In patients with severe aortic stenosis, long-term decreased cardiac output leads to systemic hypoperfusion, which could result in the overactivation of the adrenergic and renin-angiotensin systems, hyperinsulinemia, and pancreatic β-cell dysfunction leading to insulin resistance, all of which are indicative of abnormal glucose metabolism [34]. The gene discussed is REN; the disease is Hyperinsulinemia.