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 fatty acid supplementation through inhibition of platelet activation. fatty acids (omega-3 and omega-6) will be evaluated for protection from agonist-mediated platelet activation in platelets from type 2 diabetics and healthy controls. Post-menopausal women with type 2 diabetes mellitus and healthy post-menopausal women will be treated with omega-3 and omega-6 fatty acid supplements to determine protection from platelet activation and thrombosis in this high risk population.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTPrimrose oil
T2DM patients and matched controls subjects will be given Primrose oil for 2 months, followed by 2-week washout. Blood will be drawn at the beginning, during, and following treatments and platelet function will be assessed.
DIETARY_SUPPLEMENTFish Oil
T2DM patients and matched controls subjects will be given Fish oil for 2 months, followed by 2-week washout. Blood will be drawn at the beginning, during, and following treatments and platelet function will be assessed.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| platelet reactivity | through study completion, an average of 1 year | decreased platelet activity ex vivo translating to protection from clot formation in vivo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| fatty acid incorporation | through study completion, an average of 1 year | measure altered levels of essential fatty acids in blood and platelets following treatment |
| Oxylipin production | through study completion, an average of 1 year | determine the oxylipin products formed following each intervention |
Countries
United States
Outcome results
None listed