| TNF-alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. | |
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MedLine Citation:
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PMID: 21047923 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT AND OBJECTIVE: Obesity is associated with activation of the TNF-α system, increased inflammatory markers, and insulin resistance. Although studies in rodents suggest that attenuation of TNF activity improves glucose homeostasis, the effect of prolonged inhibition of TNF-α with etanercept on inflammation and glucose homeostasis in a human model of obesity is not known. DESIGN AND PARTICIPANTS: Forty obese subjects with features of metabolic syndrome were randomized to etanercept or placebo, 50 mg twice weekly for 3 months, followed by 50 mg once weekly for 3 months. OUTCOME MEASURES: Subjects underwent oral glucose tolerance testing and measurement of serum inflammatory biomarkers and adipokines. Subcutaneous fat biopsy was performed in a subset for measurement of adipokine and TNF-α mRNA expression. RESULTS: Visceral adiposity was significantly associated with serum concentrations of TNF receptor 1 (TNFR1), TNFR2, and vascular cell adhesion molecule-1 and adipose tissue expression of TNF-α and SOCS-3 (all P < 0.05). Insulin resistance as assessed by homeostasis model assessment was significantly associated with TNFR1, C-reactive protein, IL-6, and soluble intracellular adhesion molecule-1 (sICAM-1) (all P < 0.05). Etanercept significantly improved fasting glucose (treatment effect vs. placebo over 6 months, -10.8 ± 4.4%, P = 0.02). Etanercept also increased the ratio of high molecular weight adiponectin to total adiponectin (+22.1 ± 9.2% vs. placebo, P = 0.02), and decreased levels of sICAM-1 (-11 ± 2% vs. placebo, P < 0.0001). In contrast, body composition, lipids, C-reactive protein, and IL-6 were unchanged after 6 months. CONCLUSIONS: Prolonged therapy with etanercept improved fasting glucose, increased the ratio of high molecular weight to total adiponectin, and decreased sICAM-1 in obese subjects with abnormal glucose homeostasis and significant subclinical inflammation. |
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Authors:
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Takara L Stanley; Markella V Zanni; Stine Johnsen; Sarah Rasheed; Hideo Makimura; Hang Lee; Victor K Khor; Rexford S Ahima; Steven K Grinspoon |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-03 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 96 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-06 Completed Date: 2011-02-04 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E146-50 Citation Subset: AIM; IM |
Affiliation:
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Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adipokines
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blood* Anti-Inflammatory Agents, Non-Steroidal / therapeutic use Biological Markers / blood Blood Glucose Body Composition Female Glucose Tolerance Test Humans Immunoglobulin G / therapeutic use* Male Metabolic Syndrome X / blood, complications, therapy* Obesity / blood, complications, therapy* Receptors, Tumor Necrosis Factor / therapeutic use* Subcutaneous Fat / metabolism* Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
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1 UL1 RR025758-01/RR/NCRR NIH HHS; F32 DK080642-02/DK/NIDDK NIH HHS; F32 DK085969-01/DK/NIDDK NIH HHS; K23 DK087857-02/DK/NIDDK NIH HHS; K23 DK089910-01/DK/NIDDK NIH HHS; K23 DK089910-01/DK/NIDDK NIH HHS; K23 DK089910-02/DK/NIDDK NIH HHS; K24 DK064545-06/DK/NIDDK NIH HHS; K24 DK064545-09/DK/NIDDK NIH HHS; M01-RR-01066/RR/NCRR NIH HHS; P01-DK049210/DK/NIDDK NIH HHS; P30 DK040561-15/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adipokines; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Biological Markers; 0/Blood Glucose; 0/Immunoglobulin G; 0/Receptors, Tumor Necrosis Factor; 185243-69-0/TNFR-Fc fusion protein |
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