Osama A Tolba El Razaky
Tanta University, Egypt
Title: Prevention of diabetic cardiomyopathy in pediatrics
Biography
Biography: Osama A Tolba El Razaky
Abstract
Background: The development of Diabetic cardiomyopathy (DCM) is multi-factorial and several pathophysiologic mechanisms have been proposed to explain structural and functional changes associated with DCM. α-lipoic acid (ALA) a powerful antioxidant may has a protective role in diabetic cardiac dysfunction. Aim of the work: This study aimed to assess the potential role of oxidative stress, inflammatory cytokines, apoptosis and fibrosis in diabetic cardiac insult. It also investigated the possible protective role of α-lipoic acid on diabetic left ventricular (LV) dysfunction in type 1 diabetic children and adolescents. Subjects & Methods: 30 patients were randomized to receive insulin treatment (n=15) or insulin plus α-lipoic acid 300 mg twice daily (n=15). Age and sex matched healthy control children and adolescents (n=15) were also included. Patients were evaluated with conventional 2-dimensional echocardiographic examination (2D), pulsed tissue Doppler (PTD), and 2-dimensional longitudinal strain echocardiography (2DS) before and after therapy.3D strain (longitudinal, circumferential, area and radial strain) were estimated. Plasma level of glutathione, malondialdhyde (MDA), nitric oxide, tumor necrosis factor-α (TNF-α), Fas Ligand (Fas-L), matrix metalloproteinase-2 (MMP-2) and troponin-I were determined before and after treatment. Results: Diabetic patients had significant lower level of glutathione and significant higher levels of malondialdhyde (MDA), nitric oxide, tumor necrosis factor-α (TNF-α), Fas Ligand (Fas-L), matrix metalloproteinase-2 (MMP-2) and troponin-I than control subjects. Increased expression of transforming growth factor-β (TGF-β) mRNA in peripheral blood mononuclear cells was also observed in diabetic patients. 2D global longitudinal strain and 3D longitudinal, circumferential and area strain were significantly decreased in diabetic children. α-lipoic acid significantly increased glutathione level and significantly decreased MDA, nitric oxide, TNF-α, Fas L, MMP-2, troponin I levels and TGF-β gene expression levels. Moreover, α-lipoic acid significantly increased mitral e/a ratio, ventricular global peak systolic strain in diabetic patients. There were significant negative correlation between Global peak systolic strain (G) and glutathione and significant positive correlations between G and MDA, NO, TNF-α and Fas-L. In addition, a significant positive correlation between e/a ratio and glutathione (r=0.515) and significant negative correlations between e/a and MDA, NO, TNF-α and Fas-L were also observed. Conclusion: These data suggest that oxidative stress, inflammatory cytokines such as TNF-α, apoptosis and fibrosis play a role in the development of diabetic cardiac dysfunction and that α-lipoic acid may have a beneficial role in the management of type 1 diabetic patients as a cardioprotective therapy and prevention of development of diabetic cardiomyopathy.
