脂蛋白(a)与老年2型糖尿病肾病肾功能不全的关系

近年来研究发现,终末期肾功能衰竭、血液透析和腹膜透析患者血清脂蛋白(a)〔Lp(a)〕浓度也升高,但对Lp(a)与老年糖尿病肾病早期肾功能不全之间的关系研究较少,我们对老年糖尿病肾病肾功能不全患者的Lp(a)及其他脂蛋白、血脂和载脂蛋白进行了测定和分析。     

脂蛋白(a)与糖尿病肾病相关性的研究进展

大量证据表明,脂蛋白(a)[LP(a)]与冠心病、脑卒中和钙化性主动脉瓣狭窄等心脑血管疾病密切相关.随着研究的深入,发现LP(a)与糖尿病肾病也有一定的相关性,可能在其发生发展、临床诊断及治疗上发挥一定的作用.本文就脂蛋白(a)的结构特点、遗传、代谢及与糖尿病肾病的相关性最新进展予以综述.     

住院2型糖尿病患者血清脂蛋白(a)水平及与糖尿病肾病的关系

目的 研究2型糖尿病患者血清脂蛋白(a)水平的变化,探讨其与糖尿病肾病的关系.方法 2007年1月至2008年11月我院内分泌代谢科收治的2型糖尿病患者1238例,年龄15～89岁,记录血压、体质量及病程,入院第2天测定卒腹及餐后2 h血糖、血脂谱、肾功能及尿白蛋白排泄率,应用肾脏病膳食改良试验公式计算肾小球滤过率.分别根据患者年龄、尿白蛋白排泄率及脂蛋白(a)水平进行分层.采用t检验、方差分析、多元逐步回归分析等进行统计学分析.结果 不同年龄组患者血清脂蛋白(a)水平差异无统计学意义(F=1.144,P>0.05).大量蛋白尿组血清脂蛋白(a)水平显著高于正常蛋白尿组和微量蛋白尿组(F=4.113,P<0.05).研究队列按照血清脂蛋白(a)的四分位点分为四组,随着血清脂蛋白(a)水平的升高,尿白蛋白排泄率逐渐升高(F=7.877,P<0.01),而肾小球滤过率逐渐降低(F=4.479,P<0.01).血清脂蛋白(a)与血清总胆固醇、低密度脂蛋白胆固醇、尿白蛋白排泄率呈正相关(r值分别为0.152、0.169、0.18,均P<0.01),与肾小球滤过率呈负相关(r=-0.061,P<0.01).多元逐步同归分析结果显示:影响尿白蛋白排泄率的主要因素包括收缩压、血清脂蛋白(a)水平、低密度脂蛋白胆固醇、肾小球滤过率、年龄.结论 2型糖尿病患者血清脂蛋白(a)水平不受年龄、病程及血糖控制情况的影响,是尿白蛋白排泄率的独立影响因素.     

脂蛋白(a)检测在2型糖尿病肾病患者中的临床价值

目的探讨血清脂蛋白(a)〔LP(a)〕与各因素的相关性及LP(a)检测在2型糖尿病肾病(T2DN)患者中的临床价值。方法选择2型糖尿病(T2DM)患者119例,其中单纯糖尿病患者36例(A组),糖尿病肾病(DN)患者83例(B组);正常对照组30例(NC组)。检测各组患者LP(a)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)等生化指标,进行单一因素方差分析。119例糖尿病患者组以LP(a)为因变量,与各检测指标作简单线性相关分析。采用受试者工作特征曲线(ROC曲线)分析并获得B组的最适临界点(cutoff值)。结果 LP(a)水平在A组、B组升高明显(P﹤0.01)。尿微量白蛋白(UMA)、GGT与LP(a)关系最密切。LP(a)ROC曲线下面积为0.818,在最适cutoff值为200 mg/L时,灵敏度、特异度分别为77.4%、76.8%。结论 Lp(a)与T2DN密切相关;可以被视为该疾病的一个独立危险因子,有可能成为T2DN的一个早期预防和监测指标。     

糖尿病肾病患者血脂异常及血清脂蛋白(a)与糖尿病肾病的关系

目的研究糖尿病肾病患者血脂变化及血清脂蛋白(a)[Lp(a)]与糖尿病肾病(DN)的关系。方法将110例2型糖尿病患者分为正常蛋白尿组(A组,43例)、微量蛋白尿组(B1组,37例)和大量蛋白尿组(B2组,30例)3组,分别检测其血脂及脂蛋白(a)水平,并与对照组(50例)比较。结果与对照组比较,2型糖尿病患者各组甘油三脂(TG)、低密度脂蛋白胆固醇(LDLC)和Lp(a)水平均升高,B1组、B2组与A组比较及B2组与B1组比较,Lp(a)均升高,差异有显著性(P<0.01);B1组、B2组胆固醇(TC)水平升高及高密度脂蛋白胆固醇(HDLC)、载脂蛋白A1(ApoA1)水平降低,B2组载脂蛋白B(ApoB)水平升高,差异有显著性(P<0.01);TG、LDLC、ApoB的升高与尿白蛋白排泄率(UAER)呈正相关,TG、LDLC升高与空腹血糖(FBG)呈正相关。Lp(a)与尿白蛋白排泄率呈正相关,与其它血脂变化无相关性。结论脂蛋白(a)水平升高可能继发于糖尿病肾病的肾脏损害,随肾脏损害的加重而逐步升高;高脂血症促进糖尿病肾病的发生和发展,糖尿病则加重血脂紊乱,形成恶性循环。     

血清脂蛋白(a)和凝血纤溶的改变与2型糖尿病肾病关系的研究

脂蛋白（a）[Lp（a）]是与低密度脂蛋白（LDL）极为相似的蛋白质,已被认为可作为一种相对独立的蛋白,能与纤溶酶原竞争结合受体,在功能上具有影响纤维蛋白溶解的特性。在2型糖尿病。肾病患者中,血清Lp（a）的生成增多,分解减少,造成体内Lp（a）水平升高,并且通过多种机制影响机体的凝血纤溶系统,打破凝血纤溶的平衡,造成体内的高凝状态以及继发性纤溶活性的增强,从而引起糖尿病患者。肾脏损害的发生发展。     

糖尿病肾病患者肾功能不全的临床特点

作者分析２０例糖尿病肾病患者肾功能不全的临床特点，认为：（１）防治糖尿病肾病肾功能不全应强调早发现，早诊断糖尿病及糖尿病肾病；（２）老年患者出现肾功能不全，蛋白尿，而肾肝不缩小，尿量不减少者应考虑糖尿病可能；（３）糖尿病人应长期严格控制血糖，血压，注意处理高脂血症；（４）对糖尿病患者应特别注意防治心，脑，肺及感染合并症。     

2型糖尿病肾病患者血清脂蛋白(a)质量浓度与纤溶功能的相关性探讨

目的　探讨 2型糖尿病肾病患者血清脂蛋白 (a) [Lp(a) ]质量浓度与纤溶功能的关系。方法　 132例 2型糖尿病肾病患者分为A组 [尿白蛋白排泄率 (UAER) >2 0 0 μg/min ,n =4 2 ]、B组 (UAER介于 2 0 μg/min～ 2 0 0 μg/min ,n =4 0 )、C组 (UAER <2 0 μg/min ,n =5 0 ) ,健康对照组 (D组 ) 80例 ,均测定血脂 [包括血清Lp(a) ]、组织型纤溶酶原激活物 (tPA)及纤溶酶原激活物抑制剂 (PAI)活性、糖化血红蛋白A1c(GHbA1c)、内生肌酐清除率 (Ccr)和肱动脉血压。结果　A和B组血清Lp(a)较C组和D组明显升高 (P <0 0 1) ,且Lp(a)与PAI活性正相关 (r =0 6 8,P <0 0 5 ) ,与tPA活性负相关 (r =- 0 72 ,P <0 0 1)。结论　Lp(a)和 2型糖尿病肾病时纤溶功能障碍密切相关 ,是促使糖尿病肾病病变进展的重要因素。     

老年2型糖尿病患者血清脂蛋白(a)水平与载脂蛋白(a)基因多态性分析

本文对老年 2型糖尿病患者血清脂蛋白 (a)水平及载脂蛋白 (a)多态性进行了分析 ,以探讨老年糖尿病与高脂蛋白 (a)血症的关系及其载脂蛋白 (a)遗传表型的分布特点 ,同时分析脂蛋白 (a)与糖尿病并发症的相关性。用酶联免疫吸附法测定脂蛋白 (a)水平 ,用十二烷基磺酸钠 -聚丙烯酰胺凝胶电泳和Westernblot技术测定脂蛋白(a)遗传表型。结果发现 :① 3组 (老年 2型糖尿病、非老年 2型糖尿病与老年健康对照组 )脂蛋白 (a)浓度差异无统计学意义 (P >0 .0 5 ) ,脂蛋白 (a)与血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇及其亚型、低密度脂蛋白胆固醇、载脂蛋白A和B水平无相关性 (P >0 .1) ;②老年 2型糖尿病组合并高血压、糖尿病性视网膜病变和糖尿病肾病者的血清脂蛋白 (a)浓度明显高于无合并相应疾病者 (P <0 .0 5或P <0 .0 0 1) ;③ 3组共检出 13种载脂蛋白 (a)基因型 ,在老年 2型糖尿病合并症患者中 ,低分子质量的S1和S2基因型明显多于其它组及无合并症者     

2型糖尿病患者血清脂蛋白(a)水平及其与冠心病的关系

目的　探讨 2型糖尿病患者血清脂蛋白 (a) [Lp(a) ]水平及其与冠心病的关系。方法　选择 90例 2型糖尿病及 6 8例健康对照者测定其血清Lp(a)、总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL C)水平 ;计算低密度脂蛋白胆固醇 (LDL C)水平及TC、TG、LDL C与HDL C比值。结果　 (1)糖尿病组血清Lp(a)水平与对照组比较差异无显著性意义 (P >0 .0 5 )。 (2 )将 2型糖尿病患者分为糖尿病伴冠心病和单纯糖尿病亚组后发现 :①糖尿病伴冠心病亚组血清Lp(a)水平明显高于单纯糖尿病亚组 [(2 3.78± 2 3.73)mg/dlvs (13.31± 10 .6 6 )mg/dl;P <0 .0 1]及对照组 [(2 3.78± 2 3.73)mg/dlvs (16 .2 8± 17.95 )mg/dl;P <0 .0 5 ];②糖尿病伴冠心病亚组血清Lp(a)水平与LDL C呈正相关关系 (r =0 .32 16 ,P <0 .0 5 )。结论　 2型糖尿病患者血清Lp(a)水平增高可能与冠心病发病有密切关系。     

2型糖尿病肾病血清脂蛋白检测及其临床意义

目的　探讨血清脂蛋白 [Lp(a) ]在糖尿病肾病 (DN)发生发展中的作用。方法　根据2 4h尿蛋白质排泄率 (UAER)的测定结果 ,将 14 6例糖尿病患者分为三组 ,糖尿病组 (DM组 )、早期糖尿病肾病组 (EDN组 )和临床糖尿病肾病组 (CDN组 ) ,99名健康者作对照组 ,分别测定各组LP(a)水平 ,并对全部患者LP(a)与尿UAER呈直线相关分析。结果　DM组LP(a)水平高于对照组(P <0 .0 5 ) ,EDN组及CDN组LP(a)水平明显高于DM组 ,LP(a)与UAER呈直线正相关 (r =0 .435 8,P <0 .0 1)。结论　LP(a)与糖尿病有一定的联系 ,并与糖尿病肾病的发生发展密切相关。     

慢性肾衰竭患者血清脂蛋白（a）变化及其临床意义探讨

目的观察慢性肾衰竭（CRF）患者血清脂蛋白（a）[LP（a）]水平的变化及其与心脑血管疾病的关系。方法回顾分析102例慢性肾衰竭患者的临床及实验室资料,探讨患者血LP（a）水平与心脑血管疾病的关系。结果CRF患者无论透析与否,其血LP（a）水平均较健康对照组显著升高（P〈0．05）,血液透析组（HD组）LP（a）水平升高及高密度脂蛋白（HDL．C）水平下降比非透析组（ND）更明显（P〈0．01）,而HD组与ND组患者血总胆固醇（CHOL）、低密度脂蛋白（LDL-C）、三酰甘油（TG）浓度差异无统计学意义。CRF伴心脑血管疾病患者的血LP（a）水平比无心脑血管疾病患者明显升高（P〈0．05）。结论CRF患者存在严重的脂代谢紊乱,血IJP（a）水平升高可能伴随纤溶功能的低下,可能是CRF患者并发心脑血管疾病的危险因素之一。     

Plasma lipoprotein(a) [Lp(a)] concentrations and cardiovascular events in the elderly: evidence from the prospective study of pravastatin in the elderly at risk (PROSPER)

Using analyses of the large cohort (n = 5732) from the prospective study of pravastatin in the elderly at risk (PROSPER), we tested the hypothesis that Lp(a) concentration is an independent predictor of major vascular events and cognitive impairment in the elderly.

Baseline Lp(a) levels were measured on fresh samples from 5732 subjects aged 70–82, who were followed for 3.2 years on average.

Lp(a) levels were not significantly different across the age range in PROSPER, but were significantly higher in women (geometric mean 14.8 versus 12.4 mg/dl, P < 0.0001). Those with a history of vascular disease had significantly higher Lp(a) levels, which remained after adjustment (P < 0.0001). There was no statistically significant association between baseline Lp(a) and the risk of the primary endpoint (CHD death, non-fatal MI and fatal or non-fatal stroke) (hazard ratio 1.05, 95% CI 1.00–1.11, P = 0.077), but after adjustment for baseline risk factors this did achieve statistical significance (1.06, 1.005–1.12, P = 0.032). Finally, there was no statistically or clinically significant association between any adjusted baseline or dynamic cognition variables and Lp(a), and nor was there any significant association between Lp(a) and indices of disability throughout the study.

This is the first study of the association between Lp(a) and a range of cardiovascular endpoints including cognitive and disability indices in the elderly. The main finding is that Lp(a) level, while influenced by a number of baseline characteristics, is not a significant predictor of cognitive function or levels of disability, but is a predictor of combined cardiovascular events over an average 3.2 year follow-up.     

糖尿病肾病脂蛋白(a)质量浓度变化对尿白蛋白排泄率的影响

目的探讨血清脂蛋白(a)[Lp(a)]质量浓度变化与糖尿病肾病(DN)进展之间的关系以及降低血清Lp(a)质量浓度在防治DN进展中的意义。方法对广东省东莞市人民医院2002-04～2004-09门诊及住院270例糖尿病患者分为单纯糖尿病(SDM)组、早期糖尿病肾病(EDN)组和临床糖尿病肾病(CDN)组各90例,比较其与正常对照组的血清Lp(a)水平;两组DN患者在常规治疗基础上每晚服用氟伐他汀40mg。分析血清Lp(a)质量浓度变化与DN进展之间的关系。结果⑴SDM组血清Lp(a)质量浓度与正常对照组比较无显著性差异(P>0.05),EDN、CDN组血清Lp(a)质量浓度明显高于正常对照组和SDM组(P<0.01),CDN组血清Lp(a)质量浓度明显高于EDN组(P<0.01)。血清Lp(a)质量浓度与尿白蛋白排泄率(UAER)呈直线正相关(r=0.396,P<0.01)。⑵两组DN患者血清Lp(a)水平显著降低(P<0.01)。结论血清Lp(a)质量浓度升高与DN进展有关,降低血清Lp(a)质量浓度能有效减轻EDN患者的蛋白尿、改善肾功能,但对CDN患者无效。     

血脂蛋白(a)浓度与中青年患者心肌梗死的关系

目的:研究脂蛋白(a)[Lp(a)]水平与中青年患者心肌梗死(MI)发生的关系.方法:对112例中青年MI患者(MI组)、160例非MI的冠心病患者(非MI组)及180例正常人(正常对照组)进行冠状动脉造影,并检查血清Lp(a)浓度.结果:与正常对照组比较,非MI组和MI组LP(a)水平明显增高,而后者更高.3组LP(a)增高率分别是16.7%,34.4%和61.6%;在高LP(a)水平,MI患者占44.8%,而低LP(a)水平,MI患者占14.4%,以上均差异有统计学意义(均P＜0.01).结论:中青年患者MI的发生与Lp(a)水平增高有关.     

Apolipoprotein(a) and cardiovascular disease in Type 2 (non-insulin-dependent) diabetic patients with and without diabetic nephropathy

Summary The relative mortality from cardiovascular disease is on average increased five-fold in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy compared to non-diabetic subjects. We assessed the possible contribution of dyslipidaemia in general and elevated serum apolipoprotein(a) (apo(a)) in particular. Type 2 diabetic patients with normo-, micro- and macroalbuminuria were compared with healthy subjects. Each group consisted of 37 subjects matched for age, sex and diabetes duration. Serum creatinine in the nephropathy group was 105 (54–740) mol/l. The prevalence of ischaemic heart disease (resting ECG, Minnesota, Rating Scale) was 57, 35, 19 and 2% in macro-, micro- and normoalbuminuric diabetic patients and healthy subjects, respectively. The prevalence of ischaemic heart disease was higher in all diabetic groups as compared to healthy subjects (p<0.05), and higher in macroalbuminuric as compared to normoalbuminuric diabetic patients (p<0.01). There was no significant difference between apo(a) in the four groups: 161 (10–1370), 191 (10–2080), 147 (10–942), 102 (10–1440) U/l (median (range)) in macro-, micro- and normoalbuminuric groups and healthy subjects. Serum total-cholesterol, HDL-cholesterol and LDL-cholesterol were not significantly different when comparing healthy subjects and each diabetic group. Apolipoprotein A-I was lower (p<0.05) in all diabetic groups as compared to healthy subjects (nephropathy vs healthy subjects): 1.50±0.25 vs 1.69±0.32 g/l (mean ± SD). Triglyceride was higher (p<0.05) in patients with nephropathy and microalbuminuria as compared to healthy subjects (nephropathy vs healthy subjects): 2.01 (0.66–14.7) vs 1.09 (0.41–2.75) mmol/l (median (range)). Apolipoprotein B was higher (p<0.02) in patients with nephropathy as compared to the other three groups (nephropathy vs healthy subjects): 1.54±0.47 vs 1.33±0.30 g/l. In conclusion, our case-control study has confirmed that Type 2 diabetic patients with increased urinary albumin excretion frequently suffer from dyslipidaemia and cardiovascular disease. However, our study revealed no significant elevation in serum concentration of apo(a) in patients with diabetic nephropathy, but numbers were small.     

Raised serum apolipoprotein (a) in active diabetic retinopathy

Summary Progressive capillary occlusion often leads to severe retinopathy within 15–20 years of the onset of Type 1 (insulin-dependent) diabetes mellitus. Lipoprotein (a), a complex formed by apolipoprotein (a), apo B-100 and lipids, is considered an independent, genetically determined, predictor of cardiovascular disease. It may have antifibrinolytic properties in view of its similarity to plasminogen. To test the hypothesis that circulating lipoprotein (a) is associated with the process that leads to clinically active diabetic retinopathy, we measured the circulating levels of apolipoprotein (a) (which are strictly correlated with those of lipoprotein (a)) in two groups of patients with Type 1 diabetes of at least 15 years duration: 25 with active retinopathy and 27 without clinically detectable retinal lesions. Thirty-eight healthy subjects of the same age and sex served as controls. Serum apolipoprotein (a) was higher in the patients with active retinopathy (36(2-193) U/dl, geometric mean and range) than in those without clinically detectable retinal lesion (17(1–160)) and the control subjects (14(0–115)), p < 0.01 in both cases. The distribution of apolipoprotein (a) levels was skewed to the left, as expected, in the patients without clinically evident retinal lesions and the control groups, but there was a bimodal trend of distribution among those with active retinopathy. The levels of glycated haemoglobin were similar in the two groups of diabetic patients, and no significant differences were found for total and HDL cholesterol, triglycerides or apolipoproteins A1 and B between them and the control subjects. These preliminary results suggest that serum apolipoprotein (a) is elevated in patients with active retinopathy. The role of this lipoprotein as a predictor or a pathogenic effector of diabetic retinopathy, or both deserves further investigation.     

女性高血压病绝经前后脂蛋白(a)及血脂含量分析

目的 观察女性高血压病患者绝经前后血清脂蛋白（ａ）「Ｌｐ（ａ）」及血脂水平的变化。方法 本组纳入女性高血压患者１１３例,分绝经前及绝缘 后组。测定晨 起空腹静脉血中Ｌｐ（ａ）、总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、低密度脂蛋白胆固（ＬＤＬ－Ｃ）、高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）。将各指标与对照线比较以及高血压患者绝经一间比较。结果 高血压组,Ｌｐ（ａ）、ＴＣ、ＴＧ、ＬＤＬ－Ｃ均高于对照组,ＨＤＬ－Ｃ