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Tissue Factor Pathway Inhibitor and Other Endothelium-Dependent Hemostatic Factors in Elderly Individuals With Normal or Impaired Glucose Tolerance and Type 2 Diabetes

¹ Department of Endocrinology, University Hospital, Maastricht, the Netherlands
² Departments of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, the Netherlands
³ Department of Hematology, University Hospital, Maastricht, the Netherlands

OBJECTIVE—Impaired glucose tolerance (IGT) is believed to be a prediabetic phase that precedes the development of type 2 diabetes. In elderly subjects, IGT and diabetes are both independently associated with the occurrence of cardiovascular disease. Endothelial damage precedes atherosclerotic changes of the vascular wall. Therefore, several markers of endothelial dysfunction were examined in elderly subjects with IGT and elderly patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), and thrombomodulin were studied as markers of endothelial dysfunction in a population-based study of elderly subjects with normal glucose tolerance (NGT) or IGT and type 2 diabetes. In addition to these endothelium-dependent factors, we also investigated tissue factor pathway inhibitor (TFPI) activity in relation to metabolic parameters and cardiovascular risk factors.

RESULTS—All data were adjusted for age. Increased levels of vWF antigen, t-PA antigen, and PAI-1 activity were seen in the IGT and diabetic group compared with the NGT group. TFPI activity and thrombomodulin levels were increased in all elderly subjects, and no differences were seen between the groups. There was a positive association between HbA_1c and TFPI activity and vWF antigen. Fasting blood glucose levels correlated with vWF antigen, t-PA antigen, and PAI-1 activity, whereas urine albumin excretion correlated with TFPI activity, vWF antigen, and PAI-1 activity. Serum insulin levels correlated strongly not only with vWF antigen and t-PA antigen but also with PAI-1 activity. This correlation did not change after further adjustment for serum glucose and HbA_1c, which may suggest that in the elderly subjects, impaired fibrinolysis is probably associated with insulin resistance. There were no associations between the endothelium-dependent hemostatic factors and lipids, except for a negative correlation between HDL cholesterol and thrombomodulin.

CONCLUSIONS—In elderly subjects with IGT, several endothelium-dependent hemostatic factors are already consistently increased, indicating endothelial damage in this stage.

Abbreviations: CV, coefficient of variation • ELISA, enzyme linked immunosorbent assay • F_{1 + 2}, prothrombin fragments 1 + 2 • IGT, impaired glucose tolerance • NGT, normal glucose tolerance • PAI-1, plasminogen activator inhibitor type-1 • TFPI, tissue factor pathway inhibitor • t-PA, tissue-plasminogen activator • vWF, von Willebrand factor

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