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Table of Contents
Vol. 42, No. 6, 2005
Issue release date: November – December
Section title: Research Paper
J Vasc Res 2005;42:517–525
(DOI:10.1159/000088261)

Metabolic and Vascular Effects of Tumor Necrosis Factor-α Blockade with Etanercept in Obese Patients with Type 2 Diabetes

Dominguez H.a · Storgaard H.c · Rask-Madsen C.d · Steffen Hermann T.a · Ihlemann N.a · Baunbjerg Nielsen D.a · Spohr C.c · Kober L.b · Vaag A.c · Torp-Pedersen C.a
aCardiology Department, Research Unit, Bispebjerg University Hospital, bThe Heart Center, Rigshospitalet University Hospital, Copenhagen, cSteno Diabetes Center, Gentofte, Denmark; dJoslin Diabetes Center, Harvard Medical School, Boston, Mass., USA

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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: April 26, 2005
Accepted: June 26, 2005
Published online: October 20, 2005
Issue release date: November – December

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 2

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: http://www.karger.com/JVR

Abstract

Objective: The pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-α blockade with etanercept could reverse vascular and metabolic insulin resistance. Method and Results: Twenty obese patients with type 2 diabetes were randomized to etanercept treatment (25 mg subcutaneously twice weekly for 4 weeks) or used as controls in an open parallel study. Forearm blood flow and glucose uptake were measured during intra-arterial infusions of serotonin, sodium nitroprusside and insulin co-infused with serotonin. β-Cell function was assessed with oral and intra-venous glucose tolerance tests and whole-body insulin sensitivity by hyperinsulinemic euglycemic clamps. Plasma levels of C-reactive protein and interleukin-6 decreased significantly with etanercept (C-reactive protein from 9.9 ± 3.1 to 4.8 ± 1.4 mg l–1, p = 0.04; interleukin-6 from 3.1 ± 0.4 to 1.9 ± 0.2 ng l–1, p = 0.03). Vasodilatory responses to serotonin and sodium nitroprusside infusions remained unchanged. Insulin effect on vasodilatation and on whole-body and forearm glucose uptake remained unchanged as well. β-Cell function tended to improve. Conclusion: Although short-term etanercept treatment had a significant beneficial effect on systemic inflammatory markers, no improvement of vascular or metabolic insulin sensitivity was observed.

© 2005 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: April 26, 2005
Accepted: June 26, 2005
Published online: October 20, 2005
Issue release date: November – December

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 2

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: http://www.karger.com/JVR


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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