Glycaemic control improves fibrin network characteristics in type 2 diabetes – A purified fibrinogen model

Marlien Pieters; Namukolo Covic; Francois H. van der Westhuizen; Chandrasekaran Nagaswami; Yelena Baras; Du Toit Loots; Johann C. Jerling; Dale Elgar; Kathryn S. Edmondson; Danie G. van Zyl; Paul Rheeder; John W. Weisel

doi:10.1160/TH07-11-0699

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(04): 691-700
DOI: 10.1160/TH07-11-0699

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Glycaemic control improves fibrin network characteristics in type 2 diabetes – A purified fibrinogen model

Marlien Pieters

¹Department of Nutrition, North-West University, Potchefstroom, South Africa

,

Namukolo Covic

¹Department of Nutrition, North-West University, Potchefstroom, South Africa

,

Francois H. van der Westhuizen

²School of Biochemistry, North-West University, Potchefstroom, South Africa

,

Chandrasekaran Nagaswami

³Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

,

Yelena Baras

³Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

,

Du Toit Loots

¹Department of Nutrition, North-West University, Potchefstroom, South Africa

,

Johann C. Jerling

¹Department of Nutrition, North-West University, Potchefstroom, South Africa

,

Dale Elgar

⁴School of Pharmacy, North-West University, Potchefstroom, South Africa

,

Kathryn S. Edmondson

³Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

,

Danie G. van Zyl

⁵Department of Internal Medicine, University of Pretoria, Pretoria, South Africa

,

Paul Rheeder

⁶Division of Clinical Epidemiology, University of Pretoria, Pretoria, South Africa

,

John W. Weisel

³Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

› Author Affiliations

Abstract

Summary

Diabetic subjects have been shown to have altered fibrin network structures. One proposed mechanism for this is non-enzymatic glycation of fibrinogen due to high blood glucose. We investigated whether glycaemic control would result in altered fibrin network structures due to decreased fibrinogen glycation. Twenty uncontrolled type 2 diabetic subjects were treated with insulin in order to achieve glycaemic control. Twenty age- and body mass index (BMI)-matched non-diabetic subjects were included as a reference group. Purified fibrinogen, isolated from plasma samples was used for analysis. There was a significant decrease in fibrinogen glycation (6.81 to 5.02 mol glucose/mol fibrinogen) with a corresponding decrease in rate of lateral aggregation (5.86 to 4.62) and increased permeability (2.45 to 2.85 × 10⁻⁸ cm²) and lysis rate (3.08 to 3.27 μm/min) in the diabetic subjects after glycaemic control. These variables correlated with markers of glycaemic control. Fibrin clots of non-diabetic subjects had a significantly higher ratio of inelastic to elastic deformation than the diabetic subjects (0.10 vs. 0.09). Although there was no difference in median fiber diameter between diabetic and non-diabetic subjects, there was a small increase in the proportion of thicker fibers in the diabetic samples after glycaemic control. Results from SDS-PAGE indicated no detectable difference in factor XIIIa-crosslinking of fibrin clots between uncontrolled and controlled diabetic samples. Diabetic subjects may have altered fibrin network formation kinetics which contributes to decreased pore size and lysis rate of fibrin clots. Achievement of glycaemic control and decreased fibrinogen glycation level improves permeability and lysis rates in a purified fibrinogen model

Keywords

Diabetes - fibrin network - fibrinogen glycation - glycaemic control - hyperglycaemia

Full Text

References

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