Effects of Sleep Restriction on Glycemic Control and Cardiovascular Risk Mechanisms in Type 1 Diabetes Mellitus - Type 1 diabetes (T1D) patients are at heightened risk for cardiovascular disease (CVD), especially hypertension. They also have an increased risk of sleep disturbances. Disrupted sleep in T1D has negative implications for glycemic control and diabetes self-management, and sleep is increasingly emerging as a critical but poorly understood factor in the management of T1D and in T1D cardiovascular risk stratification. However, little is known of the relationships between sleep architecture, sleep insufficiency, blood pressure (BP), cognition, and glycemic control in T1D. Specifically, while restricted sleep is known to increase BP and promote insulin resistance in healthy subjects, very little is known of the effects of sleep loss on insulin sensitivity, neural circulatory control, biomarkers of CV risk, and executive function in T1D. Effects of sleep loss on 24-hour ambulatory blood pressure (ABP) in T1D have not been studied, and there are no randomized studies of effects of sleep restriction on cognitive function, and the consequences for errors in glycemic control, in T1D patients. Continuous glucose monitoring (CGM) offers the opportunity for very close monitoring of glucose during daytime wakefulness, and during the different sleep stages. Multiple daily injections of insulin (MDI) represent the most widely used therapy worldwide, and combined with CGM (CGM-MDI), will provide detailed and accurate insights into the effects of sleep and sleep loss on glycemic control. Building on a robust scientific premise, and compelling preliminary data we propose a randomized controlled crossover study of 34 subjects with T1D (17 males; 17 females) to examine the effects of sleep insufficiency versus adequate sleep (5 nights of restricted sleep (5 hours of sleep per night) versus 5 nights of 9 hours of sleep opportunity) on the degree and trajectory of changes in glycemic metrics, CV risk measures, and cognitive function. These stand-alone Aims are independent of each other. Specific Aim 1: To evaluate the effects of sleep restriction on insulin sensitivity (measured by insulin clamp) and glycemic metrics (measured by CGM). Specific Aim 2: To evaluate the effects of sleep restriction on 24-hour ABP, nocturnal BP dipping, and vascular control mechanisms (baroreflex sensitivity, arterial stiffness, endothelial function, and sympathetic drive). Specific Aim 3: To evaluate the effects of sleep restriction on executive function (including stimulus classification and error monitoring) measured by neurocognitive testing, and the relationship between any impairment in cognitive function and errors in carbohydrate counts, insulin administration, and glycemic control. This comprehensive study design is founded on decades of studying sleep, sleep restriction and T1D by a highly experienced cross disciplinary study team with expertise in CV risk phenotyping, randomized trials, preventive cardiology, cognition, and hypertension. These data will provide a rich, novel, and clinically important resource to understand relationships between sleep, glycemic control, CV risk and cognitive function, in T1D patients.
