The proposed studies are designed to prove the hypothesis that elevation of the Vitamin-K dependent pro-coagulant plasma proteins is significantly linked to the presence of a hypercoagulable state in subjects at high risk of developing ischemic heart disease (IHD). The presence of a hypercoagulable state will be defined by measurement of two plasma markers of the activation of coagulation, the prothrombin activation fragment F1.2 and the complex of thrombin with antithrombin, known as TAT. Two groups of subjects at high risk of IHD will be studied in separate subprojects: 1) patients with adult-onset non-insulin dependent diabetes mellitus (NIDDM), and 2) young adult first-degree relatives (FDR), children or siblings, of patients with premature IHD, defined by established criteria.
Specific Aim #1 We will examine the levels of the plasma Vitamin-K dependent pro-coagulant proteins (Factor II, VII, and X and activated Factor VII), F1.2, and TAT and serum insulin snf lipids in blood from fasting subjects with NIDDM and from a comparison group of fasting non-diabetic subjects, matched for age and gender.
Specific Aim #2 We will examine the levels of the plasma Vitamin-K dependent procoagulent proteins (Factors II, VII, X and activated Factor VIII), F1.2 and TAT and serum insulin and lipids in blood from FDR subjects, designated the """"""""high- risk"""""""" group, and form a comparison group of age- and gender-matched, fasting subjects without a family history of premature IHD, designated the """"""""low risk"""""""" group. Secondary Specific Aim #1-a We will examine the effect of an oral glucose load on the post-prandial plasma levels of Factors II, VII, X, activated Factor VII, F1.2, TAT, and serum insulin and lipids in NIDDM subjects, compared to the same variables measured in the fasting state, on blood obtained immediately before the oral glucose load. Secondary Specific Aim #1-b. We will examine the effect of drug therapy, metformin or glypizide, on the plasma levels of Factors II, VII, X, activated Factor VII, F1.2, TAT, and serum insulin and lipids in fasting NIDDM subjects after 4 weeks of drug therapy, compared to the levels of these variables in plasma obtained from these subjects in the fasting state before the start of drug therapy. Secondary Specific Aim #2a We will examine the effect of a single high-fat meal on the post-prandial levels of plasma Factors II, VII, X, activated Factor VII, F1.2, TAT, serum insulin and lipids in the """"""""high-risk"""""""" FDR subjects, compared to the levels of these variables in the plasma from these fasting FDR subjects immediately before the high-fat meal.
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