The impact of bariatric surgery on metabolic and inflammatory status are reflected in the epigenetic profile and telomere length mediated by the changes in the metabolic status of the patients. This study compared the telomere length of children born before versus after maternal bariatric surgery as a surrogate to test the influence of the mother’s metabolic status on children’s telomere length. DNA methylation telomere length (DNAmTL) was estimated from Methylation-EPIC BeadChip array data from a total of 24 children born before and after maternal bariatric surgery in the greater Quebec City area. DNAmTL was inversely associated with chronological age in children (r = − 0.80, p < 0.001) and significant differences were observed on age-adjusted DNAmTL between children born before versus after the maternal bariatric surgery. The associations found between body mass index and body fat percentage with DNAmTL in children born after the surgery were influenced by maternal triglycerides, TG/HDL-C ratio and TyG index. This study reports the impact of maternal bariatric surgery on offspring telomere length. The influence of maternal metabolic status on the association between telomere length and markers of adiposity in children suggests a putative modulating effect of bariatric surgery on the cardiometabolic risk in offspring.

Background: Severely obese patients have decreased cardiorespiratory fitness (CRF) and poor functional capacity. Bariatric surgerye 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/m(2), 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 < 0.0001) in both groups but more importantly in the exercise group (exercise group: from 18.6 +/- 4.2 to 23.2 +/- 5.7 mL/kg/min; control group: from 17.4 +/- 2.3 to 19.7 +/- 2.4 mL/kg/min; P value, group x time = 0.01). In the exercise group, determinants of absolute VO2peak (L/min) were peak exercise ventilation, oxygen pulse, and heart rate reserve (r(2) = 0.92; P < 0.0001), whereas determinants of VO2peak indexed to body mass (mL/kg/min) were peak exercise ventilation and early-to-late filling velocity ratio (r(2) = 0.70; P < 0.0001). Conclusions: A 12-week supervised training program has an additive benefit on cardiorespiratory fitness for patients who undergo bariatric surgery.

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 < 0.0001) but this decrease was not sustained at 12 months (11.1 (3.9–32.8) nmol/L, p = 0.8). When the patients were separated into tertiles according to Lp(a) levels at baseline, we observed that the Lp(a) reduction at 12 months after BPD-DS surgery remained significant but modest in patients of the top Lp(a) tertile. Our results suggest that BPD-DS surgery modestly reduces Lp(a) levels in the short term (6 months) in patients with severe obesity but this improvement is sustained over time only in patients with higher Lp(a) levels.

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.

Abstract Objective The aim of this study was to assess long-term glycemic outcomes in insulin-treated patients with type 2 diabetes (T2D) following biliopancreatic diversion with duodenal switch (BPD-DS) and identify predictors of sustained diabetes remission or relapse. Background BDP-DS confers the highest rate of T2D remission compared to other bariatric procedures. Previous studies suggest that type of anti-diabetic therapy used prior to surgery and duration of disease influence post-surgical glycemic outcomes. Short-term, progressive improvement in insulin sensitivity and beta-cell function following metabolic surgery in patients with non-insulin treated T2D has been demonstrated. Whether patients with more advanced disease can achieve sustained remission remains unclear. Methods Data from 141 patients with insulin-treated T2D who underwent BPD-DS between 1994 and 2006 with 10 years of follow up data was collected from a prospective electronic database. Results Follow-up was available in 132 patients (91%). At ten years following 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 non-remission at 10 years. Conclusions The BPD-DS maintains remission at 10 years post-operatively 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.

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. (C) 2019 Elsevier Inc. All rights reserved.

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/m(2)), 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 < 0.0001) and by 16.4% at 12 months after BPD-DS (342.9 +/- 152.3 pg/mL to 286.8 +/- 182.6 pg/mL, P = 0.04). ATX concentrations were unchanged during follow-up in the control group (P = 0.4), and not influenced by short-term CR. In patients with severe obesity, bariatric surgery induced a rapid and sustained decrease in plasma ATX levels. Acute changes in ATX may not be explained by bariatric surgery-induced CR.

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.

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. (C) 2018 American Society for Metabolic and Bariatric Surgery. All rights reserved.

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.

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 < 2.22 x 10(-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.

Morbid obesity is now recognized as a multifactorial and complex societal problem ( 1 Brauer P. Connor Gorber S. Shaw E. et al. Recommendations for prevention of weight gain and use of behavioural and pharmacologic interventions to manage overweight and obesity in adults in primary care. CMAJ. 2015; 187: 184-195 Crossref PubMed Scopus (94) Google Scholar ). Although lifestyle changes remain a key factor in the treatment of severe obesity, bariatric surgery is considered by the World Health Organization to be the only approach leading to significant, long-term beneficial outcomes in this population ( 2 Obesity: Preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000; 894: 1 Google Scholar ). Therefore it is worth emphasizing that the past decades have been marked by very significant changes in terms of surgical approaches, but most importantly, they brought about the recognition of obesity as a chronic disease ( 3 Allison D.B. Downey M. Atkinson R.L. et al. Obesity as a disease: A white paper on evidence and arguments commissioned by the Council of the Obesity Society. Obesity (Silver Spring). 2008; 16: 1161-1177 Crossref PubMed Scopus (163) Google Scholar ). As general surgeons by training, it is an honour for us to provide an introductory perspective to this Special Issue of the Canadian Journal of Diabetes dedicated to bariatric surgery. Clinical practice in obesity surgery has substantially evolved over time. This introduction provides an overview of the beginnings of bariatric surgery in North America and in Canada in particular. It also provides a more personal view of bariatric surgery, consistent with the fact that some of the articles in this Special Issue are written from the surgeon's perspective.

Background: Biliopancreatic diversion with Duodenal Switch (BPD-DS) confers the highest rate of type 2 diabetes (T2D) remission amongst metabolic surgeries. Studies suggest type of T2D therapy prior to surgery may influence outcomes.

Obesity-associated systemic hypertension (HTN) and obstructive sleep apnea (OSA) have multiple pathophysiological pathways including ectopic fat deposition, inflammation, altered adipokine profile, and increased sympathetic nervous activity. We characterized these potential mechanisms in severely obese patients with or without HTN and OSA. We also compared changes of these mechanisms at 12 months following biliopancreatic diversion with duodenal switch (BPD-DS) surgery according to HTN and OSA resolution.

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. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions. Results. Four clusters gathered genes with similar expression between day 4 to day 7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE, PLIN1, DGAT2, PNPLA2, ADIPOQ, CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for proteins implicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A, KITLG, and FGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1, COL1A2, and COL6A3, MMP1, and TGFB1). Conclusion. Dedifferentiation is associated with downregulation of transcripts encoding proteins involved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cell cycle.

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 (K m 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.

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.