Overview

The purpose of this study is to help us better understand how plasma ketones respond to a low-carb diet when combined with an SGLT2 inhibitor.

Eligibility

Inclusion criteria:

• M/F
• Age 18-60 years
• Weight stable (+/- 3 kg over past 6 months)
• Body mass index (BMI): 21-35 kg/m2
• Otherwise healthy, as determined by medical history and laboratory tests
• 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

Exclusion criteria:

        Acute or chronic medical conditions or medication that would contraindicate the
        participation in the research testing or could potentially affect metabolic function
        including, but not limited to:
          1. History or presence of cardiovascular disease (unstable angina, myocardial infarction
             or coronary revascularization within 6 months, presence of cardiac pacemaker,
             implanted cardiac defibrillator)
          2. Diagnosis of type 1 or type 2 diabetes mellitus, or prior diabetic ketoacidosis
          3. Blood pressure > 140/90 mm Hg
          4. Bleeding and clotting disorders
          5. Acute or chronic infection (such as TB, HIV or Hepatitis)
          6. Renal insufficiency (eGFR<60), nephritis, or chronic kidney disease
          7. Thyroid dysfunction (suppressed TSH, elevated TSH <10 µIU/ml if symptomatic or
             elevated TSH >10 µIU/ml if asymptomatic)
          8. Liver disease (liver function tests > 2 x normal; including NASH/NAFLD)
          9. 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)
         10. Past or present history of eating disorder (including binge eating)
         11. 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
         12. Unwilling or unable to eat the foods provided in the study diet
         13. A positive urine drug test for illicit drugs.
         14. 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)
         15. Pregnant or nursing females or females less than 6 months postpartum from the
             scheduled date of collection
         16. Regular smoking or regular nicotine use of any kind including chewing tobacco, snuff
             and vaping
         17. 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.
         18. 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.
         19. Donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the
             pretrial (screening) visit.
         20. Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women)
        Excluded medications include, but are not limited to:
          1. 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)
          2. Anti-diabetic agents
          3. Recent change to medication and/or dosing in the past 3 months
          4. Blood thinner prescription medication
          5. Chronic use of aspirin or other non-steroidal anti-inflammatory drugs, including COX-2
             inhibitors (a single aspirin daily if prescribed for cardioprotection will be allowed
             as will occasional use of aspirin and other non-steroidal drugs, provided that they
             are used for < 3 consecutive days and not during the period of metabolic testing)