Effects of Pioglitazone on Exogenous Carbohydrate Oxidation During Steady-State Exercise at High Altitude

This randomized crossover placebo controlled double blinded study will examine substrate oxidation and glucose kinetic responses to ingesting supplemental carbohydrate (glucose) during metabolically-matched, steady-state exercise with acute (~5 h) exposure to HA (460 mmHg) after short-term (5 days) use of Pioglitazone (HA+PIO), or matched placebo (HA+PLA). Eight healthy, recreationally active males between the ages of 18-39 yrs will be enrolled. Following a 48-hr muscle glycogen normalization period, volunteers will complete 80-min of metabolically-matched, steady-state (same absolute workload corresponding to ~55 ± 5% of V̇O2peak at HA) exercise on a treadmill, and consume 145 g of glucose (1.8 g/min) with HA+PIO and HA+PLA. A dual glucose tracer (13C-glucose oral ingestion and [6,6-2H2]-glucose primed, continuous infusion) technique and indirect calorimetry will be used to analyze endogenous and exogenous glucose oxidation, as well as glucose rate of appearance (Ra), disappearance (Rd), and MCR. Serial blood samples will be collected during each trial to assess endocrine and circulating substrate responses to exercise, carbohydrate, and hypoxia, with or without PIO. Isotope methodology and aerobic exercise protocols will be identical to our previous work (3, 4), allowing comparison of outcomes across studies. All trials will be conducted in the USARIEM hypobaric/hypoxic chamber and be separated by a minimum 10-d washout period.

Inclusion criteria

• Men aged 18 - 39 years
• Born at altitudes less than 2,100 m
• Physically active (exercise minimum 2 days per week)
• Have supervisor approval (permanent party military and civilians)
• Willing to refrain from alcohol, smokeless nicotine products and dietary supplement use during study periods
• Fully vaccinated against COVID-19

Exclusion criteria

• Born at altitudes greater than 2,100 m
• Musculoskeletal injuries that compromise exercise capability
• Metabolic or cardiovascular abnormalities, or gastrointestinal disorders
• Taking medication that affects macronutrient metabolism and/or the ability to participate in strenuous exercise
• Living in areas that are more than 1,200 m, or traveled to areas that are more than 1,200 m for five days or more within 2 months of data collection
• Evidence of apnea or other sleeping disorders
• Prior diagnosis of high altitude pulmonary edema or high altitude cerebral edema
• Presence of asthma or respiratory tract infections
• Smoking or vaping
• Taking medications that interfere with oxygen delivery and transport
• Anemia (HCT <38% and HBG <12.5 g/dL) and Sickle Cell Anemia/Trait
• Blood donation within 8 weeks of beginning the study
• Unwilling or unable to consume study diets or foods provided due to personal preference, dietary restrictions, and/or food allergies
• Unwilling or unable to adhere to study physical restrictions