INS and diabetes mellitus: Circulating and locally produced effector cytokines such as TNF-α, interferon-γ, IL-1β, and IL-12 may influence insulin sensitivity of peripheral tissues and can modulate insulin release in the pancreatic islets.65, 66, 67, 68 Increased glucotoxicity and lipotoxicity have been associated with immune cell infiltration of target tissues, thereby affecting diabetes-associated target organ damage and cardiovascular complications,68, 69 including the development of metabolic cardiomyopathy.70, 71 Inflammation is a key modulator of metabolic and diabetic CVD.