title: Plasma levels of advanced glycation endproducts Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and pentosidine are not independently associated with cardiovascular disease in individuals with or without type 2 diabetes: the Hoorn and CODAM studies.
abstract: OBJECTIVE
  Experimental and histological data suggest a role for advanced glycation end products (AGEs) in cardiovascular disease (CVD), particularly in type 2 diabetes (T2DM). However, the epidemiological evidence of an adverse association between AGEs and CVD remains inconclusive. We therefore investigated, in individuals with various degrees of glucose metabolism, the associations of plasma AGEs with prevalent CVD.
  
  
  METHODS
  We measured plasma levels of protein-bound N(ε)-(carboxymethyl)lysine (CML), N(ε)-(carboxyethyl)lysine (CEL), and pentosidine, in participants from two Dutch cohort studies (n = 1291, mean age 64.7 ± 8.3 years, 45% women), including 573 individuals with normal glucose metabolism, 304 with impaired glucose metabolism, and 414 with T2DM. In addition, we measured free CML, CEL, and 5-hydro-5-methylimidazolone in a subset of participants (n = 554). Data were analyzed with multiple logistic or linear regression analyses.
  
  
  RESULTS
  CEL (32 [interquartile range: 25-40] vs 28 [22-35] nmol/mmol lysine) and pentosidine (0.53 [0.43-0.67] vs 0.48 [0.40-0.59] nmol/mmol lysine) as well as free CEL (48 [39-62] vs 45 [36-56] nmol/L) and 5-hydro-5-methylimidazolone (141 [96-209] vs 116 [84-165] nmol/L) were higher in individuals with vs without CVD, whereas protein-bound CML was lower (33 [27-38] vs 34 [29-39] nmol/mmol lysine). However, these differences disappeared after adjustment for confounders. The associations did not differ consistently between individuals with and without T2DM.
  
  
  CONCLUSIONS
  We found no independent adverse associations of plasma AGEs with CVD in individuals with normal glucose metabolism, impaired glucose metabolism, and T2DM.
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Nordin M J
authors.initials: NM
authors.lastname: Hanssen
authors.forename: Lian
authors.initials: L
authors.lastname: Engelen
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.forename: Jean L J M
authors.initials: JL
authors.lastname: Scheijen
authors.forename: Maya S
authors.initials: MS
authors.lastname: Huijberts
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
authors.forename: Giel
authors.initials: G
authors.lastname: Nijpels
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: C054688:N(6)-(1-carboxyethyl)lysine; C048496:N(6)-carboxymethyllysine; D001120:Arginine; C062187:pentosidine; D005947:Glucose; D008239:Lysine