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Predictors of Responsiveness to Vitamin D Supplementation and Outcomes Assessment in Patients Undergoing Roux-En-Y Gastric Bypass Surgery

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Predictors of Responsiveness to Vitamin D Supplementation and Outcomes Assessment in Patients Undergoing Roux-En-Y Gastric Bypass Surgery Predictors of Responsiveness to Vitamin D Supplementation and Outcomes Assessment in Patients Undergoing Roux-en-Y Gastric Bypass Surgery Jessica E Kim A thesis submitted in partial fulfillment of the requirements for the degree of Masters of Science University of Washington 2013 Committee: Lingtak-Neander Chan Elizabeth Kirk Tiana Colovos Program Authorized to Offer Degree: School of Public Health Nutritional Sciences Program ©Copyright 2013 Jessica E Kim 2 University of Washington Abstract Predictors of Responsiveness to Vitamin D Supplementation and Outcomes Assessment in Patients Undergoing Roux-en-Y Gastric Bypass Surgery Jessica E Kim Chair of the Supervisory Committee: Associate Professor Lingtak-Neander Chan, Pharm D, BCNSP Interdisciplinary Faculty of Nutritional Sciences Department of Pharmacy Background: Vitamin D is one of the most common micronutrient deficiencies in the obese population awaiting Roux-en-Y gastric bypass (RYGB) surgery and often persists post-operatively despite routinely recommended supplementation, suggesting there may be variable response to this supplementation. However, there are no established indicators that allow clinicians to identify the non-responders, and factors contributing to poor vitamin D repletion after surgery remain unclear. In addition, a patient’s nutritional status is an important factor in postoperative morbidity and mortality after any major surgery, but it is unknown how vitamin D status impacts patient outcomes after bariatric procedures. The aims of this study were to identify the predictors of responsiveness to vitamin D supplementation in recipients of RYGB surgery, and to compare patient outcomes as measured by hospital readmissions and emergency room (ER) visits, between responders and non-responders in the year following surgery. Methods: The medical records of patients who underwent RYGB at the University of Washington Medical Center from 2009-2011 and had insufficient vitamin D concentrations (<30 ng/mL) at baseline were reviewed. Non-responders were defined as those who maintained serum 25(OH)D concentrations <30 ng/mL after 1 year; responders were those whose concentrations increased to ≥30 ng/mL after 1 year. Demographic, anthropometric 3 and clinical variables were compared between the two groups to identify predictors. The number of readmissions and ER visits in the year following surgery were also compared between non-responders and responders. Results: There were 40 total patients; 15 non-responders and 25 responders. Baseline serum albumin concentrations were significantly higher in responders than non- responders (3.8±0.2 g/dL vs 3.5±0.2 g/dL, p=0.001). Hospital readmissions did not vary significantly between groups, but non-responders had significantly more ER visits in the year following surgery than responders (1 vs. 0, p=0.021). Both baseline serum albumin (OR=1.70, 95%CI=1.18-2.46, p=0.005) and ER visits (OR=0.37, 95%CI=0.15-0.91, p=0.031) were found to be a predictor of being a responder post-RYGB in the unadjusted logistic regression analysis; after adjusting for age, sex, baseline 25(OH)D, season, comorbidities, baseline serum albumin, BMI and weight, 1 year weight loss and serum albumin, # of ER visits, only baseline serum albumin remained a significant predictor (OR=2.19, 95%CI=1.15-4.17, p=0.016). Conclusions: Serum albumin at baseline was a potential predictor of response to vitamin D supplementation following RYGB in a population with insufficient vitamin D concentrations at baseline residing in the Pacific Northwest. There was a significant difference in the effect of season on 1 year serum 25(OH)D concentrations between responders and non-responders, while supplement use did not significantly differ between non-responders and responders. Non-responders also sought treatment at an emergency room significantly more than responders in the year following surgery. These predictors may allow clinicians to better identify and tailor supplement dosages to avoid or correct preexisting vitamin D deficiency after Roux-en-Y gastric bypass. 4 Table of Contents Background ........................................................................................................................................................... 6 The Current State of Obesity ........................................................................................................................ 6 Surgical Interventions for Obesity: Roux-en-Y Gastric Bypass ....................................................... 6 Risks and Benefits .................................................................................................................................. 8 Vitamin D ...........................................................................................................................................................11 Vitamin D Deficiency ...........................................................................................................................13 Vitamin D Deficiency in the Bariatric Population ....................................................................18 Screening and Supplementation ...............................................................................................................20 Impact of Vitamin D on Bariatric Outcomes ........................................................................................24 Introduction ....................................................................................................................................................... 27 Methods ................................................................................................................................................................ 29 Research Design ..............................................................................................................................................29 Statistical Analysis ..........................................................................................................................................30 Results ................................................................................................................................................................... 31 Discussion ........................................................................................................................................................... 36 Tables and Figures .......................................................................................................................................... 45 References ........................................................................................................................................................... 55 5 Background The Current State of Obesity Obesity is one of the foremost public health problems in the United States, with recent National Health and Nutrition Examination Survey 2009-2010 data estimating the prevalence of obesity in the United States, defined as a body mass index (BMI) ≥30 kg/m2, to be more than one-third of the population, affecting over 78 million adults (Ogden et al., 2012). In addition, the prevalence of Class III obesity (BMI >40 kg/m2) has increased, affecting approximately 6.3% of the U.S. population (Flegal et al., 2012). Obesity is also associated with an increased hazard ratio for all-cause mortality and the American Medical Association recently recognized it as a true disease state rather than a chronic medical condition (American Medical Association House of Delegates, 2013). Obesity also increases the risk of diabetes mellitus, cardiovascular disease, hypertension and certain cancers, as well as osteoarthritis, respiratory problems and gallbladder disease (Working Group from North American Association for the Study of Obesity and the National Heart, 2000). The obesity-associated medical costs were estimated to be ~$150 billion in 2008 (Finkelstein et al., 2009), with projected future healthcare costs of treating obesity-related diseases in the United States increasing by 48-60 billion dollars a year by 2030 if current trends continue, and could account for 16-18% of total US healthcare costs (Wang et al., 2011). Surgical Interventions for Obesity: Roux-en-Y Gastric Bypass Bariatric surgery remains the most effective option for Class III obesity because conventional dietary interventions, lifestyle modifications, counseling, pharmacotherapy, or a combination of the above do not achieve a comparable magnitude in weight loss, weight maintenance, and clinical improvement of comorbid conditions compared with bariatric surgery. The American Society for Metabolic and Bariatric Surgery (ASMBS), American Association of Clinical Endocrinologists (AACE) and the Obesity Society recommend bariatric surgery in those with a BMI≥40 or ≥35 kg/m2 with comorbid conditions like type 2 diabetes, and those where medical therapies have failed and have an 6 impaired quality of life. Patients also should demonstrate appropriate motivation, psychological stability and social support (Mechanick et al., 2013). Over 220,000 bariatric surgical procedures are performed annually in the United States and Canada, with Roux-en-Y gastric bypass (RYGB) being the most commonly performed procedure (Bal et al., 2011). It is considered a restrictive and mildly malabsorptive procedure, and it results in greater overall weight loss and better improvement of comorbidities compared to other purely restrictive surgeries like gastric banding (Mechanick et al., 2009; Sjöström et al., 2007). In RYGB, the upper part
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