Specifically, treatment with PI3K–AKT–mTOR inhibitors can cause hyperglycemia and, in rare cases, diabetic ketoacidosis due to the effect of these drugs to interfere with systemic insulin signaling [152–160], and hyperinsulinemia resulting from the β-cells’ attempts to normalize blood glucose can limit the efficacy of these agents [104]. Here, INS is linked to hyperinsulinism.