Effect of High Insulin and Glucose on Blood Coagulation/Thrombosis in Healthy People

Effect of High Insulin and Glucose on Blood Coagulation/Thrombosis in Healthy People Patients with type 2 diabetes Patients with type 2 diabetes have a 2-5-fold increase in atherosclerotic vascular disease some of which is due to increased propensity for hemostasis/thrombosis. We have tested the hypothesis that hyperinsulinemia and/or hyperglycemia may affect tissue factor (TF) the main initiator and other components of the TF pathway of hemostasis. Healthy volunteers (21M/8F) participated in 4 research center studies each lasting 24 h; 1) selective hyperglycemia (high glucose, [sim] 11 mM, n=7); 2) selective hyperinsulinemia (high insulin, [sim] 1.2 nM, n=7); 3) hyper-glycemia and hyperinsulinemia (high glucose plus high insulin, n=10) and 4) euglycemia and euinsulinemia (controls, n=5). [br]Results: TF procoagulant activity (two-stage clotting assay with whole blood cell lysates) did not change in control studies but rose [sim] 2-fold during high glucose, [sim] 6-fold during high insulin and [sim] 9-fold during high glucose plus high insulin. TF protein bearing monocytes (by flow cytometry) did not change in control studies but rose from 19.8 to 31.9% (p [lt] 0.002) during high glucose plus high insulin and from 12.5 to 17.5% (p [lt] 0.02) during high insulin. Monocyte TF mRNA (by real time RT-PCR) rose 1.9-fold over controls during high glucose plus high insulin (p [lt] 0.04). Thrombin-antithrombin complexes (by ELISA) a sensitive indicator of thrombin generation, did not change during control studies but rose from 5.2 to 33.7 [mu]g/L (p [lt] 0.01) during high glucose plus high insulin, from 5.1 to 21.1 [mu]g/L (p [lt] 0.02) during high glucose and from 12.3 to 25.1 [mu]g/L (p [lt] 0.02) during high insulin. CD40 ligand bearing platelets, a sensitive and early indicator of platelet activation, did not change during control studies but rose from 32.9 to 46.1% (p [lt] 0.001) during high glucose plus high insulin, from 31.2 to 37.5% (p [lt] 0.01) during high insulin and from 33.2 to 37.2% (p [lt] 0.05) during high glucose.[br]We conclude that hyperinsulinemia and hyperglycemia but particularly the combination of both create a prothrombotic state and because of the proinflammatory action of platelet CD40 ligand may also be proatherogenic. GUENTHER BODEN, MARIA MOZZOLI, VIJENDER R. VAIDYULA, A. K. RAO 701-P Philadelphia, PA Complications - Macrovascular - Atherosclerotic CVD and Human Diabetes