Fatty Acid Regulation of Platelet Function in Diabetes
Condition: Thrombosis; Type 2 Diabetes Mellitus
MeSH terms: Thrombosis; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Observational

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.
    

Intervention name(s): omega-3 and -6 fatty acids and their 12-LOX oxylipins
Intervention type(s): Other
Intervention description(s): 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
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Adults ages 21-70. Both female and male and no preference for race or ethnicity. Subjects
        will abstain from anti-platelet therapy for 10 days. Health status will be confirmed by
        oral questioning and written questionnaire and confirmed following blood draw prior to
        evaluation of platelets with fatty acid or oxylipins.
      
Biospecimen description: 
      Platelets, plasma, and whole blood will be assessed for platelet reactivity and thrombosis
      and stored for later analysis of protein expression. DNA will be stored for assessment of
      levels of gene products throught to play a role in platelet reactivity.
    
Keywords: platelets; 12-lipoxygenase; fatty acids; DGLA; DHA; EPA; 12-LOX