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1、贰型糖尿病患者的脂蛋白(a)浓度和载脂蛋白(a)分型2型糖尿病患者的脂蛋白(a)浓度和载脂蛋白(a)分型2010-09-06 史虹莉方京冲杨秀芳沈稚舟朱禧星 【摘要】目的研究2型糖尿病患者的脂蛋白(a)Lp(a)浓度和载脂蛋白(a)apo(a)的多态性以及与糖尿病慢性并发症的关系。方法本研究用改良的Utermann和Guo方法对40名非糖尿病对照和176名2型糖尿病患者进行apo(a)分型检测，观察其与Lp(a)浓度以及微血管和大血管并发症之间的关系，包括肾脏病变、视网膜病变、神经病变、高血压、冠心病、脑梗塞。结果40名非糖尿病对照之apo(a)分型：S3S2、S4和S4S2的发生频率分别为2
2、0%、70%和10%，血清Lp(a)水平为(0.080.07)mg/L。而2型糖尿病患者S2、S3、S3S2、S4、S4S2和S4S3的发生频率分别为18.18%、20.45%、17.05%、34.09%、4.55%和5.68%，Lp(a)浓度为(0.130.11)mg/L，明显高于非糖尿病对照。与不伴有并发症的糖尿病患者比较，除糖尿病视网膜病变，伴肾脏病变、神经病变、高血压、冠心病、脑梗塞患者之apo(a)分型分布频率有显著差异。与S2基因表现型患者比较，S4表现型患者之空腹血糖、餐后2小时血糖和糖基化血红蛋白水平明显降低。不同基因表现型患者之Lp(a)浓度和尿白蛋白/肌酐水平具有明显差异，
3、S2者最高，S3者其次，S4者最低。结论2型糖尿病患者和非糖尿病对照之apo(a)基因表现型分布频率不同，同样伴有与不伴有微血管和大血管并发症的糖尿病患者之分布频率亦不同，可能与白蛋白尿和胰岛素抵抗有关。 【关键词】糖尿病，2型脂蛋白(a)载脂蛋白(a) Lipoprotein(a) concentration and apolipoprotein(a) phenotype in type 2 diabetic subjects SHI Hongli,FANG Jingchong,YANG Xiufang,et al.Diabetes Research Department,Huashan H
4、ospital,Shanghai Medical University,200040 【Abstract】ObjectiveTo investigate the lipoprotein(a) concentration and apolipoprotein(a) apo(a) polymorphism in type 2 diabetic patients and its relationship to complications. MethodsApo(a) phenotypes were tested with modified Utermann and Guo method in 40
5、non-diabetic controls and 176 type 2 diabetic subjects and the association between apo(a) phenotypes and micro- and macrovascular complications including nephropathy, neuropathy, retinopathy, hypertension, coronary heart disease and cerebral infarction was analyzed. ResultsAmong the 40 non-diabetic
6、controls, the frequencies of S3S2, S4 and S4S2 were 20%, 70% and 10% respectively and the serum Lp(a) level was (0.080.07)mg/L. While the frequencies of S2, S3, S3S2, S4, S4S2, S4S3 were 18.18%, 20.45%, 17.05%, 34.09%, 4.55% and 5.68% respectively in the diabetics and the Lp(a) concentration was (0.
7、130.11)mg/L, significantly higher in the diabetics than the non-diabetic controls. Compared with the diabetics without complications, the frequencies of apo(a) phenotypes significantly differed in patients with neuropathy, nephropathy, hypertension, coronary heart disease and cerebral infarction exc
8、ept diabetic retinopathy. Compared with patients with S2 phenotype, the levels of FPG, 2hPG and HbA1c were lower in patients with S4 phenotype. The concentration of Lp(a) and Alb/Cr were significantly different among diabetics with different apo(a) phenotypes, being highest in patients with S2, then
9、 in S3, and lowest in S4. ConclusionThere were significant differences in the frequencies of apo(a) phenotypes between type 2 diabetic subjects and non-diabetic controls, and also between diabetics with and without microvascular and macrovascular complicatios. The underlying linkage might be microal
10、buminuria and insulin resistance. 【Key words】Diabetes mellitus, type 2Lipoprotein(a)Apolipoproetin(a) (Chin J Endocrinol Metab, 1999,15:7781) 脂蛋白(a)Lp(a)是一种含有类似低密度脂蛋白颗粒的特殊脂蛋白，具有致动脉粥样硬化的作用。研究表明，高浓度的Lp(a)是糖尿病和非糖尿病患者发生血管病变的独立危险因素。血浆Lp(a)水平，在不同的个体之间变化甚大，可达上千倍，而在同一个体则相对稳定，这些主要由遗传因素所决定1-3。现已证明，血浆Lp(a)浓度变化
11、的90%由载脂蛋白(a)apo(a)基因决定4。本研究的目的在于探索2型糖尿病患者中的Lp(a)浓度和apo(a)的基因表现型，并研究其与血管并发症的关系。 对象和方法 一、对象 非糖尿病对照40例，其中男性24例，女性16例，年龄4270岁，无高脂血症、高血压、冠心病、脑梗塞、肾脏疾病和外周血管病变。入选的176例2型糖尿病患者年龄(6112)岁，3186岁为来自华山医院糖尿病门诊和病房，诊断依据WHO标准5，无泌尿系统疾病，无近期服用肾毒性药物。治疗方案为胰岛素注射和口服降糖药(OHA)。 高血压患者为有高血压史者(现服药或不服药)，或近期二次血压测试证实收缩压161mmHg(1mmHg=
12、0.133kPa)、舒张压93mmHg者。除外尿路感染后，蛋白尿患者为尿常规持续发现尿蛋白阳性，白蛋白尿包括微量白蛋白尿，尿白蛋白指数(Alb/Cr)25mg/mmolCr，大量白蛋白尿，Alb/Cr25mg/mmolCr患者为尿常规检查尿蛋白阴性而Alb/Cr2.5mg/mmolCr者，正常白蛋白尿患者为Alb/Cr2.5mg/mmolCr者。冠心病和脑梗塞患者为有冠心病和脑梗塞病史者，糖尿病神经病变的诊断主要依据临床表现，包括：肢体感觉异常或感觉消失、腱反射和振动感的消失。依据眼底镜检查结果诊断糖尿病视网膜病变，包括单纯型和增生型。 二、方法 禁食10小时后空腹采取静脉血，测定空腹血糖(FPG)和餐后2小时血糖(2hPG)、空腹C肽(F-CP)和餐后2小时C肽(2h-CP)、甘油三酯(TG)、总胆固醇(Ch)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、Lp(a)、apo(a)分型、糖基化血红蛋白(HbA1c)。同时收集尿液测定尿蛋白(Pr)、尿白蛋白(Alb)和尿肌酐(Cr)，并计算Alb/Cr。
