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Elevated lipoprotein(a) (Lp(a)) level is an independent risk factor for cardiovascular diseases. Lifestyle intervention studies targeting weight loss revealed little to no significant changes in Lp(a) levels. The impact of interventions that induce substantial weight loss, such as bariatric surgery, on Lp(a) levels is currently unclear. To determine the acute and long-term impact of bariatric surgery on Lp(a) levels in patients with severe obesity. Sixty-nine patients with severe obesity underwent biliopancreatic diversion with duodenal switch (BPD-DS) surgery. The lipid profile was evaluated and Lp(a) levels were measured before surgery and at 6 and 12 months after BPD-DS surgery. Median Lp(a) levels at baseline were 11.1 (4.1–41.6) nmol/L. Six months and 12 months after the BDP-DS surgery, we observed an improvement of lipid profile. At 6 months, we observed a 13% decrease in Lp(a) levels (9.7 (2.9–25.6) nmol/L, p

There is little data regarding the risks and benefits of bariatric surgery in patients with coronary artery disease (CAD). We aimed to assess the short- and long-term cardiovascular outcomes of patients with CAD undergoing bariatric surgery. Patients with a history of CAD were identified from a dedicated database with prospectively collected outcomes, comprising all 6795 patients who underwent bariatric surgery between January 1992 and October 2017. Patients were matched with patients who did not have CAD before the bariatric surgery procedure. The primary endpoints were mortality (cardiac and noncardiac) and major adverse cardiocerebral events (MACCE), including all-cause death, myocardial infarction, stroke, and myocardial revascularization at 30 days after bariatric surgery and throughout follow-up. After propensity score matching, 249 patients with chronic CAD were matched with 249 patients without CAD. Throughout follow-up (7.4 years; interquartile range 4.1 to 11.5, maximum 22 years), mortality (mainly cardiac mortality) remained significantly higher in the CAD compared with the non-CAD group (18% vs 10%, hazard ratio [HR] 1.70, 95% confidence interval [CI]: 1.03 to 2.79, p = 0.037). At 30 days, MACCE rate was significantly higher in the CAD compared with the non-CAD group (3.6% vs 0.4%, p = 0.011), essentially driven by non-ST elevation myocardial infarctions. After 30 days, MACCE rates remained significantly higher in the CAD group (30% vs 14%, HR 2.18, 95% CI: 1.45-3.28, p = 0.0002). In conclusion, patients with severe obesity and CAD referred to bariatric surgery were at a higher risk of early and late MACCE compared with non-CAD severely obese patients. Further study is required to define how this cardiovascular risk compares with nonoperated patients.

The benefit of exercise training on lipid profile in bariatric surgery patients is scarce. We assess the effect of a supervised exercise-training program on lipid profile following bariatric surgery. A total of 60 patients were prospectively recruited, of those 49 completed the study (age 41 ± 11 years; body mass index 45.9 ± 6.1 kg/m2, 75% women). The bariatric surgery procedures performed were sleeve gastrectomy (SG) (n = 24) and biliopancreatic diversion with duodenal switch (BPD-DS) (n = 25). Of the 49 patients who completed the study, 34 had been randomized to a 12-week supervised exercise training program (exercise group) between the 3rd and the 6th month following bariatric surgery (SG = 17 and BPD-DS = 17). Fasting blood samples and anthropometric measurements were performed preoperatively and at 3, 6, and 12 months after bariatric surgery. At 6 months and 12 months, percentage of weight loss was similar between groups (6 months: − 29.6 ± 5.5 vs. − 27.8 ± 7.7%; P = 0.371; 12 months: − 38.4 ± 10.4 vs. − 37.9 ± 9.5%; P = 0.876 exercise vs. control). Both groups had an increase in HDL values between the 3nd and the 6th month following bariatric surgery. There was a significantly greater increment in HDL values in the exercise group (0.18 ± 0.14 vs. 0.07 ± 0.12 mmol/L, P = 0.014; exercise vs. control). Our results showed a beneficial effect of a 12-week supervised exercise-training program in bariatric surgery patients showing similar weight loss on HDL-cholesterol levels without additional effect on LDL-cholesterol levels.

Background Biliopancreatic diversion with duodenal switch (BPD-DS) confers the highest rate of type 2 diabetes (T2D) remission compared with other bariatric procedures. Previous studies suggest that type of antidiabetic therapy used before surgery and duration of disease influence postsurgical glycemic outcomes. Short-term, progressive improvement in insulin sensitivity and beta-cell function after metabolic surgery in patients with noninsulin-treated T2D has been demonstrated. Whether patients with more advanced disease can achieve sustained remission remains unclear. Objective The aim of this study was to assess long-term glycemic outcomes in insulin-treated patients with T2D after BPD-DS and identify predictors of sustained diabetes remission or relapse. Setting University-affiliated tertiary care center. Methods Data from 141 patients with insulin-treated T2D who underwent BPD-DS between 1994 and 2006 with 10 years of follow-up data were collected from a prospective electronic database. Results Follow-up was available in 132 patients (91%). At 10 years after metabolic surgery, 90 patients (68.1%) had a complete remission of diabetes, 3 (2.3%) had a partial remission, 21 (15.9%) had an improvement, and 3 (2.3%) were unchanged in their diabetes status. Fourteen patients died during the 10-year follow-up period. Relapse after an initial period of remission occurred in 15 (11.4%) patients. Insulin discontinuation was achieved in 97%. Duration of diabetes was an independent predictor of nonremission at 10 years. Conclusions The BPD-DS maintains remission at 10 years postoperatively in patients with more advanced diabetes. Long-term benefits of the BPD-DS on weight loss and glycemic control should be considered when offering metabolic surgery to patients with insulin-treated T2D.

Apolipoprotein D (ApoD) is a lipocalin participating in lipid transport. It binds to a variety of ligands, with a higher affinity for arachidonic acid, and is thought to have a diverse array of functions. We investigated a potential role for ApoD in insulin sensitivity, inflammation, and thrombosis—processes related to lipid metabolism—in severely obese women. We measured ApoD expression in a cohort of 44 severely obese women including dysmetabolic and non-dysmetabolic patients. Physical and metabolic characteristics of these women were determined from anthropometric measurements and blood samples. ApoD was quantified at the mRNA and protein levels in samples from three intra-abdominal adipose tissues (AT): omental, mesenteric and round ligament (RL). ApoD protein levels were highly variable between AT of the same individual. High ApoD protein levels, particularly in the RL depot, were linked to lower plasma insulin levels (−40%, p = 0.015) and insulin resistance (−47%, p = 0.022), and increased insulin sensitivity (+10%, p = 0.008). Lower circulating pro-inflammatory PAI-1 (−39%, p = 0.001), and TNF-α (−19%, p = 0.030) levels were also correlated to high ApoD protein in the RL AT. ApoD variability between AT was consistent with different accumulation efficiencies and/or metabolic functions according to the anatomic location of fat depots. Most statistically significant correlations implicated ApoD protein levels, in agreement with protein accumulation in target tissues. These correlations associated higher ApoD levels in fat depots with improved metabolic health in severely obese women.

Context Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol (LDL-C) concentrations. In patients with severe obesity, biliopancreatic diversion with duodenal switch (BPD-DS) surgery induces substantial weight loss and influences lipoprotein metabolism. The effect of BPD-DS on PCSK9 levels is unknown. Objectives To determine the acute and chronic impact of BPD-DS on PCSK9 levels and whether the acute impact of BPD-DS could be explained by BPD-DS-associated caloric restriction (CR). Design, Settings, and Participants PCSK9 levels were measured in 20 men and 49 women (age, 41.5 ± 11.1 years) with severe obesity before, 24 hours, 5 days, and 6 and 12 months after BPD-DS and in a comparable control group (n = 31) at baseline and at 6 and 12 months. PCSK9 levels were also measured during 3-day CR in patients (n = 7) with severe obesity and type 2 diabetes. Results PCSK9 levels increased 13.4% after 24 hours (248.7 ± 64.8 to 269.7 ± 63.8 ng/mL; P = 0,02) and decreased 9.5% at 12 months compared with baseline (217.6 ± 43.0 ng/mL; P < 0,0001). LDL-C levels decreased 36.2% after 24 hours (2.6 ± 0.7 to 1.7 ± 0.6 mmol/L; P < 0.0001) and 30% at 12 months compared with baseline (1.7 ± 0.5 mmol/L; P < 0.0001). Compared with baseline levels, PCSK9 levels were lower at day 2 but not at day 1 or 3 after CR. Conclusion BPD-DS is associated with acute increases in PCSK9 levels that do not appear to be explained by CR but may be due to an acute response following surgery. BPD-DS induces chronic reductions in both PCSK9 and LDL-C levels.

Objective Our objective was to compare the ECLIA from Roche versus the LC–MS/MS method for quantitation of serum 25-hydroxy-vitamin D in patients who have undergone bariatric surgery. Design and methods Cross-sectional and correlational studies were performed on three different groups for the 25-OH-D levels quantitated by both methods. The control group of apparently healthy subjects was randomly selected in a clinical chemistry laboratory. Test groups were patients who had undergone bilio-pancreatic diversion (BPD) and were supplemented either with vitamin D 2 or with vitamin D 3 . The number of samples per group was established according to the CLSI recommendation protocol (EPO9-A2-IR). Results The agreement of LC-MS/MS with the Roche method was acceptable in the apparently healthy subjects group and in the post-BPD D 3 -supplemented group with an average bias of − 1.7% and − 9.2%, respectively. However, this agreement was unacceptable in the post-BPD D 2 -supplemented group with an average bias of − 45.3%. The LC–MS/MS enabled us to detect four patients who had excess vitamin D or poisoning with vitamin D for which it was necessary to stop the supplementation with vitamin D in the D 2 -supplemented group. Conclusion Despite the apparent good agreement between the Roche method and LC–MS/MS in the healthy subjects group and in the post-DBP D 3 -supplemented patient group, a considerable bias seems to exist, particularly in the presence of D 2 . The LC–MS/MS method is therefore the most accurate method to follow the vitamin D 2 -supplemented bariatric population.

Background Severely obese patients have decreased cardiorespiratory fitness (CRF) and poor functional capacity. Bariatric surgery–induced weight loss improves CRF, but the determinants of this improvement are not well known. We aimed to assess the determinants of CRF before and after bariatric surgery and the impact of an exercise training program on CRF after bariatric surgery. Methods Fifty-eight severely obese patients (46.1 ± 6.1 kg/m2, 78% women) were randomly assigned to either an exercise group (n = 39) or usual care (n = 19). Exercise training was conducted from the 3rd to the 6th months after surgery. Anthropometric measurements, abdominal and mid-thigh computed tomographic scans, resting echocardiography, and maximal cardiopulmonary exercise testing was performed before bariatric surgery and 3 and 6 months after surgery. Results Weight, fat mass, and fat-free mass were reduced significantly at 3 and 6 months, without any additive impact of exercise training in the exercise group. From 3 to 6 months, peak aerobic power (VO2peak) increased significantly (P Conclusions A 12-week supervised training program has an additive benefit on cardiorespiratory fitness for patients who undergo bariatric surgery.

SummaryObjective A novel single-nucleotide polymorphism (SNP) associated with morbid obesity was recently identified by exome sequencing. The purpose of this study was to follow up this low-frequency coding SNP located within the SYPL2 locus and associated with body mass index in order to reveal novel associations with obesity-related traits. Methods The body mass index-associated SNP (rs62623713 A>G [chr1:109476817/hg19]) and two tagging SNPs within the SYPL2 locus, rs9661614 T>C (chr1:109479215) and rs485660 G>A (chr1:109480810), were genotyped in the obesity (n = 3,017) and the infogene (n = 676) cohorts, which were further combined, leading to a larger cohort of 3,693 individuals. Association testing was performed by general linear models in the obesity cohort and validated by joint analysis in the combined cohort. Results rs9661614 and rs485660 were significantly associated with hip circumference (HC) in the obesity cohort, with heterozygotes exhibiting a significantly lower HC. These results were validated by joint analysis for rs9661614 (false discovery rate [FDR]-corrected P = 7.5 × 10−4) and, to a lesser extent, for rs485660 (FDR corrected P = 3.9 × 10−2). The association with HC remained significant for rs9661614 when tested independently in women (FDR-corrected P = 1.7 × 10−2), but not for rs485660 (FDR-corrected P = 0.2). Both associations were absent in men. Conclusions This study reveals strong evidence for a novel association between rs9661614 (T>C) and HC in women, which likely reflects a preferential association of SYPL2 to a gynoid profile of fat distribution. The study findings support a clinical significance of SYPL2 worth considering when assessing risk factors associated with obesity.

Semicarbazide-sensitive amine oxidase (SSAO), identical to primary amine oxidase or vascular adhesion protein-1, is a membrane enzyme that generates hydrogen peroxide. SSAO is highly expressed at the adipocyte surface, and its plasma levels increase with type 2 diabetes. Since visceral adipose tissue (AT) is more tightly associated with obesity complications than subcutaneous (SC) abdominal fat, we compared SSAO activity in plasma and 4 distinct AT locations in 48 severely obese women (body mass index (BMI), averaging 54 ± 11 kg/m2), with or without a dysmetabolic profile. Higher glucose and triacylglycerol levels vs lower high-density lipoprotein (HDL)-cholesterol characterized dysmetabolic women (DYS; n = 25) from non-dysmetabolic (NDYS; n = 23), age- and weight-matched subjects. SC, mesenteric (ME), omental (OM), and round ligament (RL) fat locations were collected during bariatric surgery. SSAO capacity to oxidize up to 1 mM benzylamine was determined in AT and plasma with radiometric and fluorimetric methods. Plasma SSAO was higher in the DYS group. SSAO activity was higher in fat than in plasma, when expressed as radiolabeled benzaldehyde per milligram of protein. In ATs from DYS women, protein content was 10 % higher, and basal hydrogen peroxide release lower than in NDYS subjects, except for RL location. The SSAO affinity towards benzylamine did not exhibit regional variation and was not altered by a dysmetabolic profile (Km averaging 184 ± 7 μM; n = 183). Although radiometric and fluorimetric methods gave different estimates of oxidase activity, both indicated that AT SSAO activity did not vary according to anatomical location and/or metabolic status in severely obese women.

The goal of this article is to present an overview of selection criteria, surgical technique, and perioperative outcomes of biliopancreatic diversion with duodenal switch. The standard follow-up requirements, including vitamin supplementation, and long-term risks associated with metabolic surgery are also discussed. Most of the data reported here are based on the authors' experience with 4000 biliopancreatic diversions with duodenal switch performed in their institution since 1990.

Background Biliopancreatic diversion with duodenal switch (BPD-DS) with a 100-cm common channel has been our treatment of choice for morbid obesity since the early 1990s. This procedure offers excellent long-term weight loss but can be associated with significant side effects. Objectives To assess the effect on clinical and nutritional parameters of increasing the common channel to 200 cm. Settings University-affiliated tertiary care center. Methods Patients who underwent a BPD-DS with a 200-cm common channel (study group, n=36) were matched 1:1 for age, sex, body mass index (BMI), and main co-morbidities with patients who underwent a BPD-DS with a 100-cm common channel (control group). The strict alimentary limb was 150 cm in both groups. Results The mean age was 55±9 versus 53±7 years ( P = .3), with 50% women and a BMI of 49±8 kg/m 2 versus 50±6 kg/m 2 ( P = .9). Follow-up rate was 97%, with a minimum follow-up of 3 years. There were no significant differences in the remission rate of major co-morbidities between the 2 groups. At 3 years, the excess weight loss was 61±22% versus 68±18% ( P = .18) and the total weight loss was 33±11% versus 38±9% ( P = .055) in the study group versus control group, respectively. The study group had a lower incidence of severe protein deficiency (11% versus 19%, P = .3) and hyperparathyroidism (17.1% versus 35.3%, P = .17); required a lower amount of vitamins A and D ( P P = .03). Conclusion In this population, BPD-DS with a 200-cm common channel offered similar remission rate of co-morbidities compared with standard BPD-DS. It was associated with similar weight loss at nadir, followed by a more significant weight regain. It might yield a lower rate of nutritional complications. Long-term randomized data are needed to detect other potential advantages.

Introduction: N-myristoyltransferase (NMT) is implicated in myristoylation, required for bio- logical activities of several proteins. Its gene N-myristoyltransferase 1 (NMT1) has been found to be overexpressed and hypermethylated in Visceral Adipose Tissue (VAT) of severely obese individuals with Metabolic Syndrome (MetS+) versus without (MetS-). Objective: The aim of this study was to verify the associations between NMT1 gene polymor- phisms Single Nucleotide Polymorphisms (SNPs) and metabolic complications among obese subjects. Methods: Associations between SNPs and determinants of MetS were tested with 1752 obese participants undergoing a bariatric surgery. The effect of selected SNPs on methylation, and correlation with expression levels of NMT1 were verified in subgroups. Results: Rs2239921 was significantly associated with systolic (p=0.03) and diastolic (p

Aims: To test the potential association of cytosine-phosphate-guanine dinucleotides (CpG)-single-nucleotide polymorphisms (SNPs) located within actin-related protein 2/3 complex subunit 3 (ARPC3), a gene recently linked to adipogenesis and lipid accumulation, with metabolic syndrome (MetS) features in severely obese patients. Methods: Prioritized SNPs within the ARPC3 locus were genotyped and tested for associations with MetS features in a cohort of 1,749 obese patients with and without MetS. Association testing with CpG methylation levels was performed in a methylation sub-cohort of 16 obese men. Results: A significant association was found between the CpG-SNP rs3759384 (C>T) and plasma triglyceride (TG) levels (false discovery rate-corrected p = 3.5 × 10-2), with 0.6% of the phenotypic variance explained by the CpG-SNP, and with TT homozygotes showing the highest plasma TG levels (1.89 mmol/l). The carriers of the rs3759384 T allele also showed a significant decrease in methylation levels of the ARPC3 promoter-associated CpG site cg10738648 in both visceral adipose tissue and blood. ARPC3 expression levels showed a strong correlation with plasma TG levels (r = 0.70; p = 0.02). Conclusions: The increased plasma TG levels found in homozygous rs3759384 T allele carriers argue for a relevant role of this CpG-SNP in lipid management among obese individuals, which may be driven by an epigenetic-mediated mechanism.

Severe obesity is often characterized by ectopic fat deposition, which is related to development of type 2 diabetes (T2D). Thus, resolution of T2D may not be linearly associated with weight loss. The importance of ectopic fat reduction after bariatric surgery and T2D resolution is uncertain.The aim of this pilot study is to compare body composition and body fat distribution in severely obese patients with or without T2D after biliopancreatic diversion with duodenal switch (BPD-DS) surgery in relation to diabetes resolution.Sixty-two severely obese patients were evaluated at baseline, 6, and 12 months. Of these, 40 patients underwent BPD-DS surgery. Anthropometric measurements and abdominal and mid-thigh computed tomography scans were performed at each visit.Before BPD-DS surgery, obese patients with T2D had higher weight as well as greater ectopic fat deposition in the abdomen and mid-thigh level than obese patients without T2D (p 0.05). Resolution of T2D was 65 and 90 % at 6 and 12 months, respectively. No difference in body composition changes at 6 and 12 months could be found between patients without T2D, patients with T2D resolution, and patients who remained T2D. Resolution of T2D was associated with a greater absolute loss of visceral adipose tissue (VAT) in comparison to patients without T2D (-1175 ± 570 cm(3) vs. -729 ± 394 cm(3) at 6 months and -1647 ± 816 cm(3) vs. -1103 ± 422 cm(3) at 12 months; all p ≤ 0.05).Ectopic fat mobilization, particularly the absolute loss of VAT, may play a major role in T2D resolution following BPD-DS surgery, regardless of the amount of weight loss.

Gene expression (qPCR) was compared in round ligament (RL), omental (OME) and mesenteric (MES) ATs from 48 severely obese women (BMI, 54±11 kg/m(2); 38±9 yrs). The mRNA levels of enzymes of lipid metabolism (LPL, HSL, and PDE-3B), cortisol production (11βHSD-1), adipogenesis (PPAR-γ1/2), thrombosis and inflammation (PAI-1, IL-6, TNF-α and adiponectin) were determined. AT-LPL mRNA was highest in RL. The highest PDE-3B and lowest PAI-1 mRNA levels were observed in RL and MES. The lowest IL-6 and TNF-α and the highest adiponectin and PPAR-g1/2 mRNA levels were found in RL AT. 11βHSD-1 was highest in RL and OME. A higher lipogenic and adipogenic, and lower pro-inflammatory and pro-thrombotic profiles of the RL suggest a lesser deleterious impact on obesity-related complications.

Biliopancreatic diversion with duodenal switch (BPD-DS) is one of the most effective surgical approaches for the treatment of severe obesity. The objective of this study is to compare perioperative complications and long-term results of open BPD-DS in elderly versus younger patients. All patients aged 60 years and above who underwent a primary open BPD-DS in our center were selected (n = 105). Patients were matched 1:1 for sex, BMI, the presence of type 2 diabetes (T2DM), and year of surgery with a group of younger patients (aged ≤55 years). The mean age of the patients was 62.3 ± 2.0 vs. 40.4 ± 7.0 years (p ≤ 0.0001). Initial BMI and prevalence of T2DM were similar in both groups, at 50.9 kg/m2 and 57 %, respectively. Mean operative time (178.6 ± 46.7 vs. 162.5 ± 39.9 min, p = 0.01), hospital stay (10.2 ± 8.3 vs. 6.3 ± 1.5 days, p = 0.0001), and blood loss (593 ± 484 vs. 474 ± 241 ml, p = 0.05) were significantly higher in elderly patients. No difference in 30-day mortality rate was observed (0.9 % in each group). There was no significant difference in major complication rate (16.2 vs. 8.6 %, p = 0.09). At a mean follow-up of 7.1 ± 4.1 years, excess weight loss (67.6 ± 19.2 vs. 72.7 ± 20.7 %, p = 0.06) and BMI (32.2 ± 5.7 vs. 30.8 ± 6.6 kg/m2, p = 0.15) were not significantly different. No significant difference was observed between the two groups for the resolution of T2DM (p = 0.53) and obstructive sleep apnea (p = 0.44). Open BPD-DS is associated with similar long-term benefits in elderly and younger patients, in terms of weight loss and resolution or improvement of obesity-related comorbidities. Perioperative complications might be more frequent in the elderly population, but this was not associated with increased mortality.

Biliopancreatic diversion (BPD) is a complex bariatric operation requiring meticulous surveillance which has impeded its broad adoption. Improvements in surgical care and technique, better teaching programs, and stringent norms for follow-up have contributed to increased safety of BPD for patients with BMI

Background Substantial improvements in health-related quality of life measured by generic questionnaires (most often the Short Form-36) have been noted over the long term in patients with morbid obesity who had undergone bariatric surgery. Objectives To obtain long-term follow-up data on disease-specific quality of life in patients who underwent bariatric surgery (biliopancreatic diversion with duodenal switch) in 2007 to 2008. Setting Quebec Heart and Lung Institute, Quebec, Canada. Methods This study is a follow-up of the validation study, the Laval Questionnaire, an obesity-specific measure of health-related quality of life developed to be used in clinical trials. Patients who contributed to the validation study in 2007 to 2008 were administered the Laval Questionnaire again at long-term follow-up. Results Of 112 patients who contributed to the validation study, 90 were available for this long-term follow-up study (retention rate: 80%). Median follow-up was 8.8 years. For all 6 domains of the Laval Questionnaire, the improvements in quality-of-life scores were much larger than our best estimate of the minimal clinically important difference. In others, we observed some decline in quality-of-life scores over time after initial changes that occurred 1 to 2 years after surgery, during the so-called "honeymoon period." Improvements in quality of life were clearly related to surgery. Conclusion This study confirms that bariatric surgery using biliopancreatic diversion with duodenal switch improves disease-specific quality of life in the short and long term. It also demonstrates that the Laval Questionnaire is responsive to treatment-induced changes.

Objective To assess the rapid improvement of insulin sensitivity and β-cell function following biliopancreatic diversion with duodenal switch (BPD-DS) and determine the role played by caloric restriction in these changes. Methods Standard meals were administrated before and on day 3, 4, and 5 after BPD-DS to measure total caloric intake, glucose excursion, insulin sensitivity, and secretion in matched type 2 diabetes and normoglycemic (NG) subjects. In a second set of study, other subjects with type 2 diabetes had the same meal tests prior to and after a 3-day caloric restriction identical to that observed after BPD-DS and then 3 days after actually undergoing BPD-DS. Results Improvement of HOMA-IR occurred at day 3 after BPD-DS in diabetes and after 3 days of caloric restriction. The disposition index (DI) improved rapidly in diabetes after BPD-DS and to a similar extent after caloric restriction. DI was higher and did not change after BPD-DS in NG. Changes in glucagon-like peptide-1, gastric inhibitory peptide, peptide tyrosine tyrosine, ghrelin, and pancreatic polypeptide levels were not associated with modulation of DI in the participants. Conclusions Caloric restriction is the major mechanism underlying the early improvement of insulin sensitivity and β-cell function after BPD-DS in type 2 diabetes.

Aim:ADRB3 DNA hypermethylation was recently associated with dyslipidemia in familial hypercholesterolemia (FH). In this study, we verified whether ADRB3 DNA methylation in blood and visceral adipose tissue (VAT) was associated with obesity and its related complications. Methods: DNA methylation levels were measured in the blood of 61 FH men, and the blood and VAT of 30 severely obese men. Common ADRB3 polymorphisms were genotyped in all subjects. Results: Higher ADRB3 DNA methylation levels were significantly associated with lower low-density lipoprotein cholesterol levels (r = -0.40; p = 0.01) in FH, and with a lower waist-to-hip ratio (r = -0.55; p = 0.01) and higher blood pressure (r = 0.43; p = 0.05) in severely obese men. ADRB3 g.-843C>T and p.W64R polymorphisms were found to be strongly associated (p < 0.001) with ADRB3 DNA methylation and mRNA levels. Conclusion: Although further studies are needed, these results suggest that epigenetic changes at the ADRB3 gene locus might be involved in the development of obesity and its related metabolic complications.

Background: Methylamine, a natural soluble amine present in foods, is known to be a substrate of primary amine oxidase (PrAO) widely expressed in animal tissues. Methylamine has been reported to activate glucose transport in fat cells and to facilitate glucose disposal in rabbits but the interests and limits of such insulin-mimicking actions have not been further explored. This work aimed to perform a preclinical study of the inter-individual variations of these biological properties to study the putative link between PrAO activity and insulin resistance. Methods: Methylamine was tested on human adipocyte preparations and in rabbit pancreatic islets to determine its influence on glucose uptake and insulin release, respectively. PrAO activity and related responses were determined in adipose tissues obtained from two cohorts of non-obese and obese women. Results: Adipose tissue PrAO activity was negatively correlated with insulin resistance in high-risk obese women. PrAO-dependent activation of glucose uptake was negatively correlated with body mass index and reflected the decrease of insulin responsiveness of human fat cells with increasing obesity. Methylamine exhibited antilipolytic properties in adipocytes but was unable to directly activate insulin secretion in isolated pancreatic islets. Conclusions: PrAO activation by its substrates, e.g., methylamine, increases glucose utilization in human adipocytes in a manner that is linked to insulin responsiveness. Methylamine/PrAO interaction can therefore contribute to adipose tissue enlargement but should be considered as potentially useful for diabetes prevention since it could limit lipotoxicity and facilitate glucose handling, at the expense of favoring healthy fat accumulation.

Autotaxin (ATX), an adipose tissue‐derived lysophospholipase, has been involved in the pathophysiology of cardiometabolic diseases. The impact of bariatric surgery on circulating ATX levels is unknown. We examined the short‐ (24 h, 5 days) and longer‐term (6 and 12 months) impact of bariatric surgery; as well as the short‐term effect of caloric restriction (CR) on plasma ATX levels in patients with severe obesity. We measured ATX levels in 69 men and women (mean age: 41 ± 11 years, body mass index: 49.8 ± 7.1 kg/m2), before and after biliopancreatic diversion with duodenal switch surgery (BPD‐DS) as well as in a control group (patients with severe obesity without surgery; n = 34). We also measured ATX levels in seven patients with severe obesity and type 2 diabetes who underwent a 3‐day CR protocol before their BPD‐DS. At baseline, ATX levels were positively associated with body mass index, fat mass, insulin resistance (HOMA‐IR) as well as insulin and leptin levels and negatively with fat‐free mass. ATX concentrations decreased 26.2% at 24 h after BPD‐DS (342.9 ± 152.3 pg/mL to 253.2 ± 68.9 pg/mL, P

In the past 10 years, most bariatric surgeries have seen an important reduction in the early complication rate, partly associated with the development of the laparoscopic approach. Our objective was to assess the current early complication rate associated with biliopancreatic diversion with duodenal switch (BPD-DS) since the introduction of a laparoscopic approach in our institution, a university-affiliated tertiary care center.A consecutive series of 1000 patients who had undergone BPD-DS from November 2006 to January 2010 was surveyed. The primary endpoint was the mortality rate. The secondary endpoints were the major 30-day complication rate and hospital stay10 days. The data are reported as a mean ± SD, comparing the laparoscopic (n = 228) and open (n = 772) groups.The mean age of the patients was 43 ± 10 years (40 ± 10 years in the laparoscopy group versus 44 ± 10 years in the open group, P.01). The preoperative body mass index was 51 ± 8 kg/m(2) (47 ± 7 laparoscopy versus 52 ± 8 kg/m(2) open, P.01). The conversion rate in the laparoscopy group was 2.6%. There was 1 postoperative death (.1%) from a pulmonary embolism in the laparoscopy group. The mean hospital stay was shorter after laparoscopic surgery (6 ± 6 d versus 7 ± 9 d, P = .01), and a hospital stay10 days was more frequent in the open group (4.4% versus 7%, P = .04). Major complications occurred in 7% of the patients, with no significant differences between the 2 groups (7% versus 7.4%, P = .1). No differences were found in the overall leak or intra-abdominal abscess rate (3.5% versus 4%, P = .1); however, gastric leaks were more frequent after open surgery (0% versus 2%, P = .02). During a mean 2-year follow-up, 1 additional death occurred from myocardial infarction, 2 years after open BPD-DS.The early and late mortality rate of BPD-DS is low and comparable to that of other bariatric surgeries.

International audience; Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release was measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.

A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTL) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. To pinpoint candidate genes for testing the association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. A genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites. The genome-wide association study conducted to identify the SNPs (meQTL) associated with methylation levels at variable CpG sites revealed 2292 significant associations ( P −11 ) involving 2182 unique meQTLs regulating the methylation levels of 174 variable CpG sites. Two meQTLs disrupting CpG sites located within the collagen-encoding COL11A2 gene were tested for associations with MetS and its components in a cohort of 3021 obese individuals. Rare alleles of these meQTLs showed association with plasma fasting glucose levels. Further analysis conducted on these meQTL suggested a biological impact mediated through the disruption of transcription factor (TF)–binding sites based on the prediction of TF-binding affinities. The current study identified meQTL in the VAT of severely obese men and revealed associations of two COL11A2 meQTL with fasting glucose levels.

Background Biliopancreatic diversion with duodenal switch (BPD-DS) has long been considered as the bariatric procedure with the highest peri-operative and long-term complication rate. However, modern peri-operative care, including laparoscopic and staged-approach, has significantly reduced the complication rate related to this procedure. The goal of this article is to provide an overview of the current outcomes of laparoscopic BPD-DS in a high volume centre. Methods All patients who had a laparoscopic BPD-DS with a hand-sewn anastomosis performed between 2011 and 2015 (N = 566) were reviewed. Data were obtained from our prospectively maintained electronic database and are reported as a Mean ± standard deviation. Results The mean age of the 566 patients was 41 ± 10 years, with 78 % women. Initial body mass index was 49 ± 6 kg/m2. There was no 90-days mortality. Hospital stay was 4.5 ± 3 days. Major 30-days complications occurred in 3.0 % (n = 17) of the patients and minor complications in 2.5 % (N = 14). Excess weight loss was 81 ± 14 % at 12 m, 88 ± 13 % at 24 m, 83 ± 14 % at 36 months. Total body weight loss (kg) was 57 ± 13 kg at 12 months, 63 ± 14 kg at 24 months and 61 ± 17 kg at 36 months. Hemoglobin A1C (HbA1C) dropped from 6.1 ± 1 % to 4.7 ± 0.5 % (p

The lipase A, lysosomal acid, cholesterol esterase enzyme (LIPA) is involved in the hydrolysis of triglycerides (TGs) and cholesteryl esters (CEs) delivered to lysosomes. LIPA deficiency in human causes two distinct phenotypes characterized by intracellular storage of CE and derangements in the control of cholesterol production, namely the Wolman disease (WD) and the CE storage disease (CESD). To test the potential association of LIPA gene polymorphisms with obesity-related metabolic complications, promoter, exons, and intronic flanking regions of the LIPA gene were first sequenced in 25 individuals. From the 14 common polymorphisms identified, 12 tagging single-nucleotide polymorphisms (tSNPs) were genotyped in a cohort of 1,751 obese individuals. After adjustments for the effect of age, sex, diabetes, and medication, the C allele of SNP rs1051338 was associated with lower blood pressure (BP; systolic (SBP) P = 0.004; diastolic (DBP) P = 0.006). Three of the tested SNPs were associated with modifications of the plasma lipid profile. The G/G genotype of rs2071509 was associated with higher high-density lipoprotein cholesterol (HDL-C) levels (P = 0.009) and minor allele of rs1131706 was also associated with higher HDL-C (P = 0.004) and an association between rs3802656 and total cholesterol (total-C)/HDL-C ratio was identified (P = 0.04). These results thus suggest that LIPA polymorphisms contribute to the interindividual variability observed in obesity-related metabolic complications.

Background Biliopancreatic diversion with duodenal switch (DS) has been the standard surgical approach for the treatment of morbidly obese patients at our institution since the early 1990s. The published data, however, have shown the use of the DS to be limited to the treatment of super-morbidly obese patients (body mass index [BMI] ≥50 kg/m 2 ). The aim of the present study was to present our long-term results with the DS in patients with an initial BMI of 2 . Methods This was a retrospective study of all patients with a BMI 2 who had undergone DS from June 1992 to May 2005. The data are reported as the mean ± standard deviation. Results The data from 810 consecutive patients, with a mean initial BMI of 44.2 ± 3.6 kg/m 2 , were reviewed. The mean follow-up was 103 ± 49 months. Major perioperative complications occurred in 5.8% of patients, including 5 deaths (.6%). The initial excess weight loss was 76% ± 22%, and the excess weight loss was >50% in 89% of patients. Malnutrition required readmission in 4.3% and surgical revision in 1.5%. The prevalence of severe albumin deficiency ( Conclusion These results showed that in non super-obese patients, DS was very efficient in terms of weight loss and patient satisfaction. This was associated with a 1.5% risk of revision for malnutrition. However, nutritional deficiencies required frequent readjustment of supplements, particularly for calcium, vitamin A, and vitamin D.

The prevalence of morbid obesity and its associated metabolic complications has risen rapidly in the past decade. Recently, we have established the transcriptome of the visceral adipose tissue of nondiabetic severely obese men with and without metabolic syndrome (MetS) that provided new candidate genes for cardiovascular disease (CVD) risk factors. The oxysterol-binding protein–like protein 11 (OSBPL11) that belongs to the OSBP family of intracellular receptors was one of the genes found to be significantly overexpressed in the MetS group. To determine whether OSBPL11 gene polymorphisms are associated with CVD risk factors and diabetes, OSBPL11 gene promoter and coding regions were sequenced in 25 individuals and six tagging single-nucleotide polymorphisms (SNPs) capturing 85% of gene sequence–derived common genetic variability (minor allele frequency (MAF) > 5%) were genotyped in two samples for a total of 962 obese individuals. Using a multistage experimental design, χ2-tests and logistic regressions were applied to compare genotype frequencies and to compute odds ratios (ORs) for low and high CVD risk groups. Significant associations between rs1055419 and diastolic blood pressure (OR = 0.53; P = 0.01) were found whereas IVS12+95 T>C, a newly discovered SNP, was associated with low-density lipoprotein–cholesterol levels (OR = 1.63; P < 0.001), hyperglycemia/diabetes (OR = 1.48; P < 0.004) as well as with MetS per se (OR = 1.56; P < 0.01). These results suggest that the OSBPL11 gene is involved in cholesterol and glucose metabolism in obese individuals.

This was a retrospective study, performed 10 years after surgery, to compare the results between biliopancreatic diversion (BPD) with distal gastrectomy (DG) versus BPD with duodenal switch (DS).Complete follow-up data were available for 96% of patients, allowing a comparison of weight loss, revision, side effects, and complications at 10 years.After BPD-DS, weight loss was 25% greater than after BPD-DG (46.8 +/- 21.7 kg versus 37.5 +/- 22 kg, respectively; P.0001). The need for revision decreased from 18.5% to 2.7% (P.0001), and the prevalence of vomiting during the previous month was 50% less (23.7-50.6%, P.0001) after BPD-DS compared with after BPD-DG. Late complications were the same for both procedures. Blood analysis showed that, after BPD-DS, the levels of calcium, iron, and hemoglobin were significantly greater and the parathyroid hormone level was lower than after BPD-DG (71.3 +/- 44.2 versus 103.0 +/- 64.0 ng/L, respectively; P.0001).The DS greatly improved the BPD, as it was initially proposed. The use of the DS increased weight loss, decreased the need for revision, resulted in fewer side effects, and improved the absorption of nutrients.

Background: The present retrospective study aims to provide additional evidence supporting the fact that waist circumference, in severe obesity, is not a good clinical marker to identify individuals with the metabolic syndrome or an altered metabolic profile. Methods: Relationships between waist circumference and metabolic profile of pre- (n=165) and postmenopausal (n=43) severely obese women were compared to associations observed in pre- (n=52) and postmenopausal (n=35) moderately obese women. Results: Results showed that abdominal obesity assessed by waist circumference was more highly correlated with fasting glycemia, HDL-cholesterol and the cholesterol/HDL-cholesterol ratio in moderately than in severely obese women, before menopause. After menopause, waist circumference was not a valuable predictor of metabolic abnormalities in both groups. Moreover, when waist circumference was included as a criterion of the metabolic syndrome (as defined by the NCEP ATP III guidelines) in severely obese women, the prevalence of this metabolic condition was over-estimated by 72%. Conclusion: These results emphasize the uselessness of waist circumference to assess the prevalence of the metabolic syndrome or an altered metabolic profile in severely obese women.

To test the potential association of cytosine-phosphate-guanine dinucleotides (CpG)-single-nucleotide polymorphisms (SNPs) located within actin-related protein 2/3 complex subunit 3 (ARPC3), a gene recently linked to adipogenesis and lipid accumulation, with metabolic syndrome (MetS) features in severely obese patients.Prioritized SNPs within the ARPC3 locus were genotyped and tested for associations with MetS features in a cohort of 1,749 obese patients with and without MetS. Association testing with CpG methylation levels was performed in a methylation sub-cohort of 16 obese men.A significant association was found between the CpG-SNP rs3759384 (CT) and plasma triglyceride (TG) levels (false discovery rate-corrected p = 3.5 × 10-2), with 0.6% of the phenotypic variance explained by the CpG-SNP, and with TT homozygotes showing the highest plasma TG levels (1.89 mmol/l). The carriers of the rs3759384 T allele also showed a significant decrease in methylation levels of the ARPC3 promoter-associated CpG site cg10738648 in both visceral adipose tissue and blood. ARPC3 expression levels showed a strong correlation with plasma TG levels (r = 0.70; p = 0.02).The increased plasma TG levels found in homozygous rs3759384 T allele carriers argue for a relevant role of this CpG-SNP in lipid management among obese individuals, which may be driven by an epigenetic-mediated mechanism.

Background Leptin (LEP) and adiponectin (ADIPOQ) genes encode adipokines that are mainly secreted by adipose tissues, involved in energy balance and suspected to play a role in the pathways linking adiposity to impaired glucose and insulin homeostasis. We have thus hypothesized that LEP and ADIPOQ DNA methylation changes might be involved in obesity development and its related complications. The objective of this study was to assess whether LEP and ADIPOQ DNA methylation levels measured in subcutaneous (SAT) and visceral adipose tissues (VAT) are associated with anthropometric measures and metabolic profile in severely obese men and women. These analyses were repeated with DNA methylation profiles from blood cells obtained from the same individuals to determine whether they showed similarities. Methods Paired SAT, VAT and blood samples were obtained from 73 severely obese patients undergoing a bioliopancreatic diversion with duodenal switch. LEP and ADIPOQ DNA methylation and mRNA levels were quantified using bisulfite-pyrosequencing and qRT-PCR respectively. Pearson’s correlation coefficients were computed to determine the associations between LEP and ADIPOQ DNA methylation levels, anthropometric measures and metabolic profile. Results DNA methylation levels at the ADIPOQ gene locus in SAT was positively associated with BMI and waist girth whereas LEP DNA methylation levels in blood cells were negatively associated with body mass index (BMI). Fasting LDL-C levels were found to be positively correlated with DNA methylation levels at LEP-CpG11 and -CpG17 in blood and SAT and with ADIPOQ DNA methylation levels in SAT (CpGE1 and CpGE3) and VAT (CpGE1). Conclusions These results confirm that LEP and ADIPOQ epigenetic profiles are associated with obesity. We also report associations between LDL-C levels and both LEP and ADIPOQ DNA methylation levels suggesting that LDL-C might regulate their epigenetic profiles in adipose tissues. Furthermore, similar correlations were observed between LDL-C and LEP blood DNA methylation levels suggesting a common regulatory pathway of DNA methylation in both adipose tissues and blood. Electronic supplementary material The online version of this article (doi:10.1186/s12881-015-0174-1) contains supplementary material, which is available to authorized users.

Despite well-established variations in the health risks posed by visceral vs. subcutaneous abdominal (SCABD) fat depots, surprisingly little is known on the differences within a given adipose tissue (AT) among severely obese patients displaying varying metabolic dysfunction. We thus compared, by quantitative PCR, the expression profile of a number of genes in the SCABD, omental (OME), and mesenteric (MES) depots of severely obese women with (DYS; n = 25) or without (NDYS; n = 23) a dysmetabolic profile. Fasting insulinemia and HOmeostasis Model Assessment-insulin resistance (HOMA-IR) were higher and plasma adiponectin level lower in DYS women (p

Mature adipocytes can reverse their phenotype to become fibroblast-like cells. This is achieved by ceiling culture and the resulting cells, called dedifferentiated fat (DFAT) cells, are multipotent. Beyond the potential value of these cells for regenerative medicine, the dedifferentiation process itself raises many questions about cellular plasticity and the pathways implicated in cell behavior. This work has been performed with the objective of obtaining new information on adipocyte dedifferentiation, especially pertaining to new targets that may be involved in cellular fate changes. To do so, omental and subcutaneous mature adipocytes sampled from severely obese subjects have been dedifferentiated by ceiling culture. An experimental design with various time points along the dedifferentiation process has been utilized to better understand this process. Cell size, gene and protein expression as well as cytokine secretion were investigated. Il-6, IL-8, SerpinE1 and VEGF secretion were increased during dedifferentiation, whereas MIF-1 secretion was transiently increased. A marked decrease in expression of mature adipocyte transcripts (PPARγ2, C/EBPα, LPL and Adiponectin) was detected early in the process. In addition, some matrix remodeling transcripts (FAP, DPP4, MMP1 and TGFβ1) were rapidly and strongly up-regulated. FAP and DPP4 proteins were simultaneously induced in dedifferentiating mature adipocytes supporting a potential role for these enzymes in adipose tissue remodeling and cell plasticity.

Background: In order to evaluate the impact of severe obesity and its treatment on quality of life (QoL), it would be important to first identify the areas of QoL most likely to be affected by the disease. Methods: We first constructed a list of 187 items potentially related to QoL of patients with morbid obesity. From this list, consecutive candidates for bariatric surgery were asked to identify what they felt were the most significant items and to grade their importance. The item impact was determined from the proportion of patients who identified it as important, and the mean importance score attributed to this item (impact score = frequency X importance). Results: 100 patients (68 female; mean body mass index 51.5 kg/m2; mean age 42) were interviewed. Overall, the impact of morbid obesity was more important in women than in men. The areas of impairment were very similar in both groups, with the important difference that women ranked their dissatisfaction with physical appearance higher than men. The items having the most important impact on QoL clustered into 7 domains: 1) activity/mobility; 2) symptoms; 3) personal hygiene/clothing; 4) emotions; 5) social interactions; 6) sexual life; and 7) eating behavior. Conclusion: The impact of morbid obesity on QoL is not limited to the activity/mobility domain. Morbid obesity contributes to the impairment of all domains of what is usually referred to as "health-related quality of life".

Background: Obesity is well known to be associated with an increased prevalence of metabolic complications. Severe obesity is thus expected to have more important alterations of the metabolic profile than moderate obesity. This study aimed to compare the metabolic profile of pre- and postmenopausal severely obese women with moderately obese women. Methods: First, the metabolic profile of pre- (n=165) and postmenopausal (n=43) severely obese women (body mass index (BMI) ≥40 kg/m2) was compared to that of pre- (n=52) and postmenopausal (n=35) moderately obese women (BMI of 30-40 kg/m2). Thereafter, pre- and postmenopausal severely obese women were divided into two subgroups according to the presence/absence of a dysmetabolic profile. We used for comparison, a group of pre- and postmenopausal moderately obese women without a dysmetabolic profile. Results: The metabolic profile of pre- and postmenopausal severely obese women was less deteriorated than expected when compared to moderately obese women. Moreover, severely obese women with or without a dysmetabolic profile displayed comparable or even lower plasma levels of cholesterol, HDL and LDL-cholesterol, and a lower cholesterol/HDL-cholesterol ratio than moderately obese women (P≤0.05). After menopause, the metabolic profile of severely obese women, dysmetabolic or not, was similar to that of moderately obese women. Blood pressure was, however, higher in severely obese women compared to moderately obese women, only before menopause (P≤0.0001). Conclusion: These results indicate that despite their large accumulation of adipose tissue, most of the severely obese women had a metabolic profile less deteriorated than expected, when compared to moderately obese women.

This study was carried out to determine the effects of the biliopancreatic diversion (BPD), a bariatric surgery applied to the treatment of morbidly obese humans, on energy balance in rats. BPD was performed on a group of male Wistar rats. Body weight and food intake were measured daily throughout the study. Feces were also collected to assess energy losses and the determination of digestible energy. Energy expenditure and body composition were also determined for the 50-day length of the protocol. On the day of killing, the brain, the entire intestinal tract and white and brown adipose tissues were collected and weighed. Expression of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the ARC nucleus were assessed by in situ hybridization. Marked changes in the regulation of energy balance were observed in the BPD-operated rats. A decrease in digestible energy and food intake coupled with an increase in the fecal energy density and protein fecal energy led to an important weight loss in the BPD-operated rats. This weight loss was observed in the loss of fat mass (specifically the white epididymal, inguinal, retroperitoneal and brown adipose tissues). The rats modified their food intake pattern to be able to potentially eat more during the entire day. An increase in the surfaces of all intestinal structures (muscular and mucosal layers) was observed in the BPD-operated rats. The NPY and AgRP expression in the brain were both shown to be greater in the BPD-operated rats than in the control animals. At the beginning of the study, the surgery led to an energy expenditure decrease, which, however, did not persist throughout the study despite the fact that BPD-operated rats exhibited persistent lower fat free masses. BPD led to a noticeable reduction in weight and fat gains in rats, which was in large part owing to a decrease in digestible energy intake led to by the gastrectomy, the intestinal malabsorption inherent to the surgery and to potentially a thermogenesis stimulation that occurred in the second end of the study. The reduction in energy gain occurs despite adaptations to thwart the intestinal malabsorption and the hunger signals from the central nervous system.

This is to introduce a new test "negative alliesthesia" for measuring satiation after bariatric surgery. It is a test that is well known by physiologists but has never been used clinically. It is based on the observation that repeated pleasant gustatory stimuli turn into unpleasantness in the process of satiation.We measured the time it took for a repeatedly ingested sweet stimulus to become first unpleasant (negative alliesthesia) and then intolerable (satiety). At the same time, we measured the degree of pleasure aroused by the sweet stimulus (hedonic rating). The test was given to 9 patients before and 3 and 6 months after the duodenal switch procedure and in 10 morbidly obese patients, three times, 3 months apart.The test showed that negative alliesthesia and satiety were three times faster after surgery. The negative alliesthesia time decreased from 16.0 +/- 3.9 minutes to 5.7 +/- 1.4 minutes (P0.0004). The satiety time decreased from 26.7 +/- 5.0 minutes to 10.7 +/- 1.3 minutes (P0.001). Finally, the hedonic rating for the sweet stimulus decreased from 78.8% +/- 15.7% to 49.9% +/- 13.0% at 3 months and 39.3% +/- 20.6% at 6 months after surgery, without, however, reaching statistical significance.The duodenal switch modified negative alliesthesia. It is too soon to say what place this test may have in bariatric surgery, but its simplicity and ingenuity are attractive.

Both weight loss and gastrointestinal surgery for obesity can cause liver disease, making their role in the treatment of obesity-related liver disease controversial.Six hundred eighty-nine severely obese women (n=551) and men (n=138), BMI=47+/-9 kg.m(-2) (mean+/-SD), without known liver disease, underwent biliopancreatic diversion (BPD) with liver biopsy. Fourteen patients (2%) had cryptogenic cirrhosis, 11 of whom underwent multiple repeat biopsies. After 38+/-18 kg weight loss, 104 of the 689 patients underwent routine second biopsies during reoperations 41+/-25 months after BPD. All biopsy specimens were graded for steatosis, fibrosis, and inflammation by a blinded hepatopathologist.All 689 patients lost weight accompanied by improvements in the metabolic syndrome. Among the 104 patients who underwent reoperation, severe fibrosis (grade 3-5) decreased in 28 whereas mild fibrosis (grade 1-2) appeared in 42. Increased fibrosis was related to low-normal serum albumin, uncontrolled diarrhea, low intake of alcohol, and menopausal status. Fibrosis and inflammation decreased over time (P.01). The 11 patients with cirrhosis exhibited decreased fibrosis from a mean grade 5 to grade 3, as well as reduced inflammation, Mallory bodies, and glycogenated nuclei. Seven patients had disappearance and 2 regression of nodules and fibrous bridging.The metabolic syndrome of obesity is a determinant of liver fibrosis and cirrhosis, treatable by substantial weight loss after malabsorptive surgery.

This prospective study evaluated bone changes after biliopancreatic diversion (BPD) consisting of a distal gastrectomy, a 250 cm alimentary channel, and a 50 cm common channel. Thirty-three consecutive patients had clinical, biochemical, and bone mineral density analysis before surgery and 4 and 10 years after surgery. Iliac crest bone biopsies and special tests including parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-OH2-D), bone-specific alkaline phosphatase (BAP), and osteocalcin were obtained at surgery and 4 years postoperatively. Over the years, with close metabolic surveillance, additional calcium and vitamin D were given as indicated. After BPD, serum levels of calcium and vitamin D were decreased and serum levels of PTH, BAP, and osteocalcin were increased. Bone turnover and mineralization were both increased. Mean osteoid volume (P < 0.0007) and bone formation rate in relation to bone volume (P < 0.02) were increased. Static measures of bone were altered as follows: cortical thickness decreased (P < 0.01) and trabecular bone volume increased (P < 0.01). Ten years after surgery, overall bone mineral density was unchanged at the hip and was decreased by 4% at the lumbar spine. Overall fracture risk, based on the Z score, was unchanged. Preoperative factors predicting bone loss included menopause, smoking, and preexisting osteopenia. An elevated level of 1,25-OH2-D was also found to be a predictor of future bone loss (r = 0.40; P < 0.002). After surgery, a greater increase in bone markers and bone turnover was associated with an increased risk of bone loss. Although elevated osteocalcin levels were associated with overall bone loss (r = 0.52; P < 0.002), lower albumin levels were associated only with bone loss at hip level (r = 0.44; P < 0.02), whereas lower calcium levels were associated only with the loss at the lumbar spine (r = 0.39; P < 0.02). Ten years after surgery, bone loss at the hip continued to depend on albumin levels (r = 0.37; P < 0.03). We concluded that bone was relatively tolerant to the metabolic changes due to BPD. Provided that there is close surveillance for metabolic disturbances, the use of appropriate supplements, and the avoidance of malnutrition, the beneficial effects of surgery far outweigh the risk of postoperative bone disease.

In addition to recognized complications after general surgical operations, those related to laparoscopic malabsorptive bariatric procedures are particular and mandate careful attention and follow-up in the postoperative period to maintain surgical benefits and good health of patients. Today, biliopancreatic diversion with duodenal switch represents the most commonly performed malabsorptive weight loss procedure. It is often offered to patients with high body mass indices suffering from advanced severe clinical obesity and its associated cardiovascular, pulmonary, and metabolic comorbidities. Because the number of bariatric procedures involving gastrointestinal reconfiguration has increased dramatically, it is important for primary and emergency care providers, in addition to general and bariatric surgeons, to be prepared for timely recognition and management of potentially serious postoperative complications and emergencies. This chapter reviews important early and late surgical, non-nutritional complications specific to laparoscopic biliopancreatic diversion with or without duodenal switch.

The choice of first-stage operation in bilio-pancreatic diversion with duodenal switch (BPD-DS) is controversial. There are no published long-term comparisons of one- and two-stage BPD-DS outcomes. During 2001–2009, among 1,762 patients scheduled for BPD-DS 48 had duodenal switch (DS) and 53 sleeve gastrectomy (SG) as first-stage procedures. We compared prospectively updated outcomes of 42 DS (100 % open) and 49 SG (88 % laparoscopic), 13 of whom completed their second stage, to a control group of 91 patients with open one-stage BPD-DS. One-year mean percent excess weight loss (%EWL) was greater after SG than DS (47 ± 19 vs. 39 ± 13 SD; p = 0.01) with earlier nadir (16 ± 10 vs. 45 ± 30 months; p