Prior metabolic surgery reduced COVID-19 severity: Systematic analysis from year one of the COVID-19 pandemic.

Background: Obesity is a risk factor for COVID-19 severity. Recent studies suggest that prior metabolic surgery (MS) modifies the risk of COVID-19 severity. Methods: COVID-19 outcomes were compared between patients with MS (n = 287) and a matched cohort of unoperated patients (n = 861). Multiple logistic regression was used to identify predictors of hospitalization. A systematic literature review and pooled analysis was conducted to provide overall evidence of the influence of prior metabolic surgery on COVID-19 outcomes. Results: COVID-19 patients with MS had less hospitalization (9.8% versus 14.3%, p = 0.049). Age 70+, higher BMI, and low weight regain after MS were associated with more hospitalization after COVID-19. A systematic review of 7 studies confirmed that MS reduced the risk of post-COVID-19 hospitalization (OR = 0.71, 95%CI = [0.61-0.83], p < 0.0001) and death (OR = 0.44, 95%CI = [0.30-0.65], p < 0.0001). Conclusion: MS favorably modifies the risks of severe COVID-19 infection. Older age and higher BMI are major risk factors for severity of COVID-19 infection.

Clinical significance of iron deficiency among candidates for metabolic surgery.

BACKGROUND: Iron deficiency (ID), a known complication after metabolic surgery, is common among preoperative patients in the presence of inflammation. Evidence is now accumulating that preoperative ID may adversely affect perioperative outcomes. OBJECTIVES: To investigate the relationship between preoperative iron status and the risk of postoperative severe anemia. In addition, this study investigates the relationship between preoperative iron status and length of surgical stay SETTING: A large regional tertiary health system. METHODS: Among patients who underwent metabolic surgery between 2004 and 2020, 5171 patients had a full iron nutritional assessment prior to surgery. Study patients were divided into multiple smaller groups (10 female groups and 7 male groups) on the basis of levels of serum ferritin and Transferrin Saturation (T Sat) < or ≥20%. Study patients were followed after surgery and the time to the development of severe anemia (hemoglobin < 8 gm/dL) was recorded. Hospital length of stay (LOS) was analyzed in relation to preoperative iron status. RESULTS: Lower ferritin levels were associated with older age in males (P = .0001) and younger age in females (P < .0001). For males, after adjustment for age, body mass index (BMI), and year of surgery, surgical LOS was prolonged in those with T Sat <20% (P = .0041). For females the time until the development of severe anemia was associated with baseline iron status (P < .0001). CONCLUSIONS: Male preoperative patients for metabolic surgery with T Sat <20% are at risk for increased surgical LOS. Females with low ferritin levels consistent with ID are at increased risk for the development of postoperative severe anemia.

Rates of Recurrent Marginal Ulcer in Gastric Bypass Patients Undergoing Revisional Surgery.

INTRODUCTION: The rate of marginal ulcer (MU) following primary Roux-en-Y Gastric Bypass (RYGB) is approximately .6-16%. Few studies have evaluated recurrence rates following surgical revision for MU. The primary aim of this study was to determine the rate of MU recurrence following revision. The secondary aim was to evaluate the impact of truncal vagotomy (TV) on the recurrence rates and analyze potential risk factors associated with the recurrence of MU after revision. METHODS: We conducted a retrospective cohort study examining data at a single tertiary academic medical center. Adult patients with a history of RYGB who underwent gastrojejunostomy revision for recurrent MU between the years of 2003-2020 were included. We sought to determine our overall rate of MU following revision, with and without TV. Additionally, we examined the association of risk factors with MU recurrence. Fisher's exact test was used to determine the statistical significance of recurrence rates between the groups. RESULTS: We included 90 patients in the study. The overall recurrence rate for MU was 16.7%. Of the 90 patients, 35 (35.4%) patients underwent TV at the time of revision. The recurrence rate of MU after GJ revision with TV was 14.3% in comparison to those without TV, 18.2% (P = .775). Smoking, steroid, alcohol use, history of cardiac surgery/intervention, and helicobacter pylori were not significantly associated with recurrent MU following revision. CONCLUSIONS: The rate of recurrence after revision for MU is high. Adding TV trended towards decreased MU recurrence after revisional surgery, however not significant. Larger studies are needed to evaluate risk factors associated with recurrent MU after revision.

Stratified Preoperative A1c is not Significantly Associated With Clavien-Dindo Major Complications Following Bariatric Surgery in the MBSAQIP Database.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is highly prevalent comorbidity in patients with morbid obesity. It is still unclear whether a cutoff value of preoperative A1c represents an increased risk for major postoperative complications following Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG). METHODS: Retrospective MBSAQIP Participant Use File cohort for both years 2017 and 2018 were analyzed to evaluate the relationship between HbA1c in patients with morbid obesity and T2DM undergoing bariatric surgery, and the 30 days postoperative major complications by Clavien-Dindo classification (III/IV). We used an HbA1c cutoff of <7, > =7, and stratified by 1% increment for a total of 11 groups. We used univariate and multivariate logistic regression to analyze the outcome of the complications. Predicted probabilities were calculated for major complications. All statistical tests were two-sided with a P-value of less than .05 considered as a cut-off for statistical significance. RESULTS: Of 42,181 patients that met inclusion criteria, there were 20,955 identified with HbA1c <7%, and 21,226 patients with HbA1c >7%. Utilizing HbA1c <7% as a cutoff, we found no consistent statistical significance in the major postoperative complication in patients with HbA1c >7%, and when stratified with 1% increment between groups. We also found no significance between groups with risk adjustment. CONCLUSIONS: Extensive analysis of the large MBSAQIP cohort didn't result in a clinically significant association between stratified HbA1c and 30-day Clavien-Dindo major complications (III/IV) following Roux-en-Y Gastric Bypass (RYGB) and (SG).

Germline Mutations in CIDEB and Protection against Liver Disease.

BACKGROUND: Exome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets. METHODS: We performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations. RESULTS: The multistage analysis involved 542,904 persons with available data on liver aminotransferase levels, 24,944 patients with various types of liver disease, and 490,636 controls without liver disease. We found that rare coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk of liver disease. We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. The burden of rare predicted loss-of-function variants plus missense variants in CIDEB (combined carrier frequency, 0.7%) was associated with decreased alanine aminotransferase levels (beta per allele, -1.24 U per liter; 95% confidence interval [CI], -1.66 to -0.83; P = 4.8×10-9) and with 33% lower odds of liver disease of any cause (odds ratio per allele, 0.67; 95% CI, 0.57 to 0.79; P = 9.9×10-7). Rare coding variants in CIDEB were associated with a decreased risk of liver disease across different underlying causes and different degrees of severity, including cirrhosis of any cause (odds ratio per allele, 0.50; 95% CI, 0.36 to 0.70). Among 3599 patients who had undergone bariatric surgery, rare coding variants in CIDEB were associated with a decreased nonalcoholic fatty liver disease activity score (beta per allele in score units, -0.98; 95% CI, -1.54 to -0.41 [scores range from 0 to 8, with higher scores indicating more severe disease]). In human hepatoma cell lines challenged with oleate, CIDEB small interfering RNA knockdown prevented the buildup of large lipid droplets. CONCLUSIONS: Rare germline mutations in CIDEB conferred substantial protection from liver disease. (Funded by Regeneron Pharmaceuticals.).

Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes.

Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. We describe an association with favorable fat distribution (p = 1.8 × 10-09), favorable metabolic profile and protection from type 2 diabetes (~28% lower odds; p = 0.004) for heterozygous protein-truncating mutations in INHBE, which encodes a circulating growth factor of the activin family, highly and specifically expressed in hepatocytes. Our results suggest that inhibin ßE is a liver-expressed negative regulator of adipose storage whose blockade may be beneficial in fat distribution-associated metabolic disease.

Expression of taste signaling elements in jejunal tissue in subjects with obesity.

Taste-signaling proteins, which are expressed throughout the digestive tract, are involved in regulating metabolism and immunity. This study aimed to determine if these genes are expressed and altered in jejunal tissues from patients with extreme obesity who received bariatric surgery. Reverse transcription polymerase chain reaction revealed that phospholipase C beta 2 and transient receptor potential channel M5 expression was downregulated in the jejunum of patients with a body mass index above 50, whereas gustducin expression remained unchanged. Our data suggest that taste-signaling dysregulation might contribute to obesity.

Effects of sustained weight loss on outcomes associated with obesity comorbidities and healthcare resource utilization.

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 <0.0001). Female Weight Loss Maintainers had a 19% and 24% lower risk of developing any cancer (p = 0.0022) or obesity-related cancer (p = 0.0021), respectively. No significant trends were observed for opioid use. Weight loss Rebounders and Maintainers had increased risk (14% and 25%) of future treatment for anxiety/depression (both <0.0001). Weight loss maintenance of >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.

Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted 1H-NMR Metabolomics.

Determining biomarkers and better characterizing the biochemical progression of nonalcoholic fatty liver disease (NAFLD) remains a clinical challenge. A targeted 1H-NMR study of serum, combined with clinical variables, detected and localized biomarkers to stages of NAFLD in morbidly obese females. Pre-surgery serum samples from 100 middle-aged, morbidly obese female subjects, grouped on gold-standard liver wedge biopsies (non-NAFLD; steatosis; and fibrosis) were collected, extracted, and analyzed in aqueous (D2O) buffer (1H, 600 MHz). Profiled concentrations were subjected to exploratory statistical analysis. Metabolites varying significantly between the non-NAFLD and steatosis groups included the ketone bodies 3-hydroxybutyrate (↓; p = 0.035) and acetone (↓; p = 0.012), and also alanine (↑; p = 0.004) and a putative pyruvate signal (↑; p = 0.003). In contrast, the steatosis and fibrosis groups were characterized by 2-hydroxyisovalerate (↑; p = 0.023), betaine (↓; p = 0.008), hypoxanthine (↓; p = 0.003), taurine (↓; p = 0.001), 2-hydroxybutyrate (↑; p = 0.045), 3-hydroxyisobutyrate (↑; p = 0.046), and increasing medium chain fatty acids. Exploratory classification models with and without clinical variables exhibited overall success rates ca. 75-85%. In the study conditions, inhibition of fatty acid oxidation and disruption of the hepatic urea cycle are supported as early features of NAFLD that continue in fibrosis. In fibrosis, markers support inflammation, hepatocyte damage, and decreased liver function. Complementarity of NMR concentrations and clinical information in classification models is shown. A broader hypothesis that standard-of-care sera can yield metabolomic information is supported.

Differential DNA methylation and changing cell-type proportions as fibrotic stage progresses in NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by changes in cell composition that occur throughout disease pathogenesis, which includes the development of fibrosis in a subset of patients. DNA methylation (DNAm) is a plausible mechanism underlying these shifts, considering that DNAm profiles differ across tissues and cell types, and DNAm may play a role in cell-type differentiation. Previous work investigating the relationship between DNAm and fibrosis in NAFLD has been limited by sample size and the number of CpG sites interrogated. RESULTS: Here, we performed an epigenome-wide analysis using Infinium MethylationEPIC array data from 325 individuals with NAFLD, including 119 with severe fibrosis and 206 with no histological evidence of fibrosis. After adjustment for latent confounders, we identified 7 CpG sites whose DNAm associated with fibrosis (p < 5.96 × 10-8). Analysis of RNA-seq data collected from a subset of individuals (N = 56) revealed that gene expression at 288 genes associated with DNAm at one or more of the 7 fibrosis-related CpGs. DNAm-based estimates of cell-type proportions showed that estimated proportions of natural killer cells increased, while epithelial cell proportions decreased with disease stage. Finally, we used an elastic net regression model to assess DNAm as a biomarker of fibrotic stage and found that our model predicted fibrosis with a sensitivity of 0.93 and provided information beyond a model based solely on cell-type proportions. CONCLUSION: These findings are consistent with DNAm as a mechanism underpinning or marking fibrosis-related shifts in cell composition and demonstrate the potential of DNAm as a possible biomarker of NAFLD fibrosis.

Iron deficiency is highly prevalent among candidates for metabolic surgery and may affect perioperative outcomes.

BACKGROUND: 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 of <30 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%. OBJECTIVES: 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. SETTING: Geisinger Medical Center, Danville, Pennsylvania. METHODS: The study cohort included 3,723 patients who underwent pre- operative nutritional assessment which included markers of iron nutrition over the period 2004-2018. RESULTS: The cohort included 2,988 women (80.3%) and 735 men (19.7%); body mass index: 49.4 ± 9 kg/m2. The diagnosis of ID was based on ferritin level <30 ng/mL (true ID) and/or TSAT < 20% representing a combination of true ID and inflammation (serum ferritin ≥ 30 ng/mL and TSAT < 20%). A total of 399 patients (10.8%) were anemic. A serum ferritin level of < 30 ng/mL was found in 488 patients (13%; 481 women and 7 men). Of these, 122 patients (25.2%) were also anemic. An additional 1,204 had serum ferritin ≥ 30 ng/mL and TSAT < 20%. Overall, 1,692 patients (45.4%) in this cohort had laboratory evidence of ID by current criteria that adjusts for the very high prevalence of inflammation. Men with serum ferritin levels ≥30 ng/mL with TSAT < 20% had an increased surgical length of stay. CONCLUSION: The 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 level <30 ng/mL and TSAT < 20%. ID in the presence of inflammation is often unrecognized and has implications regarding surgical outcomes after metabolic surgery.

Roux-en-Y Gastric Bypass Surgery Has Early Differential Effects on Bile Acids and the Levels of Complement Component 3 and Acylation-Stimulating Protein.

BACKGROUND: Bile acids have been implicated in the mechanism by which Roux-en-Y gastric bypass (RYGB) can induce remission of type 2 diabetes (T2D). Our goal was to identify circulating proteins whose levels changed after RYGB when dysglycemic parameters normalized. MATERIALS AND METHODS: This was a retrospective study of 26 participants who underwent RYGB. Blood proteins were identified using two-dimensional electrophoresis and mass spectroscopy. Complement proteins were measured using immunoassays and bile acids measured using ultra-high-performance liquid chromatography and mass spectroscopy. RESULTS: A total of 7/452 blood proteins were found to change 2 days after RYGB. Complement component 3 (C3) was selected because of its regulation by bile acids and the glucoregulatory function of its proteolytically processed product C3adesArg or acylation-stimulating protein (ASP). The median (inter-quartile range/IQR) C3 level was 47.4 (34.5, 65.9) mg/dL before surgery decreasing to 40.9 (13.4, 64.1) mg/dL within 2 days after surgery (p = 0.0292). The median (IQR) ASP level increased from 2.8 (0.9, 7.3) nM before surgery to 8.0 (5.3, 14.1) nM within 2 days after surgery (p = 0.0016). ASP levels increased in 14/17 (82%) with T2D remission and in 6/6 with normoglycemia but decreased in 3/3 with persistent T2D. Of ten bile acids measured, the levels of ursodeoxycholic acid (UDCA) were significantly decreased after RYGB and the levels of taurodeoxycholic acid (TDCA) were significantly decreased with T2D remission. CONCLUSIONS: These data further support an association of C3 with glucose metabolism and implicate bile acids and ASP in the early remittive effects of RYGB on T2D.

The relationship between specialized pro-resolving lipid mediators, morbid obesity and weight loss after bariatric surgery.

Obesity and diabetes are associated with chronic inflammation. Specialized pro-resolving lipid mediators (SPMs)-resolvins (Rv), protectins (PD) and maresins (MaR)-actively resolve inflammation. Bariatric surgery achieves remission of diabetes, but mechanisms are unclear. We measured SPMs and proinflammatory eicosanoid levels using liquid chromatography-tandem mass spectrometry in 29 morbidly obese subjects (13 with diabetes) and 15 nondiabetic, mildly obese subjects. Compared to the mildly obese, the morbidly obese had higher levels of SPMs-RvD3, RvD4 and PD1-and white blood cells (WBC) and platelets. Post-surgery, SPM and platelet levels decreased in morbidly obese nondiabetic subjects but not in diabetic subjects, suggesting continued inflammation. Despite similar weight reductions 1 year after surgery (44.6% vs. 46.6%), 8 diabetes remitters had significant reductions in WBC and platelet counts whereas five non-remitters did not. Remitters had a 58.2% decrease (p = 0.03) in 14-HDHA, a maresin pathway marker; non-remitters had an 875.7% increase in 14-HDHA but a 36.9% decrease in MaR1 to a median of 0. In conclusion, higher levels of RvD3, PD1 and their pathway marker, 17-HDHA, are markers of leukocyte activation and inflammation in morbid obesity and diabetes and diminish with weight loss in nondiabetic but not diabetic subjects, possibly representing sustained inflammation in the latter. Lack of diabetes remission after surgically-induced weight loss may be associated with reduced ability to produce MaR1 and sustained inflammation.

New concepts in the diagnosis and management approach to iron deficiency in candidates for metabolic surgery: should we change our practice?

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 result 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 using 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 that has been heretofore largely unrecognized and inadequately treated. The assessment of iron status using the currently recommended markers in the presence of chronic inflammatory diseases and repletion of depleted stores for surgical candidates with deficiency during the preoperative period present an important opportunity for mitigating this condition in postoperative patients.

Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention.

Cancer treatments are often more successful when the disease is detected early. We evaluated the feasibility and safety of multicancer blood testing coupled with positron emission tomography-computed tomography (PET-CT) imaging to detect cancer in a prospective, interventional study of 10,006 women not previously known to have cancer. Positive blood tests were independently confirmed by a diagnostic PET-CT, which also localized the cancer. Twenty-six cancers were detected by blood testing. Of these, 15 underwent PET-CT imaging and nine (60%) were surgically excised. Twenty-four additional cancers were detected by standard-of-care screening and 46 by neither approach. One percent of participants underwent PET-CT imaging based on false-positive blood tests, and 0.22% underwent a futile invasive diagnostic procedure. These data demonstrate that multicancer blood testing combined with PET-CT can be safely incorporated into routine clinical care, in some cases leading to surgery with intent to cure.

Clinical Practice Guidelines for the Perioperative Nutrition, Metabolic, and Nonsurgical Support of Patients Undergoing Bariatric Procedures - 2019 Update: Cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists.

OBJECTIVE: The development of these updated clinical practice guidelines (CPGs) was commissioned by the American Association of Clinical Endocrinologists (AACE), The Obesity Society (TOS), American Society for Metabolic and Bariatric Surgery (ASMBS), Obesity Medicine Association (OMA), and American Society of Anesthesiologists (ASA) 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). CONCLUSIONS: 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.

Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists.

OBJECTIVE: The development of these updated clinical practice guidelines (CPG) was commissioned by the American Association of Clinical Endocrinologists, The Obesity Society, the American Society of Metabolic and Bariatric Surgery, the Obesity Medicine Association, and the American Society of Anesthesiologists boards of directors in adherence to the American Association of Clinical Endocrinologists 2017 protocol for standardized production of CPG, 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 healthcare 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). CONCLUSIONS: 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.

Late Relapse of Diabetes After Bariatric Surgery: Not Rare, but Not a Failure.

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 <6.5% [48 mmol/mol] with patients off medications) in the 1st year after surgery. These 425 patients were followed for a median of 8 years (range 5-14) to characterize late relapse of diabetes. 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.

Association of Genetic Risk of Obesity with Postoperative Complications Using Mendelian Randomization.

BACKGROUND: The extent to which obesity and genetics determine postoperative 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 and 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 and 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 was constructed from 97 obesity-risk single-nucleotide polymorphisms for a Mendelian randomization study to determine the association of genetic risk of 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/m2) had increased risk of incisional hernia (odds ratio [OR] 1.7-5.5, p < 3.1 × 10-20), and people with obesity (BMI ≥ 30 kg/m2) had increased risk of postoperative infection (OR 1.2-2.3, p < 2.5 × 10-5). In the eMERGE cohort, genetically predicted BMI was associated with incisional hernia (OR 2.1 [95% CI 1.8-2.5], p = 1.4 × 10-6) and postoperative infection (OR 1.6 [95% CI 1.4-1.9], p = 3.1 × 10-6). Association findings were similar after limitation of the cohorts to those who underwent abdominal procedures. CONCLUSIONS: Clinical and Mendelian randomization studies suggest that obesity, as measured by BMI, is associated with the development of postoperative incisional hernia and infection.