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.

PUBLIC HEALTH RELEVANCE: Emerging data suggests that obstructive sleep apnea (OSA) can alter glucose metabolism and increase cardio-metabolic risk. While continuous positive airway pressure therapy (CPAP) is effective in treating OSA, its effects on glycemic variability and postprandial hyperglycemia are unknown. The central focus of this proposal is to delineate the impact of OSA and its treatment with CPAP on glycemic measures, such as postprandial hyperglycemia and glycemic variability that are known to predict future cardiovascular risk.