1. Serum peroxiredoxin-4, a biomarker of oxidative stress, is associated with the development of nephropathy in patients with type 2 diabetes (Zodiac-65).
- Author
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Bourgonje, Arno R., van Goor, Harry, Bakker, Stephan J.L., Hillebrands, Jan-Luuk, Bilo, Henk J.G., Dullaart, Robin P.F., and van Dijk, Peter R.
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TYPE 2 diabetes , *OXIDATIVE stress , *KIDNEY diseases , *DIABETIC nephropathies , *SYSTOLIC blood pressure , *BLOOD pressure - Abstract
Oxidative stress is implicated in the development and progression of type 2 diabetes (T2D). Peroxiredoxin-4 is an antioxidant protein, which may serve as biomarker of oxidative stress, and has previously been associated with new-onset T2D. In this study, we investigated associations between circulating peroxiredoxin-4 and the risk of developing new-onset microvascular complications in T2D patients. Serum peroxiredoxin-4 was measured in 536 patients with T2D with (n = 257) and without (n = 279) baseline microvascular complications who participated in a primary-care based cohort study (Zwolle Outpatient Diabetes project Integrating Available Care [ZODIAC] study). Over a median follow-up of 3.4 years, 38 (13.6%) developed nephropathy, defined as albuminuria in two consecutive urine samples. In multivariable Cox proportional hazards regression analyses, peroxiredoxin-4 was associated with new-onset nephropathy (hazard ratio [HR] per doubling 1.78 [95% CI: 1.27–2.49], P < 0.001) after adjustment for potential confounding factors, including age, sex, disease duration, HbA1c levels, macrovascular complications, systolic blood pressure, and even high-sensitive C-reactive protein. There was no interaction of peroxiredoxin-4 with hs-CRP impacting on new-onset nephropathy. No significant associations were found with new-onset retinopathy or neuropathy. In conclusion, circulating peroxiredoxin-4 associates positively with an increased risk of developing nephropathy in T2D independent and irrespective of low-grade inflammation. [Display omitted] • Circulating peroxiredoxin-4 levels may represent a systemic biomarker of oxidative stress. • High serum peroxiredoxin-4 levels associate with the development of diabetic nephropathy. • Serum peroxiredoxin-4 levels and new-onset diabetic nephropathy associated independently of low-grade inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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