Obstructive sleep apnea and glycemic dysregulation in adults with type 1 diabetes

Most adults with Type 1 Diabetes (T1D) do not achieve optimal glycemic control, and thus have increased cardiovascular risk. Obstructive sleep apnea (OSA) is a highly common sleep disorder that is strongly linked to cardiometabolic dysregulation. About 50% of adults with T1D have OSA. Among adults with T1D, those with

OSA have poorer glycemic control and have higher risk of diabetes-related complications. Despite strong biological plausibility, it is unknown how OSA impacts glycemic control in T1D. Our overall goal is to investigate the role OSA in glycemic dysregulation in adults with T1D. We hypothesize that OSA exerts negative effects on

glucose regulation in T1D, leading to suboptimal glycemic control and thus increasing cardiovascular risk in T1D. We further hypothesize that suboptimal glycemic control in adults with T1D occurs in part through OSA- induced alterations in counterregulatory hormone release and lipid metabolism, subsequently worsening

glycemic control. To test these hypotheses, we propose a rigorous sleep intervention study with a within- subject, cross-over design in adults with T1D and OSA (n=40) who are using an insulin pump and continuous glucose monitoring (CGM). Participants will be studied under two 14-day study conditions in randomized order

with a 4-week washout: untreated OSA and treated OSA. We will perform the same assessments in each study condition. We will apply all-night CPAP intervention under continuous in-lab supervision to achieve complete resolution of OSA. Thus, we will use CPAP as a tool to eliminate OSA i.e., “turn off” the disease

state. Participants will continue their daily routine activities outside the lab. Sleep will be objectively assessed during the study. We will determine to what extent OSA contributes to suboptimal glycemic control in adults with T1D (Aim1). We will compare 14-day CGM profiles (key clinical CGM metrics) between untreated OSA vs.

treated OSA conditions. We will also determine how alterations in counterregulatory hormone release and lipid metabolism in the setting of OSA account for suboptimal glycemic control in adults with T1D (Aim 2). We will compare 24-hour blood profiles under controlled in-lab conditions with standardized meals between untreated

OSA vs. treated OSA conditions and determine how specific hormonal (e.g., glucagon, catecholamines) and metabolic factors contribute to glycemic dysregulation. We will concurrently assess additional biological and behavioral factors: sleep stages (e.g., slow wave sleep), insulin dose, subjective sleepiness and sleep quality,

and diabetes self-management behaviors. We will also measure resting heart rate and 24-hour ambulatory blood pressure, and fasting lipids to determine how OSA impacts these intermediate markers of cardiovascular risk. The proposed work will be the first intervention study to rigorously examine the role of OSA in glycemic

dysregulation in adults with T1D. Our study will combine real-life and in-lab assessments to determine specific biological and behavioral factors that may contribute to suboptimal glycemic control in adults with T1D and OSA. The findings may help identify sleep as a novel intervention target to improve T1D management.