Bariatric Surgery as Metabolic Surgery for Diabetic

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Bariatric Surgery as Metabolic Surgery for Diabetic Patients Aristotelis V. Kalyvas1,#, Konstantinos Vlachos*,1,2,#, Mohammed Abu-Amara3, John S Sampalis2 and Georgios Glantzounis1 1

Department of Surgery, University Hospital of Ioannina, Greece; 2Department of Surgery, McGill University, Montreal, Quebec, Canada; 3Department of Surgery, Royal Free hospital, London, UK Abstract: The recent increase in the prevalence of obesity seems to be responsible for the increase in T2 Diabetes Mellitus (T2DM). At present around 50 % of T2DM patients are obese and this percentage appears set to increase in the near future. Successful management of T2DM in obese patients is a complicated task, as many parameters such as blood pressure, LDL-cholesterol levels have to be adequately controlled along with HbA1c levels. There is a substantial amount of evidence showing that bariatric surgery achieves long term remission of diabetes in the majority of obese patients and improves significantly comorbidities associated with DM such as dyslipidemia, hypertension, and obstructive sleep apnea. It seems that early surgical intervention before irreversible b-cell damage has occurred, increases the chances of long term T2DM resolution. However, at present a very small percentage (< 2%) of obese patients with T2DM is treated surgically. The present review focuses on the efficacy and safety of the main bariatric procedures. It also emphasizes the mechanism with which bariatric surgery exerts its therapeutic effect and on the long term results on T2DM remission.

Keywords: Bariatric surgery, metabolic surgery, obesity, Type 2 Diabetes Mellitus, remission of diabetes, safety.

1. INTRODUCTION The term «bariatric surgery» is derived etymologically from the Greek words “baros”, meaning “weight”, and “iatriki”, meaning “medicine”. It is a term that originates back in the 1950s and is used to describe a surgical procedure which aims at the reduction of weight, for the treatment of obesity. Over recent decades, obesity has been increasing rapidly, and nowadays it has become not only a medical, but also a sociological and economic problem of pandemic proportions. According to data from the World Health Organization, more than 500 million people were obese in 2008, and more than 700 million people are expected to reach obesity by 2015 [1]. The prevalence of obesity nearly doubled between 1980 and 2008. What is also worth noting is that obesity, once associated with high-income countries, is now also prevalent in middle-income or even developing countries and appears regardless of gender, age, ethnicity or educational level. This can be attributed to a large extent to the adoption of westernized lifestyles, although the complex interaction of environment and human behavior with the genetic predisposition should not be ignored. That means that obesogenic habits such as sedentary behavior and consumption of high-calories but low quality food are the main causes that result in an increasing imbalance between energy intake and energy expenditure [1]. Social and economic development as well as policies in the areas of agriculture, transport, urban planning, environment, education, food processing, distribution and marketing influence dietary habits and preferences as well as physical activity patterns, leading to a steady rise in the prevalence of obesity. Statistics from the WHO suggest that globally, 44% of diabetes, 23% of ischaemic heart disease and 7–41% of certain cancers are attributable to overweight and obesity and 2.8 million people die every year as a result of being obese. Taking into account the obvious consequences, namely the related comorbidities and the alarming rise in mortality and morbidity rates, as well as the less obvious repercussions such as the reduced work capacity and the increased costs brought upon the national health systems (obese *Address correspondence to this author at the Department of Surgery, School of Medicine, University of Ioannina, 45110, Ioannina, Greece; E-mail: [email protected] #

Authors equally contributed. 1381-6128/14 $58.00+.00

individuals were found to have medical costs that were approximately 30-42% greater than their normal weight peers) [2, 3] it is not an overstatement to say that obesity constitutes a major public health issue and an international health threat. Unfortunately, obesity not only represents a serious worldwide health crisis, but it also has a number of aspects that need to be tackled. Obesity is associated with several serious conditions including coronary artery disease, liver disease, obstructive sleep apnea, osteoarthritis, depression and last but not least Type 2 Diabetes Mellitus (T2DM). As a result of the increased comorbidities that obese patients develop, obesity is associated with an increased risk of death. Studies have shown that the cardiovascular mortality is 50% greater in obese patients and 90% greater in severely obese patients when compared to those of average weight [4]. As far as T2DM patients are concerned, 50% are obese and by 2030 they are expected to reach 438 million, according to the predictions of the International Diabetes Federation (IDF) [5]. It seems that the increase in the prevalence of obesity is responsible for the recent increase in T2DM. Obesity exacerbates metabolic and cardiovascular risk factors such as insulin resistance, dyslipidemia and hypertension [6]. The combination of these conditions and the related elevated risk of diabetes and cardiovascular disease have been described since the 1950s as the “metabolic syndrome” (former X syndrome) and even though its existence as a distinct entity is challenged by some, the link between the aforementioned factors cannot be questioned. Therefore, it can be concluded that an intervention on the combination of diabetes and obesity - often referred to as “diabesity”- is an imperative, but also challenging therapeutic target. So far, the predominant therapeutic approach to T2DM has been the conventional one, including counseling of obese patients on a combination of diet, lifestyle, goals of weight loss and pharmacological therapy with anti-diabetic agents [7]. Unfortunately, the results of conventional therapy are often discouraging [8]. Traditionally used drugs such as sulphonylureas and metformin, and newer ones such as the glitazones and glucagon-like peptide 1 agonists, all have a role but do not provide adequate control in many cases [9, 10]. Stepwise algorithms of treatment can lead to treatment failure [11] and the adoption of a more aggressive pharmaceutical approach has the risk of causing weight gain, a prospect that in

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the cases of obese patients must be avoided [12]. Moreover, in view of obesity and T2DM as parts of an even wider metabolic disorder, achieving an optimal glycaemic state (HbA1c 35 kg/m2, with sustainable weight loss effects and long-term control of co-morbidities. While BPD results in greater weight loss and resolution of comorbidities compared to other bariatric surgical procedures, it produces the highest mortality rate. After BPD close nutritional surveillance and supplementation are mandatory. Basics of the Surgical Technique (Fig. 1D & E) Laparoscopic BPD is a complex but feasible surgical bariatric procedure. Typically the technique is performed by dividing the small bowel 250 cm above the ileo-cecal valve with a stapler, and then forming a bilio-pancreatic limb by joining the bowel proximal to the transection to a point 100 cm above the ileo-cecal valve. The bowel distal to the transection is elevated to form an alimentary limb to the upper abdomen. Sleeve resection creates a gastric tube of approximately 100 cm3 (smaller than the standard sleeve gastrectomy). The duodenum is divided 3 cm distal to the pylorus, and duodeno-ileostomy establishes continuity of the alimentary limb.


Kalyvas et al.

Fig. (1). Common bariatric surgical procedures. (A) Laparoscopic Adjustable Gastric Banding (B) Laparoscopic Sleeve Gastrectomy (C) Roux-en-Y Gastric Banding (D) Billiopancreatic Diversion (E) Billiopancreatic Diversion with Duodenal Switch.

Limb length affects not only the weight loss but also determines the possible complications. A limb that is too long will not deliver an adequate weight loss effect, whereas one too short limb will produce exhaustive diarrhea and nutritional complications. Gastric remnant size should provide some restriction but not prevent the initial phase of protein digestion. 2.3. Risks of Bariatric Surgery (Table 1) In general, morbidity and mortality which accompany bariatric surgery are low. The overall mortality varies from 0.1% to 1% depending on the bariatric procedure. In particular, the 30 day mortality is 0.1 %, 0.5 % and 1.1% for restrictive procedures, gastric bypass and biliopancreatic diversion with a duodenal switch, respectively [48, 49]. Complications can be categorized into two groups: short-term and long-term complications. Short-term complications comprise wound infections (2.3%), staple line leaks (3%), haemorrhage (1.7%) and pulmonary manifestetions (2.2%) [15]. Long-term complications include osteoporosis, vitamin and mineral insufficiencies, and hypoglycaemia. The American Association of Clinical Endocrinologists, The Obesity Society and the American Society for Metabolic and Bariatric Surgery have published clinical guidelines for the potential prevention and management of these complications [50]. Certain complications have a greater affinity for specific surgical approaches. Nutritional complications- most often severe- such as hypoalbuminaemia and insufficiencies in vitamin D and calcium, are most routinely noted with BPD. Due to its possible negative effect on cardiovascular disease -as indicated in the current literature- and its high prevalence in BPD, Vitamin D insufficiency is considered a highly undesirable complication and for this reason BPD should, generally, be avoided. 2.4. Indications for Bariatric Surgery in Morbid Obesity and T2DM besity has been associated for several years with a wide spectrum of comorbidities. As well as T2DM many others comorbidities are present in the context of obesity. Some of these are hyperlipi-

demia, hypertension, obstructive sleep apnea, heart disease, liver disease, stroke, asthma, back and lower extremity weight-bearing degenerative problems [51, 52]. Unfortunately, the effectiveness of diet therapy and several pharmaceutical agents seem to be restricted to treating obesity in the long term . While this can be explained by the inability of conservative treatment to maintain reduced body weight, a plethora of controlled and uncontrolled cohort studies demonstrate that surgery delivers the most sustainable weight loss effect [53]. Furthermore, the American Gastroenterological Association’s (AGA) medical position statement on obesity considers bariatric surgery to be the most effective treatment for achieving long-term weight loss [54]. So, which patients should be offered bariatric surgery? In 1991, the National Institutes of Health established guidelines for the surgical therapy of morbid obesity [55]. According to these guidelines, bariatric surgery was considered appropriate for patients with a BMI greater than 40 kg/m2 or with BMI greater than 35 kg/m2 combined with severe obesity-related comorbidities, such as T2DM, hypertension, and cardiovascular disease [55]. Since then, many institutions have tried to produce their own guidelines in a national or international level. Some of these are the International Diabetes Federation [15] (2011), the American Diabetes Association [56] (2011), the Scottish Intercollegiate Guidelines Network [57] (2010), the Bariatric Scientific Collaborative Group [58] (2007) and the National Institute for Health and Clinical Excellence [59] (2006) . All of these guidelines have been developed according to the 1991 NIH guidelines [55]. Prospective patients must fulfill specific prerequisites which are similar in all mentioned guidelines. In particular, patients must acknowledge all the essential information about the surgery and its possible risks, must have an acceptable risk for surgery, must be committed to the long-term follow up, must have been through previous, failed non-surgical weight-loss attempts, and must have no specific contraindications to surgery. On the other hand, contraindications to bariatric surgery include major depression or psychosis, severe cardiac disease with prohibitive anesthetic risks, severe coagulopathy, noncompliance with nutritional requirements and vitamin supplementation and alcohol or drug abuse.

Bariatric Surgery as Metabolic Surgery for Diabetic Patients

Table 1.

Current Pharmaceutical Design, 2014, Vol. 20, No. 00

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Risks of bariatric surgery.

Overall

Laparoscopic adjustable gastric banding

Sleeve gastrectomy

Roux-en-y gastric bypass

Biliopancreatic diversion ± duodenal switch

30 day mortality

0.05-1.1%

0.05-0.18%

0.4-0.46%

0.16-0.5%

0.75-1.11%

[174-176]

[172, 173]

[174, 175, 180]

[175, 180]

Morbidity at 1 year [171]

-

4.6%

10.8%

14.9%

25.6%

Short-term complications < 30d

wound infections (2.3%), staple line leaks (3%), hemorrhage (1.7%) and pulmonary manifestations (2.2%) [15]

Gastric or esophageal perforation, wound infection, hemorrhage [178]

Staple line leak, hemorrhage, stricture, splenic injury, wound infection [179]

Abdominal pain, anastomotic leaks, intestinal obstruction, hemorrhage, wound infection, DVT/pulmonary embolism [14]

Abdominal pain, Wound infection, dehiscence, anastomotic leak [14, 170]

Long-term complications > 30d

osteoporosis, vitamin and mineral insufficiencies, hypoglycaemia.

Band slippage, band erosion into the stomach, weight regain [178]

GERD, choledocholithiasis-bile duct stricture [177]

Anastomotic stricture, intestinal obstruction, incisional hernia, gastric ulcer, cholelithiasis, nutritional deficiencies [14]

Incisional hernia, severe nutritional deficiencies (protein malnutrition, hypoalbuminaemia, anemia, excessive fat malabsorption), gastric ulcer, cholelithiasis, renal calculi [14, 170]

All of the aforementioned guidelines have been developed according to the 1991 NIH guidelines [55]. However, the NIH guidelines were developed in a period of lower-level technological status, surgical expertise and restricted knowledge of the pathophysiological effects of bariatric surgery. More specifically, before the advent of minimally invasive bariatric surgery and the establishment LAGB and LSG procedures, as well as, before essential data from long-term studies and randomized clinical trials had enlightened us in order to evaluate the effect of bariatric surgery on T2DM. Generally speaking, Body-mass index (BMI) values and the presence of associated comorbidities usually determine the appropriateness of the patients to undergo bariatric surgery. Nevertheless, discussion is taking place about the role of BMI in the decision for surgical intervention. Pories et al believe that BMI should not be the principal feature of surgical indication. Should our decision, on whether a patient is candidate for bariatric surgery, be predominantly taken according to BMI cutoffs, we actually ignore the impact of race, gender, body fat composition and age on the relation between BMI and metabolic risk [60]. The International Diabetes Federation statement for obese T2DM suggests fitting criteria alterations for ethnicity (especially for Asian) and people with poorly controlled diabetes, particularly on the basis of failed medical weight-loss attempts and difficulty in controlling associated major comorbidities. Taking that into account, we should reexamine which diabetic patients we consider eligible for bariatric surgery, based on the latest available evidence and risk-benefit evaluation. Despite information about the benefits of surgical intervention in obese individuals with T2DM [61], below 1% (aproximately 0,52%/year) among suitable patients receive the surgical treatment. In the UK, the percentage of eligible patients undergoing bariatric surgery is even less (< 0,5%/year) [21].

Consequently, the impact of surgery on body weight and metabolic function, indicate that bariatric surgery should be a component of the standard therapy for T2DM, and not the last choice. 2.5. Effects of Bariatric Surgery In a nutshell, it has been demonstrated that Bariatric surgery achieves long-term weight loss, as well as minimizing obesity related comorbidities, and simultaneously, improves the quality of life and reduces number of sick days and treatment costs [62-66] The majority of morbidly obese patients who undergo bariatric surgery experience at least improvement of diabetes, hypertension, hyperlipidaemia, and obstructive sleep apnea. In addition, overall cause-specific mortality is shown to diminish remarkably [67, 68]. Moreover, the Swedish Obese Subjects Study conducted by Sjostrom and colleagues demonstrated that bariatric surgery may reduce the incidence of cancer in the patients who receive this treatment [69]. Finally, the 2009 Cochrane review, including patients with T2DM and a control group (without T2DM), concluded that bariatric surgery yields a greater weight loss effect than conventional medical therapy in obese individuals, with BMI >30 kg/m2, as well as ameliorating major obesity comorbidities and improving healthrelated quality of life [14]. 2.5.1. Effects on Weight Loss Non surgical management should always be the first choice treatment for obesity. The physicians should combine diet and exercise, and at the same time, should aim to educate the patients about nutrition issues while support ing them with behavioral strategies in order to help them achieve effective and sustainable weight-loss [53]. Often, unfortunately, non surgical treatment for obesity fails to sustain the reduced body weight. On the other hand, a large literature of controlled and uncontrolled cohort studies


shows that surgery has produced the longest period of sustained weight loss [53]. Weight loss caused by bariatric surgery is due to reduced energy intake as opposed to energy expenditure. Therefore, RYGB, LAGB, and LSG procedures, primarily, cause a decrease in energy intake and hence cause weight loss [70], while weight loss after BPD is due to a combination of decreased energy intake and malabsorption. In 2004 a meta-analysis was performed by Buchwald and his colleagues. A total of 136 fully extracted studies were included for a total of 22094 patients. The baseline mean body mass index for 16.944 patients was 46.9. The mean (95% confidence interval) percentage of excess weight loss was 61.2% for all patients. However, weight-loss effects were not the same among different procedures. Particularly, excess weight loss was 47.5% for patients who underwent gastric banding, 61.6% for gastric bypass, 68.2% for gastroplasty and 70.1% for biliopancreatic diversion or duodenal switch [16] . In a more recent systematic review and meta-analysis, published in 2009, Buchwald and his colleagues [13] tried to define the effect of bariatric surgery on body weight and type 2 diabetes. 621 studies and 135,246 patients, with a mean BMI of 47.9 kg/m2, were included. The meta-analysis demonstrated that overall weight loss was 38.5 kg or 55.9% excess body weight. The percentage of excess weight-loss at 2 years was 63%, 49% and 73% for RYGB, LAGB and BPD respectively [71]. The Swedish Obese Subjects (SOS) Study was carried out in the early 1990s. The objective of the study was the prospective assessment of 10-year mortality in a large group of morbidly obese patients, who underwent bariatric surgery [72]. The mean weight loss in the surgical group of the study was 23.4% of baseline body weight 2 years after surgery and 16.3% 10 years after surgery. At the same time, the control group of morbidly obese patients treated by conventional medical treatment remained substantially weight stable [72]. Similar results were produced by a smaller prospective study, conducted by Pontiroli et al , which examines the outcome of diabetes in morbid obese patients according to the type of treatment (LAGB or conservative medical therapy). 73 morbid obese patients underwent LAGB, while 43 eligible morbid obese patients refused surgery for personal reasons [73]. In a 4-year follow-up, BMI decreased from 45 to 37.7 kg/m2 in the LAGB group and remained steady in the non-surgical group. In a prospective unblinded randomized control trial conducted by Dixon and his colleagues, 60 patients with BMI ranging from 30 to 40 kg/m2 and recently diagnosed T2DM (