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Metabolic surgery in diabetes

Introduction

Bariatric surgery, now frequently referred to as metabolic surgery, is an important treatment modality for type 2 diabetes mellitus (T2DM), leading to diabetes remission in many patients, independent of weight loss. Such surgery is still frequently considered to be weight loss surgery and as such many guidelines and treatment algorithms recommend these surgeries in patients with a particular body mass index (BMI), often BMI >35 kg/m2. However, there is now a substantial body of evidence to suggest that the effect of these surgeries on diabetes is such that metabolic surgery may even be appropriate for the treatment of T2DM in patients with much lower BMI.

This themed collection comprises a selection of recent full-text articles and chapters from the Springer Nature portfolio, as well as links to selected articles sourced from other prominent publishers, that discuss this important topic.

Content

  1. Mechanisms and rationale
  2. Patient and procedure selection
  3. Post-surgery management
  4. Outcomes
  5. Complications

Instructions

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Mechanisms and rationale

Bariatric surgery: Prevalence, predictors, and mechanisms of diabetes remission

This paper describes the potential mechanisms by which bariatric surgery, in particular Roux-en-Y gastric bypass surgery, leads to diabetes remission.

Summary points
  • Currently available evidence suggests that Roux-en-Y gastric bypass (RYGB) surgery is the most effective treatment for achieving remission in diabetes.
  • Potential mechanisms for diabetes remission following RYGB surgery include involvement of enterohepatic pathways, central pathways controlling energy balance, and the gut microbiota.
  • Enterohepatic pathways, such as the fibroblast growth factor (FGF) 19 – cholesterol 7 alpha-hydroxylate 1 (CYP7A1) bile acid pathway, may be involved in diabetes remission following RYGB surgery. This may be via secretion of bile acids from the gallbladder into the now empty duodenum, giving ‘digestate-free’ bile acids, which may be more bioactive, with more potent stimulation of FGF 19 and potentially also of glucagon-like peptide 1 (GLP-1) production.
  • Changes in the microbiome have been reported to occur following RYGB surgery, with metagenomic sequencing before and 3 months after RYGB revealing changes in the bacteria species composition of the gut microbiome.
  • Currently available data suggest that weight loss following RYGB is unlikely to be a major contributing factor to diabetes remission.
  • A simple mathematic tool, the DiaRem score, has been developed for predicting the probability that RYGB will result in diabetes remission in a patient.
  • While current understanding of diabetes remission remains incomplete, it is encouraging that RYGB surgery leads to remission in the majority of patients.

Argyropoulos G. Curr Diab Rep 2015; 15: 15. doi: 10.1007/s11892-015-0590-9

Role of the gut on glucose homeostasis: Lesson learned from metabolic surgery

This review summarizes findings from relevant randomized controlled trials investigating the impact of bariatric surgery on metabolic outcomes, and examines the role of the small intestine in driving such effects.

Summary points
  • Randomized controlled trials support the use of bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD), for the treatment of type 2 diabetes mellitus, independent of baseline body mass index.
  • The three major surgical procedures are RYBG (stomach remnant 30mL), BPD (stomach remnant 400mL) and sleeve gastrectomy (stomach remnant 100mL). Sleeve gastrectomy does not bypass the intestine, whereas in RYGB, the duodenum and first portion of the jejunum is bypassed, and in BPD, the duodenum, entire jejunum and the first portion of the ileum are excluded from food transit.
  • RYGB has been shown to be associated with increased insulin secretion and reduced hepatic glucose production, whereas BPD is associated with reduced insulin secretion, due to rapid normalization of insulin sensitivity.
  • Regulation of blood glucose concentration is achieved via a number of mechanisms, many of which involve the small intestine, including gastric emptying, glucose absorption and insulin secretion.
  • Proposed mechanisms by which bariatric surgery influences the role of the small intestine in glucose regulation include changes in gastric emptying, alterations in glucose absorption and nutrient sensing, incretin-mediated effects, ghrelin-associated changes, and changes in the gut microbiota.
  • The small intestine plays a primary role in glucose homeostasis - the jejunum senses nutrients and regulates glucose production, and the entire small intestine secretes both glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, thereby enhancing insulin secretion. Manipulation of these regions in bariatric surgery has a substantial impact on these glucose-regulating actions.

Kamvissi-Lorenz V et al. Curr Atheroscler Rep 2017; 19: 9. doi: 10.1007/s11883-017-0642-5

Evidence base for bariatric surgery

This chapter reviews the most common bariatric surgical procedures, with a focus on weight loss and remission of comorbidities, including type 2 diabetes mellitus.

Summary points
  • In addition to treating obesity, bariatric surgery has been shown to reduce metabolic complications of obesity, such as type 2 diabetes mellitus (T2DM).
  • There are many different bariatric procedures, associated with different levels of risk and differing efficacy. These include laparoscopic adjustable gastric banding, laparoscopic Roux-en-Y gastric bypass (LRYGB), gastroplasties, laparoscopic sleeve gastrectomy (LSG), laparoscopic mini-gastric bypass, and laparoscopic biliopancreatic diversion and duodenal switch surgery (BDP-DS).
  • Of these surgery types, those that evoke metabolic changes in addition to weight loss due to reduced intake, are preferred in the treatment of diabetes. These include LRYGB, LSG, and BPD-DS.
  • Elucidating the mechanisms involved in weight loss following bariatric surgery is an ongoing process, and it is now understood that to successfully treat obesity, a multidisciplinary approach is needed.
  • Evidence for the role of bariatric surgery in the management of morbidly obese patients with T2DM comes primarily from meta-analyses and cohort studies, but recently, two randomized controlled trials (the STAMPEDE trial from the USA and a single center study in Italy) have provided level I evidence for the role of bariatric surgery in the treatment of T2DM.
  • In 2010, the International Diabetes Federation Taskforce on Epidemiology and Prevention of Diabetes established guidelines for the role of bariatric surgery in patients with T2DM, recommending bariatric surgery in patients with a body mass index (BMI) ≥35 kg/m2, and in patients with a BMI of 30–35 kg/m2 with poorly controlled diabetes despite appropriate lifestyle changes and pharmacotherapy.
  • Surgery is not the answer for all patients, but should be considered as an option by those involved in the care of obese and diabetic patients.

Leuratti L, Khwaja HA, Kerrigan DD. In: Obesity, bariatric and metabolic surgery: A practical guide. Edited by Agrawal S. Springer International Publishing, 2015. doi: 10.1007/978-3-319-04343-2_7


Patient and procedure selection

Metabolic surgery in the treatment algorithm for type 2 diabetes: A joint statement by international diabetes organizations

This joint statement, developed by several international diabetes organizations, provides guidelines regarding metabolic surgery in the treatment of type 2 diabetes mellitus.

Summary points
  • The 2nd Diabetes Surgery Summit (DSS-II), involving the American Diabetes Association, International Diabetes Federation, Chinese Diabetes Society, Diabetes India, European Association for the Study of Diabetes, and Diabetes UK, was convened to review available evidence and develop recommendations integrating medical and surgical therapies in a treatment algorithm for type 2 diabetes mellitus (T2DM).
  • The gastrointestinal tract is an important target for T2DM treatment, and metabolic surgery has been shown to achieve excellent results in terms of control of hyperglycemia and reduction of cardiovascular risk factors.
  • Several bariatric surgeries are associated with T2DM remission in most patients, and although such remission has been shown to erode over time, a substantial proportion of patients experience prolonged benefits – for example, the median disease-free period following Roux-en-Y gastric bypass surgery is 8.3 years.
  • In those who are appropriate surgical candidates, metabolic surgery should be a recommended treatment option for T2DM in patients with class III obesity (body mass index [BMI] ≥40 kg/m2) regardless of level of glycemic control and in patients with class II obesity (BMI 35.0–39.9 kg/m2) with inadequately controlled hyperglycemia despite lifestyle and optimal medical therapy.
  • Metabolic surgery should be considered an option in type 1 diabetes mellitus patients with class I obesity (BMI 30.0–34.9 kg/m2) and inadequately controlled hyperglycemia despite treatment.
  • Metabolic surgery should be performed in high-volume centers utilizing multidisciplinary teams.
  • Ongoing long-term monitoring of micronutrient status, nutritional supplementation and support is necessary following surgery.
  • Metabolic surgery is a potentially cost-effective treatment option in obese patients with T2DM.

Rubino F et al. Diabetes Care 2016; 39: 861-877. doi: 10.2337/dc16-0236

Operation of choice for metabolic surgery

This chapter discusses the various currently accepted metabolic surgeries in the treatment of type 2 diabetes mellitus, in terms of current evidence and potential mechanisms.

Summary points
  • The International Diabetes Federation considers Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric banding (LAGB), sleeve gastrectomy (SG), biliopancreatic diversion (BPD), and the duodenal switch variant (BPD-DS) as accepted metabolic procedures.
  • Observational and nonrandomized trials have shown marked sustained improvement in type 2 diabetes mellitus (T2DM) in morbidly obese and less obese patients following metabolic surgery. For example, meta-analyses involving >100 studies have shown 80% early complete diabetes remission and 75% remission >2 years after surgery.
  • Recent evidence from randomized controlled trials indicates that bariatric surgery is superior to conventional medical therapy for management of T2DM.
  • There are few high-quality studies comparing the various surgical procedures in terms of diabetes outcomes, but overall, the diversionary procedures have been shown to have more profound effects on metabolic measures than non-diversionary procedures.
  • The standard metabolic procedures each have their own risks and benefits, with more extensive procedures such as BPD associated with greater weight loss and metabolic benefits but also with greater risk.
  • The exact mechanisms for the metabolic effects of the various surgical procedures remain to be elucidated. Based on available evidence, potential mechanisms include: physical restriction in meal size; attenuation of appetite mediated by reduction in ghrelin following SG and RYGB; loss of fat mass leading to normalization of inflammatory cytokines and adipokines, resulting in improved insulin sensitivity.
  • LAGB and SG are the safest but least effective procedures for glycemic control; RYGB carries more risk but is much more effective. BPD appears to be the most effective antidiabetic procedure but is associated with higher risk.

Schauer PR, Aminian A, Brethauer SA. In: The ASMBS textbook of bariatric surgery: Volume 1 bariatric surgery. Edited by Nguyen NT et al. Springer-Verlag New York, 2015; 1: 331. doi: 10.1007/978-1-4939-1206-3_29

Bariatric surgery: A potential treatment for type 2 diabetes in youth

Here, the authors review the burden of type 2 diabetes among adolescents and discuss bariatric surgery in this population.

Summary points
  • The incidence and prevalence of type 2 diabetes mellitus (T2DM) in adolescents are increasing markedly, with nearly 85,000 adolescents predicted to be affected by 2050 in the US.
  • Available evidence suggests that T2DM may have a more aggressive pathogenesis in adolescents than in adults, with a more rapid decline in β-cell function, requiring more intensive medication and greater need for insulin.
  • Potential complications of T2DM in adolescents include cardiovascular complications, renal complications, and cerebrovascular complications.
  • Lifestyle interventions and medical therapies are often ineffective in this patient population, hence weight-loss procedures are being examined as options for the treatment of obesity and T2DM in adolescents.
  • Studies have shown substantial improvements in weight and cardiovascular risk in youth following various bariatric weight-loss procedures, and improvements in glucose and carbohydrate metabolism following gastric bypass surgery in adolescents with and without T2DM have also been observed.
  • There is some evidence to suggest that remission rates following gastric bypass and vertical sleeve gastrectomy may be even greater among adolescents than adults with T2DM.
  • The risks of bariatric surgery, both surgical and nutritional complications, must be considered.
  • When considering timing of surgery in severely obese adolescents, diabetes duration, the speed of treatment escalation, glycemic control and rate of β-cell decline following diagnosis should be key considerations.

Shah AS et al. Diabetes Care 2016; 39: 934–940. doi: 10.2337/dc16-0067


Post-surgery management

Clinical management of type 2 diabetes mellitus after bariatric surgery

A significant proportion of individuals undergoing bariatric surgery experience residual type 2 diabetes mellitus. This article outlines strategies for the clinical management of these patients.

Summary points
  • Three central mechanisms are purported to explain the effects of bariatric surgery on type 2 diabetes mellitus (T2DM):
    • Caloric restriction
    • Alterations in nutrient flow producing changes in gut hormone secretion.
    • Reductions in lipotoxicity and changes in adipose tissue hormone secretion.
  • Factors that may be associated with non-remission and relapse of diabetes following bariatric surgery include older age, limited weight loss, insulin use and poor glycemic control prior to surgery, as well as longer duration of diabetes prior to surgery.
  • Management of T2DM following bariatric surgery may involve diet (nutritious low-carbohydrate, low fat and high-fiber diet) and increased physical activity, as well as medical therapy.
  • Recommended medical therapy includes the following:
    • Metformin, thiazolidinediones (second-line after metformin), with sulfonylureas with metformin possibly useful to prevent further β-cell failure.
    • Basal and prandial insulin if no response to insulin sensitizers or secretagogues.
    • Incretin analogs.
    • SGLT-2 inhibitors, particularly for those with weight regain.
    • Phentermine-topiramate in those with weight regain or suboptimal weight loss.
    • Orlistat for residual diabetes associated with inadequate weight loss or weight regain.
    • Lorcaserin to promote or maintain adequate weight loss.
  • Available evidence suggests diabetes reoccurrence following bariatric surgery is due to either inadequate weight loss or to weight regain, combined with exhaustion of insulin-secreting pancreatic β-cells.
  • The authors propose pharmacologic intervention to reduce weight and increase insulin sensitivity, followed by treatments promoting insulin secretion if initial treatment is unsuccessful.

Khanna V, Kashyap SR. Curr Atheroscler Rep 2015; 17: 59. doi: 10.1007/s11883-015-0537-2

Nutritional management after bariatric surgery

This chapter outlines the dietary changes that are necessary following bariatric surgery, and discusses the importance of monitoring of nutritional status and supplementation for deficiencies to ensure optimal long-term outcomes.

Summary points
  • While associated with significant beneficial effects, bariatric surgery can also lead to several problems, including nutritional deficiencies, metabolic bone disease and renal stones.
  • Appropriate nutritional management post-surgery is vital, to monitor nutritional status, minimize complications and maximize weight loss.
  • A multiple phase diet following bariatric surgery is common, with a ‘normal’ diet often resuming after 6–8 weeks. Stages and timings vary by individual bariatric center, due to personal preferences of the surgeon and dietician.
  • In the long-term, all patients should be encouraged to follow a balanced, low-fat and low-sugar diet, with patients following recommended postoperative dietary advice having better weight-loss in the long term.
  • All patients should take a complete multivitamin and mineral supplement to minimize potential deficiencies.
  • Significant nutrients that should be monitored following surgery include protein, iron, vitamin B12 (one of the most common deficiencies following bariatric surgery), folate, thiamine, calcium and vitamin D, fat-soluble vitamins (A, E and K), zinc, copper and selenium.
  • Routine monitoring is imperative following bariatric surgery, with the dietician playing an important role in managing long-term outcome.

Pinnock GL. In: Obesity, bariatric and metabolic surgery: A practical guide. Edited by Agrawal S. Springer International Publishing, 2016. doi: 10.1007/978-3-319-04343-2_65


Outcomes

Bariatric surgery versus intensive medical therapy for diabetes: 5-year outcomes

Here, the 5-year results from a randomized study comparing intensive medical therapy alone or with either Roux-en-Y gastric bypass or sleeve gastrectomy are presented, showing the effects of these two surgeries to be durable and significantly better than medical therapy alone.

Summary points
  • The Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial was a three-group randomized controlled trial involving 150 obese patients with type 2 diabetes mellitus who were randomized to intensive medical therapy alone or with either gastric bypass or sleeve gastrectomy.
  • Of the 134 patients who completed the 5-year follow up, a glycated hemoglobin level of ≤6% (primary study endpoint) at 5 years was achieved in 2 of 38 patients receiving medical therapy, compared with 14/49 for gastric bypass and 11/47 for sleeve gastrectomy.
  • At 5 years, both surgical procedures were superior to intensive medical therapy for achieving glycated hemoglobin of ≤6% without use of diabetes medication (remission), ≤6.5% without use of diabetes medication and ≤7% with use of diabetes medication.
  • The reductions in glycated hemoglobin levels and body mass index (BMI) in the surgical groups were similar among patients with a BMI of <35 kg/m2 and those with a BMI of 35 kg/m2 or more.
  • At 5 years, cardiovascular and glucose-lowering medication use was reduced from baseline in the two surgical groups, and reductions in body weight, BMI, waist circumference and waist-to-hip ratio, as well as in triglyceride levels, were greater after surgery than after intensive medical therapy, as were increases in high-density lipoprotein.
  • Changes in quality of life measures were significantly better in both the gastric bypass and sleeve gastrectomy groups than in the intensive medical therapy group at 5 years.
  • The results of this 5-year follow-up show that the beneficial effects of bariatric surgery on glycemic control are durable, even among patients with mild obesity.

Schauer PR et al. N Engl J Med 2017; 376: 641–651. doi: 10.1056/NEJMoa1600869

Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5-year follow-up of an open-label, single-center, randomized controlled trial

Five-year results of a randomized controlled trial comparing metabolic surgery and conventional medical treatment in obese patients with type 2 diabetes mellitus (T2DM) are presented here, with results supporting the addition of surgery to the treatment algorithm for T2DM.

Summary points
  • Sixty patients with type 2 diabetes mellitus (T2DM) and a body mass index of at least 35 kg/m2 were randomized to receive medical treatment, Roux-en-Y gastric bypass or biliopancreatic diversion; 53 patients completed 5 years’ follow-up.
  • The primary endpoint was rate of diabetes remission (fasting glucose concentration of ≤5.6 mmol/L and HbA1c of ≤6.5% without active pharmacological treatment for at least 1 year) at 2 years.
  • At 5 years, 0/15 patients in the medical treatment group and 19 (50%) of the 38 patients in the surgery group (7/19 in the gastric bypass and 12/19 in the biliopancreatic diversion group) had achieved diabetes remission.
  • Hyperglycemia relapsed in 15/34 (44%) surgery patients who achieved 2-year diabetes remission, but these patients maintained a mean HbA1c of 6·7% at 5 years with diet and either metformin or no medication; overall, 31/38 surgical patients maintained HbA1c <7% with little or no glucose-lowering medication.
  • At 5 years, surgically treated patients had significantly lower plasma total cholesterol, LDL cholesterol and triglyceride concentrations than medically treated patients, with surgically treated patients also having better scores on quality of life measures than medically treated patients.
  • In summary, surgery was shown to be more effective than medical treatment for long-term control of T2DM among obese patients, supporting consideration of surgery in the treatment algorithm for T2DM.

Mingrone G et al. Lancet 2015; 386: 964–973. doi: 10.1016/S0140-6736(15)00075-6

Gastric bypass surgery vs intensive lifestyle and medical intervention for type 2 diabetes: The CROSSROADS randomized controlled trial

This paper presents the results of the randomized CROSSROADS study, demonstrating that gastric bypass surgery is superior to intensive medical and lifestyle intervention in patients with type 2 diabetes with mild-to-moderate obesity.

Summary points
  • In the prospective randomized controlled CROSSROADS (Calorie Reduction Or Surgery: Seeking to Reduce Obesity And Diabetes Study) trial, a population-based recruitment strategy was used to enroll patients with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 30–45 kg/m2, to compare Roux-en-Y (RYGB) surgery to an intensive lifestyle and medical intervention (ILMI).
  • Of 1808 screened candidates, 43 were randomized, 23 to surgery and 20 to the ILMI, with 32 participants included in analyses (five surgery participants and six ILMI participants had a baseline BMI of <35 kg/m2).
  • The primary outcome, percentage of participants in each group who achieved diabetes remission at 1 year (HbA1c <6.0% off all diabetes medications) was met in 60% of participants after RYGB vs 5.9% with ILMI, with an odds ratio for diabetes remission at 1 year after RYGB compared with ILMI of 19.8 (95% confidence interval 2.0, 194.6).
  • Diabetes remission was not predicted by baseline BMI, age or sex, or amount of weight lost during 1 year, and there was no correlation between change in body weight and change in HbA1c at 6 or 12 months among those who underwent RYGB.
  • Overall, at 1 year, surgery was superior to the ILMI for diabetes remission, glycemic control, reductions in body weight, adiposity, systolic blood pressure, estimated insulin resistance, use of diabetes medications and hypertension, and overall health state.
  • There were 64 adverse events in the ILMI group and 31 in the RYGB group, with more hypoglycemic events with ILMI (n=43) than RYGB (n=16).
  • Of note, RYGB was shown to be both safe and effective regardless of BMI, with no greater risk among people with a BMI of <35 kg/m2, the currently accepted threshold for bariatric surgery, calling into question the practice of using strict BMI cutoffs as the primary criteria for surgical selection in patients with T2DM.

Cummings DE et al. Diabetologia 2016; 59: 945–953. doi: 10.1007/s00125-016-3903-x

Longer-term physiological and metabolic effects of gastric bypass surgery

This review summarizes the metabolic and physiological effects of Roux-en-Y gastric bypass surgery on pancreatic function, peripheral insulin sensitivity and gastrointestinal remodeling.

Summary points
  • The acute metabolic response to gastric bypass surgery is thought to occur via mechanisms such as improved incretin response, elevated insulin secretion, β-cell protection and proliferation, and increased gut glucose utilization.
  • Diabetes reversal after Roux-en-Y gastric bypass (RYGB) surgery may occur via preservation of β-cell function and mass, with two emerging hypotheses for this response:
    • The foregut hypothesis – nutrients entering the duodenum stimulate release of an unknown hormone, an anti-incretin. Bypassing this section of the gut inhibits release of this anti-incretin, allowing normal glycemic control. 
    • The hindgut hypothesis – food entering the lower gut stimulates incretin hormone release (glucagon-like peptide 1), acting on the pancreas to amplify glucose-induced insulin secretion and thus regulation of blood glucose concentrations.
  • Improved glycemic control following surgery is associated with acute improvement in β-cell function and survival, leading to compensation of insulin resistance via elevated insulin secretion – the more persistent response in the RYGB group may be due to decreased accumulation of truncal fat and elevated β-cell function.
  • Many of the long-term metabolic improvements that occur following bariatric surgery may be explained by the significant weight loss that occurs.
  • Gastric bypass surgery has a profound metabolic effect on the liver, skeletal muscle and adipose tissue, with evidence of significant long-term changes in expression and sensitivity of proteins in the insulin-signaling pathway in skeletal muscle.
  • Several studies support long-term remodeling of the gastrointestinal mucosa after bariatric surgery, with data suggesting that gastric bypass surgery may improve glycemic control by stimulating intestinal hypertrophy and glucose utilization.
  • Bariatric surgery alters exposure of nutrients to bile acids, with the bile acids increasingly recognized as signaling molecules playing a crucial role in lipid and glucose homeostasis.

Mosinski JD, Kirwan JP. Curr Diab Rep 2016; 16: 50. doi: 10.1007/s11892-016-0747-1

Glycemic control and reduction of cardiovascular risk following bariatric surgery

This chapter examines the effects of the currently used bariatric procedures on cardiovascular risk factors.

Summary points
  • The four most common bariatric procedures, Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), vertical sleeve gastrectomy (VSG) and biliopancreatic diversion (BDP) are all associated with significant improvements in cardiovascular risk factors, but specific effects differ.
  • The extent of weight loss following bariatric surgery varies by procedure, with the greatest losses occurring with BDP, followed by RYGB and VSG, all of which are associated with rapid loss, followed by AGB, which is associated with more gradual loss.
  • Bariatric surgery is also associated with significant improvements in glycemic control, although the magnitude varies by procedure, with the greatest effects again seen with BPD, followed by RYGB and VSG, with a substantially lesser effect with AGB.
  • Bariatric surgery is associated with diabetes remission in a high proportion of patients, although over 10 years, many patients experience relapse.
  • Alterations in lipid metabolism also occur following bariatric surgery, particularly with BPD, followed by RYGB and VSG.
  • Current evidence suggests that all four procedures lead to initial improvements in blood pressure but significant, sustained changes are only seen with RYGB and BPG.
  • Bariatric surgery has also been shown to attenuate systemic inflammation, which with RYGB, VSG and BPD may be due to the anti-inflammatory effects of glucagon-like peptide 1.
  • There is also evidence to suggest that bariatric surgery may prevent, halt and even reverse progression of renal impairment associated with type 2 diabetes mellitus and obesity.

Elliott JA, le Roux CW. In: Obesity, bariatric and metabolic surgery: A practical guide. Edited by Agrawal S. Springer International Publishing, 2015. doi: 10.1007/978-3-319-04343-2_55

Clinical outcomes of metabolic surgery: Microvascular and macrovascular complications

In this article, the authors review background information, clinical findings to date and current research regarding microvascular and macrovascular outcomes following bariatric surgery.

Summary points
  • Data on the impact of bariatric surgery on microvascular outcomes (complications related to renal disease and diabetes-related eye disease and neuropathy) and macrovascular outcomes (coronary artery, cerebrovascular and peripheral vascular diseases), including cardiovascular death, are scarce.
  • Tight glycemic control reduces microvascular complications, but macrovascular complications and cardiovascular mortality remain difficult to address.
  • While there is substantial evidence for glycemia-lowering effects of bariatric surgery in patients with type 2 diabetes mellitus, remission after surgery is not durable in all patients, with many relapsing at some point.
  • Current evidence suggests that the amount of time spent in each of three intermediate health states (unremitted diabetes, durable diabetes remission and diabetes remission followed by relapse) may significantly affect the incidence of micro- and macrovascular complications.
  • Nonsurgical treatment modalities have demonstrated a consistent reduction in risk of microvascular disease, and a number of small studies have also reported favorable outcomes in renal function markers following bariatric surgery.
  • Studies available to date have shown important reductions in risk of both microvascular and macrovascular outcomes following bariatric surgery, including reductions in risk of all-cause mortality and cardiovascular mortality, cardiovascular events and incidence of albuminuria.
  • High-quality randomized controlled trials are needed to define the impact of bariatric surgery on long-term micro- and macrovascular outcomes.

Adams TD et al. Diabetes Care 2016; 39: 912–923. doi: 10.2337/dc16-0157

Healthcare costs during 15 years after bariatric surgery for patients with different baseline glucose status

In this study, Keating et al. assessed 15-year healthcare costs associated with bariatric surgery compared with conventional medical therapy in obese patients with various baseline glucose states.

Summary points
  • Healthcare costs were assessed over 15 years in 2010 obese patients who chose to undergo bariatric surgery and compared with a contemporaneously matched obese control group of 2037 patients using Swedish healthcare registers.
  • In the surgery group, 13% underwent gastric bypass, 19% underwent gastric banding and 68% underwent vertical-banded gastroplasty.
  • Fifteen-year drug costs did not differ between surgery and control groups in euglycemic patients but lower 15-year drug costs were observed in the surgery than the control group in patients with prediabetes and in patients with diabetes. Greater 15-year inpatient costs were observed in the surgery group for all glucose subgroups.
  • Total healthcare costs were higher in surgery patients in the euglycemic and prediabetes subgroups, while no difference was detected between treatment groups in patients with diabetes.
  • In this study, in which surgery was performed between 1987 and 2001, the rate of laparoscopic surgery was only 11%, compared with 97% in 2012 in Sweden, with such surgery associated with significantly lower costs than open surgery. Additionally, the majority of patients underwent gastric banding and later had re-operations to convert to gastric bypass.
  • Overall, for obese patients with type 2 diabetes mellitus, the upfront costs of bariatric surgery appear to be offset by the prevention of further healthcare and drug use.

Keating C et al. Lancet Diabetes Endo 2015; 3: 855–865. doi: 10.1016/S2213-8587(15)00290-9


Complications

Post-gastric bypass hypoglycemia

In this review, the authors discuss the definitions, diagnosis and management of post-gastric bypass hypoglycemia.

Summary points
  • Roux-en-Y bypass (RYGB) surgery, while very effective for diabetes remission, is associated with potentially significant complications, including post-RYGB surgery hypoglycemia (PGBH), with prevalence estimates ranging from as low as 1% in older literature to as high as 34%, depending on reporting and the definition used.
  • It is important to distinguish PGBH from other forms of hypoglycemia, which are characterized by impaired endogenous insulin production and functional β-cell disorders.
  • The underlying pathology of PGBH has yet to be fully elucidated but recent studies point to a role of the incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide.
  • Another proposed mechanism for PGBH is altered intestinal glucose absorption, associated with changes in gut microbiota, bile acid levels and composition.
  • The first step in evaluation of a patient in whom PGBH is suspected is obtaining a thorough clinical history, with attention on timing and onset of symptoms and relation to nutrient ingestion; a review of current medications may also be helpful.
  • Diagnosis of PGBH should be made based on a mixed meal challenge test rather than an oral glucose challenge test.
  • Following diagnosis of PGBH, the goal of therapy should be reduction of frequency and severity of episodes, with the first approach to treatment comprising strict changes in diet and, if necessary, pharmacologic therapies (such as acarbose, somatostatin analogs, diazoxide or calcium channel blockers).

Rariy CM, Rometo D, Korytkowski M. Curr Diab Rep 2016; 16: 19. doi: 10.1007/s11892-015-0711-5

Thirty-day (early) complications of bariatric surgical procedures

It is important to recognize and manage acute bariatric surgical complications. This chapter outlines complications that occur within the first 30 days after bariatric surgery.

Summary points
  • There are several potentially serious complications that may occur in the first 30 days following Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), laparoscopic adjustable gastric band (LAGB) and biliopancreatic diversion, and it is important for general surgeons to be able to recognize and manage these.
  • A large database study reported a 30-day complication rate following RYGB of 8.7%, with the most commonly encountered early complications including bleeding (2.1%), leak (1.8%), port-site related complications (0.6%) and small bowel obstruction (1.0%).
  • In a recent review, the complication rate following SG was not significantly different from that with RYGB; the reported leak rate was 2.3% versus 1.9% in RYGB. Management of leak is a challenging clinical problem with serious sequelae if not promptly recognized and treated.
  • In patients who have undergone LAGB, presentation with abdominal pain, nausea, intractable reflux or intolerance of oral intake, fluid should be withdrawn from the band, and a plain abdominal X-ray should be taken to evaluate band slippage. Complications requiring reoperation within the first 30 days are rare: one large study reported a rate of complications requiring emergency reoperation of 0.2%.
  • Biliopancreatic diversion/duodenal switch has been shown to have the highest rate of short-term complications, with 30-day morbidity estimates ranging from 7% to 8.6% for one-stage procedures.
  • Patients undergoing bariatric surgery are at high risk for venous thromboembolism (VTE), given obesity itself is an independent risk factor, although with widespread use of thromboprophylaxis, the rate of VTE following bariatric surgery ranges between 0.21% and 0.42% within 90 days of surgery.
  • Mesenteric thrombosis is a rare, but potentially fatal, complication following laparoscopic bariatric surgery – with an incidence of 0.3% for all bariatric patients and 1% for SG.
  • Outcomes after complications in the early postoperative period after bariatric surgery depend upon early recognition and treatment.

Hamad GG, Guerrero VT. In: Bariatric surgery complications. Edited by Blackstone R. Springer, Cham, 2017. doi: 10.1007/978-3-319-43968-6_2

Late complications of bariatric procedures

This chapter outlines complications that occur at least 30 days after initial bariatric surgery.

Summary points
  • Late-stage complications in bariatric surgery are defined as those occurring at least 30 days after the initial procedure.
  • Late-stage complications associated with these procedures include band slippage and band erosion, megaesophagus, port problems (malfunctions, infection, port-site hernia), intestinal obstruction, marginal ulceration, nutritional deficiencies (protein malnutrition, vitamin deficiency, anemia, Wernicke’s encephalopathy) and gastric outlet obstruction.
  • Thirty-day morbidity and mortality are extremely low for laparoscopic adjustable gastric band. Late-stage complication rates range in various studies from 10% to 25%, predominantly band slippage and port-site issues (infection, malfunctioning port), with less common but concerning complications include band erosion and megaesophagus.
  • Complications that can occur following Roux-en-Y gastric bypass (RYGB) include intestinal obstruction, a rare but well-known complication of this procedure with rates ranging from 1.5% to 5%, and marginal ulcerations (ulcers occurring at the gastrojejunal anastomosis), which may occur at any time following RYGB.
  • Late complications for sleeve gastrectomy are rare, with the main issues with this surgery being nutritional deficiencies and port-site hernias (an issue common to all bariatric procedures).
  • Late-stage complications associated with biliopancreatic diversion with duodenal switch include those common to other procedures, including marginal ulcers, intestinal obstruction, and port-site hernias, as well as those specific to this procedure, namely gastric outlet obstruction and nutritional deficiencies relating to the malabsorptive nature of the procedure.

Kurian M, Creange C. In: Bariatric surgery complications. Edited by Blackstone R. Springer, Cham, 2017. doi: 10.1007/978-3-319-43968-6_3