Are Mitochondrial Fusion and Fission Impaired in Leukocytes of Type 2 Diabetic Patients?

Mitochondrial fusion/fission alterations have been evaluated in different tissues of type 2 diabetic (T2D) patients. However, it is not known whether mitochondrial dynamics is disturbed in the leukocytes of T2D patients and whether glycemic control affects its regulation. Anthropometric and metabolic parameters in 91 T2D patients (48 with glycated hemoglobin [HbA1c] <6.5% and 43 with HbA1c >6.5%) were characteristic of the disease when compared with 78 control subjects. We observed increased reactive oxygen species production in leukocytes from diabetic patients, together with a reduced mitochondrial oxygen consumption rate, especially in poorly controlled patients. Mitochondrial fusion was reduced and fission was increased in diabetic patients, and both features were accentuated in patients with poor glycemic control. Furthermore, leukocyte rolling flux rose in parallel to HbA1c levels. The induction of leukocyte-endothelial interactions in diabetic patients was related to reduced mitochondrial fusion and higher mitochondrial fission. Our findings suggest that mitochondrial dynamics could be influenced by glycemic control in leukocytes of diabetic patients, in which there is decreased mitochondrial fusion and elevated fission related to enhanced leukocyte-endothelial interactions. These findings lead to the hypothesis that poor glycemic control during T2D may alter mitochondrial dynamics and could eventually promote leukocyte-endothelial interactions and the onset of cardiovascular diseases. Antioxid. Redox Signal. 25, 108-115.