RESEARCH PROJECT: GLYCOGEN STORAGE DISEASE TYPE I AND ATHEROSCLEROSIS a multicentre study

BACKGROUND Glycogen storage disease (GSD) type I is characterized by hypoglycaemia, hyperuricemia, hyperlactatemia and hyperlipidemia Despite appropriate dietary treatment GSD I patients often show a lipid profile similar to that found in people who have a significant risk of atherosclerosis [T. Geberhiwot et al. 2007]

BACKGROUND GSD I patients can have other important cardiovascular risk factors: -obesity -microalbuminuria -hypertension -insulin resistance

BACKGROUND In diabetic patients high glycemic levels induce the formation of Advanced Glycation End products (AGE) AGE-RAGE interaction triggers an increase of reactive oxygen species The imbalance between free radicals and antioxidant defences is fundamental in determining atherosclerosis [Giuliano et al. 1996]

Is GSD I associated with atherosclerosis? Several studies until 2007 concluded that the answer is NO! Possible explanation: -more antioxidant defence [Wittenstein et al 2002] -reduced platelet function [Muhlhausen et al 2005] -increased cholesterol efflux [Nguyen D et al 2005] -Increased adiponectin [Tamaki T. et al 2007] -low levels of AGE [den Hollander et al 2007]

Is GSD I associated with atherosclerosis ? More recent studies concluded that the answer is YES!! -Yekeler et al 2007: study including 13 patients with GSD Ia -Bernier et al 2009: study including 28 patients (age 13-41) with GSD Ia and Ib significant increase in carotid IMT in GSD subjects compared with healthy controls

OBJECTIVES To evaluate the presence or absence of atherosclerosis in GSD type I in a larger cohort of patients then in previous studies To examine possible pathogenic or protective factors influencing atherosclerosis, focusing our attention on the non-enzymatic glycation of proteins and the oxido-reductive balance

SUBJECTS AND METHODS Eligible patients with GSD type Ia and Ib who are 13 years or older (without hepatic transplantation) Healthy non-smoking, control subjects, matched for age and sex (Padua)

SUBJECTS AND METHODS Each participant Centre for each patient will evaluate: -Clinical history, BMI and blood pressure -Routine laboratory analysis (glycemia, lipid profile, renal function, C reactive protein, uric acid, microalbuminuria)

SUBJECTS AND METHODS To evaluate the presence of atherosclerosis: -B-mode ultrasound imaging with estimation of the carotid intima-media thickness (IMT) - Doppler CW with measurement of the ankle- brachial-pressure index (ABI)

SUBJECTS AND METHODS University of Padua will measure: -AGE, esRAGE, Pentosidine, -Malondialdehyde, Nitrotyrosine -vit A, vit E, Glutathione -ox LDL, Ab antiox LDL

METABOLIC CENTRES CURRENTLY INVOLVED Policlinico Universitario Padova Istituto Giannina Gaslini Genova Ospedale San Paolo Milano Ospedale San Gerardo Monza Charles Dent Metabolic Unit London