title: Amadori-albumin correlates with microvascular complications and precedes nephropathy in type 1 diabetic patients.
abstract: BACKGROUND
  Amadori-albumin, a major glycated protein, is involved in experimental hyperglycaemia-induced microvascular complications, and is associated with advanced nephropathy in Type I diabetic patients in humans. Our aim was to assess the association of Amadori-albumin with early nephropathy and with retinopathy in Type I diabetic patients and the involvement of chronic low-degree inflammation therein.
  
  
  METHODS
  Amadori-albumin, the Amadori product of haemoglobin (HbA1c), C-reactive protein, and fibrinogen levels were measured in the EUCLID study, a 2-year randomised, double-blind, placebo-controlled trial of lisinopril in 447 Type I diabetic patients. Retinal photographs were taken in 341 patients at baseline and 294 at follow up.
  
  
  RESULTS
  Amadori-albumin was positively associated with albumin the excretion rate and retinopathy status (P = 0.0001 and P = 0.02 for trend, respectively) and with the progression from normoalbuminuria to (micro)albuminuria (38.6 U mL(-1) in nonprogressors, 44.3 U mL-1 in progressors; P = 0.02), but not with the development or progression of retinopathy during a 2-year follow up. Amadori-albumin levels at baseline were associated with C-reactive protein and fibrinogen (P = 0.0007 and P = 0.0001, respectively). C-reactive protein and fibrinogen were also associated with albumin excretion rates (P = 0.03 and P = 0.01, respectively) and retinopathy status (P = 0.02 and P = 0.0006, respectively). Adjustment for these inflammatory markers did not markedly attenuate the association between Amadori-albumin and the albumin excretion rate, while adjustment for fibrinogen, but not C-reactive protein, abolished the association between Amadori-albumin and retinopathy. Lisinopril had no impact on the association between the levels of Amadori-albumin and albumin excretion rates or retinopathy.
  
  
  CONCLUSIONS
  Amadori-albumin was associated with early nephropathy and with retinopathy in Type I diabetic patients and preceded an increase in albumin excretion rate, but not retinopathy. A chronic low-degree inflammation does not appear to be involved in Amadori-albumin-associated microvascular complications in Type I diabetes.
authors.affiliation: Academic Hospotal Vrije Universiteit, Amsterdam, The Netherlands. C.Schalkwijk@AZVU.NL
authors.forename: C G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: N
authors.initials: N
authors.lastname: Chaturvedi
authors.forename: H
authors.initials: H
authors.lastname: Twaafhoven
authors.forename: V W M
authors.initials: VW
authors.lastname: van Hinsbergh
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D000418:Albumins / Q000032:analysis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000097:blood; D003930:Diabetic Retinopathy / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis
chemical_list: D000418:Albumins; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D017706:Lisinopril