Anthony Petrick

A Role for Fibroblast Growth Factor 19 and Bile Acids in Diabetes Remission After Roux-en-Y Gastric Bypass

OBJECTIVE Roux-en-Y gastric bypass (RYGB) in humans can remit type 2 diabetes, but the operative mechanism is not completely understood. In mice, fibroblast growth factor (FGF) 15 (FGF19 in humans) regulates hepatic bile acid (BA) production and can also resolve diabetes. In this study, we tested the hypothesis that the FGF19–BA pathway plays a role in the remission of human diabetes after RYGB surgery. RESEARCH DESIGN AND METHODS Cohorts of diabetic and nondiabetic individuals of various body weights were used. In addition, RYGB patients without diabetes (No-Diabetes), RYGB patients with diabetes who experienced remission for at least 12 months after surgery (Diabetes-R), and RYGB patients with diabetes who did not go into remission after surgery (Diabetes-NoR) were studied. Circulating FGF19 and BA levels, hepatic glycogen content, and expression levels of genes regulating the FGF19–BA pathway were compared among these groups of patients using pre- and postoperative serum samples and intraoperative liver biopsies. RESULTS Preoperatively, patients with diabetes had lower FGF19 and higher BA levels than nondiabetic patients, irrespective of body weight. In diabetic patients undergoing RYGB, lower FGF19 levels were significantly correlated with increased hepatic expression of the cholesterol 7alpha-hydroxylase 1 (CYP7A1) gene, which modulates BA production. Following RYGB surgery, however, FGF19 and BA levels (particularly cholic and deoxycholic acids) exhibited larger increases in Diabetic-R patients compared with nondiabetic and Diabetic-NoR patients. CONCLUSIONS Taken together, the baseline and postoperative data implicate the FGF19–CYP7A1–BA pathway in the etiology and remission of type 2 diabetes following RYGB surgery.

Preoperative weight loss before bariatric surgery.

HYPOTHESIS Preoperative weight loss reduces the frequency of surgical complications in patients undergoing bariatric surgery. DESIGN Review of records of patients undergoing open or laparoscopic gastric bypass. SETTING A comprehensive, multidisciplinary obesity treatment center at a tertiary referral center that serves central Pennsylvania. PATIENTS A total of 881 patients undergoing open or laparoscopic gastric bypass from May 31, 2002, through February 24, 2006. INTERVENTION All preoperative patients completed a 6-month multidisciplinary program that encouraged a 10% preoperative weight loss. MAIN OUTCOME MEASURES Loss of excess body weight (EBW) and total and major complication rates. RESULTS Of the 881 patients, 592 (67.2%) lost 5% or more EBW and 423 (48.0%) lost more than 10% EBW. Patients referred for open gastric bypass (n = 466) were generally older (P < .001), had a higher body mass index (P < .001), and were more often men (P < .001) than those undergoing laparoscopic gastric bypass (n = 415). Total and major complication rates were higher in patients undergoing open gastric bypass (P < .001 and P = .03, respectively). Univariate analysis revealed that increasing preoperative weight loss is associated with reduced complication frequencies for the entire group for total complications (P =.004) and most likely for major complications (P = .06). Controlling for age, sex, baseline body mass index, and type of surgery in a multiple logistic regression model, increased preoperative weight loss was a predictor of reduced complications for any (P =.004) and major (P = .03) complications. CONCLUSION Preoperative weight loss is associated with fewer complications after gastric bypass surgery.

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

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.

Risk Factors Associated With Mortality After Roux-en-Y Gastric Bypass Surgery

Objective:We sought to identify the major risk factors associated with mortality in Roux-en-Y gastric bypass (RYGB) surgery. Background:Bariatric surgery has become an established treatment for extreme obesity. Bariatric surgery mortality has steadily declined with current rates of less than 0.5%. However, significant variation in the mortality rates has been reported for specific patient cohorts and among bariatric centers. Methods:Clinical outcome data from 185,315 bariatric surgery patients from the Bariatric Outcome Longitudinal Database were reviewed. Of these, 157,559 patients had either documented 30 or more day follow-up data, including mortality. Multiple demographic, socioeconomic, and clinical factors were analyzed by univariate analysis for their association with 30-day mortality after gastric bypass. Variables found to be significant were entered into a multiple logistic regression model to identify factors independently associated with 30-day mortality. On the basis of these results, a RYGB mortality risk score was developed. Results:The overall 30-day mortality rate for the entire bariatric surgery cohort was 0.1%. Of the 81,751 RYGB patients, the mortality rate was 0.15%. Factors significantly associated with 30-day gastric bypass mortality included increasing body mass index (BMI) (P < 0.0001), increasing age (P < 0.005), male gender (P < 0.001), pulmonary hypertension (P < 0.0001), congestive heart failure (P = 0.0008), and liver disease (P = 0.038). When the RYGB risk score was applied, a significant trend (P < 0.0001) between increasing risk score and mortality rate is found. Conclusions:Increasing BMI, increasing age, male gender, pulmonary hypertension, congestive heart failure, and liver disease are risk factors for 30-day mortality after RYGB. The RYGB risk score can be used to determine patients at greater risk for mortality after RYGB surgery.

High allelic burden of four obesity SNPs is associated with poorer weight loss outcomes following gastric bypass surgery.

Genome‐wide association and linkage studies have identified multiple susceptibility loci for obesity. We hypothesized that such loci may affect weight loss outcomes following dietary or surgical weight loss interventions. A total of 1,001 white individuals with extreme obesity (BMI >35 kg/m2) who underwent a preoperative diet/behavioral weight loss intervention and Roux‐en‐Y gastric bypass surgery were genotyped for single‐nucleotide polymorphisms (SNPs) in or near the fat mass and obesity‐associated (FTO), insulin induced gene 2 (INSIG2), melanocortin 4 receptor (MC4R), and proprotein convertase subtilisin/kexin type 1 (PCSK1) obesity genes. Association analysis was performed using recessive and additive models with pre‐ and postoperative weight loss data. An increasing number of obesity SNP alleles or homozygous SNP genotypes was associated with increased BMI (P < 0.0006) and excess body weight (P < 0.0004). No association between the amounts of weight lost from a short‐term dietary intervention and any individual obesity SNP or cumulative number of obesity SNP alleles or homozygous SNP genotypes was observed. Linear mixed regression analysis revealed significant differences in postoperative weight loss trajectories across groups with low, intermediate, and high numbers of obesity SNP alleles or numbers of homozygous SNP genotypes (P < 0.0001). Initial BMI interacted with genotype to influence weight loss with initial BMI <50 kg/m2, with evidence of a dosage effect, which was not present in individuals with initial BMI ≥50 kg/m2. Differences in metabolic rate, binge eating behavior, and other clinical parameters were not associated with genotype. These data suggest that response to a surgical weight loss intervention is influenced by genetic susceptibility and BMI.

Bariatric Surgery: Shedding the Monetary Weight of Prescription Costs in the Managed Care Arena

Background: Prescription costs for treatment of comorbidities associated with morbid obesity is a considerable annual health-care expenditure. This study addressed the effect of Roux-en-Y gastric bypass (RYGBP) on diabetic and anti-hypertensive pharmaceutical utilization and cost savings at our institution. Methods: Retrospective data from the electronic database of 51 consecutive patients, who underwent RYGBP from March 2001 to May 2002 were studied. Patients had BMI >40 associated with obesity-related diabetes and hypertension. Prescription medications utilized by this cohort were reviewed preoperatively and at 3- and 9-month intervals postoperatively. Significance was analyzed by paired t-test. Results: Prevalence of diabetes and hypertension was 55.7% (29/53) and 44.3% (24/53) respectively, and 34% (18/53) patients had both co-morbidities. Preoperatively, patients were on an average of 2.44 ± 1.86 medications at a cost of

An electronic health record-enabled obesity database.

187.24 ±

The influence of iron status and genetic polymorphisms in the HFE gene on the risk for postoperative complications after bariatric surgery: a prospective cohort study in 1,064 patients

237.41 per month. Postoperatively, the mean number of medications was reduced to 0.56 ± 0.81 agents (P<0.001) at a monthly cost of

Prevalence and Risk Factors for Bariatric Surgery Readmissions: Findings From 130,007 Admissions in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program.

42.53 ± 116.60 (P<0.001). Conclusions: RYGBP can decrease the prescription medication requirements, resulting in significant cost-savings in the treatment of obesity-related hypertension and diabetes. This study found a 77.3% reduction in total cost of diabetic and anti-hypertensive medications.

A Patient-Centered Electronic Tool for Weight Loss Outcomes after Roux-en-Y Gastric Bypass

BackgroundThe effectiveness of weight loss therapies is commonly measured using body mass index and other obesity-related variables. Although these data are often stored in electronic health records (EHRs) and potentially very accessible, few studies on obesity and weight loss have used data derived from EHRs. We developed processes for obtaining data from the EHR in order to construct a database on patients undergoing Roux-en-Y gastric bypass (RYGB) surgery.MethodsClinical data obtained as part of standard of care in a bariatric surgery program at an integrated health delivery system were extracted from the EHR and deposited into a data warehouse. Data files were extracted, cleaned, and stored in research datasets. To illustrate the utility of the data, Kaplan-Meier analysis was used to estimate length of post-operative follow-up.ResultsDemographic, laboratory, medication, co-morbidity, and survey data were obtained from 2028 patients who had undergone RYGB at the same institution since 2004. Pre-and post-operative diagnostic and prescribing information were available on all patients, while survey laboratory data were available on a majority of patients. The number of patients with post-operative laboratory test results varied by test. Based on Kaplan-Meier estimates, over 74% of patients had post-operative weight data available at 4 years.ConclusionA variety of EHR-derived data related to obesity can be efficiently obtained and used to study important outcomes following RYGB.