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精准医学:糖尿病护理的未来?

Precision medicine: The future in diabetes care?

作者信息

Scheen André J

机构信息

Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, University of Liège, Liège, Belgium; Clinical Pharmacology Unit, CHU Liège, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium.

出版信息

Diabetes Res Clin Pract. 2016 Jul;117:12-21. doi: 10.1016/j.diabres.2016.04.033. Epub 2016 Apr 26.

Abstract

Personalized medicine aims at better targeting therapeutic intervention to the individual to maximize benefit and minimize harm. Type 2 diabetes (T2D) is a heterogeneous disease from a genetic, pathophysiological and clinical point of view. Thus, the response to any antidiabetic medication may considerably vary between individuals. Numerous glucose-lowering agents, with different mechanisms of action, have been developed, a diversified armamentarium that offers the possibility of a patient-centred therapeutic approach. In the current clinical practice, a personalized approach is only based upon phenotype, taking into account patient and disease individual characteristics. If this approach may help increase both efficacy and safety outcomes, there remains considerable room for improvement. In recent years, many efforts were taken to identify genetic and genotype SNP's (Single Nucleotide Polymorphism's) variants that influence the pharmacokinetics, pharmacodynamics, and ultimately the therapeutic response of oral glucose-lowering drugs. This approach mainly concerns metformin, sulphonylureas, meglitinides and thiazolidinediones, with only scarce data concerning gliptins and gliflozins yet. However, the contribution of pharmacogenetics and pharmacogenomics to personalized therapy still needs to mature greatly before routine clinical implementation is possible. This review discusses both opportunities and challenges of precision medicine and how this new paradigm may lead to a better individualized treatment of T2D.

摘要

个性化医疗旨在更精准地针对个体进行治疗干预,以实现效益最大化和危害最小化。从基因、病理生理和临床角度来看,2型糖尿病(T2D)是一种异质性疾病。因此,个体对任何抗糖尿病药物的反应可能会有很大差异。目前已经研发出了多种作用机制不同的降糖药物,这一多样化的药物库为以患者为中心的治疗方法提供了可能。在当前的临床实践中,个性化方法仅基于表型,同时考虑患者和疾病的个体特征。尽管这种方法可能有助于提高疗效和安全性,但仍有很大的改进空间。近年来,人们进行了许多努力来识别影响口服降糖药物的药代动力学、药效学以及最终治疗反应的基因和基因型单核苷酸多态性(SNP)变体。这种方法主要涉及二甲双胍、磺脲类、格列奈类和噻唑烷二酮类药物,而关于二肽基肽酶-4抑制剂和钠-葡萄糖协同转运蛋白2抑制剂的相关数据仍然很少。然而,在能够常规临床应用之前,药物遗传学和药物基因组学对个性化治疗的贡献仍需要大幅完善。本综述讨论了精准医疗的机遇与挑战,以及这种新范式如何可能带来更好的T2D个体化治疗。

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