Fatty Acid Regulation of Platelet Function in Diabetes

12-lipoxygenase and 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 inhibition prevents platelet activation in part by inhibiting 12-lipoxygenase
oxidation of free fatty acids in the platelet. These 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 results 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 12-lipoxygenase 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

- African American and Caucasian

- T2DM patients on controlled medication (taking metformin)

Exclusion Criteria:

- Dietary supplement within 2 weeks of enrollment

- Fish and plant oil supplements 2 months prior to enrollment

- NSAIDS and aspirin 1 week prior to enrollment

- Smoking

- Cardiovascular event within 6 months prior to enrollment

- Other anti-platelet treatment including phosphodiesterase (PDE) and P2Y12R inhibitors

- Estimated Glomerular Filtration Rate (eGFR) below 30 (severe renal insufficiency)

- eGFR above 90