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Atherogenic vascular and lipid phenotypes in young patients with Type 1 diabetes are associated with diabetes high-risk HLA genotype

Odermarsky, Michal LU ; Ramelius, Anita LU ; Lernmark, Åke LU ; Sjöblad, Sture LU and Liuba, Petru LU (2007) In American Journal of Physiology: Heart and Circulatory Physiology 293(5). p.3175-3179
Abstract
Expression of human leukocyte antigen (HLA) class II molecules on islet endothelial cells is a central vascular event in the pathogenesis of Type 1 diabetes. Previous studies demonstrated the ability of other vascular endothelial cells to express HLA and thereby to process islet autoantigens on their surface. We investigated whether the HLA-DQ2/8 genotype, which confers the highest risk for Type 1 diabetes, is associated with early atherosclerosis in youths with this disease. Brachial artery endothelium-dependent, flow-mediated dilation (BA-FMD) and carotid artery intima-media thickness (CA-IMT), as well as markers of systemic inflammation [C-reactive protein (CRP), fibrinogen, and orosomucoid], HbA(1C), LDL, HDL, and total cholesterol,... (More)
Expression of human leukocyte antigen (HLA) class II molecules on islet endothelial cells is a central vascular event in the pathogenesis of Type 1 diabetes. Previous studies demonstrated the ability of other vascular endothelial cells to express HLA and thereby to process islet autoantigens on their surface. We investigated whether the HLA-DQ2/8 genotype, which confers the highest risk for Type 1 diabetes, is associated with early atherosclerosis in youths with this disease. Brachial artery endothelium-dependent, flow-mediated dilation (BA-FMD) and carotid artery intima-media thickness (CA-IMT), as well as markers of systemic inflammation [C-reactive protein (CRP), fibrinogen, and orosomucoid], HbA(1C), LDL, HDL, and total cholesterol, were assessed in 86 children and adolescents with Type 1 diabetes (mean age and diabetes duration, 15 and 7 yr, respectively) between 2004 and 2006. HLA genotypes were determined in dried blood spots by an oligoblot hybridization method. As a result, HLA-DQ2/8 was detected in 34 patients (DQ2/8). When this group was compared with the remaining patients (non-DQ2/8, n = 52), there were no differences in age, diabetes duration, HbA(1C), body mass index, inflammatory markers, and IMT (P >= 0.4). In the DQ2/8 group, LDL-to-HDL ratio was elevated compared with that in the non-DQ2/8 group (1.8 vs. 1.3, respectively; P = 0.001), whereas FMD did not significantly differ between the groups (5.3% vs. 6.7%, respectively; P = 0.08). When patients were further categorized in relation to CRP (cut- off value, 1 mg/ l), BA-FMD was significantly lower (3%, P < 0.01), whereas LDL-to-HDL ratio increased further (2.2, P < 0.001) in the subgroup of DQ2/8 and CRP >= 1 patients compared with the remaining three subgroups. These associations remained significant after adjustment for age, diabetes duration, and HbA(1C) by analysis of covariance. The brachial artery responses to nitroglycerine were similar in all subgroups. In conclusion, the diabetes-predisposing HLA-DQ2/8 genotype in children and adolescents with Type 1 diabetes interferes with endothelial and lipid-related mechanisms of early atherosclerosis, possibly in part through inflammatory pathways. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
vascular function, genetics, lipids
in
American Journal of Physiology: Heart and Circulatory Physiology
volume
293
issue
5
pages
3175 - 3179
publisher
American Physiological Society
external identifiers
  • wos:000251400100067
  • scopus:36148978532
ISSN
1522-1539
DOI
10.1152/ajpheart.00795.2007
language
English
LU publication?
yes
id
64df6dc0-ec20-4622-b2eb-c79c63bec064 (old id 966426)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17906106&dopt=Abstract
date added to LUP
2008-01-30 07:32:13
date last changed
2017-01-01 04:54:36
@article{64df6dc0-ec20-4622-b2eb-c79c63bec064,
  abstract     = {Expression of human leukocyte antigen (HLA) class II molecules on islet endothelial cells is a central vascular event in the pathogenesis of Type 1 diabetes. Previous studies demonstrated the ability of other vascular endothelial cells to express HLA and thereby to process islet autoantigens on their surface. We investigated whether the HLA-DQ2/8 genotype, which confers the highest risk for Type 1 diabetes, is associated with early atherosclerosis in youths with this disease. Brachial artery endothelium-dependent, flow-mediated dilation (BA-FMD) and carotid artery intima-media thickness (CA-IMT), as well as markers of systemic inflammation [C-reactive protein (CRP), fibrinogen, and orosomucoid], HbA(1C), LDL, HDL, and total cholesterol, were assessed in 86 children and adolescents with Type 1 diabetes (mean age and diabetes duration, 15 and 7 yr, respectively) between 2004 and 2006. HLA genotypes were determined in dried blood spots by an oligoblot hybridization method. As a result, HLA-DQ2/8 was detected in 34 patients (DQ2/8). When this group was compared with the remaining patients (non-DQ2/8, n = 52), there were no differences in age, diabetes duration, HbA(1C), body mass index, inflammatory markers, and IMT (P &gt;= 0.4). In the DQ2/8 group, LDL-to-HDL ratio was elevated compared with that in the non-DQ2/8 group (1.8 vs. 1.3, respectively; P = 0.001), whereas FMD did not significantly differ between the groups (5.3% vs. 6.7%, respectively; P = 0.08). When patients were further categorized in relation to CRP (cut- off value, 1 mg/ l), BA-FMD was significantly lower (3%, P &lt; 0.01), whereas LDL-to-HDL ratio increased further (2.2, P &lt; 0.001) in the subgroup of DQ2/8 and CRP &gt;= 1 patients compared with the remaining three subgroups. These associations remained significant after adjustment for age, diabetes duration, and HbA(1C) by analysis of covariance. The brachial artery responses to nitroglycerine were similar in all subgroups. In conclusion, the diabetes-predisposing HLA-DQ2/8 genotype in children and adolescents with Type 1 diabetes interferes with endothelial and lipid-related mechanisms of early atherosclerosis, possibly in part through inflammatory pathways.},
  author       = {Odermarsky, Michal and Ramelius, Anita and Lernmark, Åke and Sjöblad, Sture and Liuba, Petru},
  issn         = {1522-1539},
  keyword      = {vascular function,genetics,lipids},
  language     = {eng},
  number       = {5},
  pages        = {3175--3179},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Heart and Circulatory Physiology},
  title        = {Atherogenic vascular and lipid phenotypes in young patients with Type 1 diabetes are associated with diabetes high-risk HLA genotype},
  url          = {http://dx.doi.org/10.1152/ajpheart.00795.2007},
  volume       = {293},
  year         = {2007},
}