【摘要】 目的:探讨噻唑烷二酮类药物对老年男性2型糖尿病患者的抗动脉粥样硬化作用,并了解该种作用发生的相关因素。方法:①选择2002-03/2003-03哈尔滨医科大学附属第二医院老年病科门诊就诊的男性2型糖尿病患者45例。符合纳入标准的2型糖尿病患者24例,均签署知情同意书。随机将受试者分为3组:对照组(给予格列吡嗪5mg/次,3次/d),罗格列酮4mg/d组(给予罗格列酮4mg/次,1次/d)和罗格列酮8mg/d组(给予罗格列酮8mg/d),每组8例。本实验共进行6个月。根据罗格列酮治疗3个月糖化血红蛋白下降的情况又分为2亚组:反应亚组(n=10,下降>1%为反应亚组)和非反应亚组(n=6,下降<1%为非反应亚组)。②于服药前,服药后3,6个月分别测定身高、体质量、收缩压、舒张压、空腹血糖、糖化血红蛋白、空腹血浆胰岛素、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、三酰甘油及高敏C反应蛋白、纤维蛋白原和颈动脉内膜中层厚度。并计算胰岛素抵抗指数和体质量指数。血浆胰岛素采用双相、双步时间依赖性荧光免疫法测定。高敏C反应蛋白运用比浊法检测。纤维蛋白原运用CA-1500全自动血栓/止血测定系统枸橼酸抗凝血浆检测。颈动脉内膜中层厚度应用高分辨B-型超声仪测定。③各组间比较应用方差分析,组内治疗前后比较应用HotellingT2检验。应用Pearsson相关分析和多元线性回归分析影响颈动脉内膜中层厚度的因素。结果:实验过程中无因肝肾功能改变以及药物不耐受而退出试验者,24例均进入结果分析。①对照组治疗3和6个月后空腹血糖,糖化血红蛋白,三酰甘油水平明显低于治疗前(P<0.01),其余指标无显著改变。罗格列酮治疗组在治疗3和6个月后空腹血糖、糖化血红蛋白、胰岛素抵抗指数、三酰甘油、纤维蛋白原,C反应蛋白和颈动脉内膜中层厚度明显低于治疗前(P<0.05～0.01);罗格列酮治疗组治疗后空腹胰岛素下降,但治疗6个月时才明显低于治疗前和对照组(P<0.01);罗格列酮治疗组治疗6个月后空腹胰岛素明显低于治疗3个月后(P<0.01),罗格列酮4mg/d治疗组治疗6个月后胰岛素抵抗指数较治疗3个月后明显减少(P<0.05),其余指标于治疗3和6个月后差异不明显。②反应亚组和非反应亚组治疗3和6个月后胰岛素抵抗指数、三酰甘油、纤维蛋白原、C反应蛋白、颈动脉内膜中层厚度均明显低于治疗前(P<0.01),且除胰岛素抵抗指数外上述各项二亚组间差异不明显。反应亚组治疗3和6个月后空腹血糖、糖化血红蛋白、空腹胰岛素、胰岛素抵抗指数、三酰甘油、纤维蛋白原、C反应蛋白、颈动脉内膜中层厚度均较低于治疗前(P<0.01),空腹血糖、糖化血红蛋白明显低于非反应亚组(P<0.05～0.01),反应亚组治疗6个月后空腹胰岛素和胰岛素抵抗指数明显低于非反应亚组和治疗3个月后(P<0.05～0.01)。反应亚组治疗6个月后低密度脂蛋白胆固醇水平明显高于非反应亚组和治疗前(P<0.05,0.01)。③Pearson相关分析表明,颈动脉内膜中层厚度的变化只与C反应蛋白的变化呈显著正相关(r=0.298,P<0.05),而与糖化血红蛋白、胰岛素抵抗指数等指标改变不相关(r=-0.018,-0.218,P>0.05)。多元线性回归分析也显示颈动脉内膜中层厚度只与C反应蛋白相关(回归系数b=0.435,P<0.05),而与糖脂代谢指标无关。结论:罗格列酮的抗动脉粥样硬化作用主要依赖于其降糖外作用,并可能与抗炎作用有关,此作用无剂量和时间依赖性。更多还原

【Abstract】 AIM: To study the effects of thiazolidinediones (TZDs) on anti-atherosclerosis in elder male patients with type 2 diabetes, and understand related factors induced this function. METHODS: 1 Forty-five male patients with type 2 diabetes, who were diagnosed at the outpatient clinic of Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University from March 2002 to March 2003, were selected. Twenty-four patients with type 2 diabetes were accorded with the inclusion criteria, and all signed the informed consents. The testees were assigned randomly into 3 groups: control group (treated with glipizide 5 mg every time, 3 times a day), rosiglitazone 4 mg per day group (giving 4 mg rosiglitazone every time, once a day) and rosiglitazone 8 mg per day group (giving 8 mg rosiglitazone per day) with 8 cases in each group. This experiment was performed for 6 months totally. According to treatment for 3 months with rosiglitazone and the decrease of glucose ferrohemoglobin, they were divided into 2 subgroups: response subgroup (n=10, decrease by > 1%) and no response subgroup (n=6, decrease by <1%). 2 The changes in height, body mass, systolic pressure, diastolic pressure, fasting glucose, glycosylated hemoglobin, fasting serum insulin, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triacylglycerol, high sensitivity C-reactive protein, fibrinogen and carotid intermedium thickness were measured at the time of beginning, 3 and 6 months after management. The insulin resistance index (IRI) and body mass index were calculated. Plasm insulin was detected with two-phase-step time dependence fluorescent immunization method. The high sensitivity C-reactive protein was detected with turbidimetry. The fibrinogen was detected with CA-1 500 full automatic thromb/hemostasis system citric acid anti-coagulated blood method. The carotid intermedium thickness was detected with high-resolution B-ultrasound. 3 Group comparison and endogroup comparison were managed with analysis of variance and Hotelling T2 test. Multifactors affected the carotid intermedium thickness were analyzed with Pearsson correlation analysis and multiple linear regression analysis.RESULTS: No one refused experiment for changes of liver-renal function and medicine intolerance. All the 24 subjects were involved in the result analysis. 1 The concentration of fasting serum glucose, glycosylated hemoglobin and triacylglycerol at the time of 3 and 6 months treatment in the control group were markedly lower than those before management (P < 0.01). Other data had no markedly changes in the control group. The fasting glucose, glycosylated hemoglobin, IRI, triacylglycerol, fibrinogen, C-reactive protein and carotid intermedium thickness at the time of 3 and 6 months treatment in the rosiglitazone group were lower significantly than those before treatment (P < 0.05-0.01). The fasting insulin decreased after treatment in the rosiglitazone group, but it was lower significantly than before treatment and that in the control group after treatment for 6 months (P < 0.01). The fasting insulin in rosiglitazone group after treatment for 6 months was lower significantly than after treatment for 3 months (P < 0.01). The IRI in the rosiglitazone 4 mg per day group after being treated for 6 months decreased significantly as compared with that after being treated for 3 months (P < 0.05). The differences of other indexes after being treated for 3 or 6 months were insignificant. 2 At the time of 3 and 6 months, IRI, triacylglycerol, fibrinogen, C-reactive protein and carotid intermedium thickness were lower significantly than those before treatment (P < 0.01) in the response subgroup and no response subgroup, and the difference of above-mentioned items (except IRI) was unobvious between the two subgroups. At the time of 3 and 6 months, fasting serum glucose, glycosylated hemoglobin, fasting serum insulin, IRI, triacylglycerol, fibrinogen, C-reactive protein and carotid intermedium thickness were lower than those before treatment (P < 0.01) in the response subgroup. Fasting serum glucose and glycosylated hemoglobin were lower significantly than those in no response group (P < 0.05-0.01). At the time of 6 months fasting serum insulin and IRI in response subgroup were obviously lower than those in no response subgroup and at the time of 3 months after treatment (P < 0.05-0.01). At the time of 6 months the level of low-density lipoprotein cholesterol in response subgroup was higher obviously than that in no response subgroup and before treatment (P < 0.05, 0.01). 3 Pearson correlation analysis showed that carotid intermedium thickness was only associated positively with C-reacive protein significantly(r=0.298,P < 0.05), while it had no relation with glycosylated hemoglobin and IRI etc. (r=-0.018, -0.218, P > 0.05). Multiple linear regression analysis revealed that carotid intermedium thickness was only associated with C-reactive protein (regression coefficient b=0.435,P < 0.05) and independent with other glucolipid metabolism parameters. CONCLUSION: The anti-atherogenic effect of rosiglitazone exists independently with its antidiabetic one and maybe related to anti-inflammatory effect that is without dose and time-dependence.更多还原