Mechanisms of Diabetic Cardiorenal Syndrome

The hallmark of diabetes is high blood sugars, but diabetes is not just a disorder of high blood sugars. It is also a disorder of increased blood sodium which results in increased intravascular volume that over time can result in heart failure and eventually death. The aim of this paper is to review the mechanisms of how the hyperglycemic diabetic state drives the naturemic effects of diabetes and increases the risk of heart failure and death in diabetes. This increased naturemic effect is driven by increased sodium glucose transporter (SGLT), sodium proton exchanger 3 (NHE3), intrarenal renin angiotensin (iRAS) and renal sympathetic system (RSS) activity as illustrated in figure1. In summary, hyperglycemia results in pathologic kidney function changes with an increase in intravascular volume and neurohormonal activity, which leads to increased work and stress on the heart. SGLT inhibition will partially block and reverse these defects allowing the pathologic kidney function in diabetes to move back to more normal physiologic function.