title: Dimethylarginines at the crossroad of insulin resistance and atherosclerosis.
abstract: We tested if asymmetric dimethylarginine (ADMA) contributes to the simultaneous evolution of atherosclerosis and insulin resistance. We investigated the significant predictors of insulin resistance in the context of atherosclerosis, focusing on the role ADMA, symmetric dimethylarginine (SDMA), and l-arginine play in a cohort of young atherosclerotic patients and their age-matched controls. In a case-control study, 60 patients younger than 55 years having at least 30% stenosis of the internal carotid artery and 30 age- and sex-matched controls were recruited at a community-based neurosonologic laboratory. We found a strong positive association between the homeostasis model assessment of beta-cell function and insulin resistance and the ADMA/SDMA ratio that remained statistically significant even after adjusting for all significant and a priori identified determinants (beta = 6.76; 95% confidence interval [CI], 2.13-11.39; P = .005). Interestingly, this relationship was even more pronounced in the atherosclerotic stratum (beta = 8.29; 95% CI, 1.43-15.15; P = .019), whereas, on multiple linear regression, lack of association was seen in subjects free of carotid atherosclerosis (beta = 1.39; 95% CI, -5.46 to 8.26; P = .671). We conclude that ADMA/SDMA ratio is a significant determinant of insulin resistance and may be a better parameter to monitor than ADMA alone. By accounting for the competition at the y+ transporters, ADMA/SDMA ratio could be an indicator of intracellular ADMA level.
authors.affiliation: Department of Neurology, University of Debrecen, PO Box 31, H-4012 Debrecen, Hungary. zsuga@king.pharmacol.dote.hu
authors.forename: Judit
authors.initials: J
authors.lastname: Zsuga
authors.forename: János
authors.initials: J
authors.lastname: Török
authors.forename: Mária T
authors.initials: MT
authors.lastname: Magyar
authors.forename: Attila
authors.initials: A
authors.lastname: Valikovics
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gesztelyi
authors.forename: Agota
authors.initials: A
authors.lastname: Lenkei
authors.forename: László
authors.initials: L
authors.lastname: Csiba
authors.forename: Sándor
authors.initials: S
authors.lastname: Kéki
authors.forename: Miklós
authors.initials: M
authors.lastname: Zsuga
authors.forename: Dániel
authors.initials: D
authors.lastname: Bereczki
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D050197:Atherosclerosis / Q000097:blood*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged
chemical_list: C487735:dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine