利拉鲁肽血药浓度变化对2型糖尿病合并动脉粥样硬化患者的临床影响评价

Evaluations of clinical effect of changes in blood drug concentration of lilarutin in patients with type 2 diabetes mellitus complicated with atherosclerosis

目的:探究2型糖尿病合并动脉粥样硬化患者血药利拉鲁肽浓度与其不良反应相关性,确定最佳利拉鲁肽血药浓度。方法:选取2018年2月至2019年2月在巴中市中心医院接受利拉鲁肽药物治疗的80例2型糖尿病合并动脉粥样硬化患者为研究对象。患者均在用药过程中检测利拉鲁肽血药浓度;治疗时间1年,根据血糖临床控制疗效标准确定显效、有效及无效组。分别统计各组患者治疗前、治疗后12个月不良反应及相关因子指标;ROC曲线分析降低患者不良反应的最佳血药利拉鲁肽的浓度。结果:HPLC检测利拉鲁肽血药浓度色谱图基线平稳,回归方程线性良好;显效患者42例,有效患者25例,无效患者13例,3组患者中位利拉鲁肽谷浓度分别为116.40,102.58,82.33 ng·mL^(-1),显效组中位利拉鲁肽谷浓度最高,有效组次之,无效组最后,各组之间差异有统计学意义(P<0.05)。利拉鲁肽分成A组(<100 ng·mL^(-1))、B组(100~120 ng·mL^(-1))、C组(120~140 ng·mL^(-1))及D组(>140 ng·mL^(-1))4个浓度区间;当高于120 ng·mL^(-1)时,易发生低血糖症,差异有统计学意义(P<0.05)。利拉鲁肽血药浓度对FPG、PBG、HbA1c、TC、TG、LDL-C、ALT、Cr、AIP、IMT厚度、sICAM-1、sVCAM-1及颈动脉粥样硬化面积影响性大,差异有统计学意义(P<0.05)。ROC曲线分析利拉鲁肽最佳浓度为108.44 ng·mL^(-1),差异有统计学意义(P<0.05)。结论:适度调整糖尿病合并动脉粥样硬化患者血液中利拉鲁肽浓度可以降低药物不良反应,提高临床疗效。

OBJECTIVE To explore the correlation between the plasma concentration of liraglutide and its adverse reactions in patients with type 2 diabetes mellitus(T2DM)complicated with atherosclerosis and determine its optimal plasma concentration.METHODS From February 2018 to February 2019,a total of 80 T2DM patients complicated with atherosclerosis receiving liraglutide were selected as research subjects.Blood concentration of liraglutide was detected during medication.According to the clinical efficacy standard of blood glucose control,three groups with significant,effective and ineffective effects were determined.Adverse reactions and related factors were recorded for each group before and 12 months after treatment.Receiver operating characteristic(ROC)curve was utilized for analyzing the optimal plasma concentration of liraglutide for reducing adverse reactions.RESULTS High performance liquid chromatography(HPLC)liraglutide plasma concentration had a stable baseline and an excellent linear regression equation.The effects were marked(n=42),effective(n=25)and ineffective(n=13).The median liraglutein concentration was 116.40,102.58 and 82.33 ng·mL^(-1) in three groups respectively.The median liraglutein concentration was the highest in marked effect group,followed by effective and ineffective groups.The difference was statistically significant(P<0.05).Liraglutide was divided into four concentration ranges:group A(<100 ng·mL^(-1)),group B(100-120 ng·mL^(-1)),group C(120-140 ng·mL^(-1))and group D(>140 ng·mL^(-1)).At a concentration of>120 ng·mL^(-1),hypoglycemia was prone to occur and the difference was statistically significant(P<0.05).Blood concentration of liraglutide had significant effects on FPG,PBG,HbA1c,TC,TG,LDL-C,ALT,Cr,AIP,IMT thickness,sICAM-1,sVCAM-1 and carotid atherosclerotic area with statistical significance(P<0.05).ROC curve analysis revealed that the optimal concentration of liraglutide was 108.44 ng·mL^(-1) and the difference was statistically significant(P<0.05).CONCLUSION Moderate adjustment of blood liraglutide concentration may reduce adverse reactions and improve clinical efficacies in atherosclerotic diabetics.