Surgical weight-loss to improve functional status trajectories following total knee arthroplasty: SWIFT trial: Rationale, design, and methods.

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.

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.

Examination of the Beck Depression Inventory-II Factor Structure Among Bariatric Surgery Candidates.

BACKGROUND: The Beck Depression Inventory-II (BDI-II) is frequently used to evaluate bariatric patients in clinical and research settings; yet, there are limited data regarding the factor structure of the BDI-II with a bariatric surgery population. METHODS: Exploratory factor analysis (EFA) using principal axis factoring with oblimin rotation was employed with data from 1228 consecutive presurgical bariatric candidates. Independent t tests were used to examine potential differences between sexes. Confirmatory factor analysis (CFA) was conducted with the next 383 consecutive presurgical patients to evaluate the proposed model based on EFA results. RESULTS: EFA revealed three factors: negative perceptions, diminished vigor, and cognitive dysregulation, each with adequate internal consistency. Six BDI-II items did not load significantly on any of the three factors. CFA results largely supported the proposed model. CONCLUSIONS: Results suggest that dimensions of depression for presurgical bariatric candidates vary from other populations and raise important caveats regarding the utility of the BDI-II in bariatric research.

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.

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.

Frequencies of obesity susceptibility alleles among ethnically and racially diverse bariatric patient populations.

BACKGROUND: Genetic factors likely play a role in obesity and the outcomes after bariatric surgery. Single nucleotide polymorphisms in or near the insulin-induced gene 2 (INSIG-2), fat mass and obesity-associated gene (FTO), melanocortin 4 receptor gene (MC4R), and proprotein convertase subtilisn/kexin type 1 gene (PCSK-1) have been associated with class III obesity in whites. Minimal data are available regarding the genetic susceptibility to obesity in class III obese nonwhites, especially Hispanics. Our objective was to perform a comparative analysis of 4 common genetic variants (INSIG-2, FTO, MC4R, and PCSK-1) associated with obesity in a diverse population of bariatric surgery patients to determine whether a difference exists by ethnicity (white versus Hispanic). The setting of the study was 2 university hospitals in the United States. METHODS: Bariatric surgery patients from 2 different institutions were enrolled prospectively, and genotyping was performed. Differences in the distribution of INSIG-2, FTO, MC4R, and PCSK-1 single nucleotide polymorphisms among the different ethnicities (whites and Hispanics) were compared using an additive model (0, 1, or 2 risk alleles). A propensity-matched analysis was used to account for cohort differences. RESULTS: A total of 1276 bariatric patients were genotyped for the INSIG-2, FTO, MC4R, and PCSK-1 obesity single nucleotide polymorphisms. Statistically significant differences in FTO, INSIG-2, MC4R, and PCSK-1 were seen using an additive model. FTO, PCSK-1, and MC4R (test for trend) remained significantly different in the propensity analysis. CONCLUSION: Significant differences in the frequencies of several common obesity susceptibility variants in or near FTO, PCSK-1, and MC4R were found in white and Hispanic patients with class III obesity undergoing bariatric surgery. Larger studies in more class III obese Hispanics of different nationalities are needed.

An electronic health record-enabled obesity database.

BACKGROUND: The 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. METHODS: Clinical 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. RESULTS: Demographic, 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. CONCLUSION: A variety of EHR-derived data related to obesity can be efficiently obtained and used to study important outcomes following RYGB.