Impact of Nocturnal Hypoxemia on Glucose during Sleep in High Altitude Sleep Disordered Breathing

夜间低氧血症对高原睡眠呼吸障碍睡眠期间血糖的影响

• 批准号: 10523376
• 负责人: Luu Van Pham
• 金额: $ 19.87万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10523376
• 关键词: Acute; Address; Air; Altitude; Award; Biometry; Breathing; Chronic; Clinical; Clinical Trials; Cohort Studies; Collaborations; Conduct Clinical Trials; Continuous Positive Airway Pressure; Critical Care; Cross-Over Studies; Cross-Over Trials; Data; Data Analyses; Development; Development Plans; Diabetes Mellitus; Disease; Dose; Ensure; Environment; Exhibits; Exposure to; Faculty; Funding; Glucose; Glucose Intolerance; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Home; Hour; Hyperglycemia; Hypoxemia; Hypoxia; Impairment; Insulin Resistance; Intervention; Laboratories; Link; Lung; Medicine; Mentors; Mentorship; Metabolic; Metabolic Diseases; Metabolism; Methods; Modeling; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Observational Study; Oxygen; Oxyhemoglobin; Pathogenesis; Pathogenicity; Patients; Pattern; Peru; Peruvian; Physicians; Placebos; Population; Pulse Oximetry; Randomized; Recording of previous events; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Proposals; Risk; Role; Sea; Severities; Sleep; Sleep Apnea Syndromes; Stimulus; Structure; Subgroup; Supplementation; Testing; Time; Training; Training and Infrastructure; United States National Institutes of Health; Universities; Virulence Factors; Wakefulness; Withdrawal; base; blood glucose regulation; career; career development; cohort; design; diabetes pathogenesis; experience; glucose monitor; hypertension control; improved; interstitial; meetings; member; metabolic abnormality assessment; meter; nocturnal Hypoxemia; novel; prevent; recruit; response; role model; supplemental oxygen; temporal measurement; volunteer

PROJECT SUMMARY Sleep disordered breathing (SDB) is a highly prevalent disease that is associated with increased risk for incident diabetes. Mechanisms of SDB-induced dysglycemia have not been elucidated. Hypoxemia has been implicated as a key pathogenic factor in the development of glucose intolerance and diabetes. High altitude populations, who experience chronic hypoxia, represent unique cohorts to study the role of nocturnal hypoxemia in the pathogenesis of SDB-related diabetes. Our group previously demonstrated that severity of nocturnal hypoxemia, independent of daytime oxyhemoglobin saturation, was associated with elevated hemoglobin A1c. To date, no study has shown that targeting nocturnal hypoxemia improves glucose control. In this application, we will investigate the hypothesis that nocturnal hypoxemia causes dynamic nocturnal glucose elevations, that are mitigated by oxygen. We will employ continuous glucose monitoring to examine the temporal association between glucose and oxygenation dynamics in an observational study and examine the effects of nocturnal oxygen supplementation in a randomized cross-over study. Successful completion of this proposal will provide mechanistic proof that nocturnal hypoxia is a reversible cause of dysglycemia in highlanders. The applicant, Dr. Luu Pham, is a physician in Pulmonary, Critical Care and Sleep Medicine, who seeks to develop a research career focused on the pathogenesis of SDB-related metabolic diseases. This proposal would allow the applicant dedicated time to conduct the outlined research project, as well as pursue didactic training in design and conduct of clinical trials and further quantitative methods relevant to this project and future research plans. The data generated from this research proposal will form the basis for an R01 application to examine the impact of treating of hypoxemia in the pathogenesis diabetes. The career development plan for this applicant includes a structured approach to mentoring, didactic coursework focused on a specific research goal, participation in local and national meetings and identification and regular assessment of career milestones. The research environment provided by Johns Hopkins University as well as the mentorship team described in this application will assist in Dr. Pham’s successful completion of his career and research goals. The Division of Pulmonary and Critical Care Medicine and Johns Hopkins University have a long history of training successful young clinical researchers. The pre-existing high-altitude research infrastructure and trained field staff, as well as the applicant’s established and ongoing collaboration with his team of mentors, will ensure that the study goals will be completed within the timeframe of this award. We have assembled a mentoring team of established faculty with distinct, complementary strengths in high altitude research, clinical trials, metabolic sequelae of SDB and biostatistics, relevant to this proposal. In addition, each member of the mentoring committee serves as an excellent role model for the applicant’s career development into an independent investigator.

项目概要 睡眠呼吸障碍 (SDB) 是一种高度流行的疾病，与事件风险增加相关 SDB 引起的血糖异常的机制尚未阐明。 作为高海拔人群发生葡萄糖不耐症和糖尿病的关键致病因素。 经历慢性缺氧的人代表了研究夜间低氧血症在睡眠中的作用的独特群体。 我们的研究小组先前证明了夜间低氧血症的严重程度， 与白天氧合血红蛋白饱和度无关，与 A1c 血红蛋白升高相关。 研究表明，针对夜间低氧血症可以改善血糖控制。 在此应用中，我们将研究夜间低氧血症导致动态夜间血糖的假设 我们将采用连续血糖监测来检查时间。 观察性研究中葡萄糖和氧合动力学之间的关联，并检查以下因素的影响 一项随机交叉研究的夜间氧气补充将成功完成。 提供了机制证据，证明夜间缺氧是高地人血糖异常的可逆原因。 申请人 Luu Pham 博士是一名肺科、重症监护和睡眠医学领域的医生，他致力于 发展专注于 SDB 相关代谢疾病发病机制的研究事业。 让申请人有专门的时间进行概述的研究项目，并进行教学培训 设计和进行临床试验以及与该项目和未来研究相关的进一步定量方法 该研究计划生成的数据将构成 R01 申请审查的基础。 治疗低氧血症对糖尿病发病机制的影响 该申请人的职业发展计划。 包括结构化的指导方法，专注于特定研究目标的教学课程， 参加地方和国家会议以及确定和定期评估职业里程碑。 约翰·霍普金斯大学提供的研究环境以及导师团队在 该申请将协助范博士成功完成他的职业和研究目标。 肺科和重症监护医学科和约翰·霍普金斯大学拥有悠久的成功培训历史 现有的高海拔​​研究基础设施和训练有素的现场工作人员。 由于申请人与其导师团队建立并持续的合作，将确保该研究 我们已组建了一支由既定人员组成的指导团队，将在该奖项的期限内完成目标。 在高原研究、临床试验、SDB代谢后遗症方面具有独特、互补优势的教师队伍 和生物统计学，与本提案相关。此外，指导委员会的每位成员都担任一名成员。 申请人职业发展成为独立研究者的优秀榜样。