BACKGROUND Persistent microalbuminuria in diabetic patients is a risk factor of cardiovascular mortality. Increased plasma plasminogen activator inhibitor type-1 (PAI-1) levels have been observed in diabetic patients with overt nephropathy. However, there have been few studies on diabetic patients with microalbuminuria. The expression of PAI-1 may be influenced by the polymorphism of the PAI-1 genotype promoter. The aim of this study was to investigate the relationship between the plasma PAI-1/t-PA levels, polymorphism of the PAI-1 4G/5G promoter and microalbuminuria in type 2 diabetes. METHODS: The plasma PAI-1/t-PA levels and polymorphisms of the PAI-1 promoter were measured in type 2 diabetic patients without nephropathy (n=30), and with microalbuminuria (n=30) and overt proteinuria (n=20). The correlation between the amount of urinary albumin excretion and plasma PAI-1/t-PA levels were investigated using Pearson's correlation analyses. RESULTS: The plasma PAI-1/t-PA levels and polymorphisms of the PAI-1 promoter showed no significant difference between the three groups in relation to the urinary albumin excretion. There were no differences in the plasma PAI-1/t-PA levels between the genotypes of the polymorphism of the PAI-1 promoter. No association was found between the amount of urinary albumin excretion and the plasma PAI-1/t-PA levels and genotypes of the polymorphism of the PAI-1 promoter. CONCLUSION: These results show that there was no decrease in the fibrinolytic state in type 2 diabetics with microalbuminuria, compared to normoalbuminuria, which also suggest that polymorphisms of the PAI-1 4G/5G promoter do not affect the plasma PAI-1/t-PA levels in type 2 diabetic patients with microalbuminuria.
Sung Jin Nam, Sung Rae Cho, Choo Sung Kim, Sang Gyun Woo, Hee Jin Choi, Sang Ki Kim, Jae Hong Park, In Kyu Lee, Seong Bum Han, Seung Yup Han, Chung Chul Kim
Korean Diabetes J. 1999;23(1):55-61. Published online January 1, 2001
OBJECTIVES The plasminogen activator inhibitor-1 (PAI-I) and lipoprotein(a) are considered as important fibrinolysis inhibitors. We evaluated PAI-1 and Lp(a) concentrations in Korean non-insulin- dependent diabetes mellitus (NIDDM) patients with or without peripheral vascular disorder. METHODS: By using National Diabetes Data Group (NDDG) criteria as a diabetes mellitus diagnostic criteria, a total of 127 Korean NIDDM patients were seleeted. The ankle brachial index was measured by segrnental volume plethysmography to diagnose peripheral vascular disease. We also examined clinical and biochemical parameters in NIDDM patients. RESULTS: The duration of diabetes, systolic and diastolic pressures was significantly higher in diabetic patients with peripheral vascular disease (Group 2) than in diabetic patients without peripheal vascular disease (Group 1). The 24 hour urine microalbumin and PAI-1 levels in Group 2 were also significantly higher and the HDL-cholesterol level was lower than in Group 1. There were significant correlations between the plasma level of PAI-1 and BMI (r=0.466, p=0,007) or C-peptide level(r=0.517, p=0.012). Multivariate logistic regression analysis showed that Lp(a) and PAI-1 are independent risk factors for peripheral vascular disease. CONCLUSION: In the light of these results, it seems reasonable to suggest that high levels of PAI-1 and Lp(a) in NlDDM patients may play a role in the pathogenesis of peripheral vascular disease.
BACKGROUND Conventional cardiovascular risk factors cannot fully explain high risk of cardiovascular disease in patients with non-insulin dependent diabetes mellitus(NIDDM). This study was undertaken to know whether plasma PAI-1 levels are increased in NIDDM patients, and to identify factors intluencing Pal-1 levels. METHODS: Forty three microalbuminuric, 41 normoalbuminuric NIDDM patients and 39 normal controls matched with age, sex and body mass index (BMI) participated in this study. Clinical characteristies and laboratory findings such as lipid profile, fasting serum C-peptide and PAI-1 levels were evaluated, RESULTS: NIDDM patients showed significantly higher PAI-1 levels than normal controls(44.3+17.4 ng/mL vs. 26.3+12.6ng/mL, p<0.05). However, we failed to show the differences in PAI-1 levels between NIDDM patients with microalbuminuria and normoalbuminuria. PAI-1 levels were significantly correlated to BMI, fasting plasma glucose, HbA1, triglyceride and serum C-peptide levels. Multiple regression analysis showed that serum triglyceride and fasting serum C-peptied levels were independently related to PAI-1 levels. Conclusion; These findings suggested that elevated PAI-1 levels may contribute to increased risk of cardiovascular disease in patients with NIDDM.