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Aims To investigate whether the elevation in postprandial concentrations of the gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM) and peptide YY (PYY) accounts for the beneficial changes in food preferences, sweet taste function and eating behaviour after Roux-en-Y gastric bypass (RYGB). Materials and methods This was a secondary analysis of a randomized single-blind study in which we infused GLP-1, OXM, PYY (GOP) or 0.9% saline subcutaneously for 4 weeks in 24 subjects with obesity and prediabetes/diabetes, to replicate their peak postprandial concentrations, as measured at 1 month in a matched RYGB cohort (ClinicalTrials.gov NCT01945840). A 4-day food diary and validated eating behaviour questionnaires were completed. Sweet taste detection was measured using the method of constant stimuli. Correct sucrose identification (corrected hit rates) was recorded, and sweet taste detection thresholds (EC50s: half maximum effective concencration values) were derived from concentration curves. The intensity and consummatory reward value of sweet taste were assessed using the generalized Labelled Magnitude Scale. Results Mean daily energy intake was reduced by 27% with GOP but no significant changes in food preferences were observed, whereas a reduction in fat and increase in protein intake were seen post-RYGB. There was no change in corrected hit rates or detection thresholds for sucrose detection following GOP infusion. Additionally, GOP did not alter the intensity or consummatory reward value of sweet taste. A significant reduction in restraint eating, comparable to the RYGB group was observed with GOP. Conclusion The elevation in plasma GOP concentrations after RYGB is unlikely to mediate changes in food preferences and sweet taste function after surgery but may promote restraint eating.

OBJECTIVE: Up to 37% of bariatric surgery patients suffer from insufficient weight loss or weight regain and mental health symptoms in the longer term. Cognitive behavioral therapy (CBT) may be an effective adjunct intervention to optimize patients' psychological functioning and weight loss results. To examine the value of adding preoperative CBT to bariatric surgery, three- and five-year follow-up data are presented.METHOD: In this multi-center randomized controlled trial (RCT; N = 130), a CBT group was compared to a treatment-as-usual (TAU) control group. Measurements were conducted at five time points: pretreatment (T0) and posttreatment/presurgery (T1) and at one- (T2; N = 120), three- (T3; N = 117), and five-year postsurgery (T4; N = 115). The intervention group received a 10-weeks, individual, preoperative CBT focused on self-monitoring, identifying triggers for disordered eating and goal setting for eating behavior and physical exercise, as well as postoperative lifestyle. Outcome measures included weight change, eating behavior, eating disorders, depression, quality of life (QoL), and overall psychological health.RESULTS: Preoperative CBT was not associated with better three- and five-year results than TAU regarding weight, dysfunctional eating behaviors, eating disorders, depression, overall psychological health, and QoL.DISCUSSION: Contrary to our hypothesis, three- and five-year postsurgery differences between groups regarding weight change and mental health were not significant.. Further exploration suggested that in both groups weight problems and depressive symptoms worsened at three and five-year follow-up. Future research should focus on long-term postoperative monitoring of weight and mood and on associated postoperative interventions and their specific timing.PUBLIC SIGNIFICANCE: After bariatric surgery, in the longer term weight problems re-occur in 30% of patients, which is probably partly related to psychopathology. We investigated whether cognitive behavior therapy (CBT) prior to bariatric surgery improved weight maintenance and mental health after surgery. Our study provided definite proof that preoperative CBT is not effective. Long-term postoperative monitoring and prompt psychological intervention after first signs of deterioration, are important to prevent further problems.

This scoping review summarizes current evidence with regard to the impact of bariatric surgery on psychological health in adults with obesity. While a large body of evidence reports major metabolic benefit and improved quality of life, there is also ample evidence suggesting an increased incidence of self-harming behavior, a greater likelihood of developing an alcohol problem and higher rates of completed suicide among bariatric patients. Being able to identify the "at risk" patient population requires more longitudinal research into the risk factors for psychological complications after bariatric surgery. Bariatric surgery remains an extremely valuable long-term treatment option for managing obesity; however, there is a need to invest in mitigating psychological complications after the surgery, such as depression, alcohol consumption, and other self-harming behaviors. ispartof: OBESITY SURGERY vol:31 issue:12 pages:5409-5417 ispartof: location:United States status: published

BackgroundAlthough early results of bariatric surgery are beneficial for most patients, some patients regain weight later. Cognitive behavioral therapy (CBT) has been suggested as a way to improve patients’ psychological health and maintaining weight loss in the longer term. The added value of preoperative CBT to bariatric surgery was examined. Pre- and posttreatment and 1-year follow-up data are presented.MethodsIn a multi-center randomized controlled trial, CBT was compared to a treatment-as-usual (TAU) control group. Measurements were conducted pre- and posttreatment/pre-surgery (T0 and T1) and at 1-year post-surgery (T2). Patients in the intervention group received 10 individual, weekly sessions of preoperative CBT focused on modifying thoughts and behaviors regarding eating behavior, physical exercise, and postoperative life style. Outcome measures included weight change, eating behavior, eating disorders, depression, quality of life, and overall psychological health.ResultsThough no significant differences between conditions were found per time point, in the CBT, condition scores on external eating, emotional eating, depressive symptoms, and psychological distress decreased significantly more over time between pre- (T0) and posttreatment (T1) pre-surgery compared to TAU. No significant time x condition differences were found at 1-year post-surgery (T2).ConclusionsCompared to TAU, preoperative CBT showed beneficial effects on eating behavior and psychological symptoms only from pretreatment to posttreatment/pre-surgery, but not from pre-surgery to 1-year post-surgery. Preoperative CBT does not seem to contribute to better long-term outcomes post-surgery. Recent studies suggest that the optimal time to initiate psychological treatment may be early in the postoperative period, before significant weight regain has occurred.Trial Registrationhttps://www.trialregister.nlIdentifier: Trial NL3960.

International audience; Considering the large and increasing population of women of childbearing age with history of bariatric surgery, surgical complications of bariatric surgery during pregnancy may become more frequent in the future. The aim of this study was to analyze the clinical presentation, diagnostic procedures, and treatment of surgical complications of bariatric surgery during pregnancies. A systematic literature search was performed in accordance with the PRISMA (preferred reporting items for systematic review and meta-analysis) guidelines to identify all studies published up to and including December 2018 that included women with previous bariatric surgery undergoing emergency surgery during pregnancy. Sixty-eight studies were selected, including 120 women with previous bariatric surgery undergoing emergency surgery during pregnancy. Fifty cases were reported as case reports and 70 in case series. Included patients had previous history of Roux-en-Y gastric bypass (n = 99), laparoscopic adjustable gastric banding (n = 17), Scopinaro procedure (n = 2), vertical banded gastroplasty (n = 1), or one-anastomosis gastric bypass (n = 1). Final diagnosis in 50 case reports was internal hernia in 26 cases, bowel intussusception in 10, intestinal obstruction in 2, laparoscopic adjustable gastric banding slippage in 3, bowel volvulus in 3, gastric or jejunal perforation in 2, and other complications in 4 cases. Maternal and fetal death occurred in 3 (2.5%) and 9 cases (7.5%), respectively. In the case series, the majority of women were operated for internal hernia and laparoscopic adjustable gastric banding slippage. Surgical complications of previous bariatric surgery during pregnancy have potentially severe outcomes. Availability of multidisciplinary expertise, including bariatric/digestive surgeons, and education of healthcare providers and women on clinical signs that require urgent surgical examination are recommended in this setting. Prompt diagnosis is fundamental and based on clinical and laboratory findings and on radiologic examinations if needed, including computed tomography scan or magnetic resonance if available. Rapid surgical exploration is mandatory in case of high clinical and/or radiologic suspicion. (C) 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes. © 2020 The Author(s) Published by S. Karger AG, Basel.

We aimed to assess the effectiveness of exercise training programs in adults with severe obesity undergoing bariatric surgery. A systematic search of controlled trials published up to October 2019 that assigned participants to either a preoperative or postoperative exercise training group or a nonexercise group was performed. Meta-analyses were conducted using random-effects models. Twenty-two training programs were assessed (18 performed after bariatric surgery). The effect of preoperative exercise training on postsurgery outcomes was reported in only one study. Compared with the control condition without exercise, postoperative exercise training led to higher weight loss (N = 14, mean difference [95% CI] = -1.8 [-3.2; -0.4] kg, P = 0.01), fat loss (N = 9, P = 0.01), increase in VO(2)max (N = 8, P < 0.0001), and increase in muscle strength (N = 9, P < 0.0001). No significant effect was found on lean body mass (N = 11). Preliminary evidence suggests a beneficial effect of postoperative exercise training on bone mineral density (N = 3, P < 0.001) and weight maintenance after the end of the intervention (N = 2, P < 0.001) but no significant effect on quality of life (N = 2), habitual physical activity (N = 2), or cardiometabolic outcomes (N < 4). In conclusion, exercise training performed after bariatric surgery improves physical fitness and leads to a small additional weight and fat loss and may prevent bone loss and weight regain after bariatric surgery.

Obesity, defined as a body mass index of >= 30 kg/m(2), is the most common chronic metabolic disease worldwide and its prevalence has been strongly increasing. Obesity has deleterious effects on cardiac function. The purpose of this review is to evaluate the effects of obesity and excessive weight loss due to bariatric surgery on cardiac function, structural changes and haemodynamic responses of both the left and right ventricle.

Adequate glucocorticoid replacement in patients with primary or secondary adrenal insufficiency is essential to maintain general well-being. Little is known about the effects of bariatric surgery on glucocorticoid absorption. This study evaluates glucocorticoid absorption before and after bariatric surgery, with assessment of plasma cortisol profiles in five patients receiving glucocorticoid replacement therapy for primary (n = 1) or secondary (n = 4) adrenal insufficiency. One patient underwent sleeve gastrectomy (SG), one a one-anastomosis gastric bypass (mini-GB), and three a Roux-en-Y gastric bypass (RYGB). Pharmacokinetic calculations were based on plasma cortisol measurements performed during the first 6 hours after ingestion of the morning dose. Plasma cortisol profiles were very similar before and after surgery; only minor differences were observed. After SG, plasma peak cortisol concentration and cortisol area under the curve (AUC) were higher by 23% and 24%, respectively, and time to peak cortisol was 10 minutes shorter. The mini-GB had no marked effect on pharmacokinetic parameters. In the three patients who underwent RYGB, AUC changes ranged from −12% to 20%. In conclusion, in this small number of patients with adrenal insufficiency, plasma cortisol profiles were similar before and after bariatric surgery. However, in view of individual differences in response to different types of surgery, we recommend postoperative cortisol profiling to guide appropriate glucocorticoid dose adjustment.

OBJECTIVE: There are many studies. which demonstrate that morbid obesity is associated with an increase in Thyroid Stimulating Hormone (TSH) levels. However, the effect of Laparoscopic Sleeve Gastrectomy (LSG) procedure on postoperative TSH levels is not clear. This study aims to evaluate the effect of weight loss after LSG procedure on TSH levels in euthyroid patients with morbid obesity. PATIENTS AND METHODS: 159 Euthyroid patients who applied for an LSG procedure (93.7% female, with a mean age of 34.18 +/- 10.01 years, BMI 43.2 +/- 6.82 kg/m(2)) were retrospectively analyzed for the study. The parameters used in the analysis were their serum free T3 levels (fT3), free T4 levels (fT4), and TSH levels preoperatively and at 6 months after surgery. The postoperative correlation between TSH and BMI (Body Mass Index), % EWL (Percent Excess Weight Loss), and % TWL (Total Weight Loss) levels were evaluated. RESULTS: Mean BMI change from 43.2 +/- 6.82 kg/m(2) to 30.48 +/- 5.63 kg/m(2) (p

We aimed to assess the effectiveness of exercise training programs in adults with severe obesity undergoing bariatric surgery. A systematic search of controlled trials published up to October 2019 that assigned participants to either a preoperative or postoperative exercise training group or a nonexercise group was performed. Meta-analyses were conducted using random-effects models. Twenty-two training programs were assessed (18 performed after bariatric surgery). The effect of preoperative exercise training on postsurgery outcomes was reported in only one study. Compared with the control condition without exercise, postoperative exercise training led to higher weight loss (N = 14, mean difference [95% CI] = -1.8 [-3.2; -0.4] kg, P = 0.01), fat loss (N = 9, P = 0.01), increase in VO2 max (N = 8, P

The gastrointestinal (GI) microbiota plays an important role in health and disease, including brain function and behavior. Bariatric surgery (BS) has been reported to result in various changes in the GI microbiota, therefore demanding the investigation of the impact of GI microbiota on treatment success. The goal of this systematic review was to assess the effects of BS on the microbiota composition in humans and other vertebrates, whether probiotics influence postoperative health, and whether microbiota and psychological and behavioral factors interact. A search was conducted using PubMed and Web of Science to find relevant studies with respect to the GI microbiota and probiotics after BS, and later screened for psychological and behavioral parameters. Studies were classified into groups and subgroups to provide a clear overview of the outcomes. Microbiota changes were further assessed for whether they were specific to BS in humans through the comparison to sham operated controls in other vertebrate studies. Changes in alpha diversity appear not to be specific, whereas dissimilarity in overall microbial community structure, and increases in the abundance of the phylum Proteobacteria andAkkermansiaspp. within the phylum Verrucomicrobia after surgery were observed in both human and other vertebrates studies and may be specific to BS in humans. Human probiotic studies differed regarding probiotic strains and dosages, however it appeared that probiotic interventions were not superior to a placebo for quality of life scores or weight loss after BS. The relationship between GI microbiota and psychological diseases in this context is unclear due to insufficient available data.

The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population. However, many disease conditions are associated with an alteration of the anatomy and/or physiology of the GI tract. The same holds true for some subpopulations, such as paediatric or elderly patients, or populations with different ethnicity. The variation in GI tract conditions compared to healthy adults can directly affect the kinetics of drug absorption, and thus, safety and efficacy of an oral medication. This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions. Particular focus is directed towards non-disease dependent conditions (age, sex, ethnicity, genetic factors, obesity, pregnancy), GI diseases (ulcerative colitis and Crohn's disease, celiac disease, cancer in the GI tract, Roux-en-Y gastric bypass, lactose intolerance, Helicobacter pylori infection, and infectious diseases of the GI tract), as well as systemic diseases that change the GI tract conditions (cystic fibrosis, diabetes, Parkinson's disease, HIV enteropathy, and critical illness). The current knowledge about GI conditions in special populations and their impact on drug absorption is still limited. Further research is required to improve confidence in pharmacokinetic predictions and dosing recommendations in the targeted patient population, and thus to ensure safe and effective drug therapies.Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population. However, many disease conditions are associated with an alteration of the anatomy and/or physiology of the GI tract. The same holds true for some subpopulations, such as paediatric or elderly patients, or populations with different ethnicity. The variation in GI tract conditions compared to healthy adults can directly affect the kinetics of drug absorption, and thus, safety and efficacy of an oral medication. This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions. Particular focus is directed towards non-disease dependent conditions (age, sex, ethnicity, genetic factors, obesity, pregnancy), GI diseases (ulcerative colitis and Crohn's disease, celiac disease, cancer in the GI tract, Roux-en-Y gastric bypass, lactose intolerance, Helicobacter pylori infection, and infectious diseases of the GI tract), as well as systemic diseases that change the GI tract conditions (cystic fibrosis, diabetes, Parkinson's disease, HIV enteropathy, and critical illness). The current knowledge about GI conditions in special populations and their impact on drug absorption is still limited. Further research is required to improve confidence in pharmacokinetic predictions and dosing recommendations in the targeted patient population, and thus to ensure safe and effective drug therapies. ispartof: EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES vol:147 ispartof: location:Netherlands status: published

Background: Obesity in pediatric and adolescent population has reached a universal pandemic. This study aimed to summarize the literature on the longest available outcome of bariatric surgery in morbidly obese adolescents.Methods :A systematic review was conducted to pool available data on the longest available (> 3 years) weight loss and comorbidity resolution outcome in adolescent bariatric surgery.Results: A total of 14 studies reporting the result of bariatric surgery after 3 years in 950 morbidly obese adolescents were included. Preoperative age and BMI ranged from 12 to 19 years and from 26 to 91 kg/m(2), respectively. Females were the predominant gender (72.8%). Laparoscopic roux-en-Y gastric bypass (n = 453) and adjustable gastric banding (n = 265) were the most common bariatric procedure performed. The number of patients at the latest follow-up was 677 (range from 2 to 23 years). On average, patients lost 13.3 kg/m(2) of their BMI. Among comorbidities, only diabetes mellitus resolved or improved dramatically. Of 108 readmissions, 91 led to reoperation. There was a weight regain Conclusion: Although bariatric surgery is a safe and effective procedure in the treatment of adolescent morbid obesity, long-term data is scarce regarding its nutritional and developmental complication in this growing population of patients.

PURPOSE OF REVIEW: Bariatric surgery is the most effective treatment for morbid obesity. However, 20-30% of patients undergoing bariatric surgery experience premature weight stabilization or weight regain postoperatively. We report on the recent literature of predictors of weight loss and the efficacy of cognitive behavioral therapy (CBT) in bariatric patients.RECENT FINDINGS: Preoperative disordered eating behaviors do not appear to be significantly predictive of postoperative weight loss. Postoperative disordered eating behaviors, eating disorders, and depressive symptoms have been found to be associated with less optimal weight loss results. Recent studies show that CBT can contribute in reducing disordered eating behaviors and depressive symptoms. Some studies also show that pre and postoperative CBT interventions can promote weight loss. New applications of CBT such as by telephone, internet, or virtual reality might contribute to more accessible and low-cost treatments for the large group of bariatric patients worldwide.SUMMARY: CBT seems to be effective in reducing risk factors for weight regain after bariatric surgery, such as disordered eating behavior and depression. Controlled studies with long-term follow-up and larger sample sizes are needed to investigate the long-term effect of CBT interventions on weight loss results and psychological well-being.

Purpose of reviewBariatric surgery is the most effective treatment for morbid obesity. However, 20-30% of patients undergoing bariatric surgery experience premature weight stabilization or weight regain postoperatively. We report on the recent literature of predictors of weight loss and the efficacy of cognitive behavioral therapy (CBT) in bariatric patients.Recent findingsPreoperative disordered eating behaviors do not appear to be significantly predictive of postoperative weight loss. Postoperative disordered eating behaviors, eating disorders, and depressive symptoms have been found to be associated with less optimal weight loss results. Recent studies show that CBT can contribute in reducing disordered eating behaviors and depressive symptoms. Some studies also show that pre and postoperative CBT interventions can promote weight loss. New applications of CBT such as by telephone, internet, or virtual reality might contribute to more accessible and low-cost treatments for the large group of bariatric patients worldwide.SummaryCBT seems to be effective in reducing risk factors for weight regain after bariatric surgery, such as disordered eating behavior and depression. Controlled studies with long-term follow-up and larger sample sizes are needed to investigate the long-term effect of CBT interventions on weight loss results and psychological well-being.

Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in human substrate and energy metabolism, thereby connecting the heart with several insulin-sensitive organs like adipose tissue, skeletal muscle and liver. Obesity may be associated with an impaired regulation of the natriuretic peptide system, also indicated as a natriuretic handicap. Evidence points towards a contribution of this natriuretic handicap to the development of obesity, type 2 diabetes mellitus and cardiometabolic complications, although the causal relationship is not fully understood. Nevertheless, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on current literature regarding the metabolic roles of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Furthermore, it will be discussed how exercise and lifestyle intervention may modulate the natriuretic peptide-related metabolic effects.

Background: Obesity in pediatric and adolescent population has reached a universal pandemic. This study aimed to summarize the literature on the longest available outcome of bariatric surgery in morbidly obese adolescents. Methods :A systematic review was conducted to pool available data on the longest available (> 3 years) weight loss and comorbidity resolution outcome in adolescent bariatric surgery. Results: A total of 14 studies reporting the result of bariatric surgery after 3 years in 950 morbidly obese adolescents were included. Preoperative age and BMI ranged from 12 to 19 years and from 26 to 91 kg/m(2), respectively. Females were the predominant gender (72.8%). Laparoscopic roux-en-Y gastric bypass (n = 453) and adjustable gastric banding (n = 265) were the most common bariatric procedure performed. The number of patients at the latest follow-up was 677 (range from 2 to 23 years). On average, patients lost 13.3 kg/m(2) of their BMI. Among comorbidities, only diabetes mellitus resolved or improved dramatically. Of 108 readmissions, 91 led to reoperation. There was a weight regain

Diet, exercise, cognitive behavioral therapy and pharmacotherapy are some of the means of assisting patients to lose weight, with bariatric surgery being the most effective. Over the last two decades, the increased awareness of the systemic benefits of bariatric surgery, as well as the improved safety and the wider use of the laparoscopic approach, has made bariatric surgery flourish. In the United Kingdom, the adjustable gastric band (10%), vertical sleeve gastrectomy (37%) and Roux-en-Y gastric bypass (45%) are the three most common procedures. Obesity-associated mortality and co-morbidities such as type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, renal dysfunction and depression improve significantly with bariatric surgery. The mechanisms of weight loss extend beyond restriction and malabsorption and include changes in hunger and satiety, food preferences, and possibly energy expenditure. Despite its safety and efficacy, bariatric surgery is underutilized as less than 1% of adults with obesity receive it. In view of the evolution of obesity into a global threat, access to bariatric surgery should be increased, whilst developing safer and less invasive weight loss treatments.

Modern treatment of type 2 diabetes must rely on therapy individualization. Morbid obesity confers an independent excess of risk to diabetes. In these individuals metabolic surgery is an opportunity the physician should consider, especially at the time of the diabetes diagnosis, because of its efficacy and long-term effects. In addition to the possible remission of diabetes, bariatric surgery is also associated with reduced risk of micro- and macrovascular complications. A multidisciplinary team approach is necessary to maximize the beneficial effects and minimize the adverse events of metabolic surgery and to ensure proper follow-up based on the residual possibility of developing complications. In this regard, a consensus on definition of remission must be reached to define the residual risk after antidiabetic drug withdrawal. Finally, randomized clinical trials are deemed necessary to establish the risk-to-benefit profile of glucose-lowering agents for those patients who have remained diabetic or experience a disease relapse.

IF 5.088; International audience; Obesity is undoubtedly one of the major public health challenges worldwide because of its rapid progression and deleterious effects of associated diseases. The easier access to tasty and energy-dense foods is thought to greatly contribute to this epidemic. Studies also report that obese subjects and animals (rats and mice) preferentially consume foods rich in fat when they can choose. The origin of this eating behavior remains elusive. Over the last decade, the existence of a taste of fat, besides textural and olfactory cues, was supported by a growing number of studies. The existence of a sixth taste modality devoted to the detection/perception of dietary lipids might offer additive information on the quality of food. While the sense of taste is recognized to be a driving-force guiding food choice, interest in the putative relationships between lipids, gustation and obesity is only now emerging. This mini-review will attempt to summarize our current knowledge on this new field of research.

Background Obesity increases the risk of several types of cancer. Whether bariatric surgery influences the risk of obesity-related cancer is not clear. This study aimed to uncover the risk of hormone-related (breast, endometrial and prostate), colorectal and oesophageal cancers following obesity surgery. Methods This national population-based cohort study used data from the Hospital Episode Statistics database in England collected between 1997 and 2012. Propensity matching on sex, age, co-morbidity and duration of follow-up was used to compare cancer risk among obese individuals undergoing bariatric surgery (gastric bypass, gastric banding or sleeve gastrectomy) and obese individuals not undergoing such surgery. Conditional logistic regression provided odds ratios (ORs) with 95 per cent confidence intervals. Results In the study period, from a cohort of 716 960 patients diagnosed with obesity, 8794 patients who underwent bariatric surgery were matched exactly with 8794 obese patients who did not have surgery. Compared with the no-surgery group, patients who had bariatric surgery exhibited a decreased risk of hormone-related cancers (OR 0·23, 95 per cent c.i. 0·18 to 0·30). This decrease was consistent for breast (OR 0·25, 0·19 to 0·33), endometrium (OR 0·21, 0·13 to 0·35) and prostate (OR 0·37, 0·17 to 0·76) cancer. Gastric bypass resulted in the largest risk reduction for hormone-related cancers (OR 0·16, 0·11 to 0·24). Gastric bypass, but not gastric banding or sleeve gastrectomy, was associated with an increased risk of colorectal cancer (OR 2·63, 1·17 to 5·95). Longer follow-up after bariatric surgery strengthened these diverging associations. Conclusion Bariatric surgery is associated with decreased risk of hormone-related cancers, whereas gastric bypass might increase the risk of colorectal cancer.

Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in human substrate and energy metabolism, thereby connecting the heart with several insulin-sensitive organs like adipose tissue, skeletal muscle and liver. Obesity may be associated with an impaired regulation of the natriuretic peptide system, also indicated as a natriuretic handicap. Evidence points towards a contribution of this natriuretic handicap to the development of obesity, type 2 diabetes mellitus and cardiometabolic complications, although the causal relationship is not fully understood. Nevertheless, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on current literature regarding the metabolic roles of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Furthermore, it will be discussed how exercise and lifestyle intervention may modulate the natriuretic peptide-related metabolic effects.

Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92%) but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients.

Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92%) but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients.

Background: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, although limited by availability and operative risk. The gut hormones Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Oxyntomodulin (OXM) are elevated postprandially after RYGB, which has been postulated to contribute to its metabolic benefits. Objective: We hypothesized that infusion of the three gut hormones to achieve levels similar to those encountered postprandially in RYGB patients might be effective in suppressing appetite. The aim of this study was to investigate the effect of a continuous infusion of GLP-1, OXM, and PYY (GOP) on energy intake and expenditure in obese volunteers. Methods: Obese volunteers were randomized to receive an infusion of GOP or placebo in a single-blinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Ad libitum food intake studies were performed during the infusion, and energy expenditure was measured using a ventilated hood calorimeter. Results: Postprandial levels of GLP-1, OXM, and PYY seen post RYGB were successfully matched using 4 pmol/kg/min, 4 pmol/kg/min, and 0.4 pmol/kg/min, respectively. This dose led to a mean reduction of 32% in food intake. No significant effects on resting energy expenditure were observed. Conclusion: This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake. This data suggests that triple hormone therapy might be a useful tool against obesity., A combined subcutaneous infusion of GLP-1, OXM, and PYY given to obese volunteers, matching the postprandial levels of the hormones as observed post RYGB, led to a 32% reduction in total food intake.

Introduction Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin concentrations are achieved in this population. Methods In this modelling and simulation study we used data from a trial on moxifloxacin PK. In this trial, volunteers who had previously undergone bariatric surgery (at least 6 months prior to inclusion), received two doses (intravenous and oral) of 400mg moxifloxacin administered on two occasions. Results In contrast to other papers, we found that moxifloxacin PK were best described by a three compartmental model using lean body mass (LBM) as a predictor for moxifloxacin clearance. Furthermore, we showed that the probability of target attainment for bacterial eradication against a hypothetical Streptococcus pneumoniae infection is compromised in patients with higher LBM, especially when targeting microorganisms with minimum inhibitory concentrations (MICs) of 0.5mgl-1 or higher (probability of target attainment (PTA) approaching zero). When considering the targets for suppression of bacterial resistance formation, even at MIC values as low as 0.25mgl-1, standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78kg or higher, the probability of hitting this target approaches zero. Conclusions Throughout our PK-PD simulation study, it became apparent that, whenever optimal bacterial resistance suppression is deemed necessary, the standard moxifloxacin dosing will not be sufficient. Furthermore, our study emphasizes the need for a LBM based individualized dosing of moxifloxacin in this patient population.

Background & Aims: Bariatric surgery reduces weight and improves glucose metabolism in obese patients. We investigated the effects of bariatric surgery on hepatic insulin sensitivity.Methods: Twenty-three morbidly obese (nine diabetic and fourteen non-diabetic) patients and ten healthy, lean control subjects were studied using positron emission tomography to assess hepatic glucose uptake in the fasting state and during euglycemic hyperinsulinemia. Magnetic resonance spectroscopy was performed to measure liver fat content and magnetic resonance imaging to obtain liver volume. Obese patients were studied before bariatric surgery (either sleeve gastrectomy or Roux-en-Y gastric bypass) and six months after surgery.Results: Insulin-induced hepatic glucose uptake was increased by 33% in non-diabetic and by 36% in diabetic patients at follow-up compared with baseline, but not totally normalized. The liver fat content was reduced by 76%, liver volume by 26% and endogenous glucose production by 19% in non-diabetic patients. The respective changes in diabetic patients were 73%, 24%, and 25%. Postoperatively, liver fat content and endogenous glucose production were almost normalized to lean controls, but liver volume remained greater than in control subjects.Conclusions: This study shows that bariatric surgery leads to a significant improvement in hepatic insulin sensitivity: insulin-stimulated hepatic glucose uptake was improved and endogenous glucose production reduced when measured, six-months, after surgery. These metabolic effects were accompanied by a marked reduction in hepatic volume and fat content. Overall, the gain in hepatic insulin sensitivity in diabetic patients was quite similar to non-diabetic patients for the same weight reduction. (C) 2013 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

Ghrelin, discovered in 1999, is a 28-amino-acid hormone, best recognized as a stimulator of growth hormone secretion, but with pleiotropic functions in the area of energy homeostasis, such as appetite stimulation and energy expenditure regulation. As the intrinsic ligand of the growth hormone secretagogue receptor (GHS-R), ghrelin appears to have a broad array of effects, but its primary role is still an area of debate. Produced mainly from oxyntic glands in the stomach, but with a multitude of extra-metabolic roles, ghrelin is implicated in complex neurobiological processes. Comprehensive studies within the areas of obesity and metabolic surgery have clarified the mechanism of these operations. As a stimulator of growth hormone (GH), and an apparent inducer of positive energy balance, other areas of interest include its impact on carcinogenesis and tumour proliferation and its role in the cancer cachexia syndrome. This has led several authors to study the hormone in the cancer setting. Ghrelin levels are acutely reduced following an oesophagectomy, a primary treatment modality for oesophageal cancer. We sought to investigate the nature of this postoperative ghrelin suppression, and its neurobiological implications.

Objective There is evidence that executive function, and specifically inhibitory control, is related to obesity and eating behavior. The goal of this study was to determine whether personality traits and inhibitory control predict weight loss after bariatric procedures. Although the impressive weight reduction after bariatric surgery has been shown in short- and medium-term studies, the effect of personality traits on this reduction is uncertain. Specifically, the effect of impulsivity is still largely unknown. Setting Patients attending either a multidisciplinary information session or outpatient clinic at the Imperial Weight Management Centre were recruited with informed consent into the trial over a 4-month period from January to April 2013. Participants were invited to attend behavioral testing on an outpatient basis in a silent room invigilated by a single researcher. Methods Forty-five bariatric patients participated in the study (25 patients had a gastric bypass, with a mean BMI of 41.8 and age of 39.0 years; 20 had a sleeve gastrectomy, with a mean BMI of 47.2 and age of 49.0 years). All patients completed personality measures of impulsivity—Barratt's Impulsivity Scale, as well as behavioral measures of impulsivity—the stop-signal reaction-time (SSRT) task measuring inhibitory control and the temporal discounting task measuring reward processing. Those measures were examined in relation to weight loss 6 months after surgery. Results The surgical procedure and changes in the behavioral measure of inhibitory control (SSRT) were found to be significant predictors of reduction in body mass index (BMI) in patients undergoing bariatric surgery. The sleeve gastrectomy group found a reduction in BMI of 14.1%, which was significantly less than the 25% reduction in BMI in the gastric bypass group. The direction (parameter estimate) of the significant effect was positive for SSRT change, which indicates that pre- and postreduction in impulsivity predicts reduction in BMI. Conclusion Impulsivity measures predict weight reduction in patients undergoing bariatric surgery. This result has implications for predicting outcomes from surgical treatments of obesity.

The purpose of this review is to evaluate the influence of bariatric surgery on the use and pharmacokinetics of some frequently used drugs. A PubMed literature search was conducted. Literature was included on influence of bariatric surgery on pharmacoepidemiology and pharmacokinetics. Drug classes to be searched for were antidepressants, antidiabetics, statins, antihypertensive agents, corticosteroids, oral contraceptives, and thyroid drugs. A reduction in the use of medication by patients after bariatric surgery has been reported for various drug classes. Very few studies have been published on the influence of bariatric surgery on the pharmacokinetics of drugs. After bariatric surgery, theoretically, reduced drug absorption may occur. Correct dosing and choosing the right dosage form for drugs used by patients after bariatric surgery are necessary for optimal pharmacotherapy. Therefore, more clinical studies are needed on the influence of bariatric surgery on the pharmacokinetics of major drugs.

The purpose of this review is to evaluate the influence of bariatric surgery on the use and pharmacokinetics of some frequently used drugs. A PubMed literature search was conducted. Literature was included on influence of bariatric surgery on pharmacoepidemiology and pharmacokinetics. Drug classes to be searched for were antidepressants, antidiabetics, statins, antihypertensive agents, corticosteroids, oral contraceptives, and thyroid drugs. A reduction in the use of medication by patients after bariatric surgery has been reported for various drug classes. Very few studies have been published on the influence of bariatric surgery on the pharmacokinetics of drugs. After bariatric surgery, theoretically, reduced drug absorption may occur. Correct dosing and choosing the right dosage form for drugs used by patients after bariatric surgery are necessary for optimal pharmacotherapy. Therefore, more clinical studies are needed on the influence of bariatric surgery on the pharmacokinetics of major drugs.

International audience; An attraction for palatable foods rich in lipids is shared by rodents and humans. Over the last decade, the mechanisms responsible for this specific eating behavior have been actively studied, and compelling evidence implicates a taste component in the orosensory detection of dietary lipids [i.e., long-chain fatty acids (LCFA)], in addition to textural, olfactory, and postingestive cues. The interactions between LCFA and specific receptors in taste bud cells (TBC) elicit physiological changes that affect both food intake and digestive functions. After a short overview of the gustatory pathway, this review brings together the key findings consistent with the existence of a sixth taste modality devoted to the perception of lipids. The main steps leading to this new paradigm (i.e., chemoreception of LCFA in TBC, cell signaling cascade, transfer of lipid signals throughout the gustatory nervous pathway, and their physiological consequences) will be critically analyzed. The limitations to this concept will also be discussed in the light of our current knowledge of the sense of taste. Finally, we will analyze the recent literature on obesity-related dysfunctions in the orosensory detection of lipids ("fatty" taste?), in relation to the overconsumption of fat-rich foods and the associated health risks.

IF 4.066; International audience

OBJECTIVEMorbid obesity is a growing problem worldwide. The current treatment options have limitations regarding effectiveness and complication rates. New treatment modalities are therefore warranted. One of the options is deep brain stimulation (DBS) of the nucleus accumbens (NAC). This review aims to summarize the current knowledge on NAC-DBS for the treatment of morbid obesity.METHODSStudies were obtained from multiple electronic bibliographic databases, supplemented with searches of reference lists. All animal and human studies reporting on the effects of NAC-DBS on body weight in morbidly obese patients were included. Articles found during the search were screened by 2 reviewers, and when deemed applicable, the relevant data were extracted.RESULTSFive relevant animal experimental papers were identified, pointing toward a beneficial effect of high-frequency stimulation of the lateral shell of the NAC. Three human case reports show a beneficial effect of NAC-DBS on body weight in morbidly obese patients.CONCLUSIONSThe available literature supports NAC-DBS to treat morbid obesity. The number of well-conducted animal studies, however, is very limited. Also, the optimal anatomical position of the DBS electrode within the NAC, as well as the optimal stimulation parameters, has not yet been established. These matters need to be addressed before this strategy can be considered for human clinical trials.

The expansion of the obesity epidemic is accompanied with an increase in bariatric procedures, in particular in women of reproductive age. The weight loss induced by the surgery is believed to reverse the negative impact of overweight and obesity on female reproduction, however, research is limited to in particular retrospective cohort studies and a growing number of small case-series and case-(control) studies. AURORA is a multicenter prospective cohort study. The main objective is to collect long-term data on reproductive outcomes before and after bariatric surgery and in a subsequent pregnancy. Women aged 18–45 years are invited to participate at 4 possible inclusion moments: 1) before surgery, 2) after surgery, 3) before 15 weeks of pregnancy and 4) in the immediate postpartum period (day 3–4). Depending on the time of inclusion, data are collected before surgery (T1), 3 weeks and 3, 6, 12 or x months after surgery (T2-T5) and during the first, second and third trimester of pregnancy (T6-T8), at delivery (T9) and 6 weeks and 6 months after delivery (T10-T11). Online questionnaires are send on the different measuring moments. Data are collected on contraception, menstrual cycle, sexuality, intention of becoming pregnant, diet, physical activity, lifestyle, psycho-social characteristics and dietary supplement intake. Fasting blood samples determine levels of vitamin A, D, E, K, B-1, B-12 and folate, albumin, total protein, coagulation parameters, magnesium, calcium, zinc and glucose. Participants are weighted every measuring moment. Fetal ultrasounds and pregnancy course and complications are reported every trimester of pregnancy. Breastfeeding is recorded and breast milk composition in the postpartum period is studied. AURORA is a multicenter prospective cohort study extensively monitoring women before undergoing bariatric surgery until a subsequent pregnancy and postpartum period. Retrospectively registered (July 2015 - NCT02515214 )

Introduction Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin concentrations are achieved in this population. Methods In this modelling and simulation study we used data from a trial on moxifloxacin PK. In this trial, volunteers who had previously undergone bariatric surgery (at least 6 months prior to inclusion), received two doses (intravenous and oral) of 400mg moxifloxacin administered on two occasions. Results In contrast to other papers, we found that moxifloxacin PK were best described by a three compartmental model using lean body mass (LBM) as a predictor for moxifloxacin clearance. Furthermore, we showed that the probability of target attainment for bacterial eradication against a hypothetical Streptococcus pneumoniae infection is compromised in patients with higher LBM, especially when targeting microorganisms with minimum inhibitory concentrations (MICs) of 0.5mgl-1 or higher (probability of target attainment (PTA) approaching zero). When considering the targets for suppression of bacterial resistance formation, even at MIC values as low as 0.25mgl-1, standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78kg or higher, the probability of hitting this target approaches zero. Conclusions Throughout our PK-PD simulation study, it became apparent that, whenever optimal bacterial resistance suppression is deemed necessary, the standard moxifloxacin dosing will not be sufficient. Furthermore, our study emphasizes the need for a LBM based individualized dosing of moxifloxacin in this patient population.

Hardy T, Abu-Raddad E, Porksen N, De Gaetano A. Evaluation of a mathematical model of diabetes progression against observations in the Diabetes Prevention Program. Am J Physiol Endocrinol Metab 303: E200-E212, 2012. First published May 1, 2012; doi:10.1152/ajpendo.00421.2011.-The seminal publication of the Diabetes Prevention Program (DPP) results in 2002 has provided insight into the impact of major therapies on the development of diabetes over a time span of a few years. In the present work, the publicly available DPP data set is used to calibrate and evaluate a recently developed mechanistic mathematical model for the long-term development of diabetes to assess the model's ability to predict the natural history of disease progression and the effectiveness of preventive interventions. A general population is generated from which virtual subject samples corresponding to the DPP enrollment criteria are selected. The model is able to reproduce with good fidelity the observed time courses of both diabetes incidence and average glycemia, under realistic hypotheses on evolution of disease and efficacy of the studied therapies, for all treatment arms. Model-based simulations of the long-term evolution of the disease are consistent with the transient benefits observed with conventional therapies and with promising effects of radical improvement of insulin sensitivity (as by metabolic surgery) or of beta-cell protection. The mechanistic diabetes progression model provides a credible tool by which long-term implications of antidiabetic interventions can be evaluated.

International audience; P>Physical activity is a cornerstone in the medical management of obesity and could be important for weight loss following bariatric surgery. This review aims to describe the evolution of physical activity following massive weight loss induced by bariatric surgery, and to identify the relationship between physical activity and amount of weight loss. A literature search identified 20 publications (19 studies) reporting physical activity data in relation to bariatric surgery. All studies were observational. Self-assessment of physical activity was used in all the studies. Objective measures (pedometry) were used in two studies. The time frame for physical activity assessment varied: before surgery in two publications, after surgery in nine, and longitudinal pre- to post-operative evolution in nine. The latter nine publications found an increase in physical activity after bariatric surgery. In 10/13 studies where it was described, there was a positive relationship between physical activity level and amount of weight loss. In conclusion, observational evidence of self-reported physical activity suggests that physical activity increases after bariatric surgery and that physical activity is associated with surgically induced weight loss. However, these findings warrant further evaluation using objective measures of physical activity and testing in controlled trials.

Background The low-grade inflammatory condition present in morbid obesity is thought to play a causative role in the pathophysiology of insulin resistance (IR). Bariatric surgery fails to improve this inflammatory condition during the first months after surgery. Considering the close relation between inflammation and IR, we conducted a study in which insulin sensitivity was measured during the first months after bariatric surgery. Different methods to measure IR shortly after bariatric surgery have given inconsistent data. For example, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels have been reported to decrease rapidly after bariatric surgery, although clamp techniques have shown sustained insulin resistance. In the present study, we evaluated the use of steady-state plasma glucose (SSPG) levels to assess insulin sensitivity 2 months after bariatric surgery. Methods Insulin sensitivity was measured using HOMA-IR and SSPG levels in 11 subjects before surgery and at 26% excess weight loss (approximately 2 months after restrictive bariatric surgery). Results The SSPG levels after 26% excess weight loss did not differ from the SSPG levels before surgery (14.3 ± 5.4 versus 14.4 ± 2.7 mmol/L). In contrast, the HOMA-IR values had decreased significantly (3.59 ± 1.99 versus 2.09 ± 1.02). Conclusion During the first months after restrictive bariatric surgery, we observed a discrepancy between the HOMA-IR and SSPG levels. In contrast to the HOMA-IR values, the SSPG levels had not improved, which could be explained by the ongoing inflammatory state after bariatric surgery. These results suggest that during the first months after restrictive bariatric surgery, HOMA-IR might not be an adequate marker of insulin sensitivity.

International audience; OBJECTIVE Obesity alters gut microbiota ecology and associates with low-grade inflammation in humans. Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of morbid obesity resulting in drastic weight loss and improvement of metabolic and inflammatory status. We analyzed the impact of RYGB on the modifications of gut microbiota and examined links with adaptations associated with this procedure. RESEARCH DESIGN AND METHODS Gut microbiota was profiled from fecal samples by real-time quantitative PCR in 13 lean control subjects and in 30 obese individuals (with seven type 2 diabetics) explored before (M0), 3 months (M3), and 6 months (M6) after RYGB. RESULTS Four major findings are highlighted: 1) Bacteroides/Prevotella group was lower in obese subjects than in control subjects at MO and increased at M3. It was negatively correlated with corpulence, but the correlation depended highly on caloric intake; 2) Escherichia coli species increased at M3 and inversely correlated with fat mass and leptin levels independently of changes in food intake; 3) lactic acid bacteria including Lacto-bacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus decreased at M3; and 4) Faecalibacterium prausnitzii species was lower in subjects with diabetes and associated negatively with inflammatory markers at MO and throughout the follow-up after surgery independently of changes in food intake. CONCLUSIONS These results suggest that components of the dominant gut microbiota rapidly adapt in a starvation-like situation induced by RYGB while the F. prausnitzii species is directly linked to the reduction in low-grade inflammation state in obesity and diabetes independently of calorie intake. Diabetes 59:3049-3057, 2010