A prospective cohort study to determine the role of obesity in diverticulitis

项目总结 结肠憩室炎是一种常见的疾病(每100,000人年有209例)，造成5.5美元 每年的医疗保健支出为10亿美元。憩室炎是手术的主要适应症，医院 入院和门诊就诊，妇女的疾病负担更大。绝经后年龄妇女 与年龄相近的绝经前妇女相比，患憩室炎的风险最高 年龄相仿的男人。这种差异的原因尚不清楚，但可能是由于相关的新陈代谢变化。 更年期的患者。更年期与代谢综合征的所有组成部分的发展有关 包括内脏脂肪堆积、致动脉粥样硬化性血脂异常、胰岛素抵抗和高血压。在那里的时候 令人信服的证据表明肥胖会增加憩室炎的风险，但这种联系的机制尚不清楚。 我们认为代谢综合征解释了这种联系。确立代谢综合征在 憩室炎风险将从根本上重新定义这种疾病，并开辟新的研究路线，利用现有的 目前用于治疗代谢综合征的治疗方法。更年期激素疗法起作用 不能预防绝经后代谢功能障碍，并与心血管风险增加有关 事件，特别是在已有代谢综合征的妇女中。在有限的工作中，更年期激素 治疗的使用也与憩室炎风险的增加有关。在现有的高质量基础上构建 证据和我们自己的初步数据，拟议的申请旨在证明新陈代谢 综合征和临床前肥胖生物标志物在憩室炎中起作用。我们的中心假设是 憩室炎是一种代谢性疾病。我们计划使用一个大型的、持续的、预期的队列来检验这一假设 由国家环境健康科学研究所进行的研究(姐妹研究)。这个成熟的群体 在美国和波多黎各的50,884名女性中，有很好的特征是有存档的血液样本，足够 追踪观察事件憩室炎、标准化数据收集和详细的协变量，包括 生殖特征。这项拟议研究的目的是：1)前瞻性地确定 代谢综合征(高血压、2型糖尿病、血脂异常和中心性肥胖)和发病率 憩室炎，2)前瞻性地确定更年期激素治疗和事件之间的关联 绝经后女性的憩室炎，以及3)前瞻性地确定肥胖与 相关血清生物标志物与事件憩室炎的关系。这是治疗憩室炎的一种新方法 背离了当前的模式，并创造了多种新的医疗和行为 憩室炎的治疗和预防策略。了解更年期与绝经之间的关系 激素治疗和偶发的憩室炎创造了立即改变激素处方的可能性 对高危女性的治疗，将对生物机制产生重要的见解 潜在的憩室炎。

PROJECT SUMMARY Colonic diverticulitis is a common (209 cases per 100,000 person-years) disease that is responsible for $5.5 billion dollars in health care expenditures annually. Diverticulitis is a leading indication for operations, hospital admissions, and ambulatory visits, with a greater burden of disease in women. Postmenopausal age women are at highest risk of developing diverticulitis when compared to either similar age premenopausal women or similar age men. The reason for this disparity is unknown but may be due to metabolic changes associated with menopause. Menopause is associated with the development of all components of metabolic syndrome including visceral fat accumulation, atherogenic dyslipidemia, insulin resistance, and hypertension. While there is compelling evidence that obesity increases diverticulitis risk, the mechanism for this association is unclear. We believe metabolic syndrome explains this association. Establishing a role for metabolic syndrome in diverticulitis risk would radically redefine this disease and open new lines of research to utilizing existing therapies that are currently used for the treatment of metabolic syndrome. Menopausal hormone therapy does not prevent postmenopausal metabolic dysfunction and is associated with an increased risk of cardiovascular events, particularly in women with preexisting metabolic syndrome. In limited work, menopausal hormone therapy use has also been associated with increased diverticulitis risk. Building on existing, high-quality evidence and our own preliminary data, the proposed application aims to demonstrate that metabolic syndrome and preclinical obesity biomarkers play a role in diverticulitis. Our central hypothesis is that diverticulitis is a metabolic disease. We plan to test this hypothesis using a large, ongoing, prospective cohort study (Sister Study) conducted by the National Institute of Environmental Health Sciences. This mature cohort of 50,884 women in the U.S. and Puerto Rico is well characterized with archived blood samples, sufficient follow up to observe incident diverticulitis, standardized data collection, and detailed covariates including reproductive characteristics. The aims of the proposed study are 1) to prospectively determine the association between metabolic syndrome (hypertension, type 2 diabetes, dyslipidemia, and central obesity) and incident diverticulitis, 2) to prospectively determine the association between menopausal hormone therapy and incident diverticulitis in postmenopausal women, and 3) to prospectively determine the association between obesity- related serum biomarkers in relation to incident diverticulitis. This is a novel approach to diverticulitis that diverges from the current paradigm and creates the potential for multiple new medical and behavioral strategies for diverticulitis treatment and prevention. Understanding the association between menopausal hormone therapy and incident diverticulitis creates the possibility of immediate change in prescribing hormone therapy to women at increased risk and will generate important insights into the biological mechanisms underlying diverticulitis.