Medication and supplement pharmacokinetic changes following bariatric surgery: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements. METHODS: Systematic searches of bibliographic databases were conducted to identify studies. Pooled effect estimates from different surgical procedures were calculated using a random-effects model. RESULTS: Quantitative data were synthesized from 58 studies including a total of 1985 participants. Whilst 40 medications and 6 supplements were evaluated across these studies, heterogeneity and missing information reduced the scope of the meta-analysis to the following medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. There were no significant differences in PK parameters post-surgery for the drugs atorvastatin and omeprazole, and supplements calcium, ferritin, and zinc supplements. Paracetamol showed reduced clearance (mean difference [MD] = -15.56 L/hr, p = 0.0002, I2 = 67%), increased maximal concentration (MD = 6.90 µg/ml, p = 0.006, I2 = 92%) and increased terminal elimination half-life (MD = 0.49 hr, p < 0.0001, I2 = 3%) post-surgery. The remaining 36 medications and 2 supplements were included in a systematic review. Overall, 18 of the 53 drugs and supplements showed post-operative changes in PK parameters. CONCLUSION: This study demonstrates heterogeneity in practice and could not reach conclusive findings for most PK parameters. Prospective studies are needed to inform best practice and enhance patient healthcare and safety following bariatric surgery.

Investigating the alterations of endocannabinoidome signaling in the human small intestine in the context of obesity and type 2 diabetes.

Background: Human studies have linked obesity-related diseases, such as type-2 diabetes (T2D), to the modulation of endocannabinoid signaling. Cannabinoid CB1 and CB2 receptor activation by the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA), both derived from arachidonic acid, play a role in homeostatic regulation. Other long chain fatty acid-derived endocannabinoid-like molecules have extended the metabolic role of this signaling system through other receptors. In this study, we aimed to assess in depth the interactions between the circulating and intestinal tone of this extended eCB system, or endocannabinoidome (eCBome), and their involvement in the pathogenesis of diabetes. Methods: Plasma and ileum samples were collected from subjects with obesity and harboring diverse degrees of insulin resistance or T2D, who underwent bariatric surgery. The levels of eCBome mediators and their congeners were then assessed by liquid chromatography coupled to tandem mass spectrometry, while gene expression was screened with qPCR arrays. Findings: Intestinal and circulating levels of eCBome mediators were higher in subjects with T2D. We found an inverse correlation between the intestinal and circulating levels of monoacylglycerols (MAGs). Additionally, we identified genes known to be implicated in both lipid metabolism and intestinal function that are altered by the context of obesity and glucose homeostasis. Interpretation: Although the impact of glucose metabolism on the eCBome remains poorly understood in subjects with advanced obesity state, our results suggest a strong causative link between altered glucose homeostasis and eCBome signaling in the intestine and the circulation.

Acceptability and Feasibility of the Telehealth Bariatric Behavioral Intervention to Increase Physical Activity Before Bariatric Surgery: A Single-Case Experimental Study (Part I).

BACKGROUND: Physical activity (PA) can play an important role in optimizing metabolic/bariatric surgery (MBS) outcomes. However, many MBS patients have difficulty increasing PA, necessitating the development of theory-driven counseling interventions. This study aimed to (1) assess the feasibility and acceptability of the TELEhealth BARIatric behavioral intervention (TELE-BariACTIV) trial protocol/methods and intervention, which was designed to increase moderate-to-vigorous intensity physical activity (MVPA) in adults awaiting MBS and (2) estimate the effect of the intervention on MVPA. METHODS: This trial used a repeated single-case experimental design. Twelve insufficiently active adults awaiting MBS received 6 weekly 45-min PA videoconferencing counseling sessions. Feasibility and acceptability data (i.e., refusal, recruitment, retention, attendance, and attrition rates) were tracked and collected via online surveys, and interviews. MVPA was assessed via accelerometry pre-, during, and post-intervention. RESULTS: Among the 24 patients referred to the research team; five declined to participate (refusal rate = 20.8%) and seven were ineligible or unreachable. The recruitment rate was 1.2 participants per month between 2021-09 and 2022-07. One participant withdrew during the baseline phase, and one after the intervention (retention rate = 83.3%). No participant dropouts occurred during the intervention and 98.6% of sessions were completed. Participants' anticipated and retrospective acceptability of the intervention was 3.2/4 (IQR, 0.5) and 3.0/4 (IQR, 0.2), respectively. There was a statistically significant increase in MVPA [Tau-U = 0.32(0.11; 0.51)] from pre- to post-intervention. CONCLUSION: Despite a low recruitment rate, which could be explained by circumstances (COVID-19 pandemic), results support feasibility, acceptability, and preliminary efficacy of the TELE-Bari-ACTIV intervention for increasing MVPA in patients awaiting MBS.

Attitudes and Behaviors towards Food and Weight in Late Pregnancy: A Comparative Approach between Individuals with and without Previous Bariatric Surgery.

The aims of this study were to compare, between pregnant individuals with and without bariatric surgery: (1) eating behaviors, (2) intuitive eating components and, (3) attitudes towards weight gain. This retrospective study included data collected in healthy pregnant individuals with and without previous bariatric surgery who were recruited at the Centre Hospitalier Universitaire (CHU) de Québec-Université Laval. Pregnant individuals who underwent bariatric surgery (biliopancreatic bypass with duodenal switch [n = 14] or sleeve gastrectomy [n = 5]) were individually matched, for age (±0.4 years) and body mass index (BMI) (±0.3 kg/m2), with pregnant individuals who have not received bariatric surgery. In the second trimester, participants completed the Three Factor Eating Questionnaire (TFEQ) and the Intuitive Eating Scale 2 (IES-2). In the third trimester, participants completed the French version of the Pregnancy Weight Gain Attitude Scale assessing attitudes towards weight gain. Pregnant individuals who have had bariatric surgery had a higher score for flexible restraint and a lower score for situational susceptibility to disinhibition compared to individuals who have not had undergone bariatric surgery (2.89 ± 1.15 vs. 1.95 ± 1.31; p = 0.04 and 1.11 ± 1.29 vs. 2.79 ± 1.44, respectively; p < 0.001). Regarding intuitive eating, pregnant individuals who experienced bariatric surgery had a higher score for reliance on internal hunger and satiety cues and a lower one for unconditional permission to eat compared with those who had not experienced bariatric surgery (3.99 ± 0.81 vs. 3.30 ± 1.03; p = 0.02 and 3.28 ± 0.54 vs. 3.61 ± 0.68, respectively; p = 0.03). No difference in attitudes towards weight gain was observed between groups. Overall, pregnant individuals who had undergone bariatric surgery had different eating behaviors and intuitive eating components compared to pregnant individuals without bariatric surgery. These results need to be confirmed in further studies with larger sample sizes.

IL-6 Trans-Signaling Is Increased in Diabetes, Impacted by Glucolipotoxicity, and Associated With Liver Stiffness and Fibrosis in Fatty Liver Disease.

Many people living with diabetes also have nonalcoholic fatty liver disease (NAFLD). Interleukin-6 (IL-6) is involved in both diseases, interacting with both membrane-bound (classical) and circulating (trans-signaling) soluble receptors. We investigated whether secretion of IL-6 trans-signaling coreceptors are altered in NAFLD by diabetes and whether this might associate with the severity of fatty liver disease. Secretion patterns were investigated with use of human hepatocyte, stellate, and monocyte cell lines. Associations with liver pathology were investigated in two patient cohorts: 1) biopsy-confirmed steatohepatitis and 2) class 3 obesity. We found that exposure of stellate cells to high glucose and palmitate increased IL-6 and soluble gp130 (sgp130) secretion. In line with this, plasma sgp130 in both patient cohorts positively correlated with HbA1c, and subjects with diabetes had higher circulating levels of IL-6 and trans-signaling coreceptors. Plasma sgp130 strongly correlated with liver stiffness and was significantly increased in subjects with F4 fibrosis stage. Monocyte activation was associated with reduced sIL-6R secretion. These data suggest that hyperglycemia and hyperlipidemia can directly impact IL-6 trans-signaling and that this may be linked to enhanced severity of NAFLD in patients with concomitant diabetes. ARTICLE HIGHLIGHTS: IL-6 and its circulating coreceptor sgp130 are increased in people with fatty liver disease and steatohepatitis. High glucose and lipids stimulated IL-6 and sgp130 secretion from hepatic stellate cells. sgp130 levels correlated with HbA1c, and diabetes concurrent with steatohepatitis further increased circulating levels of all IL-6 trans-signaling mediators. Circulating sgp130 positively correlated with liver stiffness and hepatic fibrosis. Metabolic stress to liver associated with fatty liver disease might shift the balance of IL-6 classical versus trans-signaling, promoting liver fibrosis that is accelerated by diabetes.

Factors Associated with Excess Skin After Bariatric Surgery: a Mixed-Method Study.

PURPOSE: After metabolic and bariatric surgery (MBS), many patients have excess skin (ES), which can cause inconveniences. Identifying factors related to ES quantity and inconveniences is crucial to inform interventions. The aim of this study was to identify sociodemographic, physical, psychosocial, and behavioral factors associated with ES quantity and inconveniences. MATERIALS AND METHODS: A mixed-method study with a sequential explanatory design was conducted with 124 adults (92% women, Mage 46.5 ± 9.9 years, Mtime post-MBS 34.2 ± 27.6 months). During phase I, ES quantity (arms, abdomen, thighs) and inconveniences and sociodemographic, anthropometric, clinical, and behavioral outcomes were assessed. In phase II, 7 focus groups were performed with 37 participants from phase I. A triangulation protocol was completed to identify convergences, complementarities, and dissonances from quantitative and qualitative data. RESULTS: Quantitative data indicate only ES quantity on arms was associated with ES inconveniences on arms (r = .36, p < .01). Total ES quantity was associated with maximal body mass index (BMI) reached pre-MBS (r = .48, p < .05) and current BMI (r = .35, p < .05). Greater ES inconvenience was associated with higher social physique anxiety and age (R2 = .50, p < .01). Qualitative data were summarized into 4 themes: psychosocial experiences living with ES, physical ailments due to ES, essential support and unmet needs, and beliefs of ES quantity causes. CONCLUSION: Measured ES quantity is related to higher BMI, but not reported inconveniences. Greater self-reported ES quantity and inconveniences were associated with body image concerns.

Prevalence of Helicobacter pylori Infection in Bariatric Surgery Patients.

OBJECTIVE: To determine the rate of histology-proven Helicobacter pylori (HP) infection in patients undergoing bariatric surgery and to identify risk factors for HP infection. METHODS: 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. RESULTS: 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% (n = 405). There was no significant difference in sex, BMI, and body weight between HP + and HP - patients. Logistic regressions identified age as a risk factor for HP infection in this population (OR 1.02, p < 0.0001, CI 95% 1.01-1.03 for every 1-year increase, OR 1.26, p < 0.0001, CI 95% 1.14-1.40 for every 10-year increase). CONCLUSIONS: The rate of histology-proven HP infection is low in patients with severe obesity who present for bariatric surgery and is associated with age.

Hypoabsorptive surgeries cause limb-dependent changes in the gut endocannabinoidome and microbiome in association with beneficial metabolic effects.

OBJECTIVE: To determine whether the metabolic benefits of hypoabsorptive surgeries are associated with changes in the gut endocannabinoidome (eCBome) and microbiome. METHODS: Biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) were performed in diet-induced obese (DIO) male Wistar rats. Control groups fed a high-fat diet (HF) included sham-operated (SHAM HF) and SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW). Body weight, fat mass gain, fecal energy loss, HOMA-IR, and gut-secreted hormone levels were measured. The levels of eCBome lipid mediators and prostaglandins were quantified in different intestinal segments by LC-MS/MS, while expression levels of genes encoding eCBome metabolic enzymes and receptors were determined by RT-qPCR. Metataxonomic (16S rRNA) analysis was performed on residual distal jejunum, proximal jejunum, and ileum contents. RESULTS: BPD-DS and SADI-S reduced fat gain and HOMA-IR, while increasing glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels in HF-fed rats. Both surgeries induced potent limb-dependent alterations in eCBome mediators and in gut microbial ecology. In response to BPD-DS and SADI-S, changes in gut microbiota were significantly correlated with those of eCBome mediators. Principal component analyses revealed connections between PYY, N-oleoylethanolamine (OEA), N-linoleoylethanolamine (LEA), Clostridium, and Enterobacteriaceae_g_2 in the proximal and distal jejunum and in the ileum. CONCLUSIONS: BPD-DS and SADI-S caused limb-dependent changes in the gut eCBome and microbiome. The present results indicate that these variables could significantly influence the beneficial metabolic outcome of hypoabsorptive bariatric surgeries.

Association between Circulating Amino Acids and COVID-19 Severity.

The severity of the symptoms associated with COVID-19 is highly variable, and has been associated with circulating amino acids as a group of analytes in metabolomic studies. However, for each individual amino acid, there are discordant results among studies. The aims of the present study were: (i) to investigate the association between COVID-19-symptom severity and circulating amino-acid concentrations; and (ii) to assess the ability of circulating amino-acid levels to predict adverse outcomes (intensive-care-unit admission or hospital death). We studied a sample of 736 participants from the Biobanque Québécoise COVID-19. All participants tested positive for COVID-19, and the severity of symptoms was determined using the World-Health-Organization criteria. Circulating amino acids were measured by HPLC-MS/MS. We used logistic models to assess the association between circulating amino acids concentrations and the odds of presenting mild vs. severe or mild vs. moderate symptoms, as well as their accuracy in predicting adverse outcomes. Patients with severe COVID-19 symptoms were older on average, and they had a higher prevalence of obesity and type 2 diabetes. Out of 20 amino acids tested, 16 were significantly associated with disease severity, with phenylalanine (positively) and cysteine (inversely) showing the strongest associations. These associations remained significant after adjustment for age, sex and body mass index. Phenylalanine had a fair ability to predict the occurrence of adverse outcomes, similar to traditionally measured laboratory variables. A multivariate model including both circulating amino acids and clinical variables had a 90% accuracy at predicting adverse outcomes in this sample. In conclusion, patients presenting severe COVID-19 symptoms have an altered amino-acid profile, compared to those with mild or moderate symptoms.

Bariatric Surgery Should Be Offered to Active-Duty Military Personnel: a Retrospective Study of the Canadian Armed Forces' Experience.

PURPOSE: Like most Western armies, obesity affects Canadian Armed Forces (CAF) personnel. Bariatric surgery is an effective treatment for obesity. However, this is not yet accepted for active-duty soldiers in most countries. The CAF have approved bariatric surgery since 2005. Our aim is to assess weight loss, resolution of obesity-related comorbidities, and impacts of bariatric surgery on military careers. MATERIALS AND METHODS: We retrospectively reviewed the perioperative data, long-term bariatric results, and military outcomes of 108 CAF active-duty military personnel who underwent bariatric surgery in Canada over a 61-month period. RESULTS: The cohort was predominantly male (66.7%) with a mean preoperative body mass index (BMI) of 43.6 ± 5.8 kg/m2. Roux-Y gastric bypass was performed in 59 patients, sleeve gastrectomy in 29, and gastric banding in 20. All the surgeries were performed laparoscopically. The total body weight loss at the last follow-up visit was 22.5 ± 11.0%. Remission or improvement of hypertension was observed in 91.2%, diabetes in 85.7%, gastroesophageal reflux disorder (GERD) in 43.6%, sleep apnea in 43.1%, and dyslipidemia in 42.9%. One patient (0.9%) was medically released due to postoperative complications. Fifteen patients (13.9%) were deployed postoperatively. The combined deployable and possibly deployable statuses increased from 35.4% preoperatively to 47.9% postoperatively. CONCLUSION: This is the largest series of bariatric surgeries performed in active-duty military personnel. Bariatric surgery is effective and safe and improves deployability without impairing military careers. These results are relevant to the military of many industrialized countries. Bariatric surgery should be considered for all active-duty military personnel who meet surgical criteria for the treatment of obesity.

Human gut microbiota after bariatric surgery alters intestinal morphology and glucose absorption in mice independently of obesity.

OBJECTIVE: Bariatric surgery is an effective treatment for type 2 diabetes (T2D) that changes gut microbial composition. We determined whether the gut microbiota in humans after restrictive or malabsorptive bariatric surgery was sufficient to lower blood glucose. DESIGN: Women with obesity and T2D had biliopancreatic diversion with duodenal switch (BPD-DS) or laparoscopic sleeve gastrectomy (LSG). Faecal samples from the same patient before and after each surgery were used to colonise rodents, and determinants of blood glucose control were assessed. RESULTS: Glucose tolerance was improved in germ-free mice orally colonised for 7 weeks with human microbiota after either BPD-DS or LSG, whereas food intake, fat mass, insulin resistance, secretion and clearance were unchanged. Mice colonised with microbiota post-BPD-DS had lower villus height/width and crypt depth in the distal jejunum and lower intestinal glucose absorption. Inhibition of sodium-glucose cotransporter (Sglt)1 abrogated microbiota-transmissible improvements in blood glucose control in mice. In specific pathogen-free (SPF) rats, intrajejunal colonisation for 4 weeks with microbiota post-BPD-DS was sufficient to improve blood glucose control, which was negated after intrajejunal Sglt-1 inhibition. Higher Parabacteroides and lower Blautia coincided with improvements in blood glucose control after colonisation with human bacteria post-BPD-DS and LSG. CONCLUSION: Exposure of rodents to human gut microbiota after restrictive or malabsorptive bariatric surgery improves glycaemic control. The gut microbiota after bariatric surgery is a standalone factor that alters upper gut intestinal morphology and lowers Sglt1-mediated intestinal glucose absorption, which improves blood glucose control independently from changes in obesity, insulin or insulin resistance.

Preoperative predictors of type 2 diabetes remission after bilio-pancreatic diversion with duodenal switch.

BACKGROUND: Many patients achieve short-term type 2 diabetes (T2D) remission after bariatric surgery, but relapses are common. Diabetes outcomes after bariatric surgery vary across procedures and populations. T2D remission scores are simple clinical tools developed to predict remission after bariatric surgery. However, they have never been tested after Biliopancreatic diversion with duodenal switch (BPD-DS). OBJECTIVES: The aim of this study was to compare the predictive value of T2D remission scores and preoperative diabetes characteristics in predicting T2D remission after BPD-DS. SETTING: Quebec Heart and Lung Institute - Laval University. METHODS: We retrospectively identified 918 patients with preoperative T2D who had undergone BPD-DS. Retrospective chart review was performed and variables used to calculate predictive scores were captured. T2D status was assessed annually for up to 10 years postop. Predictive values for each score (DiarRem, Ad Diarem, and Diabetter) and single preoperative diabetes characteristics used to construct these algorithms were evaluated by area under receiver operating characteristic curves (AUC). RESULTS: Diabetter showed greater performance for prediction of durable diabetes remission than other algorithms with acceptable discriminative ability (AUC between .69 and .79), but was not superior to T2D duration as a single predictor (P = .24 and P = .18). At 10 years, T2D duration had a better discriminative ability for the prediction of T2D remission than all 3 predictive models (AUC = .85, P < .05). CONCLUSIONS: Better chances for T2D remission following BPD-DS are associated with a shorter duration or T2D before surgery. Duration of T2D alone offers an excellent predictive ability and is a convenient alternative to diabetes remission scores to estimate chances of long-term diabetes remission after BPD-DS.

Acceptability and Feasibility of the Telehealth Bariatric Behavioral Intervention to Increase Physical Activity: Protocol for a Single-Case Experimental Study.

BACKGROUND: Regular physical activity (PA) is recommended to optimize weight and health outcomes in patients who have undergone metabolic and bariatric surgery (MBS). However, >70% of patients have low PA levels before MBS that persist after MBS. Although behavioral interventions delivered face-to-face have shown promise for increasing PA among patients who have undergone MBS, many may experience barriers, preventing enrollment into and adherence to such interventions. Delivering PA behavior change interventions via telehealth to patients who have undergone MBS may be an effective strategy to increase accessibility and reach, as well as adherence. OBJECTIVE: This paper reports the protocol for a study that aims to assess the feasibility and acceptability of the protocol or methods and the Telehealth Bariatric Behavioral Intervention (TELE-BariACTIV). The intervention is designed to increase moderate-to-vigorous intensity PA (MVPA) in patients awaiting bariatric surgery and is guided by a multitheory approach and a patient perspective. Another objective is to estimate the effect of the TELE-BariACTIV intervention on presurgical MVPA to determine the appropriate sample size for a multicenter trial. METHODS: This study is a multicenter trial using a repeated (ABAB'A) single-case experimental design. The A phases are observational phases without intervention (A1=pre-MBS phase; A2=length personalized according to the MBS date; A3=7 months post-MBS phase). The B phases are interventional phases with PA counseling (B1=6 weekly pre-MBS sessions; B2=3 monthly sessions starting 3 months after MBS). The target sample size is set to 12. Participants are inactive adults awaiting sleeve gastrectomy who have access to a computer with internet and an interface with a camera. The participants are randomly allocated to a 1- or 2-week baseline period (A1). Protocol and intervention feasibility and acceptability (primary outcomes) will be assessed by recording missing data, refusal, recruitment, retention, attendance, and attrition rates, as well as via web-based acceptability questionnaires and semistructured interviews. Data collected via accelerometry (7-14 days) on 8 occasions and via questionnaires on 10 occasions will be analyzed to estimate the effect of the intervention on MVPA. Generalization measures assessing the quality of life, anxiety and depressive symptoms, and theory-based constructs (ie, motivational regulations for PA, self-efficacy to overcome barriers to PA, basic psychological needs satisfaction and frustration, PA enjoyment, and social support for PA; secondary outcomes for a future large-scale trial) will be completed via web-based questionnaires on 6-10 occasions. The institutional review board provided ethics approval for the study in June 2021. RESULTS: Recruitment began in September 2021, and all the participants were enrolled (n=12). Data collection is expected to end in fall 2023, depending on the MBS date of the recruited participants. CONCLUSIONS: The TELE-BariACTIV intervention has the potential for implementation across multiple settings owing to its collaborative construction that can be offered remotely. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39633.

Neck circumference is a better correlate of insulin resistance markers than other standard anthropometric indices in patients presenting severe obesity.

BACKGROUND: Previous studies have demonstrated stronger associations between metabolic alterations and neck circumference (NC) than with body mass index (BMI) or waist circumference (WC). However, most of these studies were performed in individuals presenting overweight or mild obesity. OBJECTIVE: To determine which adiposity index among BMI, WC, NC and fat mass (FM) can best predict metabolic alterations in men and women presenting severe obesity. METHODS: Anthropometric and plasma biochemical parameters were measured in 81 participants presenting severe obesity (19 men, 62 women; age: 44.5 ± 8.9 years; BMI: 43.5 ± 4.1 kg/m2). Multiple linear regressions were used to determine the best predictors of metabolic alterations among each adiposity index. RESULTS: NC was positively correlated with fasting insulin concentrations, C-peptide concentrations and HOMA-IR values and negatively correlated with HDL-C concentrations. NC was the best predictor of glucose homeostasis indices and HDL-C concentrations in models also including sex, BMI, WC, and FM. The ROC curve analysis indicated that a NC ≥ 37.8 cm best predicted type 2 diabetes. CONCLUSIONS: NC seems a better predictor of insulin resistance and lower HDL-C concentrations in patients presenting severe obesity compared to other standard anthropometric indices, and particularly in women. The small sample size in men prevent us to draw clear conclusions. NC could be useful in targeting patients with metabolic alterations who could benefit from medical or surgical treatment of obesity.

Impact of weight loss on brain age: Improved brain health following bariatric surgery.

Individuals living with obesity tend to have increased brain age, reflecting poorer brain health likely due to grey and white matter atrophy related to obesity. However, it is unclear if older brain age associated with obesity can be reversed following weight loss and cardiometabolic health improvement. The aim of this study was to assess the impact of weight loss and cardiometabolic improvement following bariatric surgery on brain health, as measured by change in brain age estimated based on voxel-based morphometry (VBM) measurements. We used three distinct datasets to perform this study: 1) CamCAN dataset to train the brain age prediction model, 2) Human Connectome Project (HCP) dataset to investigate whether individuals with obesity have greater brain age than individuals with normal weight, and 3) pre-surgery, as well as 4, 12, and 24 month post-surgery data from participants (n = 87, age: 44.0 ± 9.2 years, BMI: 43.9 ± 4.2 kg/m2) who underwent a bariatric surgery to investigate whether weight loss and cardiometabolic improvement as a result of bariatric surgery lowers the brain age. As expected, our results from the HCP dataset showed a higher brain age for individuals with obesity compared to individuals with normal weight (T-value = 7.08, p-value < 0.0001). We also found significant improvement in brain health, indicated by a decrease of 2.9 and 5.6 years in adjusted delta age at 12 and 24 months following bariatric surgery compared to baseline (p-value < 0.0005 for both). While the overall effect seemed to be driven by a global change across all brain regions and not from a specific region, our exploratory analysis showed lower delta age in certain brain regions (mainly in somatomotor, visual, and ventral attention networks) at 24 months. This reduced age was also associated with post-surgery improvements in BMI, systolic/diastolic blood pressure, and HOMA-IR (T-valueBMI=4.29, T-valueSBP=4.67, T-valueDBP=4.12, T-valueHOMA-IR=3.16, all p-values < 0.05). In conclusion, these results suggest that obesity-related brain health abnormalities (as measured by delta age) might be reversed by bariatric surgery-induced weight loss and widespread improvements in cardiometabolic alterations.

Molecular remodeling of adipose tissue is associated with metabolic recovery after weight loss surgery.

BACKGROUND: Bariatric surgery is an effective therapy for individuals with severe obesity to achieve sustainable weight loss and to reduce comorbidities. Examining the molecular signature of subcutaneous adipose tissue (SAT) following different types of bariatric surgery may help in gaining further insight into their distinct metabolic impact. RESULTS: Subjects undergoing biliopancreatic diversion with duodenal switch (BPD-DS) showed a significantly higher percentage of total weight loss than those undergoing gastric bypass or sleeve gastrectomy (RYGB + SG) (41.7 ± 4.6 vs 28.2 ± 6.8%; p = 0.00005). Individuals losing more weight were also significantly more prone to achieve both type 2 diabetes and dyslipidemia remission (OR = 0.75; 95%CI = 0.51-0.91; p = 0.03). Whole transcriptome and methylome profiling showed that bariatric surgery induced a profound molecular remodeling of SAT at 12 months postoperative, mainly through gene down-regulation and hypermethylation. The extent of changes observed was greater following BPD-DS, with 61.1% and 49.8% of up- and down-regulated genes, as well as 85.7% and 70.4% of hyper- and hypomethylated genes being exclusive to this procedure, and mostly associated with a marked decrease of immune and inflammatory responses. Weight loss was strongly associated with genes being simultaneously differentially expressed and methylated in BPD-DS, with the strongest association being observed for GPD1L (r2 = 0.83; p = 1.4 × 10-6). CONCLUSIONS: Present findings point to the greater SAT molecular remodeling following BPD-DS as potentially linked with higher metabolic remission rates. These results will contribute to a better understanding of the metabolic pathways involved in the response to bariatric surgery and will eventually lead to the development of gene targets for the treatment of obesity. Trial registration ClinicalTrials.gov NCT02390973.

Intra-abdominal adipose depot variation in adipogenesis, lipogenesis, angiogenesis, and fibrosis gene expression and relationships with insulin resistance and inflammation in premenopausal women with severe obesity

Although severe obesity is associated with insulin resistance (IR) and inflammation, secretory function of intra-abdominal adipose tissues and their relationships with IR and inflammation markers remain poorly understood. Aims were to measure gene expression of adipogenic (C/EBPα/β, PPARγ-1/2, SREBP-1c, LXRα), lipogenic (SCD1, DGAT-1/2), angiogenic (VEGFα, leptin), and fibrotic (LOX, COL6A3) factors in the round ligament (RL), omental (OM), and mesenteric (ME) fat depots and to evaluate their relationships with IR and inflammation markers in 48 women with severe obesity undergoing bariatric surgery. Gene expression was assessed by RT-qPCR, and plasma glucose and insulin (HOMA-IR calculated), PAI-1, IL-6, TNFα, adiponectin, and leptin levels were determined. C/EBPβ and PPARγ-1/2 mRNA levels were more expressed in the OM (0.001

Guidelines for Canadian bariatric surgical and medical centres: a statement from the Canadian Association of Bariatric Physicians and Surgeons.

SummaryThe goal of this statement is to offer standardization in bariatric care across Canada, to provide patients with optimal access to obesity treatment and potentially improve outcomes by reducing complications, length of hospital stay and readmission rate. The definition of Canadian standards also aims to promote a comprehensive, multidisciplinary approach to patients with obesity, to define the minimal qualifications for surgical and medical training and to offer credentialling for bariatric surgical and medical centres. In addition, we emphasize the importance of developing a national registry for the assessment of quality of care across the country and to evaluate outcomes of long-term treatment. These recommendations are based on expert opinion as well as the most recent clinical evidence.

Dietary intakes in pregnant women with previous bariatric surgery.

PURPOSE: To (1) assess dietary intakes of pregnant women with previous bariatric surgery in comparison with Dietary Reference Intakes (DRIs); (2) compare their dietary intakes as well as their diet quality with a control group of pregnant women with no history of bariatric surgery. METHODS: Twenty-eight (28) pregnant women with previous surgery (sleeve gastrectomy, n = 7 and biliopancreatic diversion with duodenal switch, n = 21) were matched for pre-pregnancy body mass index with 28 pregnant women with no history of bariatric surgery. In at least one trimester, participants completed a minimum of 2 Web-based 24-h dietary recalls from which energy, macro- and micronutrient intakes as well as the Canadian Healthy Eating Index (C-HEI) were derived. RESULTS: No differences were observed for energy intake between groups. All women had protein intakes within the recommended range, but most women with previous surgery had carbohydrate (67%) and dietary fiber intakes (98%) below recommendations. In both groups, mean total fat, saturated fatty acids, free sugars and sodium intakes were above recommendations, as opposed to mean vitamin D, folic acid and iron dietary intakes below recommendations for most women. Compared with the control group, pregnant women with previous bariatric surgery had lower overall C-HEI scores. CONCLUSION: These results suggest that pregnant women with previous bariatric surgery would benefit from a nutritional follow-up throughout their pregnancy. LEVEL OF EVIDENCE: III: Evidence obtained from well-designed cohort or case-control analytic studies.

Intra-abdominal adipose depot variation in adipogenesis, lipogenesis, angiogenesis, and fibrosis gene expression and relationships with insulin resistance and inflammation in premenopausal women with severe obesity.

Although severe obesity is associated with insulin resistance (IR) and inflammation, secretory function of intra-abdominal adipose tissues and their relationships with IR and inflammation markers remain poorly understood. Aims were to measure gene expression of adipogenic (C/EBPα/ß, PPARγ-1/2, SREBP-1c, LXRα), lipogenic (SCD1, DGAT-1/2), angiogenic (VEGFα, leptin), and fibrotic (LOX, COL6A3) factors in the round ligament (RL), omental (OM), and mesenteric (ME) fat depots and to evaluate their relationships with IR and inflammation markers in 48 women with severe obesity undergoing bariatric surgery. Gene expression was assessed by RT-qPCR, and plasma glucose and insulin (HOMA-IR calculated), PAI-1, IL-6, TNFα, adiponectin, and leptin levels were determined. C/EBPß and PPARγ-1/2 mRNA levels were more expressed in the OM (0.001