Protocol: 985661 

Diabetes is well known to cause proteinuria (protein in urine), chronic kidney disease, and end-stage renal disease. These have been, and continue to be, appropriately well-studied. The purpose of this research study is to study the variety of electrolyte disorders (Electrolyte disorders result in an imbalance of minerals in the body. For the body to function properly, certain minerals need to be maintained in an even balance. Otherwise, vital body systems, such as the muscles and brain, can be negatively affected.) which have not been well studied, particularly with currently available techniques. 

Our long-term goal is to understand these diabetic electrolyte disorders using such up-to-date techniques to understand electrolyte disorders. The current focus will be on sodium glucose cotransporter 2 inhibitors (SGLT2i) which have been found to cause an unusual form of diabetic ketoacidosis (high levels of blood acids called ketones) which appears much different than that long known in type 1 diabetes (T1DM). SGLT2i were introduced into clinical practice for type 2 diabetes (T2DM) in 2013. They increase urinary glucose excretion and thereby improve glycemic control. They have many favorable attributes including weight loss. 

Most significantly, one agent (empagliflozin) has recently been shown to have impressive benefits on all cause and cardiovascular mortality and on hospitalizations for heart failure. This contrasts dramatically with almost all other agents which reduce serum glucose. Importantly, these effects also began to be seen very early (3 months) and were seemingly independent of most cardiovascular determinants (risk factors for cardiovascular disease include behavioral factors as well as such social factors as poverty, stress, and hereditary factors). There were also favorable outcomes for kidney injury as well. Thus, these impressive results from SGLT2i point toward their expanded use in patients with diabetes.