Biomarkers of Oxidative Stress in Look AHEAD

描述(由申请人提供)： 超重和糖尿病会增加心血管疾病的风险，但 解释这一影响的机制(S)仍有待澄清。氧化 低密度脂蛋白(LDL)被认为是导致动脉粥样硬化的原因之一。 糖尿病可能会增加氧化应激，这可能会导致 糖尿病患者发生心血管疾病的风险。卡路里限制和 开始运动可能会在短期内增加氧化应激，并可能 从而对心血管疾病产生不利影响。从长远来看，新陈代谢 适应可能会减少氧化应激。这种适应，连同 有益于改变脂蛋白的浓度、组成和性质， 可能允许表达减肥对心血管的有益影响 终端。然而，体重减轻对脂蛋白测定的影响 超重糖尿病患者的氧化/氧化应激和抗氧化状态 从未被调查过。这项研究的目标是确定如何减肥 通过密集的生活方式干预实现，包括改变饮食和锻炼 超重人群脂蛋白氧化/氧化应激与抗氧化状态 糖尿病患者。该项目的主要目标是确定 强化生活方式干预对AS脂蛋白氧化的影响 以氧化型低密度脂蛋白自身抗体进行评估。其他 氧化应激和抗氧化剂状态评估的互补指标 通过循环浓度的亲脂性抗氧化剂，将 在生活方式干预和社区护理(控制)之间 超前研究。这样的比较将在干预后的早期进行 稍后，当新陈代谢适应被预期时。通过对比子组 定义为对饮食或运动的不同依从性，按性别、更年期 地位、种族和年龄，次要目标将考虑 脂蛋白氧化/氧化应激和抗氧化状态不同 这样的子群。其他目标将考虑脂蛋白的差异 上述亚群之间的氧化/氧化应激可用以下方式解释 脂蛋白浓度、组成或性质的差异， 碳水化合物代谢，或抗氧化剂状态。这项研究的结果将 为心血管疾病的差异提供一种潜在的机制解释 干预和社区护理团体之间的终点。

DESCRIPTION (provided by applicant): Overweight and diabetes increase risk of cardiovascular disease but the mechanism(s) that account for this effect remain to be clarified. Oxidation of low-density lipoprotein (LDL) is thought to contribute to atherosclerosis. Diabetes may increase oxidative stress, and this may contribute to increased risk of cardiovascular disease in diabetics. Caloric restriction and the initiation of exercise may increase oxidative stress in the short term and may thus adversely affect cardiovascular disease. Over the long term, metabolic adaptation may reduce oxidative stress. Such adaptation, together with beneficial changes in lipoprotein concentration, composition, and character, may allow expression of beneficial effects of weight loss on cardiovascular endpoints. However, the influence of weight loss on measures of lipoprotein oxidation/oxidative stress and antioxidant status in overweight diabetics has never been investigated. The goal of this study is to determine how weight loss achieved by intensive lifestyle intervention including diet and exercise alters lipoprotein oxidation/oxidative stress and antioxidant status in overweight diabetic individuals. The primary aim of this project is to determine the influence of intensive lifestyle intervention on lipoprotein oxidation as assessed by autoantibodies to oxidized low-density lipoprotein. Other complementary indices of oxidative stress, and antioxidant status as assessed by circulating concentrations of lipophilic antioxidants, will be compared between lifestyle intervention and community care (control) arms of the Look AHEAD study. Such comparisons will be performed both early after intervention and later when metabolic adaptation is expected. By contrasting subgroups defined by differential compliance to diet or exercise, by gender, menopausal status, ethnicity, and age, secondary aims will consider whether changes in lipoprotein oxidation/oxidative stress and antioxidant status differ between such subgroups. Other aims will consider whether differences in lipoprotein oxidation/oxidative stress among the above subgroups can be accounted for by differences in lipoprotein concentration, composition, or character, carbohydrate metabolism, or antioxidant status. The results of this study will provide a potential mechanistic explanation for differences in cardiovascular endpoints between intervention and community care groups.