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Clinical significance of failure to lose weight 10 years after roux-en-y gastric bypass.

ABSTRACT: BACKGROUND:Although Roux-en-Y gastric bypass (RYGB) induces short-term weight loss and co-morbidity amelioration, long-term data suggest that a subset of patients return to their preoperative body mass index (BMI). OBJECTIVES:To identify the clinical implications of 10-year weight loss failure after RYGB. SETTING:An academic teaching hospital. METHODS:Adults undergoing RYGB (1985-2004) were included in this study (n = 1087). Absolute weight loss failure was defined as ?0% reduction in excess BMI 10 years after surgery. Univariate analyses compared co-morbidity rates and resolution by weight loss classification. Multivariable regression modeling analyzed preoperative predictors of 10-year percent reduction in excess BMI and weight loss failure. RESULTS:Complete follow-up was available for 617 (57%) patients with a 10-year median percent reduction in excess BMI of 57.1%; 10.2% of patients had weight loss failure. Prevalence of all co-morbidities decreased, even in patients with weight loss failure (all P<.05). Compared with patients with successful weight loss, patients with weight loss failure had similar rates of resolution of pre-existing co-morbidities, except for reduced resolution of apnea and cardiac co-morbidities (both P<.05). Risk factors for weight loss failure included lower BMI, nongovernmental insurance, longer travel time to hospital, and year of surgery. Nongovernmental insurance (odds ratio 2.03, P = .036) conferred the highest adjusted odds of weight loss failure. CONCLUSIONS:The vast majority of patients experience dramatic health improvement 10 years after RYGB, even though some patients fail to maintain their weight loss. Renewed focus should be placed on prevention and treatment of chronic disease, with further investigation of weight loss independent mechanisms of health improvement.

SUBMITTER: Hawkins RB

PROVIDER: S-EPMC5761744 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Clinical significance of failure to lose weight 10 years after roux-en-y gastric bypass.

Hawkins Robert B RB Mehaffey J Hunter JH McMurry Timothy L TL Kirby Jennifer J Malin Steven K SK Schirmer Bruce B Hallowell Peter T PT

Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery 20170809 10

<h4>Background</h4>Although Roux-en-Y gastric bypass (RYGB) induces short-term weight loss and co-morbidity amelioration, long-term data suggest that a subset of patients return to their preoperative body mass index (BMI).<h4>Objectives</h4>To identify the clinical implications of 10-year weight loss failure after RYGB.<h4>Setting</h4>An academic teaching hospital.<h4>Methods</h4>Adults undergoing RYGB (1985-2004) were included in this study (n = 1087). Absolute weight loss failure was defined a ...[more]

PMID: 28919184

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Project description:BackgroundThe mechanisms of weight loss and metabolic improvements following bariatric surgery in skeletal muscle are not well known; however, epigenetic modifications are likely to contribute. The aim of our study was to investigate skeletal muscle DNA methylation after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Muscle biopsies were obtained basally from seven insulin-resistant obese (BMI > 40 kg/m2) female subjects (45.1 ± 3.6 years) pre- and 3-month post-surgery with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. Four lean (BMI < 25 kg/m2) females (38.5 ± 5.8 years) served as controls. We performed reduced representation bisulfite sequencing next generation methylation on DNA isolated from the vastus lateralis muscle biopsies.ResultsGlobal methylation was significantly higher in the pre- (32.97 ± 0.02%) and post-surgery (33.31 ± 0.02%) compared to the lean (30.46 ± 0.02%), P < 0.05. MethylSig analysis identified 117 differentially methylated cytosines (DMCs) that were significantly altered in the post- versus pre-surgery (Benjamini-Hochberg q < 0.05). In addition, 2978 DMCs were significantly altered in the pre-surgery obese versus the lean controls (Benjamini-Hochberg q < 0.05). For the post-surgery obese versus the lean controls, 2885 DMCs were altered (Benjamini-Hochberg q < 0.05). Seven post-surgery obese DMCs were normalized to levels similar to those observed in lean controls. Of these, 5 were within intergenic regions (chr11.68,968,018, chr16.73,100,688, chr5.174,115,531, chr5.1,831,958 and chr9.98,547,011) and the remaining two DMCs chr17.45,330,989 and chr14.105,353,824 were within in the integrin beta 3 (ITGB3) promoter and KIAA0284 exon, respectively. ITGB3 methylation was significantly decreased in the post-surgery (0.5 ± 0.5%) and lean controls (0 ± 0%) versus pre-surgery (13.6 ± 2.7%, P < 0.05). This decreased methylation post-surgery was associated with an increase in ITGB3 gene expression (fold change + 1.52, P = 0.0087). In addition, we showed that ITGB3 promoter methylation in vitro significantly suppressed transcriptional activity (P < 0.05). Transcription factor binding analysis for ITGB3 chr17.45,330,989 identified three putative transcription factor binding motifs; PAX-5, p53 and AP-2alphaA.ConclusionsThese results demonstrate that weight loss after RYGB alters the epigenome through DNA methylation. In particular, this study highlights ITGB3 as a novel gene that may contribute to the metabolic improvements observed post-surgery. Future additional studies are warranted to address the exact mechanism of ITGB3 in skeletal muscle.

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Clinical significance of failure to lose weight 10 years after roux-en-y gastric bypass.

Publications

Clinical significance of failure to lose weight 10 years after roux-en-y gastric bypass.

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