Acute Hyperbaric Oxygen Treatment Increases Hepatic Insulin Sensitivity and Muscle Reactive Oxygen Species in T2D

Acute Hyperbaric Oxygen (HBO) Treatment Increases Hepatic Insulin Sensitivity and Muscle Reactive Oxygen Species in Type 2 Diabetes

Diabetes mellitus type 2 (T2D) is characterized by insulin resistance of liver and skeletal muscle, which is at least partly due to impaired muscle mitochondrial function. Long-term HBO therapy, as applied for treating the diabetic foot syndrome, has been shown to improve blood glucose concentrations. To study the underlying mechanisms, we want to examin the short-term effect of HBO treatment on insulin sensitivity and mitochondrial oxidative capacity and production of reactive oxygen species (ROS) in a randomized, double blinded, placebo-controlled cross-over trial.

Study Overview

• Status: Completed
• Conditions: Type 2-diabetes
• Intervention / Treatment: Device: 100% O2 in oxygen chamber; Device: 21% O2 in oxygen chamber

Detailed Description

In total 14 patients are planned. Each participant participates in both experimental parts (100% O2 and ambient air). They are examined immediately after each HBO/ ambient air therapy. The allocation is randomized treated every three weeks with 2-hour therapies using pure O2 or indoor air. Randomized and double-blinded in a cross-over setting, one group of patients with type 2 diabetes is first treated with HBO therapy and the other group is first treated with room air. Here, an ambient pressure of 2.4 ATM is built up and then administered for respiration over a total of 90 minutes of pure O2. Patients are examined on two consecutive days for each part of the study.On the first day serum samples are taken and a sample is taken from the vastus lateralis muscle. A magnetic resonance spectroscopic examination (MRS) is performed on the patient subsequently. In this case, phosphorus metabolites (absolute quantification of ATP, Pi) and the ATP synthase flow rate (fATP) are determined non-invasively by means of 31P MRS and TG storage (HCL) by means of 1H-MRS.

On the next day of the trial patients are treated with HBO therapy or room air. A hyperinsulinemic-euglycemic clamp test (120-300 min) with administration of deuterated glucose (D- [6,6-2H2] glucose) (0-120 min) to measure muscular and hepatic insulin resistance will be performed after the end of HBO therapy or room air treatment performed. Indirect calorimetry determines energy consumption and substrate selection (lipid and glucose oxidation) in hyperinsulinaemia. After the end of the HBO therapy or room air treatment and 30 minutes after the start of the clamp test, a sample is taken from the vastus lateralis muscle again.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Düsseldorf, NRW, Germany, 40225
      • German Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 and ≤ 75 years
• Type 2 diabetes
• HbA1c ≥ 6 and ≤ 9%
• BMI ≤ 35 kg / m2

Exclusion Criteria:

• Treatment with thiazolidinedione in the last 6 months
• Uncontrolled hyperglycemia (FPG ≥ 240 mg / dl)
• vitamin supplement (washing out at least 4 weeks)
• Patients requiring revascularization
• Serum CRP ≥ 5 mg / dl
• Previous treatment for HBO therapy
• Secondary diabets according to ADA criteria (type 3 B-H, eg pancreopriver diabetes)
• Type 4 diabetes (gestational diabetes), pregnancy
• poor glycemic control (HbA1c> 9.0%)
• Hyperlipidemia (low density triglycerides and lipoproteins ≥ double upper Reference limit)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperbaric oxygenation; Patients with T2D receive an 2 hour treatment with 100 % oxygen in a hyperbaric chamber	Device: 100% O2 in oxygen chamber; Application of 100% O2 in an hyperbaric oxygen chamber; Device: 21% O2 in oxygen chamber; Application of ambient air (21% O2) in an hyperbaric oxygen chamber
Experimental: Ambient Air; Patients with T2D receive an 2 hour treatment with 21% oxygen in a hyperbaric chamber	Device: 100% O2 in oxygen chamber; Application of 100% O2 in an hyperbaric oxygen chamber; Device: 21% O2 in oxygen chamber; Application of ambient air (21% O2) in an hyperbaric oxygen chamber

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in rate of glucose disappearance	measurement of whole body insulin sensitivity with hyperinsulinamic euglycemic clamp test	12 months

Collaborators and Investigators

• Sponsor: German Diabetes Center
• Investigators: Principal Investigator: Michael Roden, Prof., MD, German Diabetes Center

Publications and helpful links

General Publications

• Sarabhai T, Mastrototaro L, Kahl S, Bonhof GJ, Jonuscheit M, Bobrov P, Katsuyama H, Guthoff R, Wolkersdorfer M, Herder C, Meuth SG, Dreyer S, Roden M. Hyperbaric oxygen rapidly improves tissue-specific insulin sensitivity and mitochondrial capacity in humans with type 2 diabetes: a randomised placebo-controlled crossover trial. Diabetologia. 2023 Jan;66(1):57-69. doi: 10.1007/s00125-022-05797-0. Epub 2022 Sep 30.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Actual): September 20, 2022
• Study Completion (Actual): September 20, 2022

Study Registration Dates

• First Submitted: September 11, 2019
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: HBO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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