Weight Regain after Metabolic Surgery: Comparison
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Los pacientes sometidos a cirugía metabólica tienen factores que van desde factores anatomo-quirúrgicos, metabólicos endocrinos, patrones de alimentación y actividad física, salud mental y psicológicos. Algunos de estos últimos pueden explicar los posibles mecanismos fisiopatológicos neuroendocrinos, metabólicos y adaptativos que causan la alta prevalencia de recuperación de peso en pacientes posbariátricos.

Patients undergoing metabolic surgery have factors ranging from anatomo-surgical, endocrine metabolic, eating patterns and physical activity, mental health and psychological factors. Some of the latter can explain the possible pathophysiological neuroendocrine, metabolic, and adaptive mechanisms that cause the high prevalence of weight regain in postbariatric patients.

  • metabolic surgery
  • obesity
  • metabolic syndrome

1. Introducctióon

L The World Health Organización Mundial de la Salud (OMStion (WHO) define el sobrepeso y las overweight and obesidad como una acumulación aty as an abnormal, excesiva y dañina de grasa porque es un factor de riesgosive and harmful fat accumulation because it is a well-known independiente bien conocido para afecciones mórbidas como ent risk factor for morbid conditions like diabetes mellitus (DM), diyslipidaemia, enfermedades cardiovasculares y cá diseases, and cancer [ 1 ] [1]. .Over Durante las últimas cuatro décadas, lathe last four decades, the prevalencia de lae of obesidad ha aumentado a un ritmo alarmante en países con estilos de vida occidentalizados, convirtiéndose en uno de los principales problemas de salud como consecuencia de laty has increased at an alarming rate in countries with Westernized lifestyles, becoming one of the major health concerns as a consequence of morbilidad, la dity, mortalidad y la carga económica sobre los sistemas nacionales de salud en todo elty and the economic burden on national healthcare systems worldwide mundo [ 2 , 3 , 4 , 5 ][2][3][4][5]. DeIn hecho, desdfact, since 1975, laobesity prevalencia de la obesidad se ha triplicado ee has shown a three-fold increase in adultos y cinco veces mayor en niños ys and a five-fold increase in children and adolescentes. Además, según las últimas proyeccioness. Furthermore, according to the latest regionales y nacionales del informe Atlas Mundial de Obesidad 2023 sobre and national projections by the 2023 World Obesity Atlas report on obesidad, la mayoría de la población mundialty, the majority of the global population (51%, o más de 4 mil millones de personas) sufrirá sobrepeso ur over 4 billion individuals) will be suffering from being overweight or obesidadty, definida como masa corporal. Índice (IMCed as a Body Mass Index (BMI) ≥ 25 kg/m 2 eand IMCBMI ≥ 30 kg/m 2 . Si las tendencias actuales continúan, el impacto económico mundial delIf current trends continue, the global economic impact of exceso de peso podría alcanzar los 4,32 billones de dólares anualess weight could reach $4.32 trillion annually, equivalente al 3% del PIB mundial [ to 3% of the global GDP 6 , 7 ][6][7].
A p Desar dpite las múmultiples estrategias terapéuticas para la pérdida de peso therapeutic strategies for weight loss (WL), que combinan varios esquemasing several nutricionales, actividad física, terapia tional schemes, physical activity, cognitivo-conductual e intervención fe-behavioral therapy, and pharmacológica, el manejo médico de laogic intervention, medical obesidad es una tarea desafiante, que a menudo produce un éxitoty management is a challenging endeavor, often yielding limitado, ya que lased success, as lifestyle-based intervenciones basadas en el estilo de vida por sí solas resultan insutions alone prove insufficientes en lograr una pérdida de peso s in achieving significativa a largo plazo en algunos pacientes, lo que ont long-term weight loss in some patients, occasionalmente conduce a un efecto rebote en el que losly leading to a rebound effect where individuos recuperan más peso del inicialmenteals regain more weight than initially presente [ at 8the ,beginning 9[8][9]. On ].
Porthe othero lado, los fármacos aprobados para la hand, the drugs approved for obesidad son oty are orlistat, fphenterminae/topiramatoe, naltrexonae/bupropión y los agonistas de los on, and the Glucagon-like peptide receptores del péptido similar al glucagón, como l agonists, like Liraglutida o se or Semaglutida, aunque estos tratamientos pueden ser costosos y tener efectos adversos. Por lo tanto, ee, although these treatments can be expensive and may have adverse effects. Thus, it is importante to carefully considerar cuidadosamente los posiblesr the potential beneficios y riesgos de la terapia farmacológica antes de iniciar el tratamiento en personas conts and risks of drug therapy before starting treatment in individuals with obesidadty [ 10 ][10]. Es Gimportavente mencionar que se han logrado grandes avances farmacológicos, los cuales se discutirán con mayor profundidad a continuación.
Ant this challenge, along with the need for an effective este desafío, junto con la necesidad de un tratamiento eficaz y duradero, la cirugía metabólica (EM) ha demostrado su eficacia para perder cantidades masivas de grasa tantond long-lasting treatment, metabolic surgery (MS) has proved its efficacy in losing massive amounts of both subcutánea como aneous and visceral [fat 11 ][11], lowhich que implica diinvolves differentes técnicas diseñadas para techniques designed to corregir oct or controlar la obesidad. , con el objetivo de mejorar la calidad de vida mediante el logro de una WL adecuada y duradera con obesity, aiming to improve quality of life by achieving adequate and long-lasting WL with minimal complicacionetions mínimas [ 12 ][12].
E In 2022, lthe American Sociedad Estadounidense de Cirugíaty for Metabólica y Bariátricaolic and Bariatric Surgery (ASMBS) y la Federaciónand Internactional para la Cirugía de laFederation for the Surgery of Obesidad y los Trastornosty and Metabólicoolic Disorders (IFSO) afirman que sestates that MS is recomienda la EM en caso de: IMCmended in case of: BMI ≥ 35 kg/m 2 (indrependientemente degardless of presencia, ausencia , o gravedad de las comorbilidade, absence, or severity of co-morbidities), pacientes con diabetes tipo 2 e IMCtients with T2D and BMI ≥ 30 kg/m 2 , personas con un IMC de 30 a 34,individuals with BMI of 30–34.9 kg/m2 2who quedo no logran perder peso ni mejorar la comorbilidad utilizando métodos no quirúrgicos. Además, et achieve weight loss or co-morbidity improvement using nonsurgical methods. Also, it is importante to considerar factores geográficos; por ejemplo, la obesidad en personas asiáticas se reconoce como un IMC geographic factors; for example, obesity in Asiatic people is recognized as BMI > 25–27,.5 kg/m 2 , por lo que la EM podría realizarse en estos casos. Por otro lado, la edad no es un criterio deso MS could be performed in these cases. On the other hand, age is not an exclusión oon or inclusión para la EM, y podría realizarse en niños y on criteria for MS, and could be performed in Children and adolescentes con IMCs with BMI > 120% delof the 95th percentil 95 y una comorbilidad mayor, o un IMCe and a major co-morbidity, or a BMI > 140% delof the 95th percentile 95[13][14][15][16]. [ MS 13 , 14 , 15 , 16 ].
Los procedimiurentos de EM se habían divididos had tradicionalmente en categoríastionally been divided into restrictivase, malabsortivas y mixtas; sin embargo, ahora se sabe que la EM puede causar pérdida de peso no solo a través de estos mecanismos sino también a través delptive and mixed categories; however, it is now known that MS can cause weight loss not only through these mechanisms but also through appetite control del apetito, alteraciones de lastions of hormonas del eje cerebro-intestinoes of the gut brain axis, alteraciones en la fitions in bile acid physiología de los ácidos biliares y lay and intestinal microbiota int[17][18][19][20]. Evestinal [ though 17MS , 18 , 19 , 20 ]. Asunqccessfue la EM logra disminuir con éxito un porcentajelly manages to decrease a significativo del peso corporal, no todos los pacientes pueden mantener la pérdida de peso lograda y sorprendentemente podrían recuperar el peso perdidont percentage of body weight, not all patients can maintain the weight loss achieved and could surprisingly regain the lost weight [[21]; 21this ]; undeste eired scenario no deseado podría afectar la salud física ycould affect the patient’s physical and mental del pacientehealth.

2. CMetabomplicaciones de la cirugía metabólic Surgery Complica

Como

tions

Ase mencionó anteriormente, la EM es un procedimiento con una tasa de complicaciones baja y un margen de riesgo mínimo. En general, lapreviously mentioned, MS is a low-complication rate procedure with a minimum margin of risk. Overall, the combinación de técnicas quirúrgicas mejoradas, experiencia de los cirujanos, selección de pacientes, atencióntion of improved surgical techniques, surgeon expertise, patient selection, perioperatoria, manejo posive care, post-operatorio y avances en tecnología e investigación han dado como ive management, and advancements in technology and research have resultado una disminución ned in a notable en ladecrease in the incidencia dee of complicaciones relacionadas con la cirugía bariátrica. No obstante, no está exenta detions linked to bariatric surgery. Nonetheless, it is not exempt from complicaciones y la EM se ha asociado contions, and MS has been associated with adverse surgical complicaciones quirúrgicas adversas, incluidastions, including high-mortality complicacionetions de[22]. alFurta mortalidad [ 22 ]. Adhermoremás, Pallati et al. [ 23 ][23], ein una revisión sistemática y un metanálisis de 160.000 pacientes bariátricos, informaron una tasa da systematic review and meta-analysis of 160,000 bariatric patients, reported a post-operative complicaciones posoperatorias de entre el 10 y el 17% y una tasa detions rate between 10–17% and a 7% reoperación del 7%tion rate; favorablemente, la tasa dy, the mortalidad se mantuvo baja (0,08–0,ty rate remained low (0.08–0.35%).
Las complicacion Thes perioperatorias o de corto plazo se puedenive or short-term complications can be dividir en menores y mayores; Lased into minor and major; the most common minor complicaciones menores más comunes suelen estar en el sitio quirúrgico (sangrado del puerto otions are usually at the surgical site (port bleeding or hematoma, skin infecciones de la piel y dolortions, and post-operative neuropático posoperatorio), desequilibrio hidroathic pain), hydro electrolítico e infecciones delyte imbalance, and urinary tracto urinario. Las infections. Major complicaciones mayores incluyen fugas ations involve anastomóticas, hemorragia intraotic leaks, intra-abdominal, l bleeding, small bowel perforación del intestino delgado,tion, myocardial infarto de miocardio ction, and pulmonary embolia pulmonarsm <30 días después de la EM. Normalmente, la frecuencia de estasays after MS. Typically, these early complicaciones tempranas es inferior al 1,6% y la tasa dtions frequency is below 1.6%, and the mortalidad es <0,ty rate is <0.7% [ 22 ][22]. LaPos fugas posquirúrgicas pueden surgir de lat-surgical leaks can arise from the gastrojejunal anastomosis gastroyeyunal del BGYR (1,68 a 2,of the RYGB (1.68–2.05%); en lain vertical sleeve gastrectomía vertical en manga y, they emergen de la línea de grapas (2,2%). Las hemorragias a menudo comienzan en la línea de grapas, pero también pueden provenir de úlceras a from the staple line (2.2%). Hemorrhages often begin in the staple line but can also come from anastomóticas o remanentes gástricaotic or gastric remnant ulcers [ 24 ][24].
Ad Moreovemásr, aunque laslthough mid- and long-term complicaciones a medio y largo plazo están bientions have been well descritasbed, establecer suishing their exact incidencia exacta es difícil debido al número cada vez más importante de pacientes que faltan a suse is difficult due to the increasingly significant number of patients who miss their follow-up visitas de seguimiento con el paso del tiempo. Estass as time goes by. These complicaciones son etions are stenosis, obowel obstrucción intestinal, úlceras marginales,tion, marginal ulcers, ventral hernia ventral, fí, fistula, enfermedad por reflujo gastroesofágico y gastroesophageal reflux disease, and metabolic complicaciones metabólicas como nefrolittions like nephrolithiasis e hipogluand hypoglycemia [ 25 ][25]. EIn estethis contexto, la estenosis , gastroyeyunal es unajejunal stenosis is a common complicación común, con una tasa de tion, with an incidencia que oscila entre el 4% y el e rate ranging from 4% to 27%, similar a la enfermedad por reflujo gastroesofágico, que ocurre en el 12% de los casos. Mientras tanto, la eto gastroesophageal reflux disease, which occurs in 12% of cases. Meanwhile, gastric stenosis gástrica es poco común y solo ocurre en el 1% de los pacientes. Las hernias internis uncommon, only occurring in 1% of the patients. Internal hernias generalmente causanly cause small bowel obstrucciones del intestino delgado después de un tions after gastric bypass gástrico o, rara vez, por adherencias ior rarely by intraperitoneales en el 2-3% de los paciente adhesions in 2–3% of the patients [ 25 ][25]. Several kinds of ulcers, most marginal, arise within the first 12 months after gastric bypass; their estimated incidence is around 16%, contrasting the much lower incidence of fistulas (1.2%). Unfortunately, fistulas can appear in almost any location of the digestive tract following surgery; gastro-gastric fistulas are an especially alarming RYGB complication. Another rare complication is hernias, which have a frequency of less than 1% in laparoscopic procedures; however, the frequency increases to around 8% for open procedures [24]. Additionally, vitamin and mineral deficiencies are also described as possible complications. Regarding nutritional deficiencies, biliopancreatic diversion leads to a more significant decrease in liposoluble vitamins, copper, and zinc compared to gastric bypass; contrarily, vitamin B12 deficiency, due to decreased levels of its intrinsic factors, is more frequently caused by gastric bypass in comparison to any other procedure [26]. In contrast to these low surgical complications, 10–20% of the patients are expected to regain a significant weight proportion in the long term. Likewise, it has been reported that 20–25% of the lost weight can be regained in a ten-year course, starting nearly 24 months after the surgery; thus, the mean weight regained after the surgery is 10 kg, ranging from 0.5 to 60 kg [27]. In this context, WR is considered clinically significant when WR is greater than or equal to 15% of the lowest weight reached while maintaining this increase for at least six months [28].

3. Risk Factors for Weight Regain after MS: Is It All about the Surgery?

The multifactorial nature behind WR after MS has hampered the comprehension of its mechanisms, and thus, the therapeutic approach. Psychological, behavioral, endocrine metabolic, genetic, and anatomical factors have been associated with WR [29,30][29][30].

3.1. Anatomic and Surgical Factors

The leading anatomical abnormality associated with WR is the enlargement of the gastric pouch (>6 cm long or >5 cm wide) and gastrojejunal stoma (diameter > 2 cm), and gastro-gastric fistula (GGF), which are mainly sequelae of procedures such as RYGB and vertical sleeve gastrectomy (VSG) [31,32,33][31][32][33]. A GGF is an abnormal communication between the proximal gastric pouch and the distal gastric remnant. Consequently, food detours to the “previous route” instead of the duodenum, increasing the available gastric volume and food’s absorption surface impairing the properties of MS [34,35,36][34][35][36]. By contrast, gastrojejunal stoma dilation leads to accelerated gastric pouch emptying and, therefore, a lack of satiety, instead accommodating larger amounts of food within the gastric pouch. Heneghan et al. [32] assessed the potential causes of WR by gastroscopy in patients submitted to RYGB (n = 380), reporting that only 28.8% of those who had WR (n = 205) had a normal-sized stoma, contrasting to 63.4% in patients who had successful weight loss (n = 175). Simultaneously, univariate statistical analysis demonstrates that the length and dilation of the stoma are the most influencing factors of WR; interestingly, the multivariate analysis only found the latter to be an independent factor for WR. Similarly, a retrospective study carried out by Yimcharoen et al. [33] reported that out of 205 patients with WR after RYGB, 58.9% had dilation of the gastrojejunal stoma, 28% had enlargement of the gastric pouch, and 12.3% had both of these findings. Similarly, a study in people submitted to RYGB reported that limb length does not influence post-MS weight changes [37]. Still, this could be attributed to the methodology, study sample size, and confounding variables that could induce WR and enlargement of the gastric pouch, such as patients’ lifestyles and psychological status.

3.2. Endocrine and Metabolic Factors

RYGB has been associated with episodes of hypoglycemia, a significant clinical component of the dumping syndrome (DS). In a study involving 36 RYGB patients, Roslin et al. [38] assessed their glucose levels six months after the procedure. They found that 11 patients had weight regain exceeding 10%, and six of these experienced hypoglycemia two hours after glucose load. Likewise, a study performed by Varma et al. [39] on 428 American patients who underwent MS determined that the odds of WR were significantly higher in those who had symptoms of hypoglycemia (OR: 1.66; 95% CI: 1.04–2.65). The authors have suggested that the causal relation could be due to metabolic changes produced by glucose homeostasis effects on appetite and gastrointestinal functioning [39]. Additionally, it has been proved that in the long term, post-MS patients with WR exhibit alterations in the levels of gastrointestinal and neuronal peptides related to appetite and satiety, which could indicate that changes in hormonal parameters contribute to WR [40].

3.3. Lifestyle: Eating Patterns and Physical Activity

Implementing lifestyle changes that counter the “obesogenic” environment before surgery is essential to achieve meaningful results in the WL after MS. In this context, it has been described how post-MS patients regain weight by eventually neglecting their lifestyle changes [41]. Furthermore, once the patients reach their target weight, some may increase their caloric intake, an expected eating behavior two years after the surgery [42,43][42][43]. Some of patients either fail to keep adequate control of their post-MS nutritional status or refuse entirely to follow the dietary patterns suggested by the weight management team, contrarily, maintain a high caloric intake attributed to a large intake of high-fat food, junk food, sweets, and high-sugar drinks, leading to suboptimal WL or even WR [41,43,44][41][43][44]. Bassan et al. [44,45][44][45] conducted a retrospective study that included 80 patients at least 24 months after MS and reported that 23.7% presented a WR greater than 10% of the lowest post-operative weight. Moreover, supported by multivariate analysis, a positive association between Healthy Eating Index and WR was observed (OR 0.95; p = 0.04), correlating to similar results found by other authors [44,46][44][46]. Furthermore, common maladaptive eating patterns among post-MS patients, such as binge eating and grazing, are considered risk factors for reduced WL [47]. Grazing can be defined as repeated episodes of consuming small quantities of food over a long time and is usually accompanied by feelings of guilt and loss of control [47,48][47][48]. A systematic review including 994 post-MS patients showed 16.6–46.6% engaged in grazing and 47% engaged in WR; an association was found between these two variables regardless of the type of MS and the author’s definition of grazing [49]. Another factor linked to WR is dysphagia, a frequent complication after RYGB [50]. In a prospective cohort study by Runge et al. [51] on 245 post-MS patients, a higher WR was observed in those with dysphagia (n = 49) in comparison to the control group (n = 196) (37% vs. 25%). These things considered, patients with dysphagia are more likely to incline their diet partially or even entirely towards soft or liquid food since they are absorbed faster and produce less satiety, favoring a higher caloric intake and thus a positive energy balance that could explain the WR [51,52][51][52]. Regarding the food preferences observed after MS, although patients reported a diminished explicit liking for sweet foods at 3 months post-surgery and a lower desire to consume them at both 3- and 12-months post-surgery, intake of high-sugar foods was maintained in another study [53]. In this regard, a meta-analysis showed that bariatric surgery could be effective on energy and fat intake; however, there was no effect on carbohydrate intake [54], being considered another risk factor for developing weight gain after MS. Besides unhealthy dietary habits, sedentarism or lack of physical activity can also be risk factors for WR. According to Rosenberg et al. [55], only 10–24% of the patients who underwent MS had performed the minimum physical activity to maintain their health status. Moreover, in a study by Yanos et al. [56] on 97 patients submitted to RYGB, 26% exhibited WR, associated with nocturnal eating, alcohol consumption, and diet and physical activity modifications. Correspondingly, Freire et al. [44] reported a lower incidence of WR among post-MS patients who exercised than those who did not.

3.4. Psychological Factors and Mental Health

Neuropsychiatric and Psychological disorders have been linked to WR and can hinder adherence to dietary and behavioral intervention plans during and after MS [46]. Binge eating disorder (BED), defined by The Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) as the uncontrolled consumption of larger and more than usual food quantities within two hours, is one of the main predictors of WR after MS [57]. However, BED prevalence among post-MS patients varies significantly according to the criteria used by different authors, ranging from under 5% to almost 24% [58,59][58][59]. Still, it has been demonstrated that BED is related to reduced WL or even WR two years after the procedure, along with developing worse maladaptive eating behaviors than prior MS [47,60][47][60]. Similarly, other eating disorders, such as soft food and night eating, have been recognized as predictors of WR after MS [61]. Furthermore, psychiatric disorders increase the risk of WR during post-operative periods; for instance, Rutledge et al. [62] showed that those individuals presenting two or more psychiatric disorders were six times more likely to develop WR post-MS. Under this framework, depression stands out among the most common disorders in bariatric patients, and although the association between this and WR or failure in post-MS WL has been demonstrated, as well as its presence predisposes individuals to be more prone to develop eating disorders, the results of studies tend to contradict each other since some show that depression is diminished after MS or, failing that, no causal relationships are observed in their analyses [56,63,64,65,66][56][63][64][65][66]. Similarly, patients with WR have high clinical or borderline anxiety and stress levels; however, these were not associated with higher energy consumption [66,67][66][67]. Finally, drug use and alcoholism have been described as influential factors in WR, as post-MS patients may seek relief from other substances through “addiction transfer” to substitute the needs established by the brain reward system for excessive energy consumption prior to MS [60,68,69][60][68][69]. Odom et al. [65] followed up on 203 post-RYGB patients, showing that decreased post-MS well-being, increased need to eat, and preoccupation with drug or alcohol use (addictive behavior) were independent predictors of WR. Thus, it is clear that bariatric patients need pre- and post-MS psychological assessment to ensure expected outcomes in WL and avoid relapse in maladaptive habits related to WR [70].

3.5. Preoperative and Other Factors

Numerousos estudios han encontrado factores studies have found preoperatorios que puedenive factors that may predisponer a los pacientes a la WR. Un estudio se patients to WR. A prospectivo de 782 pacientes bariátricos mostró que ape study of 782 bariatric patients showed that approximadamente el 50% de ellostely 50% of them presentaban WR, teniendo los pacientes del grupo superobesos un mayor poed WR, with patients in the super-obese group having a higher percentaje de fracaso quirúrgico (18,8%) y WR. Los autorege of surgical failure (18.8%) and WR. The authors concluyeron que las personas con un IMC más alto antes de la cirugía tienen más probabilidades de sufrir ded that individuals with higher BMI before surgery are more likely to WR [ 71 ][71]. EIn particular, Keith et al. [ 72 ][72], ein su estudiotheir retrospectivoe study, describieron que factoresed that preoperatorios como el sexo masculino ive factors such as male sex ( p = 0,.020), la raza blancawhite race ( p < 0,001) y el alto nivel.001), and high socioeconómicoomic level ( p = 0,.035) se asociaron con WR. Además, cuando se realizó el análisis multivariado, sewere associated with WR. Furthermore, when multivariate analysis was performed, it was observó que los pacientesed that socioeconómicamente favorecidos tenían más probabilidades de tener WR que el restoomically advantaged patients were more likely to have WR than the rest (OR: 1,82, IC 1,18 a 2,79). Sin embargo, otros autores han discrepado con este estudio ya que sus análisi.82, CI 1.18 to 2.79). However, other authors have differed with this study since their analyses establecen que el sexo femenino y la raza negra podríanish that female sex and black race could be considerarseed risk factores de riesgo paras for WR [ 37 , 73 , 74 ][37][73][74]. Althounque se ha destacado la edad como un posible factor gh age has been highlighted as a possible preoperatorio relacionado con la WR, los ive factor related to WR, resultados entre los estudios varíans among studies vary significativamente, y se informa que tanto losntly, with both young and older adultos jóvenes como los mayores (>60 años) son propensos a las (>60 years) reported to be prone to WR [ 73 , 75 , 76 ][73][75][76]. AdMoreovemás, el tiempo transcurrido después de la cirugía, la r, time elapsed after surgery, iron deficienciay de[77], hieworro [ 77k ], la actividad laboral relacionada con la alimentación y ctivity related to eating, and comorbilidades como la DM2 se han relacionado con la dities such as T2DM have been linked to WR [ 78 ][78].
Sorprendent Rementearkably, los medicamentos para los trastornos psiquiátricotions for psychiatric disorders, incluidos losding tricyclic antidepresivos tricíclicos, el ácido sants, valproico, el litio y los acid, lithium, and antipsicóticos, así como loychotics, as well as antidiabéticos, los esetic drugs, steroides y los anticons, and contraceptivos, se han asociado con el aumento de peso y la modulaciónes, have been associated with weight gain and positiva del apetitoe appetite modulation [ 79 ][79]. EIn este sentido, los pacientes con EM tratados con cualquiera de estos fármacos podrían, en teoría, tener un alto riesgo de sufrirthis regard, post-MS patients treated with any of these drugs could theoretically be at high risk for WR [[80]. 80In ]. Aaddemás, existen factores genéticoition, there are genetic factors relacionados con el desarrollo de lated to the development of obesidad y la biología del tejido adiposo (TA) que podrían estarty and adipose tissue (AT) biology that could be implicados en la WRted in post-EM. Entre estos, se destacan los polimorfismos genéticos de los MS WR. Among these, genetic polymorphisms of AT adrenorreceptores AT, como el gens such as the ADRB2 ( gene (Gly16Arg yand Gln27Glu ), y los relacionados con laand those related to leptina, como el, such as LEPR-gene (LEPR ( LEPR Lys109Arg , LEPR Gln223Arg , LEPR Lys656Asn ) [ 81), stand out ][81].

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