title: Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes.
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.
  
  
  OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Egypt.
authors.forename: Sahar K
authors.initials: SK
authors.lastname: Hegazy
authors.forename: Osama A
authors.initials: OA
authors.lastname: Tolba
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Mostafa
authors.forename: Manal A
authors.initials: MA
authors.lastname: Eid
authors.forename: Dalia R
authors.initials: DR
authors.lastname: El-Afify
mesh_terms: D000293:Adolescent; D000975:Antioxidants / Q000008:administration & dosage; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D008063:Thioctic Acid / Q000008:administration & dosage*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008063:Thioctic Acid