The Impact of Exercise on Cardiometabolic Health during Shiftwork: A Proof of Concept Study - PROJECT SUMMARY & ABSTRACT Approximately one-fourth of the US working population is required to work nontraditional hours including evening, rotating, and night shifts. Night shift workers have increased risk of cardiovascular disease, obesity, and type 2 diabetes. Circadian misalignment has been implicated as one potential mechanism for this increased cardiometabolic disease risk. This hypothesis is supported by experimental studies demonstrating that acute circadian misalignment decreases endothelial function, increases blood pressure, promotes dysglycemia, decreases insulin sensitivity, decreases energy expenditure, and decreases carbohydrate oxidation. Despite these negative health consequences associated with circadian misalignment, there has been limited effort to identify and evaluate effective countermeasures to night shiftwork. It is well known that aerobic exercise is a powerful lifestyle habit for treating and preventing cardiometabolic disease. However, previous research has not rigorously examined whether a guidelines-based bout of aerobic exercise is sufficient for counteracting the cardiometabolic impairments caused by circadian misalignment. Thus, a well-controlled, definitive trial is necessary to evaluate the effectiveness of aerobic exercise as a countermeasure. Prior to a definitive trial, a proof-of-concept study is warranted to optimize the study protocols, train staff, and improve patient experience. The overall objective of this proposal is to determine the feasibility and preliminary efficacy of a guidelines-based dose of aerobic exercise as a countermeasure to the harmful cardiometabolic effects associated with night shiftwork. We will employ a randomized crossover study with a rigorous 6-day simulated shiftwork, inpatient protocol in 8 healthy men and women. For Aim 1, We will assess the feasibility of recruitment processes, the inpatient protocol and intervention, and assessment methodologies. In addition, we will obtain quantitative and qualitative feedback from participants on their experience in the study to refine the study design and implementation in a future definitive trial. For Aim 2, we will determine the preliminary effect of a guidelines- based dose of aerobic exercise on cardiometabolic outcomes during circadian misalignment. Cardiometabolic outcomes of interest will include endothelial function (flow-mediate dilation), 24h ambulatory blood pressure, insulin sensitivity (hyperinsulinemic euglycemic clamp), 24h glucose (continuous glucose monitoring), and 24h energy expenditure and substrate oxidation (whole-room calorimetry). Results of this study will inform a future definitive trial. If aerobic exercise is an effective countermeasure to circadian misalignment, future studies can focus on the optimal dose and timing of exercise as well as how to best translate findings into practice. If aerobic exercise is not an effective countermeasure, future studies can focus on other countermeasures (behavioral or pharmacological) to circadian misalignment.
