Hypoxic Exercise and Glucose Metabolism

NCT04280991 | Completed

• 1 other identifier: NL68218.068.18 / METC 18-059
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity; Insulin Resistance; Impaired Glucose Tolerance in Obese

Keywords

Metabolism; Hypoxia; Glucose metabolism

Outcome Measures

Primary Outcomes (1)

• Average 24 hour glucose concentration (at day 4)

  Glucose concentration will be measured in the interstitial fluid of the subcutaneous adipose tissue every 5 min using a glucose sensor (Enlite Glucose Sensor MiniMed; Medtronic) (iPro2 Professional CGM MiniMed; Medtronic, Northridge, CA, USA), which 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 cumulative effects of the 4 day exercise regimens will be determined using the average 24h glucose levels collected on day 4.

  Change of average glucose concentration compared to moderate intensity exercise under normoxia (21% oxygen) at day 4

Secondary Outcomes (17)

• Glycemic variability over 24 hours

  Change of glycemic variability over 24 hours compared to moderate intensity exercise under normoxia (21% oxygen) at day 2, 3, 4 and 5

• Time in hyper/hypoglycaemia

  Change of time spent in hyper/hypoglycemia compared to moderate intensity exercise under normoxia (21% oxygen) at day 2, 3, 4 and 5

• Energy expenditure

  Change of energy expenditure compared to moderate intensity exercise under normoxia (21% oxygen) at day 5 during the meal-test

• Substrate oxidation

  Change of substrate oxidation compared to moderate intensity exercise under normoxia (21% oxygen) at day 5 during the meal-test

• Systolic and diastolic blood pressure

  Change of systolic and diastolic blood pressure compared to moderate intensity exercise under normoxia (21% oxygen) at day 1, 2, 3, 4 and 5 under fasting conditions.

Study Arms (2)

Moderate intensity exercise under mild normobaric hypoxia

EXPERIMENTAL

The participants will perform moderate intensity exercise at heart rate corresponding with 50%WMAX (determined during maximal workload test) under mild normobaric hypoxia (FiO2: 15%), two times 30 minutes per day for 4 consecutive days on a cycle ergometer. 24h glucose concentration will be monitored continuously. Afterwards, a meal test challenge will be performed at day 5 to determine fasting/postprandial substrate oxidation.

Other: Moderate intensity exercise under mild normobaric hypoxia and normoxia

Moderate intensity exercise under normoxia

PLACEBO COMPARATOR

The participants will perform moderate intensity exercise at 50% WMAX (determined during maximal workload test) under normoxia (FiO2: 21%) two times 30 minutes per day for 4 consecutive days on a cycle ergometer. 24h glucose concentration will be monitored continuously. Afterwards, a meal test challenge test will be performed at day 5 to determine fasting/postprandial substrate oxidation.

Other: Moderate intensity exercise under mild normobaric hypoxia and normoxia

Interventions

Moderate intensity exercise under mild normobaric hypoxia and normoxia OTHER

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.

Moderate intensity exercise under mild normobaric hypoxia; Moderate intensity exercise under normoxia

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• overweight or obese (BMI \>28 kg/m2)
• impaired glucose tolerance (2h glucose: \>7.8 - 11.1 mmol/L)
• subjects have to be weight-stable for at least 3 months prior to participation (no change in bodyweight: \<3kg change)

You may not qualify if:

• cardiovascular disease (determined by questionnaire, blood pressure (Subjects with moderate to severe hypertension (grade 2 or 3 based on WHO criteria)
• type 2 diabetes mellitus
• cancer
• asthma
• bronchitis
• chronic obstructive pulmonary disease
• lung fibrosis
• obstructive sleep apnea
• use of oxygen at home situation
• resting SpO2 ≤93%
• abnormal pre-bronchodilator forced expiratory volume (FEV1) and forced vital capacity (FVC)
• liver or kidney malfunction (determined based on ALAT and creatinine levels, respectively)
• disease with a life expectancy shorter then 5 years
• lactose intolerance
• abuse of products (alcohol consumption \> 15 units/week)

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Department of Human Biology, Maastricht University Medical Centre

Maastricht, 6200MD, Netherlands

Location

MeSH Terms

Conditions

Obesity; Insulin Resistance; Hypoxia

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Signs and Symptoms, Respiratory

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2019
• First Posted: February 21, 2020
• Study Start: July 22, 2019
• Primary Completion: December 18, 2020
• Study Completion: December 18, 2020
• Last Updated: November 1, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)