Context: Type 2 diabetes (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation.

Objective: To examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM.

Design: Three study protocols were used: 1) acute correction of hyperglycemia (with IV insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia and 3) 24 h of combined hyperinsulinemia and hyperglycemia.

Setting: Clinical research center

Study participants: 18 type 2 diabetes (T2DM) patients and in 22 non-diabetic controls.

Results: Basal TF procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc) and thrombin-anti-thrombin complexes (TAT) were higher in T2DM than in non-diabetic controls indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2–4 h resulted in a small (7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30% whereas raising insulin and glucose levels together, increased TF-PCA (by 80%), and TAT and F1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA.

We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.