Chemical characterization and receptor modeling of PM10 in the surroundings of the opencast lignite mines of Western Macedonia, Greece.

The Western Macedonian Lignite Center (WMLC) in northwestern Greece is the major lignite center in the Balkans feeding four major power plants of total power exceeding 4 GW. Concentrations of PM10 (i.e., particulate matters with diameters ≤10 µm) are the main concern in the region, and the high levels observed are often attributed to the activities related to power generation. In this study, the contribution of fugitive dust emissions from the opencast lignite mines to the ambient levels of PM10 in the surroundings was estimated by performing chemical mass balance (CMB) receptor modeling. For this purpose, PM10 samples were concurrently collected at four receptor sites located in the periphery of the mine area during the cold and the warm periods of the year (November-December 2011 and August-September 2012), and analyzed for a total of 26 macro- and trace elements and ionic species (sulfate, nitrate, chloride). The robotic chemical mass balance (RCMB) model was employed for source identification/apportionment of PM10 at each receptor site using as inputs the ambient concentrations and the chemical profiles of various sources including the major mine operations, the fly ash escaping the electrostatic filters of the power plants, and other primary and secondary sources. Mean measured PM10 concentrations at the different sites ranged from 38 to 72 µg m-3. The estimated total contribution of mines ranged between 9 and 22% in the cold period increasing to 36-42% in the dry warm period. Other significant sources were vehicular traffic, biomass burning, and secondary sulfate and nitrate aerosol. These results imply that more efficient measures to prevent and suppress fugitive dust emissions from the mines are needed.

A multi-component classifier for nonalcoholic fatty liver disease (NAFLD) based on genomic, proteomic, and phenomic data domains.

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.

Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery.

Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D) mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs) as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR) transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

The impact of obstructive sleep apnea on nonalcoholic fatty liver disease in patients with severe obesity.

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.

Utility of Ultrasound, Transaminases, and Visual Inspection to Assess Nonalcoholic Fatty Liver Disease in Bariatric Surgery Patients.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common in adults with extreme obesity and can impact long-term health and survival. Liver biopsy is the only accurate test for diagnosis and staging, but is invasive and costly. Non-invasive testing offers an attractive alternate, but the overall accuracy remains a significant issue. This study was conducted to determine the accuracy and clinical utility of pre-operative ultrasound and liver transaminase levels, as well as intra-operative hepatic visual inspection, for assessing presence of NAFLD as confirmed by hepatic histology. METHODS: Data was collected prospectively from 580 morbidly obese adult patients who underwent Roux-en-Y gastric bypass surgery with intraoperative wedge biopsy between January 2004 and February 2009. Complete data for ultrasound, ALT and AST levels, and documented visual inspection was available for 513 patients. RESULTS: The prevalence of NAFLD was 69 % and that of NASH was 32 %. The individual non-invasive clinical assessments demonstrated low sensitivity, specificity, and accuracy for detecting the presence of steatosis, steatohepatitis, or fibrosis. The combination of normal or abnormal results for all tests improved predictive utility. Abnormal tests with all three assessments had a sensitivity of 95-98 % and a specificity of 28-48 % for major histologic findings in NAFLD/NASH. Normal tests with all three assessments had a sensitivity of 12-22 % and a specificity of 89-97 % for major histologic findings in NAFLD/NASH. CONCLUSIONS: Although individual clinical tests for NAFLD have limited accuracy, the use of combined clinical tests may prove useful.

Perturbations of fibroblast growth factors 19 and 21 in type 2 diabetes.

Fibroblast growth factors 19 and 21 (FGF19 and FGF21) have been implicated, independently, in type 2 diabetes (T2D) but it is not known if their circulating levels correlate with each other or whether the associated hepatic signaling mechanisms that play a role in glucose metabolism are dysregulated in diabetes. We used a cross-sectional, case/control, experimental design involving Class III obese patients undergoing Roux-en-Y bariatric surgery (RYGB), and measured FGF19 and FGF21 serum levels and hepatic gene expression (mRNA) in perioperative liver wedge biopsies. We found that T2D patients had lower FGF19 and higher FGF21 serum levels. The latter was corroborated transcriptionally, whereby, FGF21, as well as CYP7A1, ß-Klotho, FGFR4, HNF4α, and glycogen synthase, but not of SHP or FXR mRNA levels in liver biopsies were higher in T2D patients that did not remit diabetes after RYGB surgery, compared to T2D patients that remitted diabetes after RYGB surgery or did not have diabetes. In a Phenome-wide association analysis using 205 clinical variables, higher FGF21 serum levels were associated with higher glucose levels and various cardiometabolic disease phenotypes. When serum levels of FGF19 were < 200 mg/mL and FGF21 > 500 mg/mL, 91% of patients had diabetes. These data suggest that FGF19/FGF21 circulating levels and hepatic gene expression of the associated signaling pathway are significantly dysregulated in type 2 diabetes.

Bariatric surgery: prevalence, predictors, and mechanisms of diabetes remission.

Type 2 diabetes is a chronic disease that can be treated with pharmacologic and/or lifestyle interventions, but in most cases it does not get cured. One of the few interventions, however, that can remit diabetes is the Roux-en-Y gastric bypass (RYGB) surgery. Approximately 63 % of patients undergoing RYGB surgery experience diabetes remission, but the underlying mechanisms are poorly understood. Some studies implicate enterohepatic pathways with bile acids, fibroblast growth factor 19 (FGF19), and glucagon-like peptide 1 (GLP-1) being the primary components. Here, we discuss these enterohepatic changes and highlight the roles of bile acids, FGF19, and GLP-1 in diabetes remission. We also describe how we can now actually predict, prior to surgery, the probability for remitting diabetes after RYGB surgery by using the DiaRem score. Deeper understanding of the mechanisms of diabetes remission by RYGB surgery could provide the basis for developing more effective interventions for curing the disease.

Genome-wide analysis of hepatic lipid content in extreme obesity.

AIMS: Individuals with type 2 diabetes have an increased risk of developing non-alcoholic fatty liver disease (NAFLD), and NAFLD patients are also at greater risk for developing type 2 diabetes. Although the relationship between type 2 diabetes and NAFLD is highly interconnected, the pathogenic mechanisms linking the two diseases are poorly understood. The goal of this study was to identify genetic determinants of hepatic lipid accumulation through association analysis using histological phenotypes in obese individuals. METHODS: Using the Illumina HumanOmniExpress BeadChip assay, we genotyped 2,300 individuals on whom liver biopsy data were available. RESULTS: We analyzed total bilirubin levels, which are linked to fatty liver in severe obesity, and observed the strongest evidence for association with rs4148325 in UGT1A (P < 5.0 × 10(-93)), replicating previous findings. We assessed hepatic fat level and found strong evidence for association with rs4823173, rs2896019, and rs2281135, all located in PNPLA3 and rs10401969 in SUGP1. Analysis of liver transcript levels of 20 genes residing at the SUGP1/NCAN locus identified a 1.6-fold change in the expression of the LPAR2 gene in fatty liver. We also observed suggestive evidence for association between low-grade fat accumulation and rs10859525 and rs1294908, located upstream from SOCS2 and RAMP3, respectively. SOCS2 was differentially expressed between fatty and normal liver. CONCLUSIONS: These results replicate findings for several hepatic phenotypes in the setting of extreme obesity and implicate new loci that may play a role in the pathophysiology of hepatic lipid accumulation.

The effect of insurance status on pre- and post-operative bariatric surgery outcomes.

BACKGROUND: This study compared pre- and post-surgical data and outcomes among gastric bypass patients based on the type of insurance (Medicaid, Medicare, or private). METHODS: Data were examined from 2553 consecutive RYGB patients at a rural ASMBS Center of Excellence. RESULTS: Participants were primarily female (80.5 %), Caucasian (97.1 %), and middle-aged (45.9 years). Medicaid patients' BMI at consultation was significantly higher than the other two groups (p < 0.001). Time to surgery was significantly longer for Medicaid (13.2 %) and Medicare (7.1 %) patients compared with privately insured patients (p < 0.001). Pre-surgical weight loss and post-surgical percent of excess weight loss nadir did not differ among the groups. Type 2 diabetes remission rates were comparable across insurance groups. CONCLUSIONS: Medicaid patients, although demographically different from their privately insured and Medicare counterparts, will benefit from surgery with comparable weight loss results and overall diabetes remission rates.

Preoperative use of incretins is associated with increased diabetes remission after RYGB surgery among patients taking insulin: a retrospective cohort analysis.

OBJECTIVE: The main goal of this study was to determine the effects of incretins on type 2 diabetes (T2D) remission after Roux-en-Y gastric bypass (RYGB) surgery for patients taking insulin. BACKGROUND: Type 2 diabetes is a chronic disease with potentially debilitating consequences. RYGB surgery is one of the few interventions that can remit T2D. Preoperative use of insulin, however, predisposes to significantly lower T2D remission rates. METHODS: A retrospective cohort of 690 T2D patients with at least 12 months follow-up and available electronic medical records was used to identify 37 T2D patients who were actively using a Glucagon-like peptide 1 (GLP-1) agonist in addition to another antidiabetic medication, during the preoperative period. RESULTS: Here, we report that use of insulin, along with other antidiabetic medications, significantly diminished overall T2D remission rates 14 months after RYGB surgery (9%) compared with patients not taking insulin (56%). Addition of the GLP-1 agonist, however, increased significantly T2D early remission rates (22%), compared with patients not taking the GLP-1 agonist (4%). Moreover, the 6-year remission rates were also significantly higher for the former group of patients. The GLP-1 agonist did not improve the remission rates of diabetic patients not taking insulin as part of their pharmacotherapy. CONCLUSIONS: Preoperative use of antidiabetic medication, coupled with an incretin agonist, could significantly improve the odds of T2D remission after RYGB surgery in patients also using insulin.

Even modest prediction accuracy of genomic models can have large clinical utility.

Whole Genome Prediction (WGP) jointly fits thousands of SNPs into a regression model to yield estimates for the contribution of markers to the overall variance of a particular trait, and for their associations with that trait. To date, WGP has offered only modest prediction accuracy, but in some cases even modest prediction accuracy may be useful. We provide an illustration of this using a theoretical simulation that used WGP to predict weight loss after bariatric surgery with moderate accuracy (R (2) = 0.07) to assess the clinical utility of WGP despite these limitations. Prevention of Type 2 Diabetes (T2DM) post-surgery was considered the major outcome. Treating only patients above predefined threshold of predicted weight loss in our simulation, in the realistic context of finite resources for the surgery, significantly reduced lifetime risk of T2DM in the treatable population by selecting those most likely to succeed. Thus, our example illustrates how WGP may be clinically useful in some situations, and even with moderate accuracy, may provide a clear path for turning personalized medicine from theory to reality.

Internalized weight bias in weight-loss surgery patients: psychosocial correlates and weight loss outcomes.

PURPOSE: In this study, we examined the relationship between pre-operative internalized weight bias and 12-month post-operative weight loss in adult bariatric surgery patients. METHODS: Bariatric surgery patients (n=170) from one urban and one rural medical center completed an internalized weight bias measure (the weight bias internalization scale, WBIS) and a depression survey (Beck depression inventory-II, BDI-II) before surgery, and provided consent to access their medical records. RESULTS: Participants (BMI=47.8 kg/m2, age=45.7 years) were mostly female (82.0 %), White (89.5 %), and underwent gastric bypass (83.6 %). The average WBIS score by item was 4.54 ± 1.3. Higher pre-operative WBIS scores were associated with diminished weight loss at 12 months after surgery (p=0.035). Pre-operative WBIS scores were positively associated with depressive symptoms (p<0.001). CONCLUSION: Greater internalized weight bias was associated with more depressive symptoms before surgery and less weight loss 1 year after surgery.

Extension of GWAS results for lipid-related phenotypes to extreme obesity using electronic health record (EHR) data and the Metabochip.

A variety of health-related data are commonly deposited into electronic health records (EHRs), including laboratory, diagnostic, and medication information. The digital nature of EHR data facilitates efficient extraction of these data for research studies, including genome-wide association studies (GWAS). Previous GWAS have identified numerous SNPs associated with variation in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). These findings have led to the development of specialized genotyping platforms that can be used for fine-mapping and replication in other populations. We have combined the efficiency of EHR data and the economic advantages of the Illumina Metabochip, a custom designed SNP chip targeted to traits related to coronary artery disease, myocardial infarction, and type 2 diabetes, to conduct an array-wide analysis of lipid traits in a population with extreme obesity. Our analyses identified associations with 12 of 21 previously identified lipid-associated SNPs with effect sizes similar to prior results. Association analysis using several approaches to account for lipid-lowering medication use resulted in fewer and less strongly associated SNPs. The availability of phenotype data from the EHR and the economic efficiency of the specialized Metabochip can be exploited to conduct multi-faceted genetic association analyses.

Does IRISIN Have a BRITE Future as a Therapeutic Agent in Humans?

The epidemic of obesity has contributed to the rapid rise in comorbid conditions such as cardiovascular disease, type 2 diabetes, sleep apnea, and hypertension among others. Therefore, there is a critical need to develop therapeutic strategies to reduce the prevalence of the disease. Skeletal muscle cells secrete signaling cytokines/peptides (referred to as myokines) that act in autocrine, paracrine, and endocrine fashion. Myokines have been hypothesized to contribute to the immediate and chronic benefits of exercise and may thus serve as attractive therapeutic agents for the treatment of obesity. The recent discovery of the irisin, a proposed myokine, has gained much attention over the last two years as a potential therapeutic agent. Preliminary studies demonstrated that irisin has the potential to induce "browning" of white adipocytes in mice. If these findings in mice could be translated to humans, irisin could be a potential therapeutic agent for the treatment of obesity. Limitations with the available antibodies, however, have raised concerns regarding the detectability of irisin in circulation. Moreover, the gene encoding irisin, FNDC5, is expressed robustly not only in muscle but also in various white adipose tissues (WAT) in humans, raising the possibility for increased thermogenesis through autocrine mechanisms. Here we will discuss the browning of WAT, the discovery of irisin, and its potential role in improving metabolic health in humans.

A patient-centered electronic tool for weight loss outcomes after Roux-en-Y gastric bypass.

BACKGROUND. Current patient education and informed consent regarding weight loss expectations for bariatric surgery candidates are largely based on averages from large patient cohorts. The variation in weight loss outcomes illustrates the need for establishing more realistic weight loss goals for individual patients. This study was designed to develop a simple web-based tool which provides patient-specific weight loss expectations. METHODS. Postoperative weight measurements after Roux-en-Y gastric bypass (RYGB) were collected and analyzed with patient characteristics known to influence weight loss outcomes. Quantile regression was used to create expected weight loss curves (25th, 50th, and 75th %tile) for the 24 months after RYGB. The resulting equations were validated and used to develop web-based tool for predicting weight loss outcomes. RESULTS. Weight loss data from 2986 patients (2608 in the primary cohort and 378 in the validation cohort) were included. Preoperative body mass index (BMI) and age were found to have a high correlation with weight loss accomplishment (P < 0.0001 for each). An electronic tool was created that provides easy access to patient-specific, 24-month weight loss trajectories based on initial BMI and age. CONCLUSIONS. This validated, patient-centered electronic tool will assist patients and providers in patient teaching, informed consent, and postoperative weight loss management.

Preoperative prediction of type 2 diabetes remission after Roux-en-Y gastric bypass surgery: a retrospective cohort study.

BACKGROUND: About 60% of patients with type 2 diabetes achieve remission after Roux-en-Y gastric bypass (RYGB) surgery. No accurate method is available to preoperatively predict the probability of remission. Our goal was to develop a way to predict probability of diabetes remission after RYGB surgery on the basis of preoperative clinical criteria. METHODS: In a retrospective cohort study, we identified individuals with type 2 diabetes for whom electronic medical records were available from a primary cohort of 2300 patients who underwent RYGB surgery at the Geisinger Health System (Danville, PA, USA) between Jan 1, 2004, and Feb 15, 2011. Partial and complete remission were defined according to the American Diabetes Association criteria. We examined 259 clinical variables for our algorithm and used multiple logistic regression models to identify independent predictors of early remission (beginning within first 2 months after surgery and lasting at least 12 months) or late remission (beginning more than 2 months after surgery and lasting at least 12 months). We assessed a final Cox regression model with a consistent subset of variables that predicted remission, and used the resulting hazard ratios (HRs) to guide creation of a weighting system to produce a score (DiaRem) to predict probability of diabetes remission within 5 years. We assessed the validity of the DiaRem score with data from two additional cohorts. FINDINGS: Electronic medical records were available for 690 patients in the primary cohort, of whom 463 (63%) had achieved partial or complete remission. Four preoperative clinical variables were included in the final Cox regression model: insulin use, age, HbA1c concentration, and type of antidiabetic drugs. We developed a DiaRem score that ranges from 0 to 22, with the greatest weight given to insulin use before surgery (adding ten to the score; HR 5·90, 95% CI 4·41­7·90; p<0·0001). Kaplan-Meier analysis showed that 88% (95% CI 83­92%) of patients who scored 0­2, 64% (58­71%) of those who scored 3­7, 23% (13­33%) of those who scored 8­12, 11% (6­16%) of those who scored 13­17, and 2% (0­5%) of those who scored 18­22 achieved early remission (partial or complete). As in the primary cohort, the proportion of patients achieving remission in the replication cohorts was highest for the lowest scores, and lowest for the highest scores. INTERPRETATION: The DiaRem score is a novel preoperative method to predict the probability of remission of type 2 diabetes after RYGB surgery. FUNDING: Geisinger Health System and the US National Institutes of Health.

Modulation of fibroblast growth factor 19 expression by bile acids, meal replacement and energy drinks, milk, and coffee.

BACKGROUND: The enterohepatic pathway involving the fibroblast growth factor 19 (FGF19) and bile acids (BA) has been linked with the etiology and remission of type 2 diabetes (T2D) following Roux-en-Y gastric bypass (RYGB) surgery. Specifically, diabetic patients had lower FGF19 circulating levels but postoperative FGF19 and BA levels were higher in diabetic patients that experience remission of T2D, as compared to non-diabetic patients and diabetic patients that do not experience remission. It has been proposed that this may be due to the direct flow of digestate-free bile acids into the ileum benefiting mostly T2D patients without severe diabetes. METHODS/RESULTS: We used a human colorectal cell line (LS174T) that endogenously expresses FGF19, real time PCR, and Elisas for precise quantitation of FGF19 mRNA and secreted protein levels. We report here that BA and fractions of BA stimulated FGF19 in vitro but this effect was partially blocked when BA were pre-incubated with a lipoprotein mix which emulates digested food. In addition, we show that FGF19 mRNA was stimulated by meal replacement drinks (Ensure, Glucerna, SlimFast), non-fat milk, and coffee which has been linked with reduced risk for developing diabetes. Pure caffeine and the 5-hour Energy drink, on the other hand, decreased FGF19 mRNA. CONCLUSIONS: In summary, FGF19 expression in vitro is modifiable by popular drinks suggesting that such approaches could potentially be used for modulating FGF19 expression in humans.

Gastrointestinal symptoms in morbid obesity.

BACKGROUND: Several reports have shown an increased prevalence of gastrointestinal (GI) symptoms in obese subjects in community-based studies. To better understand the role of the GI tract in obesity, and because there are limited clinic-based studies, we documented the prevalence of upper and lower GI symptoms in morbidly obese individuals in a clinic setting. OBJECTIVE: The aim of our study was to compare the prevalence of GI symptoms in morbidly obese individuals in a weight management clinic with non-obese individuals with similar comorbidities as morbidly obese individuals in an Internal Medicine clinic. METHODS: Class II and III obese patients BMI >35 kg/m(2) (N = 114) and 182 non-obese patients (BMI <25 kg/m(2)) completed the GI symptoms survey between August 2011 and April 2012 were included in this study. The survey included 24 items pertaining to upper and lower GI symptoms. The participants rated the frequency of symptoms as absent (never, rarely) or present (occasionally, frequently). The symptoms were clustered into five categories: oral symptoms, dysphagia, gastroesophageal reflux, abdominal pain, and bowel habits. Responses to each symptom cluster were compared between obese group and normal weight groups using logistic regression. RESULTS: Of the 24 items, 18 had a higher frequency in the obese group (p < 0.005 for each). After adjusting for age and gender, the obese patients were more likely to have upper GI symptoms: any oral symptom (OR = 2.3, p = 0.0013), dysphagia (OR 2.9, p = 0.0006), and any gastroesophageal reflux (OR 3.8, p < 0.0001). Similarly, the obese patients were more likely to have lower GI symptoms: any abdominal pain (OR = 1.7, p = 0.042) and altered bowel habits (OR = 2.8, p < 0.0001). CONCLUSION: These observations suggest a statistically significant increase in frequency of both upper and lower GI symptoms in morbidly obese patients when compared to non-obese subjects.

Clinical factors associated with weight loss outcomes after Roux-en-Y gastric bypass surgery.

OBJECTIVE: Gastric bypass surgery is an effective therapy for extreme obesity. However, substantial variability in weight loss outcomes exists that remains largely unexplained. Our objective was to determine whether any commonly collected preoperative clinical variables were associated with weight loss following Roux-en-Y gastric bypass (RYGB) surgery. METHODS: The analysis was based on a prospectively recruited observational cohort of 2,365 patients who underwent Roux-en-Y gastric bypass surgery from 2004 to 2009. Weight loss was stratified into three major phases, early (0-6 months), nadir, and long-term (>36 months). Multivariate regression models were constructed using a database of over 350 variables. RESULTS: A total of 12-14 preoperative variables were independently associated (P < 0.05) with each of the temporal weight loss phases. Preoperative variables associated with poorer nadir and long-term weight loss included higher baseline BMI, higher preoperative weight loss, iron deficiency, use of any diabetes medication, nonuse of bupropion medication, no history of smoking, age >50 years, and the presence of fibrosis on liver biopsy. CONCLUSIONS: Several variables previously associated with poorer weight loss after RYGB surgery including age, baseline BMI, and type 2 diabetes were replicated. Several others suggest possible clinical interventions for postoperative management of RYGB patients to improve weight loss outcomes.