Abstract
The possible beneficial effects of coenzyme Q10 (CoQ10) supplementation on disease progression and oxidant status in diabetes remains debated. In the present study, patients with type 1 and type 2 diabetes were treated with oral CoQ10, 100mg twice daily for 12weeks. We assessed total antioxidant capacity, intra- and extracellular levels of the redox regulating protein glutaredoxin 1 (Grx1), CoQ10, oxidized LDL-cholesterol, lipid profile and HbA1c. We have previously shown that extracellular Grx1 is increased in patients with type 2 diabetes compared to healthy subjects. In the present study, CoQ10 treatment significantly decreased serum Grx1 activity as well as total antioxidant capacity independent of type of diabetes, indicating an improvement to a less oxidized extracellular environment. The effect on serum Grx1 activity was more prominent in patients not on statin treatment. Conversely, intracellular Grx1 activity as well as mRNA levels increased independent of statin treatment. There was a significant improvement in oxidized LDL-cholesterol and lipid profile, with a tendency to improved metabolic control (HbA1c). Additionally, we describe for the first time that CoQ10 is a direct substrate for glutathione, and that Grx1 catalyzes this reaction, thus presenting a novel mechanism for CoQ10 reduction which could explain our findings of an increased intracellular Grx1. In conclusion, 12weeks CoQ10 treatment significantly improved the extracellular redox balance and lipid profile, indicating that prolonged treatment may have beneficial effects also on clinical outcome in diabetes.
Highlights
Glutaredoxins (Grxs) are redox proteins that catalyze glutathione (GSH) dependent thiol disulfide oxidation reduction reactions in the cytosol or mitochondria [1,2]
We have previously shown that glutaredoxin 1 (Grx1) plasma activity is increased in type 2 diabetes mellitus (DM) compared to healthy subjects, suggesting that extracellular Grx1 activity is a marker of oxidative stress
Statin use was more frequent in the type 2 DM group (67% of type 2 DM patients were on statin treatment compared to 31% of type 1 DM patients), and the baseline lipid profile was significantly dysregulated in the type 2 DM group
Summary
Glutaredoxins (Grxs) are redox proteins that catalyze glutathione (GSH) dependent thiol disulfide oxidation reduction reactions in the cytosol or mitochondria [1,2]. (DM) have an oxidized intracellular environment compared to healthy subjects as hyperglycemia impairs the redox balance and produces ROS [3,4], which triggers diabetes complications, and DM related morbidity and mortality [5,6,7]. We have previously shown that Grx plasma activity is increased in type 2 DM compared to healthy subjects, suggesting that extracellular Grx activity is a marker of oxidative stress. Recent studies have shown that upregulation of Grx attenuates revascularization after arterial ischemia [9], implying the importance of low Grx levels especially in DM patients who have an increased risk of developing atherosclerosis, and that long term CoQ10 treatment improves morbidity in chronic heart failure
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