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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05147116

Enrollment

Registered

2021-12-07

Start date

2022-02-17

Completion date

2023-01-30

Last updated

2025-01-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type2 Diabetes

Brief summary

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

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.

Interventions

OTHERSleeping in a tent

Participants will spend 10 consecutive nights of sleeping in a tent

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

OTHER

Masking

SINGLE (Subject)

Masking description

Participants will undergo both the hypoxia and sham conditions and will be blinded to the conditions in which they are in.

Intervention model description

Single blind, randomized, balanced, crossover design study

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
Δ Mean AUC (Area Under the Curve) Plasma [Glucose]	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.	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.

Secondary

Measure	Time frame	Description
Δ Body Mass	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.	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.
Δ Total Minutes of Physical Activity (Light, Moderate, Moderate to Vigorous Physical Activity).	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.	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.
Δ Sleep Efficiency (Percentage of Time Spent Asleep While in Bed)	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.	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.
Δ IL-6	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.	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.
Δ TNFɑ	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.	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.

Countries

United Kingdom

Participant flow

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Total	—
Age, Continuous	64 years STANDARD_DEVIATION 9	—
BMI	29.7 kg/m2 STANDARD_DEVIATION 3.9	—
DBP	80 mmHg STANDARD_DEVIATION 11	—
HbA1c	61.1 mmol/mol STANDARD_DEVIATION 14.1	—
Height	1.72 m STANDARD_DEVIATION 0.09	—
Mass	87.5 kg STANDARD_DEVIATION 14.6	—
Race and Ethnicity Not Collected	—	— Participants
Region of Enrollment United Kingdom	13 Participants	—
SBP	132 mmHg STANDARD_DEVIATION 13	—
Sex: Female, Male Female	4 Participants	—
Sex: Female, Male Male	9 Participants	—
T2DM duration	9.3 years STANDARD_DEVIATION 7	—

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 13	0 / 13
other Total, other adverse events	0 / 13	0 / 13
serious Total, serious adverse events	0 / 13	0 / 13

Outcome results

Primary

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.