IRS1 and type 2 diabetes mellitus: Meanwhile, animals with diet-induced obesity (DIO), a model of type 2 diabetes mellitus (T2DM), that were fed a 40% or 60% high-fat diet (HFD) during different periods displayed cognitive impairment accompanied by increased phosphorylation of neural IRS1 at different Ser residues (mSer1097, mSer307, or mSer612) at different ages [20,21,22].