Rebreathing-induced Hypoxia and Glucose Levels

Study Overview
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Brief Summary
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The aim of this research project is to determine the effect of repeated maximal voluntary apneas on glucose uptake during an oral glucose tolerance test in healthy individuals, individuals with prediabetes and patients with type 2 diabetes.

Detailed Description
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It is predicted that 1 in 3 adults will develop diabetes by 2050, implying that a large percentage of the population will become at high risk for cardiovascular disease, the most common cause of death in patients with type 2 diabetes. While regular exercise reduces insulin resistance and the elevated glucose levels associated with type 2 diabetes, only 28% of the adult population with diabetes meet physical activity recommendations. There is therefore an urgent need to identify alternative, non-pharmacological interventions that prevent and treat type 2 diabetes. A reduced oxygen availability, or hypoxia, is widely implicated in the development of insulin resistance. Paradoxically, hypoxia also triggers glucose uptake independently from the actions of insulin. Indeed, breathing low levels of oxygen stimulates glucose uptake in skeletal muscles by activating 5' adenosine monophosphate-activated protein kinase (AMPK). Discrepancies on the effect of hypoxia on glucose homeostasis may be attributed to the duration and type (nocturnal vs. diurnal) of hypoxic exposure. For example, the many severe hypoxic bouts associated with obstructive sleep apnea are associated with a worsened glycemic control while hypoxic exposure consisting of a limited number of short bouts of moderate hypoxia improves glycemic control. Therefore, an intervention that can induce brief hypoxic conditions, as observed through a reduced fraction of inspired oxygen, could attenuate the postprandial increase in glucose levels. Fraction of inspired oxygen can be reduced by rebreathing into a low-volume closed-circuit system containing ambient air for few minutes. Thus, the aim of this research project is to determine the effect of few bouts of rebreathing-induced hypoxia on glucose uptake during an oral glucose tolerance test in healthy individuals, individuals with prediabetes and patients with type 2 diabetes. If our expected outcomes are met, our next step will be to determine whether repeated sessions of rebreathing-induced hypoxia (5 sessions per week over 1-3 months) results in improvements in glycemic control.

Official Title
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Effect of Rebreathing-induced Hypoxia on the Response to an Oral Glucose Tolerance Test

Conditions
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Hypoxemia

Intervention / Treatment
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* Behavioral: Rebreathing-induced hypoxia
* Behavioral: Spontaneous breathing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 to 80 years old Exclusion Criteria: Have uncontrolled stage 2 hypertension (˃140/90 mmHg) Are smokers Are pregnant Have a history of cardiovascular disease or indication of cardiovascular disease such as myocardial infarction, left ventricular hypertrophy, ischemic heart disease (or prior ischemia), stroke, and/or other vascular disease Have a history of lung disease Are taking insulin or more than one antihypertensive medication Have poorly controlled diabetes: HbA1c levels ˃ 9% Have been previously diagnosed with diabetic complications (nephropathy, neuropathy, retinopathy) by their family doctor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Spontaneous breathing<br>Participants will be spontaneously breathing during an oral glucose tolerance test. | Behavioral: Spontaneous breathing<br>* Participants will be spontaneously breathing during an oral glucose tolerance test.<br>|
| Experimental: Rebreathing-induced hypoxia<br>Participants will rebreathe room air from a low-volume closed-circuit system for a period of 2 minutes. | Behavioral: Rebreathing-induced hypoxia<br>* Participants will rebreathe room air from a low-volume closed-circuit system for a period of 2 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma glucose levels | Plasma glucose levels obtained from a venous catheter during a 2-hour oral glucose tolerance test | Collected at min 0, 30, 60, 90 and 120 minutes of the oral glucose tolerance test |