Examining the Effects of Morning and Evening Exercise on Glucose Regulation in Adults With Prediabetes

Participant Recruitment, Screening, and Randomization. Participants (n=20, females=10) will be recruited from the University of Colorado Denver Anschutz Medical Campus (CU AMC) and the surrounding Denver Metro area using campus emails and flyers. Volunteers who meet initial eligibility criteria will be scheduled for an in-person screening visit including screening labs (thyroid stimulating hormone (TSH), complete blood count (CBC), comprehensive metabolic panel (CMP), lipid panel, glycated hemoglobin (A1c), urine pregnancy test in women (beta human chorionic gonadotropin), 12-lead electrocardiogram (ECG), medical history review, and physical exam with a physician or advanced practice provider. Potential participants will complete the physical activity readiness questionnaire (PAR-Q) to further screen for contraindications to exercise. 38 Potential participants will also be screened for obstructive sleep apnea using the WatchPat (Itamar Medical, Israel) with an apnea hypopnea index score > 5 being exclusionary as it significantly affects systemic metabolism. The WatchPat uses a combination of peripheral arterial tone, pulse oximetry, heart rate, accelerometers, and a snore detector to measure respiratory effort-related arousals and has been validated. 39,40 Participants who meet study eligibility criteria below will be block randomized in a 1:1 ratio (stratified by sex) to complete either AM-Ex or PM-Ex first in the crossover study.

Study Protocol and Assessments. The study will be performed at the CU AMC Anschutz Health and Wellness Center (AHWC) and the CU AMC Clinical Translational Research Center (CTRC). See Facilities and Other Resources for details of the AHWC and CTRC. Participants will undergo assessments at baseline and again after completing each of the exercise conditions.

Supervised AM and PM Exercise Conditions. Participants will complete a 3-day aerobic exercise condition (Note: 1 bout of exercise has been shown to shift melatonin). Exercise will be performed at 70% of age-predicted MHR for 45 minutes per day. Individual participant exercise time windows will be defined by the individual's habitual wake time (measured by actigraphy), with AM-Ex occurring at 0-3 hours and PM-Ex occurring at 9-12 hours post habitual wake time. These time windows were chosen to define morning and evening for several reasons. Firstly, during the traditional workday, most adults engage in exercise either prior to their work day or after their work day before bed. Secondly, these time windows have been demonstrated to be when circadian patterns of SI and melatonin are most evident and consistent. 13,35 Exercise sessions will be performed on the treadmill at the AHWC and supervised by study staff. HR monitors (Polar H10) will be worn to ensure achievement of target intensity. Session time (time of day), duration, and mean intensity will be recorded for each session. Exercise sessions will be separated by a 3-4 week washout period to both minimize training effects on SI and to account for phases of the menstrual cycle, as different menstrual phases have been shown to exhibit differing SI.

Dietary Prescription. During each condition, participants will be asked to eat a balanced diet consisting of approximately 50% carbohydrate, 30% fat, 20% protein. A controlled diet was chosen to reduce the effects of different meal compositions on the following day insulin clamp trial and so a standardized free-living day could be examined via CGM.

Assessments. All measures will be performed at baseline and after each exercise condition.