ImpaCt Of Shiftwork on METabolic Flexibility and Skeletal Muscle Clocks

Inclusion criteria

• Age 21-45 yrs
• Employed as a healthcare worker in either dayshift (N=15) or nightshift work (N=30).
• Nightshift is defined as 12 months of consecutive nightshift work, who had 10 or more nightshifts per month (6 h between 10 PM and 8 AM, with no shift duration > 12 h).
• Dayshift is defined as 12 months of consecutive dayshift work, who had 10 or more dayshifts per month (6h between 8 AM and 10 PM, with no shift duration > 12 h).
• Weight Stable (+/- 3 kg over past 6 months)
• BMI between 18.5-29.9 kg/m2
• Understands the procedures and agrees to participate by giving written informed consent
• Willing and able to comply with scheduled visits, laboratory tests, and other study procedures including
• Only low to moderate caffeine users (<500 mg/day, or up to approximately 5 cups [1 cup=8 ounces] of coffee/day.

Exclusion criteria

• Acute or chronic medical conditions or medication that would contraindicate participation in the research testing or could potentially affect metabolic function including, but not limited to:
• History or presence of cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, presence of cardiac pacemaker, implanted cardiac defibrillator)
• Type 1 or Type 2 diabetes mellitus
• Obesity (BMI ≥ 30 kg/m2)
• Bleeding and clotting disorders
• Uncontrolled hypertension (BP >160 mmHg systolic or >100 mmHg diastolic)
• Acute or chronic infections (such as TB, HIV, or Hepatitis)
• Renal insufficiency or nephritis (eGFR<60), nephritis, or chronic kidney disease
• Chronic obstructive pulmonary disease
• Thyroid dysfunction (suppressed TSH, elevated TSH <10 µIU/ml if symptomatic or elevated TSH >10 µIU/ml if asymptomatic)
• Liver disease (liver function tests > 2 x normal; including nonalcoholic steatohepatitis [NASH] and non-alcoholic fatty liver disease [NAFLD])
• Diagnosed or being treated for sleep disorders
• History of Cushing's disease or syndrome
• Pregnant or nursing females or females less than 6 months postpartum from the scheduled date of collection
• Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women) during screening
• Participation in studies involving investigational drug(s) within 30 days prior to Screening
• Gastrointestinal disorders (including inflammatory bowel disease or malabsorption, swallowing disorders, suspected or known strictures, fistulas or physiological/mechanical GI obstruction, history of gastrointestinal surgery, Crohn's disease or diverticulitis)
• Past or present history of psychiatric disease, including major depressive illness or bipolar disorder, as well as claustrophobia since part of the protocol will involve being confined to a small room for whole-body indirect calorimetry
• Unwilling or unable to eat foods provided in study procedures
• Nickel allergy
• Lidocaine allergy
• Any malignancy not considered cured, except basal cell carcinoma and squamous cell carcinoma of the skin (a participant is considered cured if there has been no evidence of cancer recurrence in the previous 5 years)
• Use of antibiotics within 3 months of screening
• Illicit drug use (negative tests at screening)
• Regular smoking or regular nicotine use of any kind including chewing tobacco, snuff and vaping
• History of regular alcohol consumption exceeding 7 drinks/week for female participants or 14 drinks/week for male participants (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening.
• Excessive caffeine use (>500 mg/day, or exceeding 5 cups [1 cup= 8 ounces] of coffee/day)
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to Screening (participants may not donate blood any time during the study, through the final study day)
• Presence of any condition that, in the opinion of the Investigator, compromises participant safety or data integrity or the participant's ability to complete study days.
• More than 1-day a week of intentional exercise

Excluded medications include, but are not limited to:

• Any prescription medication or other drug that may influence metabolism (e.g. diet/weight-loss medication, psychiatric medications, corticosteroids, or other medications at the discretion of the PI and/or study team)
• Medications that strongly impact bleeding, clotting, bruising, or platelets (e.g. blood thinner prescription medications)
• Recent change to medication and/or dosing in the past 3 months
• Chronic use of aspirin or other non-steroidal anti-inflammatory drugs, including COX-2 inhibitors