scholarly journals Reduced Plasma Magnesium Levels in Type-1 Diabetes Associate with Prothrombotic Changes in Fibrin Clotting and Fibrinolysis

2020 ◽  
Vol 120 (02) ◽  
pp. 243-252 ◽  
Author(s):  
Amélie I. S. Sobczak ◽  
Fladia A. Phoenix ◽  
Samantha J. Pitt ◽  
Ramzi A. Ajjan ◽  
Alan J. Stewart
Keyword(s):  
Type 1 Diabetes ◽  
Plasma Concentrations ◽  
Fibrin Clot ◽  
Magnesium Concentration ◽  
Maximum Absorbance ◽  
Lysis Time ◽  
Fibrin Fiber ◽  
Plasma Magnesium ◽  
Pai 1

AbstractIndividuals with type-1 diabetes mellitus (T1DM) have a higher risk of thrombosis and low plasma magnesium concentrations. As magnesium is a known regulator of fibrin network formation, we investigated potential associations between fibrin clot properties and plasma magnesium concentrations in 45 individuals with T1DM and 47 age- and sex-matched controls without diabetes. Fibrin clot characteristics were assessed using a validated turbidimetric assay and associations with plasma magnesium concentration were examined. Plasma concentrations of fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and lipids were measured and fibrin fiber diameters assessed using scanning electron microscopy. Fibrin clot maximum absorbance was unchanged in subjects with T1DM compared with controls, while lysis time was prolonged (p = 0.0273). No differences in fibrin fiber diameters or in lipid profile were observed between T1DM and controls. PAI-1 concentration was lower in the T1DM group compared with the controls (p = 0.0232) and positively correlated with lysis time (p = 0.0023). Plasma magnesium concentration was lower in the T1DM group compared with controls (p < 0.0001). Magnesium concentration negatively correlated with clot maximum absorbance (p = 0.0215) and lysis time (p = 0.0464). A turbidimetric fibrin clot lysis assay performed in a purified system that included PAI-1 and 0 to 3.2 mM Mg2+ showed a shortening of lysis time with increasing Mg2+ concentrations (p = 0.0004). Our findings reveal that plasma magnesium concentration is associated with changes in fibrin clot and lysis parameters.

Human Thrombin and Calcium Bound Factor Xa Significantly Shorten tPA-Induced Fibrin Clot Lysis Time via Neutralization of Plasminogen Activator Inhibitor Type 1 Activity

1998 ◽  
Vol 80 (07) ◽  
pp. 161-166 ◽  
Author(s):  
Tetsumei Urano ◽  
Nobuo Nagai ◽  
Megumi Matsuura ◽  
Hayato Ihara ◽  
Yumiko Takada ◽  
...  
Keyword(s):  
Factor Xa ◽  
Plasminogen Activator Inhibitor ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Lysis Time ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1

SummaryEmploying a fibrin clot lysis assay, we reassessed the significance of the neutralization of plasminogen activator inhibitor type 1 (PAI-1) activity by thrombin and factor-Xa in fibrinolysis. When PAI-1 enriched fibrin clots were formed using increasing concentrations of thrombin (0.1, 0.5, 1.0 IU/ml), their lysis times became shorter (43.8 ± 4.9, 25.7 ± 3.7, 13.9 ± 0.8 h respectively). Times were shortened further by either heparin (43.9 ± 11.0, 12.1 ± 2.6, 3.6 ± 0.2 h respectively) or vitronectin (17.0 ± 1.6, 1.9 ± 0.7, 0.9 ± 0.0 h respectively). Factor-Xa together with Ca++ shortened the clot lysis time further. Fibrin autography revealed that both enzymes dose dependently interfered with complex formation between tPA and PAI-1, making large amounts of tPA remaining to be free form. The mechanism seems to play a role in the coagulation associated enhancement of fibrinolysis.

scholarly journals Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients

Diabetologia ◽  
2013 ◽  
Vol 57 (2) ◽  
pp. 366-372 ◽  
Author(s):  
Kate Downes ◽  
M. Loredana Marcovecchio ◽  
Pamela Clarke ◽  
Jason D. Cooper ◽  
Ricardo C. Ferreira ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Plasma Concentrations ◽  
Young Patients ◽  
C Peptide

scholarly journals ACE, PAI-1, decorin and Werner helicase genes are not associated with the development of renal disease in European patients with Type 1 diabetes

1999 ◽  
Vol 15 (4) ◽  
pp. 247-253 ◽  
Author(s):  
S. De Cosmo ◽  
M. Margaglione ◽  
V. Tassi ◽  
M. Garrubba ◽  
S. Thomas ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Renal Disease ◽  
Pai 1

C0284 Does a tight fibrin clot in premenopausal women with type 1 diabetes explain the lack of gender difference in cardiovascular disease?

2012 ◽  
Vol 130 ◽  
pp. S122
Author(s):  
Aleksandra Antovic ◽  
Nils Håkan Wallèn ◽  
Graciela Elgue ◽  
Koteiba Majeed ◽  
Peter Henriksson ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Gender Difference ◽  
Premenopausal Women ◽  
Fibrin Clot

Effect of acute variations of insulin and glucose on plasma concentrations of asymmetric dimethylarginine in young people with Type 1 diabetes

2008 ◽  
Vol 115 (12) ◽  
pp. 361-369 ◽  
Author(s):  
M. Loredana Marcovecchio ◽  
Barry Widmer ◽  
David B. Dunger ◽  
R. Neil Dalton
Keyword(s):  
Type 1 Diabetes ◽  
Risk Factor ◽  
Young People ◽  
Asymmetric Dimethylarginine ◽  
Plasma Concentrations ◽  
Young Patients ◽  
Glucose Levels ◽  
Significant Fall ◽  
Plasma Adma

ADMA (asymmetric dimethylarginine), an endogenous inhibitor of nitric oxide synthase, is considered a major risk factor for cardiovascular disease and progression of renal disease. In the present study we aim to investigate the effect of acute variations in plasma glucose and insulin on plasma ADMA levels in young people with T1D (Type 1 diabetes). Fifteen young patients (ten males) with T1D, median age 18.3 (13.2–24.4) years, HbA1c (glycated haemoglobin) 9% (6.4–13.6%), underwent an overnight (18:00–08:00 hours) variable insulin infusion for euglycaemia, followed by a hyperinsulinaemic–euglycaemic clamp (08:00–12:00 hours). Blood samples were collected every 15 min for determination of ADMA, SDMA (symmetric dimethylarginine), valine, phenylalanine, arginine, creatinine and glucose. Insulin levels were assessed every 30 min. During the overnight period, glucose levels increased following the evening meal. In response to the protein intake there was a significant increase in ADMA, arginine, valine, phenylalanine and creatinine. For the remaining part of the night, glucose levels progressively decreased reaching 5 mmol/l by 04:00 hours. ADMA and SDMA did not change significantly. During the hyperinsulinaemic clamp, a significant fall in ADMA was observed, from 0.468±0.056 to 0.364±0.050 μmol/l (P<0.001). A significant fall was also found in SDMA, valine, phenylalanine, arginine and the ADMA/SDMA ratio (all P<0.001), but not in creatinine levels. No correlation was found between insulin sensitivity and ADMA. We conclude that acute changes in glycaemia do not significantly affect plasma ADMA levels whereas infusion of insulin significantly reduces ADMA, suggesting an important role for insulin in the regulation of this cardiovascular risk factor.

scholarly journals Evaluation of Vascular Endothelial Function in Children with Type 1 Diabetes Mellitus

2021 ◽  
Vol 10 (21) ◽  
pp. 5065
Author(s):  
Karolina Nocuń-Wasilewska ◽  
Danuta Zwolińska ◽  
Agnieszka Zubkiewicz-Kucharska ◽  
Dorota Polak-Jonkisz
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Endothelial Dysfunction ◽  
Type 1 Diabetes Mellitus ◽  
Diabetes Mellitus Type 1 ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Linear Correlations ◽  
Pai 1

Diabetic kidney disease belongs to the major complications of diabetes mellitus. Here, hyperglycaemia is a key metabolic factor that causes endothelial dysfunction and vascular changes within the renal glomerulus. The aim of the present study was to assess the function of the vascular endothelium in children with type 1 diabetes mellitus (type 1 diabetes) by measuring selected endothelial lesion markers in blood serum. The selected markers of endothelial lesions (sVCAM-1, sICAM-1, sE-SELECTIN, PAI-1, ADMA and RAGE) were assayed by the immunoenzymatic ELISA method. The study involved 66 patients (age: 5–18 years) with type 1 diabetes and 21 healthy controls (age: 5–16 years). In the type 1 diabetes patients, significantly higher concentrations of all of the assayed markers were observed compared to the healthy controls (p < 0.001). All of the evaluated markers positively correlated with the disease duration, the age, and BMI of the patients, while only PAI-1 and sE-SELECTIN were characteristic of linear correlations with the estimated glomerular filtration rate (eGFR). It can be concluded that endothelial inflammatory disease occurs in the early stages of type 1 diabetes mellitus in children. The correlations between PAI-1, sE-SELECTIN, and eGFR suggest an advantage of these markers over other markers of endothelial dysfunction as prognostic factors for kidney dysfunction in children with type 1 diabetes.

scholarly journals The cleavage and inactivation of plasminogen activator inhibitor type 1 by neutrophil elastase: the evaluation of its physiologic relevance in fibrinolysis

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1056-1061
Author(s):  
K Wu ◽  
T Urano ◽  
H Ihara ◽  
Y Takada ◽  
M Fujie ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Plasminogen Activator Inhibitor ◽  
Clot Lysis ◽  
Lysis Time ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
Clot Lysis Time

The effect of the proteolytic cleavage of plasminogen activator inhibitor type 1 (PAI-1) by human neutrophil elastase (HNE) on fibrinolysis was investigated. HNE cleaved active PAI-1 and produced low molecular weight forms of inactive PAI-1, as previously reported. Latent PAI-1 was resistant to HNE treatment. Vitronectin (VN) partially protected the cleavage. NH2-terminal sequence analysis indicated that the cleavage site was Val355-Ser356 (P4-P3). The effects of PAI-1 cleavage by HNE on clot lysis was studied in a purified system. Clot lysis time without PAI-1 was 20.0 +/- 5.0 minutes and was prolonged to 86.7 +/- 2.9 minutes by 68 nmol/L of PAI-1. It was shortened when HNE (from 0.6 nmol/L to 80 nmol/L) was added and returned to the value obtained without PAI-1 by 80 nmol/L of HNE (20.0 +/- 5.8 minutes). However, in the absence of PAI-1, elastase did not enhance clot lysis at all. Euglobulin clot lysis time was also shortened after HNE treatment. The cleavage and inactivation of PAI-1 by HNE was shown to be a novel pathway to enhance fibrinolysis.

scholarly journals Increased Plasma Concentrations of Midregional Proatrial Natriuretic Peptide Is Associated With Risk of Cardiorenal Dysfunction in Type 1 Diabetes

2014 ◽  
Vol 28 (6) ◽  
pp. 772-779 ◽  
Author(s):  
Simone Theilade ◽  
Tine Willum Hansen ◽  
Jens Peter Goetze ◽  
Peter Rossing
Keyword(s):  
Type 1 Diabetes ◽  
Natriuretic Peptide ◽  
Plasma Concentrations

scholarly journals Plasma concentrations of 8-hydroxy-2′-deoxyguanosine and risk of kidney disease and death in individuals with type 1 diabetes

Diabetologia ◽  
2017 ◽  
Vol 61 (4) ◽  
pp. 977-984 ◽  
Author(s):  
Manuel Sanchez ◽  
Ronan Roussel ◽  
Samy Hadjadj ◽  
Abdul Moutairou ◽  
Michel Marre ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Plasma Concentrations

scholarly journals Anabolic–Androgenic Steroid Abuse Impairs Fibrin Clot Lysis

2020 ◽  
Author(s):  
Johannes Jakobsen Sidelmann ◽  
Jørgen Brodersen Gram ◽  
Jon J. Rasmussen ◽  
Caroline Kistorp
Keyword(s):  
Plasma Concentrations ◽  
Coagulation Factor ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Cross Sectional ◽  
Plasmin Inhibitor ◽  
Pai 1 ◽  
Fibrin Structure ◽  
Structure Properties

AbstractAbuse of anabolic–androgenic steroids (AASs) is suspected to increase the risk of cardiovascular disease (CVD) and cardiovascular mortality in otherwise healthy individuals. AAS abuse may increase the incidence of CVD by altering the hemostatic balance toward a procoagulant state. Studies on the effect of AAS abuse on the fibrinolytic system, however, have either demonstrated a profibrinolytic effect or no effect of AAS abuse, but the overall effect of AAS on fibrinolysis has not been addressed so far. This cross-sectional study investigated the effect of AAS on fibrin clot lysis, fibrin structure, and the hemostatic proteins, potentially affecting these measures in current and former AAS abusers and healthy age-matched controls. The study population consisted of 37 current and 33 former AAS abusers, along with 30 healthy age-matched controls. Fibrin clot lysis, fibrin structure properties, fibrinogen, coagulation factor XIII (FXIII) plasminogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI) were determined. Fibrin clot lysis was significantly reduced in participants abusing AAS compared with former abusers and controls (p < 0.001). Plasma fibrinogen, plasminogen, and plasmin inhibitor were significantly increased in current abusers (p < 0.05). No significant differences were observed with respect to measures of fibrin structure properties, PAI-1, and TAFI (p > 0.05). In conclusion, AAS abuse depresses fibrin clot lysis. This effect is not associated with alterations in fibrin structure but is rather caused by increased plasma concentrations of fibrinogen, FXIII, and plasmin inhibitor. These findings suggest that AAS abuse may be associated with increased thrombotic disease.

Sign in / Sign up

Export Citation Format

Share Document