FOXO1 and type 2 diabetes mellitus: In this setting, pharmacologic or genetic inhibition of autophagy or FOXO1 exacerbates β-cell death, whereas in T2D pancreata autophagy markers are diminished and inversely associated with HbA1c, consistent with a progressive breakdown of HIF-1α–FOXO1–autophagy signaling as metabolic disease advances [33,39].