This occurs because simple carbohydrates (e.g., fructose and glucose) involve (i) de novo synthesis of free fatty acids (FFA) in the liver, causing lipotoxicity [224] and (ii) hyperinsulinemia, which leads to systemic inflammation [225] by stimulating NF-kB nuclear translocation, the extracellular release of proinflammatory mediators from macrophages and ultimately systemic insulin resistance [226]. The gene discussed is NFKB1; the disease is hyperinsulinism.