title: Increased all-cause mortality in patients with type 1 diabetes and high-expression mannan-binding lectin genotypes: a 12-year follow-up study.
abstract: OBJECTIVE
  Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this.
  
  
  METHODS
  We studied an existing 12-year prospective cohort with type 1 diabetes with 198 patients with diabetic nephropathy (121 men, age 41 years [95% CI 40-42], estimated glomerular filtration rate [eGFR] 67 mL/min/1.73 m(2) [95% CI 63-70]) and 174 normoalbuminuric patients (103 men, age 43 years [95% CI 41-44], eGFR 93 mL/min/1.73 m(2) [95% CI 91-95]). Mortality rates were compared according to the concentration-determining MBL2 genotype or the MBL concentration. Patients were classified as having high or low MBL expression genotypes. The effect of MBL concentration was estimated by comparing patients with MBL concentrations above or below the median.
  
  
  RESULTS
  Ninety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07-2.43) for patients with high MBL expression genotypes versus patients with low MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26-2.87], P = 0.002).
  
  
  CONCLUSIONS
  High MBL expression genotypes and high MBL concentrations are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark The Danish Diabetes Academy, Odense, Denmark jakob.oestergaard@clin.au.dk.
authors.forename: Jakob A
authors.initials: JA
authors.lastname: Østergaard
authors.affiliation: Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Lajer
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.affiliation: Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark Faculty of Health, Aarhus University, Aarhus, Denmark Nordsjællands Hospital, Hillerød, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Troels K
authors.initials: TK
authors.lastname: Hansen
mesh_terms: D000328:Adult; D003167:Complement Activation / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D004812:Epidemiologic Methods; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism*
chemical_list: D037601:Mannose-Binding Lectin