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ALPHA-LIPOIC ACID AND ANTI-OXIDANT DIET IMPROVES ENDOTHELIAL DYSFUNCTION IN CHILDREN AND ADOLESCENTS WITH TYPE 1 DIABETES PREVENT 2 STUDY University of Milan Department of Pediatrics “L. Sacco Hospital” Elisa Giani, MD Scaramuzza Andrea, MD Endothelial dysfunction: a nutritional approach Background  Atherosclerosis and its vascular damage leading cause of mortality and morbidity in diabetic patients1-2 .  Diabetes-related vascular complications rare in pediatric patients. Early functional
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    ALPHA-LIPOIC ACID AND ANTI-OXIDANT DIET IMPROVES ENDOTHELIAL DYSFUNCTION IN CHILDREN AND ADOLESCENTS WITH TYPE 1 DIABETES PREVENT 2 STUDY University of Milan Department of Pediatrics “L. Sacco Hospital”  Elisa Giani, MD Scaramuzza Andrea, MD  E. Giani, MD Endothelial dysfunction: a nutritional approach Background  Atherosclerosis and its vascular damage leading cause of mortality and morbidity in diabetic patients 1-2  .  Diabetes-related vascular complications rare in pediatric patients. Early functional and structural abnormalities may be present a few years after diabetes onset 3  .  Endothelial dysfunction 4 , surrogate marker of cardio-vascular disease, is the loss of structural and/or functional features 5 .  Endothelial dysfunction produced by several mechanisms:  hyperglycemia (enhances ROS, reduces antioxidant reserves, increases AGE as well as the activation of the protein kinase C and polyol pathways)  6    lower plasma concentration of vitamin C    a higher circulating levels of reactive protein C  7    lack of insulin  anti-oxidative, nitrosative, and inflammatory stress action 8 . 1. Asicioglu E, et al. (2010) Eur J Endocrinol 162:711  – 717 2. Sibal Let al. Home PD (2009) Diabetologia 52:1464  – 1473 3. Pozza RD, et al (2007) J Clin Endocrinol Metab 2:2053  – 2057 4. Widlansky ME, et al. (2003) J Am Coll Cardiol 42:1149  – 1160 5. Granger DN, Senchenkova San Rafael (CA): Morgan & Claypool Life Sciences; 2010. 6. King GL, Loeken MR (2004) Histochem Cell Biol 122:333  – 338 7. Azza A. et al. Pediatr. Cardiol. March 2014 8. Dandona et al. Diabetes Care. 2010 Nov;33(11):2416-23  E. Giani, MD Endothelial dysfunction: a nutritional approach Detecting Endothelial Function 1. Kuvin JT et al. Am Heart J 2003 2. Fisher NDL et al. J Hypertens 2003 & 2006 3. Mahmud FH et al. Cong Heart Dis 2006 4. Haller MJ et al. Pediatr Diabetes 2007 5. Kuvin JT et al. Vascular Med 2007 6. Hambourg NM et al. Circulation 2008 7. Mahmud FH et al. J Pediatr 2008  EndoPAT overcome operator dependent disadvantages and invasivity of flow-mediated dilation.  EndoPAT detects plethysmographic pressure changes in the finger tips caused by the arterial pulse, and translates this data to a peripheral arterial tone  (PAT).  EndoPAT provides a measure for arterial stiffness  via the augmentation index (AI), a measure for arterial endothelial function 1 .  Framingham study and other studies found a significant inverse relation between endothelial function (‘ EndoScore ’ or reactive hyperemia index ,  RHI ) and multiple cardiovascular risk factors (male sex, body mass index, total/HDL cholesterol, diabetes, smoking, and lipid-lowering treatment) 1-7 .   E. Giani, MD Endothelial dysfunction: a nutritional approach Background: Prevent 1 Study (2012) ( PREVention of ENdothelial dysfunction in Type 1 diabetes)    Aim  was to evaluate the prevalence   of   early endothelial dysfunction , measured by mean of reactive hyperemia ( peripheral artery tonometry ) in  73 children and adolescents  aged 16.0 ± 3.5 years  type 1 diabetes 8.2 ± 5.2 years  mean HbA1c value: 8.08 ± 1.12 % (range: 6.05-12.2 %)  Endothelial dysfunction was observed in 76.7% of patients (n=56)  Reactive Hyperemia Index : 1.31±0.18 vs. 2.2±0.41 (normal value >1.67)  HbA1c  was significantly higher in patients with endothelial dysfunction either as actual value at the baseline (8.29% vs. 7.39%, p= 0.005) or as mean value since the diabetes onset (8.22% vs. 7.7%, p= 0.05)
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