Peter Benotti

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

BACKGROUNDnAbout 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.nnnMETHODSnIn 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.nnnFINDINGSnElectronic 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 4·41–7·90; p<0·0001). Kaplan-Meier analysis showed that 88% (95% CI 83–92%) of patients who scored 0–2, 64% (58–71%) of those who scored 3–7, 23% (13–33%) of those who scored 8–12, 11% (6–16%) of those who scored 13–17, and 2% (0–5%) of those who scored 18–22 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.nnnINTERPRETATIONnThe DiaRem score is a novel preoperative method to predict the probability of remission of type 2 diabetes after RYGB surgery.nnnFUNDINGnGeisinger Health System and the US National Institutes of Health.

Open versus Laparoscopic Roux-en-Y Gastric Bypass: A Comparative Study of Over 25,000 Open Cases and the Major Laparoscopic Bariatric Reported Series

Background: Laparoscopic bariatric surgery has experienced a rapid expansion of interest over the past 5 years, with a 470% increase. This rapid expansion has markedly increased overall cost, reducing surgical access. Many surgeons believe that the traditional open approach is a cheaper, safer, equally effective alternative. Methods: 16 highly experienced open bariatric surgeons with a combined total of 25,759 cases representing >200 surgeon years of experience, pooled their open Roux-en-Y gastric bypass (ORYGBP) data, and compared their results to the leading laparoscopic (LRYGBP) papers in the literature. Results: In the overall series, the incisional hernia rate was 6.4% using the standard midline incision. Utilizing the left subcostal incision (LSI), it was only 0.3%. Return to surgery in <30 days was 0.7%, deaths 0.25%, and leaks 0.4%. Average length of stay was 3.4 days, and return to usual activity 21 days. Small bowel obstruction was significantly higher with the LRYGBP. Surgical equipment costs averaged ∼

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

3,000 less for open cases. LRYGBP had an added expense for longer operative time. This more than made up for the shorter length of stay with the laparoscopic approach. Conclusions: The higher cost, higher leak rate, higher rate of small bowel obstruction, and similar long-term weight loss results make the open RYGBP our preferred operation. If the incision is taken out of the equation (i.e. use of the LSI), the significant advantages of the open technique become even more obvious.

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

An electronic health record-enabled obesity database.

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.

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

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.

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

BackgroundGastric bypass surgery is a highly effective therapy for long-term weight loss in severely obese patients, but carries significant perioperative risks including infection, wound dehiscence, and leaks from staple breakdown. Iron status can affect immune function and wound healing, thus may influence peri-operative complications. Common mutations in the HFE gene, the gene responsible for the iron overload disorder hereditary hemochromatosis, may impact iron status.MethodsWe analyzed 1064 extremely obese Caucasian individuals who underwent open and laparoscopic Roux-n-Y gastric bypass surgery at the Geisinger Clinic. Serum iron, ferritin, transferrin, and iron binding capacity were measured pre-operatively. All patients had intra-operative liver biopsies and were genotyped for the C282Y and H63D mutations in the HFE gene. Associations between surgical complications and serum iron measures, HFE gene status, and liver iron histology were determined.ResultsWe found that increased serum iron and transferrin saturation were present in patients with any post-operative complication, and that increased serum ferritin was also increased in patients with major complications. Increased serum transferrin saturation was also associated with wound complications in open RYGB, and transferrin saturation and ferritin with prolonged lengths of stay. The presence of 2 or more HFE mutations was associated with overall complications as well as wound complications in open RYGB. No differences were found in complication rates between those with stainable liver iron and those without.ConclusionSerum iron status and HFE genotype may be associated with complications following RYGB surgery in the extremely obese.

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

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, β-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.

Evaluation of the Association Between Preoperative Clinical Factors and Long-term Weight Loss After Roux-en-Y Gastric Bypass

BackgroundNonalcoholic 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.MethodsData 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.ResultsThe prevalence of NAFLD was 69xa0% and that of NASH was 32xa0%. 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 95–98xa0% and a specificity of 28–48xa0% for major histologic findings in NAFLD/NASH. Normal tests with all three assessments had a sensitivity of 12–22xa0% and a specificity of 89–97xa0% for major histologic findings in NAFLD/NASH.ConclusionsAlthough individual clinical tests for NAFLD have limited accuracy, the use of combined clinical tests may prove useful.

All-Cause and Specific-Cause Mortality Risk After Roux-en-Y Gastric Bypass in Patients With and Without Diabetes

ImportancenWeight loss after bariatric surgery varies, yet preoperative clinical factors associated with long-term suboptimal outcomes are not well understood.nnnObjectivenTo evaluate the association between preoperative clinical factors and long-term weight loss after Roux-en-Y gastric bypass (RYGB).nnnDesign, Setting, and ParticipantsnFrom June 2001 to September 2007, this retrospective cohort study followed up RYGB patients before surgery to 7 to 12 years after surgery. The setting was a large rural integrated health system. Of 1033 eligible RYGB patients who consented to participate in longitudinal research and completed surgery before October 2007, a total of 726 (70.3%) had a weight entered in the electronic medical record 7 or more years after surgery and were included in the analyses after exclusions for pregnancy and mortality. Date of the long-term weight measurement was recorded between August 2010 and January 2016.nnnMain Outcomes and MeasuresnThe primary outcome was percentage weight loss (%WL) at 7 to 12 years after surgery. Preoperative clinical factors (>200) extracted from the electronic medical record included medications, comorbidities, laboratory test results, and demographics, among others.nnnResultsnAmong the 726 study participants, 83.1% (nu2009=u2009603) were female and 97.4% (nu2009=u2009707) were of white race, with a mean (SD) preoperative body mass index (calculated as weight in kilograms divided by height in meters squared) of 47.5 (7.4). From the time of surgery to long-term follow-up (median, 9.3 postoperative years), the mean (SD) %WL was 22.5% (13.1%). Preoperative insulin use, history of smoking, and use of 12 or more medications before surgery were associated with greater long-term postoperative %WL (6.8%, 2.8%, and 3.1%, respectively). Preoperative hyperlipidemia, older age, and higher body mass index were associated with poorer long-term postoperative %WL (-2.8%, -8.8%, and -4.1%, respectively).nnnConclusions and RelevancenFew preoperative clinical factors associated with long-term weight loss after RYGB were identified. Preoperative insulin use was strongly associated with better long-term %WL, while preoperative hyperlipidemia, higher body mass index, and older age were associated with poorer %WL. Our findings provide additional insight into preoperative identification of RYGB patients at higher risk for long-term suboptimal outcomes.