title: Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes--the EURODIAB Prospective Complications Study.
abstract: OBJECTIVE
  The pathogenesis of vascular complications in type 1 diabetes is poorly understood, but may involve chronic, low-grade inflammation. We investigated the association of markers of inflammation with vascular complications in type 1 diabetes.
  
  
  METHODS
  A cross-sectional nested case-control study of the follow-up data of the EURODIAB Prospective Complications Study. This study included 543 individuals (278 men) with type 1 diabetes diagnosed at <36 years of age. Cases (n=348) had complications of diabetes, controls (n=195) had no complications.
  
  
  RESULTS
  C-reactive protein, interleukin-6 and tumour necrosis factor-alpha levels, which were combined in an inflammatory marker Z-score, were associated with albuminuria, retinopathy and cardiovascular disease. Calculated means (95% confidence intervals) of the marker Z-score were -0.15 (-0.22 to -0.07), 0.10 (-0.05 to 0.25), and 0.28 (0.15 to 0.41), p for trend <0.0001, in individuals with normo-, micro- and macroalbuminuria; -0.23 (-0.33 to -0.13), 0.14 (0.02 to 0.25) and 0.20 (0.07 to 0.32), p for trend <0.0001, in individuals with no, non-proliferative and proliferative retinopathy; and -0.28 (-0.39 to -0.18) and 0.06 (-0.08 to 0.20), p<0.001, in individuals without and with cardiovascular disease. Per 1 SD increase of the inflammatory marker Z-score, GFR decreased by -4.6 (-6.6 to -2.6) ml per min per 1.73 m(2) (p<0.001).
  
  
  CONCLUSIONS
  We have shown that markers of inflammation are strongly and independently associated with microvascular complications and cardiovascular disease in type 1 diabetes. These data suggest that strategies to decrease inflammatory activity may help to prevent the development of vascular complications in type 1 diabetes.
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Schram
authors.forename: N
authors.initials: N
authors.lastname: Chaturvedi
authors.forename: C G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: J H
authors.initials: JH
authors.lastname: Fuller
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000473:pathology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008297:Male; D008833:Microcirculation / Q000473:pathology / Q000502:physiology*
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced