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

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.

Hyperoxia and the cardiovascular system: experiences with hyperbaric oxygen therapy.

Hyperoxia has been described to induce bradycardia by direct stimulation of the parasympathetic nervous system. Also, hyperoxia has been found to increase blood pressure by an elevation of vascular resistance. However, the latter effect itself would induce bradycardia by baroreceptor stimulation. This single-arm monocentric retrospective study aims to evaluate the correlation between these effects by investigating the relation between oxygen (O2) administration and heart rate over time. Data were collected from 23 patients without cardiovascular problems undergoing hyperbaric oxygen therapy (2.4 bar) retrospectively. During single oxygen bouts, transcutaneously measured partial pressure of O2 was increased. During this surge of oxygen pressure, the arterial blood pressure was increased while the heart rate was decreased. Respiration rate was maintained independently from breathing 100% O2 or air. During single oxygen bouts, the half-life of transcutaneously measured partial pressure of O2 was 5.4 ± 2.1 mmHg/s, and the half-life of heart rate was 0.45 ± 0.19 beats/min. It has been shown that hyperbaric oxygen therapy increases the transcutaneously measured partial pressure of O2. This increase was rather fast, followed by a rather slow decrease in HR. This finding does not support direct vagal activation. Heart rate is not decreased due to a direct vagal activation during hyperbaric oxygen therapy. Our single-arm, retrospective study has additionally confirmed that oxidative stress injures the endothelium, and the reduced endothelial-derived vasodilators cause vasoconstriction. As a consequence, blood pressure increases, and heart rate is then further decreased via the baroreceptor reflex.