In parallel, ROS also triggers the NF-κB signaling cascade, resulting in the upregulation of pro-inflammatory cytokines (e.g., IL-6 and TNF-α), enhanced leukocyte adhesion, endothelial apoptosis, and foam cell formation—all hallmark processes in the development of atherosclerosis (25).As an integrated measure of overall glycemic variability, an elevated GRI may exacerbate metabolic disturbances and amplify oxidative and inflammatory responses, thereby accelerating macrovascular injury in patients with diabetes mellitus; (26). The gene discussed is TNF; the disease is atherosclerosis.