Fatty Acid Regulation of Platelet Function in Diabetes

Sponsor

University of Michigan (Other)

Overall Status

Completed

CT.gov ID

NCT02373332

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Locations

69.6

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Thrombosis Type 2 Diabetes Mellitus	Other: omega-3 and -6 fatty acids and their 12-LOX oxylipins

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.

Study Design

Study Type:

Observational

Actual Enrollment :

90 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Fatty Acid Regulation of Platelet Function in Diabetes

Study Start Date :

Aug 1, 2013

Actual Primary Completion Date :

May 21, 2019

Actual Study Completion Date :

May 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Healthy subjects 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 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
Type 2 diabetes mellitus (T2DM) patients T2DM patients for oxylipin effect Platelets from healthy donors will be assessed for regulation of platelet reactivity by fatty acids and 12-lipoxygenase oxylipins.

Arm

Intervention/Treatment

Healthy subjects

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

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

Type 2 diabetes mellitus (T2DM) patients

T2DM patients for oxylipin effect Platelets from healthy donors will be assessed for regulation of platelet reactivity by fatty acids and 12-lipoxygenase oxylipins.

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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