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

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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.