Impact of Treatment with GLP1 Receptor Agonists, Liraglutide 3.0 mg and Semaglutide 1.0 mg, While on a Waiting List for Bariatric Surgery.

BACKGROUND: Weight loss before undergoing metabolic and bariatric surgery (MBS) has been suggested to reduce perioperative complications, although with controversial results. The objective of this study is to evaluate the impact of treatment with GLP1-R agonists (liraglutide 3.0 mg and semaglutide 1.0 mg) on preoperative weight loss and patients' decisions regarding MBS while on a surgical waiting list. MATERIALS AND METHODS: One hundred and two patients on a waiting list for MBS started treatment with GLP1-RA for at least 6 months. Changes in weight at 26 and 52 weeks, the number of patients achieving >5% weight loss, and patients' decisions regarding MBS were evaluated. RESULTS: After 52 weeks, patients lost 16.9 ± 7.2% of weight with semaglutide 1.0 mg and 16.1 ± 5.8% of weight with liraglutide 3.0 mg. All patients lost ≥5% of initial weight, 84.7% lost ≥10%, 54.6% lost ≥15%, and 27.5% reached ≥20%. A total of 68.6% of participants were satisfied with the achieved weight loss and withdrew from the waiting list for MBS. A threshold of >15.1% weight loss had the greatest sensitivity and specificity for the final decision regarding undergoing MBS. CONCLUSIONS: Losing >15% of initial weight after 52 weeks of treatment with liraglutide 3.0 mg or semaglutide 1.0 mg during the waiting list for MBS impacts patients' decisions regarding the final acceptance or rejection of the procedure.

Combined Effect of Genetic Variants on Long-Term Weight Response after Bariatric Surgery.

The pathophysiology of body weight control involves complex interactions between hormonal, environmental, behavioral and genetic factors. The purpose of this study was to analyze the association between single nucleotide polymorphisms (SNPs) of 13 genes encoding gastrointestinal peptides, their receptors or the proteins involved in their expression, with long-term weight response in a cohort of 375 patients undergoing bariatric surgery (BS). To evaluate weight response, we combined several variables to define specific response phenotypes six years after surgery. The study protocol was registered in ISRCTN (ID80961259). The analysis of the selected SNPs was performed via allelic discrimination using Taqman® probes (Applied Biosystems, Foster City, CA, USA). The genotype association study was performed using the SNPstat program, with comparisons adjusted for sex, age, initial body mass index, type 2 diabetes, hypertension diagnosis and the type of surgery. We identified eight genetic variants associated with the weight response to BS, independently of the presurgery patient profile and the type of surgical technique, from which we calculated the unweighted risk score (RS) for each phenotype. The highest scoring category in each RS was significantly associated with lower weight loss (p = 0.0001) and greater weight regain (p = 0.0012) at the end of the follow-up.

Mixed Meal Tolerance Test Versus Continuous Glucose Monitoring for an Effective Diagnosis of Persistent Post-Bariatric Hypoglycemia.

Gastric bypass determines an increase in incretin secretion and glucose excursions throughout the day and may sometimes entail the development of severe post-bariatric hypoglycemia (PBH). However, there is no consensus on the gold standard method for its diagnosis. In this study, we evaluated the usefulness of a mixed meal tolerance test (MMTT) and continuous glucose monitoring (CGM) for the diagnosis of PBH, defined as glucose levels <54 mg/dL (3.0 mmol/L). We found that hypoglycemia occurred in 60% of patients after the MMTT and in 75% during CGM, and it was predominantly asymptomatic. The MMTT confirmed the diagnosis of PBH in 88.9%of patients in whom surgery had been performed more than three years ago, in comparison to 36.4% in cases with a shorter postsurgical duration. CGM diagnosed nocturnal asymptomatic hypoglycemia in 70% of patients, and daytime postprandial hypoglycemia in 25% of cases. The mean duration of asymptomatic hypoglycemia was more than 30 min a day. Patients with ≥2% of their CGM readings with hypoglycemia exhibited a higher degree of glucose variability than those with <1% of the time in hypoglycemia. Our results show that the MMTT may be a useful dynamic test to confirm the occurrence of hypoglycemia in a large number of patients with persistent and recurrent PBH during long-term follow-up after gastric bypass. CGM, on its part, helps identify hypoglycemia in the real-world setting, especially nocturnal asymptomatic hypoglycemia, bringing to light that PBH is not always postprandial.

Influence of CLOCK Gene Variants on Weight Response after Bariatric Surgery.

The Circadian Locomotor Output Cycles Kaput (CLOCK) gene has been linked to metabolic dysfunction and obesity. The purpose of this study was to analyze the association between single nucleotide polymorphisms (SNPs) of CLOCK gene with obesity and with long-term weight response after different bariatric surgery (BS) techniques. The cohort includes 375 patients with morbid obesity (MO) and 230 controls. In the association study of SNPs with weight response we combined several variables as phenotype at 6 years after surgery. The study protocol was registered in ISRCTN (ID80961259). The analysis of the selected SNPs was performed by allelic discrimination using Taqman® probes. The genotype association study was performed using the SNPStats program, with comparisons adjusted for sex, age, initial Body Mass Index, type 2 diabetes and hypertension diagnosis, and type of surgery. In the case-control study two of three SNPs were significantly associated with MO. The variant rs1801260 had a protective effect for MO whereas the TT genotype of rs3749474 variant had the strongest association with MO (OR = 2.25 (1.39-3.66); p = 0.0006). In the linear regression analysis both variants showed significant association with long-term weight loss and weight regain after BS, independently of the pre-surgery patient profile.

Obesity in the COVID era: A global health challenge. / Obesidad en tiempos de COVID-19. Un desafío de salud global.

Obesity is a chronic disease that leads to an increased risk of mortality and morbidity, and the impact of the COVID-19 pandemic may create a new health challenge. There is clear evidence showing that some biological and social factors associated with obesity involve an increased risk of COVID-19 infection, hospitalization, and greater severity compared to people with normal weight. Undoubtedly, obesity involves a low-grade proinflammatory state that produces a dysregulation of the immune system that compromises its ability to respond to respiratory infection by COVID-19 and so produces a worsening of the disease. In this review, the main epidemiological and pathophysiological data that associate obesity with COVID-19 are described.

[Obesity in the COVID era: A global health challenge]. / Obesidad en tiempos de COVID-19. Un desafío de salud global.

Obesity is a chronic disease that leads to an increased risk of mortality and morbidity, and the impact of the COVID-19 pandemic may create a new health challenge. There is clear evidence showing that some biological and social factors associated with obesity involve an increased risk of COVID-19 infection, hospitalization, and greater severity compared to people with normal weight. Undoubtedly, obesity involves a low-grade proinflammatory state that produces a dysregulation of the immune system that compromises its ability to respond to respiratory infection by COVID-19 and so produces a worsening of the disease. In this review, the main epidemiological and pathophysiological data that associate obesity with COVID-19 are described.

Expression analysis of a cholecystokinin system in human and rat white adipose tissue.

AIM: Cholecystokinin (CCK) participates in the storage of dietary triglycerides in white adipose tissue (WAT). Our goal was to characterize, both in subcutaneous (Sc-WAT) and visceral WAT (Vis-WAT), the functional expression of the two known CCK receptors, CCK-1 (CCK-1R) and CCK-2 (CCK-2R), as well as of CCK. MAIN METHODS: Gene and protein expression was assessed in different cell types of rat and human WAT by means of RT-PCR and western-blot, respectively. The functionality of CCK-Rs was tested by quantifying protein kinase B (Akt) phosphorylation after treatment of pre-adipocytes with the bioactive fragment of CCK, CCK-8. The CCK receptor subtype involved in Akt phosphorylation was investigated by using selective CCK-1R (SR-27,897) and CCK-2R antagonists (L-365,260). KEY FINDINGS: In rats, CCK-1R (Cckar) and CCK-2R (Cckbr) gene expression was detected in the two types of WAT analyzed as well as in isolated adipocytes, mesenchymal stem cells and pre-adipocytes. CCK-1R and CCK-2R proteins were identified in adipocytes and, to a minor extent, in pre-adipocytes. In addition, CCK-2R were detected in subcutaneous mesenchymal stem cells. Gene expression of the CCK precursor preproCCK as well as CCK immunoreactivity were also found in Sc-WAT and Vis-WAT. In human WAT, CCK gene expression as well as CCK-2Rs and CCK were also identified. CCK-8 evoked Akt phosphorylation in rat pre-adipocytes, and this effect was antagonized by SR-27,897 and L-365,260. SIGNIFICANCE: Our data show that both human and rat WAT express a complete CCK system, and suggest that CCK may have an autocrine/paracrine role in regulating adipose tissue biology.

Long-Term Food Tolerance After Bariatric Surgery: Comparison of Three Different Surgical Techniques.

BACKGROUND: Food tolerance has been related to quality of life after bariatric surgery. However, long-term results about this issue are quite limited. The aim of this study was to evaluate the long-term food tolerance in obese patients submitted to surgery, comparing the results between gastric bypass (GBP), long alimentary modified biliopancreatic diversion (MBPD), and long alimentary modified duodenal switch (MDS). METHODS: A cross-sectional analytic study was performed. Food tolerance was studied with a questionnaire based on subjective alimentary satisfaction, tolerance to different foods, and frequency of vomiting and regurgitation. A food tolerance score was obtained (1 point being the worst possible tolerance and 27 points being a perfect one). Information was obtained with a telephone interview. RESULTS: One hundred ninety-six patients submitted to bariatric surgery were included. Ninety-nine patients were submitted to GBP, 54 to MBPD, and 43 to MDS. One hundred and sixty-one patients (82.1%) were not lost during a mean follow-up time of 87.9 months. Mean food tolerance score was 24.2. Tolerance satisfaction was good or excellent in 73.3% of the patients. Red meat was the worst tolerated food, but nearly 80% of the patients could tolerate it without any problem. Mean food tolerance score was 24.6, 24.0, and 23.7 for GBP, MBPD, and MDS, respectively. There were no significant differences between these procedures in food tolerance score, alimentary satisfaction, or frequency of vomiting. CONCLUSIONS: Long-term food tolerance after bariatric surgery is good. No differences between GBP, MBPD, and MDS were found.

Metabolic surgery: quo vadis?

The impact of bariatric surgery beyond its effect on weight loss has entailed a change in the way of regarding it. The term metabolic surgery has become more popular to designate those interventions that aim at resolving diseases that have been traditionally considered as of exclusive medical management, such as type 2 diabetes mellitus (T2D). Recommendations for metabolic surgery have been largely addressed and discussed in worldwide meetings, but no definitive consensus has been reached yet. Rates of diabetes remission after metabolic surgery have been one of the most debated hot topics, with heterogeneity being a current concern. This review aims to identify and clarify controversies regarding metabolic surgery, by focusing on a critical analysis of T2D remission rates achieved with different bariatric procedures, and using different criteria for its definition. Indications for metabolic surgery for patients with T2D who are not morbidly obese are also discussed.

Bariatric surgery in type 1 diabetes mellitus; long-term experience in two cases.

In patients with obesity and type 2 diabetes, recommendations for bariatric surgery are well established. However, no consensus exists regarding its role for the management of patients with type 1 diabetes and morbid obesity. We present the long-term follow-up of two women with type 1 diabetes, morbid obesity and associated comorbidities, who underwent malabsorptive bariatric surgery. More than four years after the procedure, both have a body mass index (BMI) within the normal range and HbA1c levels below 7%. Also, they have been able to reduce their insulin requirements in more than 50%, their associated comorbidities have disappeared, and their overall quality of life has significantly improved. We compare our results with other recently published ones, emphasizing potential indications of bariatric surgery for patients with type 1 diabetes.

Las indicaciones de la cirugía bariátrica en los pacientes con diabetes tipo 2 y obesidad están bien establecidas, pero no existe consenso que contemple esta posibilidad de tratamiento en los pacientes con diabetes tipo 1 que presentan obesidad severa. Presentamos la evolución a largo plazo de dos mujeres diagnosticadas de diabetes tipo 1 (DM1) y que presentaban obesidad mórbida y comorbilidades asociadas que fueron intervenidas mediante la realización de una cirugía bariátrica malabsortiva. Tras seguimiento de más de 4 años, ambas pacientes mantienen un BMI dentro de la normalidad, concentraciones de hemoglobina glicada < 7%, reducción de sus necesidades de insulina en más del 50 %, remisión de las comorbilidades y clara mejoría de su calidad de vida. Se analizan estos resultados en comparación a otros publicados previamente con la finalidad de señalar las potenciales indicaciones de la cirugía bariátrica en pacientes con DM 1.

Dermatitis and optic neuropathy due to zinc deficiency after malabsortive bariatric surgery.

We present a patient who underwent successful classic duodenal switch and developed a marked dermatitis with a significant functional limitation. This is an unusual complication, despite the relatively moderate prevalence of nutrient deficiency after this type of bariatric surgery. We discuss possible pathogenic mechanisms and emphasize the importance of an appropriate nutritional management.

Se presenta el caso de una mujer sometida a cirugía bariátrica malabsortiva que desarrolló una llamativa dermopatía y neuropatía secundarias al déficit de zinc. Se trata de una complicación muy poco frecuente, a pesar de la prevalencia de déficit de micronutrientes que se ha observado tras este tipo de intervención. Se discute la patogenia y se recalca el papel del correcto manejo nutricional como tratamiento eficaz.

Update on pharmacology of obesity: benefits and risks.

The prevalence of obesity in Western countries has increased at a much greater pace than the development of new efficient and safe drugs, beyond mere lifestyle changes, for the treatment of overweight. Numerous different types of drugs which had been used in the past for the treatment of obesity have currently been withdrawn due to undesirable long-term side effects. The only available drug in Europe is orlistat, which serves only as an aid for the treatment of obesity. In the USA, however, a few central adrenergic-mediators, for instance, diethylpropion and phentermine, have been available for decades to treat obesity during a short-term period (less than 12 weeks). The Food and Drug Administration (FDA) has recently approved lorcaserin and the combination phentermine/ topiramate for the treatment of obesity. The first one is a selective serotonin 2C receptor agonist that works by decreasing food intake with few side effects. Its outcomes on weight are modest, but may be helpful in certain selected patients. The phentermine/topiramate combination has proved to be highly effective, achieving a 10% reduction in weight in the majority of patients, although attention must be drawn to the possible development of side effects in both the short and the long-term follow-up. Further investigation regarding the mechanisms involved in weight balance will anticipate the development of new expectations for the treatment of obesity in the near future.

El incremento de la prevalencia de obesidad en los países occidentales no ha sido paralela al desarrollo de nuevos fármacos eficaces y seguros a largo plazo para el tratamiento del exceso de peso más allá de los cambios en el estilo de vida. La larga lista de fármacos que se han utilizado para el tratamiento de la obesidad han tenido que ser retirados por efectos secundarios indeseables para la salud a largo plazo. En Europa solo contamos con orlistat, como único fármaco coadyuvante para el tratamiento de la obesidad, mientras que en EEUU hace décadas disponen de unos pocos fármacos adrenérgicos de acción central (como Dietilpropion o Phentermine) para un tratamiento a corto plazo (inferior a 12 semanas). Recientemen te, la Food and Drug Administration (FDA), acaba de aprobar la lorcaserina y la combinación de Phentermine y topiramate. Lorcaserine es un agonista específico del receptor serotoninérgico 2c, con actividad anorexígena y pocos efectos secundarios. Sus efectos sobre el peso son moderados, pero pueden ser de utilidad en algunos pacientes seleccionados. La combinación de phentermine y topiramate es muy eficaz alcanzando un 10% de pérdida de peso en una mayoría de pacientes, aunque debemos estar atentos acerca de sus potenciales efectos secundarios a corto y largo plazo. La profundización en la investigación de los mecanismos implicados en la regulación del peso corporal conllevará nuevas expectativas de tratamientos para la obesidad en un futuro próximo.

Severe vitamin A deficiency after malabsortive bariatric surgery.

Vitamin A deficiency may occur after malabsorptive bariatric surgery. However, it rarely entails important functionally limiting symptoms. We present the case of a woman who underwent bariatric surgery and developed ocular dryness, xeroderma and hearing loss due to severe vitamin A deficiency. We illustrate an outstanding and exceptional case of the consequences of an excessive and uncontrolled malabsorption.

Aunque el déficit de vitamina A puede desarrollarse tras la realización de cirugía bariátrica malabsortiva, raramente conlleva la aparición de síntomas que repercutan en la situación funcional del paciente. Presentamos el caso de una mujer que desarrolló xeroftalmia, xerodermia e hipoacusia secundarias a déficit muy severo de vitamina A. Ilustramos el llamativo y excepcional ejemplo de la repercusión de una malabsorción descontrolada.