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

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          Abstract

          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 pre-operative clinical variables were associated with weight loss following Roux-en-Y gastric bypass surgery.

          DESIGN

          The analysis was based on a prospectively recruited observational cohort of 2365 patients who underwent Roux-en-Y gastric bypass surgery from 2004-2009. 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 pre-operative variables were independently associated (p<0.05) with each of the temporal weight loss phases. Pre-operative variables associated with poorer nadir and long-term weight loss included: higher baseline BMI, higher pre-operative weight loss, iron deficiency, use of any diabetes medication, non-use of bupropion medication, no history of smoking, aged >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 post-operative management of RYGB patients to improve weight loss outcomes.

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          Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years.

          Didier Look, N V Christou, L MacLean (2006)
          To complete a long-term (>10 years) follow-up of patients undergoing isolated roux-en-Y gastric bypass for severe obesity. Long-term results of gastric bypass in patients followed for longer than 10 years is not reported in the literature. Accurate weights were recorded on 228 of 272 (83.8%) of patients at a mean of 11.4 years (range, 4.7-14.9 years) after surgery. Results were documented on an individual basis for both long- and short-limb gastric bypass and compared with results at the nadir BMI and % excess weight loss (%EWL) at 5 years and >10 years post surgery. There was a significant (P 50 kg/m) from the nadir to 5 years and from 5 to 10 years. The super obese lost more rapidly from time zero and gained more rapidly after reaching the lowest weight at approximately 2 years than the morbidly obese patients. There was no difference in results between the long- and short-limb operations. There was a significant increase in failures and decrease in excellent results at 10 years when compared with 5 years. The failure rate when all patients are followed for at least 10 years was 20.4% for morbidly obese patients and 34.9% for super obese patients. The gastric bypass limb length does not impact long-term weight loss. Significant weight gain occurs continuously in patients after reaching the nadir weight following gastric bypass. Despite this weight gain, the long-term mortality remains low at 3.1%.
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            Nicotine decreases food intake through activation of POMC neurons.

            Yan Rao, Alfonso Abizaid, Bing Gao … (2011)
            Smoking decreases appetite, and smokers often report that they smoke to control their weight. Understanding the neurobiological mechanisms underlying the anorexic effects of smoking would facilitate the development of novel treatments to help with smoking cessation and to prevent or treat obesity. By using a combination of pharmacological, molecular genetic, electrophysiological, and feeding studies, we found that activation of hypothalamic α3β4 nicotinic acetylcholine receptors leads to activation of pro-opiomelanocortin (POMC) neurons. POMC neurons and subsequent activation of melanocortin 4 receptors were critical for nicotinic-induced decreases in food intake in mice. This study demonstrates that nicotine decreases food intake and body weight by influencing the hypothalamic melanocortin system and identifies critical molecular and synaptic mechanisms involved in nicotine-induced decreases in appetite.
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              Rational design of a combination medication for the treatment of obesity.

              Kishore Gadde, Patrick Mahlen O'Neil, Maria Guttadauria … (2008)
              Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau. Here, we explore combination therapy with bupropion (BUP), a putative stimulator of melanocortin pathways, and an opioid antagonist, naltrexone (NAL), to antagonize an inhibitory feedback loop that limits sustained weight reduction. In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro-opiomelanocortin (POMC) neurons in mouse brain. A subsequent study further characterized the effect of combination BUP+NAL treatment on food intake in lean and obese mice. Finally, a randomized, blinded, placebo-controlled trial in obese adult subjects was conducted. Randomization included: BUP (300 mg) + NAL (50 mg), BUP (300 mg) + placebo (P), NAL (50 mg) + P or P+P for up to 24 weeks. BUP+NAL stimulated murine POMC neurons in vitro and caused a greater reduction in acute food intake than either monotherapy, an effect consistent with synergism. Combined BUP+NAL provided sustained weight loss without evidence of an efficacy plateau through 24 weeks of treatment. BUP+NAL completers diverged from NAL+P (P < 0.01) and P+P (P < 0.001) at week 16 and from BUP+P by week 24 (P < 0.05). The combination was also well tolerated. Translational studies indicated that BUP+NAL therapy produced synergistic weight loss which exceeded either BUP or NAL alone. These results supported the hypothesis that NAL, through blockade of beta-endorphin mediated POMC autoinhibition, prevents the classic weight loss plateau observed with monotherapies such as BUP. This novel treatment approach (BUP+NAL) holds promise for the treatment of obesity.\
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 101264860
                Journal ID (pubmed-jr-id): 32902
                Journal ID (nlm-ta): Obesity (Silver Spring)
                Journal ID (iso-abbrev): Obesity (Silver Spring)
                Title: Obesity (Silver Spring, Md.)
                ISSN (Print): 1930-7381
                ISSN (Electronic): 1930-739X
                Publication date Nihms-submitted: 15 July 2013
                Publication date (Electronic): 06 February 2014
                Publication date (Print): March 2014
                Publication date PMC-release: 01 September 2014
                Volume: 22
                Issue: 3
                Pages: 888-894
                Affiliations
                [1 ] Geisinger Obesity Research Institute, Geisinger Clinic, Danville, PA 17822
                [2 ] Center for Health Research, Danville, PA 17822
                [3 ] Weis Center for Research, Geisinger Clinic, Danville, PA 17822
                [4 ] Dept of Surgery, Geisinger Medical Center, Danville, PA 17822
                [5 ] Dept of Surgery, St. Francis Medical Center, Trenton, NJ
                Author notes
                Corresponding Author Current Address: Glenn S. Gerhard, MD Professor Department of Biochemistry and Molecular Biology Institute for Personalized Medicine Department of Pathology and Laboratory Medicine Pennsylvania State University College of Medicine, 500 University Drive, MC - H171 Hershey, PA 17033 Phone - 717-531-8585 Fax - 717-531-7072 ggerhard@ 123456hmc.psu.edu
                Article
                Manuscript ID: NIHMS494386
                DOI: 10.1002/oby.20529
                PMC ID: 3819407
                PubMed ID: 23804287
                SO-VID: bc1ba0a1-b7a3-4c22-a29e-95fccc5cb400
                History
                Categories
                Subject: Article

                ScienceOpen disciplines: Medicine
                Keywords: obesity,gastric bypass,weight loss
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: obesity, gastric bypass, weight loss

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