| Objective: Diabetic nephropathy (DN) is a common and serious microvascular complication of diabetic mellitus. In the United States and Europe, diabetes is the most common cause leading to end stage renal disease (ESRD). In our country, with life extending of the diabetic patients , the morbidity of DN is rising year by year. The pathogenesis of DN is complicated and has not yet been fully clarified. According to current researches, the possible pathogenesis can be summarized into the follow ing areas: hyperglycemia-related biochemical metabolic abnormaliti es; renal hemodynamic changes; the role of Cytokines and grow -th factor; genetic factors and so on. In recent years, the immune theory and the inflammation theory have drawn more attention. Among these, the injury of vascular endothelial cell and the activation of platelet are closely related to the occurrence and development of DN. whereas the mechanism needs further study. Von Willebrand factor(vWF) is a sensitive indicator that reflects the injury and dysfunction of the endothelial cell. Platelet granule membrane protein 140(GMP-140) is a major component of the selectin family belonging to the cell adhesion molecule and is a golden standard of the platelet activation.It is closely related to kidney disease. On this trial, the plasma vWF and GMP-140 levels in patients with DM and DN are determined, the levels of blood pressure (BP), body mass index (BMI),age, duration of diabetes,fasting blood glucose(FBG),hemoglobin- A1c (HbA1c), triglyceride (TG),total cholesterol (TC), high density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol (LDL-C) , Fibrinogen (Fib), Platelet (PLT), Mean platelet volume (MPV) , Platelet hematocrit (PCT) , platelet distribution width (PDW)and urinary albumin excretion rate (UAER) are determined as well, in order to study the role of vWF and GMP-140 played in the pathogenesis of DN and the factors impacted on them.Methods: According to the diagnostic standards of diabetic putting forward by WHO in 1999,a total of 90 patients with T2DM were recruited in group DM in this study,composing of 44 male and 46 female.These patients were further divided into three subgroups according to their urinary albumin excretion rate (UAER): 30 patients with normal albuminuria (UAER<20g /min) were included in group SDM, 30 patientswith microal- buminuria(UARE 20~200 g/min) were included in group EDN and 30 patients with macroalbuminria(UAER>200g/min) were included in group CDN. Meanwhile, 30 heathy individuals se- lected from population for regular physical examination were included in heathy control group (group NC), consisted of 13 male and 17 female.There were no statistically significant differences among the four groups in conditions such as sex ratio ,age and body mass index, etc.According to the clinical criteria, the following selected objects in group DM were excluded: suffering urinary tract infection, primary kidney disease, lung or liver dysfunction, hemorrhagic disease, macrovascular disease, angina or myocar -dial infarction, cerebral infarction previously and essential hypertension. And they must have the following conditions: normal ECG; B-prompted showed no carotid artery plaque; no acute complications of diabetes have been happened in last three weeks; no drugs that can impact on platelet function such as heparin, aspirin and dipyridamole, have been taken in last two weeks;no diuretics and vasoactive agents have been taken in last one week.In group NC, the following selected objects were excluded: suffering diabetes mellitus, hypertension, dyslipidemia ,cardi- ovascular, cerebrovascular, liver or kidney systems disease, hemorrhagic disease, infection recently and having familial history of diabetes and hypertension.Fast blood samples were taken from the elbow vein in every selected object and separated. The plasma levels of vWF and GMP-140 were determined by enzyme linked immunosor- bent assay (ELISA) method.In all subjects,blood pressurese, height and weight were measured and BMI were calculated, and age was recorded . TG, TC ,HDL-C ,LDL-C,Fib,PLT,MPV,PDW,PCT were de- termined as well. In all diabetic subjects, duration of diabetes was recorded ,and FBG,HbA1c ,UAER were determined.The data were dealt with statistical software SPSS 13.0 version.Normal distribution and equal variance station were tested in groups.Normal distributed data were presented as mean士standard deviation. Analysis of variance (ANOVA) were applied in the comparison between groups, q-tests were used in the unequal variance station.The factors impacted on vWF and GMP-140 were analyzed by multiple linear stepwise regress- ion .Results:1. Comparisons of clinical characteristics :①There was no significant difference in age,sex ratio and BMI between group DM and group NC(P>0.05).②Compared with group SDM, the duration of diabetes were significantly longer in group EDN and CDN(P<0.01, P<0.01);Compared with group EDN, it was significantly longer in group CDN(P<0.01).③Compared with group NC, SBP were significantly higher in group DM(P<0.01, P<0.01,P<0.01); Compared with group SDM,SBP was significantly higher in group CDN(P<0.01), no significant difference in group EDN(P>0.05); Compared with group EDN ,SBP was significantly higher in group CDN(P<0.01).Compared with group NC,SDM,and EDN ,DBP was significantly higher in group CDN(P<0.01, P<0.01,P<0.01),no significant difference among group NC,SDM and EDN(P>0.05).2. Comparisons of laboratory characteristics:①There was no significant difference in FPG among diabetic groups(P>0.05). Compared with group SDM, HbA1c were significantly higher in group EDN and CDN(P<0.05, P<0.01); HbA1c was significant- ly higher in group CDN than in group EDN(P<0.05).②Com- pared with group NC, TG were significantly higher in DM groups(P<0.01, P<0.01,P<0.01); Compared with group SDM, TG was significantly higher in group CDN(P<0.01)and there was no significant difference in group EDN (P>0.05); there was no significant difference in TG between group EDN and group CDN(P>0.05). Compared with group NC, TC were significantly higher in DM groups(P<0.01, P<0.01,P<0.01); Compared with group SDM, TC was significantly higher in group CDN(P<0.01) and there was no significant difference in group EDN (P>0.05);TC was significantly higher in group CDN than in group EDN(P<0.01). Compared with group NC, HDL-C were significantly lower in group EDN and CDN(P<0.01, P<0.01),no significant difference in group SDM (P>0.05); Compared with group SDM, HDL-C was significantly lower in group CDN(P< 0.01) and no significant difference in group EDN(P>0.05); Compared with group EDN, HDL-C was significantly lower in group CDN(P<0. 05). Compared with group NC, LDL-C were significantly higher in group EDN and CDN(P<0.05, P<0.01), no significant difference in group SDM(P>0.05); Compared with group SDM, LDL-C was significantly higher in group CDN(P<0.01) and no significant difference in group EDN (P>0.05); Compared with group EDN, LDL-C was significantly higher in group CDN(P<0.01).③Compared with group NC, Fib were significantly higher in DM groups(P<0.01, P<0.01,P<0.01); Compared with group SDM, Fib was significantly higher in group CDN(P<0.01)and there was no significant difference in group EDN (P>0.05); Compared with group EDN, Fib was significantly higher in group CDN(P<0.01).Compared with group NC, PDW were significantly higher in DM groups (P< 0.05, P<0.01,P<0.01); Compared with group SDM, PDW was significantly higher in group CDN(P<0.01)and there was no significant difference in group EDN (P>0.05); there was no significant difference in PDW between group EDN and group CDN(P>0.05). There was no significant difference in PLT,MPV and PCT among group NC,SDM ,EDN and CDN(P>0.05).3.①The plasma levels of vWF in group SDM , EDN and CDN were 1030.03±324.06 mU/ml, 1153.93±374.44 mU/ml, 1274.64±395.02 mU/ml.They were all significantly higher than that in group NC (796.99±275.45mU/ml). Compared with group SDM, vWF was significantly higher in group CDN(P<0.01),and no significant difference in group EDN(P>0.05);There were no significant difference in vWF between group CDN and EDN(P >0.05).②The plasma levels of GMP-140 in group SDM , EDN and CDN were 22.22±11.09 mg/ml, 23.30±9.56 mg/ml, 30.14±10.28mg/ml.They were significantly higher than that in group NC( 12.12±5.79 mg/ml). Compared with group SDM, GMP- 140 in group CDN was significantly higher(P<0.01),and no significant difference in group EDN(P>0.05); GMP-140 was difference in group EDN(P>0.05); GMP-140 was significantly higher in group CDN than in group EDN(P<0.01).4. The main factors affected on the plasma level of vWF were LDL-C,HDL-C,age. The main factors affected on the plasma level of GMP-140 were HbA1c,SBP,LDL-C.Conclusions:1. Compared with group NC,The plasma levels of vWF and GMP-140 in group SDM , EDN and CDN were significantly higher.And the plasma levels of vWF and GMP-140 in group CDN were significantly higher than those in group SDM.It indicated that vWF and GMP-140 played an important part in the pathogenesis of DN.2.The plasma level of vWF was influenced by LDL-C,HDL-C,age and the plasma level of GMP-140 was influenced by HbA1c,SBP,LDL-C .It indicated that synergistic action of many factors led to an increase in the levels of vWF and GMP-140 in diabetic patients, aggravating endothelial damage, enhancing platelet activation and thereby accelerating the process of DN.3.Monitoring the levels of vWF and GMP-140 effective- ly is of great significance in assessing patient's condition and guiding the rational use of clinical drugs in order to retard the progress of DN.
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