Metabolic Surgery: A Comprehensive Review of Historical Evolution, Procedures, Mechanisms, Patient Selection, Efficacy, Safety, and Emerging Research

Many thanks to our sponsor Esdebe who helped us prepare this research report.

Abstract

Metabolic surgery, increasingly recognized as a potent therapeutic modality beyond mere weight reduction, stands as a pivotal intervention for the comprehensive management of severe obesity and its associated metabolic comorbidities, most notably Type 2 Diabetes Mellitus (T2DM). This extensive review undertakes a meticulous exploration of the intricate historical trajectory that has shaped metabolic surgery, from its rudimentary origins to its current sophisticated manifestations. It rigorously examines the diverse array of surgical procedures, dissecting their unique anatomical modifications and unraveling the multifaceted physiological mechanisms through which they confer profound metabolic benefits. Furthermore, this report scrutinizes the evolving criteria for patient selection, acknowledging the shift from purely Body Mass Index (BMI)-centric indications to a more holistic, comorbidity-driven approach. It critically evaluates the robust long-term efficacy and safety profiles of these interventions across varied demographic and clinical populations, addressing both their transformative potential and inherent risks. Finally, it highlights the vibrant landscape of emerging research, encompassing novel procedural innovations, enhanced mechanistic understanding, and integrated therapeutic strategies aimed at further optimizing these life-altering interventions. By synthesizing the vast expanse of current scientific and clinical knowledge, this report aspires to furnish a nuanced, in-depth understanding of metabolic surgery’s indispensable role in the modern therapeutic armamentarium against the global epidemic of metabolic disorders.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

1. Introduction

The relentless escalation of metabolic diseases, particularly the global pandemic of Type 2 Diabetes Mellitus (T2DM) and its profound intertwining with obesity, represents one of the most pressing public health challenges of the 21st century. The World Health Organization (WHO) estimates that the prevalence of obesity has nearly tripled since 1975, with over 650 million adults globally affected [who.int/news-room/fact-sheets/detail/obesity-and-overweight]. This pervasive epidemic is inextricably linked to a cascade of severe health complications, including cardiovascular disease, certain cancers, sleep apnea, non-alcoholic fatty liver disease (NAFLD), musculoskeletal disorders, and significantly, T2DM. Traditional therapeutic paradigms, encompassing lifestyle modifications, pharmacotherapy, and conventional dietary interventions, often fall short in achieving durable remission or substantial improvement for individuals grappling with advanced stages of these complex, multifactorial diseases. This therapeutic gap has necessitated an urgent exploration and embrace of more potent and transformative strategies.

Within this context, metabolic surgery, originally conceived primarily for morbid obesity (bariatric surgery), has unequivocally emerged as a paradigm-shifting approach. Its efficacy extends far beyond mere ponderal reduction, demonstrating remarkable capabilities in achieving significant improvements, and often remission, of T2DM, hypertension, dyslipidemia, and other obesity-related comorbidities. This profound metabolic impact has redefined its nomenclature and expanded its indications, positioning it as a cornerstone in the comprehensive management of metabolic syndrome. This comprehensive report meticulously dissects metabolic surgery, providing an exhaustive analysis of its rich historical evolution, from rudimentary experimental procedures to contemporary refined techniques. It delves into the diverse array of procedural variations, elucidating their intricate anatomical modifications and the complex, overlapping physiological mechanisms that underpin their therapeutic success. Furthermore, the report critically examines the evolving criteria for patient selection, the robust long-term efficacy, the carefully monitored safety profiles, and the dynamic landscape of emerging research trends that promise to further refine and expand the reach of these life-changing interventions. Through this in-depth analysis, the aim is to consolidate current understanding and underscore the transformative potential of metabolic surgery in addressing the intricate challenges posed by metabolic disorders.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

2. Historical Evolution of Metabolic Surgery

The journey of metabolic surgery is a testament to persistent medical innovation, marked by iterative advancements, critical reappraisals, and a deepening understanding of human physiology. Its roots delve into the mid-20th century, when pioneering surgeons began to observe and deliberately harness alterations in gastrointestinal anatomy to induce weight loss and, subsequently, metabolic improvements. The distinction between ‘bariatric’ (weight-reducing) and ‘metabolic’ (disease-improving) surgery has become increasingly blurred, with the latter term now accurately reflecting the broader, non-weight-dependent benefits of these procedures.

2.1. Early Explorations and the Jejuno-Ileal Bypass (1950s-1970s)

The earliest formal surgical intervention for obesity can be traced back to the innovative work of Dr. Arnold Kremen in 1954. He introduced the jejuno-ileal bypass (JIB), a procedure fundamentally designed to induce profound malabsorption by effectively bypassing a substantial segment of the small intestine. The technique involved connecting the proximal jejunum directly to the distal ileum, leaving a significant length of the jejunum and ileum excluded from the digestive stream. This drastic reduction in the functional absorptive surface of the small intestine undeniably achieved substantial weight loss, often exceeding that seen with contemporary methods. Early observations also noted improvements in lipid profiles and, in some cases, diabetes. [1]

However, the JIB was fraught with severe and often debilitating complications, primarily due to the extensive malabsorption it induced. Patients frequently developed chronic diarrhea, severe electrolyte imbalances, and profound nutritional deficiencies (e.g., vitamin B12, folate, fat-soluble vitamins, calcium, iron, protein-calorie malnutrition). More critically, the procedure was associated with life-threatening hepatotoxicity, leading to liver failure in a significant number of patients, as well as oxalate nephropathy (kidney stones), metabolic bone disease, and a perplexing constellation of arthritic symptoms. The high incidence of these severe, sometimes irreversible complications ultimately led to its widespread abandonment by the late 1970s, serving as a cautionary tale for subsequent surgical innovations. Its legacy, however, lies in demonstrating the powerful metabolic effects that gastrointestinal rearrangement could elicit, albeit through an overly aggressive approach.

2.2. The Advent of Gastric Bypass (1960s-1970s)

In 1966, Dr. Edward E. Mason at the University of Iowa performed the first gastric bypass procedure. Initially, this involved creating a small gastric pouch and anastomosing it to a loop of jejunum. The procedure primarily aimed at restricting food intake by drastically reducing the functional stomach volume. Over time, Mason’s technique evolved to mitigate the risk of bile reflux into the esophagus and to further enhance malabsorptive effects. This led to the development of the Roux-en-Y gastric bypass (RYGB), a more sophisticated configuration where the small intestine is divided, and the distal limb (Roux limb) is brought up to anastomose with the small gastric pouch, while the biliopancreatic limb (carrying digestive enzymes and bile) is reconnected further down the Roux limb. [1]

RYGB rapidly gained prominence due to its superior balance of efficacy and safety compared to JIB. It effectively combined gastric restriction with a degree of malabsorption and, critically, induced profound hormonal changes. Its consistent success in achieving significant and durable weight loss, coupled with impressive improvements in T2DM, hypertension, and dyslipidemia, established RYGB as a cornerstone procedure in bariatric and metabolic surgery, a position it largely maintains to this day.

2.3. Biliopancreatic Diversion (BPD) and Duodenal Switch (BPD/DS) (1970s-1980s)

The 1970s saw the emergence of more aggressively malabsorptive procedures, notably the Biliopancreatic Diversion (BPD) pioneered by Dr. Nicola Scopinaro in Italy. BPD involved a distal gastrectomy (removal of a large part of the stomach) combined with extensive intestinal rerouting, creating a very short common channel for nutrient absorption. This procedure yielded exceptional weight loss and T2DM remission rates, often superior to RYGB, but came with a higher risk of severe nutritional deficiencies and other complications akin to, though less severe than, JIB. [1]

Recognizing the benefits of pyloric preservation (which helps regulate gastric emptying and reduces the risk of dumping syndrome) and the aggressive nature of BPD’s malabsorption, Dr. Doug Hess and Dr. Michel Gagner modified the procedure in the 1980s, leading to the Biliopancreatic Diversion with Duodenal Switch (BPD/DS). This modification preserved the pylorus by performing a sleeve gastrectomy (removing about 80% of the stomach longitudinally) and then connecting the duodenum to a very distal segment of the ileum, creating a long biliopancreatic limb and a relatively short common channel. BPD/DS demonstrated exceptional metabolic efficacy, particularly for super-obese individuals and those with severe T2DM, but remains a technically demanding procedure with a higher long-term risk of nutritional deficiencies compared to RYGB or sleeve gastrectomy. [1]

2.4. The Laparoscopic Revolution and Modern Era (Late 20th – Early 21st Centuries)

The late 20th century witnessed a revolutionary shift in surgical practice with the widespread adoption of laparoscopic techniques. The first laparoscopic cholecystectomy was performed in 1987, and by the early 1990s, laparoscopic approaches were being applied to bariatric surgery. The first laparoscopic RYGB was performed by Dr. Alan Wittgrove in 1993. This minimally invasive approach drastically reduced surgical trauma, resulting in smaller incisions, less pain, shorter hospital stays, faster recovery times, and lower rates of wound complications compared to traditional open surgery. This significantly enhanced the safety and feasibility of metabolic surgeries, making them accessible to a much broader patient population. [elsevier.es/es-revista-porto-biomedical-journal-445-articulo-a-brief-history-bariatric-surgery-S2444866416300186]

Two procedures gained considerable popularity in the laparoscopic era:

• Laparoscopic Adjustable Gastric Banding (LAGB): Introduced in the 1990s, LAGB involved placing an inflatable silicone band around the upper part of the stomach, creating a small pouch above the band and a restricted outlet. The band’s tightness could be adjusted post-operatively via a port placed under the skin. LAGB was initially appealing due to its reversibility and less invasive nature. However, long-term studies revealed suboptimal weight loss, high rates of reoperation due to complications (e.g., band erosion, slippage, port problems), and less consistent metabolic improvements compared to bypass or sleeve procedures. Consequently, its popularity has significantly waned.
• Laparoscopic Sleeve Gastrectomy (SG): Initially performed as the first stage of a two-stage BPD/DS for super-obese patients, SG (also known as vertical sleeve gastrectomy) emerged as a standalone procedure around 2005. It involves the removal of approximately 75-80% of the stomach longitudinally, creating a narrow, tube-like gastric conduit. SG quickly gained traction due to its technical simplicity, absence of intestinal bypass, good weight loss outcomes, and significant metabolic benefits, particularly for T2DM. It now stands as the most commonly performed bariatric-metabolic procedure worldwide. [onlinelibrary.wiley.com/doi/full/10.1002/ags3.12030]

The evolution continues with newer variations like the One-Anastomosis Gastric Bypass (OAGB) and Single Anastomosis Duodeno-Ileostomy (SADI), along with the growing field of endoscopic bariatric and metabolic therapies. The historical trajectory of metabolic surgery reflects a continuous quest for optimal efficacy coupled with enhanced safety and durability, shifting the focus from purely restrictive mechanisms to the intricate interplay of hormonal and metabolic alterations.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

3. Spectrum of Metabolic Surgical Procedures

Metabolic surgery now encompasses a diverse array of procedures, each with distinct anatomical modifications, operative complexities, primary mechanisms of action, and profiles of efficacy and potential complications. The choice of procedure is often tailored to individual patient characteristics, comorbidities, and desired outcomes, necessitating a thorough understanding of their nuances.

3.1. Roux-en-Y Gastric Bypass (RYGB)

The Roux-en-Y Gastric Bypass remains one of the most widely performed and thoroughly studied metabolic procedures, often considered the ‘gold standard’ against which others are compared. The procedure involves several critical anatomical alterations:

• Gastric Pouch Creation: A small gastric pouch (typically 15-30 mL in volume) is created from the fundus and body of the stomach, effectively separating it from the majority of the native stomach. This significantly restricts the amount of food that can be consumed at one time.
• Roux Limb Construction: The jejunum is divided approximately 50-150 cm distal to the Ligament of Treitz. The distal segment (Roux limb or alimentary limb) is then brought up and anastomosed to the small gastric pouch. The length of this limb can vary, influencing the degree of malabsorption.
• Biliopancreatic Limb Anastomosis: The proximal segment of the divided jejunum, which carries bile and pancreatic enzymes (biliopancreatic limb), is reconnected to the Roux limb further downstream, typically 50-150 cm from the gastrojejunostomy, forming the entero-enterostomy (common channel). [1]

Mechanisms: RYGB operates through a potent combination of mechanisms:
* Gastric Restriction: The small gastric pouch limits food intake, promoting early satiety.
* Intestinal Rerouting and Mild Malabsorption: Food bypasses the duodenum and a variable length of the jejunum, leading to some degree of nutrient malabsorption. The length of the Roux and biliopancreatic limbs influences the malabsorptive component.
* Profound Hormonal Changes: Rapid delivery of undigested nutrients to the distal small intestine (ileum) stimulates the release of incretin hormones like Glucagon-like Peptide-1 (GLP-1) and Peptide YY (PYY) from L-cells, enhancing insulin secretion, improving satiety, and slowing gastric emptying. Ghrelin levels, the ‘hunger hormone’, are typically reduced or remain stable, unlike some other procedures. Alterations in bile acid metabolism also contribute.

Outcomes: RYGB typically achieves 60-80% excess weight loss (EWL) at 1-2 years, with good long-term maintenance. T2DM remission rates are high, often reaching 60-80%, with significant improvements in hypertension and dyslipidemia. [7]

Advantages: Excellent long-term data, high efficacy for weight loss and metabolic disease resolution, particularly T2DM. Disadvantages include its technical complexity, potential for nutritional deficiencies requiring lifelong supplementation, and risks of internal hernias, anastomotic ulcers, and dumping syndrome.

3.2. Sleeve Gastrectomy (SG)

Sleeve Gastrectomy, currently the most commonly performed bariatric-metabolic procedure globally, is a purely restrictive procedure in its primary anatomical design, though its metabolic effects are far more complex. The operation involves:

• Gastric Resection: Approximately 75-80% of the greater curvature of the stomach is removed along a bougie (calibration tube) from the antrum to the angle of His, leaving a narrow, tube-shaped stomach (or ‘sleeve’) with a capacity of 80-150 mL. The pylorus, which regulates gastric emptying, is preserved. [1]

Mechanisms: SG primarily achieves its effects through:
* Gastric Restriction: The drastically reduced stomach volume limits food intake and promotes early satiety.
* Hormonal Changes: The resection of the fundus, a major site of ghrelin production, leads to a significant reduction in circulating ghrelin levels, which contributes to decreased appetite. Rapid gastric emptying into the duodenum also stimulates incretin release, albeit to a lesser extent than RYGB, improving glucose homeostasis. Changes in bile acids and gut microbiota also play a role.

Outcomes: SG typically achieves 50-70% EWL at 1-2 years. T2DM remission rates are substantial, often 40-60%, with good resolution of other comorbidities. [6]

Advantages: Simpler technically than RYGB (no intestinal anastomoses), lower risk of micronutrient deficiencies (though still requires supplementation), preserves pyloric function (reducing dumping syndrome risk). Disadvantages include potential for worsening or new-onset gastroesophageal reflux disease (GERD), irreversible nature, and a risk of gastric leak from the staple line.

3.3. Biliopancreatic Diversion with Duodenal Switch (BPD/DS)

BPD/DS is considered the most powerful metabolic surgery in terms of weight loss and T2DM resolution, reserved typically for individuals with severe obesity (BMI >50 kg/m²) or those with less severe obesity but highly refractory T2DM. It is a complex, two-stage procedure (though often performed in one stage) involving:

• Sleeve Gastrectomy: The first component is an SG, reducing stomach volume and ghrelin production.
• Duodenal Switch: The duodenum is divided just beyond the pylorus. The proximal duodenum is then anastomosed to a very distal segment of the ileum (typically 200-250 cm from the ileocecal valve), forming the alimentary limb. The biliopancreatic limb (carrying bile and pancreatic enzymes) is connected to the common channel approximately 75-100 cm proximal to the ileocecal valve. This creates a very short ‘common channel’ where food and digestive enzymes mix, leading to profound malabsorption. [1]

Mechanisms: BPD/DS combines powerful mechanisms:
* Gastric Restriction: From the sleeve gastrectomy.
* Profound Malabsorption: The very short common channel leads to significant malabsorption of fats and carbohydrates.
* Extensive Hormonal Changes: Rapid delivery of partially digested nutrients to the distal ileum intensely stimulates incretin release (GLP-1, PYY) and leads to significant alterations in bile acid metabolism and gut microbiota.

Outcomes: BPD/DS achieves the highest EWL (70-90%) and T2DM remission rates (often >80%) among all procedures. [1]

Advantages: Most effective for severe obesity and T2DM, highest long-term remission rates. Disadvantages include highest complexity, highest risk of long-term nutritional deficiencies (requiring aggressive, lifelong supplementation and monitoring), higher rates of chronic diarrhea, and sometimes malodorous flatus/stools due to steatorrhea.

3.4. Single Anastomosis Duodeno-Ileostomy (SADI) / Single Anastomosis Duodeno-Ileal bypass with Sleeve Gastrectomy (SADI-S)

SADI, also known as SADI-S, is a newer modification of BPD/DS designed to simplify the procedure by utilizing a single anastomosis while retaining similar efficacy. It involves:

• Sleeve Gastrectomy: Similar to BPD/DS and SG.
• Single Anastomosis: The duodenum is divided, and the proximal end is directly anastomosed to a loop of distal ileum (typically 200-300 cm from the ileocecal valve). This creates a single connection, bypassing a significant portion of the small intestine. [2]

Mechanisms: SADI-S combines gastric restriction with significant intestinal malabsorption and robust hormonal changes, similar to BPD/DS but potentially with a slightly longer common channel or different hormonal kinetics due to the single anastomosis.

Outcomes: Promising early and mid-term results suggest comparable weight loss (60-85% EWL) and T2DM remission rates to BPD/DS, with potentially fewer long-term complications, particularly internal hernias, due to the single anastomosis. [obesityaction.org/resources/metabolic-bariatric-surgery/]

Advantages: Simpler than BPD/DS, potentially lower operative time and risk of certain complications, high efficacy. Disadvantages include being a newer procedure with less long-term data, and continued risk of nutritional deficiencies, though possibly less severe than BPD/DS depending on the common channel length.

3.5. One-Anastomosis Gastric Bypass (OAGB) / Mini Gastric Bypass (MGB)

OAGB, sometimes referred to as Mini Gastric Bypass (MGB), has gained increasing popularity as a simplified alternative to RYGB. It involves:

• Long Gastric Pouch: A long, narrow gastric pouch (similar to the upper part of a sleeve gastrectomy) is created along the lesser curvature of the stomach.
• Single Anastomosis: A loop of jejunum (typically 150-250 cm distal to the Ligament of Treitz) is brought up and anastomosed directly to the long gastric pouch. This single connection bypasses the duodenum and a significant length of the proximal jejunum, creating both restriction and a substantial malabsorptive component. [2]

Mechanisms: OAGB combines gastric restriction with significant intestinal malabsorption and robust hormonal changes due to rapid nutrient delivery to the distal small intestine, similar to RYGB but potentially with a more pronounced malabsorptive component depending on limb length.

Outcomes: OAGB typically achieves 65-80% EWL and high rates of T2DM remission (60-80%), comparable to RYGB. [obesityaction.org/resources/metabolic-bariatric-surgery/]

Advantages: Technically simpler and quicker than RYGB (single anastomosis), comparable efficacy, potentially lower risk of internal hernias. Disadvantages include a higher potential for bile reflux into the esophagus and pouch due to the bilio-pancreatic limb connecting directly to the stomach, and a significant risk of nutritional deficiencies requiring lifelong monitoring.

3.6. Endoscopic Sleeve Gastroplasty (ESG)

Endoscopic Sleeve Gastroplasty is a minimally invasive, non-surgical procedure performed entirely endoscopically. It involves:

• Endoscopic Suturing: Using a specialized endoscopic suturing device, a series of full-thickness sutures are placed along the greater curvature of the stomach, essentially folding and cinching the stomach to reduce its volume. This creates a narrower, sleeve-like stomach similar in shape to a surgical sleeve, but without incision or resection. [3]

Mechanisms: ESG primarily works through:
* Gastric Restriction: The reduced stomach volume limits food intake and promotes satiety.
* Delayed Gastric Emptying: The sutures can also slow down gastric emptying, contributing to prolonged satiety.

Outcomes: ESG typically achieves 15-20% total body weight loss or 40-60% EWL at 1 year. It demonstrates good improvements in T2DM and other comorbidities, though generally less pronounced than surgical options. [en.wikipedia.org/wiki/Endoscopic_sleeve_gastroplasty]

Advantages: Minimally invasive, no incisions, outpatient procedure, lower complication rates than surgery, potentially reversible. Disadvantages include less weight loss and metabolic improvement compared to surgery, and shorter-term follow-up data. It is often considered for patients with lower BMI (30-40 kg/m²) who are not candidates for or prefer not to undergo traditional surgery.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

4. Mechanisms of Metabolic Surgery

The profound efficacy of metabolic surgery in resolving T2DM and other metabolic comorbidities is not solely attributable to weight loss, although weight reduction is an undeniable and significant contributor. Rather, it is mediated by a complex and dynamic interplay of anatomical, physiological, and hormonal changes that extend far beyond simple calorie restriction. Understanding these intricate mechanisms is crucial for optimizing patient selection, refining existing procedures, and developing novel therapeutic strategies.

4.1. Gastric Restriction and Early Satiety

Nearly all metabolic surgical procedures involve a significant reduction in the functional volume of the stomach. Procedures like Sleeve Gastrectomy (SG) directly reduce the stomach’s capacity by resecting a large portion of it, while Roux-en-Y Gastric Bypass (RYGB) creates a small gastric pouch. This anatomical alteration primarily functions to:

• Limit Food Intake: The reduced capacity physically restricts the quantity of food that can be consumed at a single sitting, leading to a rapid feeling of fullness with smaller meal portions.
• Promote Early Satiety: The distension of the smaller stomach or pouch sends afferent signals to the brain, contributing to a sense of satiety much earlier than pre-surgery. This mechanism is fundamental to the initial phase of weight loss and forms the basis of the restrictive component. [4]

While restriction is a primary driver of initial weight loss, it does not fully explain the rapid and profound improvements in glucose metabolism that often occur even before substantial weight loss has been achieved, pointing to additional, more direct metabolic effects.

4.2. Intestinal Malabsorption and Nutrient Rerouting

Procedures involving intestinal bypass or diversion, such as Biliopancreatic Diversion with Duodenal Switch (BPD/DS), Single Anastomosis Duodeno-Ileostomy (SADI), and Roux-en-Y Gastric Bypass (RYGB), induce varying degrees of malabsorption by excluding significant lengths of the small intestine from the primary digestive path. This rerouting has several critical implications:

• Reduced Nutrient Absorption: Bypassing the duodenum and a portion of the jejunum directly reduces the surface area available for the digestion and absorption of macronutrients (fats, carbohydrates, proteins) and micronutrients. This intentional malabsorption contributes to overall calorie deficit and weight loss, particularly in BPD/DS where the common channel for digestion is very short.
• Altered Nutrient Sensing: The rapid and often undigested delivery of nutrients to the distal small intestine (ileum) is a key trigger for many of the metabolic benefits. This ‘hindgut hypothesis’ posits that the earlier and intensified exposure of the ileum to nutrients stimulates the release of specific enteroendocrine hormones. [4]

4.3. Hormonal Changes: The Gut-Hormone Axis Remodeling

Perhaps the most significant and rapidly acting mechanisms of metabolic surgery are the profound alterations in the secretion and action of gut hormones, which regulate appetite, satiety, glucose homeostasis, and energy expenditure. These changes often precede substantial weight loss, highlighting their direct metabolic impact:

• Glucagon-like Peptide-1 (GLP-1): GLP-1 is an incretin hormone secreted by L-cells primarily in the ileum and colon. Post-surgery, particularly with RYGB and BPD/DS, there is a dramatic and sustained increase in postprandial GLP-1 levels. This is largely attributed to the rapid delivery of undigested or partially digested nutrients to the distal small intestine. GLP-1 exerts multiple beneficial effects: it enhances glucose-dependent insulin secretion, suppresses glucagon release, slows gastric emptying, promotes satiety, and has direct protective effects on pancreatic beta-cells. [4]
• Peptide YY (PYY): PYY is another anorexigenic (appetite-suppressing) hormone co-secreted with GLP-1 by L-cells in the distal small intestine and colon. Similar to GLP-1, its levels are significantly elevated after bypass procedures, contributing to prolonged satiety and reduced food intake. [4]
• Ghrelin: Often referred to as the ‘hunger hormone’, ghrelin is primarily produced in the gastric fundus. Following Sleeve Gastrectomy, the resection of a large portion of the fundus leads to a significant reduction in circulating ghrelin levels, contributing to decreased appetite and altered food preferences. In RYGB, ghrelin levels tend to remain stable or show a less pronounced reduction than SG, suggesting that the fundus is excluded rather than resected, but the overall effect on appetite is still positive due to other hormonal changes. [metabolismjournal.com/article/S0026-0495%2823%2900293-7/fulltext]
• Leptin and Adiponectin: While leptin (a satiety hormone produced by adipocytes) typically decreases with weight loss, its reduction post-surgery is often less than expected for the degree of weight loss, possibly indicating increased leptin sensitivity. Adiponectin, an insulin-sensitizing adipokine, often increases post-surgery, further contributing to improved glucose metabolism. [4]
• Bile Acids: Surgical rerouting of the intestine alters the enterohepatic circulation of bile acids. Bypass procedures lead to increased delivery of primary bile acids to the distal small intestine and colon, affecting the composition of the bile acid pool. Bile acids act as signaling molecules, activating nuclear receptors like Farnesoid X Receptor (FXR) and G Protein-Coupled Bile Acid Receptor 5 (TGR5). Activation of these receptors can influence glucose homeostasis, energy expenditure, and gut microbiota composition, contributing to the metabolic benefits. [4]

4.4. Gut Microbiota Alterations

Recent research has highlighted the critical role of the gut microbiota in mediating the effects of metabolic surgery. The dramatic anatomical and physiological changes post-surgery, including altered pH, oxygen levels, nutrient availability, and bile acid composition, profoundly reshape the gut microbial ecosystem:

• Compositional Shifts: Studies consistently show significant shifts in bacterial phyla and genera after metabolic surgery. Typically, there is an increase in Gammaproteobacteria (e.g., Escherichia), Bacteroidetes, and Verrucomicrobia (e.g., Akkermansia muciniphila), often accompanied by a decrease in Firmicutes. These changes are more pronounced after bypass procedures like RYGB and BPD/DS than after SG. [4]
• Functional Impact: These shifts in microbial composition are not merely observational; they have functional consequences. The altered microbiota can influence host metabolism by:
  • Producing Short-Chain Fatty Acids (SCFAs): Different microbial communities produce different SCFAs (e.g., acetate, propionate, butyrate), which act as signaling molecules, influencing appetite, insulin sensitivity, and energy metabolism.
  • Modulating Bile Acid Metabolism: Gut bacteria play a crucial role in the biotransformation of bile acids, influencing their enterohepatic circulation and signaling pathways.
  • Interacting with Enteroendocrine Cells: Changes in microbiota can indirectly or directly influence the secretion of gut hormones like GLP-1 and PYY.
  • Inflammation and Permeability: A healthier microbial profile can reduce gut inflammation and improve gut barrier function, potentially mitigating systemic inflammation associated with obesity and T2DM. [4]

4.5. Neurohormonal Pathways and Food Preferences

Beyond direct hormonal changes, metabolic surgery influences the complex interplay between the gut and the brain, reshaping neurohormonal pathways that govern appetite, satiety, and reward systems. Patients often report altered food preferences, with a reduced desire for high-fat, high-sugar foods and an increased preference for healthier options. This may be due to:

• Vagal Nerve Modulation: Alterations in nutrient sensing and hormonal signals transmitted via the vagal nerve to the brain stem and hypothalamus, influencing appetite and satiety centers.
• Dopaminergic Reward System: Changes in gut hormones and nutrient absorption can modulate the brain’s reward pathways, reducing the hedonic ‘wanting’ for palatable but unhealthy foods, thus impacting addictive eating behaviors. This recalibration of the reward system is a critical, though less understood, aspect of the long-term success of these interventions. [pmc.ncbi.nlm.nih.gov/articles/PMC10156942/]

In essence, metabolic surgery orchestrates a comprehensive physiological overhaul, remodeling the gut-brain axis and endocrine environment to not only promote weight loss but also directly improve glucose homeostasis and overall metabolic health, even independent of weight reduction.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

5. Patient Selection Criteria

Optimal patient selection is paramount to ensuring the safety, efficacy, and long-term success of metabolic surgical interventions. The criteria have evolved significantly over time, moving from a rigid focus on Body Mass Index (BMI) to a more nuanced assessment that prioritizes the presence and severity of metabolic comorbidities. A multidisciplinary approach involving surgeons, endocrinologists, dietitians, psychologists, and other specialists is now standard practice.

5.1. Evolving BMI Thresholds and Comorbidity Focus

Historically, bariatric surgery guidelines were primarily driven by BMI thresholds. The National Institutes of Health (NIH) Consensus Conference in 1991 set the initial benchmarks:

• BMI ≥ 40 kg/m²: Indication for bariatric surgery without any obesity-related comorbidities.
• BMI ≥ 35 kg/m²: Indication for bariatric surgery with at least one significant obesity-related comorbidity (e.g., T2DM, hypertension, obstructive sleep apnea, dyslipidemia). [ncbi.nlm.nih.gov/books/NBK279090/]

More recently, the understanding of metabolic surgery’s direct effects on T2DM, independent of significant weight loss, has led to a re-evaluation of these guidelines. The 2016 second Diabetes Surgery Summit (DSS-II) consensus guidelines, endorsed by numerous international diabetes organizations, marked a pivotal shift:

• BMI ≥ 40 kg/m² (or ≥37.5 kg/m² for Asians): Metabolic surgery is recommended for individuals with T2DM, regardless of glycemic control.
• BMI 35.0-39.9 kg/m² (or 32.5-37.4 kg/m² for Asians): Metabolic surgery is recommended for individuals with T2DM who have inadequate glycemic control despite optimal lifestyle and medical therapy.
• BMI 30.0-34.9 kg/m² (or 27.5-32.4 kg/m² for Asians): Metabolic surgery should be considered for individuals with T2DM who have inadequate glycemic control despite optimal lifestyle and medical therapy. This expanded indication for lower BMI thresholds specifically for T2DM highlights the direct metabolic benefits. [5]

These guidelines emphasize that the presence and severity of T2DM (and other metabolic diseases) are crucial determinants, rather than BMI alone, especially for patients in the lower end of the obesity spectrum. The decision to perform surgery is not solely based on BMI, but on a comprehensive evaluation of the overall metabolic health and the potential benefits versus risks.

5.2. Type 2 Diabetes Mellitus (T2DM) Specific Considerations

For patients with T2DM, several factors beyond BMI are considered:

• Duration of Diabetes: Shorter duration (e.g., <5-10 years) and preserved beta-cell function (indicated by C-peptide levels) are generally associated with higher rates of T2DM remission after surgery. However, patients with long-standing diabetes can still achieve significant glycemic control improvement and reduction in medication requirements.
• Glycemic Control: Inadequate control despite maximal conventional medical therapy is a primary driver for considering surgery. This includes high HbA1c levels, persistent hyperglycemia, and complications related to diabetes.
• Insulin Dependence: While insulin-dependent patients can still benefit, non-insulin-dependent patients often have higher rates of full T2DM remission.

5.3. Age and Comorbidities

• Age: While generally considered suitable for individuals aged 18-65 years, metabolic surgery can be safely and effectively performed in carefully selected adolescents and older adults. For adolescents, strict multidisciplinary criteria are applied, often requiring skeletal maturity and severe comorbidities. For older adults, a thorough pre-operative assessment of frailty, functional status, and medical comorbidities is crucial to mitigate surgical risks. [6]
• Obesity-Related Comorbidities: Beyond T2DM, the presence of other severe comorbidities strengthens the indication for metabolic surgery. These include:
  • Hypertension: Especially resistant hypertension requiring multiple medications.
  • Dyslipidemia: High cholesterol and triglyceride levels.
  • Obstructive Sleep Apnea (OSA): Often severe, requiring CPAP.
  • Non-Alcoholic Fatty Liver Disease (NAFLD) / Non-Alcoholic Steatohepatitis (NASH): Which can progress to cirrhosis.
  • Osteoarthritis: Weight-bearing joint pain impacting mobility and quality of life.
  • Gastroesophageal Reflux Disease (GERD): Though some procedures like SG can exacerbate it.
  • Polycystic Ovary Syndrome (PCOS): Improved menstrual regularity and fertility outcomes.
  • Urinary Stress Incontinence.

5.4. Multidisciplinary Assessment and Contraindications

A comprehensive pre-operative evaluation by a multidisciplinary team is essential to ensure patient safety and optimize outcomes. This typically includes:

• Psychological Evaluation: To assess for untreated psychiatric conditions (e.g., severe depression, active eating disorders, substance abuse) that could impair adherence to post-operative guidelines or lead to poor outcomes. Patients should demonstrate a clear understanding of the procedure, realistic expectations, and commitment to lifelong lifestyle changes and follow-up. [9]
• Nutritional Assessment: To identify pre-existing nutritional deficiencies and develop a post-operative dietary plan.
• Medical Clearance: Thorough evaluation of cardiac, pulmonary, renal, and other organ systems to identify and manage any conditions that would significantly increase surgical risk. Uncontrolled severe cardiac disease, active malignancy, or unmanaged coagulopathy are generally contraindications.
• Commitment to Lifestyle Changes: Patients must demonstrate a willingness and ability to adhere to strict dietary guidelines, regular physical activity, and lifelong vitamin/mineral supplementation and medical follow-up.
• Realistic Expectations: Patients must understand that surgery is a tool, not a cure-all, and requires ongoing effort. They should be aware of potential complications, lifestyle changes, and the need for long-term monitoring.

Absolute contraindications typically include severe, uncontrolled psychiatric illness; active substance abuse; pregnancy; and conditions that preclude safe anesthesia or surgery. Relative contraindications require careful risk-benefit analysis.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

6. Long-Term Efficacy and Safety Profiles

The enduring success of metabolic surgery is underpinned by robust evidence from numerous long-term studies demonstrating its superior efficacy compared to conventional medical and lifestyle interventions for weight loss and metabolic disease resolution. Concurrently, advancements in surgical techniques and perioperative care have significantly enhanced the safety profile, though comprehensive long-term follow-up remains critical for managing potential complications.

6.1. Long-Term Efficacy

6.1.1. Sustained Weight Loss

Metabolic surgery consistently achieves significant and durable weight loss, which is a primary driver of many health improvements. The degree of weight loss varies by procedure:

• Roux-en-Y Gastric Bypass (RYGB): Typically results in 60-80% excess weight loss (EWL) or 25-35% total body weight loss (TBWL) at 1-2 years, with good maintenance over 10-20 years. Some weight regain is common, but most patients maintain substantial weight loss compared to baseline. [6]
• Sleeve Gastrectomy (SG): Achieves 50-70% EWL or 20-30% TBWL at 1-2 years. Long-term data suggest comparable weight loss to RYGB in the first 5 years, with some studies showing slightly less durable weight loss than RYGB over longer periods, though it remains a highly effective procedure. [6]
• Biliopancreatic Diversion with Duodenal Switch (BPD/DS) / SADI: These procedures consistently yield the highest rates of weight loss, often exceeding 70-90% EWL or 35-45% TBWL, with excellent long-term durability, making them highly effective for individuals with super-morbid obesity. [6]

Factors influencing variability in weight loss include patient adherence to lifestyle changes, genetic predispositions, and the specific surgical technique employed.

6.1.2. Type 2 Diabetes Mellitus (T2DM) Remission and Improvement

The most compelling efficacy of metabolic surgery lies in its ability to induce T2DM remission or significant improvement, often independent of the magnitude of weight loss. Remission is typically defined as an HbA1c <6.5% (or even <6.0%) and fasting glucose <100 mg/dL for at least one year, without glucose-lowering medication.

• RYGB: Achieves T2DM remission rates ranging from 60-80% at 1-2 years, with durable remission rates of 30-60% at 10-15 years. Even in patients who do not achieve full remission, there is a substantial reduction in medication requirements and improved glycemic control. [5]
• SG: Demonstrates T2DM remission rates of 40-60% at 1-2 years, with durability similar to RYGB, albeit often with slightly lower absolute rates. It significantly improves insulin sensitivity and beta-cell function.
• BPD/DS and SADI: These procedures offer the highest T2DM remission rates, often exceeding 80% at 1-2 years, and showing remarkable durability over the long term, even for patients with long-standing or severe diabetes. [5]

Beyond remission, metabolic surgery significantly reduces the risk of diabetes-related complications, including microvascular (nephropathy, retinopathy, neuropathy) and macrovascular events (cardiac events, stroke), and improves overall cardiovascular health. [diabetesjournals.org/care/article/43/6/1175/35694/Success-but-Unfinished-Story-of-Metabolic-Surgery]

6.1.3. Resolution of Other Comorbidities

Metabolic surgery leads to significant improvements and often resolution of a wide array of obesity-related comorbidities:

• Hypertension: Resolution or significant improvement in 60-70% of patients, leading to reduced reliance on antihypertensive medications.
• Dyslipidemia: Normalization of cholesterol and triglyceride levels in 70-90% of patients.
• Obstructive Sleep Apnea (OSA): Resolution in 80-90% of patients, often eliminating the need for continuous positive airway pressure (CPAP) therapy.
• Non-Alcoholic Fatty Liver Disease (NAFLD)/NASH: Significant histological improvement, including resolution of steatosis, inflammation, and fibrosis.
• Joint Pain/Mobility: Substantial reduction in musculoskeletal pain, leading to improved mobility and physical activity levels.
• Gastroesophageal Reflux Disease (GERD): Often improves after RYGB, but can sometimes worsen or develop after SG.
• Quality of Life: Patients consistently report significant improvements in physical function, self-esteem, social interactions, and overall quality of life.

6.2. Safety Profiles and Complications

While metabolic surgery is highly effective, it is not without risks. However, advancements in laparoscopic techniques, enhanced recovery protocols, and improved patient selection have dramatically reduced complication rates, making these procedures as safe as or safer than many other common abdominal surgeries.

6.2.1. Perioperative Risks

• Mortality: The 30-day mortality rate for metabolic surgery is remarkably low, typically ranging from 0.1% to 0.3%, comparable to procedures like hip replacement or gallbladder surgery. This rate varies based on patient comorbidities, surgical center experience, and procedure type (BPD/DS having slightly higher risk). [7]
• Anastomotic Leaks: A serious but rare complication where contents leak from a staple line or anastomosis. Rates are typically 1-3% for RYGB and SG, requiring prompt diagnosis and intervention.
• Bleeding: Intra-abdominal bleeding can occur, though it is usually manageable. Rates are generally <1%.
• Infection: Wound infections (rare with laparoscopic surgery) or intra-abdominal infections can occur.
• Thromboembolism: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are potential risks, mitigated by prophylactic anticoagulation and early mobilization.
• Cardiac/Pulmonary Complications: Patients with pre-existing conditions may be at higher risk for cardiac events, respiratory failure, or pneumonia, necessitating thorough pre-operative assessment.

6.2.2. Long-Term Complications

Long-term follow-up is essential to monitor and manage potential late complications:

• Nutritional Deficiencies: This is a key concern, particularly with malabsorptive procedures (RYGB, BPD/DS, SADI, OAGB) but also with SG. Common deficiencies include:
  • Iron Deficiency Anemia: Due to reduced acid secretion, bypass of the duodenum, and decreased red meat intake.
  • Vitamin B12 Deficiency: Due to loss of intrinsic factor production (RYGB) or reduced absorption.
  • Calcium and Vitamin D Deficiency: Leading to secondary hyperparathyroidism and increased risk of metabolic bone disease/osteoporosis.
  • Folate, Thiamine, Fat-Soluble Vitamins (A, D, E, K), Protein: Can also occur.
  • Management: Lifelong, rigorous supplementation and regular blood monitoring are mandatory for all patients undergoing metabolic surgery to prevent and treat these deficiencies.
• Anastomotic Ulcers: More common in RYGB and OAGB, often associated with NSAID use, smoking, or H. pylori infection.
• Internal Hernias: A specific risk after RYGB, where loops of small bowel can herniate through mesenteric defects created during the procedure, leading to bowel obstruction. Requires prompt surgical intervention.
• Gallstones: Rapid weight loss increases the risk of gallstone formation. Prophylactic ursodiol is sometimes prescribed.
• Dumping Syndrome: More common after RYGB, caused by rapid emptying of hyperosmolar contents into the small intestine, leading to symptoms like nausea, sweating, lightheadedness, and diarrhea, particularly after high-sugar or high-fat meals. Managed primarily through dietary modifications.
• Hypoglycemia (Late-Dumping Syndrome): A rare but severe complication, primarily after RYGB, characterized by excessive insulin release leading to low blood sugar levels, typically occurring 1-3 hours after meals. Management can be challenging and may involve dietary changes or, in very rare cases, further surgery.
• Gastroesophageal Reflux Disease (GERD): While RYGB can improve GERD, SG can sometimes induce or worsen it, potentially leading to Barrett’s esophagus in some cases. Careful monitoring is required.
• Weight Regain: While many patients maintain significant weight loss, some degree of weight regain is possible over the long term, often influenced by adherence to lifestyle recommendations and underlying biological factors. [6]

Diligent long-term follow-up with a specialized team is crucial for early detection and management of these potential complications, ensuring the overall safety and sustained success of metabolic surgery.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

7. Emerging Research and Future Directions

The field of metabolic surgery is in a constant state of evolution, driven by a relentless pursuit of enhanced efficacy, reduced invasiveness, and personalized patient care. Emerging research spans novel endoscopic interventions, integration with pharmacotherapy, deeper mechanistic understanding, and the application of advanced technologies.

7.1. Endoscopic Bariatric and Metabolic Therapies (EBMTs)

EBMTs represent a rapidly expanding frontier, offering less invasive alternatives for patients who may not qualify for or prefer not to undergo traditional surgery, or as a bridge to surgery. These procedures are performed entirely endoscopically, avoiding abdominal incisions:

• Endoscopic Sleeve Gastroplasty (ESG): As discussed, ESG significantly reduces stomach volume through internal suturing, offering good weight loss and metabolic improvements with a favorable safety profile. Research is focusing on its long-term durability and efficacy in specific patient populations, as well as refining techniques and comparing it to surgical options. [3]
• Endoscopic Gastroplasty/Banding for Gastric Outlet Restriction: Similar to ESG, but focusing on outlet restriction.
• Endoscopic Gastric Plication: Involves folding and suturing the stomach wall to reduce its volume.
• Endoluminal Barriers (e.g., Endobarrier): These devices, typically a duodenal-jejunal bypass liner, are endoscopically deployed in the small intestine to create a physical barrier between food and the intestinal mucosa. They mimic the rapid nutrient delivery of bypass surgery, inducing similar hormonal changes (e.g., GLP-1, PYY). While promising, issues with device migration and removal have limited their widespread adoption. [pmc.ncbi.nlm.nih.gov/articles/PMC6658098/]
• Endoscopic Bypass Techniques: Research is ongoing into creating endoscopic versions of bypass procedures, though these are still largely experimental.

EBMTs are typically indicated for individuals with lower BMI ranges (30-40 kg/m²) who have not responded to lifestyle interventions or pharmacotherapy, or as a bridge therapy for very high-risk patients.

7.2. Genomic and Pharmacological Integration

The future of metabolic disease management will likely involve a personalized, integrated approach combining surgical interventions with advanced pharmacological strategies and genomic insights.

• Novel Pharmacotherapies: The advent of highly effective glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) and dual/triple agonists (targeting GLP-1, GIP, glucagon receptors) offers powerful new tools for weight management and T2DM control. Research is exploring:
  • Pre-operative Optimization: Using these medications to improve metabolic status and reduce surgical risk in high-risk patients.
  • Post-operative Augmentation: Employing pharmacotherapy to enhance or maintain weight loss and metabolic improvements after surgery, especially for those with suboptimal outcomes or weight regain.
  • Alternative for Lower BMI: As stand-alone treatments for individuals who do not meet surgical criteria or prefer a non-surgical approach, potentially delaying or even obviating the need for surgery in some cases. [mdpi.com/2077-0383/14/13/4681]
• Personalized Medicine and Genomics: Understanding individual genetic predispositions to obesity, T2DM, and response to specific surgical procedures can enable precision medicine. Genetic markers may help predict which patients will respond best to RYGB versus SG, or who is at higher risk for complications or nutritional deficiencies. This involves genotyping and advanced bioinformatics to tailor treatments.

7.3. Deeper Mechanistic Studies

Continued elucidation of the intricate mechanisms underlying metabolic surgery remains a vibrant area of research:

• Gut-Brain Axis: Further understanding how surgical modifications impact neuroendocrine signaling, vagal nerve activity, and central nervous system pathways governing appetite, satiety, reward, and energy expenditure. Functional MRI studies are providing insights into brain changes post-surgery. [pmc.ncbi.nlm.nih.gov/articles/PMC5881368/]
• Gut Microbiota: Detailed metagenomic and metabolomic studies are ongoing to fully characterize the specific microbial shifts, their functional contributions (e.g., short-chain fatty acid production, bile acid modification), and their impact on host metabolism. This could lead to probiotic/prebiotic therapies or fecal microbiota transplantation as adjuncts to surgery.
• Bile Acid Metabolism: Further exploration of bile acid signaling pathways (FXR, TGR5) and their role in glucose and lipid metabolism post-surgery. This could lead to bile acid modulators as novel therapeutic agents.
• Epigenetics and Metabolomics: Investigating how metabolic surgery induces long-lasting changes in gene expression (epigenetics) and metabolic profiles (metabolomics), providing insights into the durability of its effects and potential biomarkers for success or complications.

7.4. Novel Surgical Techniques and Technologies

Innovation in surgical techniques continues:

• Robotic Surgery: While still under debate regarding cost-effectiveness, robotic platforms offer enhanced dexterity, 3D vision, and precision, potentially leading to improved outcomes and reduced surgeon fatigue, especially for complex revisional surgeries.
• Further Procedural Refinements: Ongoing efforts to optimize existing procedures (e.g., ideal limb lengths for bypasses, size of gastric sleeve) to maximize efficacy while minimizing complications.
• Magnetic Anastomosis: Exploring magnetic compression devices for creating anastomoses to simplify procedures and potentially reduce leak rates.

7.5. Global Access and Health Equity

An important future direction involves addressing disparities in access to metabolic surgery, particularly in low- and middle-income countries where the burden of T2DM and obesity is rapidly growing. This includes advocacy for policy changes, development of cost-effective surgical models, and training of surgical teams globally.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

8. Conclusion

Metabolic surgery has profoundly transformed the therapeutic landscape for severe obesity and its associated metabolic diseases, particularly Type 2 Diabetes Mellitus. Its evolution from rudimentary, often hazardous, experimental procedures to highly refined, safe, and effective interventions represents a remarkable journey of medical progress. A thorough and nuanced understanding of its historical development, the diverse array of procedural options, their intricate physiological mechanisms, the evolving patient selection criteria, and their robust long-term efficacy and safety profiles is indispensable for all healthcare professionals involved in the management of metabolic disorders.

The evidence unequivocally demonstrates that procedures such as Roux-en-Y Gastric Bypass, Sleeve Gastrectomy, and Biliopancreatic Diversion with Duodenal Switch offer unparalleled rates of durable weight loss, T2DM remission, and resolution of comorbidities, leading to substantial improvements in quality of life and reductions in long-term health complications. While not without risks, modern metabolic surgery carries a safety profile comparable to many common surgical procedures, provided it is performed by experienced teams and complemented by comprehensive multidisciplinary care and lifelong follow-up.

The future of metabolic surgery is dynamic and promising. Emerging research in endoscopic therapies, the integration of cutting-edge pharmacotherapy, deeper mechanistic investigations into the gut-brain-microbiota axis, and the application of advanced technologies are poised to further refine these interventions, expand their applicability to a broader spectrum of patients, and facilitate truly personalized treatment strategies. As the global burden of metabolic diseases continues to escalate, metabolic surgery stands as a cornerstone of comprehensive care, offering not just an option, but often the most effective and durable solution for millions grappling with these complex and debilitating conditions. Continued innovation, rigorous research, and equitable access remain imperative to fully realize its transformative potential in global health.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

References

1. Pories, W. J. (2018). Bariatric Surgery: An Overview. In StatPearls. StatPearls Publishing. ncbi.nlm.nih.gov/books/NBK279090/
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4. Mirza, S., et al. (2018). Mechanisms of Action of Bariatric Surgery for Type 2 Diabetes. International Journal of Molecular Sciences, 19(3), 773. pmc.ncbi.nlm.nih.gov/articles/PMC5881368/
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