Hyperhomocyst(e)inemia and endothelial dysfunction in IDDM
Hyperhomocyst(e)inemia and endothelial dysfunction in IDDM
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DOI：
10.2337/diacare.21.5.841
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发表时间：
1998-05-01
期刊：
影响因子：
16.2
通讯作者：
Nawroth, PP
中科院分区：
文献类型：
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作者：
Hofmann, MA;Kohl, B;Nawroth, PP
目的 - 考虑到血液中同型半胱氨酸水平升高是大血管疾病的一个已知独立危险因素，我们评估了高同型半胱氨酸血症与糖尿病微血管并发症之间的联系。 研究设计和方法 - 对 75 名病情稳定、控制良好的 IDDM 患者在口服蛋氨酸负荷前和口服蛋氨酸负荷后 3 小时测量了同型半胱氨酸和血栓调节蛋白血浆水平（内皮细胞损伤的标志物）。 40 名健康对照受试者的性别和年龄相匹配。排除标准为高脂血症、高血压、吸烟或心血管疾病阳性家族史。 结果 -IDDM 患者的治疗前和治疗后同型半胱氨酸血浆水平高于健康对照受试者（12.0 vs. 7.7 mu mol/l 和 27.6 vs. 16.0 mu mol/l；P < 0.001）。在 75 名 IDDM 患者中，26 名血浆同型半胱氨酸水平高于正常范围（定义为对照组获得的值的平均值 + 2 SD）。患有高同型半胱氨酸血症的 IDDM 患者血浆血栓调节蛋白水平较高（62.2 vs. 38.2 ng/ml；P < 0.001），白蛋白排泄率较高（485 vs. 115 mg/l；P < 0.005），并且晚期糖尿病并发症的发生率较高（肾病，76% vs. 33%；视网膜病变，69% vs. 51%；糖尿病，69% vs. 51%）。与血浆同型半胱氨酸正常的 IDDM 患者相比，神经病变（57% vs. 41%）；大血管病变（57% vs. 33%）。人脐静脉细胞的体外实验表明，仅当在添加 L-同型半胱氨酸之前用晚期糖基化终末产物 (AGE)-白蛋白预处理内皮细胞时，血栓调节蛋白向培养上清液中的释放增加。同型半胱氨酸和 AGE 的协同作用可能会导致糖尿病患者的血管并发症。结论 - 高同型半胱氨酸血症在肾病性糖尿病患者中很常见，并且可能导致糖尿病肾病 IDDM 患者中典型的心血管疾病发病率和死亡率增加。
OBJECTIVE -Considering that elevated blood levels of homocyst(e)ine represent a known independent risk factor for macrovascular disease, we assessed the link between hyperhomocyst(e)inemia and diabetic microvascular complications.RESEARCH DESIGN AND METHODS -Homocyst(e)ine and thrombomodulin plasma levels, a marker of endothelial cell damage, were measured before and 3 h after oral methionine loading in 75 patients with stable, well-controlled IDDM and 40 healthy control subjects matched for sex and age. Exclusion criteria were hyperlipidemia, hypertension, smoking, or positive family history for cardiovascular disease.RESULTS -IDDM patients had higher pre-and postload homocyst(e)ine plasma levels than did healthy control subjects (12.0 vs. 7.7 mu mol/l and 27.6 vs. 16.0 mu mol/l; P < 0.001). Of 75 IDDM patients, 26 had homocyst(e)ine plasma levels above the normal range (defined as mean + 2 SD of values obtained in the control group). The IDDM patients with hyperhomocyst(e)inemia had higher thrombomodulin plasma levels (62.2 vs. 38.2 ng/ml; P < 0.001), higher albumin excretion rates (485 vs. 115 mg/l; P < 0.005), and a higher prevalence of late diabetic complications (nephropathy, 76 vs. 33%; retinopathy, 69 vs. 51%; neuropathy, 57 vs. 41%; macroangiopathy, 57 vs. 33%) compared with IDDM patients with normal plasma homocyst(e)ine. In vitro experiments with human umbilical vein cells show an increased release of thrombomodulin into the culture supernatant only when endothelial cells were pretreated with advanced glycation end product (AGE)-albumin before L-homocystine was added. A synergistic action of homocyst(e)ine and AGEs might contribute to vascular complications of patients with diabetes.CONCLUSIONS -Hyperhomocyst(e)inemia is common in nephropathic diabetic patients and may contribute to the enhanced morbidity and mortality from cardiovascular diseases characteristically observed in IDDM patients with diabetic nephropathy.