title: ADAMTS13 activity as a novel risk factor for incident type 2 diabetes mellitus: a population-based cohort study.
abstract: ADAMTS13 is a protease that breaks down von Willebrand factor (VWF) multimers into smaller, less active particles. VWF has been associated with an increased risk of incident type 2 diabetes mellitus. Here, we determine whether ADAMTS13 activity and VWF antigen are associated with incident diabetes.
  
  
  
  This study included 5176 participants from the Rotterdam Study, a prospective population-based cohort study. Participants were free of diabetes at baseline and followed up for more than 20 years. Cox proportional hazards models were used to examine the association of ADAMTS13 activity and VWF antigen with incident diabetes.
  
  
  
  ADAMTS13 activity was associated with an increased risk of incident diabetes (HR 1.17 [95% CI 1.08, 1.27]) after adjustment for known risk factors and VWF antigen levels. Although ADAMTS13 activity was positively associated with fasting glucose and insulin, the association with incident diabetes did not change when we adjusted for these covariates. ADAMTS13 activity was also associated with incident prediabetes (defined on the basis of both fasting and non-fasting blood glucose) after adjustment for known risk factors (HR 1.11 [95% CI 1.03, 1.19]), while the VWF antigen level was not. VWF antigen was associated with incident diabetes, but this association was attenuated after adjustment for known risk factors.
  
  
  
  ADAMTS13 activity appears to be an independent risk factor for incident prediabetes and type 2 diabetes. As the association between ADAMTS13 and diabetes did not appear to be explained by its cleavage of VWF, ADAMTS13 may have an independent role in the development of diabetes.
authors: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.|Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors: Paul S
authors: PS
authors: de Vries
authors: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.|Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Thijs T W
authors: TT
authors: van Herpt
authors: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Symen
authors: S
authors: Ligthart
authors: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Albert
authors: A
authors: Hofman
authors: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.|Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.|Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: M Arfan
authors: MA
authors: Ikram
authors: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Mandy
authors: M
authors: van Hoek
authors: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Eric J G
authors: EJ
authors: Sijbrands
authors: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Oscar H
authors: OH
authors: Franco
authors: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Moniek P M
authors: MP
authors: de Maat
authors: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Frank W G
authors: FW
authors: Leebeek
authors: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. a.dehghan@imperial.ac.uk.|Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK. a.dehghan@imperial.ac.uk.
authors: Abbas
authors: A
authors: Dehghan
mesh_terms: D000071120:ADAMTS13 Protein / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014841:von Willebrand Factor; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; Diabetes; Epidemiology; Incidence; Prediabetes; Risk factor; Von Willebrand factor