Fatty Acid Regulation of Platelet Function in Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Fatty Acid Regulation of Platelet Function in Diabetes

Conditions
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Thrombosis, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Other: omega-3 and -6 fatty acids and their 12-LOX oxylipins


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy subjects<br>Healthy subjects for oxylipin effect Platelets from healthy donors will be assessed for regulation of platelet reactivity by fatty acids and 12-lipoxygenase oxylipins. | Other: omega-3 and -6 fatty acids and their 12-LOX oxylipins<br>* 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<br>|
| Type 2 diabetes mellitus (T2DM) patients<br>T2DM patients for oxylipin effect Platelets from healthy donors will be assessed for regulation of platelet reactivity by fatty acids and 12-lipoxygenase oxylipins. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inhibition of platelet activation | following blood draw, the ability of fatty acids or their oxylipins to inhibit platelet activation will be assessed. | one-time blood draw | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DHA, platelets, 12-lipoxygenase, fatty acids, DGLA, EPA, 12-LOX