Obesity, Inflammation and Thrombosis: LOOK AHEAD

描述(由申请人提供)：肥胖糖尿病患者数量的增加，加上他们高心血管发病率、死亡率和医疗保健支出，给美国带来了巨大的公共卫生问题。肥胖的糖尿病患者炎症增加，凝血平衡受损，这两者都被认为是动脉粥样硬化血栓事件风险增加的原因。尽管通过饮食治疗、锻炼和体重管理改变生活方式作为基础疗法被多个国家组织推荐，但还没有前瞻性的临床试验表明，任何方式都能通过减肥显著减少心血管事件。Look Ahead(糖尿病健康行动)研究是一项大型多中心试验，旨在检验与接受糖尿病支持和教育(DSE)的对照组相比，通过饮食和锻炼的强化生活方式干预(ILI)减肥是否会减少肥胖糖尿病患者的心血管事件。前瞻性试验定量评估了个人改变生活方式的哪些方面(饮食、体力活动)，以及对肥胖、健身和传统风险因素(血压、血脂、血糖控制)的影响。建议的目标是与前瞻性研究人员一起设计的，以检查饮食和运动对炎症和凝血平衡受损的影响。在这项资助中，我们提出了以下目标：1)研究肥胖测量(体重、体重指数、腰围等)之间的联系。在前瞻性试验中登记的50%的患者的基础水平和促炎(IL-6，CRP)和抗炎(脂联素亚型)脂肪细胞因子和凝血平衡受损的参数(PAI-1，纤维蛋白原，D-二聚体，TAFI)，以及饮食摄入、体力活动、健康、性别、种族和心血管危险因素和疾病的存在如何影响这种关系；2)比较ILI和DSE在基线和1年之间对炎性标志物和受损的凝血平衡的变化的影响，并检查变化如何与肥胖、饮食摄入量、健康和体力活动的变化相关；3)在一项病例对照研究中，检查体重减轻的更大程度如何导致衡量炎症、氧化应激、神经激素调节和凝血平衡受损途径的参数发生更大的变化。

DESCRIPTION (provided by applicant): The increased number of obese diabetic individuals, coupled with their high cardiovascular morbidity, mortality, and healthcare expenditures, poses an enormous public health problem for the United States. Obese diabetic patients have increased inflammation and impaired coagulant balance, which are both thought to contribute to increased risk for atherothrombotic events. Although lifestyle modification with diet therapy, exercise, and weight management is recommended as foundation therapy by multiple national organizations, there are no prospective clinical trials that have shown significant cardiovascular event reduction by weight loss achieved by any modality. The Look AHEAD (Action for Health in Diabetes) study is a large multicenter trial designed to examine whether weight loss through intensive lifestyle intervention (ILI) with both diet and exercise will reduce cardiovascular events in obese diabetic individuals compared with a control group that receives diabetes support and education (DSE). The Look AHEAD trial has quantitatively assessed which aspects of lifestyle were modified by individuals (diet, physical activity) and effects on adiposity, fitness, and traditional risk factors (blood pressure, lipids, glycemic control). The proposed aims have been designed in conjunction with the Look AHEAD investigators to examine the effects of diet and exercise on inflammation and impaired coagulant balance. In this grant, we propose the following aims: 1) examine the association between measurements of obesity (weight, body mass index, waist, etc.) at baseline and levels of proinflammatory (IL-6, CRP) and anti-inflammatory (adiponectin isoforms) adipocytokines and parameters of impaired coagulant balance (PAI-1, fibrinogen, D-dimer, TAFI) in 50% of patients enrolled in the Look AHEAD trial and how this relationship is influenced by dietary intake, physical activity, fitness, gender, ethnicity, and presence of cardiovascular risk factors and disease; 2) compare the effects of ILI versus DSE on changes in inflammatory markers and impaired coagulant balance between baseline and year 1 and examine how changes are related to changes in adiposity, dietary intake, fitness, and physical activity; 3) examine how greater reductions in weight loss lead to greater changes in parameters that measure pathways of inflammation, oxidative stress, neurohormonal regulation, and impaired coagulant balance in a case-control study.