Insulin stimulates monocyte membrane associated tissue factor activity

The benefits of intensive insulin therapy for type 2 diabetics with cardiovascular disease (CVD) are highly controversial. We performed in vitro studies to determine whether insulin has any effect on whole blood coagulation and assess how insulin responds to monocyte membrane associated tissue factor (mmaTF) induced hypercoagulability. Mercuric ion (Hg²⁺), which has been shown to increase mmaTF-dependent procoagulant activity in whole blood, was used to stimulate similar pathways in our experiment. We spiked human citrated whole blood with HgCl₂ and Humulin-N^® (HN) at final concentrations of control, 0.02 U/mL HN, 0.004 U/mL HN, 0.002 U/mL HN, 0.005% HgCl₂, 0.02 U/mL HN:0.005% HgCl₂, 0.004 U/mL HN:0.005% HgCl₂, and 0.002 U/mL HN:0.005% HgCl₂. The samples (n=12) were incubated at 37°C for 10 minutes and recalcified with CaCl₂ to initiate clotting. The clotting time (CT) was measured with an Amelung KC4A Micro. The results indicate that HN by itself has no effect on CT. However, each concentration of HN:HgCl₂ exhibited a shorter CT than either HN or HgCl₂ alone (p<0.02 in each case). Studies with bovine pancreas insulin yielded similar results. This data indicates that insulin is stimulating mmaTF activity, and warrants the implementation of coagulation monitoring protocols for intensive insulin therapy.