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: 10595638
• 负责人: anne peery
• 金额: $ 49.76万
• 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/10595638
• 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; Disparity; Diverticulitis; Dyslipidemias; Endocrine; Event; Future; Gastrointestinal Diseases; Glucose; Goals; Gonadal Steroid Hormones; Health Expenditures; High Risk Woman; Hospitalization; Hypertension; IL18 gene; Inflammatory; Insulin Resistance; Interleukin-1 beta; 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; 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; menopausal hormone therapy; 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.

项目摘要 结肠憩室炎是一种常见的（每100,000人年），造成5.5美元 每年有十亿美元的医疗保健支出。憩室炎是手术的主要迹象，医院 入院和卧床访问，女性疾病负担更大。绝经后妇女 与类似年龄的绝经前妇女或 年龄相似。这种差异的原因尚不清楚，但可能是由于代谢变化而引起的 与更年期。更年期与代谢综合征的所有组成部分的发展有关 包括内脏脂肪积累，动脉粥样硬化血脂血症，胰岛素抵抗和高血压。那里 有令人信服的证据表明肥胖会增加憩室炎的风险，这种关联的机制尚不清楚。 我们认为，代谢综合征解释了这种关联。建立代谢综合征的作用 憩室炎的风险从根本上重新定义了这种疾病，并开放了新的研究线以利用现有 目前用于治疗代谢综合征的疗法。更年期激素治疗确实 不能防止绝经后代谢功能障碍，并且与心血管的风险增加有关 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的风险增加有关。基于现有的高质量 证据和我们自己的初步数据，拟议的应用程序旨在证明这种代谢 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 憩室炎是一种代谢疾病。我们计划使用大型，持续的前瞻性队列来检验这一假设 国家环境健康科学研究所进行的研究（姐妹研究）。这个成熟的队列 在美国和波多黎各的50,884名妇女中，有足够的归档血液样本的特征 跟进以观察事件憩室炎，标准化​​数据收集和详细协变量，包括 生殖特征。拟议研究的目的是1）前瞻性确定关联 在代谢综合征（高血压，2型糖尿病，血脂异常和中枢性肥胖）之间 憩室炎，2）前瞻性确定更年期激素治疗与入射之间的关联 绝经后妇女的憩室炎和3）前瞻性地确定肥胖之间的关联 相关的血清生物标志物与入射憩室炎有关。这是一种新颖的憩室炎方法 与当前范式有所不同，并为多种新的医学和行为提供了潜力 憩室炎治疗和预防的策略。了解更年期之间的关联 激素疗法和事件憩室炎创造了直接改变激素的可能性 对风险增加的女性进行治疗，并将对生物学机制产生重要的见解 潜在的憩室炎。