Dietary Quality, Body Adiposity, and Risk of Rheumatoid Arthritis in Women

7.项目总结/摘要 类风湿性关节炎（RA）是最常见的自身免疫性炎症性疾病，其特征在于持续性关节炎， 滑膜炎和全身性炎症。RA通常被认为是一种多因素疾病， 遗传因素和环境暴露。虽然一些个别的饮食因素已被确定， 与类风湿关节炎的发展有关，很少有研究检查了整体饮食质量的影响， 饮食模式对RA风险的影响。在我们以前的研究中，我们已经证明，坚持饮食 美国人的指南或遵循谨慎的饮食模式与降低RA风险相关，而 西方饮食模式或饮食炎症模式，其特征是高摄入红色和加工 肉类，精制谷物，甜点和糖果，以及高脂肪乳制品，会增加年轻人和 中年妇女。然而，很少有人知道是否修改饮食质量的影响， 随后的RA风险。通常，在伦理上或实际上不可能进行完全随机化的试验， 研究饮食和罕见疾病的风险，而不是重复饮食措施的大型纵向研究， 提供独特的机会，使用高级因果关系评估饮食变化对降低RA风险的影响， 推理模型，这将与最高风险人群（如一级亲属）直接相关 RA患者。 膳食因素直接或间接地在肥胖的发生中起重要作用。人士 肥胖者患主要慢性病的风险增加。我们还确定肥胖是一个重要的危险因素， RA，虽然生物学机制尚未了解。需要进一步的研究来评估这些影响 体重增加或减轻对RA风险的因果关系模型。脂肪细胞产生的脂肪因子 组织，导致慢性炎症状态，可能在肥胖相关的发展中发挥核心作用。 并发症 在本申请中，我们建议评估膳食质量的改变作为一种潜在的策略， 使用完善的因果推理模型：边际结构模型预防RA的未来发展。 这项研究也扩展了我们早期的工作，检查体重变化和体脂分布的影响 RA风险。我们还将研究是否循环脂肪因子与增加的风险， 发展RA，并介导饮食质量和肥胖与RA风险的相关性， 在NHS和NHS II队列中嵌套的病例对照研究。

7. PROJECT SUMMARY / ABSTRACT Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease, characterized by persistent synovitis and systemic inflammation. RA is generally considered as a multifactorial disease, caused by both genetic factors and environmental exposures. Although some individual dietary factors have been identified to be associated with the development of RA, few studies have examined the effects of overall dietary quality and dietary patterns on RA risk. In our previous studies, we have demonstrated that adherence to the Dietary Guidelines for Americans or following a Prudent dietary pattern is associated with reduced RA risk, while a Western dietary pattern or a dietary inflammatory pattern, characterized by high intakes of red and processed meats, refined grains, desserts and sweets, and high-fat dairy products, increases RA risk in young and middle-aged women. However, little is known about whether modifying dietary quality influences subsequent RA risk. Often, it is not ethically or practically possible to conduct a perfectly randomized trial to study diet and risk of rare diseases, instead large longitudinal studies with repeated dietary measures can provide unique opportunities to evaluate the effect of diet changes on RA risk reduction using advanced causal inference models, which will have direct relevance for populations at highest risk such as first degree relatives of RA patients. Dietary factors directly and indirectly play an important role in the genesis of obesity. Individuals with obesity are at increased risk of major chronic diseases. We also identified obesity as a significant risk factor of RA, although the biologic mechanism is not yet understood. Further study is needed to evaluate the influences of weight gain or weight loss on the risk of RA using causal models. The adipokines produced by the adipose tissue, leading to a chronic inflammatory state, may play a central role in the development of obesity-related complications. In this application we propose to evaluate the modification of dietary quality as a potential strategy to prevent future development of RA using well-established causal inference models: Marginal Structural Models. This study also extends our earlier work to examine the influences of weight changes and body fat distribution on RA risk. We will also examine whether circulating adipokines associated with an increased risk of developing RA, and mediate the observed associations of dietary quality and obesity with RA risk in a matched case-control study nested in NHS and NHS II cohorts.