Zimmermann J, Schramm L, Wanner C, Mulzer E, Henrich H A, Langer R, Heidbreder E
Department of Medicine, University of Würzburg, Germany.
Clin Nephrol. 1996 Oct;46(4):230-6.
Patients with IDDM, especially those with albuminuria are at high risk for macrovascular and microvascular complications. Besides the major classic risk factors altered hemorheology may also play a role. Plasma viscosity, erythrocyte aggregation and erythrocyte deformability are the major determinants of blood flow in the microcirculation. Therefore, these hemorheological parameters and plasma protein composition were evaluated in 58 IDDM-patients with none (N0), incipient (N1: albuminuria 30-300 mg/day) and overt clinical nephropathy (N2: albuminuria > 300 mg/day). As an estimate of endothelial injury plasma levels of von Willebrand Factor (vWF) were investigated. Patients with incipient and clinical nephropathy exhibited increasing blood levels of fibrinogen (N0 = 2.47 +/- 0.09, N1 = 2.71 +/- 0.15, N2 = 3.49 +/- 0.24 g/l, p < 0.001), alpha 2-macroglobulin (N0 = 257 +/- 11, N1 = 251 +/- 21, N2 = 382 +/- 43 mg/100 ml, p < 0.01) and haptoglobin (N0 = 174 +/- 16, N1 = 216 +/- 39, N2 = 278 +/- 36 mg/100 ml, p < 0.05), whereas serum albumin concentration decreased (N0 = 5.1 +/- 0.1, N1 = 4.7 +/- 0.1, N2 = 4.1 +/- 0.2 g/100 ml, p < 0.001). In the same patients erythrocyte aggregation (N0 = 10.0 +/- 0.4, N1 = 12.1 +/- 0.5, N2 = 12.9 +/- 0.6, p < 0.001), plasma viscosity (N0 = 1.34 +/- 0.01, N1 = 1.38 +/- 0.02, N2 = 1.40 +/- 0.02 mPas, p < 0.05) and erythrocyte rigidity (N0 = 0.05 +/- 0.01, N1 = 0.15 +/- 0.05, N2 = 0.09 +/- 0.02, p < 0.05) were increased, predominantly in those with overt clinical nephropathy. Erythrocyte aggregation was positively correlated with plasma concentrations of fibrinogen (r = 0.65, p < 0.001) and alpha 2-macroglobulin (r = 0.35, p < 0.05), but negatively with plasma albumin concentration (r = -0.49, p < 0.001). Plasma viscosity was positively correlated with plasma concentrations of fibrinogen (r = 0.46, p < 0.001) and haptoglobin (r = 0.46, p < 0.001). Von Willebrand Factor levels were higher in patients with overt clinical nephropathy (N0 = 126 +/- 8, N1 = 136 +/- 12, N2 = 163 +/- 14%, p < 0.09, PN0-N2 < 0.05). A significant correlation between vWF and the rheological determinants could not be detected. These data demonstrate that blood rheology is profoundly altered in patients with IDDM and nephropathy. Elevated levels of vWF may indicate endothelial damage, and changes in plasma viscosity as well as erythrocyte aggregability seem to be the result of altered plasma protein composition due to proteinuria. These abnormalities in hemorheology may be an aggravating factor promoting microvascular and macrovascular damage in patients with type I diabetes mellitus and nephropathy.
胰岛素依赖型糖尿病（IDDM）患者，尤其是伴有蛋白尿的患者，发生大血管和微血管并发症的风险很高。除了主要的经典危险因素外，血液流变学改变也可能起作用。血浆粘度、红细胞聚集性和红细胞变形性是微循环中血流的主要决定因素。因此，我们对58例无肾病（N0）、早期肾病（N1：蛋白尿30 - 300mg/天）和显性临床肾病（N2：蛋白尿>300mg/天）的IDDM患者的这些血液流变学参数和血浆蛋白组成进行了评估。作为内皮损伤的一项指标，我们研究了血管性血友病因子（vWF）的血浆水平。早期肾病和临床肾病患者的纤维蛋白原（N0 = 2.47±0.09，N1 = 2.71±0.15，N2 = 3.49±0.24g/L，p < 0.001）α2 - 巨球蛋白（N0 = 257±11，N1 = 251±21，N2 = 382±43mg/100ml，p < 0.01）和触珠蛋白（N0 = 174±16，N1 = 216±39，N2 = 278±36mg/100ml，p < 0.05）血液水平升高，而血清白蛋白浓度降低（N0 = 5.1±0.1，N1 = 4.7±0.1，N2 = 4.1±0.2g/100ml，p < 0.001）。在同一批患者中，红细胞聚集性（N0 = 10.0±0.4，N1 = 12.1±0.5，N2 = 12.9±0.6，p < 0.001）、血浆粘度（N0 = 1.34±0.01，N1 = 1.38±0.02，N2 = 1.40±0.02mPas，p < 0.05）和红细胞刚性（N0 = 0.05±0.01，N1 = 0.15±0.05，N2 = 0.09±0.02，p < 0.05）升高，主要是在显性临床肾病患者中。红细胞聚集性与血浆纤维蛋白原浓度（r = 0.65，p < 0.001）和α2 - 巨球蛋白浓度（r = 0.35，p < 0.05）呈正相关，但与血浆白蛋白浓度呈负相关（r = -0.49，p < 0.001）。血浆粘度与血浆纤维蛋白原浓度（r = 0.46，p < 0.001）和触珠蛋白浓度（r = 0.46，p < 0.001）呈正相关。显性临床肾病患者的血管性血友病因子水平较高（N0 = 126±8，N1 = 136±12，N2 = 163±14%，p < 0.09，PN0 - N2 < 0.05）。未检测到vWF与血液流变学决定因素之间的显著相关性。这些数据表明，IDDM和肾病患者的血液流变学发生了深刻改变。vWF水平升高可能表明内皮损伤，血浆粘度和红细胞聚集性的变化似乎是由于蛋白尿导致血浆蛋白组成改变的结果。这些血液流变学异常可能是促进I型糖尿病和肾病患者微血管和大血管损伤的一个加重因素。
