Multiple mechanisms are likely to account for this modification: (i) the affinity of ApoA-I for the small HDL particles typical of T2DM is reduced, leading to the dissociation of ApoA-I and the consequent accelerated clearance by the kidneys; (ii) the synthesis of ApoA-I may be reduced through a mechanism of inhibition of transcription factors driven by high glucose levels; (iii) the ApoA-I expression is reduced as a consequence of the insulin resistance [41]; (iv) the binding of the pro-inflammatory protein serum amyloid A (SAA) to HDL is accompanied by the removal of ApoA-I [37]. The gene discussed is APOA1; the disease is Insulin resistance.