HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: dc07-1569v1 31/5/995    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted 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 Request Permissions Google Scholar Articles by Wannamethee, S. G. Articles by Lowe, G. D.O. PubMed PubMed Citation Articles by Wannamethee, S. G. Articles by Lowe, G. D.O. Social Bookmarking                What's this?

Tissue Plasminogen Activator, von Willebrand Factor, and Risk of Type 2 Diabetes in Older Men

¹ Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, U.K.
² Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, U.K.
³ Department of Community Health Sciences, St. George's, University of London, London, U.K.

Corresponding author: Dr. S. Goya Wannamethee, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Rowland Hill St., London NW3 2PF, U.K. E-mail: goya{at}pcps.ucl.ac.uk

OBJECTIVE—The objective of this study was to assess the relationship between putative markers of endothelial dysfunction (tissue plasminogen activator [t-PA] antigen and von Willebrand factor [vWF] antigen) and development of type 2 diabetes, as well as the role of inflammation, adipokines, hepatic function, and insulin resistance in modifying these relationships.

RESEARCH DESIGN AND METHODS—This was a prospective study of 3,562 nondiabetic men aged 60–79 years followed up for an average of 7 years during which there were 162 incident cases of type 2 diabetes.

RESULTS—Elevated t-PA (top third) was associated with a near threefold increase in risk of diabetes compared with the risk in those in the bottom third after adjustment for lifestyle factors and waist circumference (relative risk [RR] 2.98 [95%CI 1.79–5.00]; P_trend < 0.0001); weaker but significant (marginal) associations were seen with vWF (1.24 [0.83–1.85]; P = 0.05 for trend). Both biomarkers of endothelial dysfunction correlated significantly with markers of inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]), hepatic function (-glutamyl transferase [GGT]), and insulin resistance, with t-PA showing stronger associations with adiposity, hepatic function, and insulin resistance than vWF. t-PA was also significantly and inversely associated with adiponectin. Adjustment for IL-6, adiponectin, and GGT attenuated the association of incident diabetes with vWF (1.06 [0.71–1.60]), but the relationship seen with t-PA remained significant (adjusted RR 2.19 [1.29–3.70]). Subsequent adjustment for insulin attenuated the association further, but t-PA was still associated with a significant increase in risk (1.66 [0.96–2.85]; P_trend = 0.02).

CONCLUSION—t-PA antigen, but not vWF antigen, is independently associated with risk of type 2 diabetes.

Abbreviations: ALT, alanine transaminase • CHD, coronary heart disease • CRP, C-reactive protein • ELISA, enzyme-linked immunosorbent assay • GGT, -glutamyl transferase • HOMA-IR, homeostasis model assessment of insulin resistance • IL, interleukin • PAI-1 • plasminogen activator inhibitor type 1 • t-PA, tissue plasminogen activator antigen • vWF, von Willebrand factor

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?