High Altitude and Exogenous Carbohydrate Oxidation

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Mechanistic Effects of Acute Hypobaric Hypoxia on Exogenous Carbohydrate Utilization During Steady-state Aerobic Exercise

Conditions
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Glucose Metabolism, High Altitude

Intervention / Treatment
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* Other: Sea Level
* Other: High Altitude


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sea Level<br>Carbohydrate metabolism measured at SL | Other: Sea Level<br>* Carbohydrate consumed at 1.8 g/min during treadmill exercise at SL<br>|
| Experimental: High Altitude<br>Carbohydrate metabolism measured at HA | Other: High Altitude<br>* Carbohydrate consumed at 1.8 g/min during treadmill exercise at HA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 7 hours | 
| 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 | 7 hours |