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Short-term intestinal lipase inhibition in normal-weight individuals does not affect postprandial peptide YY3-36 and glucagon-like peptide-1 levels, hunger or satiety.
Nguyen, NN, Kolobova, I, Wolfe, BM, Purnell, JQ
Diabetes, obesity & metabolism. 2020;(12):2499-2503
Abstract
Fat malabsorption associated with Roux-en-Y gastric bypass (RYGB) may contribute to elevated postprandial glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) after the procedure, leading to sustained weight loss and appetite reduction. This study investigated whether fat malabsorption via orlistat increases GLP-1 and PYY and if these increases would be proportional to changes in hunger and satiety. Five healthy participants received standardized meals with 120 mg orlistat or placebo in a randomized, double-blinded, crossover design for 3 days. On the final day, glucose, insulin, GLP-1, PYY3-36 and visual analogue scores for hunger and satiety were measured over a 14-hour period that included three meals. Fasting, 14-hour area under the curve (AUC) and meal-related AUC for glucose and insulin were similar, although postprandial increases in peak insulin and glucose were greater with orlistat. PYY3-36 , GLP-1, hunger and satiety were not different. In conclusion, short-term orlistat administration does not enhance postprandial GLP-1 or PYY3-36 or affect hunger or satiety in normal-weight individuals. Furthermore, fat malabsorption from RYGB is unlikely to mediate subsequent postprandial increases in GLP-1 and PYY.
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The Science of Obesity Management: An Endocrine Society Scientific Statement.
Bray, GA, Heisel, WE, Afshin, A, Jensen, MD, Dietz, WH, Long, M, Kushner, RF, Daniels, SR, Wadden, TA, Tsai, AG, et al
Endocrine reviews. 2018;(2):79-132
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Abstract
The prevalence of obesity, measured by body mass index, has risen to unacceptable levels in both men and women in the United States and worldwide with resultant hazardous health implications. Genetic, environmental, and behavioral factors influence the development of obesity, and both the general public and health professionals stigmatize those who suffer from the disease. Obesity is associated with and contributes to a shortened life span, type 2 diabetes mellitus, cardiovascular disease, some cancers, kidney disease, obstructive sleep apnea, gout, osteoarthritis, and hepatobiliary disease, among others. Weight loss reduces all of these diseases in a dose-related manner-the more weight lost, the better the outcome. The phenotype of "medically healthy obesity" appears to be a transient state that progresses over time to an unhealthy phenotype, especially in children and adolescents. Weight loss is best achieved by reducing energy intake and increasing energy expenditure. Programs that are effective for weight loss include peer-reviewed and approved lifestyle modification programs, diets, commercial weight-loss programs, exercise programs, medications, and surgery. Over-the-counter herbal preparations that some patients use to treat obesity have limited, if any, data documenting their efficacy or safety, and there are few regulatory requirements. Weight regain is expected in all patients, especially when treatment is discontinued. When making treatment decisions, clinicians should consider body fat distribution and individual health risks in addition to body mass index.
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Proceedings of the 2017 ASPEN Research Workshop-Gastric Bypass: Role of the Gut.
Jain, AK, le Roux, CW, Puri, P, Tavakkoli, A, Gletsu-Miller, N, Laferrère, B, Kellermayer, R, DiBaise, JK, Martindale, RG, Wolfe, BM
JPEN. Journal of parenteral and enteral nutrition. 2018;(2):279-295
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Abstract
The goal of the National Institutes of Health-funded American Society for Parenteral and Enteral Nutrition 2017 research workshop (RW) "Gastric Bypass: Role of the Gut" was to focus on the exciting research evaluating gut-derived signals in modulating outcomes after bariatric surgery. Although gastric bypass surgery has undoubted positive effects, the mechanistic basis of improved outcomes cannot be solely explained by caloric restriction. Emerging data suggest that bile acid metabolic pathways, luminal contents, energy balance, gut mucosal integrity, as well as the gut microbiota are significantly modulated after bariatric surgery and may be responsible for the variable outcomes, each of which was rigorously evaluated. The RW served as a timely and novel academic meeting that brought together clinicians and researchers across the scientific spectrum, fostering a unique venue for interdisciplinary collaboration among investigators. It promoted engaging discussion and evolution of new research hypotheses and ideas, driving the development of novel ameliorative, therapeutic, and nonsurgical interventions targeting obesity and its comorbidities. Importantly, a critical evaluation of the current knowledge regarding gut-modulated signaling after bariatric surgery, potential pitfalls, and lacunae were thoroughly addressed.
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Use of prescribed opioids before and after bariatric surgery: prospective evidence from a U.S. multicenter cohort study.
King, WC, Chen, JY, Belle, SH, Courcoulas, AP, Dakin, GF, Flum, DR, Hinojosa, MW, Kalarchian, MA, Mitchell, JE, Pories, WJ, et al
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2017;(8):1337-1346
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BACKGROUND Limited evidence suggests bariatric surgery may not reduce opioid analgesic use, despite improvements in pain. OBJECTIVE To determine if use of prescribed opioid analgesics changes in the short and long term after bariatric surgery and to identify factors associated with continued and postsurgery initiated use. SETTING Ten U.S. hospitals. METHODS The Longitudinal Assessment of Bariatric Surgery-2 is an observational cohort study. Assessments were conducted presurgery, 6 months postsurgery, and annually postsurgery for up to 7 years until January 2015. Opioid use was defined as self-reported daily, weekly, or "as needed" use of a prescribed medication classified as an opioid analgesic. RESULTS Of 2258 participants with baseline data, 2218 completed follow-up assessment(s) (78.7% were female, median body mass index: 46; 70.6% underwent Roux-en-Y gastric bypass). Prevalence of opioid use decreased after surgery from 14.7% (95% CI: 13.3-16.2) at baseline to 12.9% (95% CI: 11.5-14.4) at month 6 but then increased to 20.3%, above baseline levels, as time progressed (95% CI: 18.2-22.5) at year 7. Among participants without baseline opioid use (n = 1892), opioid use prevalence increased from 5.8% (95% CI: 4.7-6.9) at month 6 to 14.2% (95% CI: 12.2-16.3) at year 7. Public versus private health insurance, more pain presurgery, undergoing subsequent surgeries, worsening or less improvement in pain, and starting or continuing nonopioid analgesics postsurgery were significantly associated with higher risk of postsurgery initiated opioid use. CONCLUSION After bariatric surgery, prevalence of prescribed opioid analgesic use initially decreased but then increased to surpass baseline prevalence, suggesting the need for alternative methods of pain management in this population.
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Alcohol and other substance use after bariatric surgery: prospective evidence from a U.S. multicenter cohort study.
King, WC, Chen, JY, Courcoulas, AP, Dakin, GF, Engel, SG, Flum, DR, Hinojosa, MW, Kalarchian, MA, Mattar, SG, Mitchell, JE, et al
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2017;(8):1392-1402
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BACKGROUND Empirical evidence suggests Roux-en-Y gastric bypass (RYGB) increases risk of developing alcohol use disorder (AUD). However, prospective assessment of substance use disorders (SUD) after bariatric surgery is limited. OBJECTIVE To report SUD-related outcomes after RYGB and laparoscopic adjustable gastric banding (LAGB). To identify factors associated with incident SUD-related outcomes. SETTING 10 U.S. hospitals METHODS The Longitudinal Assessment of Bariatric Surgery-2 is a prospective cohort study. Participants self-reported past-year AUD symptoms (determined by the Alcohol Use Disorders Identification Test), illicit drug use (cocaine, hallucinogens, inhalants, phencyclidine, amphetamines, or marijuana), and SUD treatment (counseling or hospitalization for alcohol or drugs) presurgery and annually postsurgery for up to 7 years through January 2015. RESULTS Of 2348 participants who underwent RYGB or LAGB, 2003 completed baseline and follow-up assessments (79.2% women, baseline median age: 47 years, median body mass index 45.6). The year-5 cumulative incidence of postsurgery onset AUD symptoms, illicit drug use, and SUD treatment were 20.8% (95% confidence interval (CI): 18.5-23.3), 7.5% (95% CI: 6.1-9.1), and 3.5% (95% CI: 2.6-4.8), respectively, post-RYGB, and 11.3% (95% CI: 8.5-14.9), 4.9% (95% CI: 3.1-7.6), and .9% (95% CI: .4-2.5) post-LAGB. Undergoing RYGB versus LAGB was associated with higher risk of incident AUD symptoms (adjusted hazard ratio or AHR = 2.08 [95% CI: 1.51-2.85]), illicit drug use (AHR = 1.76 [95% CI: 1.07-2.90]) and SUD treatment (AHR = 3.56 [95% CI: 1.26-10.07]). CONCLUSIONS Undergoing RYGB versus LAGB was associated with twice the risk of incident AUD symptoms. One-fifth of participants reported incident AUD symptoms within 5 years post-RYGB. AUD education, screening, evaluation, and treatment referral should be incorporated in pre- and postoperative care.
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Two-Year Outcomes of Vagal Nerve Blocking (vBloc) for the Treatment of Obesity in the ReCharge Trial.
Apovian, CM, Shah, SN, Wolfe, BM, Ikramuddin, S, Miller, CJ, Tweden, KS, Billington, CJ, Shikora, SA
Obesity surgery. 2017;(1):169-176
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BACKGROUND The ReCharge Trial demonstrated that a vagal blocking device (vBloc) is a safe and effective treatment for moderate to severe obesity. This report summarizes 24-month outcomes. METHODS Participants with body mass index (BMI) 40 to 45 kg/m2, or 35 to 40 kg/m2 with at least one comorbid condition were randomized to either vBloc therapy or sham intervention for 12 months. After 12 months, participants randomized to vBloc continued open-label vBloc therapy and are the focus of this report. Weight loss, adverse events, comorbid risk factors, and quality of life (QOL) will be assessed for 5 years. RESULTS At 24 months, 123 (76 %) vBloc participants remained in the trial. Participants who presented at 24 months (n = 103) had a mean excess weight loss (EWL) of 21 % (8 % total weight loss [TWL]); 58 % of participants had ≥5 % TWL and 34 % had ≥10 % TWL. Among the subset of participants with abnormal preoperative values, significant improvements were observed in mean LDL (-16 mg/dL) and HDL cholesterol (+4 mg/dL), triglycerides (-46 mg/dL), HbA1c (-0.3 %), and systolic (-11 mmHg) and diastolic blood pressures (-10 mmHg). QOL measures were significantly improved. Heartburn/dyspepsia and implant site pain were the most frequently reported adverse events. The primary related serious adverse event rate was 4.3 %. CONCLUSIONS vBloc therapy continues to result in medically meaningful weight loss with a favorable safety profile through 2 years. TRIAL REGISTRATION https://clinicaltrials.gov/ct2/show/NCT01327976.
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Treatment of Obesity: Weight Loss and Bariatric Surgery.
Wolfe, BM, Kvach, E, Eckel, RH
Circulation research. 2016;118(11):1844-55
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Plain language summary
Individuals with obesity who have been unable to lose weight through non-surgical means may be candidates for bariatric surgery. Criteria was established over 20 years ago and stated that individuals with a BMI >40 and individuals with a BMI >35-40 with other related conditions who have failed to achieve weight loss medically, are appropriate for surgery. However, individuals with less severe obesity who have type 2 diabetes have now been highlighted as possible candidates also, indicating that it is an evolving process. This review of 123 papers focused on the indications, safety and reasons for bariatric surgery and its role in the reduction of heart disease. The reason for bariatric surgery is to achieve weight loss and decrease an individual’s risk of death and conditions associated with obesity. Indications for surgery were discussed and the types of surgery that are available. Safety has improved due to a number of changes such as recognition of experience of surgeons and centres, the enactment of care protocols and a switch to minimally invasive procedures. However less invasive surgeries appear to accomplish considerably less weight loss. Benefits to body fat, blood fat levels, high blood pressure, diabetes, non-alcoholic fatty liver disease, inflammation, the ability of the blood vessels to dilate and sleep apnoea were all discussed. These were all used as evidence to support the argument that surgery improves an individual’s chances of survival compared to lifestyle interventions, as sufficiently designed trials to support this have not been performed. It was concluded that bariatric surgery has greater improved heart disease and death compared to lifestyle interventions due to the significantly higher weight loss that results.
Abstract
This review focuses on the mechanisms underlying, and indications for, bariatric surgery in the reduction of cardiovascular disease (CVD), as well as other expected benefits of this intervention. The fundamental basis for bariatric surgery for the purpose of accomplishing weight loss is the determination that severe obesity is a disease associated with multiple adverse effects on health, which can be reversed or improved by successful weight loss in patients who have been unable to sustain weight loss by nonsurgical means. An explanation of possible indications for weight loss surgery as well as specific bariatric surgical procedures is presented, along with review of the safety literature of such procedures. Procedures that are less invasive or those that involve less gastrointestinal rearrangement accomplish considerably less weight loss but have substantially lower perioperative and longer-term risk. The ultimate benefit of weight reduction relates to the reduction of the comorbidities, quality of life, and all-cause mortality. With weight loss being the underlying justification for bariatric surgery in ameliorating CVD risk, current evidence-based research is discussed concerning body fat distribution, dyslipidemia, hypertension, diabetes mellitus, inflammation, obstructive sleep apnea, and others. The rationale for bariatric surgery reducing CVD events is discussed and juxtaposed with impacts on all-cause mortalities. Given the improvement of established obesity-related CVD risk factors after weight loss, it is reasonable to expect a reduction of CVD events and related mortality after weight loss in populations with obesity. The quality of the current evidence is reviewed, and future research opportunities and summaries are stated.
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Objectively-measured sedentary time and cardiometabolic health in adults with severe obesity.
King, WC, Chen, JY, Courcoulas, AP, Mitchell, JE, Wolfe, BM, Patterson, EJ, Inabnet, WB, Dakin, GF, Flum, DR, Cook, B, et al
Preventive medicine. 2016;:12-8
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It is unknown whether sedentary behavior is independently associated with the cardiometabolic health of adults with severe obesity. Additionally, there is debate regarding how best to derive meaningful indices of sedentary time (ST) from activity monitor data. A convenience sample of adults with severe obesity (N=927; 79% female, median age 45y, median body mass index (BMI) 46kg/m(2)) completed a research assessment at one of ten US hospitals in 2006-2009 prior to bariatric surgery. Cardiometabolic health was assessed via physical measures, fasting blood samples and medication use. Indices of ST were derived from StepWatch™ activity monitor data with minimum bout durations of 1min, 10min and 30min. Cross-sectional associations were examined. Median (25th, 75th percentile) ST was 9.3h/d (8.1, 10.5) in ≥1min bouts, 6.5h/d (5.2, 8.0) in ≥10min bouts, or 3.2h/d (2.1, 4.5) in ≥30min bouts. Associations with ST were generally strongest with the ≥10min bout duration. Independent of moderate-to-vigorous intensity physical activity, BMI and other potential confounders, 1h/day ST in ≥10min bouts was associated with higher odds of diabetes by 15% (95%CI: 1.05-1.26), metabolic syndrome by 12% (95%CI: 1.01-1.24) and elevated blood pressure by 14% (95%CI: 1.02-1.26), and was associated with 1.4cm (95%CI: 0.9-1.9) larger waist circumference. Findings indicate the importance of considering ST as a distinct health risk among adults with severe obesity, and suggest a 10min minimum duration may be preferable to 1min or 30min for establishing ST from activity monitor data.
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Postoperative Behavioral Variables and Weight Change 3 Years After Bariatric Surgery.
Mitchell, JE, Christian, NJ, Flum, DR, Pomp, A, Pories, WJ, Wolfe, BM, Courcoulas, AP, Belle, SH
JAMA surgery. 2016;(8):752-7
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IMPORTANCE Severe obesity (body mass index ≥35 [calculated as weight in kilograms divided by height in meters squared]) is associated with significant medical comorbidity and increased mortality. Bariatric surgery induces weight loss, the extent of which can vary. Postoperative predictors of weight loss have not been adequately examined. OBJECTIVE To describe postoperative eating behaviors and weight control and their effects on 3-year change in weight. DESIGN, SETTING, AND PARTICIPANTS The Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study is a multicenter observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. Adults undergoing first-time bariatric surgical procedures as part of routine clinical care were recruited between 2006 and 2009 and followed up until September 2012. Participants completed detailed surveys regarding eating and weight control behaviors prior to surgery and then annually after surgery for 3 years. MAIN OUTCOMES AND MEASURES Twenty-five postoperative behaviors related to eating behavior, eating problems, weight control practices, and the problematic use of alcohol, smoking, and illegal drugs. Behaviors examined were divided into those that were never present (preoperatively or postoperatively), those that were always present (preoperatively and postoperatively), and those that underwent a healthy change after surgery (development of a positive behavior or omission of a negative behavior). RESULTS The sample included a total of 2022 participants (median age, 47 years [interquartile range, 38-55 years]; median BMI, 46 [interquartile range, 42-51]; 78% women): 1513 who had undergone Roux-en-Y gastric bypass and 509 who had undergone laparoscopic adjustable gastric banding. If we consider the cumulative effects of the 3 behaviors that explain most of the variability (16%) in 3-year percent weight change following Roux-en-Y gastric bypass, ie, weekly self-weighing, continuing to eat when feeling full more than once a week, and eating continuously during the day, a participant who postoperatively started to self-weigh, stopped eating when feeling full, and stopped eating continuously during the day after surgery would be predicted to lose a mean (SE) of 38.8% (0.8%) of their baseline weight. This average is about 14% greater weight loss compared with participants who made no positive changes in these variables (mean [SE], -24.6% [1.6%]; mean difference, -14.2%; 95% CI, -18.7% to -9.8%; P < .001) and 6% greater weight loss compared with participants who always reported positive on these healthy behaviors (mean [SE], -33.2% [0.6%]; mean difference, -5.7%; 95% CI, -7.8% to -3.5%; P < .001). CONCLUSIONS AND RELEVANCE The results suggest the importance of assessing behaviors related to eating behavior, eating problems, weight control practices, and the problematic use of alcohol, smoking, and illegal drugs in bariatric surgery candidates and patients who have undergone bariatric surgery, and they suggest that the utility of programs to modify problematic eating behaviors and eating patterns should be addressed in research.
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Change in Pain and Physical Function Following Bariatric Surgery for Severe Obesity.
King, WC, Chen, JY, Belle, SH, Courcoulas, AP, Dakin, GF, Elder, KA, Flum, DR, Hinojosa, MW, Mitchell, JE, Pories, WJ, et al
JAMA. 2016;(13):1362-71
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IMPORTANCE The variability and durability of improvements in pain and physical function following Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB) are not well described. OBJECTIVES To report changes in pain and physical function in the first 3 years following bariatric surgery, and to identify factors associated with improvement. DESIGN, SETTING, AND PARTICIPANTS The Longitudinal Assessment of Bariatric Surgery-2 is an observational cohort study at 10 US hospitals. Adults with severe obesity undergoing bariatric surgery were recruited between February 2005 and February 2009. Research assessments were conducted prior to surgery and annually thereafter. Three-year follow-up through October 2012 is reported. EXPOSURES Bariatric surgery as clinical care. MAIN OUTCOMES AND MEASURES Primary outcomes were clinically meaningful presurgery to postsurgery improvements in pain and function using scores from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) (ie, improvement of ≥5 points on the norm-based score [range, 0-100]) and 400-meter walk time (ie, improvement of ≥24 seconds) using established thresholds. The secondary outcome was clinically meaningful improvement using the Western Ontario McMaster Osteoarthritis Index (ie, improvement of ≥9.7 pain points and ≥9.3 function points on the transformed score [range, 0-100]). RESULTS Of 2458 participants, 2221 completed baseline and follow-up assessments (1743 [78.5%] were women; median age was 47 years; median body mass index [BMI] was 45.9; 70.4% underwent RYGB; 25.0% underwent LAGB). At year 1, clinically meaningful improvements were shown in 57.6% (95% CI, 55.3%-59.9%) of participants for bodily pain, 76.5% (95% CI, 74.6%-78.5%) for physical function, and 59.5% (95% CI, 56.4%-62.7%) for walk time. Additionally, among participants with severe knee or disability (633), or hip pain or disability (500) at baseline, approximately three-fourths experienced joint-specific improvements in knee pain (77.1% [95% CI, 73.5%-80.7%]) and in hip function (79.2% [95% CI, 75.3%-83.1%]). Between year 1 and year 3, rates of improvement significantly decreased to 48.6% (95% CI, 46.0%-51.1%) for bodily pain and to 70.2% (95% CI, 67.8%-72.5%) for physical function, but improvement rates for walk time, knee and hip pain, and knee and hip function did not (P for all ≥.05). Younger age, male sex, higher income, lower BMI, and fewer depressive symptoms presurgery; no diabetes and no venous edema with ulcerations postsurgery (either no history or remission); and presurgery-to-postsurgery reductions in weight and depressive symptoms were associated with presurgery-to-postsurgery improvements in multiple outcomes at years 1, 2, and 3. CONCLUSIONS AND RELEVANCE Among a cohort of participants with severe obesity undergoing bariatric surgery, a large percentage experienced improvement, compared with baseline, in pain, physical function, and walk time over 3 years, but the percentage with improvement in pain and physical function decreased between year 1 and year 3. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00465829.