TNF and Hyperglycemia: Even with moderate but stable hyperglycemia in type 2 diabetes mellitus, there may be a pathological accumulation in the blood of AGE and other aberrant metabolites, some DAMPs, including HMGB1 (high-mobility group protein B1), and an increase in the blood of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6), which is accompanied by proinflammatory activation of mesangial macrophages and other cells [86].