INS and hyperinsulinism: Naturally, correlation is not equivalent to causality, and a case could be made for macrophage activation by metabolic derangement and hyperinsulinemia, as insulin may trigger an inflammatory response in macrophages (Iida et al., 2001) as well as induce their infiltration in adipose tissue with detrimental effects on hepatic and muscle IS (Mauer et al., 2010).