RNA sequencing unravels novel L cell constituents and mechanisms of GLP-1 secretion in human gastric bypass-operated intestine.

AIMS/HYPOTHESIS: Roux-en-Y gastric bypass surgery (RYGB) frequently results in remission of type 2 diabetes as well as exaggerated secretion of glucagon-like peptide-1 (GLP-1). Here, we assessed RYGB-induced transcriptomic alterations in the small intestine and investigated how they were related to the regulation of GLP-1 production and secretion in vitro and in vivo. METHODS: Human jejunal samples taken perisurgically and 1 year post RYGB (n=13) were analysed by RNA-seq. Guided by bioinformatics analysis we targeted four genes involved in cholesterol biosynthesis, which we confirmed to be expressed in human L cells, for potential involvement in GLP-1 regulation using siRNAs in GLUTag and STC-1 cells. Gene expression analyses, GLP-1 secretion measurements, intracellular calcium imaging and RNA-seq were performed in vitro. OGTTs were performed in C57BL/6j and iScd1-/- mice and immunohistochemistry and gene expression analyses were performed ex vivo. RESULTS: Gene Ontology (GO) analysis identified cholesterol biosynthesis as being most affected by RYGB. Silencing or chemical inhibition of stearoyl-CoA desaturase 1 (SCD1), a key enzyme in the synthesis of monounsaturated fatty acids, was found to reduce Gcg expression and secretion of GLP-1 by GLUTag and STC-1 cells. Scd1 knockdown also reduced intracellular Ca2+ signalling and membrane depolarisation. Furthermore, Scd1 mRNA expression was found to be regulated by NEFAs but not glucose. RNA-seq of SCD1 inhibitor-treated GLUTag cells identified altered expression of genes implicated in ATP generation and glycolysis. Finally, gene expression and immunohistochemical analysis of the jejunum of the intestine-specific Scd1 knockout mouse model, iScd1-/-, revealed a twofold higher L cell density and a twofold increase in Gcg mRNA expression. CONCLUSIONS/INTERPRETATION: RYGB caused robust alterations in the jejunal transcriptome, with genes involved in cholesterol biosynthesis being most affected. Our data highlight SCD as an RYGB-regulated L cell constituent that regulates the production and secretion of GLP-1.

Substantial Decrease in Comorbidity 5 Years After Gastric Bypass: A Population-based Study From the Scandinavian Obesity Surgery Registry.

OBJECTIVE: To evaluate effect on comorbid disease and weight loss 5 years after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity in a large nationwide cohort. BACKGROUND: The number patients having surgical procedures to treat obesity and obesity-related disease are increasing. Yet, population-based, long-term outcome studies are few. METHODS: Data on 26,119 individuals [75.8% women, 41.0 years, and body mass index (BMI) 42.8 kg/m] undergoing primary RYGB between May 1, 2007 and June 30, 2012, were collected from 2 Swedish quality registries: Scandinavian Obesity Surgery Registry and the Prescribed Drug Registry. Weight, remission of type 2 diabetes mellitus, hypertension, dyslipidemia, depression, and sleep apnea, and changes in corresponding laboratory data were studied. Five-year follow-up was 100% (9774 eligible individuals) for comorbid diseases. RESULTS: BMI decreased from 42.8 ±â€Š5.5 to 31.2 ±â€Š5.5 kg/m at 5 years, corresponding to 27.7% reduction in total body weight. Prevalence of type 2 diabetes mellitus (15.5%-5.9%), hypertension (29.7%-19.5%), dyslipidemia (14.0%-6.8%), and sleep apnea (9.6%-2.6%) was reduced. Greater weight loss was a positive prognostic factor, whereas increasing age or BMI at baseline was a negative prognostic factor for remission. The use of antidepressants increased (24.1%-27.5%). Laboratory status was improved, for example, fasting glucose and glycated hemoglobin decreased from 6.1 to 5.4 mmol/mol and 41.8% to 37.7%, respectively. CONCLUSIONS: In this nationwide study, gastric bypass resulted in large improvements in obesity-related comorbid disease and sustained weight loss over a 5-year period. The increased use of antidepressants warrants further investigation.

The mesenteric defects in laparoscopic Roux-en-Y gastric bypass: 5 years follow-up of non-closure versus closure using the stapler technique.

BACKGROUND: Internal hernia (IH) is a common complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). Little large-volume data exist on how to handle the mesenteric defects during LRYGB. This study evaluated long-term follow-up (5.5 years) of 2443 patients with primary closure of the mesenteric defects with a stapling device at LRYGB, in comparison with a non-closed group from the same centre. METHODS: All patients (N = 4013) undergoing LRYGB over a 10-year period (2005-2015) at a single institution were evaluated. The mesenteric defects were routinely closed starting June 2010. In total, 1570 non-closure patients and 2443 patients with stapled closure of the defects were prospectively entered and the results analysed. RESULTS: Closure of the mesenteric defects increased surgical time by 4 min and did not affect the 30-day complication rate. IH incidence was significantly lower (2.5%) in the closure group compared with 11.7% in the non-closure group, at 60 months. The relative risk reduction by closing the mesenteric defects was 4.09-fold (95% CI = 2.97-5.62) as calculated using a survival model. CONCLUSIONS: Internal hernia after LRYGB occurs frequently if mesenteric defects are left unclosed. Primary closure with a hernia-stapling device is safe and significantly reduces the risk of internal hernia.

Early complications after laparoscopic gastric bypass surgery: results from the Scandinavian Obesity Surgery Registry.

OBJECTIVE: To identify risk factors for serious and specific early complications of laparoscopic gastric bypass surgery using a large national cohort of patients. BACKGROUND: Bariatric procedures are among the most common surgical procedures today. There is, however, still a need to identify preoperative and intraoperative risk factors for serious complications. METHODS: From the Scandinavian Obesity Surgery Registry database, we identified 26,173 patients undergoing primary laparoscopic gastric bypass operation for morbid obesity between May 1, 2007, and September 30, 2012. Follow-up on day 30 was 95.7%. Preoperative data and data from the operation were analyzed against serious postoperative complications and specific complications. RESULTS: The overall risk of serious postoperative complications was 3.4%. Age (adjusted P = 0.028), other additional operation [odds ratio (OR) = 1.50; confidence interval (CI): 1.04-2.18], intraoperative adverse event (OR = 2.63; 1.89-3.66), and conversion to open surgery (OR = 4.12; CI: 2.47-6.89) were all risk factors for serious postoperative complications. Annual hospital volume affected the rate of serious postoperative complications. If the hospital was in a learning curve at the time of the operation, the risk for serious postoperative complications was higher (OR = 1.45; CI: 1.22-1.71). The 90-day mortality rate was 0.04%. CONCLUSIONS: Intraoperative adverse events and conversion to open surgery are the strongest risk factors for serious complications after laparoscopic gastric bypass surgery. Annual operative volume and total institutional experience are important for the outcome. Patient related factors, in particular age, also increased the risk but to a lesser extent.

The effects of Calorie restriction and Bariatric surgery on Circulating Proneurotensin levels.

CONTEXT: Proneurotensin (pNT) is associated with obesity and T2D, but the effects of Roux-en-Y gastric bypass (RYGB) on postprandial pNT levels are not well studied. OBJECTIVE: Assess effects of RYGB versus very low-energy diet (VLED) on pNT levels in response to mixed-meal tests (MMT), and long-term effects of RYGB on fasting pNT.Study participants: Cohort 1: Nine normoglycemic (NG) and ten T2D patients underwent MMT before and after VLED, immediately post-RYGB and six weeks post-RYGB. Cohort 2: Ten controls with normal weight and ten patients with obesity and T2D, who underwent RYGB or vertical sleeve gastrectomy (VSG), were subjected to MMTs and GIP infusions pre-surgery and three months post-surgery. GLP-1 infusions were performed in normal weight participants. Cohort 3: Fasting pNT was assessed pre-RYGB (n=161), two months post-RYGB (n=92) and 1-year post-RYGB (n=118) in NG and T2D patients. pNT levels were measured using ELISA. RESULTS: Reduced fasting and postprandial pNT were evident after VLED and immediately following RYGB. Reintroduction of solid food post-RYGB increased fasting and postprandial pNT. Prior to RYGB, all patients lacked a meal response in pNT, but this was evident post-RYGB/VSG. GIP- or GLP-1 infusion had no effect on pNT levels. Fasting pNT were higher 1-year post-RYGB regardless of glycemic status. CONCLUSION: RYGB causes a transient reduction in pNT as a consequence of caloric restriction. The RYGB/VSG-induced rise in postprandial pNT is independent of GIP and GLP-1 and higher fasting pNT are maintained one year post-surgically.

Metabolic remission precedes possible weight regain after gastric bypass surgery.

OBJECTIVE: Some patients regain weight to a variable extent from 1 year after Roux-en-Y gastric bypass surgery (RYGB), though rarely reaching preoperative values. The aim of the present study was to investigate whether, when, and to what extent metabolic remission occurs. METHODS: Fasting metabolite and lipid profiles were determined in blood plasma collected from a nonrandomized intervention study involving 148 patients before RYGB and at 2, 12, and 60 months post RYGB. Both short-term and long-term alterations in metabolism were assessed. Anthropometric and clinical variables were assessed at all study visits. RESULTS: This study found that the vast majority of changes in metabolite levels occurred during the first 2 months post RYGB. Notably, thereafter the metabolome started to return toward the presurgical state. Consequently, a close-to-presurgical metabolome was observed at the time when patients reached their lowest weight and glucose level. Lipids with longer acyl chains and a higher degree of unsaturation were altered more dramatically compared with shorter and more saturated lipids, suggesting a systematic and reversible lipid remodeling. CONCLUSIONS: Remission of the metabolic state was observed prior to notable weight regain. Further and more long-term studies are required to assess whether the extent of metabolic remission predicts future weight regain and glycemic deterioration.

A New Beginning: Young Women's Experiences and Sexual Function 18 Months After Bariatric Surgery.

INTRODUCTION: Female patients expect improved quality of life, including sexual health and regain of fertility after bariatric surgery. Little has been published on to the extent to which patients' expectations are met by the weight loss after surgery. AIM: To explore how women perceive the effects of bariatric surgery on quality of life, focusing on sexual health and fertility. METHODS: A qualitative study based on thematic analysis, supported by questionnaire data. Interviews following a semistructured guide were conducted with childless women (n = 11) aged 25-34 years recruited from a university-affiliated Swedish bariatric center. The interviews took place 18 months after surgery in the participants' homes or at the hospital and were recorded and transcribed verbatim. Data were analyzed with a thematic approach. Questionnaires were filled in at the time of the interviews and compared with preoperative data using a Wilcoxon test for paired data. MAIN OUTCOME MEASURES: Participants described experiences related to female sexual health after bariatric surgery. The Hospital Anxiety and Depression Scale and the Female Sexual Function Index questionnaires were administered preoperatively and postoperatively. RESULTS: "A new beginning" was identified as the master theme, with 3 underlying subthemes: "Being worthy of love," "Exploring sexuality," and "Considering parenthood." The participants described a transformation into being more comfortable with themselves that affected all areas of life, including sexual life. These findings were supported by lower scores for depression, 6.5 vs 2, and improved total Female Sexual Function Index scores, median 23.3 preoperatively and 29.1 postoperatively, P = .012. CONCLUSIONS: Improved body image and enhanced self-esteem play important roles in improved sexual functioning in women after bariatric surgery. Nilsson-Condori E, Järvholm S, Thurin-Kjellberg A, et al. A New Beginning: Young Women's Experiences and Sexual Function 18 Months After Bariatric Surgery. Sex Med 2020;8:730-739.

Metabolic Effects of Gastric Bypass Surgery: Is It All About Calories?

Bariatric surgery is an efficient method to induce weight loss and also, frequently, remission of type 2 diabetes (T2D). Unpaired studies have shown bariatric surgery and dietary interventions to differentially affect multiple hormonal and metabolic parameters, suggesting that bariatric surgery causes T2D remission at least partially via unique mechanisms. In the current study, plasma metabolite profiling was conducted in patients with (n = 10) and without T2D (n = 9) subjected to Roux-en-Y gastric bypass surgery (RYGB). Mixed-meal tests were conducted at baseline, after the presurgical very-low-calorie diet (VLCD) intervention, immediately after RYGB, and after a 6-week recovery period. Thereby, we could compare fasted and postprandial metabolic consequences of RYGB and VLCD in the same patients. VLCD yielded a pronounced increase in fasting acylcarnitine levels, whereas RYGB, both immediately and after a recovery period, resulted in a smaller but opposite effect. Furthermore, we observed profound changes in lipid metabolism following VLCD but not in response to RYGB. Most changes previously associated with RYGB were found to be consequences of the presurgical dietary intervention. Overall, our results question previous findings of unique metabolic effects of RYGB and suggest that the effect of RYGB on the metabolite profile is mainly attributed to caloric restriction.

To Get Back on Track: A Qualitative Study on Childless Women's Expectations on Future Fertility Before Undergoing Bariatric Surgery.

BACKGROUND: In Sweden, 4700 women seek bariatric surgery annually, many of those being nulliparous. Anovulation is common among obese women, but bariatric surgery is not considered a treatment for infertility. The aim of this study was to explore the motives of women in fertile age for seeking bariatric surgery and their expectations on future fertility. MATERIALS AND METHODS: A qualitative study with semi-structured interviews with childless women (n = 12) aged 20 to 35 years. Interviews were conducted 1 to 3 weeks prior to surgery, transcribed verbatim, and analyzed with thematic analysis. RESULTS: "To get back on track" was identified as a master theme with 3 underlying subthemes, with the following headings: "A better me," "A fertile me," and "A pregnant me." The participants were hoping that weight-loss would make them feel more content with themselves, break isolation, and make it easier to find a partner. The participants considered fertility to improve after bariatric surgery, mainly based on stories from other patients of bariatric surgery. Having a child was expressed to be of great importance to them. CONCLUSIONS: Even though obese young women do not seek bariatric surgery for fertility reasons alone, there is a general perception of enhanced fertility after surgery, which is regarded as positive and important.

Alcohol Consumption in Obese Patients Before and After Gastric Bypass as Assessed with the Alcohol Marker Phosphatidylethanol (PEth).

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) causes more rapid and enhanced absorption of alcohol. RYGB patients have also been reported to use more inpatient care for alcohol-related disease than do patients after other bariatric procedures. The present study was designed to evaluate alcohol consumption level before and after gastric bypass using a sensitive and specific alcohol biomarker. MATERIALS AND METHODS: Two separate consecutive groups of patients and a group of healthy blood donors, as reference group, were included in the study. Alcohol intake was assessed using the alcohol marker phosphatidylethanol (PEth) at preoperative baseline and at 1 and 2 years postoperatively. In the first patient group (n = 133), neither surgeon nor patient was informed about the results of PEth testing. In the second group (n = 214), PEth results above 0.30 µmol/L were considered to indicate excessive alcohol consumption and led to preoperative alcohol counseling. The groups were followed for 2 and 1 year, respectively. RESULTS: PEth results were significantly lower in both patient groups at baseline as well as postoperatively compared with the reference group. In both patient groups, there was a significant increase in PEth values at postoperative follow-up compared to baseline. CONCLUSIONS: Several physiological changes postoperatively have to be considered when interpreting PEth results in obese patients with dramatic weight reductions. According to results for PEth, obese patients treated with bariatric surgery would seem to have lower alcohol consumption compared with the reference group. Although slightly increasing their PEth values postoperatively, the RYGB patients did not reach the PEth values of the reference group.

Variation in the adiponutrin gene influences its expression and associates with obesity.

Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes. The adiponutrin gene (ADPN) is downregulated by fasting and upregulated by refeeding, suggesting a role in lipogenesis. Experiments in human adipocytes confirmed that the gene is upregulated in response to insulin in a glucose-dependent fashion. Obese subjects had increased levels of subcutaneous and visceral abdominal adipose tissue ADPN mRNA. Visceral ADPN mRNA expression was correlated to measures of insulin sensitivity (fasting insulin and homeostasis model assessment). We also studied genetic variation in ADPN and its relation to obesity, lipolysis, and mRNA expression. Two ADPN polymorphisms showed association with obesity. Carriers of the obesity-associated variants showed a lesser increase in the levels of adipose tissue ADPN mRNA and an increased basal lipolysis. Our results suggest that obese subjects that are insulin resistant and/or carriers of the obesity-associated ADPN alleles fail to upregulate the gene and that upregulation of adiponutrin may be an appropriate response to orchestrate energy excess.

Gastric bypass in the pig increases GIP levels and decreases active GLP-1 levels.

Gastric bypass surgery results in remission of type 2 diabetes in the majority of patients. The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been implicated in the observed remission. Most knowledge so far has been generated in obese subjects. To isolate the surgical effects of gastric bypass on metabolism and hormone responses from the confounding influence of obesity, T2D, or food intake, we performed gastric bypass in lean pigs, using sham-operated and pair-fed pigs as controls. Thus, pigs were subjected to Roux-en-Y gastric bypass (RYGB) or sham surgery and oral glucose tolerance tests (OGTT). RYGB pigs and sham pigs exhibited similar basal and 120-min glucose levels in response to the OGTT. However, RYGB pigs had approximately 1.6-fold higher 30-min glucose (p<0.01). Early insulin release (EIR) was enhanced approximately 3.5-fold in the RYGB pigs (p<0.01). Furthermore, GIP release, both acute and sustained release (p<0.001 and p<0.01, respectively), was increased approximately 2.5-fold and 1.4-fold, respectively, in RYGB pigs. Although total GLP-1 release increased approximately 2.1-fold after RYGB (p<0.001), active GLP-1 was 33% lower (p<0.01). Interestingly basal DPP4-activity was approximately 3.2-fold higher in RYGB pigs (p<0.001). In conclusion, RYGB in lean pigs increases the response of GIP, total GLP-1, and insulin, but reduces levels of active GLP-1 in response to an oral glucose load. These data challenge the role of active GLP-1 as a contributor to remission from diabetes after RYGB.

Roux-en-Y gastric bypass versus calorie restriction: support for surgery per se as the direct contributor to altered responses of insulin and incretins to a mixed meal.

OBJECTIVE: To study the immediate effects of Roux-en-Y gastric bypass (RYGB) on glucose homeostasis, insulin, and incretin responses to mixed-meal tests compared with the effects of calorie restriction (CR). SETTING: University-affiliated bariatric surgery clinic. BACKGROUND: RYGB induces remission of type 2 diabetes (T2D) long before significant weight loss occurs. The time course and underlying mechanisms of this remission remain enigmatic. A prevailing theory is that secretory patterns of incretin hormones are altered due to rearrangement of the gastrointestinal tract. To what extent reduced calorie intake contributes to the remission of T2D is unknown. METHODS: Nine normoglycemic patients and 10 T2D patients were subjected to mixed-meal tests (MMT) 4 weeks before surgery before initiation of a very low calorie diet regimen (MMT-4 w), 1 day before surgery on a very low calorie diet regimen (MMT-1 d), on the morning of the first day after surgery (MMT+1 d; first postsurgical meal), and 6 weeks after surgery (MMT+6 w). Insulin, glucose, active glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured. RESULTS: CR lowered insulin in T2D patients, whereas glucose, GIP, and GLP-1 were unaffected. RYGB immediately increased plasma insulin and GIP. The GLP-1 response was delayed compared with the GIP response. T2D patients exhibited lower insulin responses after RYGB compared with normoglycemic patients. GIP responses were similar in both groups at all occasions, whereas T2D patients displayed markedly elevated GLP-1 responses 6 weeks after RYGB. Glucose was unaffected by CR and RYGB in both groups. Insulin sensitivity was unaffected by CR but improved with RYGB. CONCLUSION: RYGB exerts powerful and immediate effects on insulin and incretin responses to food, independently of changes caused by CR.

The impact of Roux-en-Y gastric bypass surgery on normal metabolism in a porcine model.

BACKGROUND: A growing body of literature on Roux-en-Y gastric bypass surgery (RYGB) has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreover, RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood. METHODS: In an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT) and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder. RESULTS: A similar weight development in both groups of pigs validated our experimental model. Despite similar changes in fasting insulin, RYGB-pigs had lower fasting glucose levels. During an IVGTT RYGB-pigs had higher insulin and lower glucose levels. VLDL and IDL were lower in RYGB- than in sham-pigs. RYGB-pigs had increased levels of most amino acids, including branched-chain amino acids, but these were more efficiently suppressed by glucose. Levels of bile acids in the gallbladder were higher, whereas plasma and faecal bile acid levels were lower in RYGB- than in sham-pigs. CONCLUSION: In a lean model RYGB caused lower plasma lipid and bile acid levels, which were compensated for by increased plasma amino acids, suggesting a switch from lipid to protein metabolism during fasting in the immediate postoperative period.

Effects of pH on Helicobacter pylori binding to human gastric mucins: identification of binding to non-MUC5AC mucins.

Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer. The microbe is found in the gastric mucus layer where a pH gradient ranging from acidic in the lumen to neutral at the cell surface is maintained. The aim of the present study was to investigate the effects of pH on H. pylori binding to gastric mucins from healthy individuals. At pH 3, all strains bound to the most charged MUC5AC glycoform and to a putative mucin of higher charge and larger size than subunits of MUC5AC and MUC6, irrespective of host blood-group. In contrast, at pH 7.4 only Le(b)-binding BabA-positive strains bound to Le(b)-positive MUC5AC and to smaller mucin-like molecules, including MUC1. H. pylori binding to the latter component(s) seems to occur via the H-type-1 structure. All strains bound to a proteoglycan containing chondroitin sulphate/dermatan sulphate side chains at acidic pH, whereas binding to secreted MUC5AC and putative membrane-bound strains occurred both at neutral and acidic pH. The binding properties at acidic pH are thus common to all H. pylori strains, whereas mucin binding at neutral pH occurs via the bacterial BabA adhesin and the Le(b) antigen/related structures on the glycoprotein. Our work shows that microbe binding to membrane-bound mucins must be considered in H. pylori colonization, and the potential of these glycoproteins to participate in signalling events implies that microbe binding to such structures may initiate signal transduction over the epithelial layer. Competition between microbe binding to membrane-bound and secreted mucins is therefore an important aspect of host-microbe interaction.

Short- and long-term hormonal and metabolic consequences of reversing gastric bypass to normal anatomy in a type 2 diabetes patient.

Gastric bypass (GBP) results in rapid type 2 diabetes (T2D) remission in most cases. Consequences of GBP reversal are unknown. A GBP-operated T2D patient was given mixed-meal tests before (MMTpre), 2 months (MMT2-M) and 12 months (MMT12-M) after GBP reversal. Glucose, hormones and metabolite profiles were assessed. MMT2-M displayed slightly lower glucose levels; MMT12-M displayed higher glucose and insulin levels, indicating deteriorating glycaemia. Homeostasis model assessment (HOMA)-ß was higher at MMT2-M, but reduced at MMT12-M. Matsuda index revealed slightly reduced insulin sensitivity at MMT2-M, which deteriorated further at MMT12-M. Markers for metabolic stress and insulin resistance were elevated at MMT12-M. Gastric inhibitory polypeptide (GIP) levels were increased at MMT2-M and decreased at MMT12-M. Glucagon-like peptide-1 (GLP-1) decreased at MMT2-M and further decreased at MMT12-M. In conclusion, in this patient, GBP reversal provoked deteriorating glycaemia and long-term development of insulin resistance.

Clinical Indications, Utilization, and Funding of Bariatric Surgery in Europe.

PURPOSE: The objective of this study was to evaluate the current utilization, the level of endorsement by professional societies, and health technology assessment bodies, as well as the reimbursement levels for bariatric surgery in European countries. MATERIALS AND METHODS: We performed an analysis of the indications for bariatric surgery based on national clinical and commissioning guidelines, current utilization of surgery, characteristics of patients who underwent surgery, and reimbursement tariffs in Belgium, Denmark, England, France, Germany, Italy, and Sweden. Data were obtained from national patient registries, administrative databases, and published literature for the year 2012. RESULTS: Despite clear consensus outlined in clinical guidelines, significant differences were found in the eligibility criteria for surgery. Patients with no significant comorbidities were deemed eligible if they had a body mass index (BMI) of 40 or 50 kg/m(2) in Denmark. Irrespective of the country, patients with comorbidities were eligible if they had a BMI of 35 kg/m(2). The highest utilization of bariatric surgery (number of surgeries per 1 M population) was observed in Belgium (928), Sweden (761), and France (571) while Italy (128), England (117), and Germany (72) had the lowest utilization. There was a strong negative correlation between utilization and average BMI level of the patient population (r = -.909, p = 0.005). The annual per capita spending on surgery differed significantly between countries, ranging from 0.54 in Germany to 4.33 in Belgium. CONCLUSIONS: There are significant variations in the clinical indications, utilization, and funding of bariatric surgery in European countries.

Bariatric Surgery can Lead to Net Cost Savings to Health Care Systems: Results from a Comprehensive European Decision Analytic Model.

BACKGROUND: The objective of the present study was to evaluate the cost-utility of bariatric surgery in a lifetime horizon from a Swedish health care payer perspective. METHODS: A decision analytic model using the Markov process was developed covering cardiovascular diseases, type 2 diabetes, and surgical complications. Clinical effectiveness and safety were based on the literature and data from the Scandinavian Obesity Surgery Registry. Gastric bypass, sleeve gastrectomy, and gastric banding were included in the analysis. Cost data were obtained from Swedish sources. RESULTS: Bariatric surgery was cost saving in comparison with conservative management. It also led to a substantial reduction in lifetime risk of events: from a 16 % reduction in the risk of transient ischaemic attacks to a 62 % reduction in the incidence of type 2 diabetes. Over a lifetime, surgery led to savings of euro 8408 and generated an additional 0.8 years of life and 4.1 quality-adjusted life years (QALYs) per patient, which translates into gains of 32,390 quality-adjusted person-years and savings of euro 66 million for the cohort, operated in 2012. Analysis of the consequences of a 3-year delay in surgery provision showed that the overall lifetime cost of treatment may be increased in patients with diabetes or a body mass index >40 kg/m(2). Delays in surgery may also lead to a loss of clinical benefits: up to 0.6 life years and 1.2 QALYs per patient over a lifetime. CONCLUSION: Bariatric surgery, over a lifetime horizon, may lead to significant cost savings to health care systems in addition to the known clinical benefits.

Mucosal glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide cell numbers in the super-obese human foregut after gastric bypass.

BACKGROUND: Super-obesity, a body mass index>50 kg/m(2), is difficult to treat. Many studies have focused on the anatomic changes of the intestines; the physiologic background is not clearly identified. It is established that Roux-en-Y gastric bypass (RYGB) augments secretion of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and insulin, but other aspects of gut hormone cell function in the alimentary limb are unknown. OBJECTIVE: To study the effects of laparoscopic RYGB on enteroendocrine cells. SETTING: University-affiliated, high-volume bariatric surgery center. METHODS: Eighteen nondiabetic patients were drawn from the present study (NCT 01514799), randomizing between biliopancreatic (BP) limbs of either 60 cm (BP60) or 200 cm (BP200). Demographic characteristics did not differ at baseline or 12 months. Pouch and jejunal biopsies were obtained intraoperatively and using endoscopy at 12 months. Mucosal height and density of hormone-producing cell populations were assessed and mRNA expression measured with real-time polymerase chain reaction. RESULTS: In perianastomotic jejunum, a 4.9-fold increase in GLP-1 cell density was evident 12 months after RYGB, most pronounced in the BP200-group. The densities of glucose-dependent insulinotropic polypeptide (GIP) cells and PYY immunoreactive cells were doubled after 12 months. GIP mRNA was unaffected, but GLP-1 and PYY mRNA were lower 12 months after RYGB. RYGB had no impact on villi length or density of ghrelin-, cholecystokinin-, neurotensin-, secretin-, or serotonin-producing cells after 12 months. Pouch mucosal height and cell densities of ghrelin-, histamine-, serotonin-, and somatostatin-producing cells remained unaffected by RYGB in both groups. CONCLUSIONS: RYGB selectively increased the density of incretin-producing cell populations in the jejunum. This may provide anatomic explanation for the observed increased plasma levels of incretins.