Substantial fibrin amyloidogenesis in type 2 diabetes assessed using amyloid-selective fluorescent stains

Etheresia Pretorius, Martin J. Page, Lize Engelbrecht, Graham C. Ellis, Douglas B. Kell

We have previously shown that many chronic, inflammatory diseases are accompanied, and possibly partly caused or exacerbated, by various coagulopathies, manifested as anomalous clots in the form of 'dense matted deposits'. More recently, we have shown that these clots can be amyloid in nature, and that the plasma of healthy controls can be induced to form such clots by the addition of tiny amounts of bacterial lipopolysaccharide or lipoteichoic acid. Type 2 diabetes (T2D) is also accompanied by raised levels of LPS. We use superresolution and confocal microscopies to investigate the amyloid nature of clots from healthy and T2D individuals. We show here, with the established stain thioflavin T and the novel stains Amytracker™ 480 and 680, that the clotting of plasma from type 2 diabetics is also amyloid in nature, and that this may be prevented by the addition of suitable concentrations of LPS-binding protein. This implies strongly that there is indeed a microbial component to the development of type 2 diabetes, and suggests that LBP might be used as treatment for it and its sequelae.