The Effect of Hypoxia on Type 2 Diabetes and Weight Loss

Study Overview
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Brief Summary
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The number of people with type 2 diabetes mellitus (T2DM) continuing to rise, this pandemic is expected to reach 700 million people by 2045. T2DM is a metabolic condition characterized by progressive insulin resistance and chronic hyperglycemia (high blood glucose concentrations). Hyperglycaemia increases the risk of both micro- and macrovascular damage, whilst interventions that reduce blood glucose mitigate this risk. Weight loss, achieved through exercise and dietary modification, is effective at reducing hyperglycaemia. However, despite the clear benefits of exercise and weight loss, diverse psychological, sociological and logistical factors can make it difficult for some individuals with T2DM to initiate, or adhere to, these lifestyle interventions. Alternative approaches to treatment are therefore required. The purpose of this research project is to investigate whether 10-days of overnight exposure to moderate hypoxia is effective at improving blood glucose control in individuals with T2DM and to provide insight into the physiological mechanisms responsible for any beneficial effects.

Detailed Description
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Type 2 diabetes mellitus (T2DM) is a metabolic condition characterized by progressive insulin resistance and chronic hyperglycemia (high blood glucose concentrations). Hyperglycaemia increases the risk of both micro- and macrovascular damage, whilst interventions that reduce blood glucose mitigate this risk. Weight loss, achieved through exercise and dietary modification, is effective at reducing hyperglycaemia. However, despite the clear benefits of exercise and weight loss, diverse psychological, sociological and logistical factors can make it difficult for some individuals with T2DM to initiate, or adhere to, these lifestyle interventions. With the number of people with T2DM continuing to rise, this pandemic is expected to reach 700 million people by 2045. Thus, there is a clear need for cost-effective interventions that can effectively improve glycaemic control in people with T2DM and which people will adhere to. A simple exposure to a lowered concentration of inspired oxygen (i.e. hypoxia) may represent such an intervention. In addition to the beneficial effects on glucose homeostasis that have been reported following a single acute hypoxic exposure, repeated intermittent, or continuous, hypoxic exposure may also have therapeutic potential in individuals with T2DM. In rodent models, daily hypoxic exposures returned fasting blood [glucose] to normal levels and increased glucose transporter 4 translocation in mice with T2DM. Similar effects on glucose homeostasis have been shown in overweight humans and those with insulin resistance, (during intermittent hypoxic training) which was explained, at least in part, by reduction in body mass (  1.2 kg). The mechanisms underpinning the improved glycaemic control in response to hypoxia are likely multifactorial. Specifically, our objective is to assess a novel therapeutic intervention for the treatment and management of T2DM which overcomes many of the barriers to uptake and adherence that are associated with some lifestyle interventions such as exercise and weight loss.

Official Title
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The Effects of Repeated Moderate Overnight Normobaric Hypoxia on Glucose Homeostasis, Appetite, Body Weight, Inflammation and Oxidative Stress in Individuals With Type 2 Diabetes Mellitus

Conditions
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Type2 Diabetes

Intervention / Treatment
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* Other: Sleeping in a tent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and post-menopausal women with T2DM (as diagnosed with the WHO criteria). Exclusion Criteria: Individuals with contraindications to hypoxic exposure (e.g. obstructive sleep apnoea, extant cardiac conditions or on medications such as SGLT2 inhibitors or PPAR antagonists).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single blind, randomized, balanced, crossover design study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypoxia - 15% O2<br>Participants will sleep in a tent for 10 nights. | Other: Sleeping in a tent<br>* Participants will spend 10 consecutive nights of sleeping in a tent<br>|
| Sham Comparator: Sham - room air 21% 02<br>Participants will sleep in a tent for 10 nights. | Other: Sleeping in a tent<br>* Participants will spend 10 consecutive nights of sleeping in a tent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean AUC (Area Under the Curve) Plasma [Glucose] | Does 10 days of overnight hypoxia change AUC during a oral glucose tolerance test. Units for AUC are AU (arbitrary units) which have been derived from the trapezoidal method and have been published as such. Trapezoidal method: AUC = Δx ((y0/2)+y1+y2+y3+...+(yn/2)). | Assessed on all outcome visits (2,3,4&5) across an 8 week period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduce body mass | Does 10 days of overnight hypoxia change body mass - assessed via DXA. | Assessed on all outcome visits (2,3,4&5) across an 8 week period. | 
| Redox balance (via ELISA) | Does 10 days of overnight hypoxia change redox balance (IL-6, nitrite, TNFɑ & SOD) | Assessed on all outcome visits (2,3,4&5) across an 8 week period. | 
| Total minutes of physical activity (light, moderate, moderate to vigorous physical activity). | Does 10 days of overnight hypoxia change physical activity - assessed via wrist worn accelerometery | Assessed on all outcome visits (2,3,4&5) across an 8 week period. | 
| Sleep efficiency (time in bed + time asleep) | Does 10 days of overnight hypoxia change sleep - assessed via wrist worn accelerometery | Assessed on all outcome visits (2,3,4&5) across an 8 week period. |