2型糖尿病糖耐量正常一级亲属内皮功能紊乱与早期动脉粥样硬化的相关性

Endothelial dysfunction and early atherosclerosis in first-degree relatives with normal glucose tolerance of type 2 diabetes mellitus patients

目的探讨2型糖尿病(T2DM)糖耐量正常一级亲属(FDRs)的血管内皮功能及早期动脉粥样硬化状态及其相关性,并对相关因素进行相关性分析。方法选取T2DM患者的糖耐量正常FDRs48例为观察组,选取无糖尿病家族史、无糖耐量异常史的糖耐量正常的健康者38例为对照组,酶法测定其空腹血糖(FBG)、餐后2h血糖(P2hBG)及甘油三酯(TG),化学发光法测定胰岛素(FINS),ELISA法测定血清非对称性二甲基精氨酸(ADMA)与内皮素-1(ET-1)的水平,计算稳态模型胰岛素抵抗评估指数(HOMA-IR)、β细胞功能指数(HOMA-IS)、胰岛素敏感指数(ISI)及血浆致动脉粥样硬化指数(AIP);应用高分辨率超声测定并计算肱动脉内皮依赖性舒张功能(FMD)、颈动脉中-内膜厚度(IMT)及颈动脉弹性系数(Ep)、动脉僵硬度(β)及顺应性(AC)。结果与对照组相比,观察组血清ADMA、ET-1、TG、Ln(FINS)、Ln(HOMA-IR)、Ln(HOMA-IS)、AIP、颈动脉Ep、β明显升高(P(0.05),FMD及Ln(ISI)明显降低(P(0.05);P2hBG升高,AC下降,但差异均无统计学意义(P均>0.05)。相关分析显示,Ep、β均与血清ADMA、ET-1呈正相关,与FMD呈负相关(P<0.05);根据偏相关分析,校正TG水平、Ln(HOMA-IR)、AIP、P2hBG、SBP后,Ep、β、FMD均与血清ADMA独立相关,亦与ET-1独立相关(P<0.05)。结论 T2DM糖耐量正常FDRs存在内皮功能紊乱及动脉功能改变,动脉功能改变与内皮功能紊乱存在相关性,与血清ADMA及ET-1水平独立相关,提示血清ADMA及ET-1水平有望成为预测早期动脉粥样硬化的生物学指标。

Objective To explore the status of endothelial dysfunction and early atherosclerosis in first-degree relatives（FDRs） with normal glucose tolerance of type 2 diabetes mellitus（T2DM） patients,investigate the relationship of them,and analyze the related factors by correlation analysis.Methods 48 FDRs with normal glucose tolerance of T2DM patients were enrolled in the observation group,and 38 volunteers with no family history of diabetes and impaired glucose tolerance were involved in the control group.Fasting blood-glucose（FBG）,triglyceride（TG）,and 2-hour postprandial sugar（P2hBG） were observed by the enzyme technique.Insulin（FINS） was determined by chemoiluminesence immunoassay,while dimethylarginine（ADMA） and endothelin-1（ET-1） were detected by ELISA.Insulin resistance（IR）,islet β cell function index（IS） and islet cells sensitive index（ISI） were calculated by homeostasis model assessment,and the atherogenic index of plasma（AIP） was calculated by the logarithm of the ratio of plasma concentration of triglycerides to that of HDL-cholesterol（log[TG/HDL-C]）.Flow-mediated dilation of the brachial artery（FMD）,carotid intima-media thickness（IMT）,pressure strain elasticmodulus（Ep）,stiffness parameter（β） and arterial compliance（AC） were measured by high-resolution ultrasonography.Results Compared with the controls,levels of ADMA,ET-1,TG,Ln（FINS）,Ln（HOMA-IR）,Ln（HOMA-IS）,AIP,Ep and β were obviously higher（P ﹤0.05）,and levels of FMD and Ln（ISI） were apparently lower（P ﹤0.05）.The P2hBG level increased,while the AC level declined.However,both had no statistical difference（P 〉0.05）.Ep and β had positive correlations with ADMA and ET-1 and negative correlations with FMD（P 〈0.05）.After levels of TG,Ln（HOMA-IR）,AIP,P2hBG and SBP were corrected,Ep,β and FMD had independent correlations with ADMA and ET-1（P 〈0.05）.Conclusio-ns Endothelial dysfunction and early atherosclerosis exist in FDRs with normal glucose tolerance of T2DM patients.Early atherosclerosis has a co-linearity with endothelial dysfunction,and independent correlations with serum ADMA and ET-1 levels.Therefore,serum ADMA and ET-1 levels may be biological indictors for predicting early atherosclerosis.