Furthermore, insulin resistance is associated with dysregulated neurohumoral activation of the renin–angiotensin–aldosterone system, fibrinolytic dysfunction via increased plasminogen activator inhibitor-1 (PAI-1) levels, the development of cardiac autonomic neuropathy, which may promote the development of systolic and diastolic dysfunction or cardiac arrhythmias, and endothelial dysfunction [12, 47–50]. The gene discussed is SERPINE1; the disease is endothelial dysfunction.