Abstract:
Type 2 diabetes (T2D) has many cardiovascular complications, including a thrombotic propensity. Many
such chronic, inflammatory diseases are accompanied (and may be exacerbated, and possibly even
largely caused) by amyloid fibril formation. Recognising that there are few strong genetic associations
underpinning T2D, but that amyloidogenesis of amylin is closely involved, we have been seeking to
understand what might trigger the disease. Serum levels of bacterial lipopolysaccharide are raised in
T2D, and we recently showed that fibrin(ogen) polymerisation during blood clotting can be affected
strongly by LPS. The selectivity was indicated by the regularisation of clotting by lipopolysaccharide-binding protein (LBP). Since coagulopathies are a hallmark of T2D, we wondered whether they might
too be caused by LPS (and reversed by LBP). We show here, using SEM and confocal microscopy, that
platelet-poor-plasma from subjects with T2D had a much greater propensity for hypercoagulability
and for amyloidogenesis, and that these could both be reversed by LBP. These data imply that
coagulopathies are an important feature of T2D, and may be driven by ‘hidden’ LPS. Given the
prevalence of amyloid formation in the sequelae of diabetes, this opens up novel strategies for both the
prevention and treatment of T2D.
