Thrombosis, Type 2 Diabetes Mellitus
Conditions
Keywords
platelets, 12-lipoxygenase, fatty acids, DGLA, DHA, EPA, 12-LOX
Brief summary
This study investigates the potential protective effects of altering fatty acid in the platelet as a method for prevention of platelet activation and thrombosis in type 2 diabetes mellitus. Fatty acids (omega-3 and omega-6) and their oxidized lipids will be evaluated for protection from agonist-mediated platelet activation in platelets from type 2 diabetics and healthy controls.
Detailed description
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.
Interventions
OTHERomega-3 and -6 fatty acids and their 12-LOX oxylipins
platelets from healthy subjects and T2DM patients will be isolated from their blood and treated with omega-3 and -6 fatty acids and their 12-LOX oxylipins of those fatty acids followed by assessment of protection from agonist-induced platelet activation and thrombosis
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Michigan
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| inhibition of platelet activation | one-time blood draw | following blood draw, the ability of fatty acids or their oxylipins to inhibit platelet activation will be assessed. |
Countries
United States
Outcome results
None listed