The systemic innate inflammation and the early involvement of vessels may explain why, in T2D, the first CVD event often occurs before the clinical diagnosis of diabetes (Fig. 1a), suggesting that hyperglycemia is just part of a complex systemic inflammatory process, characterized by peripheral insulin resistance with a relative insulin excess in the early phases of the disease and a wide production of inflammatory molecules by the adipocytes and liver (Fig. 1a) [1]. Here, INS is linked to type 2 diabetes mellitus.