title: Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in type 2 diabetes (ZODIAC-28).
abstract: BACKGROUND
  Oxidative stress plays an underlying pathophysiologic role in the development of diabetes complications. The aim of this study was to investigate peroxiredoxin 4 (Prx4), a proposed novel biomarker of oxidative stress, and its association with and capability as a biomarker in predicting (cardiovascular) mortality in type 2 diabetes mellitus.
  
  
  METHODS
  Prx4 was assessed in baseline serum samples of 1161 type 2 diabetes patients. Cox proportional hazard models were used to evaluate the relationship between Prx4 and (cardiovascular) mortality. Risk prediction capabilities of Prx4 for (cardiovascular) mortality were assessed with Harrell's C statistic, the integrated discrimination improvement and net reclassification improvement.
  
  
  RESULTS
  Mean age was 67 and the median diabetes duration was 4.0 years. After a median follow-up period of 5.8 years, 327 patients died; 137 cardiovascular deaths. Prx4 was associated with (cardiovascular) mortality. The Cox proportional hazard models added the variables: Prx4 (model 1); age and gender (model 2), and BMI, creatinine, smoking, diabetes duration, systolic blood pressure, cholesterol-HDL ratio, history of macrovascular complications, and albuminuria (model 3). Hazard ratios (HR) (95% CI) for cardiovascular mortality were 1.93 (1.57 - 2.38), 1.75 (1.39 - 2.20), and 1.63 (1.28 - 2.09) for models 1, 2 and 3, respectively. HR for all-cause mortality were 1.73 (1.50 - 1.99), 1.50 (1.29 - 1.75), and 1.44 (1.23 - 1.67) for models 1, 2 and 3, respectively. Addition of Prx4 to the traditional risk factors slightly improved risk prediction of (cardiovascular) mortality.
  
  
  CONCLUSIONS
  Prx4 is independently associated with (cardiovascular) mortality in type 2 diabetes patients. After addition of Prx4 to the traditional risk factors, there was a slightly improvement in risk prediction of (cardiovascular) mortality in this patient group.
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands ; Diabetes Centre, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Esther G
authors.initials: EG
authors.lastname: Gerrits
authors.affiliation: Diabetes Centre, Isala Clinics, Zwolle, The Netherlands ; Department of Gastroenterology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Alaa
authors.initials: A
authors.lastname: Alkhalaf
authors.affiliation: Diabetes Centre, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Gijs W D
authors.initials: GW
authors.lastname: Landman
authors.affiliation: Diabetes Centre, Isala Clinics, Zwolle, The Netherlands ; Langerhans Medical Research Group, Zwolle, The Netherlands.
authors.forename: Kornelis J J
authors.initials: KJ
authors.lastname: van Hateren
authors.affiliation: Diabetes Centre, Isala Clinics, Zwolle, The Netherlands ; Department of General Practice, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Klaas H
authors.initials: KH
authors.lastname: Groenier
authors.affiliation: Thermo Fisher Scientific, BRAHMS Biomarkers, Research Department, Hennigsdorf, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.affiliation: Thermo Fisher Scientific, BRAHMS Biomarkers, Research Department, Hennigsdorf, Germany.
authors.forename: Janin
authors.initials: J
authors.lastname: Schulte
authors.affiliation: Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Reinold O B
authors.initials: RO
authors.lastname: Gans
authors.affiliation: Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Diabetes Centre, Isala Clinics, Zwolle, The Netherlands ; Langerhans Medical Research Group, Zwolle, The Netherlands ; Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Nanne
authors.initials: N
authors.lastname: Kleefstra
authors.affiliation: Diabetes Centre, Isala Clinics, Zwolle, The Netherlands ; Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands ; Department of Internal Medicine, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Henk J G
authors.initials: HJ
authors.lastname: Bilo
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000401:mortality*; D003924:Diabetes Mellitus, Type 2; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000097:blood*; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D054464:Peroxiredoxins