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Some patients suffer disabling hypoglycaemia after RYGB, typically post prandially: Post Bariatric Hypoglycaemia (PBH). We hypothesised that these patients have increased glycaemic variability (GV), as assessed by continuous glucose monitoring (CGM). Method: Prospective study of 6 patients undergoing RYGB with mixed meal tests (MMT) and CGM at baseline (BL), at 1 month and at 12 months. This cohort was compared to 15 patients with hypoglycaemia. Results: RYGB leads to improvement in postprandial glucose tolerance at 120 minutes, preceded by an early peak of glucose and insulin at 30 minutes (Figure 1). Compared to pre-surgery, hypoglycaemic patients have significantly elevated peak glucose and insulin levels at 30 minutes followed by hypoglycaemia at 120 minutes. GV increases post RYGB: mean amplitude of glycaemic excursions (MAGE) median (95% CI) at BL 3.1 (2.3-6.8); 1 m 2.8 (2.2-4.2); 12 m 4.5 (3.4-5.5). PBH patients exhibit similar GV: MAGE 4.4 (3.7-6.5). The %time in range (TIR) glucose Conclusion: PBH patients exhibit exaggerated early glucose and insulin secretion to MMT. ‘Real-world’ CGM demonstrates that GV and time in hypoglycaemia is not significantly different between RYGB without PBH and patients with PBH. All patients post RYGB are at risk of hypos. Disclosure G. Tharakan: None. I.I. Ilesanmi: None. P. Behary: None. K. Alexiadou: None. C.S. Doyle: None. H. Chahal: None. S. Purkayastha: None. A. Miras: None. N. Oliver: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Self; Dexcom, Inc., Sanofi. A. Ahmed: None. S. Bloom: None. T.M. Tan: Other Relationship; Self; Novo Nordisk A/S. Funding Medical Research Council UK

A recent symposium and workshop in Khartoum, the capital of the Republic of Sudan, brought together broad expertise from three universities to address the current burden of communicable and non-communicable diseases facing the Sudanese healthcare system. These meetings identified common challenges that impact the burden of diseases in the country, most notably gaps in data and infrastructure which are essential to inform and deliver effective interventions. Non-communicable diseases, including obesity, type 2 diabetes, renal disease and cancer are increasing dramatically, contributing to multimorbidity. At the same time, progress against communicable diseases has been slow, and the burden of chronic and endemic infections remains considerable, with parasitic diseases (such as malaria, leishmaniasis and schistosomiasis) causing substantial morbidity and mortality. Antimicrobial resistance has become a major threat throughout the healthcare system, with an emerging impact on maternal, neonatal and paediatric populations. Meanwhile, malnutrition, micronutrient deficiency and poor perinatal outcomes remain common and contribute to a lifelong burden of disease. These challenges echo the United Nations (UN) sustainable development goals and concentrating on them in a unified strategy will be necessary to address the national burden of disease. At a time when the country is going through societal and political transition, we draw focus on the country and the need for resolution of its healthcare needs.

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

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.

Purpose This study aimed to determine the predictive power of the DiaRem score following Roux-en-Y gastric bypass to identify patients who would have diabetes remission at 1 year in an ethnically diverse population. Methods We performed a retrospective review of 262 patients with type 2 diabetes mellitus who underwent RYGB at the Imperial Weight Centre, UK, from 2007 to 2014. Data was collected on the parameters required to calculate the DiaRem score as well as pre- and post-surgical weight and the ethnicity of the subjects. Results The studied cohort was ethnically diverse (61.3 % Caucasian, 10.3 % Asian, 5.3 % black, 2.6 % mixed and 20.6 % other). At 1-year post-surgery, there were significant reductions in mean weight (133.4 to 94.3 kg) and BMI (46.7 to 33.3 kg/m2). The mean HbA1c decreased from 8.2 to 6.1 %, and 32.5 % of the cohort underwent either partial or complete remission. 67.8 % of the patients that were classified in group 1 of the DiaRem score (most likely to have remission) had complete remission. However, 22.9 % of the patients predicted to have the least chance of remission had either partial or complete remission. Conclusions In this ethnically diverse cohort, the DiaRem score remains a useful tool to predict diabetes remission in those that have a low DiaRem score (high chance for remission) but was more limited in its predictive power in those with a high DiaRem score (least likely to have remission). Caution must be used in the application of this model in populations other than the US white Caucasian population used to derive the score.

BACKGROUND: An excessively long-blind end of the alimentary limb following a Roux-en-Y gastric bypass (RYGB), known as a 'candy cane' (CC), may cause symptoms including abdominal pain, regurgitation and vomiting. Very few studies have examined the efficacy of surgical resection of the CC. OBJECTIVES: The aim of this study was to assess sensitivity of preoperative diagnostic tools for CC, as well as perioperative outcomes and symptom resolution after CC revision surgery. SETTING: High volume bariatric centre of excellence, United Kingdom. METHODS: Observational study of CC revisions from 2010 to 2017. RESULTS: Twenty-eight CC revision cases were identified (mean age 45 ± 9 years, female preponderance 9:1). Presenting symptoms were abdominal pain (86%), regurgitation/vomiting (43%), suboptimal weight loss (36%) and acid reflux (21%). Preoperative tests provided correct diagnosis in 63% of barium contrast swallows, 50% of upper gastrointestinal endoscopies and 29% computed tomographies. Patients presenting with pain had significantly higher CC size as compared with pain-free group (4.2 vs. 2 cm, p = 0.001). Perioperative complications occurred in 25% of cases. Complete or partial symptom resolution was documented in 73% of patients undergoing CC revision. Highest success rates were recorded in the regurgitation/vomiting group (67%). CONCLUSION: Surgical revision of CC is associated with good symptom resolution in the majority of patients, especially those presenting with regurgitation/vomiting. However, it carries certain risk of complications. CC diagnosis may frequently be missed; hence more than one diagnostic tool should be considered when investigating symptomatic patients after RYGB.

Background and aims Obesity is associated with impaired glucose tolerance which is a risk factor for cardiovascular risk. However, the oral glucose tolerance test (OGTT) is not usually performed in patients with normal fasting glycaemia, thus offering false reassurance to patients with overweight or obesity who may have post-prandial hyperglycaemia. As an alternative to resource demanding OGTTs, we aimed to examine the predictive value of anthropometric measures of total and central fat distribution for post-prandial hyperglycaemia in patients with overweight and obesity with normal fasting glycaemia enrolled in the DICAMANO study. Methods We studied 447 subjects with overweight/obesity with a fasting glucose value ≤ 5.5 mmol l−1 (99 mg dl−1) and BMI ≥ 25 kg/m2 who underwent a 75-g OGTT. Post-prandial hyperglycaemia was defined as a glucose level ≥ 7.8 mmol l−1 (140 mg dl−1) 2-h after the OGTT. The anthropometric measurements included body mass index, body adiposity index, waist circumference, neck circumference, waist-to-hip ratio and waist-to-height ratio. Results The prevalence of post-prandial hyperglycaemia was 26%. Mean 1-h OGTT glucose levels, insulin resistance and beta cell dysfunction was higher in those subjects in the highest tertile for each anthropometric measurement, irrespective of fasting glucose level. Central fat depot anthropometric measurements were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. After multivariable-adjustment for fasting plasma glucose level, smoking, and physical activity level, the odds ratio (95% confidence intervals) for the presence of post-prandial hyperglycaemia for neck circumference, waist circumference and waist-to-height ratio were 3.3 (1.4, 7.7), 2.4 (1.4, 4.4) and 2.5 (1.4, 4.5), respectively. Conclusions In this large and comprehensively phenotyped cohort, one in four subjects had post-prandial hyperglycaemia despite normal fasting glycaemia. Anthropometric indices of central fat distribution were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. These results support the association between central adiposity and glucose derangements and demonstrate the clinical usefulness of anthropometric measurements as screening tools for the selection of patients who are most likely to benefit from an OGTT. Trial registration ClinicalTrials.gov Identifier: NCT03506581. Registered 24 April 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03506581

Type 2 diabetes prevalence is increasing dramatically worldwide. Metabolic surgery is the most effective treatment for selected patients with diabetes and/or obesity. When compared to intensive medical therapy and lifestyle intervention, metabolic surgery has shown superiority in achieving glycemic improvement, reducing number of medications and cardiovascular risk factors, which translates in long-term benefits on cardiovascular morbidity and mortality. The mechanisms underlying diabetes improvement after metabolic surgery have not yet been clearly understood but englobe a complex interaction among improvements in beta cell function and insulin secretion, insulin sensitivity, intestinal gluconeogenesis, changes in glucose utilization, and absorption by the gut and changes in the secretory pattern and morphology of adipose tissue. These are achieved through different mediators which include an enhancement in gut hormones release, especially, glucagon-like peptide 1, changes in bile acids circulation, gut microbiome, and glucose transporters expression. Therefore, this review aims to provide a comprehensive appraisal of what is known so far to better understand the mechanisms through which metabolic surgery improves glycemic control facilitating future research in the field.

The role of brown adipose tissue (BAT) in pathological states of energy homeostasis and impaired adipocyte function, such as obesity has been a major area of research interest in recent years. Herein, we sought to determine the direct effects of adipokines, visfatin and leptin on BAT thermogenesis. \ud The effects of mouse recombinant visfatin, nicotinamide mononucleotide (NMN) and leptin with or without FK866 were studied on differentiated T37i cells. Treated cells were analyzed for key genes and proteins regulating BAT [UCP-1, PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM-16), PPARgamma-coactivator-1alpha (PGC-1) and receptor-interacting protein 140 (RIP-140)] using quantitative PCR and western blot analysis. Data is presented as mean P-values. \ud Both visfatin and leptin had significant concentration dependent effects on thermogenesis in brown pre-adipocytes and at physiological levels, increased uncoupling protein-1 (UCP-1) levels in brown adipocytes. These effects of visfatin were similar to that of nicotinamide mononucleotide (NMN), further strengthening the enzymatic role of visfatin. We also showed that leptin induced UCP-1 mRNA expression and protein production appears to be mediated by visfatin. High concentrations of both visfatin and leptin led to a dramatic decrease in UCP-1 protein levels, supporting the notion that visfatin levels are raised in obesity and that obese people have reduced BAT activity, plausibly through a reduction in UCP-1 levels. Additionally, we found differential regulation of key brown adipogenic genes, specifically, PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM-16), PPARgamma-coactivator-1alpha (PGC-1) and receptor-interacting protein 140 (RIP-140) by visfatin. Our observations provide novel insights in the potential actions of visfatin in BAT.

Adolescent obesity is challenging to treat even if good multidisciplinary approaches are started early. Vertical sleeve gastrectomy (VSG) is an effective intervention for long-term weight loss, but the underlying mechanisms that result in reduced calorie intake are controversial. Anecdotal evidence from the clinic and evidence in rodents after VSG suggest a decrease in the reward value of high-calorie dense foods.To determine changes in appetitive behavior of candies (high in sugar and fat) after VSG in adolescents with obesity.University hospital.Sixteen adolescents with obesity (age 15.3 ± .5 yr) who had VSG and 10 control patients (age 13.8 ± .6 yr) who had not undergone surgery were studied. Both groups completed a progressive ratio task by clicking a computer mouse on a progressive ratio schedule to receive a candy high in sugar and fat. In the task, patients were required to expend an increasing amount of effort to obtain the reinforcer until they reach a breakpoint (measure of the reward value of the reinforcer). The task was performed before VSG and 12 and 52 weeks after VSG.The VSG group's bodyweight decreased from the baseline 136.6 ± 5.1 to 110.9 ± 5.2 to 87.4 ± 3.7 kg after 12 and 52 weeks, respectively (P.001). The median breakpoint for candies decreased after VSG from the baseline 320 (160-640) to 80 (50-320) to 160 (80-560) after 12 and 52 weeks, respectively (P = .01). Breakpoints for the control patients did not change (480 [160-640] versus 640 [280-640], P = .17).VSG resulted in a reduction in the reward value of a candy, as suggested by the reduced amount of effort adolescents were prepared to expend to obtain the high-sugar and high-fat candy. The effect was most pronounced 12 weeks after surgery but was largely maintained at 1 year. Long-term attenuation of appetitive behavior may be the key to weight loss and weight loss maintenance after VSG in adolescents.

This report describes 5-year blood pressure, Hemoglobin A1c, and lipid levels among participants previously randomized to Roux-en-Y gastric bypass surgery vs no surgery for management of obesity and type 2 diabetes.

A recent randomized controlled clinical trial with 5-year follow-up demonstrates the impressive effectiveness of the combination of metabolic surgery with medical therapies and shifts the paradigm in the care of patients with obesity and type 2 diabetes mellitus.

Background The National Bariatric Surgery Registry (NBSR) is the largest bespoke database in the field in the United Kingdom. Objectives Our aim was to analyze the NBSR to determine whether the effects of obesity surgery on associated co-morbidities observed in small randomized controlled clinical trials could be replicated in a "real life" setting within U.K. healthcare. Setting United Kingdom. Methods All NBSR entries for operations between 2000 and 2015 with associated demographic and co-morbidity data were analyzed retrospectively. Results A total of 50,782 entries were analyzed. The patients were predominantly female (78%) and white European with a mean age of 45 ± 11 years and a mean body mass index of 48 ± 8 kg/m2. Over 5 years of follow-up, statistically significant reductions in the prevalence of type 2 diabetes, hypertension, dyslipidemia, sleep apnea, asthma, functional impairment, arthritis, and gastroesophageal reflux disease were observed. The "remission" of these co-morbidities was evident 1 year postoperatively and reached a plateau 2 to 5 years after surgery. Obesity surgery was particularly effective on functional impairment and diabetes, almost doubling the proportion of patients able to climb 3 flights of stairs and halving the proportion of patients with diabetes related hyperglycemia compared with preoperatively. Surgery was safe with a morbidity of 3.1% and in-hospital mortality of .07% and a reduced median inpatient stay of 2 days, despite an increasingly sick patient population. Conclusions Obesity surgery in the U.K. results not only in weight loss, but also in substantial improvements in obesity-related co-morbidities. Appropriate support and funding will help improve the quality of the NBSR data set even further, thus enabling its use to inform healthcare policy.

Roux-en-Y gastric bypass (RYGB) may improve beta cell function by mechanisms other than caloric restriction and body weight loss. We aimed to assess the impact of anatomical and hormonal alterations specific to RYGB on glucose homeostasis, β cell function and morphology.Male Zucker(fa/fa) rats underwent either RYGB (n = 11) or sham surgeries (n = 10). Five of the shams were then food restricted and body weight matched (BWM) to the RYGB rats. Six male Zucker(fa/+) rats underwent sham surgery and served as additional lean controls. Twenty-seven days after surgery, an oral glucose tolerance test (OGTT) was performed and plasma levels of glucose, insulin and glucagon-like peptide-1 (GLP-1) were measured. Immunohistological analysis of pancreatic islets was performed, and GLP-1 receptor and PDX-1 mRNA content were quantified.Shams consumed more food and gained more weight compared to both RYGB and BWM (p 0.001). Hyperglycaemia was evident in ad libitum-fed shams, whilst postprandial glucose levels were lower in RYGB compared to the BWM sham group (p 0.05). During the OGTT, RYGB rats responded with2.5-fold increase of GLP-1. Histology revealed signs of islet degeneration in ad libitum-fed shams, but not in RYGB and sham BWM controls (p 0.001). GLP-1 receptor and PDX-1 mRNA content was similar between the RYGB and BWM shams but higher compared to ad libitum shams (p 0.05).Combined molecular, cellular and histological analyses of pancreatic function suggest that weight loss alone, and not the enhancement of GLP-1 responses, is predominant for the short-term β cell protective effects of RYGB.

Bariatric surgery leads to significant long-term weight loss, particularly Roux-en-Y gastric bypass (RYGB). The mechanisms underlying weight loss have not been fully uncovered. The aim of this review is to explore the changes in food preferences, as a novel mechanism contributing to weight loss, and also focus on the underlying processes modulating eating behaviour after bariatric surgery. Patients after gastric bypass are less hungry and prefer healthier food options. They develop an increased acuity to sweet taste, which is perceived as more intense. The appeal of sweet fatty food decreases, with functional MRI studies showing a corresponding reduction in activation of the brain reward centres to high-energy food cues. Patients experiencing post-ingestive symptoms with sweet and fatty food develop conditioned aversive behaviours towards the triggers. Gut hormones are elevated in RYGB and have the potential to influence the taste system and food hedonics. Current evidence supports a beneficial switch in food preferences after RYGB. Changes within the sensory and reward domain of taste and the development of post-ingestive symptoms appear to be implicated. Gut hormones may be the mediators of these alterations and therefore exploiting this property might prove beneficial for designing future obesity treatment.

Aims/hypothesis We aimed to examine the effects of bariatric surgery on microvascular complications in patients with type 2 diabetes using objective measures. Methods Prospective case–control study of 70 obese surgical patients with type 2 diabetes undergoing gastric bypass surgery matched for age, sex and duration of diabetes to 25 medical patients treated using international guidelines. Microvascular complications were assessed before and 12–18 months after intervention using urine albumin creatinine ratio (ACR) measurements, two-field digital retinal images and peripheral nerve conduction studies (in the surgical group only). Results Urine ACR decreased significantly in the surgical group but increased in the medical group. There were no significant differences between the surgical and medical groups in the changes in retinopathy. There were no changes in the nerve conduction variables in the surgical group. Conclusions/interpretation In the short term, bariatric surgery may be superior to medical care in the treatment of diabetic nephropathy, but not retinopathy or neuropathy.

INTRODUCTION: Obesity in young people is one of the most serious public health problems worldwide. Moreover, the mechanisms preventing obese adolescents from losing and maintaining weight loss have been elusive. Laparoscopic sleeve gastrectomy (LSG) is successful at achieving long-term weight loss in patients across all age groups, including children and adolescents. Anecdotal clinical observation as well as evidence in rodents suggests that LSG induces a shift in preference of sugary foods. However, it is not known whether this shift is due to a change in the threshold for gustatory detection of sucrose, or whether LSG induces behavioral change without affecting the gustatory threshold for sugar. AIMS: The objective of this study was to determine whether adolescents who undergo LSG experience a change in their threshold for detecting sweet taste. METHODS: We studied the sucrose detection threshold of 14 obese adolescents (age 15.3 ± 0.5 years, range 12-18) who underwent LSG 2 weeks before surgery and at 12 and 52 weeks after surgery. Matched non-surgical subjects were tested on two occasions 12 weeks apart to control for potential learning of the test that may have confounded the results. Seven sucrose concentrations were used and were tested in eight blocks with each block consisting of a random seven sucrose and seven water stimuli. The subjects were asked to report whether the sample contained water or not after they tasted 15 ml of the fluid for 10 s. RESULTS: The bodyweight of the LSG group decreased from 136.7 ± 5.4 to 109.6 ± 5.1 and 86.5 ± 4.0 kg after 12 and 52 weeks, respectively (p

Purpose of Review\ud In recent years, the role of the gastrointestinal (GI) tract in energy homeostasis through modulation of the digestion and absorption of carbohydrates and the production of incretin hormones is well recognized.\ud \ud Recent Findings\ud Bariatric surgery for obesity has been a very effective method in substantially improving weight, and numerous studies have focused on intestinal adaptation after bariatric procedures. A number of structural and functional changes in the GI tract have been reported postsurgery, which could be responsible for the altered hormonal responses. Furthermore, the change in food absorption rate and the intestinal regions exposed to carbohydrates may affect blood glucose response.\ud \ud Summary\ud This review hopes to give new insights into the direct role of gut hormones, by summarising the metabolic effects of bariatric surgery.

Summary Primary amenorrhoea is defined as the failure to commence menstruation by the age of 15 years, in the presence of normal secondary sexual development. The potential causes of primary amenorrhoea extend from structural to chromosomal abnormalities. Polycystic ovarian syndrome (PCOS) is a common cause of secondary amenorrhoea but an uncommon cause of primary amenorrhoea. An early and prompt diagnosis of PCOS is important, as up to 30% of these women are predisposed to glucose intolerance and obesity, with the subgroup of women presenting with primary amenorrhoea and PCOS displaying a higher incidence of metabolic dysfunction. We describe a case of an 18-year-old female presenting with primary amenorrhoea of unknown aetiology. Although initial investigations did not demonstrate clinical or biochemical hyperandrogenism or any radiological evidence of polycystic ovaries, a raised luteinising hormone (LH) suggested a diagnosis of PCOS. If PCOS was the correct diagnosis, then one would expect intact hypothalamic GnRH and pituitary gonadotropin release. We used the novel hormone kisspeptin to confirm intact hypothalamic GnRH release and a GnRH stimulation test to confirm intact pituitary gonadotroph function. This case highlights that kisspeptin is a potential unique tool to test GnRH function in patients presenting with reproductive disorders. Learning points: Polycystic ovarian syndrome (PCOS) can present with primary amenorrhoea, and therefore, should be considered in the differential diagnosis. PCOS is a heterogeneous condition that may present in lean women with few or absent signs of hyperandrogenism. GnRH stimulation tests are useful in evaluating pituitary function; however, to date, we do not have a viable test of GnRH function. Kisspeptin has the potential to form a novel diagnostic tool for assessing hypothalamic GnRH function by monitoring gonadotropin response as a surrogate marker of GnRH release. Confirmation of intact GnRH function helps consolidate a diagnosis in primary amenorrhoea and gives an indication of future fertility.

The prevalence of obesity is increasing exponentially worldwide, becoming an international public health issue that affects quality of life, increases the risk of illness and raises healthcare costs in countries in all parts of the world. In this editorial, we analyse the latest progress in the management of obesity and associated cardiovascular risk factors, and summarise the latest randomised controlled trials that have had the biggest influence on the current changes we are experiencing in obesity management.

In this symposium report, we examine how functional neuroimaging has revolutionized the study of human eating behaviour. In the last 20 years, functional magnetic resonance and positron emission tomography techniques have enabled researchers to understand how the human brain regions that control homeostatic and hedonic eating respond to food in physiological and pathological states. Hypothalamic, brainstem, limbic and cortical brain areas form part of a well-co-ordinated brain system that responds to central and peripheral neuronal, hormonal and nutrient signals. Even in physiological conditions, it promotes the consumption of energy-dense food, because this is advantageous in evolutionary terms. Its function is dysregulated in the context of obesity so as to promote weight gain and resist weight loss. Pharmacological and bariatric surgical interventions might be more successful than lifestyle interventions in inducing weight loss and maintenance because, unlike dieting, they reduce not only hunger but also the reward value of food through their actions in homeostatic and hedonic brain regions. Functional neuroimaging is a research tool that cannot be used in isolation; its findings become meaningful and useful only when combined with data from direct measures of eating behaviour. The neuroimaging technology is continuously improving and is expected to contribute further to the in-depth understanding of the obesity phenotype and accelerate the development of more effective and safer treatments for the condition.

Background and Aims:Bariatric surgery is the most effective treatment for obesity. However, not all patients have similar weight loss following surgery and many researchers have attributed this to different pre-operative psychological, eating behavior, or quality-of-life factors. The aim of this study was to determine whether there are any differences in these factors between patients electing to have bariatric surgery compared to less invasive non-surgical weight loss treatments, between patients choosing a particular bariatric surgery procedure, and to identify whether these factors predict weight loss after bariatric surgery.Material and Methods:This was a prospective study of 90 patients undergoing gastric bypass, vertical sleeve gastrectomy, or adjustable gastric banding and 36 patients undergoing pharmacotherapy or lifestyle interventions. All patients completed seven multi-factorial psychological, eating behavior, and quality-of-life questionnaires prior to choosing their weight loss treatment. Questionnaire scores, baseline body mass index, and percent weight loss at 1 year after surgical interventions were recorded.Results and Conclusions:Surgical patients were younger, had a higher body mass index, and obesity had a higher impact on their quality of life than on non-surgical patients, but they did not differ in the majority of eating behavior and psychological parameters studied. Patients opting for adjustable gastric banding surgery were more anxious, depressed, and had more problems with energy levels than those choosing vertical sleeve gastrectomy, and more work problems compared to those undergoing gastric bypass. Weight loss after bariatric surgery was predicted by pre-operative scores of dietary restraint, disinhibition, and pre-surgery energy levels. The results of this study generate a number of hypotheses that can be explored in future studies and accelerate the development of personalized weight loss treatments.

Recruiting participants into clinical trials is notoriously difficult and poses the greatest challenge when planning any investigative study. Poor recruitment may not only have financial ramifications owing to increased time and resources being spent but could adversely influence the clinical impact of a study if it becomes underpowered. Herein, we present our own experience of recruiting into a nationally funded, multicentre, randomised controlled trial (RCT) of the Endobarrier versus standard medical therapy in obese patients with type 2diabetes. Despite these both being highly prevalent conditions, there were considerable barriers to the effectiveness of different recruitment strategies across each study site. Although recruitment from primary care proved extremely successful at one study site, this largely failed at another site prompting the implementation of multimodal recruitment strategies including a successful media campaign to ensure sufficient participants were enrolled and the study was adequately powered. From this experience, we propose where appropriate the early engagement and investment in media campaigns to enhance recruitment into clinical trials. Trial Registration:ISRCTN30845205.

Objective: To determine whether rats reaching the same body mass, having been fed either a low-fat (LFD) or a high-fat diet (HFD), differ in white adipose tissue (WAT) deposition. Methods: In experiment 1, 22 Sprague-Dawley rats of the same age were divided into 11 rats with body mass below the batch median and fed a HFD, and 11 above the median and fed a LFD. In experiment 2, 20 Sprague-Dawley rats of the same age and starting body mass were randomised to either a HFD or LFD. When all groups reached similar final body mass, WAT was quantified using magnetic resonance imaging (MRI), dissection, and plasma leptin. Results: In experiment 1, both groups reached similar final body mass at the same age; in experiment 2 the HFD group reached similar final body mass earlier than the LFD group. There were no significant differences in WAT as assessed by MRI or leptin between the HFD and LFD groups in both experiments. Dissection revealed a trend for higher retroperitoneal and epididymal adiposity in the HFD groups in both experiments. Conclusions: We conclude that at similar body mass, adiposity is independent of the macronutrient composition of the feeding regimen used to achieve it.

Despite the evidence for benefits beyond weight loss following bariatric surgery, assessments of surgical outcomes are often limited to changes in weight and remission of type 2 diabetes mellitus. To address this shortfall in assessment, the King's Obesity Staging System was developed. This system evaluates the individual in severity stages of physical, psychological, socio-economic and functional disease. These are categorised into disease domains arranged so as to allow an alphabetic mnemonic as Airways, Body Mass Index (BMI), Cardiovascular, Diabetes, Economic, Functional, Gonadal, Health Status (perceived) and (body) Image.In this cohort study, patients were assessed before and 12 months after surgery using the modified King's Obesity Staging Score. We studied 217 consecutive patients undergoing Roux-en-Y gastric bypass (RYGB; N = 148) and laparoscopic adjustable gastric band (LAGB; N = 69) using the modified King's Obesity Staging System to determine health benefits after bariatric surgery.Preoperatively, the groups had similar BMI, but the RYGB group had worse Airways, Cardiovascular, and Diabetes scores (p 0.05). After surgery, RYGB and LAGB produced improvements in all scores. In a subgroup paired analysis matched for preoperative Airways, BMI, Cardiovascular, and Diabetes scores, both procedures showed similar improvements in all scores, except for BMI where RYGB had a greater reduction than LAGB (p 0.05).Both RYGB and LAGB deliver multiple benefits to patients as evaluated by the modified King's Obesity Staging System beyond BMI and glycaemic markers. A validated staging score such as the modified King's Obesity Staging System can be used to quantify these benefits.

Objectives Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations. Design We used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity. Results Obese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients. Conclusions The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour.

The International Diabetes Federation (IDF) and the American Diabetes Association (ADA) have introduced specific criteria to define the 'optimization' of the metabolic state and glycaemic 'remission' of type 2 diabetes mellitus (T2DM) after bariatric surgery, respectively. Our objective was to assess the percentage of patients achieving these criteria. Data were collected for body mass index, glycaemic markers, lipids, blood pressure, hypoglycaemia and medication usage from 396 morbidly obese T2DM patients who underwent bariatric surgery in two centres and followed up for 2 years. At year 1, 14% of patients achieved the IDF criteria and 38% the ADA criteria, whereas at 2 years 8 and 9% satisfied these criteria, respectively. A relatively low proportion of patients achieved optimization of the metabolic state and T2DM remission. These patients may potentially benefit from the combination of bariatric surgery and adjuvant medical therapy to achieve optimal metabolic outcomes.

The clinical efficacy of bariatric surgery has encouraged the scientific investigation of the gut as a major endocrine organ. Manipulation of gastrointestinal anatomy through surgery has been shown to profoundly affect the physiological and metabolic processes that control body weight and glycaemia. The most popular bariatric surgical procedures are gastric bypass, adjustable gastric banding and vertical sleeve gastrectomy. Even though these procedures were designed with the aim of causing restriction of food intake and nutrient malabsorption, evidence suggests that their contributions to weight loss are minimal. Instead, these interventions reduce body weight by decreasing hunger, increasing satiation during a meal, changing food preferences and energy expenditure. In this Review, we have explored these mechanisms as well as their mediators. The hope is that that their in-depth investigation will enable the optimization and individualization of surgical techniques, the development of equally effective but safer nonsurgical weight-loss interventions, and even the understanding of the pathophysiology of obesity itself.

Patients with a body mass index (BMI) above 35 kg/m(2) with metabolic diseases benefit from Roux-en-Y gastric bypass (RYGB) independently of their final BMI and the amount of body weight lost. However, the weight loss independent metabolic effects induced by RYGB remain less well understood. To elucidate metabolic changes after RYGB, (1)H NMR spectroscopy-based urine metabolic profiles from RYGB (n = 7), ad libitum-fed sham (AL, n = 5), and body-weight-matched sham (BWM, n = 5) operated mice were obtained. Gut morphometry and fecal energy content were analyzed. Food intake and body weight of RYGB mice were significantly reduced (p = 0.001) compared to sham-AL. There was a strong tendency that BWM-shams required less food to maintain the same body weight as RYGB mice (p = 0.05). No differences were found in fecal energy content between the groups, excluding malabsorption in RYGB animals. Unlike RYGB-operated rats, gut hypertrophy was not observed in RYGB-operated mice. Urinary tricarboxylic acid cycle intermediates were higher in the sham groups, suggesting altered mitochondrial metabolism after RYGB surgery. Higher urinary levels of trimethylamine, hippurate and trigonelline in RYGB mice indicate that the RYGB operation caused microbial disturbance. Taken together, we demonstrate for the first time that there are RYGB specific metabolic effects, which are independent of food intake and body weight loss. Increased utilization of TCA cycle intermediates and altered gut microbial-host co-metabolites might indicate increased energy expenditure and microbial changes in the gut, respectively.

Metabolic dysregulation is a defining characteristic of type 2 diabetes, which can give rise to microvascular complications—specifically retinopathy, nephropathy, and neuropathy. Increasing evidence exists from prospective studies, cases series, and national registries to show that bariatric or metabolic surgery ameliorates hyperglycaemia in people with diabetes and prevents, delays, or improves obesity-associated complications.1–3 Yet, scarce evidence exists to show the effects of surgery in patients who have not yet reached the hyperglycaemic threshold used to define diabetes.

A large number of patients undergoing bariatric surgery are deficient in copper, and Roux-en-Y gastric bypass can further aggravate it. Delays in diagnosis and treatment of copper deficiency can leave patients with residual neurological disability. This has led to recommendation from the British Obesity and Metabolic Surgery Society that copper levels should be monitored annually after gastric bypass. This review concludes that copper deficiency in adequately supplemented patients is rare and can be adequately treated if a related haematological or neurological disorder is diagnosed. The cost of routine monitoring may therefore not be justified for adequately supplemented, asymptomatic patients who have undergone Roux-en-Y gastric bypass. The screening may however be necessary for high-risk patient groups to prevent severe complications and permanent disability.

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for patients with type 2 diabetes (T2DM). Tight glycaemic control immediately after RYGB for T2DM may improve long-term glycaemic outcomes, but is also associated with a higher risk of hypoglycaemia. We designed a treatment algorithm to achieve optimal glycaemic control in patients with insulin-treated T2DM after RYGB and evaluated its feasibility, safety and efficacy.Fifty patients following protocol-driven diabetes management were discharged on a fixed amount of metformin and glargine, with the insulin dose adjusted according to a standardised insulin sliding scale aiming for a fasting capillary glucose (FCG) of 5.5-6.9 mmol/L. Glycaemic outcome and remission of diabetes (defined as HbA1c6% and FCG levels5.6 mmol/L for at least 1 year without hypoglycaemic medication) were compared between patients who received protocol-driven treatment and a similar cohort of 49 patients following standard glycaemic management.At 1 year follow-up, the protocol-driven group showed a greater improvement in glycaemic control than the non-protocol-driven group (HbA1c -3.0 ± 0.2% vs. -1.2 ± 0.1%, P0.001; FCG levels -3.4 ± 0.2 vs. -2.0 ± 0.2 mmol/L, P = 0.02) and a higher remission rate from T2DM (50.0% vs. 6.1%, P0.001). No symptomatic hypoglycaemia was reported in either group.The protocol-driven management proved to be feasible, safe and effective in achieving targeted glycaemic control in T2DM after RYGB. The next step will be to scrutinise the efficacy of protocol-driven management in a randomised controlled clinical trial.

The mechanisms by which obesity surgery and in particular gastric bypass cause weight loss are unclear. The review will focus on the concept of alterations in the sense of taste after obesity surgery.Patients after obesity surgery and gastric bypass in particular change their eating behaviour and adopt healthier food preferences by avoiding high-calorie and high-fat foods. Patients find sweet and fatty meals less pleasant not due to postingestive side effects but through changes in the sense of taste. The acuity for sweet taste increases after gastric bypass potentially leading to increased intensity of perception. Obese patients experience higher activation of their brain taste reward and addiction centres in response to high calorie and fat tasting. Gastric bypass may reverse these taste hedonics, perhaps through the influence on gustatory pathways caused by enhanced gut hormone responses after surgery.Elucidation of the metabolic mechanism behind the alterations in taste after obesity surgery could lead to the development of novel surgical and nonsurgical procedures for the treatment of obesity.

BACKGROUND Whilst weight loss results in many beneficial metabolic consequences the immediate improvement in glycaemia after Roux en Y Gastric bypass (RYGB) remains intriguing. Duodenal jejunal bypass (DJB) induces similar glycaemic effects while not affecting calorie intake or weight loss. We studied diabetic ZDF(fa/fa) rats to compare the effects of DJB and RYGB operations on glycaemia. METHODS Male ZDF(fa/fa) rats aged 12 weeks underwent RYGB DJB or sham operations. Unoperated ZDF(fa/fa) and ZDF(fa/+w)ere used as controls. Body weight food intake fasting glucose insulin and gut hormones were measured at baseline and on postoperative days 2 10 and 35. An oral glucose tolerance test (OGTT) was performed on days 12 and 26. RESULTS DJB had similar food intake and body weight to sham operated and unoperated control ZDF(fa/fa) rats (p?=?NS) but had lower fasting glucose (p?0.05). RYGB had lower food intake body weight and fasting glucose compared to all groups (p?

Background Roux-en-Y gastric bypass (RYGB) surgery is associated with rapid postsurgical improvement in glycemic control in patients with type 2 diabetes mellitus (T2 DM). However, there is little outcome-based evidence to guide the glycemic management of this patient group preoperatively. Objectives: We conducted 2 pilot studies randomizing patients to assess the impact of intensive glucose management pre- and post-RYGB on clinical outcomes after surgery. Setting: University hospital. Methods In the GLUCOSURG-pre randomized controlled trial (RCT), 34 obese T2 DM patients with glycated hemoglobin (HbA1 c)≥8.5% (69 mmol/mol) undergoing RYGB were randomly assigned to receive either glucose optimization or no optimization 3 months preoperatively. In the GLUCOSURG-post RCT, 35 obese T2 DM patients on insulin were randomly assigned to either intensive or conservative glucose management up to 2 weeks post- RYGB. HbA1c at 1 year post-RYGB was the primary outcome. Results In GLUCOSURG-pre, the HbA1 c at 1 year postsurgery was −3.0% (51.9 mmol/mol) in the optimized and −4.0% (45.4 mmol/mol) in the nonoptimized groups (P = .06). In GLUCOSURG-post, there were no significant differences in HbA1 c at 1 year postsurgery between the intensive and conservative groups [−2.4% (44.3 mmol/mol)] versus [−2.3% (44.3 mmol/mol ), P = .73)]. Conclusions Our pilot studies suggested that neither intensive management of glycemia in the 3 months pre- RYGB, nor the first 2 weeks post-RYGB resulted in better glycemic control one year after surgery. RYGB has substantial effects on glucose control, and additional intensive glucose-lowering interventions do not confer clinical benefits compared to conservative approaches.

Background Obesity care services are often faced with the need to adapt their resources to rising levels of demand. The main focus of thisstudy was to help prioritise planned investments in new capacity allowing the service to improve patient experience and meet future anticipated demand.\ud Methods We developed computer models of patient flows in an obesity service in an Academic Health Science Centre that provides lifestyle, pharmacotherapy and surgery treatment options for the UK’s National Health Service. Using these models we experiment with different scenarios to investigate the likely impact of\ud alternative resource configurations on patient waiting times.\ud Results Simulation results show that the timing and combination of adding extra resources (eg, surgeons and physicians) to the service are important. For example, increasing the capacity of the pharmacotherapy clinics equivalent to adding one physician reduced the relevant waiting list size and waiting times, but it then led to increased waiting times for surgical patients. Better service levels were achieved when the service operates with the resource capacity of two physicians and three surgeons. The results obtained from this study had an impact on the planning and organisation of the obesity service.\ud Conclusions Resource configuration combined with demand management (reduction in referral rates) along the care service can help improve patient waiting time targets for obesity services, such as the 18 week target of UK’s National Health Service. The use of simulation models can help stakeholders understand the\ud interconnectedness of the multiple microsystems (eg, clinics) comprising a complex clinical service for the same patient population, therefore, making stakeholders aware of the likely impact of resourcing decisions on the different microsystems.

Background: Ghrelin, which is a stomach-derived hormone, increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Therefore, changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics. Objective: We investigated whether ghrelin administration (exogenous hyperghrelinemia) mimics effects of fasting (endogenous hyperghrelinemia) on the hedonic response and activation of brain-reward systems to food. Design: In a crossover design, 22 healthy, nonobese adults (17 men) underwent a functional magnetic resonance imaging (fMRI) food-picture evaluation task after a 16-h overnight fast (Fasted-Saline) or after eating breakfast 95 min before scanning (730 kcal, 14% protein, 31% fat, and 55% carbohydrate) and receiving a saline (Fed-Saline) or acyl ghrelin (Fed-Ghrelin) subcutaneous injection before scanning. One male subject was excluded from the fMRI analysis because of excess head motion, which left 21 subjects with brain-activation data. Results: Compared with the Fed-Saline visit, both ghrelin administration to fed subjects (Fed-Ghrelin) and fasting (Fasted-Saline) significantly increased the appeal of high-energy foods and associated orbitofrontal cortex activation. Both fasting and ghrelin administration also increased hippocampus activation to high-energy- and low-energy-food pictures. These similar effects of endogenous and exogenous hyperghrelinemia were not explicable by consistent changes in glucose, insulin, peptide YY, and glucagon-like peptide-1. Neither ghrelin administration nor fasting had any significant effect on nucleus accumbens, caudate, anterior insula, or amygdala activation during the food-evaluation task or on auditory, motor, or visual cortex activation during a control task. Conclusions: Ghrelin administration and fasting have similar acute stimulatory effects on hedonic responses and the activation of corticolimbic reward-cognitive systems during food evaluations. Similar effects of recurrent or chronic hyperghrelinemia on an anticipatory food reward may contribute to the negative impact of skipping breakfast on dietary habits and body weight and the long-term failure of energy restriction for weight loss.

Bariatric surgery is the most effective treatment for weight loss and glycaemic control. The focus of clinical studies and clinical experience has predominantly been on the numerical reductions of bodyweight and glucose after surgery. In this Series paper, we examine evidence on the efficacy of bariatric surgery for pancreatic, renal, retinal, peripheral nervous, cardiovascular, hepatic, and reproductive end-organ damage or disease. The overall conclusions are that, in most cases, patients' end-organ damage is expected to either stabilise or improve postoperatively. However, some of these clinical outcomes have not been assessed with robust methods and, in many cases, do not have support from randomised controlled clinical trials comparing bariatric surgery with non-surgical interventions. Such trials are urgently needed to inform patients and clinicians on whether the risks of surgery outweigh the significant benefits for end-organ health.

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal–jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A ‘medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.

Bariatric surgery has been shown to be the most effective treatment for obesity and T2DM, both in large well-matched clinical studies and randomised controlled trials. In this chapter, we have discussed the clinical efficacy of bariatric surgery and the physiological mechanisms through which it causes weight loss and improved metabolic control. We have limited our focus to the Roux-en-Y gastric bypass, the adjustable gastric band and the vertical sleeve gastrectomy, the procedures that have stood the test of time and are most commonly performed around the world.