Search

Obesity increases the risk of developing type 2 diabetes, hypertension, and hyperlipidemia. We sought to determine the impact of obesity maintenance, weight regain, weight loss maintenance, and magnitudes of weight loss on future risk and time to developing these cardiometabolic conditions. This was a retrospective cohort study of adults receiving primary care at Geisinger Health System between 2001 and 2017. Using electronic health records, patients with ≥3-weight measurements over a 2-year index period were identified and categorized. Obesity maintainers (OM) had obesity (body mass index ≥30 kg/m²) and maintained their weight within ±3% from baseline (reference group). Both weight loss rebounders (WLR) and weight loss maintainers (WLM) had obesity at baseline and lost5% body weight in year 1; WLR regained ≥20% of weight loss by end of year 2 and WLM maintained ≥80% of weight loss. Incident type 2 diabetes, hypertension, and hyperlipidemia, and time-to-outcome were determined for each study group and by weight loss category for WLM. Of the 63,567 patients included, 67% were OM, 19% were WLR, and 14% were WLM. The mean duration of follow-up was 6.6 years (SD, 3.9). Time until the development of electronic health record-documented type 2 diabetes, hypertension, and hyperlipidemia was longest for WLM and shortest for OM (log-rank test p0.0001). WLM had the lowest incident type 2 diabetes (adjusted hazard ratio [HR] 0.676 [95% confidence interval [CI] 0.617 to 0.740]; p0.0001), hypertension (adjusted HR 0.723 [95% CI 0.655 to 0.799]; p0.0001), and hyperlipidemia (adjusted HR 0.864 [95% CI 0.803 to 0.929]; p0.0001). WLM with the greatest weight loss (15%) had a longer time to develop any of the outcomes compared with those with the least amount of weight loss (7%) (p0.0001). In an integrated delivery network population, sustained weight loss was associated with a delayed onset of cardiometabolic diseases, particularly with a greater magnitude of weight loss.

Introduction Sarcopenic obesity and its association with nonalcoholic fatty liver disease (NAFLD) is under‐recognized by many healthcare providers in Western medicine due to the lack of awareness and diagnostic guidelines. The result is delayed recognition and treatment, which leads to further health deterioration and increased healthcare costs. Sarcopenic obesity is characterized by the presence of increased fat mass in combination with muscle catabolism related to chronic inflammation and/or inactivity. Previous research has recommended evaluating body composition and physical function performance to adequately diagnose sarcopenic obesity. Body composition analysis can be performed by imaging applications through magnetic resonance imaging, computed tomography, and dual‐energy x‐ray absorptiometry. Due to the cost of each device and radiation exposure for patients as evidenced in all three modalities, bioelectrical impedance analysis offers a noninvasive approach capable of providing quick and reliable estimates of lean body and fat mass. Methods and Results This review analyzes the current evidence‐based literature, indicating a lower skeletal muscle mass and increased visceral adipose tissue correlation to the advancement of fibrosis in fatty liver disease. Conclusion Given the substantial promising research conducted in predominantly Asian populations regarding body tissue distribution and NAFLD, additional prospective research is needed to extend these findings in Western populations.

The presence of chronic low-grade inflammation, commonly identified in patients with severe obesity, alters iron homeostasis and indicators of iron status, fostering the development of updated guidelines for the diagnosis of iron deficiency (ID). Current recommended diagnostic thresholds for ID in obesity derived from expert opinion include a ferritin level of30 ng/mL and/or transferrin saturation (TSAT)20%. Earlier studies of ID among candidates for metabolic surgery using low levels of ferritin or iron as diagnostic thresholds demonstrated a prevalence of 5%-20%.Using the current recommended diagnostic thresholds for ID, this study measures the prevalence of ID in a large cohort of surgical candidates and its relationship to surgical outcomes.Geisinger Medical Center, Danville, Pennsylvania.The study cohort included 3,723 patients who underwent pre- operative nutritional assessment which included markers of iron nutrition over the period 2004-2018.The cohort included 2,988 women (80.3%) and 735 men (19.7%); body mass index: 49.4 ± 9 kg/mThe prevalence of ID among surgical candidates (45.4%) is more than twice that identified as ID in earlier studies. ID was commonly identified in the absence of anemia. The most severe ID was found in those with a serum ferritin level30 ng/mL and TSAT20%. ID in the presence of inflammation is often unrecognized and has implications regarding surgical outcomes after metabolic surgery.

Low patient recruitment into diabetes prevention programs is a challenge. The primary aim of this study was to demonstrate that an increased recruitment rate can be achieved by communicating personalized risk of progression to type 2 diabetes, estimating risk reduction with weight loss, and offering program choice. Secondary aims included program participation rate, weight loss, and short-term decreased diabetes risk.In this single-arm study, persons with prediabetes from 3 primary care sites received a letter that communicated their personalized risk of progression to diabetes within 3-years, estimated risk reduction with 5, 10, 15 % weight loss, reported in pounds, and offered a choice of 5 free, 6-month, programs. A one-sided test was used to compare the recruitment rate against the maximum expected rate of (10 %).Recruitment response rate was 25.3 % (81/328, 95 % CI=[20.0 %, 29.4 %]) which was significantly higher than expected (p0.0001). Overall, 65 % of participants completed75 % of contacts. BMI, HbA1c, and diabetes risk (all p0.0001) improved at 6 months; BMI (p0.0001) and HbA1c (p0.05) improved at 12 months.Recruitment response rate was better than expected.Communicating personalized risk and reduction estimates with a choice of programs resulted in favorable outcomes, sustained at 1-year.

BACKGROUND: The extent to which obesity and genetics determine post-operative complications is incompletely understood. METHODS: We performed a retrospective study using two population cohorts with electronic health record (EHR) data. The first included 736,726 adults with body mass index (BMI) recorded between 1990-2017 at Vanderbilt University Medical Center. The second cohort consisted of 65,174 individuals from 12 institutions contributing EHR and genome-wide genotyping data to the Electronic Medical Records & Genomics (eMERGE) Network. Pairwise logistic regression analyses were used to measure the association of BMI categories with postoperative complications derived from International Classification of Disease-9 codes, including postoperative infection, incisional hernia, and intestinal obstruction. A genetic risk score (GRS) was constructed from 97 obesity-risk single nucleotide polymorphisms for a Mendelian randomization study to determine the association of genetic risk for obesity on postoperative complications. Logistic regression analyses were adjusted for sex, age, site, and race/principal components. RESULTS: Individuals with overweight or obese BMI (≥25 kg/m(2)) had increased risk for incisional hernia (Odds ratio [OR] 1.7-5.5, p

The oldest old (aged ≥80 years) are often the population subgroup at high nutritional risk due to age-related metabolic changes. We performed a validation analysis of a dietary screening tool (DST) which was developed for older adults among the oldest old. We examined dietary intakes using three 24-hour dietary recalls and the DST among 122 participants (aged 82-97) of the Geisinger Rural Aging Study. DST scores were compared with the Health Eating Index (HEI)-2015 scores, which were calculated based on three-day dietary recalls. Pearson correlations were used to characterize concurrent validity and Bland-Altman plots were used to identify potential bias. DST scores were significantly correlated with HEI scores (adjusted r = 0.68; p 0.001) in an age- and sex-adjusted model. Those within the not-at-risk DST group had significantly higher HEI scores (adjusted means = 79.6 ± 3.68) compared with those who were in the at-risk (adjusted means = 51.2 ± 1.56) and the possibly-at-risk (adjusted means = 66.3 ± 1.79) groups (p-trend0.001). The DST appears to be a valid measure of diet quality in the oldest old when compared with the HEI and may be a potential tool to assess overall diet quality in this population.

More perceived physical fatigability and poor diet quality are associated with impairments in physical function in older adults. However, the degree to which more perceived fatigability explains the association between poor diet quality and low physical function is unknown. We examined this relationship in 122 (66F, 56M) of the oldest-old participants from the Geisinger Rural Aging Study (GRAS). We used 24-h dietary recalls to assess the Healthy Eating Index (HEI), the Pittsburgh Fatigability Scale (PFS, 0–50) to assess perceived physical fatigability, and the PROMIS Physical Function 20a* to assess physical function. We grouped participants into three age categories: 80–84 (n = 51), 85–89 (n = 51), and 90+ (n = 20) years. Multiple linear regression revealed that a lower HEI was associated with higher PFS Physical score after adjusting for age group, sex, body mass index, and the number of medical conditions (p = 0.001). Several macro- and micro-nutrient intakes were also lower in those reporting more (≥15) compared to less (&lt, 15) perceived physical fatigability. Mediation analysis revealed that PFS Physical scores explained ~65% (p = 0.001) of the association between HEI total score and PROMIS19 Physical Function score. Poor diet quality may contribute to more perceived physical fatigability, which could exacerbate impairments in the oldest-old’s physical function.

Background Several dietary components have been shown to be neuroprotective against risk of neurodegeneration. However, limited observational studies have examined the role of overall diet quality on risk of Parkinson's disease. Objectives We examined the associations between diet quality and risk of Parkinson's disease in a prospective cohort study and meta-analysis. Methods Included in the cohort study were 3,653 participants (1,519 men and 2,134 women; mean age: 81.5 years) in the Geisinger Rural Aging Study longitudinal cohort in Pennsylvania. Diet quality was assessed using a validated dietary screening tool containing 25 food- and behavior-specific questions in 2009. Potential Parkinson's cases were identified using electronic health records based on ICD9 (332.*), ICD10 (G20), and Parkinson-related treatments. Hazard ratios (HRs) and 95% confidence intervals (CIs) across diet quality tertiles were calculated using Cox proportional hazards models after adjusting for potential confounders. We further performed a meta-analysis by pooling our study with four published papers on this topic. Random-effects model was utilized to calculate the pooled risk ratios and 95% confidence intervals (CIs). Results During a mean of 6.94 years of follow-up, 47 incident Parkinson's cases were documented. Having high diet quality at baseline was associated with lower Parkinson's disease risk (adjusted HR for the highest vs the lowest diet quality tertile = 0.39; 95% CI: 0.17, 0.89; p-trend = 0.02). The meta-analysis including 140,617 individuals also showed that adherence to high diet quality or a healthy dietary pattern was associated with lower risk of Parkinson's disease (pooled risk ratio = 0.64; 95% CI: 0.49, 0.83). Conclusion Having high diet quality or a healthy dietary pattern was associated with lower future risk of Parkinson's disease.

The near universal presence of chronic low-grade systemic inflammation among patients with severe obesity disrupts iron homeostasis and underlies the association between obesity and iron deficiency. Immune activation and inflammation results in a reduction in circulating iron and diminished iron bioavailability for erythropoiesis. Inflammation also alters blood levels of commonly measured markers of iron nutrition status, which makes the diagnosis of iron deficiency difficult and has led to new recommendations regarding laboratory markers for the diagnosis. Recent evidence utilizing these newly recommended laboratory markers which include levels of ferritin, C Reactive Protein, and Transferrin Saturation suggests that the actual prevalence of iron deficiency among candidates for metabolic surgery may be double or triple the prevalence identified by low levels of ferritin alone. Thus, large numbers of surgical candidates have iron deficiency which has been heretofore largely unrecognized and inadequately treated. The assessment of iron status utilizing the currently recommended markers in the presence of chronic inflammatory diseases, and repletion of depleted stores for surgical candidates with deficiency during the pre-operative period presents an important opportunity for mitigating this condition in post-operative patients.

A real-time trial of a cancer blood test Cancers diagnosed early are often more responsive to treatment. Blood tests that detect molecular markers of cancer have successfully identified individuals already known to have the disease. Lennon et al. conducted an exploratory study that more closely reflects the way in which such blood tests would be used in the future. They evaluated the feasibility and safety of incorporating a multicancer blood test into the routine clinical care of 10,000 women with no history of cancer. Over a 12-month period, the blood test detected 26 cancers of different types. A combination of the blood test and positron emission tomography–computed tomography (PET-CT) imaging led to surgical removal of nine of these cancers. Use of the blood test did not result in a large number of futile follow-up procedures. Science , this issue p. eabb9601

Summary Objective The purpose of this study was to compare body composition measurements estimated by multi‐frequency bioelectrical impedance analysis (MF‐BIA) with air displacement plethysmography (ADP) in individuals with obesity. Methods Bariatric patients were recruited from Geisinger's Center for Nutrition and Weight Management Clinic in Danville, Pennsylvania. Sixty‐two participants (age = 52.4 ± 9.3 years; body mass index = 38.9 ± 8.0 kg m−2) reported for a same‐day testing visit. Body composition was measured using a common MF‐BIA analyzer (InBody 720, Biospace Co., Beverly Hills, CA) and ADP. Results Strong relationships were observed between MF‐BIA and ADP methods (r = 0.88–0.96, P

Objective: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity.Methods: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥ 27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss.Results: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks.Conclusions: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.

The current popularity of metabolic surgery has led to increasing attention to long-term nutritional complications.The purpose of this retrospective study is to accurately define the long-term incidence of clinically significant anemia after Roux-en-Y gastric bypass (RYGB) and to identify factors that contribute to increased risk.The study cohort consisted of 2116 patients who underwent RYGB with necessary laboratory information available, and with longitudinal follow-up available (mean 5.3 ± 3.3 yr). A concurrent cohort of nonoperated patients matched for age, sex, body mass index, and baseline hemoglobin was identified (N = 1126). The RYGB and control cohorts were followed longitudinally to estimate the percent that develop mild, moderate, or severe anemia using Kaplan-Meier analysis. Predictors of severe anemia within the RYGB cohort were identified using Cox regression.The percent developing postRYGB mild, moderate, and severe anemia was 27%, 9%, and 2% at 1 year postRYGB and increased to 68%, 33%, and 11% at 5 years postRYGB. As compared with the nonoperated control cohort, the RYGB cohort was more likely to develop mild anemia (hazard ratio [HR] = 1.36, P.001), moderate anemia (HR = 1.75, P.001), and severe anemia (HR = 1.87, P.001). Severity of anemia was associated with an increasing percentage of microcytosis (P.0001). Clinical factors independently associated with an increased risk of severe anemia within the RYGB cohort included females and males40 years of age (HR = 2.97, 95% confidence interval [CI] = 1.14, 7.75, P = .026), preoperative anemia (HR = 1.65, 95% CI = 1.19, 2.29, P = .0029), preoperative low ferritin level (HR = 2.28, 95% CI = 1.39, 3.74, P = .0029), and a rapid 6-month weight loss trajectory (HR = 1.71, 95% CI = 1.22, 2.38, P = .0018).The long-term incidence of clinically significant anemia after RYGB is alarmingly high and warrants more detailed study.

Altered DNA methylation events contribute to the pathogenesis and progression of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Investigations of global DNA methylation patterns in liver biopsies representing severe NAFLD fibrosis have been limited. We used the HumanMethylation 450K BeadChip to analyze genome-wide methylation in patients with biopsy-proven grade 3/4 NAFLD fibrosis/cirrhosis (N = 14) and age- and sex-matched controls with normal histology (N = 15). We identified 208 CpG islands (CGIs), including 99 hypomethylated and 109 hypermethylated CGIs, showing statistically significant evidence (adjusted P value

Total Knee Arthroplasty (TKA, also known as total knee replacement) is a highly effective surgical intervention for the restoration of physical function and improving quality of life in patients with disabling knee osteoarthritis. Recent data suggest that obesity is a major risk factor in the pathogenesis and progression of knee osteoarthritis, with increases in body mass index (BMI, kg/m2) directly correlating with the prevalence of knee osteoarthritis. However, recent data also suggest that there are increased risks associated with TKAs when performed in patients with morbid obesity (BMI > 40 kg/m2). Patients with morbid obesity are routinely referred for weight management prior to surgery. Many of these patients fail to meet the recommended weight loss goals prior to TKA, potentially making them ineligible for surgery or placing them at increased risk for sub-optimal outcomes. Thus, the purpose of this study is to examine the potential therapeutic impact and long-term outcomes of surgically induced weight loss on TKA outcomes. Specifically, these outcomes will include measures of physical function, mobility, and indices of joint function at 1 and 2 years post-TKA compared between extremely obese patients who undergo TKA (Control group, n = 150) and those with TKA performed ~1 year after bariatric surgery (Test group, n = 150). An additional primary endpoint will be the percent of bariatric patients that negate or delay the need for TKA. Secondary endpoints include perioperative outcomes after TKA.

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85–0.92, p = 6.3 × 10−10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49–0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D., Genetic variation in ANGPTL4 is associated with lipid traits. Here, the authors find that predicted loss-of-function variants in ANGPTL4 are associated with glucose homeostasis and reduced risk of type 2 diabetes and that Angptl4−/− mice on a high-fat diet show improved insulin sensitivity.

Objective Determine the impact of long-term non-surgical weight loss maintenance on clinical relevance for osteoarthritis, cancer, opioid use, and depression/anxiety and healthcare resource utilization. Methods A cohort of adults receiving primary care within Geisinger Health System between 2001–2017 was retrospectively studied. Patients with ≥3 weight measurements in the two-year index period and obesity at baseline (BMI ≥30 kg/m2) were categorized: Obesity Maintainers (reference group) maintained weight within +/-3%; Weight Loss Rebounders lost ≥5% body weight in year one, regaining ≥20% of weight loss in year two; Weight Loss Maintainers lost ≥5% body weight in year one, maintaining ≥80% of weight loss. Association with development of osteoarthritis, cancer, opioid use, and depression/anxiety, was assessed; healthcare resource utilization was quantified. Magnitude of weight loss among maintainers was evaluated for impact on health outcomes. Results In total, 63,567 patients were analyzed including 67% Obesity Maintainers, 19% Weight Loss Rebounders, and 14% Weight Loss Maintainers; median follow-up was 9.7 years. Time until osteoarthritis onset was delayed for Weight Loss Maintainers compared to Obesity Maintainers (Logrank test p 15% weight loss was associated with the greatest decrease in incident osteoarthritis. Healthcare resource utilization was significantly higher for Weight Loss Rebounders and Maintainers compared to Obesity Maintainers. Increased weight loss among Weight Loss Maintainers trended with lower overall healthcare resource utilization, except for hospitalizations. Conclusions In people with obesity, sustained weight loss was associated with greater clinical benefits than regained short-term weight loss and obesity maintenance. Higher weight loss magnitudes were associated with delayed onset of osteoarthritis and led to decreased healthcare utilization.

IMPACT: Understanding dietary patterns and nutrient intakes of the aging population may help address concerns and dietary guidelines regarding their nutritional needs. OBJECTIVES/GOALS: The objective of this study is to test the hypothesis that a healthy dietary pattern in the oldest old (aged 80 years and older) is related to greater compliance with dietary recommendations and better nutrient intake profiles. METHODS/STUDY POPULATION: We conducted a cross-sectional study of 122 participants aged 82 to 97 years old from the Geisinger Rural Aging Study (GRAS) cohort in rural Pennsylvania (n = 56 men and 66 women). The main outcome measures of the investigation were the daily nutrient intakes and food group intakes evaluated from the average of three 24-hour dietary recalls. The dietary patterns were determined by cluster analysis from 28 food groups. Diet quality and adherence to the Dietary Guidelines for Americans was assessed by the Healthy Eating Index (HEI)-2015 and the Dietary Screening Tool (DST). Recommended intakes were determined by the Recommended Dietary Allowances (RDAs) or Adequate Intakes (AIs). RESULTS/ANTICIPATED RESULTS: Less than 50% of participants met the dietary recommended intakes for vitamins D, E, K, B6, dietary fiber, zinc, potassium, and calcium. The more-nutrient-dense cluster was characterized by higher intakes of fruits and vegetables. The less-nutrient-dense cluster was characterized by higher intakes of foods including desserts and sweets. After adjusting for age, sex, and energy intake, participants in the more-nutrient-dense dietary pattern had a higher intake of vitamins A, D, K, C, fiber, and potassium (p < 0.05 for all). After adjusting for age and sex, participants in the more-nutrient-dense pattern had better diet quality assessed by the (HEI)-2015 (p < 0.001) and DST (p = 0.006). DISCUSSION/SIGNIFICANCE OF FINDINGS: Among the oldest old, many participants were found to have nutrient intakes lower than the recommended levels for fundamental nutrients suggesting that dietary guidance in addition to a dietary pattern more aligned with dietary guidelines may be beneficial for supporting healthy aging.

The objective of this study was to determine whether the DiaRem, a score that predicts type 2 diabetes (T2D) remission following roux-en-y gastric bariatric surgery (RYGB), also predicts remission following laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) in white and Hispanic patients.While bariatric surgery is highly effective in reversing insulin resistance, there are patients for whom surgery will not lead to remission. To date, there is no score for predicting remission following LAGB or LSG surgery. Additionally, there is little known about how to predict whether Hispanic patients will experience remission.We conducted a retrospective cohort study of white and Hispanic patients with T2D who received bariatric surgery. There were 361 white and 130 Hispanic patients among whom 328 had RYGB surgery, 107 had LSG surgery, and 56 had LAGB surgery. We used age, diabetes treatment, and hemoglobin A1c to calculate DiaRem scores. Mann-Whitney U test was used to determine the association between DiaRem scores and remission. Area under the receiver operant curve (AUC) was used to assess the ability of the DiaRem to discriminate between patients who did and did not remit.The DiaRem was associated with partial remission in all surgery types for white and Hispanic patients (Mann-Whitney, p 0.001). The DiaRem had moderate to high discriminant ability (AUC 0.70) for all surgical and racial/ethnic groups.The DiaRem distinguishes between patients likely and unlikely to experience remission, informing expectations of patients making T2D treatment decisions.

OBJECTIVE This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status. RESEARCH DESIGN AND METHODS RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes. RESULTS Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (n = 625 with diabetes and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for patients with diabetes and 6.7 years for patients without diabetes. All-cause mortality was reduced in RYGB patients compared with control subjects only for those with diabetes at the time of surgery (adjusted hazard ratio 0.44; P < 0.0001). Mortality was not significantly improved in RYGB patients without diabetes compared with control subjects without diabetes (adjusted hazard ratio 0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control subjects with diabetes than in RYGB patients with diabetes. RYGB patients without diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases (P = 0.046) than control subjects without diabetes but were at higher risk of death from external causes (P = 0.012), including intentional self-harm (P = 0.025), than control subjects without diabetes. CONCLUSIONS All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.

Objective To examine the risk factors of developing functional decline and make probabilistic predictions by using a tree-based method that allows higher order polynomials and interactions of the risk factors. Methods The conditional inference tree analysis, a data mining approach, was used to construct a risk stratification algorithm for developing functional limitation based on BMI and other potential risk factors for disability in 1,951 older adults without functional limitations at baseline (baseline age 73.1 ± 4.2 y). We also analyzed the data with multivariate stepwise logistic regression and compared the two approaches (e.g., cross-validation). Over a mean of 9.2 ± 1.7 years of follow-up, 221 individuals developed functional limitation. Results Higher BMI, age, and comorbidity were consistently identified as significant risk factors for functional decline using both methods. Based on these factors, individuals were stratified into four risk groups via the conditional inference tree analysis. Compared to the low-risk group, all other groups had a significantly higher risk of developing functional limitation. The odds ratio comparing two extreme categories was 9.09 (95% confidence interval: 4.68, 17.6). Conclusions Higher BMI, age, and comorbid disease were consistently identified as significant risk factors for functional decline among older individuals across all approaches and analyses.

Objective: The development of these updated clinical practice guidelines (CPGs) was commissioned by the American Association of Clinical Endocrinologists (AACE), The Obesity Society, American Society of Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists Boards of Directors in adherence with the AACE 2017 protocol for standardized production of CPGs, algorithms, and checklists. Methods: Each recommendation was evaluated and updated based on new evidence from 2013 to the present and subjective factors provided by experts. Results: New or updated topics in this CPG include: contextualization in an adiposity-based chronic disease complications-centric model, nuance-based and algorithm/checklist-assisted clinical decision-making about procedure selection, novel bariatric procedures, enhanced recovery after bariatric surgery protocols, and logistical concerns (including cost factors) in the current health-care arena. There are 85 numbered recommendations that have updated supporting evidence, of which 61 are revised and 12 are new. Noting that there can be multiple recommendation statements within a single numbered recommendation, there are 31 (13%) Grade A, 42 (17%) Grade B, 72 (29%) Grade C, and 101 (41%) Grade D recommendations. There are 858 citations, of which 81 (9.4%) are evidence level (EL) 1 (highest), 562 (65.5%) are EL 2, 72 (8.4%) are EL 3, and 143 (16.7%) are EL 4 (lowest). Conclusion: Bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity. Clinical decision-making should be evidence based within the context of a chronic disease. A team approach to perioperative care is mandatory, with special attention to nutritional and metabolic issues. A1C = hemoglobin A1c; AACE = American Association of Clinical Endocrinologists; ABCD = adiposity-based chronic disease; ACE = American College of Endocrinology; ADA = American Diabetes Association; AHI = Apnea-Hypopnea Index; ASA = American Society of Anesthesiologists; ASMBS = American Society of Metabolic and Bariatric Surgery; BMI = body mass index; BPD = biliopancreatic diversion; BPD/DS = biliopancreatic diversion with duodenal switch; CI = confidence interval; CPAP = continuous positive airway pressure; CPG = clinical practice guideline; CRP = C-reactive protein; CT = computed tomography; CVD = cardiovascular disease; DBCD = dysglycemia-based chronic disease; DS = duodenal switch; DVT = deep venous thrombosis; DXA = dual-energy X-ray absorptiometry; EFA = essential fatty acid; EL = evidence level; EN = enteral nutrition; ERABS = enhanced recovery after bariatric surgery; FDA = U.S. Food and Drug Administration; G4G = Guidelines for Guidelines; GERD = gastroesophageal reflux disease; GI = gastrointestinal; HCP = health-care professional(s); HTN = hypertension; ICU = intensive care unit; IGB = intragastric balloon(s); IV = intravenous; LAGB = laparoscopic adjustable gastric band; LAGBP = laparoscopic adjustable gastric banded plication; LGP = laparoscopic greater curvature (gastric) plication; LRYGB = laparoscopic Roux-en-Y gastric bypass; LSG = laparoscopic sleeve gastrectomy; MetS = metabolic syndrome; NAFLD = nonalcoholic fatty liver disease; NASH = nonalcoholic steatohepatitis; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; OAGB = one-anastomosis gastric bypass; OMA = Obesity Medicine Association; OR = odds ratio; ORC = obesity-related complication(s); OSA = obstructive sleep apnea; PE = pulmonary embolism; PN = parenteral nutrition; PRM = pulmonary recruitment maneuver; RCT = randomized controlled trial; RD = registered dietician; RDA = recommended daily allowance; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; SIBO = small intestinal bacterial overgrowth; TOS = The Obesity Society; TSH = thyroid-stimulating hormone; T1D = type 1 diabetes; T2D = type 2 diabetes; VTE = venous thromboembolism; WE = Wernicke encephalopathy; WHO = World Health Organization.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) improves after bariatric surgery. The aim of this study was to determine whether peripheral blood mononuclear cell albumin gene expression was related to NAFLD and whether albumin (ALB) and alpha fetoprotein (AFP) expression could be detected in whole blood and visceral adipose tissue. METHODS: Using a retrospective case control study design, RNA isolated from peripheral blood mononuclear cells from patients prior to undergoing bariatric surgery was used for pooled microarray analysis. Quantitative polymerase chain reaction (QPCR) was used to analyze whole blood and visceral adipose tissue. Liver histology was obtained via intra-operative biopsy and clinical data extracted from the electronic health record. RESULTS: The albumin (ALB) gene was the second most up-regulated found in microarray analysis of peripheral blood mononuclear cell RNA from patients with hepatic lobular inflammation versus normal liver histology. Transcript levels of ALB were significantly different across those with normal (n = 50), steatosis (n = 50), lobular inflammation (n = 50), and peri-sinusoidal fibrosis (n = 50) liver histologies, with lobular inflammation 3.9 times higher than those with normal histology (p < 0.017). Albumin expression levels decreased in 11/13 patients in paired samples obtained prior to and at 1 year after Roux-en-Y gastric bypass surgery. ALB expression could be detected in 23 visceral adipose tissue samples obtained intra-operatively and in 18/19 available paired whole blood samples. No significant correlation was found between ALB expression in visceral adipose tissue and whole blood RNA samples. Alpha fetoprotein expression as a marker of early hepatocytic differentiation was detected in 17/17 available VAT RNA samples, but in only 2/17 whole blood RNA samples. CONCLUSION: Albumin RNA expression from blood cells may serve as a biomarker of NAFLD. Albumin and alpha fetoprotein appear to be ubiquitously expressed in visceral adipose tissue in patients with extreme obesity.

Background & AimsA common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.MethodsWe performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.ResultsData from 1,047,265 participants (8,303 with liver biopsies) across 42 studies was included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05]) and diagnosis of NAFLD (OR 1.22 [95% CI 1.08 - 1.39]) in Caucasian adults. The variant was also positively associated with presence of severe steatosis, NASH, and advanced fibrosis (OR: 1.32 [95% CI: 1.06 - 1.63]) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (Pz=0.002) and lower serum triglycerides (Pz=1.5×10−4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.ConclusionOur study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.

Background Formal psychosocial support programs after weight-loss surgery are limited in scope and availability. Objective This randomized pilot study evaluated the feasibility of a postoperative behavioral intervention program. Materials and methods Postoperative weight-loss surgery patients (N = 50) were recruited from February 2017–July 2017 and randomized to a four-month behavioral program or usual care wait-list. Outcomes evaluated in addition to feasibility included health-related quality of life (Short Form -36), psychosocial functioning and adherence. Secondary outcomes included within-group changes for each outcome. Results Out of eight possible sessions, intervention participants attended a mean of 4.2 sessions. Intervention group participants experienced greater improvements in the social functioning domain of health-related quality of life compared to usual care. Self-reported dietary adherence in the intervention group remained stable, while usual care group dietary adherence declined. Within the intervention group, participants also reported gains in the physical function, pain and general health aspects of quality life from baseline to post-treatment. No differences in weight, mood or other eating behaviors (e.g., loss of control, emotional eating) were evident between groups. Conclusion Though participation in a postoperative behavioral intervention varied, the program helped participants to maintain aspects of quality of life and self-reported adherence to dietary recommendations. Trial registration ClinicalTrials.gov NCT03092479

OBJECTIVE: We sought to validate an algorithm designed to identify patients with post-gastric bypass hypoglycemia (PGBH) using clinician chart review. METHODS: We conducted a chart review study of nondiabetic patients who underwent Roux-en-Y gastric bypass (RYGB) at our institution from 2004 to 2013. The EMR algorithm was based on any post-operative glucose

OBJECTIVES: Little is known regarding dietary patterns and diet composition for the oldest old (defined as adults ≥ 80 years old) who usually have compromised diet quality due to age-related decline. We examined overall dietary patterns and further related the patterns to consumption of selected nutrients as well as perceived physical and mental fatigue. We hypothesized that those that had a healthy dietary pattern would have better nutrient intake profiles and reduced perceived fatigue. METHODS: We studied a cross-section of the Geisinger Rural Aging Study (GRAS) longitudinal cohort in rural Pennsylvania that included 122 participants (56 men and 66 women) aged from 82 to 97 years old. Average daily nutrient and food group intake were calculated from the average of three dietary recalls (1 weekend and 2 weekdays) by telephone. Dietary patterns were characterized using cluster analysis of 34 food groups. Mean nutrient intake and standard errors across dietary patterns were calculated after adjusting for age, sex, and energy consumption. Mean Pittsburgh fatigability questionnaire score examining physical and mental fatigue were calculated after adjusting for age, sex, and body mass index. RESULTS: Two dietary patterns were defined: one pattern (n = 53) characterized by its higher consumption of fruits, vegetables, seafood, and whole grains, and another pattern (n = 69), with higher intake of fats and oil, refined grains, and cheese. After adjusting for potential confounders, participants in the healthier pattern had significantly higher consumption of carbohydrate, protein, fiber, vitamin A, E, K, C, B6, B12, iron, zinc, and potassium with lower intakes of fat and sodium compared with those in the less healthy pattern (P

OBJECTIVE To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice. RESEARCH DESIGN AND METHODS Outcomes of 736 patients with T2DM who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at an academic center (2004–2012) and had ≥5 years’ glycemic follow-up were assessed. Of 736 patients, 425 (58%) experienced diabetes remission (HbA1c RESULTS In 136 (32%) patients who experienced late relapse, a statistically significant improvement in glycemic control, number of diabetes medications including insulin use, blood pressure, and lipid profile was still observed at long-term. Independent baseline predictors of late relapse were preoperative number of diabetes medications, duration of T2DM before surgery, and SG versus RYGB. Furthermore, patients who relapsed lost less weight during the 1st year after surgery and regained more weight afterward. Prediction models were constructed and externally validated. CONCLUSIONS While late relapse of T2DM is a real phenomenon (one-third of our cohort), it should not be considered a failure, as the trajectory of the disease and its related cardiometabolic risk factors is changed favorably after bariatric surgery. Earlier surgical intervention, RYGB (compared with SG) and more weight loss (less late weight regain) are associated with less diabetes relapse in the long-term.

Background: Overweight and obesity are predisposing conditions for the development of prediabetes and type 2 diabetes. Insulin resistance caused by excess adiposity is a key factor in this process. Methods: The effect of Gelesis100, a novel hydrogel, was assessed in patients who were overweight or had obesity, without antidiabetic medications, and who completed the Gelesis Loss Of Weight (GLOW; NCT02307279) study. GLOW was a multicenter, double-blind, placebo-controlled pivotal study with patients randomized to 2.25 g of Gelesis100 or placebo in capsules taken with 500 mL of water before lunch and dinner while on a hypocaloric diet (-300 kcal/day) for 24 weeks. Insulin resistance was measured by homeostasis model assessment-insulin resistance (HOMA-IR). Data were analyzed using analysis of covariance and Logit models comparing Gelesis100 to placebo arms in 2 subgroups of patients based on baseline HOMA-IR (subgroup 1, HOMA-IR ≥ 3.0, subgroup 2, HOMA-IR < 3.0). Results: The overall population included 290 patients (132 males, 158 females, 91 in subgroup 1, 199 in subgroup 2, 155 on Gelesis100, 135 on placebo), who were normoglycemic, had prediabetes, or had untreated type 2 diabetes. Statistically significant difference in reduction of HOMA-IR was observed in subgroup 1 (mean baseline HOMA-IR = 5.0) but not in subgroup 2 (mean baseline HOMA-IR = 1.8). Indeed, placebo-subtracted HOMA-IR changes (mean, SE) were -22.3 ± 9.5% (P = 0.0212) and -9.0 ± 9.5% (P = 0.3432) in subgroup 1 and subgroup 2, respectively. Furthermore, in subgroup 1, patients who lost < 5% body weight (n = 44, mean body weight loss = 1.3%) had a statistically significant placebo-subtracted HOMA-IR change of -27.6 ± 13.2% (P = 0.0435), while patients who lost ≥ 5% body weight (n = 47, mean body weight loss = 9.7%) had no statistically significant placebo-subtracted HOMA-IR change (-15.6 ± 13.6%, P = 0.2584). The effect on HOMA-IR decrease was driven by significant reduction in fasting serum insulin. Safety and tolerability of Gelesis100 demonstrated no increased risk compared to placebo. Conclusion: Treatment with Gelesis100 results in a significantly higher reduction in insulin resistance compared to placebo as assessed by HOMA-IR in patients who are overweight or have obesity with elevated baseline HOMA-IR. The results also suggest a potential weight-independent effect of Gelesis100 in the reduction of insulin resistance. If these findings are confirmed in future studies with larger subgroups, Gelesis100 could become a potential new treatment for insulin-resistant clinical conditions associated with overweight and obesity.

Background: In a previous pilot weight-loss study, an association was observed between baseline fasting plasma glucose (FPG) levels and the effectiveness of the Gelesis100 treatment. The aim of this subanalysis of the Gelesis Loss Of Weight (GLOW; NCT02307279) study is to further assess the association between FPG and body weight (BW) responders in subjects with overweight or obesity treated with Gelesis100, a non-systemic hydrogel. Methods: This subanalysis was conducted in subjects who were overweight or had obesity and who completed the GLOW study. GLOW was a multicenter, double-blind, placebo-controlled pivotal study with subjects randomized to 2.25 g of Gelesis100 or placebo in capsules taken with 500 mL of water before lunch and dinner while on a hypocaloric diet (-300 kcal/day) for 24 weeks. BW responders at 5% and 10% (super-responders) were analyzed using Logit model comparing Gelesis100 to placebo arms in 2 subgroups of subjects defined by their initial FPG (two consecutive consistent values). Subgroup 1 had normoglycemia (FPG < 100 mg/dL) and subgroup 2 had prediabetes (PD) (FPG ≥ 100 mg/dL and < 126 mg/dL) or untreated type 2 diabetes (T2D) (FPG ≥ 126 mg/dL). Results: The population included 206 subjects (94 males, 112 females, 138 in subgroup 1, 68 in subgroup 2, 105 on Gelesis100, 101 on placebo). In subgroup 1 (mean baseline FPG = 91 mg/dL), BW responders at 5% and 10% in Gelesis100 arm were 60% (placebo arm = 34%, adjusted odds ratio (OR) = 3.1, P = 0.0022) and 22% (placebo arm = 15%, OR = 1.5, P = 0.4254), respectively. In subgroup 2 (mean baseline FPG = 113 mg/dL), BW responders at 5% and 10% in Gelesis100 arm were 72% (placebo arm = 56%, OR = 2.2, P = 0.1509) and 44% (placebo arm = 14%, OR = 6.1, P = 0.0071), respectively. In the overall population, baseline FPG was inversely correlated with BW percent change in the Gelesis100 arm (r = -0.24, P = 0.0144). The safety and tolerability of Gelesis100 demonstrated no increased risk compared to placebo. No serious adverse events were observed in any arm. Conclusion: Gelesis100 offers a compelling new approach in the management of overweight and obesity. Notably, in Gelesis100-treated subjects with PD or untreated T2D, the odds of being super-responders are 6 times higher compared to placebo. This finding may be used as a tool for identifying subjects who are both at higher clinical risk and more likely to achieve greater levels of BW loss when treated with Gelesis100. The mechanisms underlying this finding require further investigations. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

OBJECTIVES Diet quality has been associated with health outcomes and quality of life. However, the association between diet quality and mortality in older people, those aged 80 years and older, is understudied. Therefore, we conducted a prospective study to examine whether better diet quality, assessed by a validated dietary screening tool (DST), was associated with lower mortality in those aged 80 years and older. METHODS Our study included 1990 participants (812 men and 1178 women), with a mean age of 84.1 years at baseline (ranging from 80 to 102 years old), from the Geisinger Rural Aging Study longitudinal cohort in Pennsylvania. Baseline descriptive information was obtained in 2009, and the DST was administered via mailed survey. The DST is composed of 25 food- and behavior-specific questions associated with dietary intake that generate a diet quality score ranging from 0 (lowest) to 100 (highest). Death was identified using electronic medical record and the Social Security Death Index data. Hazard ratios (HRs) and 95% confidence intervals (CIs) across three diet quality categories were calculated by using Cox proportional hazards models after adjusting for potential confounders. RESULTS Over 8 years of follow-up (October 2009-February 2018), 931 deaths were documented. Higher diet quality was associated with lower mortality risk (P-trend = .04). Participants with high diet quality (defined as DST scores >75) had significantly lower risk of mortality compared with those with low diet quality (defined as DST scores

Objective The epidemiology of post-gastric bypass surgery hypoglycemia (PGBH) is incompletely understood. This study aimed to evaluate the risk of PGBH among nondiabetic patients and associated factors. Methods A cohort study of nondiabetic patients who underwent Roux-en-Y gastric bypass (RYGB) was conducted. PGBH was defined by any postoperative record of glucose

Objective Obstructive sleep apnea (OSA) is common among candidates for bariatric surgery. OSA and its associated intermittent hypoxia have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. A large cohort of bariatric surgery patients was studied in an effort to explore the relationship between OSA severity, hypoxia, metabolic syndrome, and the severity of NAFLD. Methods Bariatric surgery candidates who underwent both polysomnography and liver biopsy were studied. The severity of OSA as determined by the apnea-hypopnea index (AHI) and parameters of hypoxia was studied in relation to extent of abnormalities of liver histology as measured by the presence of hepatic steatosis, inflammation, and fibrosis. Results The study cohort included 362 patients with a mean age of 46.2 years and BMI of 49.9 kg/m(2) . On the basis of AHI, 26% of the cohort had no OSA, 32% mild OSA, 22% moderate OSA, and 20% severe OSA. For the study subjects without metabolic syndrome, positive correlations were found between OSA severity, as measured by AHI, and parameters of hypoxia, with the severity of NAFLD. Conclusions OSA severity and its accompanying hypoxia are associated with the severity of NAFLD.

Increased inflammation and oxidative stress associated with obesity can accelerate aging. Telomere length (TL) has the capacity to serve as an aging indicator at the cellular level. Obesity has a known association with shorter TL. This study evaluated TL of immune cells in a population of obese individuals who underwent gastric bypass surgery. Pre- and post-operative DNA samples were available for 50 subjects who had gastric bypass surgery. DNA was analyzed via quantitative polymerase chain reaction to determine TL. Changes in TL were evaluated by comparing TL at baseline to TL at 3-5 years post gastric bypass surgery. Sixty percent of the individuals in the study observed an increase in TL. Significant lengthening was observed for those with the shortest baseline TL (P=0.0011), but not for those with intermediate baseline TL (P=0.411) or longest baseline TL (P=0.207). Change in TL was negatively correlated with age and triglycerides but not correlated with weight loss induced by bariatric surgery. This study confirms that TL lengthening is observed post bariatric surgery and is the first to detect TL lengthening 3-5 years after surgery.

BACKGROUND: History of abuse may impact weight loss (WL) following bariatric surgery. Some investigations have indicated slower WL rates among patients reporting abuse; however, among studies with multiple assessments, significant differences in WL are not evidenced at later measurement. Few investigations have extended follow-up beyond 18 months, limiting understanding of the impact of abuse on weight trajectory over time. Furthermore, existing research has insufficiently accounted for forms of interpersonal trauma beyond sexual abuse (i.e., emotional, physical) that may impact WL and other health outcomes. OBJECTIVES: To determine whether post-surgical percent total WL (%TWL) and specific clinical outcomes are differentially impacted by history of interpersonal abuse. SETTING: Large, comprehensive medical center. METHODS: Retrospective data was collected from patients who underwent bariatric surgery at a single center (N = 433). Based on pre-surgical interview, patients were grouped according to reported history of interpersonal abuse (Y/N). Nonlinear repeated measures regression examined impact of abuse history on %TWL, and clinical selequae. RESULTS: Differences in %TWL at 6, 12, 18, 24 and 36 months post-surgically did not differ significantly. Further, %TWL did not differ across time, according to group. A significantly greater number of those with history of interpersonal abuse had a clinical diagnosis of depression as compared with those not reporting interpersonal abuse (38% vs. 22% respectively), p < .001. CONCLUSIONS: Interpersonal abuse history does not negatively impact %TWL post-surgically but is associated with diagnosis of depression, indicating depressive symptoms may be a viable clinical intervention target for surgery patients with interpersonal trauma history.

Background DiaRem is a validated tool for predicting the likelihood of type 2 diabetes (T2D) remission after Roux-en-Y gastric bypass (RYGB) surgery. Objectives The objective of this study was to determine if the addition of duration of T2D to DiaRem improves its ability to discriminate between patients with or without T2D remission and/or to reclassify presurgery patients into accurate risk groups. Setting Academic Medical Center. Methods This study included patients consented into a prospective registry of Roux-en-Y gastric bypass between July 2009 and November 2015 with known duration of T2D (n = 307). Electronic health record–derived duration of T2D was compared with patient reported duration of T2D in a subset of patients (n = 48). DiaRem2 was created using clinical variables from DiaRem and duration of T2D. Area under the curve and the net reclassification index were used to assess increased performance of DiaRem2. Results Self-reported duration of T2D was highly concordant with electronic health record–derived T2D duration (96% agreement). Early T2D remission occurred in 44% of patients. DiaRem2 included age, hemoglobin A1C, insulin medication use, and duration of T2D. DiaRem2 had a higher area under the curve than DiaRem (.876 versus .850, P = .026), reduced the number of remission risk groups from 5 down to 3, and reclassified patients from intermediate to either high or low remission groups (net reclassification index, P Conclusions DiaRem2 simplifies and improves the accuracy of assessing probability of T2M remission after Roux-en-Y gastric bypass. Self-reported duration of T2D is an acceptable surrogate for T2D duration derived from clinical data.

Iron deficiency and anaemia after metabolic surgery, potentially modifiable nutritional complications, are becoming an increasing cause for concern as prevalence increases with time and there is limited evidence supporting the effectiveness of the current guidelines for prophylactic oral iron supplementation and treatment for deficiency. Abnormalities in iron nutrition predisposing to deficiency are common in severely obese patients, and the low-grade systemic inflammation, also common to these patients, reduces the effectiveness of oral iron supplementation. The surgical procedures result in alterations of foregut anatomy and physiology, which limit iron absorptive capacity and daily food intake. These alterations and the limited effects of oral iron supplementation explain the high prevalence of postoperative iron deficiency and anaemia. This review outlines current mechanisms concerning the pathogenesis of disordered iron nutrition in patients with severe obesity, current gaps in knowledge, and opportunities for quality improvement.

PURPOSE: The objective of this descriptive study was to identify clinical characteristics of Roux-en-Y Gastric Bypass (RYGB) patients who died from intentional self-harm or accidental overdose postoperatively. MATERIALS AND METHODS: This retrospective, descriptive study included RYGB patients from a large rural medical center that completed surgery between January 2004 and December 2014 and died from intentional self-harm or accidental overdose through December 2015. Specific causes of death were obtained from the National Death Index and clinical data from electronic health records. Clinical characteristics explored were age, sex, time to surgery, weight loss expectations, postoperative weight loss, medication, diagnoses, psychiatric histories (diagnoses, self-harm, suicidal ideation and behaviors, medications, substance use, preoperative Beck Depression Inventory-II scores), pain, social support and reported life stressors. RESULTS: Overall, twenty-two patients of 146 total deceased patients died from intention self-harm (n = 6) or accidental overdose (n = 16) over the study period (77.3% female, mean age at time of surgery = 38.4±9.1 years). Younger age (< 40 years), history of self-harm or depression, preoperative pain and use of opioids at the time of surgery emerged as common characteristics in weight-loss surgery patients who died from intentional self-harm or accidental overdose. No trends regarding social support, life stressors, or actual or expected weight loss were identified. CONCLUSION: Certain weight-loss surgery patients may be at risk for death from self-harm or overdose and may benefit from greater surveillance postoperatively.

Numerous studies have shown that bariatric surgery in older patients is safe and effective. However, both the Agency for Healthcare Research and Quality (AHRQ) and a Medicare Evidence Advisory Committee (MEDCAC) have cited gaps in the evidence for outcomes in Medicare patients undergoing bariatric surgery. These gaps are predominantly in the safety and outcomes evidence in Medicare patients younger than 65 years old (Centers for Medicare and Medicaid Services [CMS]65).The aim of our study was to review both the safety and efficacy of gastric bypass (RYGB) and sleeve gastrectomy (SG) in Medicare patients compared with other payers.A single academic medical center.A prospectively maintained database of 3300 patients who underwent bariatric surgery between January 2007 and December 2017 was utilized. The outcomes of Medicare patients undergoing RYGB and SG were analyzed and compared to those of similar patients covered by Medicaid or Commercial insurers.There were too few patients with commercial insurance older than 65 to compare to those with Medicare (CMS ≥ 65). Mortality at 90 days for CMS ≥ 65 was 1.3% and the overall complication rate was 20.1% (minor 15.6%; major 7.1%). Total weight loss (TWL) at 6 months and 1, 2, and 3 years was 25.3%, 30.0%, 29.9%, and 29.4% respectively. For any time after surgery, 23% of CMS ≥ 65 had complete remission of diabetes and 45% had partial remission. Demographic analysis of CMS65 found Medicare patients were significantly older with more diabetes, hypertension and hyperlipidemia than those with commercial payers. Mortality at 90 days for CMS65 was 0.6% and the overall complication rate was 18.3% (minor 14.3%; major 4.7%). Mortality was not significantly different between payers. After adjustment for baseline differences and comparing to the Medicare group, the commercial group was less likely to have minor complications (P = .019), any complications (P = .007), and extended length of stay (P.001). The TWL for the entire cohort age65 at 6 months and 1, 2, and 3 years was 28.1%, 34.1%, 34.1%, and 31.8% respectively. After adjusting for differences, there was no significant difference in TWL between payers. For any time after surgery, complete remission of diabetes was 45% in CMS65 patients and partial remission was 59%. The comparison of remission between groups was then adjusted for DiaRem score and surgery type. CMS65 patients had significantly less partial remission of diabetes than commercial patients (P = .034) but no difference in complete remission.RYGB and SG are both safe and effective in Medicare patients of all ages. CMS ≥ 65 have acceptable mortality and complication rates with TWL and diabetes remission similar to younger patients. CMS65 patients are older than those with commercial insurance with more comorbid disease. While they have longer hospital stays after bariatric surgery, their weight loss and complete remission of diabetes are no different than patients with Medicaid or commercial insurance. This study helps fill an important evidence gap in bariatric surgical patients raised by both Agency for Healthcare Research and Quality, and a Medicare Evidence Advisory Committee.

BACKGROUND: Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets. METHODS: We used exome sequence data and electronic health records from 46,544 participants in the DiscovEHR human genetics study to identify genetic variants associated with serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Variants that were replicated in three additional cohorts (12,527 persons) were evaluated for association with clinical diagnoses of chronic liver disease in DiscovEHR study participants and two independent cohorts (total of 37,173 persons) and with histopathological severity of liver disease in 2391 human liver samples. RESULTS: A splice variant (rs72613567:TA) in HSD17B13, encoding the hepatic lipid droplet protein hydroxysteroid 17-beta dehydrogenase 13, was found to be associated with reduced levels of ALT (P=4.20×10(−12)) and AST (P=6.2×10(−10)). Among DiscovEHR study participants, this variant was found to be associated with a reduced risk of alcoholic liver disease (by 42% [95% confidence interval {CI}, 20 to 58] among heterozygotes and by 53% [95% CI, 3 to 77] among homozygotes), nonalcoholic liver disease (by 17% [95% CI, 8 to 25] among heterozygotes and by 30% [95% CI, 13 to 43] among homozygotes), alcoholic cirrhosis (by 42% [95% CI, 14 to 61] among heterozygotes and by 73% [95% CI, 15 to 91] among homozygotes), and nonalcoholic cirrhosis (by 26% [95% CI, 7 to 40] among heterozygotes and by 49% [95% CI, 15 to 69] among homozygotes). Associations were confirmed in two independent cohorts. The rs72613567:TA variant was associated with a reduced risk of nonalcoholic steatohepatitis, but not steatosis, in human liver samples. The rs72613567:TA variant mitigated liver injury associated with the risk-increasing PNPLA3 p.I148M allele and resulted in an unstable and truncated protein with reduced enzymatic activity. CONCLUSIONS: A loss-of-function variant in HSD17B13 is associated with a reduced risk of chronic liver disease and of progression from steatosis to steatohepatitis. (Funded by Regeneron Pharmaceuticals and others.)

Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent complication of extreme obesity. Loading of the liver with fat can progress to inflammation and fibrosis including cirrhosis. The molecular factors involved in the progression from simple steatosis to fibrosis remain poorly understood. Methods Gene expression profiling using microarray, PCR array, and RNA sequencing was performed on RNA from liver biopsy tissue from patients with extreme obesity. Patients were grouped based on histological findings including normal liver histology with no steatosis, lobular inflammation, or fibrosis, and grades 1, 2, 3, and 4 fibrosis with coexistent steatosis and lobular inflammation. Validation of expression was conducted using quantitative PCR. Serum analysis was performed using ELISA. Expression analysis of hepatocytes and hepatic stellate cells in response to lipid loading were conducted in vitro using quantitative PCR and ELISA. Results Three orthogonal methods to profile human liver biopsy RNA each identified the chemokine CCL20 (CC chemokine ligand 20 or MIP-3 alpha) gene as one of the most up-regulated transcripts in NAFLD fibrosis relative to normal histology, validated in a replication group. CCL20 protein levels in serum measured in 224 NAFLD patients were increased in severe fibrosis (p

Recent evidence suggests that microRNAs (miRNAs), small, noncoding RNA molecules that regulate gene expression, may play a role in the regulation of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). To identify miRNAs that mediate NAFLD-related fibrosis, we used high-throughput sequencing to assess miRNAs obtained from liver biopsies of 15 individuals without NAFLD fibrosis (F0) and 15 individuals with severe NAFLD fibrosis or cirrhosis (F3-F4), matched for age, sex, body mass index, type 2 diabetes status, hemoglobin A1c, and use of diabetes medications. We used DESeq2 and Kruskal-Wallis test to identify miRNAs that were differentially expressed between NAFLD patients with or without fibrosis, adjusting for multiple testing using Bonferroni correction. We identified a total of 75 miRNAs showing statistically significant evidence (adjusted P value0.05) for differential expression between the 2 groups, including 30 upregulated and 45 downregulated miRNAs. Quantitative reverse-transcription polymerase chain reaction analysis of selected miRNAs identified by sequencing validated 9 of 11 of the top differentially expressed miRNAs. We performed functional enrichment analysis of dysregulated miRNAs and identified several potential gene targets related to NAFLD-related fibrosis including hepatic fibrosis, hepatic stellate cell activation, transforming growth factor beta signaling, and apoptosis signaling. We identified forkhead box O3 and F-box WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) as potential targets of miR-182, and found that levels of forkhead box O3, but not FBXW7, were significantly decreased in fibrotic samples. These findings support a role for hepatic miRNAs in the pathogenesis of NAFLD-related fibrosis and yield possible new insight into the molecular mechanisms underlying the initiation and progression of liver fibrosis and cirrhosis.

Metabolic surgery has emerged as the preferred sustainable treatment for the disease of obesity and its formidable health comorbidities. This evolution has resulted from major advances in surgical quality care including minimally invasive techniques and the introduction of accredited multidisciplinary centers of excellence. Multidisciplinary care including obesity medicine specialists, certified bariatric nurses, dietitians, and behavioral medicine professionals has improved perioperative care and helped to identify many early and late metabolic as well as nutritional complications of these procedures.

Background Obesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long‐term cardiovascular events. Methods and Results A cohort of Roux‐en‐Y gastric bypass surgery ( RYGB ) patients was tightly matched by age, body mass index, sex, Framingham Risk Score, smoking history, use of antihypertension medication, diabetes mellitus status, and calendar year with a concurrent cohort of nonoperated control patients. The primary study end points of major cardiovascular events (myocardial infarction, stroke, and congestive heart failure) were evaluated using Cox regression. Secondary end points of longitudinal cardiovascular risk factors were evaluated using repeated‐measures regression. The RYGB and matched controls (N=1724 in each cohort) were followed for up to 12 years after surgery (overall median of 6.3 years). Kaplan–Meier analysis revealed a statistically significant reduction in incident major composite cardiovascular events ( P =0.017) and congestive heart failure (0.0077) for the RYGB cohort. Adjusted Cox regression models confirmed the reductions in severe composite cardiovascular events in the RYGB cohort (hazard ratio=0.58, 95% CI =0.42–0.82). Improvements of cardiovascular risk factors (eg, 10‐year cardiovascular risk score, total cholesterol, high‐density lipoprotein, systolic blood pressure, and diabetes mellitus) were observed within the RYGB cohort after surgery. Conclusions Gastric bypass is associated with a reduced risk of major cardiovascular events and the development of congestive heart failure.

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions that include steatohepatitis and fibrosis that are thought to emanate from hepatic steatosis. Few robust biomarkers or diagnostic tests have been developed for hepatic steatosis in the setting of obesity. We have developed a multi-component classifier for hepatic steatosis comprised of phenotypic, genomic, and proteomic variables using data from 576 adults with extreme obesity who underwent bariatric surgery and intra-operative liver biopsy. Using a 443 patient training set, protein biomarker discovery was performed using the highly multiplexed SOMAscan® proteomic assay, a set of 19 clinical variables, and the steatosis predisposing PNPLA3 rs738409 single nucleotide polymorphism genotype status. The most stable markers were selected using a stability selection algorithm with a L1-regularized logistic regression kernel and were then fitted with logistic regression models to classify steatosis, that were then tested against a 133 sample blinded verification set. The highest area under the ROC curve (AUC) for steatosis of PNPLA3 rs738409 genotype, 8 proteins, or 19 phenotypic variables was 0.913, whereas the final classifier that included variables from all three domains had an AUC of 0.935. These data indicate that multi-domain modeling has better predictive power than comprehensive analysis of variables from a single domain.