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

• Published in: Diabetologia Vol. 66; no. 1; pp. 57 - 69
• Main Authors: Sarabhai, Theresia, Mastrototaro, Lucia, Kahl, Sabine, Bönhof, Gidon J., Jonuscheit, Marc, Bobrov, Pavel, Katsuyama, Hisayuki, Guthoff, Rainer, Wolkersdorfer, Martin, Herder, Christian, Meuth, Sven G., Dreyer, Sven, Roden, Michael
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2023; Springer Nature B.V
• Subjects: Adipose tissue; Adolescent; Adult; Aged; AKT protein; Blood glucose; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - therapy; Endoplasmic reticulum; Energy metabolism; Glucose; Human Physiology; Humans; Hyperbaric oxygen; Hyperbaric Oxygenation; Hyperglycemia; Insulin; Insulin receptor substrate 1; Insulin Resistance; Internal Medicine; Liver; Magnetic resonance spectroscopy; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Mitochondria; Musculoskeletal system; Oxygen; Oxygen therapy; Phosphorylation; Placebos; Reactive oxygen species; Respiration; Serine; Skeletal muscle; Threonine; Young Adult; Hyperbaric oxygen therapy; ER stress; Insulin resistance; Mitohormesis; Antioxidative defence
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-022-05797-0

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/m 2 , HbA 1c 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- 2 H 2 ]glucose, hepatic and skeletal muscle energy metabolism were assessed by 1 H/ 31 P-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 Graphical abstract