摘要
研究背景：糖尿病是动脉粥样硬化的主要危险因素,糖尿病病人由于高血糖的作用,与体内大分子物质发生一系列反应,从而导致糖化低密度脂蛋白(G-LDL)在体内的生成与沉积,对动脉粥样硬化的发生与发展起到了促进的作用。血清中LDL与葡萄糖经非酶糖基化作用生成的G-LDL是评价糖尿病控制水平的长期指标,并且对糖尿病的动脉粥样硬化形成具有重要的诊断价值。既往将无冠心病的糖尿病归为冠心病的危险因子,目前已经升级为冠心病的等危症。目前如高血压、高血脂、肥胖和吸烟等冠心病的危险因素,均不足以解释糖尿病病人为什么有如此高的动脉粥样硬化发病率。但是临床上仍发现一部分糖尿病病人,即使有糖尿病病史5年以上,经冠脉造影检查仍未发现任何粥样斑块。
研究目的：本实验采用氯化硝基四氮唑蓝法比色法测定DM-NCHD组与DM-CHD组的G-LDL水平,探讨G-LDL与冠脉造影阴性的关系。同时使用自动生化分析仪(Sapphire600)测定总胆固醇(CHOL)、高密度脂蛋白胆固醇(HDL)和低密度脂蛋白胆固醇(LDL)、甘油三酯(TG)。TG采用磷酸甘油氧化酶法、HDL、LDL均使用化学修饰酶法。糖化血红蛋白(HbA1C)采用微柱层析法测定。研究G-LDL与冠脉造影阴性的关系,与冠脉粥样硬化程度的关系,G-LDL与TG、HbA1c、LDL、HDL、CHOL的相关性。
研究方法：根据糖尿病诊断标准(1999年WHO标准),选择济宁医学院附属医院心内科2011年6月到2012年9月心内科住院的全部糖尿病冠脉造影阴性患者49例,通过随机抽样的方法选择糖尿病冠脉造影阳性患者50例,正常对照组50例。所有入选者年龄均在55岁-75岁之间,有糖尿病的病例组糖尿病病史均超过5年,均排除肝肾功能不全、激素替代治疗、甲亢、合并肿瘤、凝血机制障碍等患者以及不同意参加本研究的患者,均签署知情同意书。所有受试者均于清晨空腹肘静脉采血,采用氯化硝基四氮唑蓝比色法。测定原理：用沉淀法分离出血清G-LDL,在碱性条件下,G-LDL使NBT还原生成紫色的化合物,其颜色的深浅与G-LDL的含量成正比,在分光光度计上测定530nm处吸光度(A)值,计算G-LDL指数=A×500,测定结果为指数,无单位。使用自动生化分析仪(Sapphire600)测定甘油三酯(TG)、总胆固醇(CHOL).高密度脂蛋白胆固醇(HDL)和低密度脂蛋白胆固醇(LDL)。TG采用磷酸甘油氧化酶法、HDLLDL均使用化学修饰酶法。糖化血红蛋白(HbA1C)采用微柱层析法测定。采用SPSS13.0统计分析软件,计量资料以均数±标准差(x±s)表示,2组间比较采用t检验,单因素组间比较采用方差分析。相关性分析应用Pearson相关分析。多因素分析采用多元线性逐步回归分析,入选标准0.05,剔除标准0.10。以P<0.05为差异有统计学意义。使用SPSS的ROC曲线过程,以血清G-LDL水平为检验变量,以冠脉造影结果为状态变量,作ROC曲线分析,并求出诊断点。
研究结果1.DM-NCHD组血清G-LDL水平低于DM-CHD组(P<0.05),高于NC组(P<0.05)。
2.血清G-LDL水平与冠脉粥样硬化程度(以Gensini评分表示)成正相关。
3.多元逐步回归显示：以G-LDL为因变量,以TG、LDL、HDL、CHOL、 HbA1c为自变量进行多元线性回归分析,结果显示G-LDL与TG呈正相关,与HbA1c.LDL、HDL、CHOL无关。
4.横轴为1-特异度,纵轴为灵敏度,ROC曲线下面积为0.805,面积标准误为0.044,血清G-LDL水平用于诊断冠脉粥样硬化有显著意义(P=0.000)。血清G-LDL为50.45时,灵敏度为0.80,特异度为0.84。研究结论糖尿病冠脉造影阴性患者血清G-LDL水平明显低于糖尿病冠脉造影阳性组,并且血清G-LDL水平与冠脉粥样硬化程度呈正相关,G-LDL有望成为评价糖尿病患者冠脉粥样硬化风险的有效指标。
Research background Diabetes is a major risk factor for atherosclerosis, diabetic patients with high blood sugar, a series of reactions and in vivo macromolecules, resulting in glycosylated low density lipoprotein (G-LDL) in the generation and deposition in vivo, occurrence and development of atherosclerosis plays a promoting role. In the past diabetes with no coronary heart disease as risk factor for coronary heart disease, at present has been upgraded to a CHD risk equivalent. At present, such as the risk of hypertension, hyperlipidemia, obesity and smoking factor of coronary heart disease, are not enough to explain why diabetic patients have such a high rate of incidence of atherosclerosis. But the clinical still found part of the diabetic patients, even had diabetes for5years, after coronary angiography has not yet found any plaque.
Research objective the experimental determination of DM-NCHD group and DM-CHD group with nitro blue tetrazolium chloride method at the G-LDL level, to explore the relationship between coronary angiography negative and G-LDL. At the same time, the use of automatic biochemical analyzer (Sapphire600) determination of total cholesterol (CHOL), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL), triglyceride (TG). TG using glycerol phosphate oxidase method, HDL, LDL are the use of chemical modification of enzyme method. Glycosylated hemoglobin (HbA1C) were measured by the micro column chromatography. Study on the relationship between coronary angiography negative and the correlation between G-LDL and G-LDL, TG, HbAlc, LDL, HDL, CHOL
Research methods According to the diagnostic criteria for diabetes (1999WHO),49of all diabetic patients with angiographically normal coronary arteries from2011June to2012September in Department of Cardiology of Affiliated Hospital of Jining Medical College Department of Cardiology in hospital patients, through random sampling method to select50cases of patients with positive diabetic coronary angiography,50cases of normal control group. All subjects were aged between55-75years of age, history of diabetes mellitus diabetic patients were over5years, were excluded from the liver and kidney dysfunction, hormone replacement therapy, patients with hyperthyroidism, tumor, disturbances of blood coagulation and do not agree with the patients involved in the study, informed consent. All subjects were in the early morning fasting venous blood, using nitro blue tetrazolium chloride method. Determination of principle:using isolated serum G-LDL precipitation method, under alkaline conditions, compound G-LDL the NBT reduction generation purple, content depth and G-LDL whose color is proportional to the measured absorbance at530nm, spectrophotometer (A) values, calculated index of G-LDL=A x500, determination the results for the index, no unit. The use of automatic biochemical analyzer (Sapphire600) determination of triglycerides (TG), total cholesterol (CHOL), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL). TG using glycerol phosphate oxidase method, HDL, LDL are the use of chemical modification of enzyme method. Glycosylated hemoglobin (HbA1C) were measured by the micro column chromatography. Using SPSS13.0statistical analysis software, the measurement data with the mean±standard deviation (x±s), between the two groups using t test, single factor between the groups was compared using analysis of variance. Multiple factors were analyzed by multiple linear stepwise regression analysis, the inclusion criteria0.05, excluding the standard0.10. With P<0.05for the difference was statistically significant. The ROC curve using SPSS, the serum G-LDL level was tested with variable, using the result of coronary artery angiography as state variables, for the analysis of ROC curve, and find out the breakpoint.
research results1.Group DM-NCHD G-LDL levels were lower in the DM-CHD group (P<0.05), higher than that of NC group (P<0.05).
2The G-LDL levels in the DM-CHD Group were positively correlated with the degree of coronary atherosclerosis.
3Multiple linear stepwise regression analysis showed that:the G-LDL as the dependent variable, TG, LDL, HDL, CHOL, HbA1c to make a multiple linear regression analysis showed that G-LDL was positively correlated with the dependent variable, TG, has nothing to do with the HbA1c, LDL, HDL CHOL.
4horizontal1-axis for the sensitivity, specificity, and area under ROC curve0.805, area of standard error is0.044, the level of serum G-LDL for diagnosis of coronary atherosclerosis was significant (P=0.000). Serum G-LDL was50.45, the sensitivity was0.80, specificity was0.84.
Research result G-LDL levels in the DM-NCHD group was significantly lower than those in the DM-CHD group, and the G-LDL levels in the DM-CHD Group were positively correlated with the degree of coronary atherosclerosis, G-LDL is expected to be the effective indicator to evaluate the risk of coronary atherosclerotic in patients with diabetes mellitus.
引文
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