,4 We and others have reported that elevated circulating concentrations of the valine-derived catabolite 3-hydroxyisobutyrate (3-HIB), dependent on the enzyme 3-Hydroxyisobutyryl-CoA Hydrolase (HIBCH), are strongly associated with the development of insulin resistance, T2D and gestational diabetes.16, 17, 18, 19, 20, 21 The rate-limiting enzymatic conversion by HIBCH of 3-HIB-CoA into free 3-HIB, which without the CoA moiety can leave the cell, may therefore be a key step in BCAA catabolism that influences fatty liver and the risk of associated diseases. The gene discussed is HIBCH; the disease is fatty liver disease.