In addition to elevated ROS production by neutrophils and M1 macrophages during T2DM-associated chronic inflammation (56–63), hyperglycaemia contributes to ROS overproduction through multiple pathways, including increased glucose auto-oxidation, AGE formation, PKC activation and various other signalling pathways involved in inflammation, angiogenesis and osteoblast differentiation [(16–21, 123–127); summarised in Figure 2]. This evidence concerns the gene PRRT2 and type 2 diabetes mellitus.