TY - JOUR
T1 - Changes in oxidative nucleic acid modifications and inflammation following one-week treatment with the bile acid sequestrant sevelamer
T2 - Two randomised, placebo-controlled trials
AU - Brønden, Andreas
AU - Larsen, Emil List
AU - Karstoft, Kristian
AU - Henriksen, Trine
AU - Vilsbøll, Tina
AU - Poulsen, Henrik Enghusen
AU - Knop, Filip Krag
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2020/2
Y1 - 2020/2
N2 - AIMS: Sevelamer has been reported to have anti-oxidative and anti-inflammatory effects as well as effects on glycaemic control and plasma lipids. The aim of this study was to determine the effects of one-week treatment with sevelamer on oxidative nucleic acid modifications and inflammation markers.METHODS: Two double-blinded studies including 30 patients with type 2 diabetes (T2D) and 20 healthy individuals were conducted. Participants were randomised to one week of treatment with sevelamer (1600 mg three times daily) or placebo. RNA and DNA oxidation, measured by urinary excretion of 8-oxo-7,8-dihydroguanosine(8-oxoGuo) and (8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxodG), and markers of inflammation were determined before and after the intervention.RESULTS: In patients with T2D there was no significant placebo-corrected reduction in 8-oxoGuo or 8-oxodG. However, a reduction in 8-oxoGuo was observed within the group treated with sevelamer (∆8-oxoGuo/creatinine (median[IQR]): -0.04 [-0.24; 0.01] nmol/mmol, p = 0.02). A sevelamer-mediated reduction in interleukin-2 (p = 0.04) and a trend towards reduction in interleukin-6 (p = 0.053) were found in patients with T2D.CONCLUSIONS: This study reveals a potential effect of sevelamer treatment on inflammation and possible oxidative RNA modifications. The potential protective effects of sevelamer in terms of cardiovascular disease in patients with T2D need further investigation.
AB - AIMS: Sevelamer has been reported to have anti-oxidative and anti-inflammatory effects as well as effects on glycaemic control and plasma lipids. The aim of this study was to determine the effects of one-week treatment with sevelamer on oxidative nucleic acid modifications and inflammation markers.METHODS: Two double-blinded studies including 30 patients with type 2 diabetes (T2D) and 20 healthy individuals were conducted. Participants were randomised to one week of treatment with sevelamer (1600 mg three times daily) or placebo. RNA and DNA oxidation, measured by urinary excretion of 8-oxo-7,8-dihydroguanosine(8-oxoGuo) and (8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxodG), and markers of inflammation were determined before and after the intervention.RESULTS: In patients with T2D there was no significant placebo-corrected reduction in 8-oxoGuo or 8-oxodG. However, a reduction in 8-oxoGuo was observed within the group treated with sevelamer (∆8-oxoGuo/creatinine (median[IQR]): -0.04 [-0.24; 0.01] nmol/mmol, p = 0.02). A sevelamer-mediated reduction in interleukin-2 (p = 0.04) and a trend towards reduction in interleukin-6 (p = 0.053) were found in patients with T2D.CONCLUSIONS: This study reveals a potential effect of sevelamer treatment on inflammation and possible oxidative RNA modifications. The potential protective effects of sevelamer in terms of cardiovascular disease in patients with T2D need further investigation.
KW - 8-oxo-7,8-dihydro-2′-deoxyguanosine
KW - 8-oxo-7,8-dihydro-guanosine
KW - Inflammation
KW - Oxidative stress
KW - Sevelamer
KW - Type 2 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=85074532473&partnerID=8YFLogxK
U2 - 10.1016/j.jdiacomp.2019.107446
DO - 10.1016/j.jdiacomp.2019.107446
M3 - Journal article
C2 - 31672458
VL - 34
JO - Journal of Diabetes and its Complications
JF - Journal of Diabetes and its Complications
SN - 1056-8727
IS - 2
M1 - 107446
ER -