Abstract
Aims/hypothesisOxidative 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.MethodsWe 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.ResultsDuring 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/interpretationOur 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-014-3278-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Highlights
MethodsType 2 diabetes mellitus is a leading cause of lifelong morbidity and all-cause mortality in many countries worldwide [1, 2]
A comparison of peroxiredoxin 4 (Prx4) levels in individuals who developed new-onset type 2 diabetes vs individuals who remained free of disease is shown in ESM Table 1
After adjusting for regression dilution bias, the OR per single unit increase in log2Prx4 was 1.67 (1.28–2.17) and 1.06 (0.76–1.48) for men and for women, respectively, in model 2. In this large prospective cohort with no diabetes at baseline, we demonstrated that circulating Prx4 concentrations are positively associated with an increased risk of new-onset type 2 diabetes even after adjusting for established diabetes risk factors
Summary
Type 2 diabetes mellitus is a leading cause of lifelong morbidity and all-cause mortality in many countries worldwide [1, 2]. The multifactorial and chronic natural history of type 2 diabetes makes it a promising, but challenging, target for therapeutic intervention in its early stages. Evidence suggests that oxidative stress plays a key role in the initiation and progression of type 2 diabetes [3]. A number of studies have identified a relationship between oxidation products or antioxidant levels and the disease state [4,5,6,7]. Clinical or observational data showing associations between oxidative stress markers and type 2 diabetes are scarce [5]. Reasons for the current lack of published population-based studies include technical difficulties in biomarker analysis and an absence of reliable assays [5, 8]
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