title: Plasma levels of advanced glycation endproducts are associated with type 1 diabetes and coronary artery calcification.
abstract: BACKGROUND
  Advanced glycation endproducts (AGEs) may play a role in the development of coronary artery calcification (CAC) in type 1 diabetes (T1DM). We studied plasma AGEs in association with T1DM and CAC, and whether or not the latter association could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED).
  
  
  METHODS
  We studied 165 individuals with and 169 without T1DM. CAC was quantified in a CAC score based on CT-scanning. Plasma levels of protein-bound pentosidine, Nϵ-(carboxymethyl)lysine (CML) and Nϵ-(carboxyethyl)lysine (CEL) were measured with HPLC/UPLC with fluorescence detection or tandem-mass spectrometry. Tetrahydropyrimidine (THP) was measured with ELISA, as were HsCRP, and sVCAM-1 and vWF, as markers for LGI and ED, respectively. Associations were analyzed with ANCOVA and adjusted for age, sex, BMI, waist-to-hip ratio, smoking, blood pressure, lipid profile, eGFR and T1DM.
  
  
  RESULTS
  Individuals with T1DM had higher plasma levels of pentosidine, CML and THP compared with controls; means (95% CI) were 0.69 (0.65-0.73) vs. 0.51 (0.48-0.54) nmol/mmol LYS, p < 0.001; 105 (102-107) vs. 93 (90-95) nmol/mmol LYS, p < 0.001; and 126 (118-134) vs. 113 (106-120) U/mL, p = 0.03, respectively. Levels of pentosidine were higher in individuals with T1DM with a moderate to high compared with a low CAC score, means (95% CI) were 0.81 (0.70-0.93) vs. 0.67 (0.63-0.71) nmol/mmol LYS, p = 0.03, respectively. This difference was not attenuated by adjustment for LGI or ED.
  
  
  CONCLUSIONS
  We found a positive association between pentosidine and CAC in T1DM. These results may indicate that AGEs are possibly involved in the development of CAC in individuals with T1DM.
authors.forename: Marcelle G A
authors.initials: MG
authors.lastname: van Eupen
authors.forename: Miranda T
authors.initials: MT
authors.lastname: Schram
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
authors.forename: Jean L J M
authors.initials: JL
authors.lastname: Scheijen
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre (MUMC) and Cardiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, Maastricht 6200, MD, the Netherlands. c.schalkwijk@maastrichtuniversity.nl.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging; D003331:Coronary Vessels / Q000000981:diagnostic imaging*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000097:blood; D014057:Tomography, X-Ray Computed; D061205:Vascular Calcification / Q000097:blood* / Q000000981:diagnostic imaging; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D011743:Pyrimidines; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; C048496:N(6)-carboxymethyllysine; D002097:C-Reactive Protein; D001120:Arginine; C062187:pentosidine; D008239:Lysine