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Blood, 1 July 2008, Vol. 112, No. 1, pp. 82-89. Prepublished online as a Blood First Edition Paper on March 3, 2008; DOI 10.1182/blood-2007-11-121723. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-121723v1 112/1/82    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Stegenga, M. E. Articles by van der Poll, T. PubMed PubMed Citation Articles by Stegenga, M. E. Articles by van der Poll, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia Michiel E. Stegenga1,2, Saskia N. van der Crabben3, Regje M. E. Blümer3, Marcel Levi4, Joost C. M. Meijers4, Mireille J. Serlie3, Michael W. T. Tanck5, Hans P. Sauerwein3, and Tom van der Poll1,2 1 Center for Infection and Immunity Amsterdam (CINIMA); 2 Center for Experimental and Molecular Medicine; and Departments of3 Endocrinology and Metabolism; 4 Vascular Medicine, and 5 Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Type 2 diabetes is associated with altered immune and hemostatic responses. We investigated the selective effects of hyperglycemia and hyperinsulinemia on innate immune, coagulation, and fibrinolytic responses during systemic inflammation. Twenty-four healthy humans were studied for 8 hours during clamp experiments in which either plasma glucose, insulin, both, or none was increased, depending on randomization. Target plasma concentrations were 5 versus 12 mM for glucose, and 100 versus 400 pmol/L for insulin. After 3 hours, 4 ng/kg Escherichia coli endotoxin was injected intravenously to induce a systemic inflammatory and procoagulant response. Endotoxin administration induced cytokine release, activation of neutrophils, endothelium and coagulation, and inhibition of fibrinolysis. Hyperglycemia reduced neutrophil degranulation (plasma elastase levels, P < .001) and exaggerated coagulation (plasma concentrations of thrombin-antithrombin complexes and soluble tissue factor, both P < .001). Hyperinsulinemia attenuated fibrinolytic activity due to elevated plasminogen activator-inhibitor-1 levels (P < .001). Endothelial cell activation markers and cytokine concentrations did not differ between clamps. We conclude that in humans with systemic inflammation induced by intravenous endotoxin administration hyperglycemia impairs neutrophil degranulation and potentiates coagulation, whereas hyperinsulinemia inhibits fibrinolysis. These data suggest that type 2 diabetes patients may be especially vulnerable to prothrombotic events during inflammatory states. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Glucose, insulin, coagulation: endotoxin as exohormone John C. Marshall Blood 2008 112: 6-7. [Full Text] [PDF]

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