Mormile A, Veglio M, Gruden G, Girotto M, Rossetto P, D'Este P, Cavallo-Perin P
Institute of Internal Medicine, University of Torino, Italy.
Acta Diabetol. 1996 Sep;33(3):241-5. doi: 10.1007/BF02048551.
Microalbuminuria and haemostasis derangements have been considered as independent risk factors for cardiovascular death in type 2 (non-insulin-dependent) diabetic patients. Few studies have assessed coagulation inhibitors in type 2 diabetic patients with normoalbuminuria and microalbuminuria. Therefore, 32 type 2 diabetic patients with normoalbuminuria (albumin excretion rate, AER < 20 mg/min, mean 7 +/- 1) and 28 type 2 diabetic patients with microalbuminuria (AER 20-200 mg/min, mean 84 +/- 11) were studied. The patients were matched for age, sex, disease duration and treatment, body mass index (BMI), blood pressure and glycohaemoglobin. Protein C and S activity, antithrombin III, thrombomodulin and prothrombin fragments 1 + 2 (F 1 + 2) were assessed together with fibrinogen, triglycerides, total and high density lipoprotein (HDL)-cholesterol concentrations. Fibrinogen, total and low density lipoprotein (LDL) concentrations were similar in the two groups, while a significant difference was observed for triglycerides (normoalbuminuric group: 128 +/- 10 mg/dl, microalbuminuric group: 184.1 +/- 17 mg/dl; P < 0.007) and HDL-cholesterol (normoalbuminuric group: 45 +/- 2 mg/dl, microalbuminuric group: 39 +/- 2 mg/dl; P < 0.05). The coagulation parameters were as follows: normoalbuminuric group: protein C activity 109% +/- 5%, protein S 95.4% +/- 5%, thrombomodulin 49.3 +/- 3 ng/ml, antithrombin III 93.3% +/- 3%, F 1 + 2 1.05 +/- 0.04 nmol/l; microalbuminuric group: protein C activity 107% +/- 4%, protein S 98.4% +/- 4%, thrombomodulin 64.4 +/- 4 ng/ml, antithrombin III 93.3% +/- 3%, F 1 + 2 1.03 +/- 0.05 nmol/l. The difference was significant for thrombomodulin (P < 0.007). A significant direct correlation was observed in the microalbuminuric group between AER and thrombomodulin (r = 0.38, P < 0.05). In conclusion, our data do not support the hypothesis that a reduction in the activity of anticoagulant physiological inhibitors (protein C, protein S, antithrombin III) could contribute to explain the higher cardiovascular risk in type 2 diabetic patients with microalbuminuria. The elevation of plasma thrombomodulin concentration in type 2 diabetic patients could be the consequence of widespread vascular damage in diabetic patients with incipient nephropathy.
微量白蛋白尿和止血功能紊乱被认为是2型（非胰岛素依赖型）糖尿病患者心血管死亡的独立危险因素。很少有研究评估正常白蛋白尿和微量白蛋白尿的2型糖尿病患者的凝血抑制剂。因此，我们对32例正常白蛋白尿的2型糖尿病患者（白蛋白排泄率，AER<20mg/min，平均7±1）和28例微量白蛋白尿的2型糖尿病患者（AER 20 - 200mg/min，平均84±11）进行了研究。患者在年龄、性别、病程和治疗、体重指数（BMI）、血压和糖化血红蛋白方面进行了匹配。同时评估了蛋白C和S活性、抗凝血酶III、血栓调节蛋白和凝血酶原片段1 + 2（F 1 + 2）以及纤维蛋白原、甘油三酯、总胆固醇和高密度脂蛋白（HDL）胆固醇浓度。两组的纤维蛋白原、总胆固醇和低密度脂蛋白（LDL）浓度相似，而甘油三酯（正常白蛋白尿组：128±10mg/dl，微量白蛋白尿组：184.1±17mg/dl；P<0.007）和HDL胆固醇（正常白蛋白尿组：45±2mg/dl，微量白蛋白尿组：39±2mg/dl；P<0.05）有显著差异。凝血参数如下：正常白蛋白尿组：蛋白C活性109%±5%，蛋白S 95.4%±5%，血栓调节蛋白49.3±3ng/ml，抗凝血酶III 93.3%±3%，F 1 + 2 1.05±0.04nmol/l；微量白蛋白尿组：蛋白C活性107%±4%，蛋白S 98.4%±4%，血栓调节蛋白64.4±4ng/ml，抗凝血酶III 93.3%±3%，F 1 + 2 1.03±0.05nmol/l。血栓调节蛋白差异显著（P<0.007）。在微量白蛋白尿组中，AER与血栓调节蛋白之间存在显著的直接相关性（r = 0.38，P<0.05）。总之，我们的数据不支持以下假设，即抗凝生理抑制剂（蛋白C、蛋白S、抗凝血酶III）活性降低有助于解释微量白蛋白尿的2型糖尿病患者心血管风险较高的原因。2型糖尿病患者血浆血栓调节蛋白浓度升高可能是早期肾病糖尿病患者广泛血管损伤的结果。
