Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Pharmacology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.
J Diabetes Complications. 2020 Feb;34(2):107446. doi: 10.1016/j.jdiacomp.2019.107446. Epub 2019 Sep 12.
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.
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.
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.
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.
已有研究表明，司维拉姆具有抗氧化和抗炎作用，还可改善血糖控制和血脂水平。本研究旨在评估司维拉姆治疗 1 周对核酸氧化修饰和炎症标志物的影响。
共进行了两项双盲研究，纳入了 30 例 2 型糖尿病（T2D）患者和 20 名健康对照者。参与者被随机分为司维拉姆（1600mg，每日 3 次）或安慰剂治疗组，各治疗 1 周。治疗前后检测尿液中 8-氧代-7,8-二氢鸟苷（8-oxoGuo）和（8-氧代-7,8-二氢-2'-脱氧鸟苷（8-oxodG）的排泄量，以评估核酸氧化情况，同时检测炎症标志物。
T2D 患者中，与安慰剂相比，8-oxoGuo 和 8-oxodG 无显著降低。然而，司维拉姆治疗组中 8-oxoGuo 降低（8-oxoGuo/creatinine 差值中位数[IQR]：-0.04[-0.24;0.01]nmol/mmol，p=0.02）。T2D 患者中，白细胞介素-2（IL-2）降低（p=0.04），IL-6 降低呈趋势（p=0.053）。
本研究揭示了司维拉姆治疗对炎症和可能的 RNA 氧化修饰的潜在作用。司维拉姆在 T2D 患者心血管疾病方面的潜在保护作用需要进一步研究。
