Hirano T, Kashiwazaki K, Moritomo Y, Nagano S, Adachi M
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Diabetes Res Clin Pract. 1997 Apr;36(1):11-8. doi: 10.1016/s0168-8227(97)01384-3.
Increased plasma plasminogen activator inhibitor type 1 (PAI-1), coagulation factor VII (FVII) and fibrinogen levels have been recognized as risk factors for cardiovascular disease. Because a substantially high incidence of cardiovascular disease has been reported in diabetic patients with nephropathy compared with those without nephropathy, we measured plasma levels of PAI-1, FVII activity and fibrinogen in non-insulin-dependent diabetic patients (NIDDM) with normoalbuminuria (without nephropathy), microalbuminuria (incipient nephropathy) and macroalbuminuria (overt nephropathy). PAI-1 and FVII levels were significantly increased in NIDDM with overt nephropathy compared with NIDDM without nephropathy. Fibrinogen levels were comparable between the patients with normo-, micro- and macro-albuminuria. Univariate regression analysis indicated that PAI-1 and FVII levels were significantly correlated with the albumin excretion rate (AER) in urine. PAI-1, FVII and fibrinogen levels were significantly correlated with the degree of insulin resistance estimated by the steady state plasma glucose concentration (SSPG) during the continuous infusion of glucose, insulin and octreotide. PAI-1 levels were correlated with plasma triglyceride (TG) levels. Multiple regression analysis revealed that AER was significantly associated with PAI-1 and FVII levels, whereas TG lost significant correlation with PAI-1 when AER, SSPG and plasma TG were entered as independent variables. SSPG retained an independent correlation with fibrinogen, PAI-1 and FVII levels. These results suggest that elevated plasma levels of PAI-1 and FVII in NIDDM patients with nephropathy are directly associated with renal damage, whereas insulin resistance widely regulates hemostatic components in NIDDM patients, irrespective of the presence of nephropathy.
血浆纤溶酶原激活物抑制剂1型（PAI-1）、凝血因子VII（FVII）和纤维蛋白原水平升高已被公认为心血管疾病的危险因素。由于据报道，与无肾病的糖尿病患者相比，患有肾病的糖尿病患者心血管疾病的发病率相当高，因此我们测量了非胰岛素依赖型糖尿病（NIDDM）患者中正常白蛋白尿（无肾病）、微量白蛋白尿（早期肾病）和大量白蛋白尿（显性肾病）患者的血浆PAI-1水平、FVII活性和纤维蛋白原水平。与无肾病的NIDDM患者相比，显性肾病的NIDDM患者PAI-1和FVII水平显著升高。正常白蛋白尿、微量白蛋白尿和大量白蛋白尿患者之间的纤维蛋白原水平相当。单因素回归分析表明，PAI-1和FVII水平与尿白蛋白排泄率（AER）显著相关。在持续输注葡萄糖、胰岛素和奥曲肽期间，PAI-1、FVII和纤维蛋白原水平与通过稳态血浆葡萄糖浓度（SSPG）估计的胰岛素抵抗程度显著相关。PAI-1水平与血浆甘油三酯（TG）水平相关。多因素回归分析显示，当将AER、SSPG和血浆TG作为自变量纳入时，AER与PAI-1和FVII水平显著相关，而TG与PAI-1失去显著相关性。SSPG与纤维蛋白原、PAI-1和FVII水平保持独立相关性。这些结果表明，患有肾病的NIDDM患者血浆PAI-1和FVII水平升高与肾损害直接相关，而胰岛素抵抗广泛调节NIDDM患者的止血成分，无论是否存在肾病。
