title: Higher plasma levels of advanced glycation end products are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-year follow-up study.
abstract: OBJECTIVE
  To investigate the associations of plasma levels of advanced glycation end products (AGEs) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunction, low-grade inflammation, and arterial stiffness.
  
  
  METHODS
  We prospectively followed 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of N(ε)-(carboxymethyl)lysine, N(ε)-(carboxyethyl)lysine, pentosidine and other biomarkers were measured at baseline. The median follow-up duration was 12.3 (interquartile range 7.6-12.5) years.
  
  
  RESULTS
  During the course of follow-up, 82 individuals (24.2%) died; 85 (25.1%) suffered a fatal (n = 48) and/or nonfatal (n = 53) CVD event. The incidence of fatal and nonfatal CVD and of all-cause mortality increased with higher baseline levels of AGEs independently of traditional CVD risk factors: hazard ratio (HR) = 1.30 (95% CI = 1.03-1.66) and HR = 1.27 (1.00-1.62), respectively. These associations were not attenuated after further adjustments for markers of renal or endothelial dysfunction, low-grade inflammation, or arterial stiffness.
  
  
  CONCLUSIONS
  Higher levels of AGEs are associated with incident fatal and nonfatal CVD as well as all-cause mortality in individuals with type 1 diabetes, independently of other risk factors and of several potential AGEs-related pathophysiological mechanisms. Thus, AGEs may explain, in part, the increased cardiovascular disease and mortality attributable to type 1 diabetes and constitute a specific target for treatment in these patients.
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands. j.nin@maastrichtuniversity.nl
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Nin
authors.forename: Anders
authors.initials: A
authors.lastname: Jorsal
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.forename: Coen D
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000401:mortality*; D003925:Diabetic Angiopathies / Q000097:blood / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D014657:Vasculitis / Q000097:blood / Q000401:mortality
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced