Background and objective: Studies using metabolomics to study bariatric surgery have shown that amino acids are one of the most changed groups of metabolites after the intervention. However, the surgery-related variation in individual amino acids, as well as the long-term impact and the differences between the types of surgeries, have been poorly studied. The aim of this study was to investigate the changes in circulating amino acids after three types of bariatric surgery up to 36 months after the intervention. Methods: We studied 63 participants diagnosed with T2D at baseline, who received either a sleeve gastrectomy, a Roux-en-Y gastric bypass or a biliopancreatic diversion with duodenal switch. We measured the concentrations of 16 circulating amino acids in fasting plasma before the surgery as well as after 4, 12, 24 and 36 months via liquid chromatography coupled with mass spectrometry (LC-MS/MS). Results: Eleven circulating amino acids were significantly modified by bariatric surgery. Glutamate, leucine and isoleucine showed the greatest decrease. Most of the changes in circulating amino acids occurred within 1 year of the operations. Only one measured plasmatic amino acid (threonine) had a significantly different change pattern according to surgery types. In repeated-measure correlations, changes in circulating amino acids were significantly associated with changes in adiposity and metabolic markers. Conclusions: Bariatric surgery changes the levels of most circulating amino acids, and the effect occurs in the short term without major differences between surgery types. The mechanisms explaining these changes are not elucidated but likely include modifications in amino acid metabolism.

To determine the rate of histology-proven Helicobacter pylori (HP) infection in patients undergoing bariatric surgery and to identify risk factors for HP infection. In a retrospective analysis, patients who underwent bariatric surgery with gastric resection in a single hospital between January 2004 and January 2019 were analyzed. For each patient, a surgical specimen was submitted for anatomopathological examination and analyzed for gastritis or other anomalies. When gastritis was present, HP infection was confirmed by the identification of curvilinear bacilli in conventional histology or by specific immunohistochemical detection of HP antigen. A total of 6388 specimens were available for review (4365 women, 2023 men) with a mean age of 44.9 ± 11.2 years and a mean body mass index (BMI) of 49.3 ± 8.2 kg/m2. Histology-proven HP infection rate was 6.3

Context Body fat distribution is a risk factor for obesity-associated comorbidities, and adipose tissue dysfunction plays a role in this association. In humans, there is a sex difference in body fat distribution, and steroid hormones are known to regulate several cellular processes within adipose tissue. Objective Our aim was to investigate if intra-adipose steroid concentration and expression or activity of steroidogenic enzymes were associated with features of adipose tissue dysfunction in individuals with severe obesity. Methods Samples from 40 bariatric candidates (31 women, 9 men) were included in the study. Visceral (VAT) and subcutaneous adipose tissue (SAT) were collected during surgery. Adipose tissue morphology was measured by a combination of histological staining and semi-automated quantification. Following extraction, intra-adipose and plasma steroid concentrations were determined by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Aromatase activity was estimated using product over substrate ratio, while AKR1C2 activity was measured directly by fluorogenic probe. Gene expression was measured by quantitative PCR. Results VAT aromatase activity was positively associated with VAT adipocyte hypertrophy (P value(adj) < 0.01) and negatively with plasma high-density lipoprotein (HDL)-cholesterol (P value(adj) < 0.01), while SAT aromatase activity predicted dyslipidemia in women even after adjustment for waist circumference, age, and hormonal contraceptive use. We additionally compared women with high and low visceral adiposity index (VAI) and found that VAT excess is characterized by adipose tissue dysfunction, increased androgen catabolism mirrored by increased AKR1C2 activity, and higher aromatase expression and activity indices. Conclusion In women, increased androgen catabolism or aromatization is associated with visceral adiposity and adipose tissue dysfunction.

OBJECTIVES:The study aimed 1) to compare trimester-specific and total gestational weight gain (GWG) between mothers who had undergone biliopancreatic diversion with duodenal switch (BPD) and two control groups of unoperated women and 2) to examine the associations between GWG, intrauterine fetal growth and neonatal birthweight.METHODS:This retrospective study included data collected in medical records of newborns and mothers from 3 groups: the first control group (PP) included mothers (n = 158) with a pre-pregnancy BMI similar to that of the surgical group (n = 63) and the second one (PS) included mothers (n = 85) with a pre-pregnancy BMI corresponding to that of the surgical group prior to BPD or a BMI > 40 kg/m2. Trimester-specific GWG was obtained using linear interpolation and compared to the recommendations.RESULTS:Women exposed to BPD have an increased prevalence of insufficient weight gain in the second and third trimesters as well as for the whole pregnancy in comparison with women in the PP group. The weekly GWG rate in the third trimester was significantly lower in women exposed to BPD, compared to both control groups. Although the newborns of women with previous BPD were significantly smaller during pregnancy and at birth, no association was found with GWG.CONCLUSION:Women exposed to BPD are at substantial risk of insufficient GWG, however, mechanisms and long-term impacts require further investigation.

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.

Insulin-like growth factor-binding protein (IGFBP)-2 is a circulating biomarker of cardiometabolic health. Here, we report that circulating IGFBP-2 concentrations robustly increase after different bariatric procedures in humans, reaching higher levels after biliopancreatic diversion with duodenal switch (BPD-DS) than after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). This increase is closely associated with insulin sensitization. In mice and rats, BPD-DS and RYGB operations also increase circulating IGFBP-2 levels, which are not affected by SG or caloric restriction. In mice, Igfbp2 deficiency significantly impairs surgery-induced loss in adiposity and early improvement in insulin sensitivity but does not affect long-term enhancement in glucose homeostasis. This study demonstrates that the modulation of circulating IGFBP-2 may play a role in the early improvement of insulin sensitivity and loss of adiposity brought about by 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.

The clinical benefit of bariatric surgery in patients with severe obesity and established coronary artery disease (CAD) is unclear. We aimed to compare the cardiovascular outcomes of severely obese CAD patients with and without bariatric surgery. Patients with a history of myocardial revascularization documented prior to bariatric surgery were identified from a dedicated database with prospectively collected outcomes. These patients were matched 1 to 1 with CAD patients who had prior revascularization but who did not undergo bariatric surgery. The primary outcomes were death (cardiac and non-cardiac) and major adverse cardio-cerebral events (MACCE), including death, myocardial infarction (MI), stroke, and repeat myocardial revascularization throughout follow-up. After propensity score matching, 116 bariatric patients were matched with 116 control patients. Ninety-eight had a history of coronary artery bypass surgery and 134 had a previous percutaneous coronary intervention. After a median follow-up of 8.9 (6.3–14.2) years, MACCE was significantly lower in the bariatric group (HR 0.65; 95% CI 0.42–1.00; P = 0.049) driven by a significant reduction in non-cardiac mortality (HR 0.49; 95% CI 0.23–1.00; P = 0.049). There was no significant difference in the rates of all-cause death (HR 0.58; 95% CI 0.33–1.01; P = 0.056), cardiovascular death (HR 0.77; 95% CI 0.31–1.85; P = 0.55), MI (HR 1.09; 95% CI 0.47–2.58; P = 0.85), stroke (HR 1.47; 95% CI 0.24–11.2; P = 0.67), and repeat myocardial revascularization (HR 0.56; 95% CI 0.27–1.13; P = 0.11). Although bariatric surgery in obese CAD patients may reduce the composite MACCE endpoint during long-term follow-up, this effect seems unrelated to cardiovascular outcomes.

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 There is solid evidence that obesity induces the acceleration of liver epigenetic aging. However, unlike easily accessible blood or subcutaneous adipose tissue, little is known about the impact of obesity on epigenetic aging of metabolically active visceral adipose tissue (VAT). Herein, we aimed to test whether obesity accelerates VAT epigenetic aging in subjects with severe obesity. Results A significant and positive correlation between chronological age and epigenetic age, estimated with a reduced version of the Horvath’s epigenetic clock, was found in both blood ( r = 0.78, p = 9.4 × 10 −12 ) and VAT ( r = 0.80, p = 1.1 × 10 −12 ). Epigenetic age acceleration, defined as the residual resulting from regressing epigenetic age on chronological age, was significantly correlated with body mass index (BMI) in VAT ( r = 0.29, p = 0.037). Multivariate linear regression analysis showed that, after adjusting for chronological age, sex and metabolic syndrome status, BMI remained significantly associated with epigenetic age acceleration in VAT (beta = 0.15, p = 0.035), equivalent to 2.3 years for each 10 BMI units. Binomial logistic regression showed that BMI-adjusted epigenetic age acceleration in VAT was significantly associated with a higher loss of excess body weight following biliopancreatic diversion with duodenal switch surgery (odds ratio = 1.21; 95% CI = 1.04–1.48; p = 0.03). Conclusions Epigenetic age acceleration increases with BMI in VAT, but not in blood, as previously reported in liver. These results suggest that obesity is associated with epigenetic age acceleration of metabolically active tissues. Further studies that deepen the physiological relevance of VAT epigenetic aging will help to better understand the onset of metabolic syndrome and weight loss dynamics following bariatric surgery.

Biliopancreatic diversion with duodenal switch (BPD-DS) decreases vitamin D and calcium absorption, which may result in secondary hyperparathyroidism. This study aimed at evaluating the prevalence of vitamin D deficiency and secondary hyperparathyroidism before and after BPD-DS.

Background: With the increase in life expectancy together with the obesity epidemic, there has been an increase in older patients undergoing bariatric surgery. There are conflicting opinions regarding the safety of performing bariatric procedures on older patients. The purpose of this study was to compare the safety of laparoscopic sleeve gastrectomy (SG) and Roux-en-Y-gastric bypass (RYGB) for older patients.

BACKGROUND Blood pressure measurement in severe obesity may be technically challenging as the cuff of the device may not fit adequately around the upper arm. The aim of the study was to assess the agreement between intra-arterial blood pressure values (gold standard) compared with forearm blood pressure measurements in severely obese patients in different arm positions. METHODS Thirty-three severely obese patients and 21 controls participated in the study. Pairs of intra-arterial blood pressures were compared with simultaneous forearm blood pressure measurement using an oscillometric device in 4 positions: (i) supine, (ii) semi-fowler with the forearm resting at heart level, (iii) semi-fowler with the arm downward, and (iv) semi-fowler with the arm raised overhead. Degree of agreement between measurements was assessed. RESULTS Overall, correlations of systolic and diastolic blood pressure measurements between the gold standard and forearm blood pressure were 0.95 (n = 722; P < 0.001) and 0.89 (n = 482; P < 0.001), respectively. Systolic blood pressure measured using the forearm approach in the supine and the semi-fowler positions with arm downward showed the best agreement when compared with the gold standard (-4 ± 11 (P < 0.001) and 2 ± 14 mm Hg (P = 0.19), respectively). In the control group, better agreement was found between the supine and semi-fowler positions with the arm resting at heart level (1 ± 9 mm Hg (P = 0.29) and -3 ± 10 mm Hg (P = 0.01), respectively). CONCLUSIONS Forearm systolic blood pressure consistently agreed with the gold standard in the supine position. This method can be of use in clinical settings when upper-arm measurement is challenging in severe obesity.

BACKGROUND:Sleeve gastrectomy (SG) has become the predominant bariatric surgery worldwide. However, the surgical management in case of failure is still debated. OBJECTIVES:To evaluate the risks and benefits of converting SG to biliopancreatic diversion with duodenal switch (BPD-DS) for suboptimal outcome after SG. SETTING:University-affiliated tertiary care center. METHODS:We included all patients who underwent a laparoscopic second-stage duodenal switch (DS) for weight loss failure after SG and had a minimal follow-up of 2 years. Patients were matched 1:1 for age, sex, body mass index, and year of surgery with a group of patients who underwent a single-stage laparoscopic BPD-DS. Data were obtained from our prospective electronic database and are reported as the mean ± standard deviation, comparing 2- versus 1-stage BPD-DS. RESULTS:A total of 118 patients were included (59 in each group). There was no significant difference in initial body mass index (53.8 ± 9.7 versus 52.7 ± 7.8 kg/m2, P = .4), age (44.0 ± 10.2 versus 43.4 ± 9.6 yr, P = .5), and sex ratio (37 female/22 male, P > .9) between the 2 groups. Mean follow-up was 59.9 ± 27 months, with an 85% (n = 100) follow-up rate. Patients were converted to BPD-DS after a mean 24.4 ± 10.2 months. There was no short- or long-term mortality. Major 90-days complications occurred in 2%, 5%, and 5% after SG, second-stage DS and single-stage BPD-DS, respectively (P > .05). At the time of conversion, the excess weight loss for SG was 39 ± 17% and total weight loss was 20 ± 9%. After DS or single-stage BPD-DS, the excess weight loss was 74.8 ± 18% versus 87.9 ± 18% at 1 year (n = 107, P = .00021), 80.2 ± 17% versus 92.3 ± 14% at 2 years (n = 100, P = .002), and 80.2 ± 18% versus 87.2 ± 16% at 3 years (n = 70, P = .6). Total weight loss was 38.7 ± 9% versus 44.5 ± 8% at 1 year (P = .0004), 41.2 ± 9% versus 46.8 ± 7% at 2 years (P = .001), and 42.3 ± 9% versus 45.1 ± 9% at 3 years (P = .2). The incidence of type 2 diabetes and hypertension before surgery were 61% versus 54% and 58% versus 47%. Remission rate for type 2 diabetes increased from 59% to 94% after second-stage DS (P = .001), which is identical to first-stage BPD-DS (94%). Remission of hypertension increased from 42% to 77% after second-stage DS (P = .03) and was 71% after first-stage BPD-DS (P = .8). CONCLUSION:Second-stage DS is an effective option for the management of suboptimal outcomes of SG, with an additional 41% excess weight loss and 35% remission rate for type 2 diabetes. At 3 years, the global outcomes of staged approach did not significantly differ from single-stage BPD-DS; however, longer-term outcomes are still needed.