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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.
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.
- metabolic surgery
- obesity
- metabolic syndrome
1. Introducctioión
The World HeLalth Organization (WHOción Mundial de la Salud (OMS) defines overweight and el sobrepeso y la obesity as an abdad como una acumulación anormal, excessive and harmful fat accumulation because it is a well-knowniva y dañina de grasa porque es un factor de riesgo independent risk factor for morbid conditions like iente bien conocido para afecciones mórbidas como diabetes mellitus (DM), dyislipidaemia, enfermedades cardiovascular diseases, and canceres y cáncer [ 1 ] [1]. . OveDur the last four decades, theante las últimas cuatro décadas, la prevalence ofia de la obesity has increased at an alarming rate in countries with Westernized lifestyles, becoming one of the major health concerns as a consequence ofdad 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 la morbidity, lidad, la mortality and the economic burden on national healthcare systemsdad y la carga económica sobre los sistemas nacionales de salud en todo el mundo [ 2 , 3 , 4 , worldwide5 [2][3][4][5]]. InDe fact, sinchecho, desde 1975, obesityla prevalence has shown a three-fold increase iia de la obesidad se ha triplicado en adults and a five-fold increase in children andos y cinco veces mayor en niños y adolescents. Furthermore, according to the latestes. Además, según las últimas proyecciones regional and national projections by the 2023 Worldes y nacionales del informe Atlas Mundial de Obesity Atlas report on obesity, the majority of the global populationdad 2023 sobre obesidad, la mayoría de la población mundial (51%, or over 4 billion individuals) will be suffering from being overweight or más de 4 mil millones de personas) sufrirá sobrepeso u obesitydad, defined as a Body Mass Index (BMIida como masa corporal. Índice (IMC) ≥ 25 kg/m 2 ande BMIIMC ≥ 30 kg/m 2 . If current trendSi las tendencias actuales continue, the global economic impact ofnúan, el impacto económico mundial del excess weight could reach $4.32 trillion annuallyo de peso podría alcanzar los 4,32 billones de dólares anuales, equivalent to 3% of the globale al 3% del PIB mundial [ GDP6 , 7 [6][7]].
D
A pespitar de mulas múltiple therapeutic strategies for weight losss estrategias terapéuticas para la pérdida de peso (WL), que combining severalan varios esquemas nutritional schemes, physical activity,cionales, actividad física, terapia cognitive-behavioral therapy, and pho-conductual e intervención farmacologic intervention, medicalógica, el manejo médico de la obesity management is a challenging endeavor, often yieldingdad es una tarea desafiante, que a menudo produce un éxito limited success, as lifestyle-basedado, ya que las interventions alone prove insufciones basadas en el estilo de vida por sí solas resultan insuficient in achievinges en lograr una pérdida de peso significant long-term weight loss in some patients, octiva a largo plazo en algunos pacientes, lo que ocasionally leading to a rebound effect wheremente conduce a un efecto rebote en el que los individuals regain more weight than initiallyos recuperan más peso del inicialmente present ate [ 8 the, beginning9 [8][9]].
On
Por the other hand, the drugs approved forro lado, los fármacos aprobados para la obesity aredad son orlistat, phfenterminea/topiramateo, naltrexonea/bupropion, and the Glucagon-like peptide receptor agonists, like Lión y los agonistas de los receptores del péptido similar al glucagón, como liraglutide or Sa o semaglutide, although these treatments can be expensive and may have adverse effects. Thus, it ia, aunque estos tratamientos pueden ser costosos y tener efectos adversos. Por lo tanto, es important to carefullye consider the potentialrar cuidadosamente los posibles benefits and risks of drug therapy before starting treatment in individuals withcios y riesgos de la terapia farmacológica antes de iniciar el tratamiento en personas con obesitydad [ 10 [10]].
G Es ivmportante men this challenge, along with the need for ancionar que se han logrado grandes avances farmacológicos, los cuales se discutirán con mayor profundidad a continuación.
Ante effecstive and long-lasting treatment, metabolic surgery (MS) has proved its efficacy in losing massive amounts of both e 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 tanto subcutaneous and ánea como visceral [ fat11 [11]], lo which involves difque implica diferent techniques designed toes técnicas diseñadas para correct orgir o control obesity, aiming to improve quality of life by achieving adequate and long-lasting WL with minimalar la obesidad. , con el objetivo de mejorar la calidad de vida mediante el logro de una WL adecuada y duradera con complicationciones [12]mínimas [ 12 ].
I
En 2022, the Americlan Society fordad Estadounidense de Cirugía Metabolic and Bariatric Surgery ólica y Bariátrica (ASMBS) andy la Federación Internatcional Federation for the Surgery ofpara la Cirugía de la Obesity anddad y los Trastornos Metabolic Disorderólicos (IFSO) states that MS isafirman que se recommended in case of: BMIienda la EM en caso de: IMC ≥ 35 kg/m 2 (rindepegardless ofndientemente de presence, absence, or severity of co-morbiditiia, ausencia , o gravedad de las comorbilidades), patients with T2D and BMIcientes con diabetes tipo 2 e IMC ≥ 30 kg/m 2 , individuals with BMI of 30–34.personas con un IMC de 30 a 34,9 kg/m 2 que who do not achieve weight loss or co-morbidity improvement using nonsurgical methods. Also, it ino logran perder peso ni mejorar la comorbilidad utilizando métodos no quirúrgicos. Además, es important toe consider geographic factors; for example, obesity in Asiatic people is recognized as BMIar factores geográficos; por ejemplo, la obesidad en personas asiáticas se reconoce como un IMC > 25–27.,5 kg/m 2 , so MS could be performed in these cases. On the other hand, age is not anpor lo que la EM podría realizarse en estos casos. Por otro lado, la edad no es un criterio de exclusion orón o inclusion criteria for MS, and could be performed in Children andón para la EM, y podría realizarse en niños y adolescents with BMIes con IMC > 120% of the 95thdel percentile and a major co-morbidity, or a BMI 95 y una comorbilidad mayor, o un IMC > 140% of the 95th del percentile 95. [ 13 , 14 , 15 , 16 [13][14][15][16]].
MS
Los procedimientos dures hade EM se habían dividido traditionally been divided intocionalmente en categorías restrictiveas, malabsorptive and mixed categories; however, it is now known that MS can cause weight loss not only through these mechanisms but also through appetite controltivas 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 del control del apetito, alterations ofciones de las hormones of the gut brain axisas del eje cerebro-intestino, alterations in bile acid phyciones en la fisiology and intestinalía de los ácidos biliares y la microbiota [17][18][19][20]. Evintestinal [ 17 , 18 , 19 though, 20 MS]. successfully manages to decrease aAunque la EM logra disminuir con éxito un porcentaje significant percentage of body weight, not all patients can maintain the weight loss achieved and could surprisingly regain the lost weighttivo del peso corporal, no todos los pacientes pueden mantener la pérdida de peso lograda y sorprendentemente podrían recuperar el peso perdido [ 21 [21]]; this undesired te escenario could affect the patient’s physical andno deseado podría afectar la salud física y mental healthdel paciente.
2. MetabColic Surgery Compmplicaciones de la cirugía metabólications
AComo se previously mentioned, MS is a low-complication rate procedure with a minimum margin of risk. Overall, themencionó anteriormente, la EM es un procedimiento con una tasa de complicaciones baja y un margen de riesgo mínimo. En general, la combination of improved surgical techniques, surgeon expertise, patient selection,ción de técnicas quirúrgicas mejoradas, experiencia de los cirujanos, selección de pacientes, atención perioperative care, post-oria, manejo posoperative management, and advancements in technology and research haveorio y avances en tecnología e investigación han dado como resulted in a ado una disminución notable decrease in theen la incidence of ia de complications linked to bariatric surgery. Nonetheless, it is not exempt fromciones relacionadas con la cirugía bariátrica. No obstante, no está exenta de complications, and MS has been associated with adverse surgical complicationciones y la EM se ha asociado con complicaciones quirúrgicas adversas, including high-mortalityidas complicationciones [22].de Furalthermora mortalidad [ 22 ]. Además, Pallati et al. [ [23]23 ], ien a systematic review and meta-analysis of 160,000 bariatric patients, reported a post-operativuna revisión sistemática y un metanálisis de 160.000 pacientes bariátricos, informaron una tasa de complications rate between 10–17% and a 7%ciones posoperatorias de entre el 10 y el 17% y una tasa de reoperation rateción del 7%; favorably, themente, la tasa de mortality rate remained low (0.08–0.dad se mantuvo baja (0,08–0,35%).
Th
Las complicaciones perioperative or short-term complications can be divided into minor and major; the most common minor complications are usually at the surgical site (port bleeding ororias o de corto plazo se pueden dividir en menores y mayores; Las complicaciones menores más comunes suelen estar en el sitio quirúrgico (sangrado del puerto o hematoma, skin infections, and post-operativeciones de la piel y dolor neuropathic pain), hydro ático posoperatorio), desequilibrio hidroelectrolyte imbalance, and urinary tract infections. Majorítico e infecciones del tracto urinario. Las complications involve aciones mayores incluyen fugas anastomotic leaks,óticas, hemorragia intra-abdominal bleeding, small bowel perforation, myocardial, perforación del intestino delgado, infarction, and pulmonarto de miocardio y embolisma pulmonar <30 days after MS. Typically, these earlyías después de la EM. Normalmente, la frecuencia de estas complications frequency is below 1.6%, and thciones tempranas es inferior al 1,6% y la tasa de mortality rate is <0.7%dad es <0,7% [ 22 [22]]. PLas fugas post-surgical leaks can arise from the gastrojejunalquirúrgicas pueden surgir de la anastomosis of the RYGB (1.68–2.gastroyeyunal del BGYR (1,68 a 2,05%); in vertical sleeve en la gastrectomy, theyía vertical en manga emerge from the staple line (2.2%). Hemorrhages often begin in the staple line but can also come fromn de la línea de grapas (2,2%). Las hemorragias a menudo comienzan en la línea de grapas, pero también pueden provenir de úlceras anastomotic or gastric remnantóticas o remanentes gástricas [ ulcers24 [24]].
Mor
Adeovermás, although mid- and long-termunque las complications have been wellciones a medio y largo plazo están bien describedtas, establishing their exactecer su incidence is difficult due to the increasingly significant number of patients who miss their follow-upia exacta es difícil debido al número cada vez más importante de pacientes que faltan a sus visits as time goes by. Theseas de seguimiento con el paso del tiempo. Estas complications are ciones son estenosis, bowel oobstruction, ción intestinal, úlceras marginal ulcers,es, hernia ventral hernia, fi, fístula, gastroesophagealenfermedad por reflux disease, and metabolic jo gastroesofágico y complications like nephrolithciones metabólicas como nefrolitiasis and hypoglycemiae hipoglucemia [ [25]25 ]. IEn thiseste context, o, la estenosis gastrojejunal stenosis is a common complication, with anyeyunal es una complicación común, con una tasa de incidence rate ranging from 4% toia que oscila entre el 4% y el 27%, similar to gastroesophageala la enfermedad por reflux disease, which occurs in 12% of cases. Meanwhile, gastric jo gastroesofágico, que ocurre en el 12% de los casos. Mientras tanto, la estenosis is uncommon, only occurring in 1% of the patients. Internal hernigástrica es poco común y solo ocurre en el 1% de los pacientes. Las hernias internas generally cause small bowelmente causan obstructions after gastricciones del intestino delgado después de un bypass or rarely bygástrico o, rara vez, por adherencias intraperitoneal adhesions in 2–3% of the patientes en el 2-3% de los pacientes [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?
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 studies have foundestudios han encontrado factores preoperative factors that mayorios que pueden predispose patients to WR. Aner a los pacientes a la WR. Un estudio prospective study of 782 bariatric patients showed that appo de 782 pacientes bariátricos mostró que aproximately 50% of themdamente el 50% de ellos presented WR, with patients in theaban WR, teniendo los pacientes del grupo super-obese group having a higher peobesos un mayor porcentage of surgical failure (18.8%) and WR. The authorje de fracaso quirúrgico (18,8%) y WR. Los autores concluded that individuals with higher BMI before surgery are more likely to WRyeron que las personas con un IMC más alto antes de la cirugía tienen más probabilidades de sufrir WR [ 71 [71]]. IEn particular, Keith et al. [ [72]72 ], ien their su estudio retrospective studyo, described thatieron que factores preoperative factors such as male sexorios como el sexo masculino ( (p = 0.,020), white racela raza blanca ( p < 0.001), and high,001) y el alto nivel socioeconomic levelómico ( (p = 0.,035) were associated with WR. Furthermore, whense asociaron con WR. Además, cuando se realizó el análisis multivariate analysis was performed, it wasdo, se observed tható que los pacientes socioeconomically advantaged patients were more likely to have WR than the restómicamente favorecidos tenían más probabilidades de tener WR que el resto (OR: 1.82, CI 1.18 to 2.79). However, other authors have differed with this study since their analyse,82, IC 1,18 a 2,79). Sin embargo, otros autores han discrepado con este estudio ya que sus análisis establish that female sex and black race could be ecen que el sexo femenino y la raza negra podrían considered riskarse factors for WRes de riesgo para WR [ 37 , 73 , 74 [37][73][74]].
Althounqugh age has been highlighted as a possible e se ha destacado la edad como un posible factor preoperative factor related to WR, orio relacionado con la WR, los results among studies varyados entre los estudios varían significantly, with both young and oldertivamente, y se informa que tanto los adults (>60 years) reported to be prone toos jóvenes como los mayores (>60 años) son propensos a la WR [73][75][76][ 73 , 75 , 76 ]. MorAdeover, time elapsed after surgery, ironmás, el tiempo transcurrido después de la cirugía, la deficiencyia de hierro [ 77 [77]], workla activity related to eating, anddad laboral relacionada con la alimentación y comorbidities such as T2DM have been linked to lidades como la DM2 se han relacionado con la WR [78][ 78 ].
R
Sorprendentemarkabente, ly,os medications for psychiatric disordermentos para los trastornos psiquiátricos, including tricyclicidos los antidepressants, ivos tricíclicos, el ácido valproic acid, lithium, ando, el litio y los antipsychotics, as well aicóticos, así como los antidiabetic drugs, éticos, los esteroids, and contraes y los anticonceptives, have been associated with weight gain andos, se han asociado con el aumento de peso y la modulación positive appetitea del apetito [ modulation79 [79]]. IEn this regard, post-MS patients treated with any of these drugs could theoretically be at high risk foeste sentido, los pacientes con EM tratados con cualquiera de estos fármacos podrían, en teoría, tener un alto riesgo de sufrir WR [80][ 80 ]. In aAddition, there are genetic factors related to the development ofemás, existen factores genéticos relacionados con el desarrollo de la obesity and dad y la biología del tejido adipose tissue (AT) biology that could beo (TA) que podrían estar implicated indos en la WR post-MS WR. Among these, genetic polymorphisms of ATEM. Entre estos, se destacan los polimorfismos genéticos de los adrenorreceptors such as thees AT, como el gen ADRB2 gene ( ( Gly16Arg andy Gln27Glu ), and those related toy los relacionados con la leptin, such asa, como el gen LEPR-gene ( ( LEPR Lys109Arg , LEPR Gln223Arg , LEPR Lys656Asn), ) [ 81 stand out [81]].
