title: Association of the pattern recognition molecule H-ficolin with incident microalbuminuria in an inception cohort of newly diagnosed type 1 diabetic patients: an 18 year follow-up study.
abstract: OBJECTIVE
  Increasing evidence links complement activation through the lectin pathway to diabetic nephropathy. Adverse complement recognition of proteins modified by glycation has been suggested to trigger complement auto-attack in diabetes. H-ficolin (also known as ficolin-3) is a pattern recognition molecule that activates the complement cascade on binding to glycated surfaces, but the role of H-ficolin in diabetic nephropathy is unknown. We aimed to investigate the association between circulating H-ficolin levels and the incidence of microalbuminuria in type 1 diabetes.
  
  
  METHODS
  We measured baseline H-ficolin levels and tracked the development of persistent micro- and macroalbuminuria in a prospective 18 year observational follow-up study of an inception cohort of 270 patients with newly diagnosed type 1 diabetes.
  
  
  RESULTS
  Patients were followed for a median of 18 years (range 1-22 years). During follow-up, 75 patients developed microalbuminuria, defined as a persistent urinary albumin excretion rate (UAER) above 30 mg/24 h. When H-ficolin levels were divided into quartile groups an unadjusted Cox proportional hazards regression model showed a significant association with risk of incident microalbuminuria during follow-up (HR, fourth vs first quartile, 2.45; 95% CI 1.24, 4.85) (p = 0.01). This remained significant after adjusting for HbA1c, systolic blood pressure, smoking and baseline UAER (HR 2.09; 95% CI 1.03, 4.25) (p = 0.04).
  
  
  CONCLUSIONS
  Our data suggest that high levels of the complement activating molecule H-ficolin are associated with an increased risk of future progression to microalbuminuria in patients with newly diagnosed type 1 diabetes.
authors: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, Building 2, DK-8000, Aarhus C, Denmark, jakob.oestergaard@clin.au.dk.
authors: Jakob A
authors: JA
authors: Østergaard
authors: Steffen
authors: S
authors: Thiel
authors: Peter
authors: P
authors: Hovind
authors: Charlotte B
authors: CB
authors: Holt
authors: Hans-Henrik
authors: HH
authors: Parving
authors: Allan
authors: A
authors: Flyvbjerg
authors: Peter
authors: P
authors: Rossing
authors: Troels K
authors: TK
authors: Hansen
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008297:Male
chemical_list: C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins