ARID4B and Premature ovarian insufficiency: BCAA insufficiency leads to premature ovarian insufficiency,40 and decreased serum BCAA levels have been observed in patients with chronic heart failure.41 A BCAA dysmetabolism model proposes that the accumulation of downstream metabolites (not BCAAs per se) promotes β-cell mitochondrial dysfunction, stress signaling, and apoptosis associated with T2D.29 Increased BCAA levels are more likely to mark the loss of insulin action than being causative.