PROJECT SUMMARY/ABSTRACT (FROM PARENT GRANT) Over one in three Americans regularly sleep less than the recommended 7 hours per night. Alarmingly, adults who maintain habitual short sleep durations (HSSD), such as medical and military personnel, emergency responders, shift workers, and students, are alarmingly ~30% more likely to develop type 2 diabetes (T2D) versus adults who maintain adequate sleep durations. Furthermore, data show that experimentally imposed sleep restriction lasting ~3 days to 2 weeks can impair insulin sensitivity to levels commonly observed in people with pre-diabetes or in aging. However, it is not known if data from rigidly controlled laboratory studies of experimental sleep restriction translates to people with real-world naturalistic HSSD. Furthermore, neither the existing data from epidemiological nor laboratory-controlled studies inform mechanisms or potential health benefits of interventions targeting HSSD. Molecular biomarkers that link risk of T2D with HSSD could help overcome these knowledge gaps by: (1) identifying mechanisms underlying risk of T2D linked to real-world HSSD and (2) informing whether sleep extension reverses such risk. Our preliminary data identified ceramides as important candidate biomarkers that link risk of T2D with short sleep duration. Ceramides are central intermediate lipids in sphingolipid metabolism and are particularly deleterious as they induce insulin resistance and are consistently associated with incidence of cardiometabolic disease including T2D. Thus, our central hypothesis is that ceramides are biomarkers that link risk of T2D with HSSD, and sleep extension is expected to lower plasma ceramides and improve insulin sensitivity. To test our central hypothesis, we will conduct a randomized controlled trial with real-world sleep extension in overweight and obese adults with HSSD. Participants will complete 1 week of baseline monitoring and then be randomized to either sleep extension (target ≥8 hours of nightly time in bed) or HSSD maintenance for 8 weeks at home (intervention segment). Following the baseline and intervention segments participants will complete rigorous overnight laboratory visits to assess plasma ceramides (targeted metabolomics assay) and insulin sensitivity (hyperinsulinemic-euglycemic clamp). Aim 1 will determine the impact of sleep extension on plasma ceramides and Aim 2 will determine the impact of sleep extension on insulin sensitivity. Our expected findings will advance the field by identifying biomarkers that link risk of T2D with HSSD and informing whether sleep extension reverses such risk. This knowledge could improve our ability to quantify, track, and reduce an individual’s risk of T2D over time, which could be especially impactful for people who are less successful with current diet and physical activity-based interventions. If effective, sleep extension would therefore help improve quality of life and reduce the health and economic burdens of T2D on society.

PROJECT NARRATIVE (FROM PARENT GRANT) Chronic sleep loss and short sleep duration are epidemic in modern society, representing an important public health issue. The goal of this project is to identify biomarkers that link adverse cardiometabolic risk with habitual short sleep duration and to determine if sleep extension reverses such risk. We expect these findings will help identify people with elevated cardiometabolic risk due to habitual short sleep duration and could improve our ability to quantify, track, and reduce an individual’s risk of type 2 diabetes over time.