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2 型糖尿病的药物遗传学:进展与展望。

Pharmacogenetics of Type 2 Diabetes-Progress and Prospects.

机构信息

Department of Genomic Medicine, D.O. Ott's Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia.

Laboratory of Biobanking and Genomic Medicine, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia.

出版信息

Int J Mol Sci. 2020 Sep 18;21(18):6842. doi: 10.3390/ijms21186842.

Abstract

Type 2 diabetes mellitus (T2D) is a chronic metabolic disease resulting from insulin resistance and progressively reduced insulin secretion, which leads to impaired glucose utilization, dyslipidemia and hyperinsulinemia and progressive pancreatic beta cell dysfunction. The incidence of type 2 diabetes mellitus is increasing worldwide and nowadays T2D already became a global epidemic. The well-known interindividual variability of T2D drug actions such as biguanides, sulfonylureas/meglitinides, DPP-4 inhibitors/GLP1R agonists and SGLT-2 inhibitors may be caused, among other things, by genetic factors. Pharmacogenetic findings may aid in identifying new drug targets and obtaining in-depth knowledge of the causes of disease and its physiological processes, thereby, providing an opportunity to elaborate an algorithm for tailor or precision treatment. The aim of this article is to summarize recent progress and discoveries for T2D pharmacogenetics and to discuss the factors which limit the furthering accumulation of genetic variability knowledge in patient response to therapy that will allow improvement the personalized treatment of T2D.

摘要

2 型糖尿病(T2DM)是一种由胰岛素抵抗和逐渐减少的胰岛素分泌引起的慢性代谢性疾病,导致葡萄糖利用受损、血脂异常和高胰岛素血症以及进行性胰岛β细胞功能障碍。全球范围内 2 型糖尿病的发病率正在增加,如今 2 型糖尿病已成为全球性流行疾病。二甲双胍、磺酰脲类药物/米格列汀类药物、DPP-4 抑制剂/GLP1R 激动剂和 SGLT-2 抑制剂等 T2D 药物作用的个体间显著差异可能是由遗传因素引起的。药物遗传学发现可能有助于确定新的药物靶点,并深入了解疾病的病因及其生理过程,从而为制定个体化或精准治疗方案提供机会。本文旨在总结 T2D 药物遗传学的最新进展和发现,并讨论限制进一步积累治疗反应中遗传变异性知识的因素,这将有助于改善 T2D 的个体化治疗。

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