title: Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study.
abstract: OBJECTIVE
  Plasma soluble receptor for AGE (sRAGE) may reflect the activity of the AGE-RAGE axis, which has been proposed as a potential mechanism linking hyperglycaemia to vascular complications in diabetes. We have therefore investigated: (1) whether sRAGE is associated with greater prevalence of cardiovascular disease (CVD) and microvascular complications in type 1 diabetic individuals; and (2) the extent to which any such associations are explained by markers of endothelial and renal dysfunction and inflammation.
  
  
  METHODS
  The study included 477 individuals (234 women; mean age 42 +/- 10 [SD] years) from the EURODIAB Prospective Complications Study. We used linear regression analyses to investigate the differences in sRAGE levels between individuals with and without vascular complications. All analyses were adjusted for age, sex, HbA(1c), duration of diabetes and other risk factors.
  
  
  RESULTS
  Individuals with CVD (n = 116) had higher levels of sRAGE than those without CVD or any microvascular complications (n = 178): beta = 0.15 (95% CI 0.04-0.27). Further adjustments for markers of endothelial (beta = 0.13 [0.02-0.24]) and renal dysfunction (beta = 0.10 [-0.01, 0.20]) and inflammation (beta = 0.12 [0.01-0.23]) attenuated these differences; altogether these variables explained about 50% of the association between sRAGE and prevalent CVD. sRAGE levels tended to be higher in the presence and across the levels of severity of albuminuria (p for trend = 0.087) and retinopathy (p for trend = 0.057); adjustments for endothelial and renal dysfunction and inflammation also attenuated these differences.
  
  
  CONCLUSIONS
  sRAGE is associated with greater prevalence of CVD in type 1 diabetic individuals, and these associations may be partly explained by endothelial and renal dysfunction and low-grade inflammation.
authors.affiliation: Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre, Maastricht, the Netherlands. j.nin@intmed.unimaas.nl
authors.forename: J W M
authors.initials: JW
authors.lastname: Nin
authors.forename: I
authors.initials: I
authors.lastname: Ferreira
authors.forename: C G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: M H
authors.initials: MH
authors.lastname: Prins
authors.forename: N
authors.initials: N
authors.lastname: Chaturvedi
authors.forename: J H
authors.initials: JH
authors.lastname: Fuller
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000293:Adolescent; D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003925:Diabetic Angiopathies / Q000097:blood*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007328:Insulin / Q000627:therapeutic use; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D007328:Insulin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic