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: 10705149
• 负责人: Luu Van Pham
• 金额: $ 19.58万
• 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/10705149
• 关键词: Acute; Address; Air; Altitude; Award; Biometry; Breathing; Chronic; Clinical; Clinical Trials; Cohort Studies; Collaborations; Conduct Clinical Trials; Continuous Glucose Monitor; Continuous Positive Airway Pressure; Critical Care; Cross-Over Studies; Cross-Over Trials; Data; Data Analyses; Dedications; 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; 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; Research Training; Risk; Role; Sea; Severities; Sleep; Sleep Apnea Syndromes; Stimulus; Structure; Subgroup; Supplementation; Testing; Time; Training; United States National Institutes of Health; Universities; Virulence Factors; Wakefulness; Withdrawal; blood glucose regulation; career; career development; cohort; design; diabetes pathogenesis; experience; hypertension control; improved; interstitial; meetings; member; metabolic abnormality assessment; meter; nocturnal Hypoxemia; novel; prevent; recruit; response; role model; supplemental oxygen; temporal measurement; volunteer; wearable monitor

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.

项目摘要 睡眠障碍呼吸（SDB）是一种高度普遍的疾病，与出现的风险增加有关 糖尿病。尚未阐明SDB诱导的血糖的机理。低氧血症已被牵涉 作为葡萄糖肠道和糖尿病发展的关键致病因素。高海拔地区， 患有慢性缺氧的人，代表着研究夜间低氧血症在 SDB相关糖尿病的发病机理。我们的小组以前证明了夜间低氧血症的严重程度， 与白天血红蛋白饱和度无关，与血红蛋白A1c升高有关。迄今为止，没有 研究表明，靶向夜间低氧血症可改善葡萄糖的控制。 在此应用中，我们将研究夜间低氧血症会导致动态夜间葡萄糖的假设 高程，通过氧气降低。我们将采用连续的葡萄糖监测来检查临时 葡萄糖和氧合动力学之间的关联在一项检查研究中，并检查 在一项随机跨界研究中补充夜间氧气。该提案的成功完成将 提供机械证明，表明夜间缺氧是高地人血糖症障碍性疾病的可逆原因。 申请人Luu Pham博士是肺部，重症监护和睡眠医学的身体，试图 发展研究职业，重点是与SDB相关的代谢疾病的发病机理。该提议将 允许申请人专门的时间进行概述的研究项目，并努力进行教学培训 设计和行为的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 计划。该研究提案产生的数据将构成R01应用程序的基础 治疗低氧血症在发病机理糖尿病中的影响。该申请人的职业发展计划 包括一种结构化的心理，教学课程，重点是特定的研究目标， 参加当地和国家会议，并定期评估职业里程碑。 约翰·霍普金斯大学（Johns Hopkins University）提供的研究环境以及所描述 该申请将有助于Pham博士成功完成其职业和研究目标。分裂 肺和重症监护医学和约翰·霍普金斯大学的培训历史悠久 年轻的临床研究人员。现有的高海拔​​研究基础设施和训练有素的现场工作人员 随着申请人与他的导师团队的建立和持续的合作，将确保该研究 目标将在此奖项的时间范围内完成。我们已经组建了一个既定的心理团队 在高海拔研究，临床试验，SDB的代谢后遗症中具有明显，完全优势的教师 和生物统计学，与该提案有关。此外，心理委员会的每个成员都是 申请人职业发展成为独立调查员的出色榜样。