Mechanisms underlying the relationship between sleep health and circadian timing with cardiometabolic risk in adolescents with type 1 diabetes

PROJECT SUMMARY Our research has shown a link between poor sleep health and late circadian timing with cardiometabolic dysfunction in adolescents with type 1 diabetes (T1D). Further, sleep health and circadian timing of adolescents with T1D participating in our research was markedly poor compared to age-based recommendations. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in T1D, which begins as early as adolescence, and current therapies are limited. Thus, it is imperative to identify countermeasures, such as sleep health and circadian timing, to improve cardiometabolic health in adolescents with T1D. Our central hypothesis is that that cardiometabolic dysfunction associated with T1D can be reduced by improving sleep health and circadian timing. We have successfully increased sleep duration and advanced circadian timing with a combined behavioral and physiological intervention in adolescents without T1D. Simultaneously intervening on sleep health and circadian timing may reverse cardiometabolic dysfunction but a gap exists with no research in adolescents with T1D. Further, no research to date has examined the physiological mechanisms underlying the relationship between sleep health and circadian timing and cardiometabolic dysfunction in adolescents with T1D. We therefore propose to utilize a combined sleep health and circadian timing intervention as a mechanistic probe to understand relationships with cardiometabolic health in adolescents with T1D. Utilizing a randomized clinical trial design and a combined free-living and in-laboratory paradigm, we will compare the effect of 1 month of optimally-timed, low-dose PM melatonin and AM bright light exposure plus increased time in bed to an attention- matched control condition in adolescents with T1D. We will evaluate changes in insulin resistance, glycemic control, and vascular functioning using rigorous assessment methods, and determine physiological mechanisms. We hypothesize that insulin sensitivity, glycemic control, and vascular function will improve with a combined sleep and circadian intervention, and that inflammation, cortisol, and leptin will act as mediators. This proposal will provide an understanding of mechanisms underlying the relationship between sleep health and circadian timing and cardiometabolic dysfunction in adolescents with T1D which is urgently needed as a first step towards developing new therapies to mitigate CVD in T1D.