We tested the hypotheses that, compared to subjects with higher plasma PCSK9, subjects with lower plasma PCSK9, identifying those with higher WAT surface expression of LDLR and CD36, have (a) higher WAT and systemic activation of NLRP3 inflammasome, and (b) higher risk factors for T2D; namely WAT dysfunction, insulin resistance, hyperinsulinemia, lower DI, and postprandial hypertriglyceridemia. This evidence concerns the gene PCSK9 and hyperinsulinism.