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Title Novel cardiovascular risk factors in childhood
Author/s Michal Odermarsky
Department/s Paediatrics (Lund)
Full-text Available as PDF
Defence date 2008-12-12
Defence time 13:00
Defence place Segerfalksalen, Wallenberg Neurocentrum, BMC Lund
Opponent professor Julian PJ Halcox
Publication/Series Lund University, Faculty of Medicine Doctoral Dissertation Series
Publishing year 2008
Volume 2008:133
Pages 92
Document type Dissertation
Language English
Publisher Dept of Pediatric, Clinical Sciences, Faculty of Medicine, Lund
Abstract English Individuals with type 1 diabetes (T1D) have a 2 to 3-fold increased risk for cardiovascular disease compared to non-diabetic subjects. Exposure to a broad panel of risk factors in childhood may cause vascular damage with potentially long-term consequences for cardiovascular morbidity.

The aims of the studies were to investigate in young patients with T1D whether: frequency of acute infections correlates with atherogenic vascular changes (Study I); diabetes-predisposing genotype HLA-DQ 2/8 is associated with phenotypes of atherosclerosis and systemic microvascular dysfunction (Study II-III); exposure to environmental tobacco smoke (ETS) affects heart rate variability (HRV), and whether this association is influenced by diabetes-risk HLA (Study IV). The aim of study V was to investigate in an animal model susceptible to vascular disease whether repeated challenge with a respiratory pathogen poses cumulative adverse effects on microvascular function.

Our findings suggest that in young patients with T1D: diabetes-risk genotype HLA DQ 2/8 is associated with functional disturbances in both large arteries and microcirculation, and with atherogenic lipid phenotype (studies II and III); frequent exposure to ETS is associated with disturbances in HRV, especially in those with diabetes-risk genotype HLA-DQ 2/8 (study IV); high frequency of RTI is associated with early signs of accelerated atherosclerosis in carotid artery, particularly in those regularly exposed to ETS (study I). At least in a hypercholesterolemic milieu, the risk of developing microvascular dysfunction seems to rise with increasing number of infectious episodes (study V).

Further studies are needed to provide additional mechanistic insights into the putative gene-environment interactions on the cardiovascular system in young patients with T1D, and to investigate eventual relationship to cardiovascular complications later in life. Also, large-scale prospective studies on young populations presenting diabetes-risk (as well as other autoimmunity-risk) HLA are needed to elucidate whether these putative gene-environment influences on the cardiovascular system may be present already before the onset of the disease predisposed by these HLA.
Subject Medicine and Health Sciences
Keywords vascular function, environmental tobacco smoke, infection, type 1 diabetes, HLA
ISBN/ISSN/Other ISSN: 1652-8220
ISBN: 978-91-86059-86-6
Supervisor Petru Liuba
Supervisor Erkki Pesonen
Supervisor Sture Sjöblad
Part of Respiratory infection recurrence and passive smoking in early atherosclerosis in children and adolescents with type 1 diabetes.
Part of Atherogenic vascular and lipid phenotypes in young patients with Type 1 diabetes are associated with diabetes high-risk HLA genotype
Part of Cutaneous Microvascular Dysfunction Is Associated With Human Leukocyte Antigen-DQ in Youths With Type 1 Diabetes.

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