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

一项前瞻性队列研究以确定肥胖在憩室炎中的作用

• 批准号: 10416129
• 负责人: anne peery
• 金额: $ 47.5万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10416129
• 关键词: APLN gene; Address; Adipocytes; Adipose tissue; Age; Archives; Automobile Driving; Behavioral; Biological; Biological Markers; Biology; Blood specimen; Central obesity; Characteristics; Colon; Data; Data Collection; Development; Disease; Diverticulitis; Dyslipidemias; Endocrine; Event; Future; Gastrointestinal Diseases; Glucose; Goals; Gonadal Steroid Hormones; Health Expenditures; High Risk Woman; Hospitalization; Hypertension; Inflammatory; Insulin Resistance; Interleukin-1 beta; Interleukin-18; Interleukin-6; Intra-abdominal; Investigation; Leptin; Medical; Menopause; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolic syndrome; National Institute of Environmental Health Sciences; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathogenesis; Patients; Persons; Play; Postmenopause; Predisposition; Premenopause; Prevention; Prevention approach; Prospective cohort; Prospective cohort study; Puerto Rico; Research; Risk; Role; Serum; Sex Differences; Sister; Testing; Variant; Visceral fat; Visit; Woman; Work; abdominal fat; adipokines; adiponectin; burden of illness; cardiovascular risk factor; cohort; cost; cytokine; data standards; follow-up; hormone therapy; insight; men; novel strategies; obesity biomarkers; operation; pre-clinical; prospective; reproductive; resistin; screening; sex

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.

项目概要 结肠憩室炎是一种常见疾病（每 10 万人年 209 例），造成 5.5 美元的损失 每年数十亿美元的医疗保健支出。憩室炎是手术、医院的主要适应症 入院和门诊就诊，女性的疾病负担更大。绝经后年龄的女性 与年龄相近的绝经前女性或 年龄相仿的男性。造成这种差异的原因尚不清楚，但可能是由于相关的代谢变化所致 患有更年期。更年期与代谢综合征所有成分的发生有关 包括内脏脂肪堆积、动脉粥样硬化性血脂异常、胰岛素抵抗和高血压。在那里 令人信服的证据表明肥胖会增加憩室炎的风险，但这种关联的机制尚不清楚。 我们相信代谢综合征可以解释这种关联。确立代谢综合征在以下领域的作用： 憩室炎风险将从根本上重新定义这种疾病，并开辟新的研究领域，利用现有的 目前用于治疗代谢综合征的疗法。更年期激素疗法确实 不能预防绝经后代谢功能障碍，并且与心血管疾病风险增加相关 事件，特别是在患有代谢综合征的女性中。在有限的工作中，更年期激素 治疗的使用也与憩室炎风险增加有关。建立在现有的、高质量的基础上 证据和我们自己的初步数据，拟议的应用旨在证明代谢 综合征和临床前肥胖生物标志物在憩室炎中发挥作用。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、前瞻性的队列来检验这个假设 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 通过存档的血液样本对美国和波多黎各 50,884 名女性的特征进行了充分的表征， 跟进观察憩室炎事件、标准化数据收集和详细的协变量，包括 生殖特征。拟议研究的目的是 1) 前瞻性地确定关联 代谢综合征（高血压、2 型糖尿病、血脂异常和中心性肥胖）与事件之间的关系 憩室炎，2) 前瞻性地确定绝经期激素治疗与事件之间的关联 绝经后妇女的憩室炎，以及3）前瞻性地确定肥胖与 与憩室炎发生相关的相关血清生物标志物。这是一种治疗憩室炎的新方法 与当前的范式不同，并创造了多种新的医学和行为的潜力 憩室炎的治疗和预防策略。了解更年期之间的关联 激素治疗和憩室炎的发生可能会导致立即改变激素处方 对风险增加的女性进行治疗，并将产生对生物学机制的重要见解 潜在的憩室炎。