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

  1. S. Goya Wannamethee, PHD1,
  2. Naveed Sattar, MD2,
  3. Ann Rumley, PHD2,
  4. Peter H. Whincup, FRCP3,
  5. Lucy Lennon, MSC1 and
  6. Gordon D.O. Lowe, DSC2
  1. 1Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, U.K.
  2. 2Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, U.K.
  3. 3Department of Community Health Sciences, St. George's, University of London, London, U.K.
  1. 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

Abstract

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]; Ptrend < 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 (γ-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]; Ptrend = 0.02).

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

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 30 January 2008. DOI: 10.2337/dc07-1569.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted January 20, 2008.
    • Received August 9, 2007.
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  1. Published online before print January 30, 2008, doi: 10.2337/dc07-1569 Diabetes Care May 2008 vol. 31 no. 5 995-1000
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