Obstructive Sleep Apnea and Glycemic Variability in Type 2 Diabetes

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）和2型糖尿病是普遍的医疗条件，每一个具有显着的不良后果。在过去的十年中，大量的经验证据表明，OSA在糖尿病患者中很普遍，这两种疾病之间的联系与肥胖无关。动物和临床研究表明，OSA患者的间歇性低氧血症和睡眠中断可能会改变葡萄糖稳态并损害血糖控制。然而，关于OSA和糖尿病之间的关系仍然存在一些问题。目前缺乏描述阻塞性睡眠呼吸暂停综合症严重程度对餐后高血糖和血糖变异性影响的研究。已经确定，虽然血糖控制的总体测量，例如糖化血红蛋白水平（HbA 1c），可以预测血管并发症，但是具有大血糖波动的餐后高血糖独立地预测患有糖尿病的个体中的血管并发症，包括颈动脉内膜中层厚度、动脉粥样硬化和大血管疾病。本发明的第一个目的是表征糖尿病患者队列中OSA严重程度、血糖控制、餐后高血糖和血糖变异性之间的横截面关联。描述这些相关性是实现本研究第二个目的的关键--确定糖尿病患者采用持续气道正压通气（CPAP）治疗OSA是否与血糖控制、餐后高血糖和血糖变异性的改善相关。为了实现这些目标，糖尿病患者将接受睡眠测试，以确定和分类OSA的严重程度。将获得活动图监测（量化睡眠持续时间）、热量摄入和葡萄糖稳态的几个指标（连续葡萄糖监测、7点自我监测血糖曲线和HbA 1c）。OSA严重程度指数将与血糖负荷指标相关，并仔细考虑混杂因素。因此，两个平行的和独特的科学调查线-横断面和干预性研究-将被用来获得一个更全面的了解相关的OSA作为葡萄糖代谢的调节剂。也许，这项研究最具创新性和实际相关性的贡献是评估CPAP治疗是否可以改善血糖控制，并被认为是糖尿病治疗设备中的“辅助”。如果本申请中提出的假设是正确的，则所得数据将对糖尿病管理产生范式转移效应。K23指导的以患者为导向的研究职业发展奖是成功开展上述拟议调查的理想平台，并实现了我成为睡眠障碍医学独立临床研究者的长期职业目标和职业抱负。通过K23机制，我期望在获奖过程中通过成功完成以下每个短期目标来实现我的长期目标：1）通过彭博公共卫生学院的临床调查研究生培训计划获得健康科学硕士学位，获得临床调查方面急需的正式培训，2）与我的专家和专门的导师团队密切合作，执行拟议的研究，以及3）在科学会议上展示研究结果，并通过在同行评审的期刊上发表。我对成为一名独立的睡眠医学临床研究者的坚定承诺证明了我决定重新定位我的职业生涯，并搬到约翰霍普金斯大学，在那里我可以沉浸在一个支持和专注的学术环境与无与伦比的导师团队。约翰霍普金斯医学院、彭博公共卫生学院以及肺部和重症监护医学部的知识和临床环境是开展拟议研究和培养临床职业的理想场所。 research.

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) and type 2 diabetes mellitus are prevalent medical conditions each with significant adverse consequences. Over the last decade, a large body of empirical evidence has shown that OSA is prevalent in patients with diabetes and that the association between these two conditions is independent of adiposity. Animal and clinical studies have demonstrated that intermittent hypoxemia and sleep disruption in OSA may alter glucose homeostasis and impair glycemic control. Several questions remain, however, about the association between OSA and diabetes. Research characterizing the impact of OSA severity on post-prandial hyperglycemia and glycemic variability are lacking. It is well established that, while global measure of glycemic control, such as glycosylated hemoglobin levels (HbA1c), can predict vascular complications, post-prandial hyperglycemic with large glycemic excursions are independently predictive of vascular complications including carotid intima-media thickness, atherosclerosis, and macrovascular disease in individuals with diabetes Accordingly, the first aim of the current proposal is to characterize the cross-sectional association between OSA severity, glycemic control, post-prandial hyperglycemia, and glycemic variability in a cohort of patients with diabetes. Characterizing these associations is central in accomplishing the second aim of the proposed investigation - determining if treatment of OSA with continuous positive airway pressure (CPAP) therapy in patients with diabetes is associated with improvements in glycemic control, post-prandial hyperglycemia, and glycemic variability. To accomplish these aims, patients with diabetes will undergo sleep testing to identify and classify OSA severity. Actigraph monitoring (to quantify sleep duration), caloric intake, and several metrics of glucose homeostasis (continuous glucose monitoring, 7- point self-monitoring blood glucose profiles, and HbA1c) will be obtained. Indices of OSA severity will be related to metrics of glycemic load with careful consideration of confounders. Thus, two parallel and unique lines of scientific inquiry - a cross-sectional and an interventional study - will be utilized to gain a ore comprehensive understanding of the relevance of OSA as a modifier of glucose metabolism. Perhaps, the most innovative and practically relevant contribution of this research is the assessment of whether CPAP therapy could improve glycemic control and be considered an "adjuvant" in the therapeutic armamentarium for diabetes. If the hypotheses proposed in this application are correct, the resulting data will have a paradigm shifting effect on diabetes management. The K23 Mentored Patient-Oriented Research Career Development Award is the ideal platform to successfully carry out the proposed investigations outlined above and fulfill my long-term career goal and professional aspiration of becoming an independent clinical investigator in sleep disorders medicine. Through the K23 mechanism, I anticipate progressing towards my long-term objective by successfully completing each of the following short-term goals over the course of the award: 1) obtaining much needed formal training in clinical investigation by pursuing a Masters in Health Science degree through the Graduate Training Program in Clinical Investigation at the Bloomberg School of Public Health, 2) working closely with my expert and dedicated mentorship team to execute the proposed research, and 3) presenting the findings at scientific meetings and through publication in peer-reviewed journals. My unwavering commitment towards becoming an independent clinical investigator in sleep medicine is evidenced by my decision to redirect my career and move to Johns Hopkins University, where I could be immersed in a supportive and dedicated academic environment with an unparalleled mentorship team. The intellectual and clinical environments at the Johns Hopkins School of Medicine, Bloomberg School of Public Health, and Division of Pulmonary and Critical Care Medicine are ideal to carry out the proposed research and foster a career in clinical research.