Hypoxic Exercise and Glucose Metabolism
Condition: Obesity; Insulin Resistance; Impaired Glucose Tolerance in Obese
MeSH terms: Insulin Resistance; Glucose Intolerance
Study type: Interventional

Summary: 
      The obesity epidemic calls for new therapeutic opportunities to prevent and treat obesity and
      its comorbidities amongst which are insulin resistance and cardiovascular diseases. Recent
      evidence suggests that tissue oxygenation plays an important role in cardiometabolic health.
      Remarkably, individuals residing at high altitude (hypobaric hypoxia) are less prone to
      develop type 2 diabetes mellitus as compared to individuals living at sea-level (normobaric
      normoxia). Furthermore, there is evidence to suggest that normobaric hypoxia exposure may
      improve glucose homeostasis and insulin sensitivity in both rodents and humans.

      The level of physical activity is an important determinant of insulin sensitivity and glucose
      homeostasis. It is well established that performing physical activity improves glucose uptake
      in the short term, and glycemic control in the long term. Interestingly, recent studies have
      demonstrated that an acute bout of exercise under hypoxic conditions (inhalation of air
      containing less oxygen) may lead to a more pronounced improvement in plasma glucose
      concentrations and/or insulin sensitivity as compared to normoxic exercise. However, the
      effects of repeated hypoxic exercise bouts on glucose profile throughout the day (i.e. 24h
      continuous glucose monitoring) remain elusive. In the present randomized, placebo-controlled,
      single-blind, cross-over study study, the investigators will investigate the effects of
      exercise under mild normobaric hypoxic conditions (FiO2, 15%) for 4 consecutive days (2 x
      30-min cycling session at 50% WMAX) on postprandial substrate metabolism and 24h-glucose
      level in overweight/obese subjects with impaired glucose tolerance. The investigators
      hypothesize that 4 consecutive days of exposure to mild hypoxia while performing moderate
      intensity exercise improves glucose homeostasis in overweight and obese individuals with
      impaired glucose homeostasis.
    

Detailed description: 
      In the present randomized, single-blind, placebo-controlled cross-over study, subjects will
      be exposed to normobaric 1) mild hypoxia (oxygen level: 15%) and 2) normoxia (oxygen level:
      21%) during exercise (2 x 30min/day on a cycle ergometer) of the same relative exercise
      intensity (equal to 50%WMAX under normoxic conditions) for 4 consecutive days. Subjects will
      be randomly assigned to each condition (computer-generated randomization plan; block size,
      n=4), separated by a washout period (3-6 weeks). To accomplish this, subjects will exercise
      in an oxygen chamber in which oxygen concentration of the ambient air and, as such, oxygen
      levels can be tightly controlled and monitored. Subjects will cycle two times a day for 30
      minutes at 50% WMAX, determined by an incremental workload test. Since we will allow 5-10 min
      for subjects to get ready to start the 30-min exercise session, and take into account a 5-min
      cooling down period before leaving the hypoxic room again, subjects will be in the room for
      45 min for each session.

      After initial screening, subjects are asked to visit the university for two periods of 5
      consecutive days each with a washout period of 3-6 weeks. During the first 4 days (time
      investment: 4.5 hours/day), subjects will be undergoing the exercise regimen, as described
      above.

        -  At day 1, on the first morning of each regimen, a glucose sensor (Enlite Glucose Sensor
           MiniMed; Medtronic). The sensor will be inserted subcutaneously, will be inserted
           subcutaneously, at 5 cm from the umbilicus, on the right side of the abdomen, and will
           be connected to a continuous glucose monitor (iPro2 Professional CGM MiniMed; Medtronic,
           Northridge, CA, USA). The sensor will remain inserted throughout the study (days 1-5).
           Furthermore, a physical activity monitor (ActivPAL3 micro monitor) will be applied at
           the same moment, to monitor physical activity of participants. At the end of day 5, the
           glucose sensor, and the physical activity monitor will be removed.

        -  At days 1-5 (time investment: 4.5 hours), fasting blood samples will be collected to
           determine plasma metabolites and inflammatory markers, and blood pressure and body
           weight will be monitored.

        -  At day 5 (time investment: 8 hours), a mixed liquid meal challenge will be performed to
           determine fasting and postprandial metabolite concentrations, and substrate oxidation
           (using indirect calorimetry). A skeletal muscle biopsy (m. vastus lateralis) will be
           collected under fasting conditions. Moreover, HOMA-IR will be used to estimate insulin
           resistance, using fasting plasma glucose and insulin values measured on the day after
           completion of the 4 day regimen.

      After initial screening, the assessment of basal metabolic rate (BMR) and the incremental
      workload test (to determine the maximal workload, WMAX), subjects will have to invest
      approximately 52 hours.
    

Intervention name(s): Moderate intensity exercise under mild normobaric hypoxia and normoxia
Intervention type(s): Other
Intervention description(s): The participant will perform the exercise interventions consisting of cycling at the heart rate corresponding with 50%WMAX (normoxia) or heart rate corresponding with 50% WMAX (hypoxia) for 30 minutes, twice a day, for 4 consecutive days. 24h glucose concentration will be monitored continuously.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Metabolism; Hypoxia; Glucose metabolism