二甲双胍对2型糖尿病患者血清前蛋白转化酶枯草溶菌素9水平的影响

Effects of Metformin on the serum PCSK9 in patients with type 2 diabetes mellitus

目的观察二甲双胍对T2DM患者血清前蛋白转化酶枯草溶菌素9(PCSK9)水平的影响。方法选取93例新诊断的T2DM患者,随机分为二甲双胍治疗组(Met组,n=47)和格列吡嗪治疗组(Gli组,n=46)。同时另选择48名健康人作为对照组(NGT组)。采用ELISA测定T2DM患者及健康人群PCSK9水平。观察治疗前后T2DM患者血清PCSK9水平变化。结果与NGT组比较,治疗前Met组、Gli组血清PCSK9水平升高[(3.93±0.71)vs(5.42±1.03)、(5.78±1.61)ng/ml,P<0.01];相关性分析显示,血清CKSP9水平与FPG、HbA_1c、胰岛素抵抗指数(HOMA-IR)、FIns、TC、LDL-C、TG、高敏C-反应蛋白(hsC-RP)、TNF-α、BMI呈正相关(r=0.578、0.638、0.556、0.610、0.578、0.592、0.589、0.638、0.561、0.552,P<0.05或P<0.01),与HDL-C呈负相关(r=-0.614,P<0.01);治疗后Met组PCSK9水平下降(P<0.05);治疗后Gli组血清PCSK9水平无明显变化(P>0.05)。多元线性回归分析显示,TNF-α、HOMA-IR是PCSK9的独立影响因素。结论T2DM患者血清PCSK9水平增高,二甲双胍可降低T2DM患者血清PCSK9的水平。

Objective To investigate the effects of Metformin on serum proprotein convertase subtilisin/kexin type 9（PCSK9）level in patients with type 2 diabetes（T2DM）. Methods 48 healthy people with normal glucose tolerance were selected as the controls（NGT group）.93 newly diagnosed T2 DM were randomized to Metformin treated group（Met,n=47）and Glipizide treated group（Gli,n=46）.Serum PCSK9 was measured by ELISA in all participants.After treatment,the changes of serum PCSK9 were observed in Met group and Gli group. Results Serum PCSK9 levels in Met group and Gli group were higher than NGT group（P〈0.01）.PCSK9 level was positively correlated with FPG,HbA1c,HOMA-IR,FIns,TC,LDL-C,TG,hsC-RP,TNF-αand BMI（r=0.578,0.638,0.556,0.610,0.578,0.592,0.589,0.638,0.561,0.552;P〈0.05 or P〈0.01）,and negatively correlated with HDL-C（r=-0.614,P〈0.01）.The levels of PCSK9 significantly decreased after treatment with Metformin（P〈0.05）.PCSK9 levels had no significant differences before and after treatment with Glipizide.Multiple regression analysis showed that TNF-αand HOMA-IR were independent related factors of PCSK9. Conclusion T2 DM patients have high levels of serum PCSK9 which can be decreased by Metformin.