Effects of Pioglitazone on Exogenous Carbohydrate Oxidation During Steady-State Exercise at High Altitude
Status:
Completed
Trial end date:
2023-07-01
Target enrollment:
Participant gender:
Summary
Apparent hypoxia-induced insulin insensitivity along with alterations in glucose kinetics
suggests reduction in glucose uptake by the peripheral tissue is a primary factor
contributing to reductions in exogenous glucose oxidation at HA. As such, the primary
objective of this study is to determine the ability of an insulin sensitizer (Pioglitazone,
PIO) to enhance exogenous glucose oxidation and metabolic clearance rate during
metabolically-matched, steady-state exercise during acute HA exposure compared to placebo
(PLA) in native lowlanders. Secondary objective of this study will be to assess the impact of
PIO on markers of inflammation and iron status compared to PLA. This randomized crossover
placebo control 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, or 4300m, barometric
pressure similar to Pike's Peak) after receiving PIO (HA+PIO), or after receiving a matched
placebo (HA+PLA). Eight healthy, recreationally active males between the ages of 18-39 yrs
will be required to complete this study. Following a 4 day glycogen normalization period
receiving PIO or PLA daily, volunteers will complete two 80-min trials, performing
metabolically-matched, steady-state aerobic (same absolute workload corresponding to ~55 ± 5%
of V̇O2peak at HA) exercise on a treadmill, and consuming 145 g of glucose (1.8 g/min); one
trial with HA+PIO and the other with 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 selectively analyze endogenous and exogenous glucose oxidation,
as well as glucose rate of appearance (Ra), disappearance (Rd) and metabolic clearance rate
(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.
All trials will occur at the same time of day in the USARIEM hypobaric/hypoxic chamber and be
separated by a minimum 10-d washout period. The primary risks associated with this study
include those associated with acute hypobaric hypoxia, exercise, and blood sampling.
Phase:
Phase 4
Details
Lead Sponsor:
United States Army Research Institute of Environmental Medicine