Glucose Metabolism, High Altitude
Conditions
Brief summary
Recent studies have reported that oxidation of exogenous carbohydrate is reduced under acute hypobaric hypoxic (high altitude; HA) conditions compared to normoxia (sea level; SL) in native lowlanders. However, the mechanisms by which HA suppresses exogenous carbohydrate oxidation are not known. This study will seek to confirm that acute HA exposure decreases exogenous carbohydrate oxidation during steady-state aerobic exercise compared to SL, and explore if the mechanism inhibiting plasma glucose uptake is insulin dependent or independent.
Detailed description
This randomized crossover study will examine substrate metabolic responses to ingesting supplemental carbohydrate during steady-state aerobic-type exercise at sea level (SL) and following acute (\ 5 h) exposure to HA (4,300 m) conditions in 10 healthy, recreationally active adults between the ages of 18-39 yrs. Following a 48-hr muscle glycogen normalization period, volunteers will complete 80-min of metabolically-matched, steady-state aerobic exercise on a treadmill, and consume 145 g of glucose (1.8 g·min-1) at SL and HA. Treadmill exercise will be performed at the same absolute workload, with speed and grade being the same at SL and HA to induce the same absolute workload between phases. SL and HA trials will occur in the US Army Research Institute of Environmental Medicine (USARIEM) hypobaric chamber and will be separated by a minimum 7-d washout period between each protocol day. 6-6-\[2H2\] glucose will be used as a tracer to assess glucose turnover. Indirect calorimetry, breath sampling for 13C/12C expired in CO2, and urine collections will be used to determine carbohydrate, fat, and protein oxidation during exercise at SL and HA. Serial blood draws will be collected during each trial to assess endocrine and circulating substrate responses to exercise, carbohydrate, and hypoxia. Muscle biopsies will be collected before and after steady-state exercise to examine intramuscular glucose transport expression and translocation, glycogen status, and activity enzyme intermediates in aerobic and anaerobic energy metabolism.
Interventions
OTHERSea Level
Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL
OTHERHigh Altitude
Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA
Sponsors
University of Arkansas
United States Army Research Institute of Environmental Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
* Men aged 18 - 39 years * Born at altitudes less than 2,100 m (\ 7,000 feet; Examples include Santa Fe, New Mexico; Laramie, Wyoming; Etc.) * Physically active based on assessment of physical activity history (2-4 days per week aerobic and/or resistance exercise) * Have supervisor approval (permanent party military and civilians) * Willing to refrain from alcohol, smokeless nicotine products and dietary supplement use during study periods * Refrain from taking any nonsteroidal anti-inflammatory drugs (NSAIDs; e.g. aspirin, Advil®, Aleve®, Naprosyn®, or any aspirin-containing product) for 10 days before and at least 5 days AFTER each muscle biopsy. (\*Tylenol® or acetaminophen is ok to use if needed for discomfort)
Exclusion criteria
* Born at altitudes greater than 2,100 m (\ 7,000 feet; Examples include Santa Fe, New Mexico; Laramie, Wyoming; Etc.) * Living in areas that are more than 1,200 m (\ 4,000 feet), or have traveled to areas that are more than 1,200 m for five days or more within the last 2 months (Examples include Ft. Huachuca, Arizona; Lima, Peru; Feldberg, Germany, Etc.) * Musculoskeletal injuries that compromise exercise capability * Metabolic or cardiovascular abnormalities (determined by resting ECG), gastrointestinal disorders (e.g., kidney disease, diabetes, cardiovascular disease, etc.) * Medication that affects macronutrient metabolism (i.e., diabetes medications, statins, corticosteroids, etc) and/or the ability to participate in strenuous exercise * Evidence of apnea or other sleeping disorders * Prior diagnosis of high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE) * Presence of asthma or respiratory tract infections (\< 1 month prior) * Allergies or intolerance to foods (including but not limited to lactose intolerance/milk allergy), vegetarian practices, or medications (including, but not limited to, lidocaine ) to be utilized in the study * Smoking or vaping * History of complications with lidocaine * Taking medications that interfere with oxygen delivery and transport (Includes sedatives, sleeping aids, tranquilizers and/or any medication that depresses ventilation, diuretics, alpha and beta blockers) * Evidence of any physical, mental, and/or medical conditions that would make the proposed studies relatively more hazardous as determined by the Office of Medical Support and Oversight * Present condition of alcoholism, anabolic steroids, or other substance abuse issues * Anemia (hematocrit \<38% and hemoglobin \<12.5 g/dL) and Sickle Cell Anemia/Trait * Abnormal prothrombin time (PT)/ partial thromboplastin time (PTT) test or problems with blood clotting * Blood donation within 8 weeks of beginning the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Exogenous Carbohydrate Oxidation | 7 hours | Use indirect calorimetry and stable isotope methodologies to measure if acute HA exposure changes the rate of exogenous carbohydrate oxidation during steady-state aerobic exercise compared to SL |
| Rate of Glucose Turnover | 7 hours | Use stable isotope methodologies to measure if acute HA exposure changes the rate of glucose turnover during steady-state aerobic exercise compared to SL |
Countries
United States
Participant flow
Pre-assignment details
No significant events happen prior to assignment of participants to a study arm.
Participants by arm
| Arm | Count |
|---|---|
| Sea Level First, Then High Altitude Carbohydrate metabolism measured at SL, then HA
Sea Level: Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL
7 day washout
High Altitude: Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA | 4 |
| High Altitude, Then Sea Level Carbohydrate metabolism measured at HA, then SL
High Altitude: Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA
7 day washout
Sea Level: Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL | 6 |
| Total | 10 |
Baseline characteristics
| Characteristic | Sea Level First, Then High Altitude | High Altitude, Then Sea Level | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 10 Participants |
| Region of Enrollment United States | 4 participants | 6 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 10 |
| other Total, other adverse events | 0 / 8 | 0 / 10 |
| serious Total, serious adverse events | 0 / 8 | 0 / 10 |
Outcome results
Primary
Rate of Exogenous Carbohydrate Oxidation
Use indirect calorimetry and stable isotope methodologies to measure if acute HA exposure changes the rate of exogenous carbohydrate oxidation during steady-state aerobic exercise compared to SL
Time frame: 7 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sea Level | Rate of Exogenous Carbohydrate Oxidation | 0.44 g/min | Standard Deviation 0.05 |
| High Altitude | Rate of Exogenous Carbohydrate Oxidation | 0.35 g/min | Standard Deviation 0.07 |
Primary
Rate of Glucose Turnover
Use stable isotope methodologies to measure if acute HA exposure changes the rate of glucose turnover during steady-state aerobic exercise compared to SL
Time frame: 7 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sea Level | Rate of Glucose Turnover | Glucose Rate of Disappearance | 14.3 mg/kg/min | Standard Deviation 2 |
| Sea Level | Rate of Glucose Turnover | Metabolic Clearance Rate | 12.1 mg/kg/min | Standard Deviation 2.3 |
| High Altitude | Rate of Glucose Turnover | Glucose Rate of Disappearance | 12.7 mg/kg/min | Standard Deviation 1.7 |
| High Altitude | Rate of Glucose Turnover | Metabolic Clearance Rate | 8.9 mg/kg/min | Standard Deviation 1.8 |