The 2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) updated the indications for Metabolic and Bariatric Surgery (MBS), replacing the previous guidelines established by the NIH over 30 years ago. The evidence supporting these updated guidelines has been strengthened to assist metabolic and bariatric surgeons, nutritionists, and other members of multidisciplinary teams, as well as patients. This study aims to assess the level of evidence and the strength of recommendations compared to the previously published criteria.
The overconsumption of palatable energy-dense foods drives obesity, but few human studies have investigated dopamine (DA) release in response to the consumption of a palatable meal, a putative mediator of excess intake in obesity. We imaged [11C]raclopride in the brain with positron emission tomography (PET) to assess striatal dopamine (DA) receptor binding pre- and post-consumption of a highly palatable milkshake (250 mL, 420 kcal) in 11 females, 6 of whom had severe obesity, and 5 of whom had healthy-weight. Those with severe obesity underwent assessments pre- and 3 months post-vertical sleeve gastrectomy (VSG). Our results demonstrated decreased post- vs. pre-meal DA receptor binding in the ventral striatum (p = 0.032), posterior putamen (p = 0.012), and anterior caudate (p = 0.018), consistent with meal-stimulated DA release. Analysis of each group separately suggested that results in the caudate and putamen were disproportionately driven by meal-associated changes in the healthy-weight group. Baseline (pre-meal) DA receptor binding was lower in severe obesity than in the healthy-weight group. Baseline DA receptor binding and DA release did not change from pre- to post-surgery. The results of this small pilot study suggest that milkshake acutely stimulates DA release in the ventral and dorsal striatum. This phenomenon likely contributes to the overconsumption of highly palatable foods in the modern environment.
Kaposiform lymphangiomatosis (KLA) is a life-threatening rare disease that can cause substantial morbidity, mortality, and social burdens for patients and their families. Diagnosis often occurs long after initial symptoms, and there are few centers in the world with the expertise to diagnose and care for patients with the disease. KLA is a lymphatic anomaly and significant advancements have been made in understanding its pathogenesis and etiology since its first description in 2014. This review provides multidisciplinary, comprehensive, and state-of-the-art information on KLA patient presentation, diagnostic imaging, pathology, organ involvement, genetics, and pathogenesis. Finally, we describe current therapeutic approaches, important areas for research, and challenges faced by patients and their families. Further insights into the pathogenesis of KLA may advance our understanding of other vascular anomalies given that similar signaling pathways may be involved.
The fact that obesity has now become a worldwide epidemic and that traditional approaches to weight loss, including diet, behavioral modification, and physical activity have yielded poor weight loss outcomes is not new. On the other hand, there is substantial and growing evidence that bariatric surgery remains the most effective treatment option for many seeking significant, sustained weight loss. As the evidence grows demonstrating that bariatric surgery yields not only sustained weight loss but the resolution or remission of obesity-related comorbidities, such as sleep apnea, hypertension, and Type II diabetes mellitus, there is an increasing number of patients undergoing these procedures. Many patients seeking bariatric surgery are women of childbearing age. Since women with obesity are at risk for infertility and/or may suffer higher complication rates during pregnancy, many consider bariatric surgery a beneficial option, particularly those seeking to optimize their chances of having a family while minimizing risks. However, there remain mixed opinions as to whether there are risks inherent in having bariatric surgery, and whether those risks differ among bariatric procedures. What is more, there has been robust discussion in the literature regarding whether there is an “ideal” time to pursue pregnancy post-bariatric surgery. The aim of this review is to discuss the risks and benefits associated with pregnancy after bariatric surgery.
Inhibition of P300 acetyltransferase activity by specific inhibitor C646 has been shown to improve insulin signaling. However, the underlying molecular mechanism of this improvement remains unclear. In this study, we analyzed P300 levels of obese patients and found that they were significantly increased in liver hepatocytes. In addition, large amounts of P300 appeared in the cytoplasm. Inhibition of P300 acetyltransferase activity by C646 drastically increased tyrosine phosphorylation of the insulin receptor protein substrates (IRS1/2) without affecting the tyrosine phosphorylation of the beta subunit of the insulin receptor (IRβ) in hepatocytes in the absence of insulin. Since IRS1/2 requires membrane translocation and binding to inositol compounds for normal functions, we also examined the role of acetylation on binding to phosphatidylinositol(4,5)P2 and found that IRS1/2 acetylation by P300 reduced this binding. In contrast, we show that inhibition of IRS1/2 acetylation by C646 facilitates IRS1/2 membrane translocation. Intriguingly, we demonstrate that C646 activates IRβ's tyrosine kinase activity and directly promotes IRβ interaction with IRS1/2, leading to the tyrosine phosphorylation of IRS1/2 and subsequent activation of insulin signaling even in the absence of insulin. In conclusion, these data reveal the unique effects of C646 in activating insulin signaling in patients with obesity and diabetes.
Major updates to 1991 National Institutes of Health guidelines for bariatric surgeryMetabolic and bariatric surgery (MBS) is recommended for individuals with a body mass index (BMI) >35 kg/m2, regardless of presence, absence, or severity of co-morbidities.MBS should be considered for individuals with metabolic disease and BMI of 30-34.9 kg/m2.BMI thresholds should be adjusted in the Asian population such that a BMI >25 kg/m2 suggests clinical obesity, and individuals with BMI >27.5 kg/m2 should be offered MBS.Long-term results of MBS consistently demonstrate safety and efficacy.Appropriately selected children and adolescents should be considered for MBS.(Surg Obes Relat Dis 2022; https://doi.org/10.1016/j.soard.2022.08.013) © 2022 American Society for Metabolic and Bariatric Surgery. All rights reserved.
To evaluate associations of ghrelin, glucagon-like peptide 1 (GLP-1), and peptide YY 3–36 (PYY3-36) with weight change after bariatric arterial embolization (BAE). Subgroup analysis of data collected during the BEAT Obesity Trial involving 7 participants with BMI > 40 who were embolized with 300- to 500-μm Embosphere Microspheres. Three participants were characterized as “responders” (top tertile of weight loss at each visit) and 4 as “non-responders” (bottom tertile of weight loss at each visit). Mean ± standard deviation participant age was 44 ± 11 years, and 6 of 7 participants were women. Participants were evaluated at baseline, 2 weeks, and 1, 3, 6, and 12 months after BAE. After fasting, participants consumed a mixed meal test at each visit; blood samples were collected at 0, 15, 30, 60, 120, 180, and 240 min. Study outcome measures were changes in weight from baseline and plasma serum hormone levels. Percentage change in ghrelin decreased significantly in non-responders at 60 and 120 min at 1 and 12 months (estimated difference between 60 vs. 0 min at 1 month: 69
Background Previously, we reported short-term improvements in auditory attention, oromotor processing speed, and executive function during the active weight loss phase following bariatric surgery that persisted out to 3 months. In this study, our aims were to investigate the relationship between weight loss and cognitive performance in these patients 1 year following vertical sleeve gastrectomy (VSG) and Roux-en Y gastric bypass (RYGB) surgery and to determine whether preoperative cognitive performance predicted weight loss. Methods Adult women ages 18–55 approved for bariatric surgery completed a cognitive battery prior to and at 2, 12, 24, and 52 weeks following VSG ( N = 17) or RYGB ( N = 18). Scores from each task were assigned to one of the following cognitive domains: auditory attention, processing speed, memory, and executive functioning. Weight loss and cognitive scores for each domain were calculated and compared between cohorts. Results RYGB surgery resulted in greater weight loss at 1-year follow-up relative to VSG. Both VSG and RYGB procedures resulted in improved performance on different measures of auditory attention and both surgery groups improved across all processing speed tasks. Within the executive function domain, both groups showed improvements, but only the RYGB procedure resulted in improved performance in the Trail Making Test. Baseline auditory attention and memory performance predicted weight loss at 1 year following RYGB but not VSG surgery. Controlling for baseline cognitive performance, percent total weight loss predicted auditory attention at 1 year following RYGB but not VSG surgery. Conclusions Bariatric surgery type may result in selective improvements in cognition during the first year following surgery. Presurgical cognitive performance as well as surgery type appears to influence weight loss outcomes.
Background Plausible phenotype mechanisms following bariatric surgery include changes in neural and gastrointestinal physiology. This pilot study aims to investigate individual and combined neurologic, gut microbiome, and plasma hormone changes pre- versus post-vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), and medical weight loss (MWL). We hypothesized post-weight loss phenotype would be associated with changes in central reward system brain connectivity, differences in postprandial gut hormone responses, and increased gut microbiome diversity. Methods Subjects included participants undergoing VSG, n = 7; RYGB, n = 9; and MWL, n = 6. Ghrelin, glucagon-like peptide-1, peptide-YY, gut microbiome, and resting state functional magnetic resonance imaging (rsfMRI; using fractional amplitude of low-frequency fluctuations [fALFF]) were measured pre- and post-intervention in fasting and fed states. We explored phenotype characterization using clustering on gut hormone, microbiome, and rsfMRI datasets and a combined analysis. Results We observed more widespread fALFF differences post-bariatric surgery versus post-MWL. Decreased post-prandial fALFF was seen in food reward regions post-RYGB. The highest number of microbial taxa that increased post-intervention occurred in the RYGB group, followed by VSG and MWL. The combined hormone, microbiome, and MRI dataset most accurately clustered samples into pre- versus post-VSG phenotypes followed by RYGB subjects. Conclusion The data suggest surgical weight loss (VSG and RYGB) has a bigger impact on brain and gut function versus MWL and leads to lesser post-prandial activation of food-related neural circuits. VSG subjects had the greatest phenotype differences in interactions of microbiome, rsfMRI, and gut hormone features, followed by RYGB and MWL. These results will inform future prospective research studying gut-brain changes post-bariatric surgery.
Background: The optimal regimen for prevention and treatment of venous thromboembolism in bariatric surgical patients remains controversial. Direct oral anticoagulants are potentially advantageous over other agents, but inadequate evidence exists regarding their effects in bariatric surgical patients. Objectives: To investigate single-dose pharmacokinetic (PK) and pharmacodynamic (PD) parameters of apixaban when administered to patients undergoing vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) and to determine whether the PK and PD parameters are affected by type of bariatric surgery and weight loss in the immediate and postoperative period up to 12 months. Setting: University Hospital and A Bariatric Center of Excellence, Baltimore, Maryland. Methods: Adults with a body mass index >= 35 kg/m(2) approved for bariatric surgery were enrolled in a single-center, open-label, nonrandomized, single-dose clinical study (NCT No. 02406885; www.clinicaltrials.gov). Apixaban PK and PD parameters were measured after a single 5 mg dose of the drug was given preoperatively and at 1, 6, and 12 months postoperatively in patients undergoing VSG and RYGB. Change in PK parameters was assessed as maximum concentration, time to maximum concentration, elimination half-life, and area under the concentration-time curve from 0-72 hours and change in PD parameters were assessed by chromogenic factor X activity. Results: Of 33 patients enrolled, 28 (14 VSG, 14 RYGB) completed all visits and were analyzed. Most patients (89%) were female, with a mean age of 43.8 years and a body mass index of 48.7 kg/m(2). Area under the concentration-time curve from 0-72 hours increased from baseline to 1 month (1009.1 to 1232.9 ng/mL/hr, P = .002), returned to baseline at 6 months (1000.9 ng/mL/hr, P = .88), and decreased significantly at 12 months (841.8 ng/mL/hr, P = .001). Maximum concentration did not change significantly. Predose factor X activity dropped significantly from 113% preoperatively to 89.8 % at 12 months postoperatively (P < .0001). Three-hour postdose factor X activity was significantly lower at 1, 6, and 12 months postoperatively versus preoperatively. However, the magnitude of the decrease from predose to 3-hour postdose was not significantly altered by surgery. Conclusion: The effect of either VSG or RYGB on apixaban PK and PD parameters is minimal. Factor X activity after 5 mg apixaban was lower in postoperative versus preoperative bariatric patients, but this effect appears to be primarily the result of a decrease in factor X activity from bariatric surgery itself and not a postoperative change in apixaban PK and PD parameters. Future studies should investigate the safety, efficacy, and clinical outcomes of apixaban and other direct oral anticoagulants perioperatively and beyond 12 months following bariatric surgery. (C) 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
Background Alterations in gut hormone secretion and reported changes in taste preferences have been suggested to contribute to the weight-reducing effects of bariatric surgery. However, a link between changes in gut hormone secretion and taste preferences following bariatric surgery has yet to be elucidated. Methods Here we examined the potential relationships between gut hormone responses (GLP-1 and PYY 3-36 peak, ghrelin trough) to a test meal of Ensure and liking ratings for taste mixtures varying in sugar and fat content before and following bariatric surgery (vertical sleeve gastrectomy (VSG): N = 4; Roux-en Y gastric bypass (RYGB): N = 8). Results Significant increases in GLP-1 and PYY 3-36 peak and a significant drop in ghrelin trough were observed following surgery. Pre- and postoperation, patients with higher p ostprandial GLP-1 or PYY 3-36 peaks gave lower liking ratings for mixtures containing a combination of fat and sugar (half and half + 20% added sugar) whereas, for the combined surgery analyses, no relationships were found with solutions comprised of high fat (half and half + 0% sugar), predominantly high sugar (skim milk + 20% added sugar), or low fat and low sugar (skim milk + 0% added sugar). Within the RYGB patients, patients with the greatest increase in postprandial GLP-1 peak from preoperation to postoperation also demonstrated the greatest decrease in liking for half & half + 20% added sugar and skim milk + 20% added sugar, but not the unsweetened version of each solution. No pre- or postoperative relationship between ghrelin and liking ratings were observed. Conclusion Gut hormone responses following bariatric surgery may contribute to taste processing of sugar+fat mixtures and together influence weight loss.
In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean +/- SD, C19+: -82.5 +/- 27.2 points; C19-: -59.8 +/- 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for similar to 50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings <= 2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
Background: Weight regain is a concerning issue in bariatric patients. We previously demonstrated that taste-related reward processing was associated with six-month weight loss outcomes following Roux-en-Y gastric bypass (RYGB) but not vertical sleeve gastrectomy (VSG). Here, we assessed whether these taste factors persisted in predicting weight loss, and weight regain, at one year post-surgery. Methods: Adult women enrolled in a longitudinal study of taste preferences following bariatric surgery completed behavioral and neuroimaging assessments at one year post-surgery. Results: RYGB produced better weight loss relative to VSG, with weight regain and greater weight loss variability observed from six months to one year post-VSG. Changes in liking for high fat at 2 weeks post-surgery from baseline remained a predictor of weight loss in RYGB, but other predictors did not persist. Average liking ratings rebounded to baseline and higher self-reported food cravings and dietary disinhibition correlated with poorer weight loss at one year post-surgery. Conclusion: Initial anatomical and metabolic changes resulting from RYGB that reset neural processing of reward stimuli in the mesolimbic pathway appear to be temporary and may be contingent upon post-operative eating behaviors returning to preoperative obesogenic tendencies. Six months post-surgery may be a critical window for implementing interventions to mitigate weight gain.
BACKGROUND:Bariatric surgery results in rapid weight loss and resolution of comorbidities such as type 2 diabetes mellitus (T2DM). We aimed to determine whether the type of surgical procedure-vertical sleeve gastrectomy (VSG) versus Roux-en-Y gastric bypass (RYGB)-was associated with sustained remission from T2DM, and to identify other independent predictors of sustained remission. METHODS:Using the IBM MarketScan database of privately insured patients in the United States, we performed a retrospective cohort study on individuals aged 18-65 y with T2DM on hypoglycemic medication, who underwent either VSG or RYGB from 2010 to 2016. Remission was defined as no refill of antidiabetic medication 180 d after a patient's medication was expected to run out and recurrence as medication refill after at least 180 d of remission. RESULTS:Of 5119 patients in our cohort, 4127 (81%) experienced remission of T2DM, and 816 (19.8%) of the 4127 patients experienced recurrence. Patients who underwent RYGB had a 24% (HR = 1.24, 95% CI: 1.16, 1.32) increased probability of achieving remission compared with VSG. RYGB had a 36% (HR = 0.64, 95% CI: 0.55, 0.74) decreased risk of recurrence compared with VSG. A higher number of diabetic medications at the time of surgery and a higher Charlson index score were associated with decreased probability of remission and an increased risk of recurrence of T2DM. CONCLUSIONS:While both procedures are initially effective, RYGB may be better than VSG at providing lasting remission of T2DM.
Background: Bariatric surgery results in rapid weight loss and resolution of many co-morbidities including hypertension. Objectives: To investigate the association of the 2 most common bariatric surgical procedures, vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB), with sustained remission from hypertension, and evaluate other independent predictors of sustained remission. Setting: Privately insured patients with hypertension in the United States undergoing bariatric surgery. Methods: A cohort of hypertensive bariatric patients was created using detailed inclusion and exclusion criteria. Remission was defined as no refill of antihypertensive medication for 30 days after patients' medication was expected to run out, and recurrence as medication refill after at least 90 days of remission. Results: Of 7006 patients in our cohort, 5874 experienced remission of their hypertension (83.8%). 745 of the 5874 (12.7%) patients later experienced recurrence. The adjusted hazard ratio of remission for VSG compared with RYGB was 1.06 (95% confidence interval [CI]; 1.0, 1.11). The adjusted hazard ratio of recurrence for VSG compared with RYGB was .84 (95% CI; .71, .97). A higher number of medications at the time of surgery was associated with a decreased likelihood of remission and an increased risk of recurrence of hypertension. Conclusion: There was no difference in the likelihood of remission of hypertension between VSG and RYGB. The number of medications at the time of surgery was the most important predictor of remission and recurrence of hypertension after surgery. (C) 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.