Fatty Acid Regulation of Platelet Function in Diabetes

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Thrombosis
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 90

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Michael Holinstat, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): May 21, 2019
• Study Completion (Actual): May 21, 2019

Study Registration Dates

• First Submitted: February 20, 2015
• First Submitted That Met QC Criteria: February 26, 2015
• First Posted (Estimate): February 27, 2015

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: May 28, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: DHA; platelets; EPA; fatty acids; 12-lipoxygenase; DGLA; 12-LOX
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Embolism and Thrombosis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Thrombosis
• Other Study ID Numbers: Michigan-114405A; R01HL114405 (U.S. NIH Grant/Contract); ODS (Other Identifier: Office of Dietary Supplementation (NIH), co-funder)