Table of Contents  

Langer and Prager: Metabolic surgery – a new frontier in the treatment of diabetes mellitus

Diabetes and obesity

The rapid increase in the prevalence of obesity and morbid obesity, and consequently the increase in the prevalence of type 2 diabetes mellitus, is one of the most challenging threats for health-care systems all over the world. In 2011, the International Diabetes Federation (IDF) suggested3 that 285 million people are suffering from diabetes today, and a further increase of this number to 438 million affected people by 2030 is to be expected.4 A recent World Health Organisation (WHO) analysis warns that currently 1.5 billion people are overweight, of whom 500 million have to be classified as obese.5 Apart from some variance between different nations, a steady increase can be observed globally for body mass index (BMI) over the last few decades.5 Obesity is considered to be the primary risk factor for type 2 diabetes mellitus.6 Therefore, obesity has to be assumed to be the greatest threat for public health in our century.

Besides type 2 diabetes mellitus, obesity and morbid obesity is associated with a large number of co-morbidities such as hypertension, coronary heart disease, dyslipidaemia, hyperuricaemia, obstructive sleep apnoea, gonarthrosis, coxarthrosis and even increased risk for several types of cancer7 (e.g. colon, breast and pancreas). All these factors contribute to this health-economic problem of immense dimensions, as already today one out of five dollars spent for health care in the USA is spent for the treatment of obesity 8. In times of ongoing national and global financial crises, public health care could reach its limit soon.

Classification of obesity

Obesity is generally defined as a BMI of more than 30 kg/m2, with morbid obesity starting at a BMI of 40 kg/m2 or more. The major advantage of using the BMI as a classification tool is its general acceptance and ease of calculation, based on the easily measured body weight and height. However, its application for the assessment of the medical sequela of obesity is limited. It is abdominal obesity that increases the risk for type 2 diabetes mellitus, as demonstrated by the Nurses' Health Study,9 which followed a cohort of 43,581 women between 1986 and 1994 in the USA. The risk of developing type 2 diabetes mellitus increased linearly with an increasing waist circumference, defining abdominal obesity by a waist circumference of 102 cm or more in men and 88 cm or more in women.10 Of the given measures of obesity, such as BMI, waist-to-hip ratio and waist-to-height ratio, the waist-to-height ratio (WtHR) represents the best predictor of cardiovascular risk and mortality, as presented by Schneider et al. in 2010.11

Subcutaneous fat and visceral fat contribute equally to the BMI value. Thus, visceral obesity is underrepresented within the BMI classification. As many indications and guidelines12 for surgical intervention for the morbidly obese are based strictly on the BMI and neglect the distribution of body fat, the biological impact of visceral obesity should be taken further into account for treatment recommendations in these patients.

Besides the fact that even a modest weight loss can dramatically improve glycaemic control in obese patients with type 2 diabetes mellitus,13 it is well known that a sustained weight loss is not commonly achieved in morbidly obese patients by lifestyle modifications or medical treatment. Furthermore, many diabetes drugs, such as insulin, promote further weight gain or increase the risk for hypoglycaemia. Some promising anti-obesity drugs have even been withdrawn from the market due to adverse cardiovascular effects14 or depression.15 So the possibilities of non-surgical interventions are limited in regard to body weight loss and amelioration of the metabolic syndrome. In contrast to lifestyle modifications and medical treatment, bariatric surgery with its wide range of different procedures has proven to achieve a durable and stable weight loss with an excessive weight loss of between 47–70% depending on the chosen surgical operation.16

Bariatric procedures

Currently, Roux-en-Y gastric bypass, laparoscopic-adjustable gastric banding, biliopancreatic diversion, and sleeve gastrectomy are the most commonly performed bariatric procedures worldwide.17

Gastric bypass

By forming a small gastric pouch connected to an alimentary limb of 100–150 cm in length, the gastric bypass combines both mechanisms of weight loss surgery, restriction and mild malabsorption. Performed in a Roux-en-Y fashion comparable with the reconstruction after distal gastrectomy, Roux-en-Y gastric bypass was first performed laparoscopically in 1993 by Wittgrove et al.18 Nowadays, Roux-en-Y gastric bypass is expected to be the most commonly performed bariatric procedure in Europe. In 2009, Henry Buchwald et al. published a diabetes remission rate of 80.3% after gastric bypass19 within their meta-analysis. In a recent study by Mingrone et al.,1 all 20 patients who underwent gastric bypass in a randomised prospective study comparing gastric bypass, biliopancreatic diversion and medical diabetes treatment, were able to discontinue their diabetes drugs within15 days after surgery.

Laparoscopic-adjustable gastric banding

Without any trans-section or stapling of the stomach or gut, gastric banding is the least invasive bariatric procedure. A band is wrapped around the upper part of the stomach, creating a small gastric pouch above the band. Advantages of gastric banding are its individual adjustability to the patients demands and its reversibility, while complications occur as band slippage, band erosion, esophageal dilatation or frequent vomiting due to food intolerance. Generally, weight loss is less after laparoscopic gastric banding compared with other bariatric procedures.16 Used in a BMI range from 30 to 40 kg/m2, Dixon et al. compared laparoscopic-adjustable banding with conventional diabetes therapy and found a significantly better diabetes remission rate in the surgical group (73% cs 13%) at two years after surgery.20 Compared with other bariatric procedures, laparoscopic-adjustable gastric banding has only minor influence on gut hormones.21

Sleeve gastrectomy

Sleeve gastrectomy was initially developed as part of the biliopancreatic diversion with duodenal switch (DS), adding restriction to the strictly malabsorptive biliopancreatic diversion. As a sole bariatric procedure it was introduced as the first part of a two-step laparoscopic gastric bypass in ‘super-super obese’ (i.e. BMI > 60kg/m2) patients.22 With a rapidly increasing number of operations performed, sleeve gastrectomy has gained enormous popularity in the bariatric world within the last five years. In 2008, sleeve gastrectomy already represented 5.4% of all bariatric procedures performed worldwide in 2008 as presented by Buchwald et al.,17 and case numbers are expected further to increase. This popularity is mainly caused by short-term results for weight loss2325 and by a wide range of advantages compared with the surgically technically more demanding Roux-en-Y gastric bypass: no dumping syndrome is expected after sleeve gastrectomy and the biliary tract remains accessible by endoscopic retrograde cholangiopancreaticography (ERCP). Furthermore, nutrient deficiencies seem less likely after sleeve gastrectomy than after Roux-en-Y gastric bypass.26,27 In 2008, Vidal et al. 28 compared diabetes remission in gastric bypass and sleeve gastrectomy patients, finding similar remission rates (84.6% vs 84.6%). In their recent publication,2 Schauer et al. found that 37% of the patients who underwent sleeve gastrectomy reached a glycated haemoglobin (HbA1c) of < 6.0% within one year, whereas the mean HbA1c dropped from 9.5% to 6.6% in this study including 50 sleeve gastrectomy patients.

Biliopancreatic diversion

The highest diabetes remission rates are found for the biliopancreatic diversion, developed by Nicola Scopinaro in 1976.29 Combining a distal gastrectomy with a bypass, resulting in a common limb length of 50–75 cm, results in malabsorption. After division of the jejunum at 250-cm proximal to the ileocoecal valve, the distal part of the jejunum is anastomosed to the stomach and the proximal part of the jejunum is anastomosed to the ileum 50–75-cm proximal to the ileocoecal valve. Whereas malabsorption is achieved by reducing the absorptive surface of the gut, there is only minor restriction depending on the size of the stomach left in place (200–500 ml). Owing to its malabsorptive effect, the most common complications are diarrhoea, anaemia, protein deficiency, iron deficiency and flatulence.30 Besides the stable weight loss results in the long-term follow-up, Scopinaro published in 200531 a 10-year recovery rate of hyperglycaemia of 97% after biliopancreatic diversion. Patients who underwent biliopancreatic diversion were able to discontinue their diabetes drugs as fast as within 15 days after surgery, as recently presented by Mingrone et al.1

Selection criteria for surgery

Back in 1991, the US National Institutes of Health (NIH) published guidelines for the application of bariatric surgery, recommending surgery for patients with a BMI of 40 or above as well as surgery for patients with a BMI of 35 and above suffering from obesity-associated comorbidities such as hypertension and type 2 diabetes mellitus.12 Despite the fact that the BMI levels set within these guidelines for recommending surgery were never confirmed by randomized clinical trials, these 21-year-old recommendations still form the basis for all patient selection criteria in bariatric surgery. With a growing scientific evidence for lower BMI indications in the diabetic obese, ‘metabolic’ instead of ‘bariatric’ indications should be should be integrated into the treatment algorithm of type 2 diabetes mellitus.

Mechanisms of surgical intervention

For decades, the mechanism of weight loss after bariatric surgery was understood and simplified strictly to only two pathways. By reducing the volume of the stomach, restriction is achieved, limiting food uptake and therefore also limiting the amount of food entering the intestine. Thus, the reduced number of up taken calories leads to a negative calorie balance. On the other side, the surgical reduction of the functional absorptive intestinal length leads to malabsorption, with less calories absorbed from the intestine. Whereas some bariatric procedures were based only on restriction (e.g. the now-abandoned vertical banded gastroplasty and laparoscopic-adjustable gastric banding) or malabsorption (biliopancreatic diversion), the gastric bypass and the duodenal switch combine these two major principles for achieving weight loss.

Gut hormones and adipocytokines

Starting with leptin32 in 1994, the discovery of adipocyte-derived substances (adipocytokines) and of gut-derived hormones regulating satiety, hunger, intestinal motility and function, and interacting with glycaemic control, widened the horizon for understanding the many functional effects of bariatric surgery not explicable by restriction and malabsorption alone. The majority of adipocytokines derive from visceral fat and play essential roles in chronic pathogenic states like inflammation, atherosclerosis, thrombosis, diabetes and hypertension.33 Bariatric surgery not only reduces the visceral fat mass, but also reduces the secretion of proinflammatory adipocytokines and increases the secretion of anti-inflammatory adipocytokines.3439

Peptide YY (PYY), the ‘ileal brake’ hormone inhibiting gastrointestinal motility and mediating satiety, is produced by the L cells in the Ileum, colon and rectum. In obese individuals, PYY is found to be decreased,40 whereas gastric bypass surgery leads to increased levels of PYY within a few days after surgery.41,42

Glucagon-like peptide 1 (GLP-1) is secreted by the ileal L cells as a response to a meal. GLP-1 reduces appetite and stimulates insulin secretion (‘incretin’) while suppressing glucagon secretion. Furthermore, it slows gastric emptying. In patients with type 2 diabetes mellitus reduced levels of GLP-1 are found,43 whereas GLP-1 levels immediately increase after gastric bypass surgery.41,44 Starting with exenatide, a growing range of GLP-1 agonists (liraglutide, lixisenatide, albiglutide and taspoglutide) have been introduced into medical diabetes therapy.45

Ghrelin is a potent 28-amino-acid peptide orexigenic hormone, discovered in 1999,46 acting as the natural ligand of the growth hormone secretagogue receptor. Approximately two-thirds are released by the stomach, mainly the fundus. Ghrelin enhances appetite and food intake by 28%. Furthermore, it leads to an increase in cortisol, adrenaline and growth hormone – as well as a decrease in insulin secretion.47 Ghrelin is secreted in a diurnal pattern and is alleviated after gastric bypass.4849 Sleeve gastrectomy leads to permanently reduced ghrelin levels,50 whereas gastric banding and diet result in an increase in Ghrelin concentration.51 Prolonged decrease of ghrelin levels could contribute to a reduction in the feeling of hunger.52 Ghrelin and PYY 3–36 act as short-term regulators of hunger and satiety, whereas insulin and leptin are more reflective of nutritional status and are long-term regulators (‘Yin and Yang of nutrition’).53

Metabolic surgery

In 2004, Buchwald et al.16 presented diabetes remission rates for bariatric surgery, analysing data from 136 studies including 22,094 patients. Diabetes completely resolved in 76.8% of the patients and resolved or improved in 86%. Thus, bariatric surgery no longer focused on weight-loss results alone, but also on metabolic improvements. With the proven efficacy of bariatric surgery for not only a stable and lasting profound weight reduction, but also metabolic changes such as glycaemic control, diabetes remission, improved lipid levels and reduced hypertension, two major surgical associations – the International Federation for the Surgery of Obesity and the American Society of Bariatric Surgeons – included the term ‘metabolic surgery’ in their name in 2007, becoming respectively the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) and the American Society of Metabolic and Bariatric Surgery (ASMBS).

Obesity and life expectancy

Obesity (BMI 30–35 kg/m2) reduces not only the quality of life, but also the life expectancy for non-smoking or smoking women, by a mean of 7.1 kg/m2 or 13.3 years, respectively.54 For nonsmoking or smoking obese men, calculations reveal a tremendous lifetime reduction of 5.8 kg/m2 or 13.7 years, respectively.

Bariatric surgery and mortality

As bariatric surgery adds potential operative danger to morbidly obese patients, studies focusing on mortality are of great interest, comparing the mortality risk of patients who underwent surgery with that of non-operated morbidly obese patients. In 2007 Adams et al. published the results from an analysis including 7925 patients, focusing on long-term mortality after gastric bypass surgery.55 Disease-specific mortality could be reduced by bariatric surgery for diabetes by 92%, for coronary heart disease by 56% and for cancer by 60%. Although the Swedish Obese Subjects (SOS) study56 revealed a reduction of all-cause mortality of 22% after 11 years, Adams et al.'s analysis found a longterm all-cause mortality reduction of 40% for the surgical patients. Thus, bariatric surgery not only affects diabetes and its associated co-morbidities such as hypertension, sleep apnoea or arthritis, but also leads to a general reduction in mortality. Many studies further demonstrate that besides weight loss and co-morbidities, the quality of life is also substantially improved after bariatric and metabolic surgery.57,58

Bariatric surgery: numbers and trends

Comparing data from 2003 with 2008, a rapid increase in the number of bariatric procedures performed worldwide can be observed, with 146,301 operations in 2003 rising to 344,221 procedures performed by 1625 surgeons in 2008.17 Currently, Roux-en-Y gastric bypass, laparoscopic-adjustable gastric banding, biliopancreatic diversion and sleeve gastrectomy are the most commonly performed and accepted bariatric procedures. Whereas similar overall growth rates for bariatric procedures could be observed between 2003 and 2008 for Europe (+97%) and the USA (+113%), the types of procedures chosen show an opposing trend when comparing the USA and Europe. The number of gastric bypasses performed in the USA decreased from 85% in 2003 to 51% in 2008, with laparoscopic-adjustable gastric banding rapidly increasing from 9% to 44%. Over the same five years gastric banding lost its predominance in Europe, dropping from 64% to 43% of all operations, whereas the gastric bypass increased from 11% to 39% of all bariatric procedures performed in Europe in 2008.

Diabetes remission rates

Analysing the results from gastric bypass, gastric banding and biliopancreatic diversion, the different weight-loss mechanisms and different influences on gut hormone regulations leads to a variability in weight-loss extent and diabetes remission rates. Many factors influence the extent of diabetes remission after bariatric surgery: the choice of bariatric procedure, the duration of diabetes prior to surgery, the pre-surgical diabetes medication (insulin vs medical treatment) and the patient's age. In 2009, Buchwald et al.19 published diabetes remission rates for the most commonly performed bariatric procedures – gastric bypass, gastric banding and biliopancreatic diversion – as 80.3%, 56.7% and 95.1%, respectively, analysing data from 621 studies including 135,246 patients. Generally, the more weight loss that can be achieved by a surgical procedure, the higher the probability for a diabetes remission after surgery – making weight loss still the strongest factor in diabetes remission.

Prospective randomized studies

To assess the potential role of bariatric surgery in the treatment algorithm of type 2 diabetes mellitus in the obese, prospective randomized studies are needed. However, it is difficult to randomize patients into two interventions like bariatric surgery and medical treatment, as the extent of intervention is completely different. With two studies published this year in the New England Medical Journal, we gain more comparative information about the efficacy of these both different treatment modalities.1,2

Published in 2012 in the New England Journal of Medicine, Mingrone et al. 1 compared bariatric surgery with conventional medical therapy, including 60 patients with a BMI of > 35 kg/m2, and a history of type 2 diabetes mellitus of at least five years. Twenty patients were assigned to medical therapy, 20 underwent gastric bypass surgery and in 20 patients was performed. The primary endpoint was the rate of diabetes remission at two years, defined as a fasting glucose level of < 100 mg/dl (5.6 mmol per litre) and HbA1c levels of < 6.5% in the absence of pharmacological therapy. After a follow-up of two years, no diabetes remission was observed in the medical therapy group, whereas diabetes remission was found in 74% of the bypass patients and in 95% of the patients who underwent biliopancreatic diversion. The HbA1c level was found to be a mean of 7.69% for the medical group, whereas surgery decreased the HbA1c level to a mean of 6.35% after gastric bypass and 4.95% after biliopancreatic diversion. Excess weight loss was similar in both surgical groups, with mean 69% and 68%, respectively, whereas only 9% excess weight loss was achieved by the medically treated patients. Furthermore, surgery led to instant glycaemic control, as all gastric bypass and biliopancreatic diversion patients were able to discontinue their pharmacological diabetes treatment within only 15 days after the operation.

The second randomized prospective study focusing on this topic was entitled ‘Bariatric surgery versus intensive medical therapy in obese patients with diabetes’, published by Schauer et al.2 in the New England Journal of Medicine in 2012. The authors included 150 patients with a BMI of 27–43 kg/m2 in this study comparing medical diabetes therapy with gastric bypass or sleeve gastrectomy. The primary endpoint of this study was an HbA1c level of 6.0% or less at 12 months after treatment. Fifty patients each were randomised to receive gastric bypass surgery, sleeve gastrectomy or intensive medical treatment. The duration of diabetes was more than eight years, comparable in all groups. In each group, 44% of the patients used insulin. Focusing on the primary endpoint, 12% of the medically treated patients reached this goal, whereas 42% of the bypass patients and 37% of the sleeve patients had HbA1c levels of < 6.0%. The mean HbA1c levels decreased in all three groups: from 8.9% to 7.5% in the medical group, from 9.3% to 6.4% in the bypass group and from 9.5% to 6.6% after sleeve gastrectomy. Insulin use remained high in the medical treatment group (38%) after 12 months, although a remarkable decrease in insulin use was found in the gastric bypass group (4%) and the sleeve gastrectomy group (8%). As expected, weight loss was better in the surgical groups, with a mean body weight loss of 27% and 24% after gastric bypass and sleeve respectively, compared with mean 5% body weight loss after medical treatment alone. Furthermore, the use of drugs to lower glucose, lipid and blood pressure significantly decreased after gastric bypass and sleeve gastrectomy, whereas medication increased in the medically treated patients.

Focusing on laparoscopic gastric banding versus medical treatment for type 2 diabetes mellitus, Dixon et al. published in 2008 their study entitled ‘Adjustable gastric banding and conventional therapy for type 2 diabetes’ including 60 patients with a BMI of 30–40 kg/m2 and a history of diabetes of less than two years.20 Thirty patients were randomized into surgical and 30 patients into medical treatment. Diabetes remission was found in 73% of the gastric banding patients and in 13% patients who received best medical diabetes care, which included a dietitian, general physician and diabetes educator with frequently scheduled follow-up visits. Comparing diabetes remission results from this study with the results of Mingrone et al.1 and Schauer et al.,2 the gastric banding patients included in this study had a shorter history of diabetes and a lower mean BMI, expectedly resulting in a better diabetes remission rate. Generally, biliopancreatic diversion and gastric bypass achieve a better diabetes remission rate than laparoscopic gastric banding, as shown in the metaanalysis of Buchwald et al.19


Metabolic surgery affects not only on diabetes remission, but also the many diabetes-associated co-morbidities like hypertension, hypercholesterolaemia, hypertrigyceridaemia and hyperuricaemia, summarized by the metabolic syndrome.

In 2004, Sjöstrom et al. published ‘Lifestyle, diabetes and cardiovascular risk factors 10 years after bariatric surgery’ in the New England Journal of Medicine, presenting the 10-year data from the SOS study.56 In this analysis, the 2-year and 10-year recovery rates from diabetes, as well from hypertriglyceridaemia, low levels of high-density lipoprotein-cholesterol, hypertension and hyperuricaemia, were more favourable in the surgically treated group. Interestingly, this study revealed better two-year rates for diabetes remission (72%) compared with 10-year data36. The patients in the SOS study not only underwent gastric bypass (5%) or gastric banding (24%), but in the majority of the patients a vertical banded gastroplasty (71%) was also performed. In all the patients, a weight regain was observed explaining the 10-year outcome. Nowadays vertical-banded gastroplasty has been abandoned owing to frequent staple-line disruption in the longer term, subsequently leading to significant weight regain.59

In their 2004 meta-analysis16 including 136 studies with a total of 22,094 patients, Buchwald et al. found a diabetes remission rate of 76% for all different surgical procedures, whereas hyperlipidaemia improved in 76% of the patients. Hypertension was found to resolve in 62% of the patients and obstructive sleep apnoea was resolved in 85%. Thus, bariatric surgery leads to an dramatic improvement in obesity-associated co-morbidities, aside from the effects on type 2 diabetes mellitus itself.

Lower body mass index indications

With the proven success in morbidly obese patients, bariatric procedures were performed even in patients with a lower BMI, focusing more on the metabolic effects of surgery than weight reduction itself. In 2006, O'Brien et al.60 published the results of a study including patients with a BMI of 30–35 randomized for laparoscopic gastric banding or a non-surgical program with a very-low-calorie (Optifast) diet, pharmacotherapy (orlistat) and lifestyle modifications. Metabolic syndrome was reduced from 38% of the patients prior to surgery to 3% postoperatively. Another study published by Dixon et al. focused on laparoscopic-adjustable gastric banding in low-BMI (30–40 kg/m2) obese patients.20 In the 30 patients randomized for surgery, a diabetes remission rate of 73% was found. Cohen et al. 61 performed gastric bypass surgery in low-BMI patients with type 2 diabetes mellitus. The BMI ranged from 32 to 35 kg/m2. All 37 patients enrolled into this study were able to discontinue their oral anti-diabetic medication postoperatively, whereas 36 of the 37 patients achieved a total remission of all their co-morbidities. Nicola Scopinaro and coworkers were able to demonstrate a reduction in HbA1c levels from 9.3% to 6.3% in 30 patients after biliopancreatic diversion with BMI from 25–35 kg/m2.62 In recent years, several new operations (omentectomy, duodeno–jejunal bypass63 and ileal transposition with or without sleeve gastrectomy64) have been designed to optimize effects on gut hormones and adipocytokines. Although they show promising results, it is too early to recommend their application outside of study protocols.

Future aspects of metabolic surgery

Metabolic surgery has proved to be an effective therapy for morbidly obese patients with type 2 diabetes mellitus. With a long duration of diabetes being the strongest predictor of postoperative non-remission of diabetes,65,66 these patients should be considered to be too late for surgery. Furthermore, BMI should not be considered the best measure of obesity for the indication for surgery. Within the near future, metabolic surgery could be considered an alternative treatment option in patients with a BMI between 30 and 35 kg/m2 when diabetes cannot be controlled adequately by an optimal medical regimen, especially in the presence of other major cardiovascular risk factors, according to the 2011 statement of the IDF.3



Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 2012; 366:1577–85.


Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 2012; 366:1567–76.


Dixon JB, Zimmet P, Alberti KG, Rubino F. Bariatric surgery: an IDF statement for obese type 2 diabetes. Arq Bras Endocrinol Metabol 2011; 55:367–82.


Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87:4–14.


Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 2011; 377:557–67.


Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2009; 52:17–30.


Basen-Engquist K, Chang M. Obesity and cancer risk: recent review and evidence. Curr Oncol Rep 2011; 13:71–6.


Cawley J, Meyerhoefer C. The medical care costs of obesity: an instrumental variables approach. J Health Econ 2011; 31:219–30.


Carey VJ, Walters EE, Colditz GA, et al. Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women. The Nurses' Health Study. Am J Epidemiol 1997; 145:614–19.


Janssen I, Katzmarzyk PT, Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health guidelines. Arch Intern Med 2002; 162:2074–9.


Schneider HJ, Friedrich N, Klotsche J, et al. The predictive value of different measures of obesity for incident cardiovascular events and mortality. J Clin Endocrinol Metab 2010; 95:1777–85.


National Institutes of Health. Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement. Am J Clin Nutr 1992; 55:615S–9S.


Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalization of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011; 54:2506–14.


Scheen AJ. Cardiovascular risk-benefit profile of sibutramine. Am J Cardiovasc Drugs 2010; 10:321–34.


Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomized trials. Lancet 2007; 370:1706–13.


Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004; 292:1724–37.


Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2008. Obes Surg 2009; 19:1605–11.


Wittgrove AC, Clark GW, Tremblay LJ. Laparoscopic gastric bypass, Roux-en-Y: preliminary report of five cases. Obes Surg 1994; 4:353–7.


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; 122:248–56.e5.


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; 299:316–23.


Shak JR, Roper J, Perez-Perez GI, et al. The effect of laparoscopic gastric banding surgery on plasma levels of appetite-control, insulinotropic, and digestive hormones. Obes Surg 2008; 18:1089–96.


Regan JP, Inabnet WB, Gagner M, Pomp A. Early experience with two-stage laparoscopic Roux-en-Y gastric bypass as an alternative in the super-super obese patient. Obes Surg 2003; 13:861–4.


Jacobs M, Bisland W, Gomez E, et al. Laparoscopic sleeve gastrectomy: a retrospective review of 1- and 2-year results. Surg Endosc 2009; 24:781–5.


Menenakos E, Stanou KM, Albanopoulos K, Papailiou J, Theodorou D, Leandros E. Laparoscopic sleeve gastrectomy performed with intent to treat morbid obesity: a prospective single-centre study of 261 patients with a median follow-up of 1 year. Obes Surg 2010; 20:276–82.


Nocca D, Krawczykowsky D, Bomans B, et al. A prospective multicenter study of 163 sleeve gastrectomies: results at 1 and 2 years. Obes Surg 2008; 18:560–5.


Gehrer S, Kern B, Peters T, Christoffel-Courtin C, Peterli R. Fewer nutrient deficiencies after laparoscopic sleeve gastrectomy (LSG) than after laparoscopic Roux-Y-gastric bypass (LRYGB)-a prospective study. Obes Surg 2010; 20:447–53.


Hakeam HA, O'Regan PJ, Salem AM, Bamehriz FY, Eldali AM. Impact of laparoscopic sleeve gastrectomy on iron indices: 1 year follow-up. Obes Surg 2009; 19:1491–6.


Vidal J, Ibarzabal A, Romero F, et al. Type 2 diabetes mellitus and the metabolic syndrome following sleeve gastrectomy in severely obese subjects. Obes Surg 2008; 18:1077–82.


Scopinaro N, Gianetta E, Civalleri D, Bonalumi U, Bachi V. Bilio-pancreatic bypass for obesity: II. Initial experience in man. Br J Surg 1979; 66:618–20.


Scopinaro N, Gianetta E, Adami GF, et al. Biliopancreatic diversion for obesity at eighteen years. Surgery 1996; 119:261–8.


Scopinaro N, Marinari GM, Camerini GB, Papadia FS, Adami GF. Specific effects of biliopancreatic diversion on the major components of metabolic syndrome: a longterm follow-up study. Diabetes Care 2005; 28:2406–11.


Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395:763–70.


Lago F, Dieguez C, Gomez-Reino J, Gualillo O. Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol 2007; 3:716–24.


Ballantyne GH, Gumbs A, Modlin IM. Changes in insulin resistance following bariatric surgery and the adipoinsular axis: role of the adipocytokines, leptin, adiponectin and resistin. Obes Surg 2005; 15:692–9.


Garcia de la Torre N, Rubio MA, Bordiu E, et al. Effects of weight loss after bariatric surgery for morbid obesity on vascular endothelial growth factor-A, adipocytokines, and insulin. J Clin Endocrinol Metab 2008; 93:4276–81.


Manco M, Fernandez-Real JM, Equitani F, et al. Effect of massive weight loss on inflammatory adipocytokines and the innate immune system in morbidly obese women. J Clin Endocrinol Metab 2007; 92:483–90.


Haider DG, Schindler K, Bohdjalian A, et al. Plasma adipocyte and epidermal fatty acid binding protein is reduced after weight loss in obesity. Diabetes Obes Metab 2007; 9:761–3.


Haider DG, Schindler K, Prager G, et al. Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrinol Metab 2007; 92:1168–71.


Simon I, Escote X, Vilarrasa N, et al. Adipocyte fatty acid-binding protein as a determinant of insulin sensitivity in morbid-obese women. Obesity 2009; 17:1124–8.


Huda MS, Wilding JP, Pinkney JH. Gut peptides and the regulation of appetite. Obes Rev 2006; 7:163–82.


le Roux CW, Welbourn R, Werling M, et al. Gut hormones as mediators of appetite and weight loss after Rouxen-Y gastric bypass. Ann Surg 2007; 246:780–5.


Chan JL, Mun EC, Stoyneva V, Mantzoros CS, Goldfine AB. Peptide YY levels are elevated after gastric bypass surgery. Obesity 2006; 14:194–8.


Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001; 86:3717–23.


Morinigo R, Moize V, Musri M, et al. J Clin Endocrinol Metab 2006; 91:1735–40.


Garber AJ. Novel GLP-1 receptor agonists for diabetes. Expert Opin Investig Drugs 2012; 21:45–57.


Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402:656–60.


Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407:908–13.


Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001; 50:1714–19.


Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346:1623–30.


Langer FB, Reza Hoda MA, Bohdjalian A, et al. Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels. Obes Surg 2005; 15:1024–9.


Schindler K, Prager G, Ballaban T, et al. Impact of laparoscopic adjustable gastric banding on plasma ghrelin, eating behaviour and body weight. Eur J Clin Invest 2004; 34:549–54.


Langer FB, Bohdjalian A, Shakeri-Manesch S, et al. Eating behaviour in laparoscopic sleeve gastrectomy – correlation between plasma gherlin levels and hunger. Eur Surg 2008; 40:1–5.


Marx J. Cellular warriors at the battle of the bulge. Science 2003; 299:846–9.


Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med 2003; 138:24–32.


Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med 2007; 357:753–61.


Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351:2683–93.


Muller MK, Wenger C, Schiesser M, Clavien PA, Weber M. Quality of life after bariatric surgery – a comparative study of laparoscopic banding vs. bypass. Obes Surg 2008; 18:1551–7.


Mamplekou E, Komesidou V, Bissias C, Papakonstantinou A, Melissas J. Psychological condition and quality of life in patients with morbid obesity before and after surgical weight loss. Obes Surg 2005; 15:1177–84.


Olbers T, Lonroth H, Dalenback J, Haglind E, Lundell L. Laparoscopic vertical banded gastroplasty–an effective long-term therapy for morbidly obese patients? Obes Surg 2001; 11:726–30.


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; 144:625–33.


Cohen R, Pinheiro JS, Correa JL, Schiavon CA. Laparoscopic Roux-en-Y gastric bypass for BMI < 35 kg/m2: a tailored approach. Surg Obes Relat Dis 2006; 2:401–4.


Scopinaro N, Adami GF, Papadia FS, et al. Effects of biliopanceratic diversion on type 2 diabetes in patients with BMI 25 to 35. Ann Surg 2011; 253:699–703.


Del Genio G, Gagner M, Cuenca-Abente F, et al. Laparoscopic sleeve gastrectomy with duodeno-jejunal bypass: a new surgical procedure for weight control. Feasibility and safety study in a porcine model. Obes Surg 2008; 18:1263–7.


Gagner M. Surgical treatment of nonseverely obese patients with type 2 diabetes mellitus: sleeve gastrectomy with ileal transposition (SGIT) is the same as the neuroendocrine brake (NEB) procedure or ileal interposition associated with sleeve gastrectomy (II-SG), but ileal interposition with diverted sleeve gastrectomy (II-DSG) is the same as duodenal switch. Surg Endosc 2011; 25:655–6.


Rubino F, Schauer PR, Kaplan LM, Cummings DE. Metabolic surgery to treat type 2 diabetes: clinical outcomes and mechanisms of action. Annu Rev Med 2010; 61:393–411.


Casella G, Abbatini F, Cali B, Capoccia D, Leonetti F, Basso N. Ten-year duration of type 2 diabetes as prognostic factor for remission after sleeve gastrectomy. Surg Obes Relat Dis 2011; 7:697–702.

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