HMGB1 and diabetes mellitus: Furthermore, the relationship between HMGB-1 and neuropathic changes induced by hyperglycaemia has been investigated in retinal neuropathy.112,113 Diabetes mellitus is associated with the activation of HMGB-1, activation of the ERK1/2 pathway, activation of cleaved caspase-3 (an apoptosis executer enzyme), and glutamate signalling pathways in rat retinas.