血清鸢尾素与2型糖尿病颈动脉粥样硬化的相关性

Association of serum irisin with carotid atherosclerosis in patients with type 2 diabetes mellitus

目的探讨2型糖尿病(T2DM)患者血清鸢尾素(Irisin)与颈动脉粥样硬化(CAS)的相关性。方法选择2014年7月—2015年10月于三峡大学仁和医院内分泌科住院的新诊断的T2DM患者92例,其中不合并CAS组(T2DM组)45例,合并CAS组(T2DM合并CAS组)47例;同期于门诊就诊的糖耐量正常的CAS患者(CAS组)46例和在体检中心经口服葡萄糖耐量试验(OGTT试验)排除T2DM的健康体检者(对照组)48名。受试者禁食8h后,测量其收缩压(SBP)、舒张压(DBP);于清晨抽取空腹肘静脉血,检测三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、糖化血红蛋白(HbA_(1c))、TNF-α、人纤溶酶原激活物抑制剂1(PAI-1)、胰岛素、超氧化物歧化酶(SOD)、Irisin、空腹血糖(FPG)和餐后2h血糖(2hPG)水平,计算胰岛素抵抗指数(HOMA-IR),并测量颈动脉内膜中层厚度(IMT)。结果 4组间的性别构成、年龄、SBP、DBP的差异均无统计学意义(P值均>0.05)。CAS组的TC、LDL-C、PAI-1、TNF-α、IMT,T2DM组的LDL-C、PAI-1、胰岛素、HOMA-IR、HbA_(1c)、TNF-α、IMT,T2DM合并CAS组的TG、TC、LDL-C、PAI-1、胰岛素、HOMA-IR、HbA_(1c)、TNF-α、IMT均显著高于对照组(P值分别<0.05、0.01);CAS组的HDL-C、SOD,T2DM组HDL-C、SOD,T2DM合并CAS组的HDL-C、SOD均显著低于对照组(P值分别<0.05、0.01)。T2DM组的胰岛素、HOMA-IR、HbA_(1c)均显著高于CAS组(P值分别<0.05、0.01)。CAS组的LDL-C、IMT,T2DM合并CAS组的LDL-C、PAI-1、胰岛素、HOMA-IR、HbA_(1c)、TNF-α、IMT均显著高于T2DM组(P值分别<0.05、0.01);T2DM合并CAS组的SOD显著低于T2DM组(P<0.05)。对照组的血清Irisin水平显著高于其他3组(P值分别<0.05、0.01),T2DM合并CAS组的血清Irisin水平显著低于CAS组和T2DM组(P值均<0.05)。血清Irisin水平与LDL-C(r=-0.531,P=0.011)、FPG(r=-0.603,P=0.002)、2hPG(r=-0.596,P=0.006)、HbA_(1c)(r=-0.596,P=0.003)、TNF-ɑ(r=-0.597,P=0.003)、胰岛素(r=-0.521,P=0.014)、HOMA-IR(r=-0.552,P=0.011)、IMT(r=-0.639,P=0.001)、PAI-1(r=-0.591,P=0.007)均呈负相关,与HDL-C(r=0.597,P=0.006)、SOD(r=0.605,P=0.002)均呈正相关,与年龄、性别、SBP、DBP、TG、TC均不相关(P值均>0.05)。以IMT为因变量,FPG、HbA_(1c)、HOMA-IR、SOD、TNF-α、Irisin、PAI-1等为自变量进行多元逐步回归分析,结果显示,Irisin(回归系数=-0.208,P=0.006)、HbA_(1c)(回归系数=9.321,P=0.022)为影响IMT的独立相关因素。回归方程:IMT=9.321×HbA_(1c)-0.208×Irisin-3.156。结论 CAS患者Irisin水平降低,Irisin与糖脂代谢、胰岛素抵抗、TNF-α、氧化应激、PAI-1关系密切,低水平的Irisin参与了CAS的发生,其机制值得进一步深入研究。

Objective To explore the correlation between serum irisin and carotid atherosclerosis （CAS） in patients with type 2 diabetes mellitus （T2DM）. Methods In this study, 45 T2DM patients （T2DM group） and 47 ＂F2DM patients combined with CAS （T2DM with CAS group）, who were admitted to our hospital between July 2014 and October 2015 were enrolled in this study. Contemporarily, 46 CAS outpatients with normal glucose tolerance （NGT） detected by oral glucose tolerance test （CAS group） and 48 healthy people （control group） were also selected into the study. Systolic blood pressure （SBP） and diastolic blood pressure （DBP） were measured 8 h after fasting in all the subjects. In the next early morning, venous blood samples were collected to test the triacylglyoerol （TG）, total cholesterol （TO）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glycosylated hemoglobin （HbA1c）, tumor necrosis factor-α （TNF-α）, human plasminogen activator inhibitor 1 （PAI-1）, fasting insulin （FINS）, superoxide dismutase （SOD）, irisin and fasting blood glucose （FPG）. Insulin resistance index （HOMA-IR） was calculated. The carotid intima-media thickness （IMT） and postprandial glucose （2hPG） were measured. Results There were no significant differences in gender, age, SBP or DBP between the 4 groups （all P〉0. 05）. Compared with those in the control group, TO, LDL-C, PAl-1, TNF-α and IMT in CAS group, LDL-C, PAI-1, FINS, HOMA-IR, HbA1c, TNF-α and IMT in T2DM group, and TG, TO, LDL-C, PAl-1, FINS, HOMA-IR, HbA1c, TNF-α and IMT in T2DM with CAS group were significantly increased （P〈0.05, 0.01）. HDL-C and SOD in CAS group, T2DM group and T2DM with CAS group were significantly lower than those in the control group （P〈0.05, 0.01）. The FINS, HOMA-IR and HbA1c in T2DM group were significantly higher than those in CAS group （P〈0. 05, 0.01）. LDL-C and IMT in CAS group, and LDL-C, PAl-1, FINS, HOMA-IR, HbAIo, TNF-α and IMT in T2DM with CAS group were significantly higher than those in T2DM group （P〈0. 05, 0.01）. SOD in T2DM with CAS group was significantly lower than that in T2DM group （P〈 0.05）. Serum irisin level in control group was significantly higher than those in the other three groups （P〈0.05, 0.01）. Serum irisin level in T2DM with CAS group was significantly lower than those in CAS group and T2DM group （both P〈0.05）. Serum irisin level was negatively correlated with LDL-C （r = - 0.531, P = 0.011）, FPG （r = （ -0.603, P=0.002）, 2hPGJ（r=-0.596, P=0.006）, HbA^c（r=-0.596, P=0.003）, TNF-a （r=-0.597, P=0.003）, insulin （r=-0.521, P=0.014）, HOMA-IR （r=-0.552, P=0.011）, IMT （r=-0.639, P= 0.001） and PAl-1 （r=-0.591, P=0.007）, positively correlated with HDL-C （r=0.597, P = 0. 006） and SOD （r=0.605, P=-0.002）, and was not correlated with age, sex, SBP, DBP, TG and TO （all P〉0.05）. Using IMT as the dependent variable, FPG, HbA1c, HOMA-IR, SOD, TNF-a, Irisin and PAl-1 as independent variables by multiple stepwise regression analysis, the results showed that irisin （regression coefficient = - 0. 208, P = 0. 006） and HbAlo （regression coefficient =9. 321, P = 0. 022） were the independent influencing factors of IMT. Regression equation was as follows： IMT-- 9.321 x HbAlo - 0. 208 , Irisin- 3. 156. Conclusion The serum level of irisin in patients with CAS is reduced, and irisin is closely associated with glucose and lipid metabolism, insulin resistance, TNF-α, oxidative stress, and PAI-I. The low level of irisin is involved in the occurrence of CAS, and the mechanism deserves further study.