Polymorphisms of the Plasminogen Activator Inhibitor- 1 Gene in Type 1 and Type 2 Diabetes, and in Patients with Diabetic Retinopathy

1994 ◽  
Vol 71 (06) ◽  
pp. 731-736 ◽  
Author(s):  
M W Mansfield ◽  
M H Stickland ◽  
A M Carter ◽  
P J Grant
Keyword(s):  
Diabetic Retinopathy ◽  
Plasminogen Activator Inhibitor ◽  
Allelic Frequency ◽  
Repeat Sequence ◽  
Dinucleotide Repeat ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Difference ◽  
Pai 1

SummaryTo identify whether genotype contributes to the difference in PAI-1 levels in type 1 and type 2 diabetic subjects and whether genotype relates to the development of retinopathy, a Hind III restriction fragment length polymorphism and two dinucleotide repeat polymorphisms were studied. In 519 Caucasian diabetic subjects (192 type 1, 327 type 2) and 123 Caucasian control subjects there were no differences in the frequency of the Hind III restriction alleles (type 1 vs type 2 vs control: allele 1 0.397 vs 0.420 vs 0.448; allele 2 0.603 vs 0.580 vs 0.552) nor in the allelic frequency at either dinucleotide repeat sequence. In 86 subjects with no retinopathy at 15 years or more from diagnosis of diabetes and 190 subjects with diabetic retinopathy there was no difference in the frequency of Hind III restriction alleles (retinopathy present vs retinopathy absent: allele 1 0.400 vs 0.467; allele 2 0.600 vs 0.533) nor in the allelic frequencies at either dinucleotide repeat sequence. The results indicate that there is no or minimal influence of the PAI-1 gene on either PAI-1 levels or the development of diabetic retinopathy in patients with diabetes mellitus.

The Effect of Insulin Treatment on the Balance between Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Type 2 Diabetic Patients

1992 ◽  
Vol 68 (03) ◽  
pp. 253-256 ◽  
Author(s):  
Thomas Vukovich ◽  
Sylvia Proidl ◽  
Paul Knöbl ◽  
Harald Teufelsbauer ◽  
Christoph Schnack ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Insulin Treatment ◽  
Plasminogen Activator Inhibitor ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type 2 Diabetic Patients ◽  
Glycemic Regulation ◽  
Type 2 Diabetic ◽  
Pai 1

SummaryBeside hypercoagulation and hyperactivated platelets disturbances of the fibrinolytic system towards hypofibrinolysis have been reported to be associated with both glycemic and lipidemic derangement in diabetic patients. In the present prospective follow-up study the effect of 16 weeks insulin treatment and glycemic regulation on plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the main regulators of fibrinolysis, was investigated in 19 type-2 diabetic patients with secondary failure to sulphonylureas. A similar glycemic regulation was obtained in a control group of 10 type 2 diabetic patients with sufficient metabolic response to strict dietary treatment and continuation of sulphonylurea treatment. Compared to 27 healthy subjects levels of tPA and PAI-1 were not significantly increased in type 2 diabetic patients before metabolic intervention. Although a hypofibrinolytic state due to an increase of PAI-1 levels was previously reported in obese hyperinsulinemic patients, no effect of insulin treatment on both tPA- and PAI-1 levels was observed in the present study including patients with only slightly increased body mass index (median 26.0 kg/m2). By correlation analysis PAI-1 levels were significantly related to serum cholesterol (R = 0.52) and glycemic control (glucose R = 0.41) in the whole group of diabetic patients at entry and in both subgroups after 16 weeks of treatment (insulin group: cholesterol R = 0.46, HbA1c R = 0.51; sulphonylurea group: cholesterol R = 0.59, HbA1c R = 0.58). In healthy subjects tPA and PAI-1 was correlated to serum insulin (R = 0.54, R = 0.56) and triglycerides (R = 0.46, R = 0.40). In conclusion, our results indicate that insulin treatment associated with metabolic improvement has no adverse effect to fibrinolysis in type 2 diabetic patients.

PAI-1 and D-Dimer in Type 2 Diabetic Women With Asymptomatic Macrovascular Disease Assessed by Carotid Doppler

2009 ◽  
Vol 16 (2) ◽  
pp. 204-208 ◽  
Author(s):  
Anna Letícia Soares ◽  
Pedro Wesley Rosário ◽  
Michelle Aparecida Ribeiro Borges ◽  
Marinez Oliveira Sousa ◽  
Ana Paula Salles Moura Fernandes ◽  
...  
Keyword(s):  
Carotid Plaque ◽  
Macrovascular Disease ◽  
Intima Media Thickness ◽  
Plasminogen Activator Inhibitor ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type 2 Diabetic ◽  
Pai 1 ◽  
D Dimer

Asymptomatic diabetic patients with different degrees of macrovascular complications can present different hemostatic changes. At this study, plasminogen activator inhibitor-1 (PAI-1) and D-dimer were evaluated in 12 women without diabetes and 64 type 2 diabetic women. All patients were classified into 3 different categories according to the carotid intima-media thickness (IMT) assessed by Doppler: 25 with <1 mm (normal), 15 with >1 mm and without plaque (intermediate), and 24 with stenosis lower than 50% of the vessel lumen (plaque). The results showed increased plasma D-dimer in type 2 diabetic women with carotid plaque when compared to the other groups. High levels of PAI-1 were observed in all the 3 groups of diabetic women when compared to women without diabetes. Our results suggest that high levels of PAI-1 in type 2 diabetic women are only associated with diabetes and are not associated with macrovascular progression; however, it seems that D-dimer plasma levels are associated with carotid plaque.

scholarly journals Plasminogen activator inhibitor-1 gene polymorphism as a risk factor for vascular complications in type 2 diabetes mellitus

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Fatma A. Khalaf ◽  
Hatem R. Ibrahim ◽  
Hanan M. Bedair ◽  
Maha M. Allam ◽  
Amr A. Elshormilisy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gene Polymorphism ◽  
Vascular Complications ◽  
Plasminogen Activator Inhibitor ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
Increased Risk ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background Diabetes mellitus (DM) can lead to microvascular and macrovascular damages through hyperglycemia that is the main cause of diabetic complications. Other factors such as hypertension, obesity, and hyperlipidemia may worsen or accelerate the others. Several studies have revealed definitive genetic predispositions to the development of type 2 diabetes mellitus (T2DM) and development of vascular complications. This study aimed to address the association between plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and T2DM, and if this gene polymorphism may have a possible role in the development of vascular complications in T2DM. This study is a case control; it included 200 patients with T2DM, 117 patients had no vascular complications, and 83 had previous vascular complications (VCs). One hundred eighty volunteer blood donors were selected as a healthy control group. All patients and controls were subjected to clinical examination, and laboratory investigations included lipid profile, fasting and 2 h blood glucose, complete blood cell count, d-dimer, PAI-1, thrombin activatable fibrinolysis inhibitor (TAFI), and detection of PAI-1 gene polymorphism by real-time polymerase chain reaction (PCR). Results The most prevalent genotype of PAI-1 gene polymorphism in all studied groups, including controls, was 4G/5G with the highest allele frequency as 4G. The 4G/5G and 4G/4G genotypes were associated with increased risk of DM development as compared to 5G/5G genotype. The 4G/5G and 4G/4G genotypes also had a highly significant increased risk of VCs among diabetic patients, as compared to 5G/5G. The 4G allele also was highly associated with DM with VCs. The d-dimer TAFI, PAI-1 showed the highest levels in 4G/5G genotype followed by 4G/4G genotype. The lowest level was expressed in 5G/5G genotype in diabetic patients with and without VCs. The univariable analysis showed that genotypes 4G/5G and 4G/4G were potentially risk factors for development of VCs with T2DM patients. Conclusion This study concludes that the PAI-1 4G/5G polymorphism may be associated with T2DM and may be considered as a risk factor for development of thrombotic events. It may also help in selection and dosing of patients being treated with anticoagulant and fibrinolytic agents. Further large-scale studies are recommended to assess the possible role of environmental factors and gene interactions in the development of T2DM vascular risks.

scholarly journals Dinucleotide repeat polymorphisms in EDN1 and NOS3 are not associated with severe diabetic retinopathy in type 1 or type 2 diabetes

Eye ◽  
1999 ◽  
Vol 13 (2) ◽  
pp. 174-178 ◽  
Author(s):  
K M Warpeha ◽  
F Ah-Fat ◽  
S Harding ◽  
C C Patterson ◽  
W Xu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Dinucleotide Repeat

scholarly journals Gender difference in plasminogen activator inhibitor-1 activity in patients with type 2 diabetes with and without albuminuria, a matched case-control study

2019 ◽  
Vol 9 (7) ◽  
pp. 484
Author(s):  
Mehrnaz Imani ◽  
Soghra Rabizadeh ◽  
Manouchehr Nakhjavani ◽  
Payam Hashemi ◽  
Shaghayegh Pezeshki ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Matched Case ◽  
Matched Case Control Study ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
Control Study

Background: Women with type 2 diabetes are more susceptible to coagulopathy disorders and endothelial dysfunction. One possible explanation is the effects of different sex hormones in inflammatory conditions. Increased plasminogen activator inhibitor-1 (PAI-1) activity has been observed as a possible predisposing factor for coagulopathy disorders and endothelial dysfunction. However, the effect of gender on PAI-1 in patients with type 2 diabetes (T2D) and albuminuria has not been studied sufficiently.Objectives: In this study, we examined whether changes of PAI-1 activity according to the albuminuria state in patients with type 2 diabetes are different in males and females.Materials and Methods: A matched case-control study was performed among participants with T2D, as 38 microalbuminuric patients were matched with 38 normoalbuminuric patients who were similar in age and body mass index (BMI). PAI-1 activity was compared between the two groups with and without gender stratification.Results: PAI-1 activity in microalbuminuric women was higher in comparison to that of the normoalbuminuric controls (P-value < 0.05). There was no significant difference in PAI-1 activity between macroalbuminuric and normoalbuminuric men. In women with type 2 diabetes and albuminuria, PAI-1 activity was independently and significantly associated with urinary albumin excretion.Conclusions: Gender differences in PAI-1 activity, seen in the early stages of diabetic nephropathy, are a possible explanation for the higher incidence of vasculopathy in women with type 2 diabetesKeywords: plasminogen activator inhibitor-1; coagulopathy; microalbuminuria; type 2 diabetes; gender

Inverse relationship between plasminogen activator inhibitor-1 activity and adiponectin in overweight and obese women

2005 ◽  
Vol 94 (12) ◽  
pp. 1190-1195 ◽  
Author(s):  
Ilse Mertens ◽  
Dominique Ballaux ◽  
Tohru Funahashi ◽  
Yuji Matsuzawa ◽  
Marc Van der Planken ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Obese Women ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Difference ◽  
Hs Crp ◽  
Visceral Adipose ◽  
The Relationship ◽  
Activator Inhibitor ◽  
Pai 1

SummaryAdipose tissue is an active endocrine organ secreting different adipokines such as plasminogen activator inhibitor-1 (PAI-1) and adiponectin, among many others. In this study, we investigated the association between PAI-1 activity and serum adiponectin levels in a group of 444 overweight and obese women and assessed the interrelationship with visceral adipose tissue (VAT; CT-scan L4-L5), insulin resistance (HOMA-IR), HDL cholesterol (HDL-chol) and inflammation (hs-CRP). PAI-1 was inversely related to adiponectin (r=-0.25, p<0.001; adjusted for age and BMI).After adjustment for age, VAT, HOMA-IR and hs-CRP, the relationship remained significant (r=-0.15; p=0.001), but disappeared after additional adjustment for HDL-chol (r=-0.09; p=0.067). Subjects were divided in two groups according to the median levels of adiponectin or PAI-1 levels. PAI-1 activity (19.1±11.4 vs. 15.8±8.6 AU/ml; p=0.003) and adiponectin levels (9.8±4.6 vs. 8.4±4.0 μg/ml; p<0.001) were significantly higher in the low adiponectin/PAI-1 groups. The difference in PAI-1 remained significant after adjustment for age and BMI (p=0.001), became borderline significant after adjustment for age and VAT (p=0.052), and disappeared after adjustment for age and HOMA-IR (p=0.116) or age and HDL-chol (p=0.443).The difference in adiponectin levels remained significant after adjustment for age, VAT, HOMA-IR and hs-CRP (p=0.006), but disappeared after additional adjustment for HDL-chol (p=0.089). Further analyses suggest a contribution of HOMA-IR and/or HDL-chol in the relationship between PAI-1 and adiponectin. HDL-chol was found to be the only factor independently determining both factors. In conclusion, in overweight and obese women, PAI-1 activity was inversely related to serum adiponectin, independent of visceral adipose tissue.

scholarly journals Effect of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator Polymorphisms on Susceptibility to Type 2 Diabetes in Malaysian Subjects

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Zaid Al-Hamodi ◽  
Riyadh Saif-Ali ◽  
Ikram S. Ismail ◽  
Khaled A. Ahmed ◽  
Sekaran Muniandy
Keyword(s):  
Type 2 Diabetes ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Additive Models ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Plasminogen ◽  
Alu Repeat ◽  
Activator Inhibitor ◽  
Pai 1

Elevated activity of plasminogen activator inhibitor-1 (PAI-1) and decreased tissue plasminogen activator (tPA) activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS) and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR=2.35,P=0.045;OR=1.67,P=0.058). On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR=3.32,P=0.013) whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS.

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