Premenopausal women in general are at low risk for cardiovascular disease (cvd) and have better fibrinolytic potential than men. In contrast, premenopausal diabetic women have a significantly increased risk of cardiovascular disease such that the disease prevalence rates of cvd in women with non-insulin dependent diabetes mellitus (niddm) may actually exceed those of men. One factor which may potentially contribute to increased cvd in this group is altered fibrinolysis. Fibrinolysis is impaired in diabetes, and data suggests that such impairments contribute to the development of cvd. Although little data exists, a recent preliminary study has demonstrated a significant impairment in fibrinolysis among premenopausal diabetic women. Characterization of an impairment in the relationship between premenopausal hormone status and fibrinolysis in diabetic women and comparison with the fibrinolytic status of diabetic men would potentially provide some insight into the increased risk of cvd in this population. The proposed study will characterize resting and activated fibrinolysis in premenopausal diabetic women and determine if fibrinolytic potential in this group is more impaired than fibrinolytic potential in age-matched diabetic men. The proposed study will compare healthy premenopausal diabetic women with age- and activity- matched diabetic men. In order to test the hypothesis, resting and activated fibrinolytic parameters will be assessed. To achieve this, blood pressure cuff inflation will be utilized to induce a brief period of stasis. Blood pressure-induced stasis allows evaluation of the endothelial response to stress. Pre- and post-stasis samples will be obtained to measure fibrinogen, euglobulin lysis time (elt), plasminogen activator inhibitor (pai), and tissue type plasminogen activator (t-pa) antigen. Insulin levels and glucose data will also be obtained. The study will be carried out by a multi-disciplinary group of researchers with extensive experience in the methods required.Data from this study should further delineate the relationship between diabetes, hormonal status and fibrinolytic potential. Future work could focus on improved tools for risk stratification. Additionally interventions to improve fibrinolytic status and thus cvd risk in this relatively healthy young target group could be elevated.
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