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

Amélie I S Sobczak,Samantha J Pitt,Ramzi A Ajjan,Fladia A Phoenix,Alan J Stewart

doi:10.1055/s-0039-3402808

Amélie I S Sobczak, Samantha J Pitt + Show 3 more

Open Access

https://doi.org/10.1055/s-0039-3402808

Copy DOI

Abstract

Individuals 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 Mg 2+ showed a shortening of lysis time with increasing Mg 2+ concentrations ( p = 0.0004). Our findings reveal that plasma magnesium concentration is associated with changes in fibrin clot and lysis parameters.

Highlights

Type-1 diabetes mellitus (T1DM) is a disease state in which the immune system of an individual destroys the β cells of the pancreas affecting insulin secretion, resulting in raised glucose levels.[1]
hemoglobin A1c (HbA1c) was higher in the T1DM group (p < 0.0001) compared with controls, while human serum albumin (HSA) concentrations were lower in the T1DM group (p 1⁄4 0.0269) compared with controls and fibrinogen concentrations were comparable between groups
We demonstrate that plasma magnesium concentration negatively associates with both fibrin clot density and with lysis time in subjects with T1DM and controls

Summary

Introduction

Type-1 diabetes mellitus (T1DM) is a disease state in which the immune system of an individual destroys the β cells of the pancreas affecting insulin secretion, resulting in raised glucose levels.[1] The incidence of T1DM varies widely across the world, with age-adjusted incidences ranging from 0.1/100,000 individuals per year in China and Venezuela to 36.5 and 36.8/100,000 individuals per year in Finland and Sardinia, respectively.[2] If T1DM is not correctly managed, the reduced insulin concentration in the blood can cause death, while the resultant elevated glucose concentration will increase the risk of microvascular complications and the risk of developing long-term vascular diseases.[3] Individuals with T1DM are estimated to have a standardized mortality ratio attributable to cardiovascular diseases of 5.7 for men and 11.3 for women compared with healthy individuals.[3,4] Despite the known increased risk of cardiovascular disease in individuals with T1DM, the pathophysiology underlying this relationship is not well understood.

Methods

Results

Discussion

Conclusion