Insulin Resistance, Pre-Diabetes, and Diabetes in Obesity-Associated Asthma

项目摘要和摘要 哮喘和肥胖症在美国很普遍。患有哮喘的肥胖患者在 肥胖相关哮喘的风险，这是一种更严重、更容易恶化的独特表型。胰岛素 抵抗、糖尿病前期和糖尿病，这是一种葡萄糖代谢紊乱的谱系，富含 肥胖，已被认为是肥胖相关哮喘发病率过高的原因之一。 在一般人群中，这些情况与肺功能和呼吸功能减弱有关。 症状，支持在肺部健康中的病理作用。然而，在以下方面存在明显的限制 文献，以及它与人类哮喘控制和严重程度的相关性，以及在肥胖患者中的相关性，是 不确定。在这项应用中，我们建议研究胰岛素抵抗、糖尿病前期和 糖尿病合并哮喘加重、哮喘控制和肺功能，以及对此的影响 与肥胖的联系。我们将在两个相辅相成的目标中执行此分析：(1)应用大数据 利用美国两个主要医疗系统的电子健康记录的流行病学项目， 将队列分析与药物流行病学技术相结合来研究假设的途径， 以及(2)一项对接受减肥手术的患有哮喘的肥胖参与者进行的前瞻性队列研究， 通过重复测量胰岛素抵抗、肺功能和患者报告的哮喘结果。这个 这些分析的结果将为胰岛素抵抗、糖尿病前期和 糖尿病与肥胖相关的哮喘。这一点尤其重要，因为这种常见的哮喘表型 几乎没有具体的治疗选择。该项目建议书将为申请者提供指导培训，以 培养以病人为中心的临床研究、药物流行病学、EHR分析的技能 技术和生物统计学。这些技能对于申请者成为一名 独立内科医生、科学家和临床流行病学家，具有哮喘和肥胖相关专业知识 哮喘。他由一个由哮喘专家组成的导师团队监督，以患者为导向的研究，EHR 流行病学和生物统计学。职业发展计划是#年研究活动的自然延续。 与他的首席导师建立不同的专业知识。研究策略和 职业发展计划将在#年在肺和重症护理医学司内实施。 约翰霍普金斯大学，利用一个协作和富有成效的研究环境，与强大的 初级教员的成功发展史。

PROJECT SUMMARY AND ABSTRACT Asthma and obesity are prevalent conditions in the United States. Obese individuals with asthma are at risk for obesity-associated asthma, a distinct phenotype that is more severe and exacerbation prone. Insulin resistance, pre-diabetes, and diabetes, a spectrum of disorders in glucose metabolism that is enriched in obesity, have been implicated as contributing to the excess morbidity observed in obesity-associated asthma. In general populations, these conditions have been associated with diminished lung function and respiratory symptoms, supporting a pathologic role in pulmonary health. However, there are significant limitations in literature, and its relevancy to asthma control and severity in humans, and among individuals with obesity, is uncertain. In this application, we propose to examine the association of insulin resistance, pre-diabetes, and diabetes with asthma exacerbations, asthma control, and lung function, as well as effect modification of this association by obesity. We will perform this analysis in two complementary aims, (1) a “big data” applied epidemiology project leveraging the electronic health record of two major health systems in the United States, combining cohort analyses with pharmaco-epidemiologic techniques to investigate the hypothesized pathway, and (2) a prospectively enrolled cohort study of obese participants with asthma who undergo bariatric surgery, with repeated measurements of insulin resistance, lung function, and patient-reported asthma outcomes. The results of these analyses will build evidence for a deleterious role of insulin resistance, pre-diabetes, and diabetes within obesity-associated asthma. This is especially important, as this common asthma phenotype has few specific treatment options. This project proposal will provide mentored training for the applicant to develop skills in the conduct of a patient-oriented clinical study, pharmacoepidemiology, EHR analytic techniques, and biostatistics. These skills will be pivotal toward the applicant's goal of becoming an independent physician-scientist and clinical epidemiologist with expertise in asthma and obesity-associated asthma. He is overseen by a mentorship team comprised of experts in asthma, patient-oriented research, EHR epidemiology, and biostatistics. The career development plan is a natural continuation of research activities in fellowship and serves to establish an expertise distinct from his principal mentor. The research strategy and career development plan will be operationalized within the Division of Pulmonary and Critical Care Medicine at the Johns Hopkins University, leveraging a collaborative and productive research environment with a strong history of successful development of junior faculty.