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Published in: Diabetologia 9/2014

Open Access 01-09-2014 | Article

Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Authors: Ali Abbasi, Eva Corpeleijn, Ron T. Gansevoort, Rijk O. B. Gans, Joachim Struck, Janin Schulte, Hans L. Hillege, Pim van der Harst, Ronald P. Stolk, Gerjan Navis, Stephan J. L. Bakker

Published in: Diabetologia | Issue 9/2014

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Abstract

Aims/hypothesis

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/interpretation

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.
Appendix
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Literature
1.
go back to reference Seshasai SR, Kaptoge S, Thompson A et al (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 364:829–841PubMedCrossRef Seshasai SR, Kaptoge S, Thompson A et al (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 364:829–841PubMedCrossRef
2.
go back to reference Danaei G, Finucane MM, Lu Y et al (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378:31–40PubMedCrossRef Danaei G, Finucane MM, Lu Y et al (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378:31–40PubMedCrossRef
4.
go back to reference Giustarini D, Dalle-Donne I, Tsikas D, Rossi R (2009) Oxidative stress and human diseases: origin, link, measurement, mechanisms, and biomarkers. Crit Rev Clin Lab Sci 46:241–281PubMedCrossRef Giustarini D, Dalle-Donne I, Tsikas D, Rossi R (2009) Oxidative stress and human diseases: origin, link, measurement, mechanisms, and biomarkers. Crit Rev Clin Lab Sci 46:241–281PubMedCrossRef
5.
go back to reference Matsushita K, Williams EK, Mongraw-Chaffin ML et al (2012) The association of plasma lactate with incident cardiovascular outcomes: the ARIC study. Am J Epidemiol 178:401–409CrossRef Matsushita K, Williams EK, Mongraw-Chaffin ML et al (2012) The association of plasma lactate with incident cardiovascular outcomes: the ARIC study. Am J Epidemiol 178:401–409CrossRef
6.
go back to reference Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A (2006) Biomarkers of oxidative damage in human disease. Clin Chem 52:601–623PubMedCrossRef Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A (2006) Biomarkers of oxidative damage in human disease. Clin Chem 52:601–623PubMedCrossRef
7.
go back to reference Strobel NA, Fassett RG, Marsh SA, Coombes JS (2011) Oxidative stress biomarkers as predictors of cardiovascular disease. Int J Cardiol 147:191–201PubMedCrossRef Strobel NA, Fassett RG, Marsh SA, Coombes JS (2011) Oxidative stress biomarkers as predictors of cardiovascular disease. Int J Cardiol 147:191–201PubMedCrossRef
8.
go back to reference Melander O, Newton-Cheh C, Almgren P et al (2009) Novel and conventional biomarkers for prediction of incident cardiovascular events in the community. JAMA 302:49–57 Melander O, Newton-Cheh C, Almgren P et al (2009) Novel and conventional biomarkers for prediction of incident cardiovascular events in the community. JAMA 302:49–57
9.
go back to reference Nabeshima A, Yamada S, Guo X et al (2013) Peroxiredoxin 4 protects against nonalcoholic steatohepatitis and type 2 diabetes in a nongenetic mouse model. Antioxid Redox Signal 19:1983–1998PubMedCentralPubMedCrossRef Nabeshima A, Yamada S, Guo X et al (2013) Peroxiredoxin 4 protects against nonalcoholic steatohepatitis and type 2 diabetes in a nongenetic mouse model. Antioxid Redox Signal 19:1983–1998PubMedCentralPubMedCrossRef
10.
go back to reference Barcelo-Batllori S, Corominola H, Claret M, Canals I, Guinovart J, Gomis R (2005) Target identification of the novel antiobesity agent tungstate in adipose tissue from obese rats. Proteomics 5:4927–4935PubMedCrossRef Barcelo-Batllori S, Corominola H, Claret M, Canals I, Guinovart J, Gomis R (2005) Target identification of the novel antiobesity agent tungstate in adipose tissue from obese rats. Proteomics 5:4927–4935PubMedCrossRef
11.
go back to reference Ding Y, Yamada S, Wang KY et al (2010) Overexpression of peroxiredoxin 4 protects against high-dose streptozotocin-induced diabetes by suppressing oxidative stress and cytokines in transgenic mice. Antioxid Redox Signal 13:1477–1490PubMedCrossRef Ding Y, Yamada S, Wang KY et al (2010) Overexpression of peroxiredoxin 4 protects against high-dose streptozotocin-induced diabetes by suppressing oxidative stress and cytokines in transgenic mice. Antioxid Redox Signal 13:1477–1490PubMedCrossRef
12.
go back to reference Wei Q, Jiang H, Xiao Z et al (2011) Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling. Proc Natl Acad Sci U S A 108:7004–7009PubMedCentralPubMedCrossRef Wei Q, Jiang H, Xiao Z et al (2011) Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling. Proc Natl Acad Sci U S A 108:7004–7009PubMedCentralPubMedCrossRef
13.
go back to reference Okado-Matsumoto A, Matsumoto A, Fujii J, Taniguchi N (2000) Peroxiredoxin IV is a secretable protein with heparin-binding properties under reduced conditions. J Biochem 127:493–501PubMedCrossRef Okado-Matsumoto A, Matsumoto A, Fujii J, Taniguchi N (2000) Peroxiredoxin IV is a secretable protein with heparin-binding properties under reduced conditions. J Biochem 127:493–501PubMedCrossRef
14.
go back to reference Schulte J, Struck J, Bergmann A, Kohrle J (2010) Immunoluminometric assay for quantification of peroxiredoxin 4 in human serum. Clin Chim Acta 411:1258–1263PubMedCrossRef Schulte J, Struck J, Bergmann A, Kohrle J (2010) Immunoluminometric assay for quantification of peroxiredoxin 4 in human serum. Clin Chim Acta 411:1258–1263PubMedCrossRef
15.
go back to reference Abbasi A, Corpeleijn E, Postmus D et al (2012) Peroxiredoxin 4, a novel circulating biomarker for oxidative stress and the risk of incident cardiovascular disease and all-cause mortality. J Am Heart Assoc 1:e002956PubMedCentralPubMedCrossRef Abbasi A, Corpeleijn E, Postmus D et al (2012) Peroxiredoxin 4, a novel circulating biomarker for oxidative stress and the risk of incident cardiovascular disease and all-cause mortality. J Am Heart Assoc 1:e002956PubMedCentralPubMedCrossRef
16.
go back to reference Schulte J, Struck J, Kohrle J, Muller B (2011) Circulating levels of peroxiredoxin 4 as a novel biomarker of oxidative stress in patients with sepsis. Shock 35:460–465PubMedCrossRef Schulte J, Struck J, Kohrle J, Muller B (2011) Circulating levels of peroxiredoxin 4 as a novel biomarker of oxidative stress in patients with sepsis. Shock 35:460–465PubMedCrossRef
17.
go back to reference Lambers Heerspink HJ, Brantsma AH, de Zeeuw D, Bakker SJ, de Jong PE, Gansevoort RT (2008) Albuminuria assessed from first-morning-void urine samples versus 24-hour urine collections as a predictor of cardiovascular morbidity and mortality. Am J Epidemiol 168:897–905PubMedCrossRef Lambers Heerspink HJ, Brantsma AH, de Zeeuw D, Bakker SJ, de Jong PE, Gansevoort RT (2008) Albuminuria assessed from first-morning-void urine samples versus 24-hour urine collections as a predictor of cardiovascular morbidity and mortality. Am J Epidemiol 168:897–905PubMedCrossRef
18.
go back to reference Mahmoodi BK, Gansevoort RT, Veeger NJ et al (2009) Microalbuminuria and risk of venous thromboembolism. JAMA 301:1790–1797 Mahmoodi BK, Gansevoort RT, Veeger NJ et al (2009) Microalbuminuria and risk of venous thromboembolism. JAMA 301:1790–1797
19.
go back to reference Abbasi A, Corpeleijn E, Postmus D et al (2010) Plasma procalcitonin is associated with obesity, insulin resistance, and the metabolic syndrome. J Clin Endocrinol Metab 95:E26–E31PubMedCrossRef Abbasi A, Corpeleijn E, Postmus D et al (2010) Plasma procalcitonin is associated with obesity, insulin resistance, and the metabolic syndrome. J Clin Endocrinol Metab 95:E26–E31PubMedCrossRef
20.
go back to reference Abbasi A, Corpeleijn E, Postmus D et al (2011) Plasma procalcitonin and risk of type 2 diabetes in the general population. Diabetologia 54:2463–2465PubMedCrossRef Abbasi A, Corpeleijn E, Postmus D et al (2011) Plasma procalcitonin and risk of type 2 diabetes in the general population. Diabetologia 54:2463–2465PubMedCrossRef
22.
go back to reference Abbasi A, Peelen LM, Corpeleijn E et al (2012) Prediction models for risk of developing type 2 diabetes: systematic literature search and independent external validation study. BMJ 345:e5900PubMedCentralPubMedCrossRef Abbasi A, Peelen LM, Corpeleijn E et al (2012) Prediction models for risk of developing type 2 diabetes: systematic literature search and independent external validation study. BMJ 345:e5900PubMedCentralPubMedCrossRef
23.
go back to reference Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R (2003) Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 26:3320–3325PubMedCrossRef Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R (2003) Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 26:3320–3325PubMedCrossRef
24.
go back to reference Hivert MF, Sullivan LM, Shrader P et al (2011) Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study. Diabetologia 54:1019–1024PubMedCentralPubMedCrossRef Hivert MF, Sullivan LM, Shrader P et al (2011) Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study. Diabetologia 54:1019–1024PubMedCentralPubMedCrossRef
25.
26.
go back to reference Balkau B, Lange C, Fezeu L et al (2008) Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 31:2056–2061PubMedCentralPubMedCrossRef Balkau B, Lange C, Fezeu L et al (2008) Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 31:2056–2061PubMedCentralPubMedCrossRef
27.
go back to reference Paynter NP, Mazer NA, Pradhan AD, Gaziano JM, Ridker PM, Cook NR (2011) Cardiovascular risk prediction in diabetic men and women using hemoglobin A1c vs diabetes as a high-risk equivalent. Arch Intern Med 171:1712–1718PubMedCentralPubMedCrossRef Paynter NP, Mazer NA, Pradhan AD, Gaziano JM, Ridker PM, Cook NR (2011) Cardiovascular risk prediction in diabetic men and women using hemoglobin A1c vs diabetes as a high-risk equivalent. Arch Intern Med 171:1712–1718PubMedCentralPubMedCrossRef
28.
go back to reference Pencina MJ, D’Agostino RB Sr, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30:11–21PubMedCentralPubMedCrossRef Pencina MJ, D’Agostino RB Sr, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30:11–21PubMedCentralPubMedCrossRef
29.
go back to reference Knuiman MW, Divitini ML, Buzas JS, Fitzgerald PE (1998) Adjustment for regression dilution in epidemiological regression analyses. Ann Epidemiol 8:56–63PubMedCrossRef Knuiman MW, Divitini ML, Buzas JS, Fitzgerald PE (1998) Adjustment for regression dilution in epidemiological regression analyses. Ann Epidemiol 8:56–63PubMedCrossRef
30.
go back to reference Wilson PW, Meigs JB, Sullivan L, Fox CS, Nathan DM, D’Agostino RB Sr (2007) Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study. Arch Intern Med 167:1068–1074PubMedCrossRef Wilson PW, Meigs JB, Sullivan L, Fox CS, Nathan DM, D’Agostino RB Sr (2007) Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study. Arch Intern Med 167:1068–1074PubMedCrossRef
31.
go back to reference El Eter E, Al Masri A, Habib S et al (2014) Novel links among peroxiredoxins, endothelial dysfunction, and severity of atherosclerosis in type 2 diabetic patients with peripheral atherosclerotic disease. Cell Stress Chaperones 19:173–181PubMedCrossRef El Eter E, Al Masri A, Habib S et al (2014) Novel links among peroxiredoxins, endothelial dysfunction, and severity of atherosclerosis in type 2 diabetic patients with peripheral atherosclerotic disease. Cell Stress Chaperones 19:173–181PubMedCrossRef
32.
go back to reference Dreja T, Jovanovic Z, Rasche A et al (2010) Diet-induced gene expression of isolated pancreatic islets from a polygenic mouse model of the metabolic syndrome. Diabetologia 53:309–320PubMedCentralPubMedCrossRef Dreja T, Jovanovic Z, Rasche A et al (2010) Diet-induced gene expression of isolated pancreatic islets from a polygenic mouse model of the metabolic syndrome. Diabetologia 53:309–320PubMedCentralPubMedCrossRef
33.
go back to reference Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–948PubMedCrossRef Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–948PubMedCrossRef
34.
go back to reference Wood ZA, Schroder E, Robin Harris J, Poole LB (2003) Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci 28:32–40PubMedCrossRef Wood ZA, Schroder E, Robin Harris J, Poole LB (2003) Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci 28:32–40PubMedCrossRef
35.
go back to reference Nickel CH, Ruedinger J, Misch F et al (2011) Copeptin and peroxiredoxin-4 independently predict mortality in patients with nonspecific complaints presenting to the emergency department. Acad Emerg Med 18:851–859PubMedCrossRef Nickel CH, Ruedinger J, Misch F et al (2011) Copeptin and peroxiredoxin-4 independently predict mortality in patients with nonspecific complaints presenting to the emergency department. Acad Emerg Med 18:851–859PubMedCrossRef
36.
go back to reference Hillege HL, Fidler V, Diercks GF et al (2002) Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 106:1777–1782PubMedCrossRef Hillege HL, Fidler V, Diercks GF et al (2002) Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 106:1777–1782PubMedCrossRef
37.
go back to reference Wormser D, Kaptoge S, Di Angelantonio E et al (2011) Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet 377:1085–1095PubMedCrossRef Wormser D, Kaptoge S, Di Angelantonio E et al (2011) Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet 377:1085–1095PubMedCrossRef
39.
go back to reference Jin DY, Chae HZ, Rhee SG, Jeang KT (1997) Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation. J Biol Chem 272:30952–30961PubMedCrossRef Jin DY, Chae HZ, Rhee SG, Jeang KT (1997) Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation. J Biol Chem 272:30952–30961PubMedCrossRef
40.
go back to reference Wong CM, Chun AC, Kok KH et al (2000) Characterization of human and mouse peroxiredoxin IV: evidence for inhibition by Prx-IV of epidermal growth factor- and p53-induced reactive oxygen species. Antioxid Redox Signal 2:507–518PubMedCrossRef Wong CM, Chun AC, Kok KH et al (2000) Characterization of human and mouse peroxiredoxin IV: evidence for inhibition by Prx-IV of epidermal growth factor- and p53-induced reactive oxygen species. Antioxid Redox Signal 2:507–518PubMedCrossRef
41.
go back to reference Giguere P, Turcotte ME, Hamelin E et al (2007) Peroxiredoxin-4 interacts with and regulates the thromboxane A(2) receptor. FEBS Lett 581:3863–3868PubMedCrossRef Giguere P, Turcotte ME, Hamelin E et al (2007) Peroxiredoxin-4 interacts with and regulates the thromboxane A(2) receptor. FEBS Lett 581:3863–3868PubMedCrossRef
42.
go back to reference Bertolotti M, Yim SH, Garcia-Manteiga JM et al (2010) B- to plasma-cell terminal differentiation entails oxidative stress and profound reshaping of the antioxidant responses. Antioxid Redox Signal 13:1133–1144PubMedCrossRef Bertolotti M, Yim SH, Garcia-Manteiga JM et al (2010) B- to plasma-cell terminal differentiation entails oxidative stress and profound reshaping of the antioxidant responses. Antioxid Redox Signal 13:1133–1144PubMedCrossRef
43.
go back to reference Pergola PE, Raskin P, Toto RD et al (2011) Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 365:327–336PubMedCrossRef Pergola PE, Raskin P, Toto RD et al (2011) Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 365:327–336PubMedCrossRef
Metadata
Title
Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study
Authors
Ali Abbasi
Eva Corpeleijn
Ron T. Gansevoort
Rijk O. B. Gans
Joachim Struck
Janin Schulte
Hans L. Hillege
Pim van der Harst
Ronald P. Stolk
Gerjan Navis
Stephan J. L. Bakker
Publication date
01-09-2014
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 9/2014
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-014-3278-9

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