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IR may be linked to endothelial dysfunction by the number of mechanisms such as disturbance in subcellular signaling pathway and PI-3-kinase/Akt pathway.[18] ACANTHOSIS NIGRICANS AND ADIPOKINES Acanthosis nigricans patients have hyperinsulinemia and may be at greater risk of atherosclerotic cardiovascular disease.[19] The commonest underlying cause of IR is excess abdominal adipose tissue which releases increased amounts of free fatty acids which directly affect insulin signaling, diminish glucose uptake in muscle, drive exaggerated triglyceride synthesis and induce gluconeogenesis in liver