Hyperglycemia Stimulates Coagulation, Whereas Hyperinsulinemia Impairs Fibrinolysis in Healthy Humans
Hyperglycemia Stimulates Coagulation, Whereas Hyperinsulinemia Impairs Fibrinolysis in Healthy Humans Michiel E. Stegenga 1 2 , Saskia N. van der Crabben 3 , Marcel Levi 4 , Alex F. de Vos 1 2 , Michael W. Tanck 5 , Hans P. Sauerwein 3 and Tom van der Poll 1 2 1 Center for Infection and Immunity Ams...
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Published in | Diabetes (New York, N.Y.) Vol. 55; no. 6; pp. 1807 - 1812 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.06.2006
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Subjects | |
Online Access | Get full text |
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Summary: | Hyperglycemia Stimulates Coagulation, Whereas Hyperinsulinemia Impairs Fibrinolysis in Healthy Humans
Michiel E. Stegenga 1 2 ,
Saskia N. van der Crabben 3 ,
Marcel Levi 4 ,
Alex F. de Vos 1 2 ,
Michael W. Tanck 5 ,
Hans P. Sauerwein 3 and
Tom van der Poll 1 2
1 Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
2 Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
3 Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
4 Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
5 Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Address correspondence and reprint requests to Michiel E. Stegenga, MD, Center for Experimental and Molecular Medicine, Academic
Medical Center, University of Amsterdam, G2-130, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. E-mail: m.e.stegenga{at}amc.uva.nl
Abstract
Type 2 diabetes and insulin resistance syndromes are associated with an increased risk for cardiovascular and thrombotic complications.
A disturbed balance between coagulation and fibrinolysis has been implicated in the pathogenesis hereof. To determine the
selective effects of hyperglycemia and hyperinsulinemia on coagulation and fibrinolysis, six healthy humans were studied on
four occasions for 6 h: 1 ) lower insulinemic-euglycemic clamp, 2 ) lower insulinemic-hyperglycemic clamp, 3 ) hyperinsulinemic-euglycemic clamp, and 4 ) hyperinsulinemic-hyperglycemic clamp. In the hyperglycemic clamps, target levels of plasma glucose were 12 versus 5 mmol/l
in the normoglycemic clamps. In the hyperinsulinemic clamps, target plasma insulin levels were 400 versus 100 pmol/l in the
lower insulinemic clamps. Hyperglycemia exerted a procoagulant effect irrespective of insulin levels, as reflected by mean
twofold rises in thrombin-antithrombin complexes and soluble tissue factor, whereas hyperinsulinemia inhibited fibrinolysis
irrespective of glucose levels, as reflected by a decrease in plasminogen activator activity levels due to a mean 2.5-fold
rise in plasminogen activator inhibitor type 1. The differential effects of hyperglycemia and hyperinsulinemia suggest that
patients with hyperglycemia due to insulin resistance are especially susceptible to thrombotic events by a concurrent insulin-driven
impairment of fibrinolysis and a glucose-driven activation of coagulation.
CVD, cardiovascular disease
HinsuEgluc, hyperinsulinemic-euglycemic
HinsuHgluc, hyperinsulinemic-hyperglycemic
LinsuEgluc, lower insulinemic-euglycemic
LinsuHgluc, lower insulinemic-hyperglycemic
PAI-1, plasminogen activator inhibitor type 1
TATc, thrombin-antithrombin complex
tPA, tissue-type plasminogen activator
Footnotes
Accepted February 22, 2006.
Received November 29, 2005.
DIABETES |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/db05-1543 |