Original Data

Rev Diabet Stud, 2013, 10(1):58-67 DOI 10.1900/RDS.2013.10.58

Alpha-Lipoic Acid Improves Subclinical Left Ventricular Dysfunction in Asymptomatic Patients with Type 1 Diabetes

Sahar K. Hegazy1, Osama A. Tolba2, Tarek M. Mostafa1, Manal A. Eid3, Dalia R. El-Afify1

1Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Egypt
2Department of Pediatrics, Faculty of Medicine, Tanta University, Egypt
3Department of Clinical Pathology, Faculty of Medicine, Tanta University, Egypt
Address correspondence to: Dalia R El-Afify, e-mail: daliaelafify@yahoo.com

Manuscript submitted February 9, 2013; resubmitted March 27, 2013; accepted April 15, 2013.

Keywords: type 1 diabetes, diabetic cardiomyopathy, alpha-lipoic acid, oxidative stress, apoptosis, fibrosis, echocardiography

Abstract

BACKGROUND: Oxidative stress plays an important role in the development of diabetic cardiomyopathy. Alpha-lipoic acid (ALA) is a powerful antioxidant that may have a protective role in diabetic cardiac dysfunction. AIM: We investigated the possible beneficial effect of alpha-lipoic acid on diabetic left ventricular (LV) dysfunction in children and adolescents with asymptomatic type 1 diabetes (T1D). SUBJECTS AND METHODS: Thirty T1D patients (aged 10-14) were randomized to receive insulin treatment (n = 15) or insulin plus alpha-lipoic acid 300 mg twice daily (n = 15) for four months. Age and sex matched healthy controls (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. Glutathione, malondialdhyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), Fas ligand (Fas-L), matrix metalloproteinase 2 (MMP-2), and troponin-I were determined and correlated to echocardiographic parameters. RESULTS: Diabetic patients had significantly lower levels of glutathione and significantly higher MDA, NO, TNF-alpha, Fas-L, MMP-2, and troponin-I levels than control subjects. The expression of transforming growth factor beta (TGF-beta) mRNA in peripheral blood mononuclear cells was also increased in diabetic patients. Significant correlations of mitral e'/a' ratio and left ventricular global peak systolic strain with glutathione, MDA, NO, TNF-alpha, and Fas-L were observed in diabetic patients. Alpha-lipoic acid significantly increased glutathione level and significantly decreased MDA, NO, TNF-alpha, Fas-L, MMP-2, troponin-I levels, and TGF-beta gene expression. Moreover, alpha-lipoic acid significantly increased mitral e'/a' ratio and left ventricular global peak systolic strain in diabetic patients. CONCLUSION: These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes.

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