Amblee Ambika
Division of Endocrinology, John H Stroger Jr Hospital of Cook County, Chicago, IL, USA ; Rush University Medical Center, Chicago, IL, USA.
Pharmgenomics Pers Med. 2014 Nov 18;7:367-77. doi: 10.2147/52761.s0. eCollection 2014.
Physicians attempt to achieve glycemic goals in patients with type 2 diabetes mellitus (T2DM) through various means, including glucose-lowering medications. There is interindividual variability in response to medications, which can be partially explained by the presence of genetic polymorphisms that affect drug metabolism. Pharmacogenomics studies the hereditary basis of interpatient variations in drug response and aims to identify subgroups of patients whose drug management could be tailored accordingly. The aim of this review is to explore patient profiling in the management of T2DM with a focus on the sodium glucose transporter inhibitor canagliflozin.
The PubMed database was searched using the terms "pharmacogenomics" and "diabetes" through May 31, 2014. Published articles and abstracts presented at national/international meetings were considered.
Genome-wide association studies have opened the door for patient profiling and research into genetic variants in multifactorial T2DM. Clinically, it may be possible to tailor the type of medication used based on the presence or absence of the various genetic variants. However, the polymorphisms studied may only explain some of the variability in response to T2DM drugs and needs further validation to ensure its authenticity. There are still unidentified factors which appear to play a role in the interindividual variability seen in clinical practice. The potential exists for pharmacogenomics to promote efficacious, safe, and cost-effective individualized diabetes management. Pharmacogenomics is still in its early stages, and the idea of defining patients genetically to predict individual responses to drugs and obtain safe and effective T2DM management is promising, in spite of existing barriers. Currently, clinical profiling of patients with T2DM and using an individualized approach with most drugs, including canagliflozin, based on comorbid conditions still remains the most accepted approach for the management of T2DM.
医生试图通过多种手段,包括使用降糖药物,来实现2型糖尿病(T2DM)患者的血糖目标。药物反应存在个体差异,部分原因可能是影响药物代谢的基因多态性的存在。药物基因组学研究患者间药物反应差异的遗传基础,旨在识别可据此调整药物治疗方案的患者亚组。本综述的目的是探讨T2DM管理中的患者特征分析,重点关注钠葡萄糖转运体抑制剂卡格列净。
截至2014年5月31日,使用“药物基因组学”和“糖尿病”检索PubMed数据库。纳入已发表的文章以及在国内/国际会议上发表的摘要。
全基因组关联研究为多因素T2DM的患者特征分析和基因变异研究打开了大门。临床上,根据各种基因变异的有无来调整所用药物的类型或许是可行的。然而,所研究的多态性可能仅能解释部分T2DM药物反应的变异性,需要进一步验证以确保其可靠性。在临床实践中,仍有一些未明确的因素似乎在个体差异中发挥作用。药物基因组学有潜力促进有效、安全且具有成本效益的个体化糖尿病管理。药物基因组学仍处于早期阶段,尽管存在现有障碍,但通过基因定义患者以预测个体药物反应并实现安全有效的T2DM管理的想法很有前景。目前,基于合并症对T2DM患者进行临床特征分析并对包括卡格列净在内的大多数药物采用个体化方法,仍然是T2DM管理中最被认可的方法。