磺酰脲类药物致2型糖尿病患者低血糖与CYP2C9基因型关系初步研究  

Preliminary studies on relationship between sulphonylureas-induced hypoglycemia and CYP2C9 genotype in patients with type 2 diabetes

作　　者：张琦[1,2] 彭妙官[1] 蒋培培[1] 黄燕萍[1] 闵运兵[1] 李梅忠[1] 黄菊芳[1] 罗劲华[1] 王丹[1] 王莹[3] 廖志红[1] 

机构地区：[1]中山大学附属第一医院东山院区内科,广州510080 [2]武警海南总队医院,海口570101 [3]中山大学达安基因股份有限公司,广州510663

出　　处：《药物不良反应杂志》2008年第6期387-391,共5页Adverse Drug Reactions Journal

基　　金："广州市2007年医药卫生科技引导"资助项目(2007-YB-185);"越秀区科技计划"资助项目(2007-WS-008)

摘　　要：目的:研究服用磺酰脲类药物的2型糖尿病患者出现低血糖与CYP2C9基因型的关系。方法:2006年11月至2007年5月使用磺酰脲类药物的2型糖尿病门诊患者纳入研究。检测患者的血糖水平和CYP2C9基因型,分析低血糖与CYP2C9基因型的关系。结果:146例2型糖尿病患者中,男43例,女103例,年龄23～79岁,平均年龄(62.5±12.4)岁。全部患者均服用磺酰脲类药物,服用的药物和剂量为:格列吡嗪5～10mg/d,格列齐特80～160mg/d,格列齐特缓释片30～60mg/d,格列美脲0.5～2mg/d及格列本脲5～10mg/d。146例患者中有74例出现低血糖。其中磺酰脲类诱发低血糖19例,其他因素诱发低血糖(进餐延迟、饮食少及过度运动等所致)55例。146例患者中13例(8.9%)为CYP2C9*1/*3基因型,其中低血糖组7例,无低血糖组6例。19例磺酰脲类诱发低血糖中6例(8.3%)为CYP2C9*1/*3基因型,55例其他因素诱发低血糖中1例(1.8%)为CYP2C9*1/*3基因型。磺酰脲类诱发低血糖组与其他因素诱发低血糖组或无低血糖组比较,CYP2C9基因型的差异有统计学意义(均P<0.05)。结论:磺酰脲类药物致2型糖尿病患者低血糖可能和CYP2C9基因突变(CYP2C9*1/*3)有关。Objective： To study on relationship between sulphonylureas-induced hypoglycemia and CYP2C9 genotype in patients with type 2 diabetes. Methods： The outpatients with type 2 diabetes receiving sulphonylureas treatment were enrolled in a study from November 2006 to May 2007 The patients＇ blood glucose levels and CYP2C9 genotype were measured. The relationship between hypoglycemia and CYP2C9 genotype was analyzed. Results： Of 146 patients with type 2 diabetes, 43 were males, 103 were females, and their ages were 23 - 79 years [ average age （ 62.5 ± 12.4） years ]. All patients received sulphonylureas. The specific drugs and dosages were as follows： glipizide 5 - 10 mg/d, gliclazide 80 - 160 mg/d, sustained-release gliclazide 30 -60 mg,/d, glimepiride 0. 5 - 2 mg/d, and glibenclamide 5 - 10 mg/d. Seventy-four cases of 146 patients developed hypoglycemia. Of the 74 cases, 19 were sulphonylureas-induced-hypoglycemia and 55 were other factor-induced hypoglycemia （ as a consequence of delayed meal, less intake of food, excessive exercises, and so on）. Of the 146 patients, 13（8.9% ） were CYP2C9 ＊ 1/＊ 3 genotype, and 7 of the 13 cases were in the hypoglycemia group, 6 were in the non-hypoglycemia group. Of 19 cases of sulphonylureas-induced hypoglycemia, 6 were CYP2C9 ＊ 1/＊ 3 genotype. Of 55 cases of other factor-induced hypoglycemia, 1 was CYP2C9 ＊ 1/＊ 3 genotype. There was a statistical difference in CYP2C9 genotype between the sulphonylureas-induced hypoglycemia group and the other factor-induced hypoglycemia group or the nonhypoglycemia group （P 〈 0.05）. Conclusion： Sulphonylureas-induced hypoglycemia occurring in patients with type 2 diabetes might link to CYP2C9 gene mutation （CYP2C9 ＊ 1/＊ 3）.

关 键 词：2型糖尿病 磺酰脲类药物 低血糖 CYP2C9 基因型 

分 类 号：R587.1[医药卫生—内分泌] R595.3[医药卫生—内科学]