Clinical trial NCT05422430: Rebreathing-induced Hypoxia and Glucose Levels
Official title: Effect of Rebreathing-induced Hypoxia on the Response to an Oral Glucose Tolerance Test
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hypoxemia
Lead sponsor: University of Texas at Austin
Sponsor class: OTHER
First posted: 2022-06-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in plasma glucose levels
timeFrame: Collected at min 0, 30, 60, 90 and 120 minutes of the oral glucose tolerance test
Secondary outcomes:
Other outcomes:
Locations:
city: Austin
country: United States
facility: The Unviersity of Texas at Austin
state: Texas
Study officials:
affiliation: UT Austin
name: Sophie Lalande
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Newhouse LP, Joyner MJ, Curry TB, Laurenti MC, Man CD, Cobelli C, Vella A, Limberg JK. Three hours of intermittent hypoxia increases circulating glucose levels in healthy adults. Physiol Rep. 2017 Jan;5(1):e13106. doi: 10.14814/phy2.13106. Epub 2017 Jan 13.
citation: Duennwald T, Gatterer H, Groop PH, Burtscher M, Bernardi L. Effects of a single bout of interval hypoxia on cardiorespiratory control and blood glucose in patients with type 2 diabetes. Diabetes Care. 2013 Aug;36(8):2183-9. doi: 10.2337/dc12-2113. Epub 2013 Mar 27.
citation: Costalat G, Lemaitre F, Tobin B, Renshaw G. Intermittent hypoxia revisited: a promising non-pharmaceutical strategy to reduce cardio-metabolic risk factors? Sleep Breath. 2018 Mar;22(1):267-271. doi: 10.1007/s11325-017-1459-8. Epub 2017 Feb 2.
citation: de Bruijn R, Richardson M, Schagatay E. Increased erythropoietin concentration after repeated apneas in humans. Eur J Appl Physiol. 2008 Mar;102(5):609-13. doi: 10.1007/s00421-007-0639-9. Epub 2007 Dec 19.