Mitochondrial respiration and hydrogen peroxide production rate in right atrial tissues from obese diabetic patients

Type 2 diabetes (T2D) is a global epidemic, with heart failure being the leading cause of premature death. Mitochondrial dysfunction, characterized by impaired energy metabolism, weakened energy transport system and increased oxidative stress, has been proposed as a key contributor to the impairment of contractile function in T2D hearts. However, direct evidence from human T2D hearts remains limited. We assessed the mitochondrial function of right atrial tissues obtained from consenting patients undergoing coronary bypass surgery, comparing T2D and non-diabetic groups. We used high-resolution respirometry and fluorometry techniques to assess mitochondrial O₂ flux and H₂O₂ production in permeabilized cardiac fibres in simulated physiological conditions supported by ATP substrate. Our findings showed that O₂ flux during oxidative phosphorylation and ATP-stimulated respiration states was similar between groups. T2D fibres exhibited a lower H₂O₂ production rate during the leak state, both per tissue mass and per O₂ consumed, but no group difference was observed in the oxidative phosphorylation respiratory state. These findings suggest that T2D, in the context of other comorbidities, such as coronary artery disease and obesity, might not contribute significantly to mitochondrial dysfunction in the human heart.