Role of 12-lipoxygenase in Platelet Reactivity and Type 2 Diabetes Mellitus

Essential fatty acids such as omega-3 and omega-6 have been shown to play important roles in regulating platelet activation, but the underlying mechanisms have not been fully elucidated as well as their true protection from thrombosis.

12-lipoxygenase oxidized fatty acids are known to play both a pro- and anti-thrombotic effect on platelets depending on the fatty acid. oxidation of arachidonic acid by 12-lipoxygenase resuts in a pro-thrombotic bioactive lipid whereas oxidation of the omega-6 fatty acid DGLA found in plant oil results in formation of a potent anti-thrombotic bioactive lipid. Determining the extent of protection from this and other bioactive lipids produced through oxygenase activity will allow for a better understanding of which fatty acid supplementation may best protect from thrombosis.

Essential fatty acids such as omega-3 (DHA/EPA) and omega-6 (DGLA) appear to be protective. However the underlying mechanism for this potential protection is not well understood. Identifying the mechanism by which these supplements protect from platelet activation may identify new approaches to preventing thrombotic events in this high risk population.

Inclusion criteria

• Healthy subjects and T2DM patients
• Postmenopausal women with T2DM
• All races and ethnicities
• T2DM patients taking 1st line diabetic treatment (i.e. Metformin)

Exclusion criteria

• Fish and plant oil supplements 2 months prior to enrollment
• NSAIDS and aspirin 1 week prior to enrollment
• Cardiovascular event within 6 months prior to enrollment
• Other anti-platelet treatment including PDE and P2Y12 inhibitors