Comprehensive Glycomic Analysis Reveals That Human Serum Albumin Glycation Specifically Affects the Pharmacokinetics and Efficacy of Different Anticoagulant Drugs in Diabetes
Comprehensive Glycomic Analysis Reveals That Human Serum Albumin Glycation Specifically Affects the Pharmacokinetics and Efficacy of Different Anticoagulant Drugs in Diabetes
复制标题
综合糖组学分析揭示人血清白蛋白糖化特异性影响糖尿病中不同抗凝药物的药代动力学和疗效
DOI：
10.2337/db19-0738
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发表时间：
2020-04-01
期刊：
影响因子：
7.7
通讯作者：
Zhang, Qunye
中科院分区：
文献类型：
--
作者：
Qiu, Hongyan;Jin, Lan;Zhang, Qunye
糖尿病患者长期高血糖导致人血清白蛋白（HSA）糖基化，可能损害HSA作为转运蛋白的功能，影响抗凝剂对糖尿病患者的治疗效果。在这项研究中，开发了一种新的质谱方法来揭示糖尿病患者和健康受试者之间的HSA糖化位点谱的差异。K199是糖尿病患者中最显著改变的糖化位点，导致糖化HSA和正常HSA与两种类型的抗凝药物肝素和华法林的不同相互作用。体外实验表明，当HSA被糖化时，与华法林的结合亲和力变得更强，而HSA与肝素的结合不受糖化的显著影响。一项药代动力学研究显示，糖尿病大鼠血浆中游离华法林水平降低。一项初步的回顾性临床研究也显示，接受华法林治疗的糖尿病患者与非糖尿病患者之间的抗凝疗效存在统计学显著差异。我们的工作表明，需要进行更大规模的研究，为糖尿病患者在使用抗凝药物或治疗其他慢性疾病的药物时提供额外的具体指导。
Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.