Curr Cardiol Rep (2015) 17: 34 DOI 10.1007/s11886-015-0588-6

ISCHEMIC HEART DISEASE (D MUKHERJEE, SECTION EDITOR)

Cardiovascular, Renal and Overall Health Outcomes After Bariatric Surgery Ji C. Tham & Carel W. le Roux & Neil G. Docherty

Published online: 18 April 2015 # Springer Science+Business Media New York 2015

Abstract Obesity is associated with significant increases in morbidity and mortality secondary, in part, to the increased burden of cardiovascular and renal diseases. Currently, bariatric surgery represents an important component of intensive approaches to the treatment of chronic and complex obesity. The efficacy of bariatric surgery extends beyond its ability to support significant and sustainable reductions in bodyweight to improvements in metabolic and cardiovascular health which are proposed to occur, in part, via weight lossindependent physiological changes. This report summarises the concept of cardiovascular and renal diseases as important constituent aspects of obese morbidity that contribute to overall impairments in health and lifespan. It furthermore describes the key features of bariatric surgical interventions, the evidence base for their beneficial effect on cardiovascular and renal diseases, and lastly provides some perspectives on the mechanisms involved.

Keywords Obesity . Cardiovascular . Renal . Bariatric . Surgery . Health outcomes This article is part of the Topical Collection on Ischemic Heart Disease J. C. Tham Musgrove Park Hospital, Taunton, UK C. W. le Roux : N. G. Docherty (*) Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland e-mail: [email protected] C. W. le Roux Gastrosurgical Laboratory, University of Gothenburg, Gothenburg, Sweden C. W. le Roux Division of Investigative Science, Imperial College London, London, UK

Introduction Risk of Cardiovascular Disease and Renal Disease Secondary to Obesity Obesity is increasingly recognised, not only as a phenotypic trait but also as the principal presenting sign of a disease process characterised by dysregulation of energy homeostasis, the aetiology of which is based on the interplay of multiple environmental influences within genetically susceptible individuals. Obesity is frequently, but not ubiquitously, associated with one or more co-morbid factors of varying severity giving rise to the idea of obese morbidity being the principal clinical problem requiring attention. Contemporary developments in relation to the efficacy of intensive interventions in obesity are therefore increasingly shifting the focus from purely weight loss-related outcomes to the consideration of metabolic, endorgan and global health status. Cardiovascular and renal diseases rank highly among the principal causes of obese morbidity as a result of diabetes, dyslipidaemia, hypertension and related complications. The drive to treat obesity is limited by finite resources, so selection of patients best placed to accrue benefit from intensive interventions is vital. Patients set to benefit most from intensive intervention are those most affected by obese morbidity, and a rationale exists for proposing that if surgery can safely be performed in such patients, then they should be prioritised for surgical intervention. In order to standardise grading of the severity of obese morbidity, the Edmonton Obesity Staging System (EOSS) has been devised [1••]. This system involves assessment of severity at four levels across medical, mental and functional domains and has been validated for the classification of obese morbidity. Secondary analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III) indicates that there is a direct step-wise relationship between the presence and severity

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of the EOSS-quantified obese morbidity and 16-year mortality rates [1••]. This analysis highlights the fact that from a costbenefit perspective, intensive interventions in the treatment of obesity should be targeted at those patients with significant progressive co-morbidities such as cardiovascular and renal diseases; in recognition of the reality that if diseases are allowed to progress too far, then even the option of surgery may constitute too little too late. Co-existence of Cardiovascular Disease and Renal Disease Type 2 diabetes mellitus (T2DM) is a major co-morbidity of obesity with associated macrovascular and microvascular complications. Not only does T2DM contribute significantly to obese morbidity, it also compounds the impact of other comorbidities. Analysis of NHANES III data demonstrates that diabetic kidney disease (DKD; abnormal glomerular filtration rate and/or albuminuria) is associated with increases in cardiovascular disease [2]. Coherent with this, the study also demonstrated that mortality rates from cardiovascular disease increase from 3.4 % in patients without diabetes and kidney disease to 19.6 % in patients with DKD, suggesting that comorbid cardiovascular and renal diseases in patients with obesity mandate more intensive interventions and follow-up. Cardiovascular Disease and Renal Disease Outcomes After Non-surgical Lifestyle-Based Interventions in Individuals with Severe Obesity As with management of any disease prior to surgical or medical interventions, attempts at lifestyle interventions should be employed first. Lifestyle interventions include decreased calorie intake and increased physical activity. From a resource perspective, such measures, if effective in the primary care setting, would be an optimal means of improving the health

Fig. 1 Patient selection and targeted outcome criteria in relation to the use of bariatric surgical approaches in the treatment of patients with severe and complex obesity. *Specific considerations include (1) selecting patients according to the Edmonton Obesity Severity System

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of patients [3]. Intensive lifestyle intervention can achieve up to 5 % weight loss; however, with medium-term follow-up, weight loss maintenance remains challenging [4]. In the Look AHEAD study on obese patients with T2DM, comparisons of intensive lifestyle intervention with controls showed greater weight loss at long-term follow-up but this was only of a small magnitude (6.0 versus 3.5 %) [5•]. Look AHEAD also did not show any evidence of improvements in cardiovascular events despite the 10-year follow-up of 5500 patients where the intensive treatment arm received the best possible diet and exercise interventions available [5•]. The Look AHEAD study has however reported that intensive lifestyle intervention results in a reduction in the incidence of very-high-risk chronic kidney disease (as defined by the Kidney Disease Improving Global Outcomes Classification) [6]. Although that study showed a significant reduction in incidence rates, the effect is again small and there are no published controlled trials at present directly comparing surgical intervention in a head-to-head manner against intensive lifestyle intervention with respect to renal function.

Bariatric Surgery—Impact on Weight, Renal Disease, Cardiovascular Disease and Mortality Bariatric surgery has been shown to decrease all-cause mortality, fatal and non-fatal cardiovascular events as well as the development and progression of diabetes and kidney injury [7, 8•, 9•, 10–13, 14•, 15, 16•, 17]. Remission of T2DM following bariatric surgery appears to facilitate the reduction in renal disease and cardiovascular disease [16•]. Therefore, in contemporary medicine, bariatric surgery represents a key therapeutic modality in the treatment of obesity in patients at risk of severe and life-threatening complications. Figure 1 highlights the key areas for consideration in the assessment, selection

and (2) reviewing co-morbidities and pre-operative optimisation of patient from the point of blood pressure, glycaemic control and weight loss

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and definition of optimal outcomes of bariatric surgery particularly in the setting of patients with significant cardiovascular and renal risk factors. What is Bariatric Surgery?—Which Procedures? Bariatric surgery is an umbrella term for a selection of surgical procedures that, in principle, are indicated and instigated in attempts to promote weight loss. Current thought has moved towards the idea that bariatric surgery helps better health by improving physiological health and global function. This shift in thinking is backed by a solid evidence base derived from randomised controlled trials demonstrating that bariatric surgery is efficacious not only as a weight loss therapy but also as a means of inducing the remission of diabetes and improving cardiovascular health. The synergistic multifactorial effects of surgery in turn explain the proven benefits of bariatric surgery in relation to morbidity, mortality and quality of life (QoL). This perspective reduces the stigma of obesity and changes expectations of patients by moving the focus away from weight loss to better health. C u r r e n t b a r i a t r i c s u rg e r y p r o c e d u r e s i n c l u d e laparoscopically placed adjustable gastric band (AGB), vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB) and the less commonly performed biliopancreatic diversion with or without duodenal switch. Presently, AGB, VSG and RYGB are the most commonly conducted procedures. The AGB involves placement of an adjustable inflatable silicone band at the gastric cardia with an attached adjustment port placed at the epigastrium in the subcutaneous layer. Thirty-day complication and mortality rate of the AGB is 1 and 0 %, respectively, with a reoperation rate within 30 days of 0.8 % [18]. At medium-term follow-up, 13.8 to 21.9 % of AGB patients required re-intervention [19••]. At long-term follow-up, the requirement for reoperation is 31 % for the AGB [13]. Reoperations are usually indicated as a consequence of band slippage, band erosion into the gastrointestinal tract and tubing leakage [20]. Long-term follow-up shows that excess weight loss can be achieved by up to 20 % of patients [21]. A Cochrane review has confirmed the efficacy of the AGB in maintaining diabetes remission in 28.6 % of patients in studies with at least 2 years of follow-up [22]. Remission from diabetes is defined as the achievement of a glycated haemoglobin (HBA1c) level of 42 mmol/mol with no requirement for medication and is present in 39.7 % of patients at 5 years [23]. Since the AGB can be removed, and does not entail any alterations in anatomical integrity and configuration, it appeals to patients that want the option of having the procedure ‘reversed’ and to those that do not want ‘reconstruction’ surgery. The VSG involves removing a majority of the stomach and leaving a tubular conduit along the lesser curve [24]. The size

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of the tubular stomach is based on a 32–36-Fr bougie which results in a tube with an estimated volume of 100 ml [25]. The 30-day mortality for VSG is at 0 % with a 30-day complication rate at 12.1 % [26]. Staple line leakage in the VSG which occur in 0.9 % of cases can be difficult to manage and results in significant morbidity [26]. Other complications include bleeding and stricture formation with reoperation rates within 30 days at an incidence rate of 2.1 % [26]. Two systematic reviews reveal significant weight loss up to 3 years, with weight loss lying between that observed for AGB and RYGB [26, 27]. Diabetes remission rates are variously reported at between 26.5 to 75 % depending on the definition used [26], and HbA1c usually decreased by a mean of 19 mmol/mol [27]. Since the VSG is a technically easier operation compared to the RYGB and has better glycaemic effect to the AGB, the procedure can be used as a definitive treatment for diabetic obese patients. The VSG can also be converted at a later date to RYGB if it does not produce the required results. The RYGB procedure involves creating a 20–30-ml gastric pouch that is anastomosed with the distal end of the transected jejunum (transection is usually performed at 50 cm distal to the duodenojejunal junction) creating the alimentary limb [28]. The proximal transected end is anastomosed to distal end at approximately 100 cm from the transected point forming the biliopancreatic limb [28]. The 30-day complication and mortality rate of RYGB is at 4.8 and 0.2 %, respectively, while the reoperation rate within 30 days for the RYGB is reported as being 3.2 % [18]. Anastomotic leakage after RYGB represents the most serious complication with leak rate estimates ranging from 0.19 to 0.78 % [29–32]. Similar to the VSG, other complications include intestinal obstruction, stricture or stenosis, haemorrhage, deep vein thrombosis or pulmonary embolism and pneumonia. At medium-term followup, 0.1 to 0.9 % of RYGB patients required re-intervention for late complications [19••]. At long-term follow-up, the requirement for reoperation is 17 % in RYGB patients [13]. Sixteenyear follow-up data report that the mean excess weight loss of the RYGB is 32 % [21]. Rate of diabetes remission is better compared to the VSG with a significant reduction in the number of diabetes medication usage [8•]. Hence, RYGB can be suggested to be the procedure of choice for diabetic obese patients with a high burden of medication use. Bariatric Surgery—Factoring in Additional Risks in Patients with Co-morbid Cardiovascular and Renal Diseases The Obesity Surgery Mortality Risk Score is a validated tool for stratifying mortality risk in bariatric surgery patients [33]. The scoring system includes hypertension as one of the independent predictors of risk and so it can be concluded that cardiovascular disease increases risk of death. Mortality risk from each bariatric surgical procedure has been summarised from an advisory report from the American Heart Association,

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and the report contains information useful for counselling and consenting of patients for bariatric surgery [34, 35]. Additionally, bariatric surgery patients with renal disease have an increased risk of complications including serious conditions such as septic shock [36]. Therefore, despite the proposition that obesity surgery will result in the greatest benefit in those with significant co-morbidities such as cardiovascular and renal diseases, it appears that these same patients have an increased predisposition to acute complications. The underlying reason for this association is likely to be related to poor physiological reserve. Hence, great care and optimisation of such patients need to be undertaken prior to offering such patients surgery. Pre-operative optimisation includes improvement of glycaemic control, reduction of weight to a safe level for surgery and cardiovascular assessment. Good glycaemic control is associated with fewer complications compared to patients with poor glycaemic control [37]. Super obese patients (BMI >40 kg/m2) may have excess intraperitoneal adiposity and enlarged liver from steatosis, and small amounts of weight reduction may ease the surgical procedure and reduce the risk of complications [38, 39]. Pre-operative weight loss can be produced with low calorie diet [40] and the use of the intragastric balloon as an adjunct [41].

to perform longer on the modified Bruce treadmill protocol illustrating improved cardiovascular and physical function. The RAND 36-item health survey, a modification of the SF-36 survey, showed better physical function, higher energy levels and perception of better general health in bariatric surgery patients compared to medical therapy patients at up to 3 years of follow-up [8•]. The improvements in physical function may be related to the reduced incidence of chest pain and shortness of breath which appears in conjunction with a reduction in prevalence of hypertension, dyslipidaemia and diabetes [11]. In the SOS study on QoL, bariatric surgery patients had better current health perceptions, better social interaction, improvements in obesity-related psychosocial functioning and less depression compared to the pre-operative state [43]. Upon closer scrutiny, the results specifically show improvements of QoL back towards the normal levels observed in the general population. Therefore, as a patient’s global health status improves, it is likely that QoL improves as a reflection of normalised functioning.

Long-Term Outcomes After Bariatric Surgery—Mortality

Cardiovascular adverse events (myocardial infarction or stroke) usually occur after harbouring risk factors, such as hypertension, hyperglycaemia, chronic inflammation and dyslipidaemia for many years. Thus long-term outcome studies are necessary to assess the effectiveness of interventions in reducing the incidence of cardiovascular events. Among 2010 bariatric surgery patients, compared with 2037 controlled subjects, the SOS study showed a 33 % reduction in relative risk of suffering from a first time fatal or non-fatal myocardial infarction or stroke [14•]. That study also showed that the risk of suffering from a fatal cardiovascular adverse event was more likely in diabetics, men, older age and smokers and directly related to total cholesterol level. Additionally, Sjostrom et al. also showed that in obese patients, cardiovascular adverse outcomes were not related to BMI but rather with the baseline level of insulin, implying the baseline metabolic state and its amenability to correction via surgery as a major predictor of benefit. Therefore, stratification of operative priority should be based on criteria such as those quantifiable using the EOSS. As discussed previously, Adams et al. showed improved cardiovascular function after RYGB in the form of increased exercise tolerance [42]. Interestingly these studies did not show a reduction in stroke. The reason for the discrepancy between myocardial infarction and stroke may be the inadequacy of power in the studies to show any significant results as stroke incidence is lower than myocardial infarction incidence [21, 44].

Mortality rate immediately after bariatric surgery is low: 0.2 % [10]. In the Swedish Obese Subjects (SOS) study, over 10year follow-up, the overall mortality risk was lower in bariatric surgery patients compared to medical therapy patients (hazard ratio of 0.76) [21]. This result suggests that despite the initial risk of surgery, the survival of patients in the long term was greater. However, it needs to be taken into account that as many as 31 % of AGB and 17 % of RYGB patients required further surgery for either complications or conversion to a different procedure [13]. Long-Term Outcomes After Bariatric Surgery—QoL The improvements in physiological indices of metabolic health and body mass may indicate improvements in health, but if these improvements do not equate to improved life for the patient, then overall efficacy should be placed in doubt and issues in relation to compliance with follow-up and on-going treatments should be anticipated. Assessment of QoL changes following surgery are therefore vital to elucidate whether physiological improvements translate into a better life from all aspects of health and functioning. In a study involving 1156 patients in Utah, the physical and mental component of the SF-36 questionnaire improved significantly in RYGB patients compared to non-surgical patients [42]. Adams et al. also showed that at 2 years, post-operative patients were able

Cardiovascular Outcomes After Bariatric Surgery

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Cardiovascular Adverse Outcomes After Bariatric Surgery—Risk Factor Improvements After bariatric surgery, hypertension is reduced from a prevalence of 57.1 to 34.0 %, dyslipidaemia 95.2 to 26.0 % and diabetes 52.4 to 44.7 % [11]. In two recent small studies, it has been shown that not only does blood pressure measurements improve but also oxygen consumption was markedly reduced, signifying the ability to perform more strenuous task [45, 46]. Valezi et al. also showed a morphologically improved myocardium along with an increase in ejection fraction, suggesting recovery from heart failure [46]. It is likely that the reduction in cardiovascular adverse outcomes is related to a reduction in those risk factors. Maintenance of risk factor reduction will therefore be beneficial, in terms of health outcomes, for patients. Cardiovascular Outcomes After Bariatric Surgery—Mechanisms for Risk Factor Improvements Improvements in risk factors are likely a result of the reversal of the metabolic syndrome. Metabolic syndrome is believed to arise from a constellation of disorders occurring secondary to chronic low-grade inflammation in visceral fat which result in metabolic dysfunction associated with T2DM, dyslipidaemia, hepatic steatosis and atherosclerosis [47, 48]. It is likely that the reduction in inflammation [49•] following bariatric surgery reduces the coagulability of blood and hence risk of thrombosis [50]. The combination of lower weight and inflammation seems also to be associated with those changes along with improvement in blood pressure. In those cases, improvements in renal function and specific promotion of diuresis and natriuresis may be a contributing factor in blood pressure improvements that in turn reduces cardiovascular risk. Increments in high-density lipoprotein and a reduction in serum triglycerides seem to correspond to a reduction in Creactive protein [50]. As a whole, the reduction of coagulability, blood pressure and improvements in lipid profile may synergise to reduce atherosclerosis and, based on Virchow’s triad, reduce risk of intravascular catastrophe. The exact underlying mechanism and physiological feedback loop to explain these findings are yet to be found but may have their source in the pleiotropic effects of surgery-induced changes in gastrointestinal hormone secretion [51] and neurohormonal feedback. The exact reasons for myocardial recovery and improvement in ejection fraction are not yet fully understood but are likely to be partly a result of lowered blood pressure. Renal Outcomes After Bariatric Surgery—Albuminuria and Chronic Kidney Disease DKD is characterised by microvascular damage at the level of the glomerulus and constitutes a major source of obese

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morbidity. It has also been increasingly recognised that obesity per se is associated with a variant of kidney disease which bears similar histopathological resemblance to focal segmental glomerulosclerosis and is now known as obesity-related glomerulopathy (ORG) [52]. Similar to steatosis in the liver, ORG is believed to occur as a consequence of lipid deposition in the kidney which in turn is associated with glomerular hyperfiltration and proteinuria. While estimated glomerular filtration rate (eGFR) is not accurate in bariatric surgery patients due to lean mass loss [53], measurement of albumin excretion rates via albumin creatinine ratios (ACRs) in spot urines or absolute excretion rates in timed urine collection is a more reliable measure because it directly quantifies the level of renal damage. Bariatric surgery has been noted to impede the progression of microvascular disease in a long-term study, wherein bariatric surgery patients had more frequent diabetes remission and a reduction in the incidence of diabetic microvascular complications including renal disease [16•]. The number of patients needed to be treated by bariatric surgery (NNT) to prevent one patient from developing albuminuria over 10 years is estimate to be nine patients, but in the case of patients with diabetes, the NNT is reduced to four [9•]. Microvascular complications, such as retinopathy, nephropathy and neuropathy, appear to be reduced more than twofold by post-operative year 2 (hazard ratio 0.44) [16•]. Renal Outcomes After Bariatric Surgery—Risk Factor Improvements Improvement in kidney function is directly related to improvements in risk factors. Risk factors for chronic kidney disease include T2DM and hypertension. At 15 years, remission rates were 30.4 % for bariatric surgery and 6.5 % for controls [16•]. Hypertension prevalence too improved as shown above in the previous section (‘Cardiovascular Adverse Outcomes After Bariatric Surgery—Risk Factor Improvements’) [11, 45, 46]. Renal Outcomes After Bariatric Surgery—Mechanisms for Risk Factor Improvements The improvement in risk factors following bariatric surgery is not well understood. Improvements seen in blood pressure [9•] may be related to restoration in homeostasis of the renin-angiotensin system through better renal perfusion or venous drainage. A recent study found that urine output increases after surgery, and this may be a surrogate indication of better renal perfusion [12]. Bariatric surgery results in increases in glucagon-like peptide-1 (GLP-1) secretion [54, 55] and the GLP-1 receptors associated with the renin system in the kidney may explain the natriuresis [56•, 57]. Also, remission from diabetes may play a role in improving glomerular function through restitution of normal insulin signaling in glomerular podocytes and attenuation of hyperfiltration [9•].

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Additionally, glomerular function may improve secondary to reductions in the pro-inflammatory state secondary to obesity. A recent study found that as patients lost weight in the postbariatric surgery period, C-reactive protein and numerous inflammatory cytokines associated with renal and/or metabolic disease were significantly reduced [49•]. Fenske et al. also found a significant reduction in proteinuria in association with reduced inflammatory markers [49•]. Other microvascular damage such as retinopathy also appears to be halted [58]. That result suggests that microvascular damage may be arrested or even potentially reversed.

Curr Cardiol Rep (2015) 17: 34 3.

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Conclusions 7.

Individuals being consulted as potential patients for bariatric surgery should be thoroughly assessed for co-morbidities and prioritised if they have multiple co-morbidities. Bariatric surgery is safe and when combined with best medical care should be considered in obese patients with a high burden of obesityrelated complications. Perhaps each different modality of bariatric procedures should be tailored to each individual patient to achieve a more personalised medicine-based approach. Cardiovascular and renal function improves with bariatric surgery, but more research is needed in those areas to ascertain the exact mechanism of action.

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Compliance with Ethics Guidelines Conflict of Interest Ji C. Tham, Carel W. le Roux and Neil G. Docherty declare that they have no conflict of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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References Papers of particular interest published recently have been highlighted as: • Of importance •• Of outstanding importance 1.•• Padwal RS, Pajewski NM, Allison DB, Sharma AM. Using the Edmonton Obesity Staging System to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ. 2011;183(14):E1059–66. The authors described a method of classifying obese patients according to co-morbidities instead of BMI which better stratifies the potential benefit achievable from bariatric surgery. 2. Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302–8.

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Kushner RF, Ryan DH. Assessment and lifestyle management of patients with obesity: clinical recommendations from systematic reviews. JAMA. 2014;312(9):943–52. Christiansen T, Bruun JM, Madsen EL, Richelsen B. Weight loss maintenance in severely obese adults after an intensive lifestyle intervention: 2- to 4-year follow-up. Obesity (Silver Spring). 2007;15(2):413–20. Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369(2):145–54. Part of the Look AHEAD research group that scrutinised the possible management of obesity with lifestyle intervention but found that cardiovascular outcomes were no different when compared to control subjects. Group LAR. Effect of a long-term behavioural weight loss intervention on nephropathy in overweight or obese adults with type 2 diabetes: a secondary analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol. 2014;2(10):801–9. Schauer PR, Burguera B, Ikramuddin S, Cottam D, Gourash W, Hamad G, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238(4):467–84. discussion 84–5. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, et al. Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med. 2014;370(21):2002–13. The authors describe a landmark study that compared bariatric surgery with medical therapy against medical therapy alone in the management of type 2 diabetes mellitus instead of the traditional surgery versus medical treatment. The message portrayed from the study proposes surgery as an adjunct to medical therapy in the treatment of obese patients. Carlsson LM, Romeo S, Jacobson P, Burza MA, Maglio C, Sjöholm K, et al. The incidence of albuminuria after bariatric surgery and usual care in Swedish obese subjects (SOS): a prospective controlled intervention trial. Int J Obes (Lond). 2014. The study shows the reversal of kidney damage as a result of bariatric surgery in the long-term. Carlsson LM, Peltonen M, Ahlin S, Anveden Å, Bouchard C, Carlsson B, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012;367(8):695–704. Delling L, Karason K, Olbers T, Sjöström D, Wahlstrand B, Carlsson B, et al. Feasibility of bariatric surgery as a strategy for secondary prevention in cardiovascular disease: a report from the Swedish obese subjects trial. J Obes. 2010. Hallersund P, Sjöström L, Olbers T, Lönroth H, Jacobson P, Wallenius V, et al. Gastric bypass surgery is followed by lowered blood pressure and increased diuresis—long term results from the Swedish Obese Subjects (SOS) study. PLoS One. 2012;7(11): e49696. Sjöström L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004;351(26):2683– 93. Sjöström L, Peltonen M, Jacobson P, Sjöström CD, Karason K, Wedel H, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307(1):56–65. The authors revealed that cardiovascular adverse events are more likely in patients with a high baseline insulin level instead of a high BMI; suggesting that management should focus on patients with poorly controlled diabetes and maintenance of good glycaemic control is vital. Sjöström L. Review of the key results from the Swedish Obese Subjects (SOS) trial—a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273(3):219–34. Sjöström L, Peltonen M, Jacobson P, Ahlin S, Andersson-Assarsson J, Anveden Å, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and

Curr Cardiol Rep (2015) 17: 34 macrovascular complications. JAMA. 2014;311(22):2297–304. This study is landmark study with very long-term follow-up that showed a high rate of type 2 diabetes mellitus remission and reduction in macrovascular and microvascular complications. 17. Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012. 18. Flum DR, Belle SH, King WC, Wahed AS, Berk P, Chapman W, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med. 2009;361(5):445–54. 19.•• Courcoulas AP, Christian NJ, Belle SH, Berk PD, Flum DR, Garcia L, et al. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA. 2013;310(22):2416–25. This study showed that weight loss outcomes fall into different distinct patterns, suggesting possible different aetiology of obesity and response to bariatric surgery. 20. O’Brien PE, Dixon JB, Brown W, Schachter LM, Chapman L, Burn AJ, et al. The laparoscopic adjustable gastric band (LapBand): a prospective study of medium-term effects on weight, health and quality of life. Obes Surg. 2002;12(5):652–60. 21. Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–52. 22. Puzziferri N, Roshek TB, Mayo HG, Gallagher R, Belle SH, Livingston EH. Long-term follow-up after bariatric surgery: a systematic review. JAMA. 2014;312(9):934–42. 23. Sultan S, Gupta D, Parikh M, Youn H, Kurian M, Fielding G, et al. Five-year outcomes of patients with type 2 diabetes who underwent laparoscopic adjustable gastric banding. Surg Obes Relat Dis. 2010;6(4):373–6. 24. Committee ACI. Updated position statement on sleeve gastrectomy as a bariatric procedure. Surg Obes Relat Dis. 2012;8(3):e21–6. 25. Rosenthal RJ, Diaz AA, Arvidsson D, Baker RS, Basso N, Bellanger D, et al. International sleeve gastrectomy expert panel consensus statement: best practice guidelines based on experience of >12,000 cases. Surg Obes Relat Dis. 2012;8(1):8–19. 26. Trastulli S, Desiderio J, Guarino S, Cirocchi R, Scalercio V, Noya G, et al. Laparoscopic sleeve gastrectomy compared with other bariatric surgical procedures: a systematic review of randomized trials. Surg Obes Relat Dis. 2013;9(5):816–29. 27. Gill RS, Birch DW, Shi X, Sharma AM, Karmali S. Sleeve gastrectomy and type 2 diabetes mellitus: a systematic review. Surg Obes Relat Dis. 2010;6(6):707–13. 28. Higa KD, Boone KB, Ho T, Davies OG. Laparoscopic Roux-en-Y gastric bypass for morbid obesity: technique and preliminary results of our first 400 patients. Arch Surg. 2000;135(9):1029–33. discussion 33–4. 29. Dillemans B, Sakran N, Van Cauwenberge S, Sablon T, Defoort B, Van Dessel E, et al. Standardization of the fully stapled laparoscopic Roux-en-Y gastric bypass for obesity reduces early immediate postoperative morbidity and mortality: a single center study on 2606 patients. Obes Surg. 2009;19(10):1355–64. 30. Jacobsen HJ, Bergland A, Raeder J, Gislason HG. High-volume bariatric surgery in a single center: safety, quality, cost-efficacy and teaching aspects in 2,000 consecutive cases. Obes Surg. 2012;22(1):158–66. 31. Hutter MM, Schirmer BD, Jones DB, Ko CY, Cohen ME, Merkow RP, et al. First report from the American College of Surgeons Bariatric Surgery Center Network: laparoscopic sleeve gastrectomy has morbidity and effectiveness positioned between the band and the bypass. Ann Surg. 2011;254(3):410–20. discussion 20–2. 32. Birkmeyer NJ, Dimick JB, Share D, Hawasli A, English WJ, Genaw J, et al. Hospital complication rates with bariatric surgery in Michigan. JAMA. 2010;304(4):435–42. 33. DeMaria EJ, Murr M, Byrne TK, Blackstone R, Grant JP, Budak A, et al. Validation of the obesity surgery mortality risk score in a

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34.

35.

36.

37.

38.

39. 40.

41.

42.

43.

44.

45.

46.

47. 48. 49.•

50.

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multicenter study proves it stratifies mortality risk in patients undergoing gastric bypass for morbid obesity. Ann Surg. 2007;246(4): 578–82. discussion 83–4. Poirier P, Alpert MA, Fleisher LA, Thompson PD, Sugerman HJ, Burke LE, et al. Cardiovascular evaluation and management of severely obese patients undergoing surgery: a science advisory from the American Heart Association. Circulation. 2009;120(1): 86–95. Poirier P, Cornier MA, Mazzone T, Stiles S, Cummings S, Klein S, et al. Bariatric surgery and cardiovascular risk factors: a scientific statement from the American Heart Association. Circulation. 2011;123(15):1683–701. Turgeon NA, Perez S, Mondestin M, Davis SS, Lin E, Tata S, et al. The impact of renal function on outcomes of bariatric surgery. J Am Soc Nephrol. 2012;23(5):885–94. Frisch A, Chandra P, Smiley D, Peng L, Rizzo M, Gatcliffe C, et al. Prevalence and clinical outcome of hyperglycemia in the perioperative period in noncardiac surgery. Diabetes Care. 2010;33(8): 1783–8. Oster G, Thompson D, Edelsberg J, Bird AP, Colditz GA. Lifetime health and economic benefits of weight loss among obese persons. Am J Public Health. 1999;89(10):1536–42. Pi-Sunyer FX. Short-term medical benefits and adverse effects of weight loss. Ann Intern Med. 1993;119(7 Pt 2):722–6. Liu RC, Sabnis AA, Forsyth C, Chand B. The effects of acute preoperative weight loss on laparoscopic Roux-en-Y gastric bypass. Obes Surg. 2005;15(10):1396–402. Zerrweck C, Maunoury V, Caiazzo R, Branche J, Dezfoulian G, Bulois P, et al. Preoperative weight loss with intragastric balloon decreases the risk of significant adverse outcomes of laparoscopic gastric bypass in super-super obese patients. Obes Surg. 2012. Adams TD, Pendleton RC, Strong MB, Kolotkin RL, Walker JM, Litwin SE, et al. Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese. Obesity (Silver Spring). 2010;18(1):121–30. Karlsson J, Taft C, Rydén A, Sjöström L, Sullivan M. Ten-year trends in health-related quality of life after surgical and conventional treatment for severe obesity: the SOS intervention study. Int J Obes (Lond). 2007;31(8):1248–61. Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond WD, et al. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007;357(8):753–61. Serés L, Lopez-Ayerbe J, Coll R, Rodriguez O, Vila J, Formiguera X, et al. Increased exercise capacity after surgically induced weight loss in morbid obesity. Obesity (Silver Spring). 2006;14(2):273–9. Valezi AC, Machado VH. Morphofunctional evaluation of the heart of obese patients before and after bariatric surgery. Obes Surg. 2011;21(11):1693–7. Haller H. Epidermiology and associated risk factors of hyperlipoproteinemia. Z Gesamte Inn Med. 1977;32(8):124–8. P B. The lean patient with type 2 diabetes: characteristics and therapy challenge. Int J Clin Pract Suppl. 2007;1533–9. Fenske WK, Dubb S, Bueter M, Seyfried F, Patel K, Tam FW, et al. Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective study. Surg Obes Relat Dis. 2012. The authors described the effects of bariatric surgery on the metabolic syndrome whereby the hallmark mild chronic inflammatory response in obesity is diminished in the post-operative setting. Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012. Ikramuddin S, Korner J, Lee WJ, Connett JE, Inabnet WB, Billington CJ, et al. Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and

34 Page 8 of 8 hyperlipidemia: the diabetes surgery study randomized clinical trial. JAMA. 2013;309(21):2240–9. 52. de Vries AP, Ruggenenti P, Ruan XZ, Praga M, Cruzado JM, Bajema IM, et al. Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease. Lancet Diabetes Endocrinol. 2014;2(5):417–26. 53. Lieske JC, Collazo-Clavell ML, Sarr MG, Rule AD, Bergstralh EJ, Kumar R. Gastric bypass surgery and measured and estimated GFR in women. Am J Kidney Dis. 2014;64(4):663–5. 54. Peterli R, Steinert RE, Woelnerhanssen B, Peters T, ChristoffelCourtin C, Gass M, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740–8. 55. Pournaras DJ, Osborne A, Hawkins SC, Vincent RP, Mahon D, Ewings P, et al. Remission of type 2 diabetes after gastric bypass

Curr Cardiol Rep (2015) 17: 34 and banding: mechanisms and 2 year outcomes. Ann Surg. 2010;252(6):966–71. 56.• Vallon V, Docherty NG. Intestinal regulation of urinary sodium excretion and the pathophysiology of diabetic kidney disease: a focus on glucagon-like peptide 1 and dipeptidyl peptidase 4. Exp Physiol. 2014;99(9):1140–5. The authors discuss the effects of glucagon-like peptide 1 on renal function and suggest the possible mechanism of improvements in renal function as a result on glucagon-like peptide receptor stimulation. 57. Docherty NG, le Roux CW. Improvements in the metabolic milieu following Roux-en-Y gastric bypass and the arrest of diabetic kidney disease. Exp Physiol. 2014;99(9):1146–53. 58. Miras AD, Chuah LL, Lascaratos G, Faruq S, Mohite AA, Shah PR, et al. Bariatric surgery does not exacerbate and may be beneficial for the microvascular complications of type 2 diabetes. Diabetes Care. 2012;35(12):e81.