title: Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study.
abstract: OBJECTIVE
  Oxidative stress plays a key role in the development of type 2 diabetes mellitus. We previously showed that the circulating antioxidant peroxiredoxin 4 (Prx4) is associated with cardiometabolic risk factors. We aimed to evaluate the association of Prx4 with type 2 diabetes risk in the general population.
  
  
  METHODS
  We analysed data on 7,972 individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (49% men, aged 28-75 years) with no diabetes at baseline. Logistic regression models adjusted for age, sex, smoking, waist circumference, hypertension and family history of diabetes were used to estimate the ORs for type 2 diabetes.
  
  
  RESULTS
  During a median follow up of 7.7 years, 496 individuals (288 men; 58%) developed type 2 diabetes. The median (Q1-Q3) Prx4 level was 0.84 (0.53-1.40) U/l in individuals who developed type 2 diabetes and 0.68 (0.43-1.08) U/l in individuals who did not develop type 2 diabetes. For every doubling of Prx4 levels, the adjusted OR (95% CI) for type 2 diabetes was 1.16 (1.05-1.29) in the whole population; by sex, it was 1.31 (1.14-1.50) for men and 1.03 (0.87-1.21) for women. Further adjustment for other clinical measures did not materially change the results. The addition of Prx4 to a validated diabetes risk score significantly improved the prediction of type 2 diabetes in men (p = 0.002 for reclassification improvement).
  
  
  CONCLUSIONS
  Our findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes. For men, taking Prx4 into consideration can improve type 2 diabetes prediction over a validated diabetes risk score; in contrast, there is no improvement in risk prediction for women.
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands, ali.abbasi@mrc-epid.cam.ac.uk.
authors.forename: Ali
authors.initials: A
authors.lastname: Abbasi
authors.forename: Eva
authors.initials: E
authors.lastname: Corpeleijn
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.forename: Rijk O B
authors.initials: RO
authors.lastname: Gans
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Janin
authors.initials: J
authors.lastname: Schulte
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Stolk
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054464:Peroxiredoxins / Q000097:blood*; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D055105:Waist Circumference / Q000502:physiology
chemical_list: D054464:Peroxiredoxins