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. 2008 Apr;99(4):691-700.
doi: 10.1160/TH07-11-0699.

Glycaemic control improves fibrin network characteristics in type 2 diabetes - a purified fibrinogen model

Marlien Pieters  1 , 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
Affiliations

Glycaemic control improves fibrin network characteristics in type 2 diabetes - a purified fibrinogen model

Marlien Pieters et al. Thromb Haemost. 2008 Apr.

Abstract

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 x 10(-8) cm(2)) and lysis rate (3.08 to 3.27 microm/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.

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Figures

Figure 1
Figure 1. Representative scanning electron micrographs of fibrin clots
A) Non-diabetic subject at baseline; B) Non-diabetic subject at end measurement; C) Uncontrolled diabetic subject; D) Controlled diabetic subject.
Figure 2
Figure 2. Histogram of fiber diameter distribution in the subsample of diabetic and non-diabetic subjects as calculated from SEM images
Figure 3
Figure 3. Representative 3D reconstructed images of purified fibrin clots from uncontrolled diabetic subjects (A, B), controlled diabetic subjects (C, D) and non-diabetic subjects (E, F) obtained by confocal microscopy (107 × 107 × 16 µm)
Lysis was induced by the addition of 1 µg/ml tPA to the lysis front. Lysis times illustrated are after 0 (A, C, E) and 10 min (B, D, E).
Figure 4
Figure 4. SDS-PA GE of FXIIIa crosslinking of fibrin clots, showing the effect of glycaemic control
Tracks 1, 3 and 5 are fibrin from uncontrolled diabetic patients after incubation with FXIIIa for 10, 45 and 90 min, respectively. Tracks 2, 4 and 6 are fibrin from controlled diabetic patients after the same incubation times. Tracks 7 and 8 are samples from uncontrolled and controlled diabetic patients respectively after 90 min of incubation without FXIII.
See this image and copyright information in PMC

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