Tissue factor pathway inhibitor and other endothelium-dependent hemostatic factors in elderly individuals with normal or impaired glucose tolerance and type 2 diabetes.
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.


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.
Leurs
Paul B
PB
Department of Endocrinology, University Hospital, Maastricht, The Netherlands. pleurs@soz.nl
Stolk
Ronald P
RP
Hamulyak
Karly
K
Van Oerle
René
R
Grobbee
Diederick E
DE
Wolffenbuttel
Bruce H R
BH
D000368:Aged; D015415:Biomarkers; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006487:Hemostasis; D006801:Humans; D007333:Insulin Resistance; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018180:Thrombomodulin / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D001786:Blood Glucose; D008074:Lipoproteins; D018180:Thrombomodulin; C051928:lipoprotein-associated coagulation inhibitor; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator