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Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus.
MedLine Citation:
PMID:  22088821     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Roux-en-Y gastric bypass (RYGB) results in profound weight loss and resolution of type 2 diabetes mellitus (T2DM). The mechanism of this remarkable transition remains poorly defined. It has been proposed that endotoxin (lipopolysaccharide [LPS]) sets inflammatory tone, triggers weight gain, and initiates T2DM. Because RYGB may diminish LPS from endogenous and exogenous sources, we hypothesized that LPS and the associated cascade of oxidative and inflammatory stress would diminish after RYGB. METHODS: Fifteen adults with morbid obesity and T2DM undergoing RYGB were studied. After an overnight fast, a baseline blood sample was collected the morning of surgery and at 180 days to assess changes in glycemia, insulin resistance, LPS, mononuclear cell nuclear factor (NF)-κB binding and mRNA expression of CD14, TLR-2, TLR-4, and markers of inflammatory stress. RESULTS: At 180 days after RYGB, subjects had a significant decrease in body mass index (52.1 ± 13.0 to 40.4 ± 11.1), plasma glucose (148 ± 8 to 101 ± 4 mg/dL), insulin (18.5 ± 2.2 mμU/mL to 8.6 ± 1.0 mμU/mL) and HOMA-IR (7.1 ± 1.1 to 2.1 ± 0.3). Plasma LPS significantly reduced by 20 ± 5% (0.567 ± 0.033 U/mL to 0.443 ± 0.022E U/mL). NF-κB DNA binding decreased significantly by 21 ± 8%, whereas TLR-4, TLR-2, and CD-14 expression decreased significantly by 25 ± 9%, 42 ± 8%, and 27 ± 10%, respectively. Inflammatory mediators CRP, MMP-9, and MCP-1 decreased significantly by 47 ± 7% (10.7 ± 1.6 mg/L to 5.8 ± 1.0 mg/L), 15 ± 6% (492 ± 42 ng/mL to 356 ± 26 ng/mL) and 11 ± 4% (522 ± 35 ng/mL to 466 ± 35 ng/mL), respectively. CONCLUSION: LPS, NF-κB DNA binding, TLR-4, TLR-2, and CD14 expression, CRP, MMP-9, and MCP-1 decreased significantly after RYGB. The mechanism underlying resolution of insulin resistance and T2DM after RYGB may be attributable, at least in part, to the reduction of endotoxemia and associated proinflammatory mediators.
Authors:
Scott V Monte; Joseph A Caruana; Husam Ghanim; Chang Ling Sia; Kelly Korzeniewski; Jerome J Schentag; Paresh Dandona
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-15
Journal Detail:
Title:  Surgery     Volume:  -     ISSN:  1532-7361     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Mosby, Inc. All rights reserved.
Affiliation:
State University of New York at Buffalo School of Pharmacy and Pharmaceutical Sciences, Amherst, NY; CPL Associates, LLC, Amherst, NY.
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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