Jörneskog G, Egberg N, Fagrell B, Fatah K, Hessel B, Johnsson H, Brismar K, Blombäck M
Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden.
Diabetologia. 1996 Dec;39(12):1519-23. doi: 10.1007/s001250050607.
High plasma fibrinogen levels are associated with vascular complications in the general population. Fibrin, the structural element in a clot, is derived from fibrinogen by activation of thrombin. An abnormal fibrin gel structure has been demonstrated in patients with myocardial infarction and in diabetic patients during poor metabolic control. In the present study the properties of fibrin gel structure were investigated in 20 patients with insulin-dependent diabetes mellitus (IDDM): 10 patients without (age: 30 +/- 8; diabetes duration: 7 +/- 6 years), and 10 patients (age: 44 +/- 7; diabetes duration: 27 +/- 9 years) with microangiopathy. Fifteen healthy subjects served as controls (age: 40 +/- 8 years). The glycosylated haemoglobin level (HbA1c) was elevated (p < 0.001) in the patients: 6.5 +/- 1.5% in diabetic patients without, and 7.1 +/- 1.0% in diabetic patients with microangiopathy. C-reactive protein and plasma fibrinogen were similar as compared to healthy control subjects. The properties of the fibrin gel structure; i.e. the permeability coefficient (Ks) and the fibre mass length ratio (mu) formed in recalcified plasma on addition of thrombin were investigated. Ks was decreased in the diabetic patients, with (6.5 +/- 2.0 cm2; p < 0.01) and without microangiopathy (6.5 +/- 2.7 cm2; p < 0.05), as compared to healthy subjects (10.0 +/- 3.4 cm2), while mu was not significantly (p = 0.14) altered. The results indicate a lower fibrin gel porosity in patients with IDDM, despite normal plasma fibrinogen and irrespective of microangiopathy. The abnormal fibrin gel structure may be due to an increased glycosylation of the fibrin (-ogen) molecule caused by long-term hyperglycaemia and may be of importance for the development of angiopathy in diabetic patients.
高血浆纤维蛋白原水平与普通人群的血管并发症相关。纤维蛋白是凝块中的结构成分,由凝血酶激活纤维蛋白原产生。在心肌梗死患者和代谢控制不佳的糖尿病患者中已证实存在异常的纤维蛋白凝胶结构。在本研究中,对20例胰岛素依赖型糖尿病(IDDM)患者的纤维蛋白凝胶结构特性进行了研究:10例无微血管病变患者(年龄:30±8岁;糖尿病病程:7±6年),以及10例有微血管病变患者(年龄:44±7岁;糖尿病病程:27±9年)。15名健康受试者作为对照(年龄:40±8岁)。患者的糖化血红蛋白水平(HbA1c)升高(p<0.001):无微血管病变的糖尿病患者为6.5±1.5%,有微血管病变的糖尿病患者为7.1±1.0%。与健康对照受试者相比,C反应蛋白和血浆纤维蛋白原相似。研究了纤维蛋白凝胶结构的特性,即加入凝血酶后在重新钙化血浆中形成的渗透系数(Ks)和纤维质量长度比(μ)。与健康受试者(10.0±3.4cm2)相比,有微血管病变(6.5±2.0cm2;p<0.01)和无微血管病变(6.5±2.7cm2;p<0.05)的糖尿病患者的Ks均降低,而μ无显著变化(p=0.14)。结果表明,IDDM患者的纤维蛋白凝胶孔隙率较低,尽管血浆纤维蛋白原正常且与微血管病变无关。异常的纤维蛋白凝胶结构可能是由于长期高血糖导致纤维蛋白(原)分子糖基化增加,这可能对糖尿病患者血管病变的发展具有重要意义。