,20, 21 private health insurers and Medicare continue to rely on the 1991 consensus conference guidelines to set a baseline for BMI above which bariatric surgery offers a favorable risk/benefit ratio. The correct placement of that baseline is of critical importance to the patient, the doctor and the payer. In particular, the time has come to address the appropriate place for bariatric surgery for the treatment of patients with Class 1 obesity. This discussion should consider whether Class 1 Obesity is a clinically relevant health problem, whether it is adequately managed by non-surgical means and whether there is evidence that bariatric surgical techniques provide a safe and cost-effective treatment approach.

The Data

Non-surgical treatment of Class 1 obesity.

In the treatment algorithm for Class 1 obesity, the safest treatment that is effective should be the preferred option. All individuals seeking weight loss should begin with non-surgical therapy and only consider bariatric surgery if they are unable to achieve sufficient long-term weight loss and comorbidity improvement with non-surgical therapies.

For most people with Class 1 obesity, however, it is clear that the non-surgical group of therapies will not provide a durable solution to their disease of obesity. Most will not lose a substantial amount of weight with these measures and most who do lose weight will regain the weight within one to two years. Systematic reviews of the numerous randomized controlled trials (RCT) of programs incorporating diets, exercise, pharmacotherapy and behavioral therapy have demonstrated a mean weight loss in the range of 2 – 6 kg at one year or less22-26 with poor maintenance of that weight loss beyond that time.27

However, within the total group of participants studied in these trials and within the general practice of bariatric medicine, there are individuals who have achieved substantial and durable weight loss and have been able to maintain that weight loss for several years. Therefore, before considering surgical treatment for obesity for any individual, an adequate trial of non-surgical therapy should always be required. If, however, the attempts at treating their obesity and obesity-related comorbidities have not been effective, we must recognize that the individual has a problem that threatens their health and life expectancy and we must seek an effective, durable therapy such as bariatric surgery.

Bariatric Surgery for Class 1 Obesity.

There is a robust body of literature to support the safety and efficacy of bariatric surgery in patients who meet current NIH criteria. Many of the published articles demonstrate clear weight loss and comorbidity benefits for patients who are at the low end of the currently accepted criteria. Though the data for bariatric surgery patients with BMI 35-40 kg/m2 cannot be directly extrapolated to the 30-35 population, it is reasonable to expect the same beneficial effects of the surgery in this lower BMI group. Further data in the lower BMI group has been needed to better define the risk/benefit ratio for this patient population.

To date, there are four randomized controlled trials (RCT) that include patients with BMI 30-35 kg/m2 .5, 28-30 Three of these trials5, 28, 29 also include patients with BMI outside of this range (as low as 25 and as high as 43). Because the overlap in BMI is large, the level of evidence is high, and the importance of optimal treatment of diabetes is critical, the data from these studies have been included in this analysis. Additionally, there are 16 observational studies31-46 and one meta-analysis47 examining the effects of bariatric surgery on diabetes in patients with BMI < 35 kg/m2. A summary of these studies is provided in Tables 2 and 3.

Randomized Trials

There are two randomized trials evaluating laparoscopic adjustable gastric banding (LAGB) in lower BMI patients. In the first study by O’Brien and colleagues, 80 patients with Class 1 obesity were randomized into a program of optimal non-surgical weight loss therapy or to gastric banding and followed for 2 years.48 The participants in the gastric banding group showed 87.2 % EWL (95% C.I. 78-97) at 2 years. BMI was reduced from a mean of 33.7 to 26.4 kg/m2. In comparison, the non-surgical group had 21.8 % EWL (12-32) at two years. Notably, 35% of the non-surgical group had lost more than 25% of excess weight at 2 yr indicating a worthwhile outcome can be achieved with non-surgical therapy for a sub-group of patients. The principal reported co-morbidity in this RCT was the metabolic syndrome which was defined by the ATP III criteria49 and was present in 38% of each group at the commencement of the study. At 2 yr, there was a highly significant reduction to 3% in the surgical group. Reduction from 38% to 24% in the control group was not significant. Additionally, the short form health survey (SF-36) was used to compare changes in the 8 domains of both groups over the two years of study. The gastric banding group showed significant improvement in all 8 domains of the SF-36 with significantly greater improvement than the non-surgical group for physical functioning, vitality and mental health. There were no major adverse events but 4 patients in the surgical group required a late revisional procedure for posterior prolapse. Four patients in the non-surgical group required cholecystectomy, possibly linked to very low calorie diet therapy.

The second LAGB trial by Dixon and colleagues randomized 60 patients with recent onset type 2 diabetes (< 2 years duration) to surgery versus conventional diabetes therapy with emphasis on weight management.28 The surgical group achieved significantly greater weight loss at two years (20% total weight loss versus 1.4%, p < 0.001) and had a 73% rate of diabetes remission (fasting glucose level <126 mg/dL [7.0 mmol/L] and glycated hemoglobin [HbA1c] value <6.2% while taking no glycemic therapy) compared to 13% of the medical treatment group (P<0.001). There was a significant reduction in the use of pharmacotherapy for glycemic control in the surgical group at 2 years and no decrease in the medically managed group. There were no serious adverse events in either group.

In a trial by Lee et al., 60 poorly controlled diabetics were randomized to laparoscopic gastric bypass or laparoscopic sleeve gastrectomy.29 The bypass procedure utilized in this trial was the loop mini-gastric bypass and there was no medical treatment arm in this study. The primary endpoint was diabetes remission (fasting glucose < 126 mg/dL and HbA1c < 6.5% without glycemic therapy) at one year. All patients completed follow-up and, overall, 70% achieved diabetes remission. Significantly more bypass patients achieved remission compared to sleeve gastrectomy patients (93% versus 47%, p<0.02). Bypass patients achieved significantly lower BMI and greater improvements in lipids and the metabolic syndrome in this study. Minor complications occurred in 10% of patients and there were no major adverse events in either group.

Schauer and colleagues randomized 150 patients to intensive medical therapy (IMT) for their diabetes versus IMT plus gastric bypass versus IMT plus sleeve gastrectomy.5 The primary endpoint for this study was the proportion of patients with a HbA1c < 6% at one year. The study did include patients with BMI up to 43 kg/m2 but 34% of the patients had a BMI < 35 kg/m2 and it is therefore included in this analysis. Patients in this study were poorly controlled diabetics with a mean preoperative mean HbA1c of 9.2% and, despite improvements in glycemic control for all groups, the surgical groups achieved significant greater glycemic control than the medical group. Mean HbA1c decreased to 7.4%, 6.6%, and 6.4% for the IMT, sleeve gastrectomy, and gastric bypass groups, respectively. The surgical groups also had significantly greater weight loss and significant reductions in cardiovascular medication compared to medical therapy. Additional surgical interventions were required in four patients in the surgery groups. These included one laparoscopic evacuation of a hematoma, one diagnostic laparoscopy to assess persistent nausea and vomiting, laparoscopic jejunostomy for feeding access after staple line leak following sleeve gastrectomy, and one laparoscopic cholecystectomy after gastric bypass. There were no deaths, episodes of serious hypoglycemia requiring intervention, malnutrition, or excessive weight loss among the three groups.

A meta-analysis by Li et al.47 evaluated 13 studies that assessed the effects of bariatric surgery on diabetes for patients with BMI < 35 kg/m2. This review included a variety of bariatric procedures (Table 2) including investigational procedures such as duodenal-jejunal bypass. There were 357 patients included in the analysis which had a small number of patients with long-term follow-up and the majority with short- and medium-term follow-up. According to the weighted mean difference calculation, bariatric surgery in this population led to 5.18 kg/m2 of BMI lowering (95% CI, 3.79-6.57, p < 0.00001), 4.8 mmol/l decrease in fasting plasma glucose (FPG) (95% CI, 3.88-5.71 mmol/l, p < 0.00001), 2.59% decrease in HbA1c (95% CI, 2.12-3.07%, p < 0.00001), 56.67 mg/dl decrease of triglyceride levels (95% CI 11.53-101.82, p = 0.01) and 48.38 mg/dl of total cholesterol reduction (95% CI 21.08-75.68, p = 0.0005). Overall, 80.0% of the patients achieved adequate glycemic control (HbA1c < 7%) without antidiabetic medication. The studies reported a low incidence of major complications (3.2%) with no mortality. The authors conclude that bariatric surgery is effective and safe for diabetic patients with BMI < 35 kg/m2.

Observational studies

The 16 observational studies included in this review were single institution prospective or retrospective analyses of lower BMI patients. There was one retrospective multi-center review of patients with BMI < 35 that utilized the Bariatric Outcomes Longitudinal Database (BOLD). These studies reported weight loss results and comorbidity reduction consistent with what has been reported for Class 2 obesity and most included changes in glycemic control as a primary or secondary endpoint. These studies contained the range of methodological deficiencies typical of single institution case series (lack of control data, propensity to bias, and lack of information on completeness of follow-up.) Most are limited by small numbers of subjects and short-term follow-up. There was also variability in the method of weight and comorbidity reporting. Laparoscopic adjustable gastric banding, sleeve gastrectomy, gastric bypass, and biliopancreatic diversion are all represented in the current literature (Table 3). 31-46

Weight loss.

The various observational studies reported a range of weight loss for different follow-up periods. Parikh41 reported 57.9% EWL at 1 yr and 53.8% at 3 yr. Sultan32 followed 53 patients after gastric banding and reported a 69.7% EWL at 2 yr. The Italian Collaborative study33 reported 71.9 % EWL in 96 patients who had been followed-up at 5 yr after gastric banding. Choi et al reported results for patients with BMI 30-35 and comorbidities as well as BMI 35-40 without comorbidities and had an overall EWL of 42% at 18 months which was no different than their cohort of band patients who meet the current NIH criteria.35

Kakoulidis et al reported 100% EWL in 23 patients who had reached 6 months of follow-up after sleeve gastrectomy.34 Three other studies with small numbers of sleeve gastrectomy patients demonstrated significant weight loss,36, 37, 45 including a study by Lee et al that reported 69% EWL one year after LSG.

Cohen et al reported his experience with 37 Class 1 obese patients who underwent RYGB.42 There was 77% EWL in 20 patients at 36 months and 81%EWL in 9 patients at 48 months. Data collected from the BOLD registry included 109 RYGB patients with BMI < 35 kg/m2 who had 69% EWL one year after surgery. Other studies of weight loss after RYGB in this patient population consistently report BMI reduction to the mid-20’s one year after surgery.37, 38

There are two small studies demonstrating excellent weight loss after biliopancreatic diversion or duodenal switch in patients with BMI < 35 kg/m2. Importantly, patients did not have excessive weight loss after this procedures and weight stabilized at a BMI around 25 kg/m2 within a year after surgery.43, 44

Health Outcomes.

In the observational studies, all studies reported resolution or improvements of various co-morbidities, but the level of detail regarding specific comorbidities was variable. Several studies focused primarily on the effects of surgery on type 2 diabetes and evaluated remission rates based on variable definitions. All of the observational studies reported positive effects on glycemic control and diabetes remission rates consistent with reports of higher BMI patients. The majority of patient groups studied were poorly controlled diabetics with preoperative HbA1c values ranging from 8% to 10%. Other cardiovascular risk factors, when reported, improved after bariatric surgery in these observational studies.

One observational study34 measured the quality of life score using BAROS with 16 of 23 patients having an excellent or very good status. Kakoulidis reported good to excellent quality of life in 22 of 23 patients 6 months after sleeve gastrectomy.34

Adverse Events.Several observational studies reported serious adverse events. In the Italian Collaborative study33 one patient died at 20 months postoperatively from sepsis after gastric perforation in association with a dilated gastric pouch. This group also reported an 8% late reoperation rate for proximal gastric enlargements, leakage from the access port or band erosion . In the report of 79 patients undergoing sleeve gastrectomy, two patients underwent reoperation for bleeding and there was one gastric fistula with sepsis.34 In a review of the BOLD database including 109 RYGB and 109 LAGB patients with BMI < 35 kg/m2, complications rates were higher after gastric bypass (18%) compared to banding (3.3%, p<0.05). Most complications were minor (nausea, vomiting, stricture) but serious complications including anastomotic leakage, intra-abdominal bleeding, and internal hernia were reported in one patient each in the RYGB group. One LAGB patient developed a band slippage in this review.46

The Special Case of Type 2 Diabetes.

Among all of the co-morbidities caused by obesity, type 2 diabetes deserves special attention. Type 2 diabetes was estimated to be present in 36 million people in the USA in 200750 and the prevalence is increasing annually. Type 2 diabetes is strongly linked to overweight and obesity. Two large epidemiological studies, the Nurses’ Health Study51 and the Health Professionals Study52 show a direct relationship between the risk of type 2 diabetes and body weight. Type 2 diabetes is associated with major health problems including micro- and macro-vascular complications, premature death and high costs to the healthcare system.

This chronic, unremitting disease has traditionally been treated with escalating regimens of medical therapy. Lifestyle interventions including weight loss and exercise is the initial mode of therapy for many patients and when a closely monitored, intense intervention strategy is used, it can achieve modest improvements in weight loss (6.2% v. 0.9% in control group, p<0.001), glycemia (0.4% reduction in HbA1c compared to 0.1% in control group, p<0.001), fitness, and some cardiovascular risk factors if intense lifestyle interventions are maintained.53 Prevention of diabetes in high-risk adults has also been demonstrated with intense lifestyle intervention as well as medication (metformin). In the Diabetes Prevention Program, diabetes incidence ten years after randomization was reduced by 34% in the lifestyle group (who lost then regained some weight long term) and by 18 % in the metformin group (who maintained some modest weight loss) compared to placebo.54 These data do support the use of intense lifestyle interventions to achieve long-term weight loss and glycemic control in a subset of patients who have class 1 obesity or are at risk for developing diabetes. Unfortunately, intense lifestyle and behavioural interventions are often not practical or sustainable in everyday practice outside of a clinical trial.

The surgical RCT’s described above consistently demonstrated significant improvement in glycemic control and higher remission rates compared to standard or intensive medical therapy for diabetic patients with BMI < 35 kg/m2. The follow up for these RCT’s is only one or two years, however. A recently published prospective study by Cohen et al. reported longer term results in 66 severely diabetic patients (mean preoperative HbA1c of 9.7%, disease duration 12.5 years) with BMI 30-35 who underwent laparoscopic gastric bypass. The median follow-up time was 5 years (30 patients had six year follow-up) and no patients were lost to follow-up. This study reported an 88% diabetes remission rate (HbA1c < 6.5% without diabetes medication) and 11% improvement rate (HbA1c < 7%, decrease in dosage of oral medication, off insulin). No patient had excessive weight loss and no patient who achieved remission had recurrence of their diabetes during the follow-up period.31

Cost-effectiveness considerations.

Demonstration of the clinical needs and the clinical effectiveness of bariatric surgery cannot be the sole determinant for advocacy of bariatric surgery for Class I obesity. An evaluation of the economic effects is also needed. Cost-benefit analyses of obesity and of bariatric surgery are now becoming available55, 56 and the economic value of more active intervention is being debated57-59

Data from a Level 2 study supports the claims of cost-effectiveness. The RCT addressing diabetes28 was subjected to careful analysis of cost-efficacy60 and cost-effectiveness61. For cost-efficacy assessment, all within-trial costs were measured including gastric banding surgery, mitigation of complications, outpatient consultations, investigations, weight loss therapies and medications. The mean 2-year intervention cost was Australian dollar (AUD)$13,400 for the gastric banding group and AUD$3,400 for the conventional therapy group. Relative to conventional therapy, the incremental cost-effectiveness ratio (ICER), which is a measure of the additional cost to achieve an additional benefit, was AUD$16,600 per case of diabetes remitted. As the mean annual costs for maintaining a patient with type 2 diabetes in Australia and including all levels of severity and complexity is estimated to be AUD$10,900,62 an early cost saving can be anticipated. The analysis was extended to a modelled lifetime61 and assumed that the mean number of years of remission was 11.4 for surgical therapy and 2.1 for conventional therapy. It was estimated that the surgical group had increased quality-adjusted life years (15.7 versus 14.5) at lesser lifetime costs (AUD$ 98,900 versus $101,400). The authors concluded that surgically induced weight loss as a therapy for type 2 diabetes was a “dominant” intervention in that it provided health benefits with a reduced long-term health care costs.

A recent systematic review and economic evaluation of bariatric surgery for different BMI groups found that bariatric surgery was a clinically effective and cost-effective intervention for moderately to severely obese people compared with non-surgical interventions. Specifically, this analysis showed that bariatric surgery for patients with BMI 30-35 produced incremental cost-effectiveness ratios that were within the cost-effective range.55

Which bariatric surgical procedure is preferred for Class I obesity?

The decision regarding the choice of bariatric procedures must take into account the risk/benefit analysis for a particular patient as well as their preferences. In the BMI 30-35 group, and for bariatric surgery in general, there is currently no predictive method to match a particular patient with a particular operation to achieve the optimal outcome. We must therefore have frank discussions with our patients and reach a mutually agreeable option. Currently, there is high level data supporting the use of laparoscopic adjustable gastric banding, gastric bypass, and sleeve gastrectomy in this population. Compared to gastric bypass and sleeve gastrectomy, LAGB has a lower rate of early, severe postoperative complications.63, 64 The effectiveness of gastric banding, however, is clearly more dependent on the quality of follow-up than other bariatric surgical procedures and may therefore be unsuitable if good aftercare is not assured and funded.65 Additionally, there are no weight loss independent effects of gastric banding that can influence metabolic improvement and many bariatric practices may not be able to achieve the excellent weight loss results with LAGB that are reported in the literature.66 Finally, some patients are averse to having a foreign body placed around their stomach. Therefore, Roux-en-Y gastric bypass and sleeve gastrectomy should also be considered as acceptable options for this patient population, particularly for patients with poorly controlled type 2 diabetes that may benefit from the additional metabolic effects these procedures provide in addition to weight loss. The presence of other specific comorbidities, such as severe gastroesophageal reflux, may also influence the choice of procedures toward gastric bypass.67 In the final analysis, it remains up to the judgement of the treating physicians and the patient to choose the option they feel is in the patient’s best interest.

Summary and Recommendations

  1. Class I obesity is a well-defined disease that causes or exacerbates multiple other diseases, decreases the duration of life, and decreases the quality of life. The patient with Class I obesity should be recognized as deserving treatment for this disease.
  2. Current options of non-surgical treatment for Class I obesity are not generally effective in achieving a substantial and durable weight reduction.
  3. For patients with BMI 30-35 who do not achieve substantial and durable weight and comorbidity improvement with non-surgical methods, bariatric surgery should be an available option for suitable individuals. The existing cut-off of BMI which excludes those with Class 1 obesity was established arbitrarily nearly 20 years ago. There is no current justification on grounds of evidence of clinical effectiveness, cost-effectiveness, ethics or equity that this group should be excluded from life-saving treatment.
  4. Gastric banding, sleeve gastrectomy, and gastric bypass have been shown in randomized, controlled trials to be safe and effective treatment for patients with BMI 30-35 in the short and medium term. References:

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  6. Flegal KM, Carroll MD, Kit BK, et al. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. Jama; 307(5):491-7.

  7. Guh DP, Zhang W, Bansback N, et al. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 2009; 9:88.

  8. Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900,000 adults: collaborative analyses of 57 prospective studies. Lancet 2009; 373:1083-96.

  9. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes. N Engl J Med. 2012; 26:366(17):1567-76.

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  14. Ni Mhurchu C, Rodgers A, Pan WH, et al. Body mass index and cardiovascular disease in the Asia-Pacific Region: an overview of 33 cohorts involving 310 000 participants. Int J Epidemiol 2004; 33(4):751-8.

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  16. Harvie M, Hooper L, Howell AH. Central obesity and breast cancer risk: a systematic review. Obes Rev 2003; 4(3):157-73.

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  34. O’Brien PE, Dixon JB, Laurie C, et al. Treatment of mild to moderate obesity with laparoscopic adjustable gastric banding or an intensive medical program: a randomized trial. Ann Intern Med 2006; 144(9):625-33.

  35. Cohen R, Pinheiro JC, Schiavon CA, et al. Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care 2012; 35:1-9.

  36. Sultan S, Parikh M, Youn H, et al. Early U.S. outcomes after laparoscopic adjustable gastric banding in patients with a body mass index less than 35 kg/m2. Surg Endosc 2009; 23(7):1569-73.

  37. Angrisani L, Favretti F, Furbetta F, et al. Italian Group for Lap-Band System: results of multicenter study on patients with BMI < or =35 kg/m2. Obes Surg 2004; 14(3):415-8.

  38. Kakoulidis TP, Karringer A, Gloaguen T, et al. Initial results with sleeve gastrectomy for patients with class I obesity (BMI 30-35 kg/m2). Surg Obes Relat Dis 2009; 5(4):425-8.

  39. Choi J, Digiorgi M, Milone L, et al. Outcomes of laparoscopic adjustable gastric banding in patients with low body mass index. Surg Obes Relat Dis 2010; 6(4):367-71.

  40. Abbatini F, Capoccia D, Casella G, et al. Type 2 diabetes in obese patients with body mass index of 30-35 kg/m2: sleeve gastrectomy versus medical treatment. Surg Obes Relat Dis 2012; 8(1):20-4.

  41. Gianos M, Abdemur A, Fendrich I, et al. Outcomes of bariatric surgery in patients with body mass index <35 kg/m2. Surg Obes Relat Dis 2012; 8(1):25-30.

  42. Huang CK, Shabbir A, Lo CH, et al. Laparoscopic Roux-en-Y gastric bypass for the treatment of type II diabetes mellitus in Chinese patients with body mass index of 25-35. Obes Surg 2011; 21(9):1344-9.

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