title: Incident microalbuminuria and complement factor mannan-binding lectin-associated protein 19 in people with newly diagnosed type 1 diabetes.
abstract: Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, eg, mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The MASP2 gene encodes MASP-2 and the alternative splice product MBL-associated protein 19 (MAp19). Both MAp19 and MASP-2 circulate in complex with MBL. We tested the hypothesis that MAp19 and MASP-2 concentrations predict the risk of incident microalbuminuria.
  
  
  
  Baseline MAp19 and MASP-2 were measured in 270 persons with newly diagnosed type 1 diabetes tracked for incidence of persistent microalbuminuria in a prospective observational 18-year-follow-up study.
  
  
  
  Seventy-five participants (28%) developed microalbuminuria during follow-up. MBL-associated protein 19 concentrations were higher in participants that later progressed to microalbuminuria as compared with those with persistent normoalbuminuria (268 ng/mL [95% CI, 243-293] vs 236 ng/mL [95% CI, 223-250], P = .02). Participants with MAp19 concentration within the highest quartile of the cohort had an increased risk of microalbuminuria as compared with participants with MAp19 concentration within the combined lower 3 quartiles in unadjusted Cox analysis, hazard ratio 1.86 ([95% CI, 1.17-2.96], P = .009). This remained significant in adjusted models, eg, adjusting for age, sex, HbA1c, systolic blood pressure, urinary albumin excretion, smoking, serum creatinine, and serum cholesterol. MBL-associated serine protease concentration was not associated with incidence of microalbuminuria.
  
  
  
  In conclusion, the results show an association between baseline MAp19 concentration and the incidence of microalbuminuria in an 18-year-follow-up study on persons with newly diagnosed type 1 diabetes.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.|The Danish Diabetes Academy, Odense, Denmark.
authors.forename: J A
authors.identifier: 0000-0002-9877-5327
authors.initials: JA
authors.lastname: Østergaard
authors.affiliation: Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: S
authors.identifier: 0000-0002-4817-155X
authors.initials: S
authors.lastname: Thiel
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: I T
authors.identifier: 0000-0002-5844-4304
authors.initials: IT
authors.lastname: Hoffmann-Petersen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: P
authors.identifier: 0000-0001-5630-5055
authors.initials: P
authors.lastname: Hovind
authors.affiliation: Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: H-H
authors.initials: HH
authors.lastname: Parving
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.|Nordsjaellands Hospital, Hillerød, Denmark.|Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: L
authors.identifier: 0000-0002-8735-966X
authors.initials: L
authors.lastname: Tarnow
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.|Faculty of Health, Aarhus University, Aarhus, Denmark.|Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: P
authors.identifier: 0000-0002-1531-4294
authors.initials: P
authors.lastname: Rossing
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: T K
authors.identifier: 0000-0002-0708-2868
authors.initials: TK
authors.lastname: Hansen
mesh_terms: D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases
keywords: complement; diabetes; kidney; lectin; microalbuminuria; nephropathy