The Effect of Hypoxia on Type 2 Diabetes and Weight Loss

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

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.

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes
• Intervention / Treatment: Other: Sleeping in a tent

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO1 2ER
      • Anthony Shepherd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypoxia 15% O2; Participants will sleep in a tent for 10 nights in hypoxia.	Other: Sleeping in a tent; Participants will spend 10 consecutive nights of sleeping in a tent
Sham Comparator: Sham (room air) 21% 02; Participants will sleep in a tent for 10 nights in normoxia.	Other: Sleeping in a tent; Participants will spend 10 consecutive nights of sleeping in a tent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Δ 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)). Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.	Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Δ Body Mass	Does 10 days of overnight hypoxia change body mass - assessed via DXA. Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.	Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.
Δ 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 accelerometry. Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.	Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.
Δ Sleep Efficiency (Percentage of Time Spent Asleep While in Bed)	Does 10 days of overnight hypoxia change sleep - assessed via wrist worn accelerometry. Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.	Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.
Δ IL-6	Does 10 days of overnight hypoxia change IL-6. Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.	Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.
Δ TNFɑ	Does 10 days of overnight hypoxia change TNFɑ. Due to the study design being a randomised crossover control trial, the results for visits 2 and 3, and, 4 and 5, have been unrandomized into the delta of pre-post hypoxia and sham interventions. Visits 2 and 4 represent baseline compared to visit 3 and 5 respectively.	Assessed on all outcome visits (2,3,4&5) across an 8 week period. Δ from pre-post hypoxia visits are calculated and compared to Δ from pre-post sham visits.

Collaborators and Investigators

• Sponsor: University of Portsmouth
• Collaborators: University College, London; University of Cambridge; Portsmouth Hospitals NHS Trust; Bournemouth University
• Investigators: Principal Investigator: Anthony Shepherd, PhD, University of Portsmouth

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2022
• Primary Completion (Actual): January 30, 2023
• Study Completion (Actual): January 30, 2023

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 6, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Signs and Symptoms, Respiratory; Diabetes Mellitus, Type 2; Diabetes Mellitus; Hypoxia
• Other Study ID Numbers: 009AS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The individual data set that is used for statistical analysis will be uploaded to our university repository and a DOI added to the paper upon publication.
• IPD Sharing Time Frame: Upon publication - no plan to remove.
• IPD Sharing Access Criteria: Dataset is open access from the URL below.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No