Mahrooz Abdolkarim, Parsanasab Hassan, Hashemi-Soteh Mohammad Bagher, Kashi Zahra, Bahar Adele, Alizadeh Ahad, Mozayeni Maliheh
Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Km 17 Khazarabad Road, Sari, Iran,
Clin Exp Med. 2015 May;15(2):159-65. doi: 10.1007/s10238-014-0283-8. Epub 2014 Apr 17.
A major predicament in certain users of metformin, which is one of the most commonly used antihyperglycemic agents for type 2 diabetes (T2DM) treatment, is the lack of appropriate response to the drug. We evaluated the role of metformin response and OCT1 (organic cation transporter1) Met420del polymorphism in a monotherapy study (metformin therapy for 12 weeks) on patients newly diagnosed with T2DM. Based on the response to metformin, patients (n = 108) were divided into two groups: responders (n = 49) and non-responders (n = 59). HbA1c levels were determined by affinity technique. The OCT1-Met420del polymorphism was genotyped by PCR-based restriction fragment length polymorphism. There was a significant association between the variable response with HbA1c and fasting blood sugar (FBS) (Wilks' λ = 0.905, p = 0.01). Responders had significantly lower HbA1c and FBS levels compared with non-responders (η (2) = 0.087, p = 0.004 for HbA1c and η (2) = 0.055, p = 0.022 for FBS). The interaction treatment-response increased the effect sizes from 32 to 58 % for HbA1c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were significantly lower in the responder group than in the non-responders (η (2) = 0.067, p = 0.01 for ALT and η (2) = 0.052, p = 0.025 for AST). This observational study showed that the variant OCT1-Met420del may be more effective on plasma glucose than HbA1c. The variable response could account for a significant proportion of the variance in HbA1c levels observed following treatment with metformin. Metformin shows a significantly greater effect on ALT and AST in responders than in non-responders.
二甲双胍是治疗2型糖尿病（T2DM）最常用的抗高血糖药物之一，某些使用二甲双胍的患者面临的一个主要困境是对该药物缺乏适当反应。我们在一项针对新诊断T2DM患者的单药治疗研究（二甲双胍治疗12周）中评估了二甲双胍反应和OCT1（有机阳离子转运体1）Met420del多态性的作用。根据对二甲双胍的反应，将患者（n = 108）分为两组：反应者（n = 49）和无反应者（n = 59）。采用亲和技术测定糖化血红蛋白（HbA1c）水平。通过基于聚合酶链反应的限制性片段长度多态性对OCT1-Met420del多态性进行基因分型。HbA1c和空腹血糖（FBS）的可变反应之间存在显著关联（威尔克斯'λ = 0.905，p = 0.01）。与无反应者相比，反应者的HbA1c和FBS水平显著更低（HbA1c的η(2)= 0.087，p = 0.004；FBS的η(2)= 0.055，p = 0.022）。治疗-反应的相互作用使HbA1c的效应大小从32%增加到58%。反应者组的丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）值显著低于无反应者（ALT的η(2)= 0.067，p = 0.01；AST的η(2)= 0.052，p = 0.025）。这项观察性研究表明，OCT1-Met420del变体对血糖的影响可能比对HbA1c的影响更大。可变反应可能在很大程度上解释了二甲双胍治疗后观察到的HbA1c水平的差异。与无反应者相比，二甲双胍对反应者的ALT和AST影响显著更大。
