Global economic development has been associated with an increased prevalence of obesity and related health problems. Increased caloric intake and reduced energy expenditure are both cited as development-related contributors to the obesity crisis, but their relative importance remains unresolved. Here, we examine energy expenditure and two measures of obesity (body fat percentage and body mass index, BMI) for 4,213 adults from 34 populations across six continents and a wide range of lifestyles and economies, including hunter-gatherer, pastoralist, farming, and industrialized populations. Economic development was positively associated with greater body mass, BMI, and body fat, but also with greater total, basal, and activity energy expenditure. Body size-adjusted total and basal energy expenditures both decreased approximately 6 to 11% with increasing economic development, but were highly variable among populations and did not correspond closely with lifestyle. Body size-adjusted total energy expenditure was negatively, but weakly, associated with measures of obesity, accounting for roughly one-tenth of the elevated body fat percentage and BMI associated with economic development. In contrast, estimated energy intake was greater in economically developed populations, and in populations with available data (n = 25), the percentage of ultraprocessed food in the diet was associated with body fat percentage, suggesting that dietary intake plays a far greater role than reduced energy expenditure in obesity related to economic development.

ObjectiveThis observational study investigated metabolomic changes in individuals with type 2 diabetes (T2D) after weight loss. We hypothesized that metabolite changes associated with T2D-relevant phenotypes are signatures of improved health.MethodsFasting plasma samples from individuals undergoing bariatric surgery (n = 71 Roux-en-Y gastric bypass [RYGB], n = 22 gastric banding), lifestyle intervention (n = 66), or usual care (n = 14) were profiled for 139 metabolites before and 2 years after weight loss. Principal component analysis grouped correlated metabolites into factors. Association of preintervention metabolites was tested with preintervention clinical features and changes in T2D markers. Association between change in metabolites/metabolite factors and change in T2D remission markers, homeostasis model assessment of beta-cell function, homeostasis model assessment of insulin resistance, and glycated hemoglobin (HbA1c) was assessed.ResultsBranched-chain amino acids (BCAAs) were associated with preintervention adiposity. Changes in BCAAs (valine, leucine/isoleucine) and branched-chain ketoacids were positively associated with change in HbA1c (false discovery rate q value <= 0.001) that persisted after adjustment for percentage weight change and RYGB (p <= 0.02). In analyses stratified by RYGB or other weight loss method, some metabolites showed association with non-RYGB weight loss.ConclusionsThis study confirmed known metabolite associations with obesity/T2D and showed an association of BCAAs with HbA1c change after weight loss, independent of the method or magnitude of weight loss.imageConclusionsThis study confirmed known metabolite associations with obesity/T2D and showed an association of BCAAs with HbA1c change after weight loss, independent of the method or magnitude of weight loss.image Summary of the study.image

Background: Idiopathic intracranial hypertension (IIH), a rare neurological disorder, has limited effective long-term treatments. Bariatric surgery has shown short-term promise as a management strategy, but long-term efficacy has not been evaluated. We investigated IIH-related outcomes 4 to 16 years postsurgery. Materials and Methods: This cross-sectional retrospective cohort study included Intracranial Hypertension Registry (IHR) participants with existing medical records that completed a bariatric surgery questionnaire at least 4 years postsurgery. Two physicians independently evaluated the IIH disease course at bariatric surgery and at the time of the questionnaire using detailed medical records. Determinations of improvements were based on within-participant comparisons between the 2 time points. IIH-related outcomes were then combined with bariatric surgery information and outcomes to assess the relationship between weight loss and alterations in IIH. Results: Among participants that underwent bariatric surgery and met study criteria (n=30) the median body mass index (BMI) at the time of surgery was 45.0 [interquartile range (IQR): 39.8-47.0], dropped to a postsurgical nadir of 27.3 (IQR: 22.8-33.1), and rose to 33.4 (IQR: 29.9-41.7) at the time of the questionnaire. Improvements in the IIH disease course at time of the questionnaire occurred in 37% of participants. However, there was a notable association between durable weight loss and IIH improvement as 90% (9 of 10) of participants that attained and maintained a BMI of 30 or below displayed improvement. Conclusions: Attaining and maintaining a BMI of 30 or below was associated with long-term improvement in the IIH disease course, including improved disease management and amelioration of signs and symptoms of participants of the IHR.

Bariatric surgery has emerged as an efficacious treatment for obesity and its comorbidities. Chronic kidney disease (CKD), similar to other comorbidities of obesity, improves with the significant and sustained weight loss resulting from bariatric surgery. In this chapter, specific obesity comorbidities are delineated, and the pathogenesis underlying these comorbidities is addressed. Indications for bariatric surgery along with descriptions of individual operations are discussed. Nutritional management recommendations after bariatric surgery, dependent on the bariatric operation performed, are given in the context of the added complexity of nutrition challenges in CKD. A review of bariatric surgery outcomes in general, and in the setting of CKD is covered. Current evidence for bariatric surgery in the overall management of transplant for end-stage kidney disease is also included. Finally, an assessment of factors considered in the cost/benefit analysis of bariatric surgery as a treatment is introduced.

Breast cancer is the most common and second deadliest malignancy in women. With rising obesity rates and building evidence for a strong association with obesity, the incidence of breast cancer can be expected to increase. Weight loss reduces breast cancer risk, the mechanisms of which are still poorly understood. As an effective therapy for obesity, bariatric surgery may be a powerful tool in breast cancer prevention and treatment. This review details the potential physiologic mechanisms that may underlie this association, as well as recently published studies that reinforce the link between bariatric surgery and a reduction in incident breast cancer. The use of bariatric surgery as an adjunct therapy in endometrial cancer also raises the potential for similar use in select breast cancer patients. Despite the expanding potential applications of bariatric surgery in this field, publications to date have been strictly observational, highlighting a need for future clinical trials.

Objective: To evaluate smoking history and change in smoking behavior, from 1 year before through 7 years after Roux-en-Y gastric bypass (RYGB) surgery, and to identify risk factors for post-surgery smoking. Background: Smoking behavior in the context of bariatric surgery is poorly described. Methods: Adults undergoing RYGB surgery entered a prospective cohort study between 2006 and 2009 and were followed up to 7 years until ≤2015. Participants (N = 1770; 80% female, median age 45 years, median body mass index 47 kg/m2) self-reported smoking history pre-surgery, and current smoking behavior annually. Results: Almost half of participants (45.2%) reported a pre-surgery history of smoking. Modeled prevalence of current smoking decreased in the year before surgery from 13.7% [95% confidence interval (CI) = 12.1–15.4] to 2.2% (95% CI = 1.5–2.9) at surgery, then increased to 9.6% (95% CI = 8.1–11.2) 1-year post-surgery and continued to increase to 14.0% (95% CI = 11.8–16.0) 7-years post-surgery. Among smokers, mean packs/day was 0.60 (95% CI = 0.44–0.77) at surgery, 0.70 (95% CI = 0.62–0.78) 1-year post-surgery and 0.77 (95% CI = 0.68–0.88) 7-years post-surgery. At 7-years, smoking was reported by 61.7% (95% CI = 51.9–70.8) of participants who smoked 1-year pre-surgery (n = 221), 12.3% (95% CI = 8.5–15.7) of participants who formerly smoked but quit >1 year pre-surgery (n = 507), and 3.8% (95% CI = 2.1–4.9) of participants who reported no smoking history (n = 887). Along with smoking history (ie, less time since smoked), younger age, household income <$25,000, being married or living as married, and illicit drug use were independently associated with increased risk of post-surgery smoking. Conclusion: Although most adults who smoked 1-year before RYGB quit pre-surgery, smoking prevalence rebounded across 7-years, primarily due to relapse.

There is marked heterogeneity in the response to weight loss interventions with regards to weight loss amount and metabolic improvement. We sought to identify biomarkers predictive of type 2 diabetes remission and amount of weight loss in individuals with severe obesity enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples using a nested design for diabetes remission over five years (n = 93 LABS, n = 80 Look AHEAD; n = 87 remitters), and for extremes of weight loss at five years (n = 151 LABS; n = 75 with high weight loss). Principal components analysis (PCA) was used for dimensionality reduction, with PCA-derived metabolite factors tested for association with both diabetes remission and weight loss. Metabolic markers were tested for incremental improvement to clinical models, including the DiaRem score. Two metabolite factors were associated with diabetes remission: one primarily composed of branched chain amino acids (BCAA) and tyrosine (odds ratio (95% confidence interval) [OR (95% CI)] = 1.4 [1.0–1.9], p = 0.045), and one with betaine and choline (OR [95% CI] = 0.7 [0.5–0.9], p = 0.02).These results were not significant after adjustment for multiple tests. Inclusion of these two factors in clinical models yielded modest improvements in model fit and performance: in a constructed clinical model, the C-statistic improved from 0.87 to 0.90 (p = 0.02), while the net reclassification index showed improvement in prediction compared to the DiaRem score (NRI = 0.26, p = 0.0013). No metabolite factors associated with weight loss at five years. Baseline levels of metabolites in the BCAA and trimethylamine-N-oxide (TMAO)-microbiome-related pathways are independently and incrementally associated with sustained diabetes remission after weight loss interventions in individuals with severe obesity. These metabolites could serve as clinically useful biomarkers to identify individuals who will benefit the most from weight loss interventions.

Background: Postbariatric hypoglycemia (PBH) can be a devastating complication for which cur-rent therapies are often incompletely effective. More information is needed regarding frequency, inci-dence, and risk factors for PBH. Objectives: To examine hypoglycemia symptoms following Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) and baseline and in-study risk factors. Setting: Multicenter, at 10 US hospitals in 6 geographically diverse clinical centers. Methods: A prospective, longitudinal cohort study of adults undergoing RYGB or LAGB as part of clinical care between 2006 and 2009 were recruited and followed until January 31, 2015, with base-line and annual postoperative research assessments. We analyzed baseline prevalence and post -operative incidence and frequency of self-reported hypoglycemia symptoms as well as potential preoperative risk factors. Results: In all groups, postoperative prevalence of hypoglycemia symptoms was 38.5%. Symptom prevalence increased postoperatively from 2.8%-36.4% after RYGB in patients without preoperative diabetes (T2D), with similar patterns in prediabetes (4.9%-29.1%). Individuals with T2D had higher baseline hypoglycemia symptoms (28.9%), increasing after RYGB (57.9%). Hypoglycemia symp-toms were lower after LAGB, with 39.1% reported hypoglycemia symptoms at only 1 postoperative visit with few (4.0%) having persistent symptoms at 6 or more annual visits. Timing of symptoms was not restricted to the postprandial state. Symptoms of severe hypoglycemia were reported in 2.6-3.6% after RYGB. The dominant risk factor for postoperative symptoms was preoperative symptoms; addi-tionally, baseline selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor use was also associated with increased risk in multivariable analysis. Weight loss and regain were not related to hypoglycemia symptom reporting. Conclusion: Hypoglycemia symptoms increase over time after RYGB, particularly in patients without diabetes. In a small percentage, symptoms can be persistent or severe and require hospitalization. Preoperative hypoglycemia symptoms and SSRI/SNRI use in RYGB patients without diabetes is associated with increased risk of symptoms. (C) 2021 Published by Elsevier Inc. on behalf of American Society for Bariatric Surgery.

ObjectiveThis study sought to determine improvements in mental and physical health–related quality of life (HRQOL) following bariatric surgery in Medicaid and commercially insured patients.MethodsUsing data from the Longitudinal Assessment of Bariatric Surgery, an observational cohort study of adults undergoing bariatric surgery (2006‐2009), changes in Short Form 36 mental component summary (MCS) and physical component summary (PCS) scores were examined in 1,529 patients who underwent Roux‐en‐Y gastric bypass, laparoscopic adjustable band, or sleeve gastrectomy and were followed for 5 years. Piecewise linear mixed‐effects models estimated MCS and PCS scores as a function of insurance group (Medicaid, N = 177; commercial, N = 1,352) from 0 to 1 year and from 1 to 5 years after surgery, with interactions between insurance group and surgery type.ResultsPatients with Medicaid had lower PCS and MCS scores at baseline. At 1 year after surgery, patients with Medicaid and commercial insurance experienced similar improvement in PCS scores (commercial‐Medicaid difference in PCS change [95% CI]: Roux‐en‐Y gastric bypass, 1.5 [−0.2, 3.3]; laparoscopic adjustable band, 1.9 [−2.2, 6.0]; sleeve gastrectomy, 6.4 [0.0, 12.8]). One‐year MCS score improvement was minimal and similar between insurance groups. In years 1 to 5, PCS and MCS scores were stable in all groups.ConclusionsBoth insurance groups experienced improvements in physical HRQOL and minimal changes in mental HRQOL.

Background: Bariatric surgery reduces cancer risk in populations with obesity. It is unclear if weight loss alone or metabolic changes related to bariatric surgery cause this effect. Objective: We evaluated the relationship between surgical weight loss and serum biomarker changes with incident cancer in a bariatric surgery cohort. Setting: Ten U.S. clinical facilities. Methods: The Longitudinal Assessment of Bariatric Surgery 2 (LABS-2) is a prospective multicenter cohort (n = 2458, 79% female, mean age = 46). We evaluated weight and serum biomarkers, measured preoperatively and 1 year postoperatively, as predictors for incident cancer. Associations were determined using Cox proportional hazards models adjusting for weight loss, age, sex, education, and smoking history. Results: Over 8759 person-years of follow-up, 82 patients reported new cancer diagnosis (936 per 100,000 person-years, 95% confidence interval [CI]: 749-1156). Cancer risk was decreased by approximately 50% in participants with 20% to 34.9% total weight loss (TWL) compared with <20% TWL (hazard ratio [HR] = .49, 95%CI: .29-.83). Reduced cancer risk was observed with percent decrease from baseline for glucose (per 10%, HR = .94, 95%CI: .90-.99), proinsulin (per 20%, HR = .95, 95% CI: .93-.98), insulin (per 30%, HR = .97, 95%CI: .96-.99), and leptin (per 20%, HR = .81, 95%CI: .68-.97), and per 15% percent increase in ghrelin (HR = .94, 95%CI: .29-.83). Conclusions: After bariatric surgery, cancer risk is reduced >50% when weight loss exceeds 20% TWL compared with patients with <20% TWL. Weight loss alone may not explain the observed risk reduction, as improvements in diabetes, leptin, and ghrelin were associated with decreased cancer risk. (C) 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

The response to weight loss intervention is heterogeneous both in weight loss amount and improvement in metabolism. We seek to identify biomarkers predictive of long-term weight loss and type 2 diabetes (T2D) remission in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies. Methods: LABS is a longitudinal observational study of 2458 consecutive cases (2006-2009) of bariatric surgery. Look AHEAD is an RCT comparing an intensive lifestyle intervention to T2D support and education in 5,145 U.S. adults with obesity and T2D enrolled between 2001-2004. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples from individuals selected based on sustained T2D remission (N=93 LABS, N=80 Look AHEAD) and extremes (top and bottom 13th percentile) of weight loss (N=151 LABS, 23 with T2D) at 4 or 5 years. We used PCA for dimensionality reduction of metabolites and logistic regression models to determine association between metabolic factors and phenotype. Improvement in model fit and net reclassification index analyses were performed to determine if metabolites improved a clinical model for predicting remission. Results: One factor composed of branched chain amino acids (BCAA) and tyrosine (p=0.045), and one composed of betaine and choline (p=0.02) were associated with T2D remission. Inclusion of these factors in a clinical prediction model improved the fit (p=0.04). Only one factor, composed of C31:1-C37:1 sphingomyelins, associated with weight loss at 5 years (p=0.036). Conclusions. Our findings define novel associations between metabolites in the BCAA and trimethylamine-N-oxide-microbiome-related pathways that are independently and incrementally associated with sustained T2D remission after weight loss. Future studies of these analytes could help in the discovery of metabolic regulatory mechanisms, and guide more personalized weight loss interventions in individuals with T2D. Disclosure L.C. Kwee: None. O. Ilkayeva: None. M. Muehlbauer: None. B.M. Wolfe: None. J.Q. Purnell: Advisory Panel; Self; Novo Nordisk A/S. H. Chen: None. C.B. Newgard: None. S.H. Shah: Research Support; Self; AstraZeneca, Verily Life Sciences LLC. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK108580)

At its peak in the 2000s, as many as 25% of bariatric procedures were adjustable gastric banding. However, the declining utilization of this procedure in the wake of more contemporary procedures warrants examination. This chapter will summarize the history and development of adjustable gastric banding, describe the mechanistic features of the once-innovative procedure, and discuss the reported outcomes of banding in the literature. A narrative summary of the over-exaggeration of predicted weight loss; frequency for revision, removal and/or conversion; and the advent of more effective procedures are all cited as factors for the procedure’s decline and ultimate failure.

ObjectiveThis study aimed to examine whether pregnancy following bariatric surgery affects long‐term maternal weight change and offspring birth weight.MethodsUsing data from the Longitudinal Assessment of Bariatric Surgery (LABS)‐2 study, linear regression was used to evaluate percent change in total body weight over a 5‐year follow‐up period among reproductive‐aged women who underwent Roux‐en‐Y gastric bypass or laparoscopic adjustable gastric banding as well as evaluate the association of bariatric procedure type and offspring birth weight.ResultsOf 727 women with preoperative age of 36.1 (6.3) years (mean [SD]) and BMI of 46.9 (7.0) kg/m2, 80 (11%) reported at least one pregnancy. After adjusting for covariates, percent change in total body weight was not significantly different between women who became pregnant and those who did not during a 5‐year follow‐up period (β = 2.02; 95% CI: −1.03 to 5.07; P = 0.19). Additionally, mean birth weight was not significantly different between mothers who underwent Roux‐en‐Y gastric bypass versus laparoscopic adjustable gastric banding (P = 0.99).ConclusionsPostoperative pregnancy did not diminish long‐term weight loss in women in the LABS‐2 study. The finding of comparable weight loss is relevant for providers counseling women of reproductive age on weight‐loss expectations and family planning following bariatric surgery.

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.

CONTEXT:Few studies have examined the clinical characteristics that predict durable, long-term diabetes remission after bariatric surgery.OBJECTIVE:To compare diabetes prevalence and remission rates during 7-year follow-up after Roux-en-Y gastric bypass (RYGB) and laparoscopic gastric banding (LAGB).DESIGN:An observational cohort of adults with severe obesity recruited between 2006 and 2009 who completed annual research assessments for up to 7 years after RYGB or LAGB.SETTING:Ten US hospitals.PARTICIPANTS:A total sample of 2256 participants, 827 with known diabetes status at both baseline and at least 1 follow-up visit.INTERVENTIONS:Roux-en-Y gastric bypass or LAGB.MAIN OUTCOME MEASURES:Diabetes rates and associations of patient characteristics with remission status.RESULTS:Diabetes remission occurred in 57% (46% complete, 11% partial) after RYGB and 22.5% (16.9% complete, 5.6% partial) after LAGB. Following both procedures, remission was greater in younger participants and those with shorter diabetes duration, higher C-peptide levels, higher homeostatic model assessment of β-cell function (HOMA %B), and lower insulin usage at baseline, and with greater postsurgical weight loss. After LAGB, reduced HOMA insulin resistance (IR) was associated with a greater likelihood of diabetes remission, whereas increased HOMA-%B predicted remission after RYGB. Controlling for weight lost, diabetes remission remained nearly 4-fold higher compared with LAGB.CONCLUSIONS:Durable, long-term diabetes remission following bariatric surgery is more likely when performed soon after diagnosis when diabetes medication burden is low and beta-cell function is preserved. A greater weight-independent likelihood of diabetes remission after RYGB than LAGB suggests mechanisms beyond weight loss contribute to improved beta-cell function after RYGB.Trial Registration clinicaltrials.gov Identifier: NCT00465829.