The Production of Reactive Oxygen Species in Response to Glutathione Supplementation and Acute Exercise

Status

Completed

Phase

Not applicable

Enrollment

20 participants (actual)

Sponsor

University of Copenhagen · Other

Design

Randomized · Double masking

Countries

1 country

Denmark

Start

May 2016

Primary completion

Dec 2017

Completion

Dec 2017

First posted

28 Oct 2016 (estimated)

Last update posted

2 May 2018

Conditions

Type 2 Diabetes · Oxidative Stress · Mitochondrial Reactive Oxygen Species Production

Objectives: The research focus of the study is the production of reactive oxygen species (ROS) in patients with type 2 diabetes (T2D) in response to glutathione (GSH) supplementation and in response to acute exercise. Oxidative stress is suggested as a possible causative factor in the pathophysiology of skeletal muscle insulin resistance. GSH is the most abundant endogenous antioxidant in the cell and thus, a crucial protector against oxidative stress and insulin resistance. It has been found that patients with T2D have a decreased level of GSH in plasma and that 1 h GSH infusion improves skeletal muscle glucose uptake by \~25% and the redox environment in patients with T2D. Therefore, we want to investigate the effect of 3 months of GSH supplementation on skeletal muscle insulin sensitivity and mitochondrial ROS production in patients with T2D and healthy controls. Hypothesis: Oral GSH supplementation will improve skeletal muscle insulin sensitivity in patients with T2D and this effect will be linked to a reduced mitochondrial ROS production in the skeletal muscle. In contrast to the link between oxidative stress and insulin resistance, ROS produced in response to exercise is an important physiological stimulus as it is suggested to play a key role in the beneficial mitochondrial biogenesis observed in response to training. It has been reported that some patients with T2D have a diminished mitochondrial biogenesis in response to training, but the reason for this defect is not known. We want to investigate the link between exercise-stimulated ROS production and the mitochondrial biogenesis response in patients with T2D and healthy controls in response to acute exercise at two different intensities. Hypothesis: Considering the pathological condition of T2D skeletal muscle (i.e. high chronic ROS level), we speculate that a lower exercise intensity, leading to a lower exercise-stimulated ROS production is a more optimal stimulus (i.e. not to high) for mitochondrial biogenesis in patients with T2D.

• Placebo comparator

  Control

  4 placebo tablets/day (2 in the morning and 2 in the evening)

• Active comparator

  Glutathione

  4 oral GSH tablets/day (2 in the morning and 2 in the evening)

1. Insulin sensitivity

   Time frame · 12 weeks

   Registry description

   Difference in insulin sensitivity (measured as glucose infusion rate during a hyperinsulinaemic euglycaemic clamp) between patients with type 2 diabetes receiving glutathione supplementation and patients with type 2 diabetes receiving placebo.