Mitochondrial Alterations and Enhanced Human Leukocyte/Endothelial Cell Interactions in Type 1 Diabetes.

Type 1 diabetes has been associated with oxidative stress. This study evaluates the rates of oxidative stress, mitochondrial function, leukocyte-endothelium interactions and adhesion molecules in type 1 diabetic patients. The study population consisted of 52 diabetic patients and 46 body-composition and age-matched controls. We assessed anthropometric and metabolic parameters, oxidative stress and mitochondrial function by evaluating reactive oxygen species (ROS) production, mitochondrial ROS production, mitochondrial membrane potential and superoxide dismutase (SOD) and catalase (CAT) expression in polymorphonuclear leukocytes from type 1 diabetic patients. In addition, we evaluated interactions between leukocytes and human umbilical vein endothelial cells (HUVEC), and serum expression of adhesion molecules (P-selectin, VCAM-1 and ICAM-1), proinflammatory cytokines (IL-6 and TNFα) and myeloperoxidase (MPO). HbA1C and glucose levels were higher in diabetic patients than in control subjects, as expected. Mitochondrial function was altered and leukocyte-endothelium interactions were enhanced in diabetic patients, which was evident in the increase in total and mitochondrial ROS production, higher mitochondrial membrane potential, enhanced leukocyte rolling and adhesion, and decreased rolling velocity. Furthermore, we observed an increase in levels of adhesion molecules P-selectin, VCAM-1, and ICAM-1 in these subjects. In addition, type 1 diabetic patients exhibited an increase in proinflammatory mediators TNFα and MPO, and a decreased expression of SOD. The enhancement of leukocyte-endothelium interactions and proinflammatory markers correlated with glucose and HbA1Clevels. Mitochondrial alteration, oxidative stress, and enhanced leukocyte-endothelium interactions are features of type 1 diabetes and may be related to cardiovascular implications.

The SGLT2 Inhibitor Empagliflozin Ameliorates the Inflammatory Profile in Type 2 Diabetic Patients and Promotes an Antioxidant Response in Leukocytes.

Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to a considerable reduction in cardiovascular risk in patients with type 2 diabetes (T2D), but the precise molecular mechanisms are still elusive. We aimed to evaluate the effects of the iSGLT2 empagliflozin on systemic inflammation and its potential antioxidant properties. This is an observational, prospective follow-up study of a cohort of fifteen patients with T2D who received 10 mg/day of empagliflozin according to standard clinical care. Measures at baseline, 12 and 24 weeks were taken. Metabolic and anthropometric parameters were evaluated. Production of mitochondrial superoxide, glutathione content, and glutathione s-reductase and catalase mRNA levels were measured in leukocytes. Serum levels of myeloperoxidase, hs-CRP and IL-10 were determined. In addition to decreased body weight and reduced glucose and HbA1c levels, we observed a reduction in superoxide production in leukocytes of diabetic patients and increased glutathione content, prominently after 24 weeks of empagliflozin treatment. Leukocyte expression of glutathione s-reductase and catalase, and serum levels of IL-10 were enhanced at 24 weeks of empagliflozin treatment. Concomitantly, reduced hs-CRP and myeloperoxidase levels were seen. This study provides evidence of the antioxidant and anti-inflammatory properties of empagliflozin treatment in humans, which may contribute to its beneficial cardiovascular effects.