We therefore investigated, in a 12 year prospective study of patients with type 1 diabetes, first, the extent to which HMGB1 levels are associated with incident fatal and non-fatal CVD as well as all-cause mortality, and second the potential mediating role of markers of LGI, endothelial and renal dysfunction and/or arterial stiffness (i.e. pulse pressure). The gene discussed is HMGB1; the disease is type 1 diabetes mellitus.