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Hyperbaric oxygen rapidly improves tissue-specific insulin sensitivity and mitochondrial capacity in humans with type 2 diabetes: a randomised placebo-controlled crossover trial.


ABSTRACT:

Aims/hypothesis

Hyperbaric oxygen (HBO) therapy may improve hyperglycaemia in humans with type 2 diabetes, but underlying mechanisms are unclear. Our objective was to examine the glucometabolic effects of HBO on whole-body glucose disposal in humans with type 2 diabetes.

Methods

In a randomised placebo-controlled crossover trial located at the German Diabetes Center, 12 male individuals with type 2 diabetes (age 18-75 years, BMI <35 kg/m2, HbA1c 42-75 mmol/mol [6-9%]), randomly allocated by one person, underwent 2-h HBO, once with 100% (240 kPa; HBO) and once with 21% oxygen (240 kPa; control, CON). Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamps with D-[6,6-2H2]glucose, hepatic and skeletal muscle energy metabolism were assessed by 1H/31P-magnetic resonance spectroscopy, while high-resolution respirometry measured skeletal muscle and white adipose tissue (WAT) mitochondrial capacity. All participants and people assessing the outcomes were blinded.

Results

HBO decreased fasting blood glucose by 19% and increased whole-body, hepatic and WAT insulin sensitivity about one-third (p<0.05 vs CON). Upon HBO, hepatic γ-ATP concentrations doubled, mitochondrial respiratory control doubled in skeletal muscle and tripled in WAT (p<0.05 vs CON). HBO increased myocellular insulin-stimulated serine-473/threonine-308 phosphorylation of Akt but decreased basal inhibitory serine-1101 phosphorylation of IRS-1 and endoplasmic reticulum stress (p<0.05 vs CON).

Conclusions/interpretation

HBO-mediated improvement of insulin sensitivity likely results from decreased endoplasmic reticulum stress and increased mitochondrial capacity, possibly leading to low-dose reactive oxygen species-mediated mitohormesis in humans with type 2 diabetes.

Trial registration

ClinicalTrials.gov NCT04219215 FUNDING: German Federal Ministry of Health, German Federal Ministry of Education and Research, North-Rhine Westfalia Ministry of Culture and Science, European-Regional-Development-Fund, German-Research-Foundation (DFG), Schmutzler Stiftung.

SUBMITTER: Sarabhai T 

PROVIDER: S-EPMC9729133 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Hyperbaric oxygen rapidly improves tissue-specific insulin sensitivity and mitochondrial capacity in humans with type 2 diabetes: a randomised placebo-controlled crossover trial.

Sarabhai Theresia T   Mastrototaro Lucia L   Kahl Sabine S   Bönhof Gidon J GJ   Jonuscheit Marc M   Bobrov Pavel P   Katsuyama Hisayuki H   Guthoff Rainer R   Wolkersdorfer Martin M   Herder Christian C   Meuth Sven G SG   Dreyer Sven S   Roden Michael M  

Diabetologia 20220930 1


<h4>Aims/hypothesis</h4>Hyperbaric oxygen (HBO) therapy may improve hyperglycaemia in humans with type 2 diabetes, but underlying mechanisms are unclear. Our objective was to examine the glucometabolic effects of HBO on whole-body glucose disposal in humans with type 2 diabetes.<h4>Methods</h4>In a randomised placebo-controlled crossover trial located at the German Diabetes Center, 12 male individuals with type 2 diabetes (age 18-75 years, BMI <35 kg/m<sup>2</sup>, HbA<sub>1c</sub> 42-75 mmol/mo  ...[more]

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