The Changes Of Fibrinolysis And Its Effects On Diabetic Angiopathies In Type 2 Diabetic Patients

Objective: Diabetic angiopathies, including macroangiopathy and microangiopathy, are serious and chronic complication in type 2 diabetes mellitus. They affect the life and exist qualities of patients. Their exact mechanism is complicated and common believed that the cooperation of several factors. In recent years, many researchs show that abnormal fibrinolysis play an important role in the pathogenesis and development of diabetic angiopathies. Because the fibrinolysis index is systemless and intactless, its conclusion is not clear. On this basis, we investigated the initiation factor of fibrinolysis: tissue-type plasminogen activator(t-PA) and its inhibitor : plasminogen activator inhibitor-1(PAI-1). We measured their serum levels in type 2 diabetic patients with or without angiopathies, and further more, researched the possible correlation with some parameters, for example, body mass index(BMI) ,waist hip ratio(WHR) ,blood pressure(BP) ,fasting blood glucose(FBG) ,fasting blood insulin(FINS) ,insulin sensitive index(ISI) ,HOMA-insulin resistance index(HOMA-IR) ,hemoglobinA1c(HbA1c) ,urinary albumin excretion rate(UAER) ,lipids, et al, in order to make clear the change tendency and influential factors of fibrinolysis in type 2 diabetic patients and provide theory basis for the early diagnosis and prevention. Methods: 63 patients with T2DM (1999 WHO diagnostic standards) were selected for this study, 31 male and 32 female, (52.70±8.37) years old, DM duration (9.27±5.54) years. They were divided into two groups based on the presence or absence of diabetic angiopathies:group A were 30 cases without diabetic angiopathies and group B were 33 cases with diabetic angiopathies ( including macroangiopathy ,microangiopathy or both ) . 25 healthy individuals were randomly selected as normal controls (NC), including 14 male and 11 female , (50.84±8.38) years old, without acute or chronic inflammatory disease, history of liver or kidney disease,immunity system,blood system disease,hypertension or DM,et al. After absolute diet for 10 hours venous blood samples were obtained in the next morning, the serum levels of t-PA and PAI-1 were measured by ELISA method. The main clinical and laboratory datas such as BMI,WHR,BP,FBG,FINS,HbA1c,UAER and lipids as well were tested in all subjects. We analyzed the change tendency and influential factors of t-PA and PAI-1 in type 2 diabetic patients without or with angiopathies. All the statistical analysis were dealt with SPSS10.0 software. All these datas were expressed as mean±SD and statistical comparisons were done by student test ,linear correlation and multiple stepwise regression analysis. Results: 1. The serum levels of t-PA were significantlydecreased (P<0.01) and the serum levels of PAI-1 were significantly increased (P<0.01) in type 2 diabetic patients as compared with normal controls. 2. The sex and age between DM groups and NC group were matched, and had no significant changes. Compared with NC group, the serum levels of t-PA were decreased (P<0.01) in A group, and were significantly decreased (P<0.001) in B group. And the serum levels of t-PA in B group were obviously lower than those in A group(P<0.001). Compared with NC group, the serum levels of PAI-1 were increased in A group(P<0.01), and significantly increased in B group(P<0.001). And the serum levels of PAI-1 in B group were obviously higher than those in A group (P<0.001). 3. In type 2 diabetic patients, the serum levels of t-PA had a obviously negative correlation with PAI-1 (r=-0.788,P<0.001). 4. By bivariate correlation analysis between DM duration,BMI,WHR,BP,FBG,FINS,ISI,HOMA-IR,HbA1c,UAER,lipids and t-PA or PAI-1, the serum levels of t-PA had a significantly negative correlation with BMI,WHR,UAER,TG ( respectively, r=-0.278,r=-0.295,r=-0.289,r=-0.338; all , P<0.01 ) and had a remarkably negative correlation with DM duration ,FBG ,FINS ,HOMA-IR ,HbA1c ,TC ( respectively, r=-0.641, r=-0.547, r=-0.657, r=-0.661 ,r=-0.566,r=-0.408;all, P<0.001), and had a positive correlation with HDL (r=0.189,P<0.05) , and had a remarkably positive correlation with ISI (r=0.718,P<0.001). The serum levels ofPAI-1 had a significantly positive associated with WHR,UAER,TG ( respectively, r=0.337,r=0.262,r=0.303; all, P<0.01), and had a remarkably positive associated with DM duration,BMI,FBG,FINS,HOMA-IR,HbA1c,TC ( respectively, r=0.706,r=0.346,r=0.625, r=0.728,r=0.749,r=0.632, r=0.351; all, P<0.001 ), and had a remarkably negative correlation with ISI (r=0.-787,P<0.001). 5. By multiple stepwise regression analysis, ISI,DM duration and TC were the influential factors of t-PA ( respectively, β=0.720,P<0.001;β=-0.294,P<0.01;β=-0.160,P<0.05) and HOMA-IR was an independent risk factors of PAI-1(β=0.803,P<0.001). Conclusion: 1. Compared with normal controls, the serum levels of t-PA are decreased and the serum levels of PAI-1 are increased in type 2 diabetic patients. It induces the fibrinolysis is impaired in those patients. And this change has happened when without diabetic angiopathies, and is more obvious when with angiopathies. It is suggested that the abnormal fibrinolysis may play an important role in the development of diabetic angiopathies, and may examine the angiopathies as an effective index. 2. There was a direct correlation between the serum levels t-PA or PAI-1 and some parameters, such as DM duration,BMI,WHR,FBG,FINS,ISI,HOMA-IR,HbA1c,UAER,TC,TG,HDL, et al. It suggests that the impaired fibrinolysis in diabetic patients dues to the cooperation of manyfactors, such as high plasma glucose,abdominal obesity,insulin resistance and dyslipidemia. They result in the development of diabetic angiopathies. 3. In the early stages of T2DM, some comprehensive treatments including improving fibrinolytic capacity can prevent and delay the development of diabetic angiopathies.