Night Owl Metabolism: Investigating the Impact of Chronotype on Glucose Metabolism in Youth

PROJECT SUMMARY/ABSTRACT Adolescents commonly develop delayed sleep schedules in normal development related to physiologic processes, turning into “night owls” (late chronotype). Youth-onset type 2 diabetes (YoT2D) is a disorder with fast progression and early complications. Delayed sleep timing has been identified as a possible modifiable

risk factor for YoT2D. Although prior studies have linked shifted sleep timing to impaired glucose metabolism, these studies may not extrapolate to youth with late chronotype as they utilize standard morning testing with oral glucose tolerance tests (OGTTs), at a time mis-aligned to the typical schedule of an individual with late

chronotype. As glucose tolerance worsens as the day progresses until the middle of the night in healthy individuals, testing at a time when youth with late chronotype are typically asleep may alter results and lead to potential mis-diagnoses. Under the expert mentorship of Drs. Sheela Magge and co-mentor, Jonathan Jun, Dr.

Talia Hitt will investigate whether alignment of glucose metabolic testing with chronotype improves glycemic outcomes and whether alignment of first morning meal timing to chronotype improves post-prandial glycemic response in youth with late chronotype. The proposed study uses a novel and rigorous randomized cross-over

study design in youth (17-23y) with late and non-late chronotype (n=35 per group) to assess the glycemic effect of “aligning” an OGTT or first-meal of day to a subject’s chronotype. Both groups will undergo 2 OGTTs (aligned and mis-aligned with chronotype) to compare glucose tolerance and insulin sensitivity within-subject

(primary outcome) and between groups (Aim 1). Then, youth will also undergo two standardized meals (aligned and mis-aligned with chronotype) while wearing continuous glucose monitoring to compare post- prandial glucose excursions within-subject and between groups (Aim 2). A pilot Exploratory Aim 3 (n=12 per

group) will investigate delayed melatonin patterns under dim-light as a potential pathophysiologic mechanism behind abnormal glucose tolerance in youth with late chronotype on morning OGTTs. This study has potential implications for both clinical and research practices, as well as meal timing recommendations. It will provide

preliminary data for a future R01 study of the relationships between sleep and circadian rhythm with glucose metabolism and YoT2D risk. This Career Development Award will develop Dr. Hitt’s training in 4 areas of focus addressing gaps in her prior research background: (1) longitudinal data analysis, (2) glucose metabolism

mathematical modeling, (3) sleep and circadian phenotyping, and (4) experimental study design. Training goals will be accomplished through didactic coursework, one-on-one meetings with expert mentors and a multi- disciplinary advisory team, the study’s research activities, and attendance at scientific and career development

seminars, and conferences. Dr. Hitt will have all needed resources and a supportive environment at Johns Hopkins. By the end of this 5-year award, Dr. Hitt will have the necessary skills to reach her long-term career goal to become an independent researcher in the intersection of youth chronobiology and glucose metabolism.