BACKGROUND:The increasing prevalence of obesity has led to a rise in bariatric surgery as an effective intervention for weight loss and associated co-morbidities. However, concerns persist regarding increased alcohol consumption after surgery. OBJECTIVES:To objectively assess long-term changes in alcohol use after bariatric surgery, we used the highly specific alcohol biomarker phosphatidylethanol (PEth). SETTING:Kalmar County Hospital, Sweden. METHODS:This longitudinal cohort study included 1238 patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy at Kalmar County Hospital from 2010 to 2020. Patients were divided into 2 cohorts based on preoperative PEth sampling (n = 327 with, n = 911 without). PEth levels were measured before surgery and at intervals up to 10 years postoperatively, using .30 μmol/L (approximately 210 ng/mL) as the threshold for heavy alcohol use. RESULTS:Mean PEth concentrations increased from .07 to .38 μmol/L (P < .001) in men and from .06 to .11 μmol/L nonsignificantly in women. The proportion of patients that postoperatively exceeded the heavy drinking threshold rose significantly over time. At 5 years, 37.5% of men and 4.8% of women had PEth values above .30 μmol/L (both P < .001). Men were at significantly higher risk (odds ratio: 7.89, 95% confidence interval: 3.76-16.57; P < .001). This pattern remained consistent at the 10-year follow-up. CONCLUSIONS:Alcohol consumption, as measured by PEth, increased significantly after bariatric surgery, particularly in men. These findings support routine postoperative alcohol screening and suggest incorporating PEth testing into long-term follow-up protocols.

Background The increasing prevalence of obesity has led to a rise in bariatric surgery as an effective intervention for weight loss and associated comorbidities. However, concerns persist regarding increased alcohol consumption following surgery. Objectives To objectively assess long-term changes in alcohol use following bariatric surgery we employed the use of the highly specific alcohol biomarker Phosphatidylethanol (PEth). Setting Kalmar County Hospital, Sweden. Methods This longitudinal cohort study included 1,238 patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at Kalmar County Hospital from 2010 to 2020. Patients were divided into two cohorts based on preoperative PEth sampling (n=330 with, n=916 without). PEth levels were measured before surgery and at intervals up to 10 years post-op, using 0.30 μmol/L (∼210 ng/mL) as the threshold for heavy alcohol use. Results Mean PEth concentrations increased from 0.07 to 0.38 μmol/L (P<0.001)in men and from 0.06 to 0.11 μmol/L non significantly in women. The proportion of patients that postoperatively exceeded the heavy drinking threshold rose significantly over time. At five years, 37.5% of men and 4.8% of women had PEth values above 0.30 μmol/L (both p<0.001). Men were at significantly higher risk (OR 7.89, 95% CI 3.76–16.57; p<0.001). This pattern remained consistent at the 10-year follow-up. Conclusions Alcohol consumption, as measured by PEth, increased significantly following bariatric surgery, particularly in men. These findings support routine postoperative alcohol screening and suggest incorporating PEth testing into long-term follow-up protocols.

Context Statin use is associated with increased risk of type 2 diabetes (T2D) and mild hyperglycemia. The underlying mechanisms are not well studied, and the effect of statin treatment on glucagon-like peptide 1 (GLP-1) secretion or production is unknown. Objective This work aimed to assess the effects of rosuvastatin on GLP-1 secretion and production. Methods We performed association studies in the Malmö Diet and Cancer study cardiovascular cohort (MDCS-CC) reexamination cohort, in vitro investigations using GLUTag cells and acute and chronic studies in female, normoglycemic C57Bl/6j mice. Results Studies in the MDCS-CC reexamination cohort (n = 3734) revealed that in individuals without T2D, statin usage was associated with higher fasting glucose-dependent insulinotropic peptide (GIP), insulin, glucose, glucagon, and homeostatic model assessment of insulin resistance, but not GLP-1. However, in patients with T2D, statin usage was associated with higher fasting GLP-1 levels. Rosuvastatin treatment or 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (Hmgcr) knockdown (KD) reduced GLP-1 secretion and increased Gcg messenger RNA in GLUTag cells. Rosuvastatin acutely reduced postprandial GLP-1 secretion, whereas chronic rosuvastatin treatment in mice caused hyperglycemia and increased postprandial GLP-1 levels. The acute effect of Hmgcr KD on GLP-1 secretion could be mimicked by targeting intracellular cholesterol using a PCSK9 inhibitor. Finally, transcriptomic alterations induced by rosuvastatin were limited to genes involved in cholesterol biosynthesis. Conclusion We have established HMGCR as a regulator of GLP-1 secretion and provide a plausible explanation for the clinically observed mild hyperglycemia associated with statin use. Given the negative acute effect on GLP-1 secretion, monitoring of blood glucose levels is recommended after prescribing rosuvastatin.

Context Proneurotensin (pNT) is associated with obesity and type 2 diabetes (T2D), but the effects of Roux-en-Y gastric bypass (RYGB) on postprandial pNT levels are not well studied.Objective This work aimed to assess the effects of RYGB vs a very low-energy diet (VLED) on pNT levels in response to mixed-meal tests (MMTs), and long-term effects of RYGB on fasting pNT.Methods Cohort 1: Nine normoglycemic (NG) and 10 T2D patients underwent MMT before and after VLED, immediately post RYGB and 6 weeks post RYGB. Cohort 2: Ten controls with normal weight and 10 patients with obesity and T2D, who underwent RYGB or vertical sleeve gastrectomy (VSG), underwent MMTs and glucose-dependent insulinotropic polypeptide (GIP) infusions pre surgery and 3 months post surgery. Glucagon-like peptide-1 (GLP-1) infusions were performed in normal-weight participants. Cohort 3: Fasting pNT was assessed pre RYGB (n = 161), 2 months post RYGB (n = 92), and 1year post RYGB (n = 118) in NG and T2D patients. pNT levels were measured using enzyme-linked immunosorbent assay.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 pNTs 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 pNTs are maintained 1 year post surgically.

Aims/hypothesisRoux-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.MethodsHuman 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.ResultsGene 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/interpretationRYGB 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.

ObjectiveSome 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. MethodsFasting 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. ResultsThis 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. ConclusionsRemission 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.

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.

It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells.

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, Jarvholm 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. Copyright (c) 2020, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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.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.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.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.

•Gastric bypass in pigs yields higher 30-min glucose in response to an oral glucose test.•Total GLP-1 and GIP are increased in gastric bypass-operated pigs compared with sham-operated pigs in response to an oral glucose tolerance test.•Active GLP-1 is decreased in gastric bypass-operated pigs compared with sham-operated pigs in response to an oral glucose tolerance test.

BackgroundA 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.MethodsIn 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.ResultsA 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.ConclusionIn 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.

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(2)] 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 +/- 5.5 to 31.2 +/- 5.5 kg/m(2) 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.

Background Diabetes remission is an important outcome after bariatric surgery. The purpose of this study was to identify risk prediction models of diabetes remission after bariatric surgery. Methods A systematic literature review was performed in MEDLINE, MEDLINE-In-Process, Embase and the Cochrane Central Register of Controlled Trials databases in April 2015. All English-language full-text published derivation and validation studies for risk prediction models on diabetic outcomes after bariatric surgery were included. Data extraction included population, outcomes, variables, intervention, model discrimination and calibration. Results Of 2330 studies retrieved, eight met the inclusion criteria. Of these, six presented development of risk prediction models and two reported validation of existing models. All included models were developed to predict diabetes remission. Internal validation using tenfold validation was reported for one model. Two models (ABCD score and DiaRem score) had external validation using independent patient cohorts with diabetes remission assessed at 12 and 14 months respectively. Of the 11 cohorts included in the eight studies, calibration was not reported in any cohort, and discrimination was reported in two. Conclusion A variety of models are available for predicting risk of diabetes following bariatric surgery, but only two have undergone external validation.

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+i 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. 2017 American Society for Metabolic and Bariatric Surgery. All rights reserved.

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)-β 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.