Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in type 2 diabetes (ZODIAC-28).

<h4>Background</h4>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 biomar...

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Main Authors: Esther G Gerrits, Alaa Alkhalaf, Gijs W D Landman, Kornelis J J van Hateren, Klaas H Groenier, Joachim Struck, Janin Schulte, Reinold O B Gans, Stephan J L Bakker, Nanne Kleefstra, Henk J G Bilo
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089719&type=printable
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author Esther G Gerrits
Alaa Alkhalaf
Gijs W D Landman
Kornelis J J van Hateren
Klaas H Groenier
Joachim Struck
Janin Schulte
Reinold O B Gans
Stephan J L Bakker
Nanne Kleefstra
Henk J G Bilo
author_facet Esther G Gerrits
Alaa Alkhalaf
Gijs W D Landman
Kornelis J J van Hateren
Klaas H Groenier
Joachim Struck
Janin Schulte
Reinold O B Gans
Stephan J L Bakker
Nanne Kleefstra
Henk J G Bilo
author_sort Esther G Gerrits
collection DOAJ
description <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
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spelling doaj-art-73ec9d2b831e45fbbe3409d282d89ad02025-08-20T02:15:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8971910.1371/journal.pone.0089719Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in type 2 diabetes (ZODIAC-28).Esther G GerritsAlaa AlkhalafGijs W D LandmanKornelis J J van HaterenKlaas H GroenierJoachim StruckJanin SchulteReinold O B GansStephan J L BakkerNanne KleefstraHenk J G Bilo<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089719&type=printable
spellingShingle Esther G Gerrits
Alaa Alkhalaf
Gijs W D Landman
Kornelis J J van Hateren
Klaas H Groenier
Joachim Struck
Janin Schulte
Reinold O B Gans
Stephan J L Bakker
Nanne Kleefstra
Henk J G Bilo
Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in type 2 diabetes (ZODIAC-28).
PLoS ONE
title Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in type 2 diabetes (ZODIAC-28).
title_full Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in type 2 diabetes (ZODIAC-28).
title_fullStr Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in type 2 diabetes (ZODIAC-28).
title_full_unstemmed Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in type 2 diabetes (ZODIAC-28).
title_short Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in type 2 diabetes (ZODIAC-28).
title_sort serum peroxiredoxin 4 a marker of oxidative stress associated with mortality in type 2 diabetes zodiac 28
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089719&type=printable
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