Role of 12-lipoxygenase in Platelet Reactivity and Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- platelet reactivity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects and T2DM patients
- •Postmenopausal women with T2DM
- •All races and ethnicities
- •T2DM patients taking 1st line diabetic treatment (i.e. Metformin)
排除标准
- •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
研究组 & 干预措施
T2DM for Omega-3 protection
platelets from Type 2 diabetes mellitus (T2DM) patients will be assessed for regulation by Fish Oil (omega-3 fatty acid).
干预措施: Fish Oil (Dietary Supplement)
Healthy control for Omega-3 protection
Platelets from healthy donors will be assessed for regulation by Fish Oil (omega-3 fatty acid).
干预措施: Fish Oil (Dietary Supplement)
T2DM patients for Omega-6 protection
platelets from Type 2 diabetes mellitus (T2DM) patients will be assessed for regulation by Primrose Oil (omega-6 fatty acid).
干预措施: Primrose oil (Dietary Supplement)
Healthy subjects for Omega-6 protection
Platelets from healthy donors will be assessed for regulation by Primrose Oil (omega-6 fatty acid).
干预措施: Primrose oil (Dietary Supplement)
结局指标
主要结局
platelet reactivity
时间窗: through study completion, an average of 1 year
decreased platelet activity ex vivo translating to protection from clot formation in vivo
次要结局
- fatty acid incorporation(through study completion, an average of 1 year)
- Oxylipin production(through study completion, an average of 1 year)
研究者
Michael Holinstat
Associate Professor
University of Michigan