Abordagem clínica e terapêutica da cetoacidose diabética euglicêmica causada pelos inibidores de SGLT2: revisão da literatura

Abstract

Diabetic ketoacidosis (DKA) is one of the most serious complications of diabetes. It is characterized by the triad of hyperglycemia (glycemia >250 mg/dl), metabolic acidosis (arterial pH <7.3 and serum bicarbonate <18 mEq/L) and ketosis. Rarely, these patients may have blood glucose levels below 200 mg/dl, which is defined as euglycemic CAD (E-CAD). Possible etiology of E-CAD includes current insulin use, decreased caloric intake, excessive alcohol consumption, chronic liver disease, and glycogen storage disorders. DKA in pregnancy has also been reported with euglycemia. Recent use of sodium glucose cotransporter 2 (SGLT2) inhibitors has shed light on another possible mechanism of euglycemic DKA. SGLT-2 inhibitors reduce blood glucose levels by increasing urinary glucose excretion, which reduces the stimulus for insulin secretion by pancreatic β cells. Insulin normally acts to inhibit hormone-sensitive lipase, thereby decreasing the generation of free fatty acids that serve as a substrate for β-oxidation and ketogenesis. With SGLT-2 inhibitors, marked glycosuria and consequent decrease in insulin secretion result in uninhibited lipolysis, increased β-oxidation, and ketogenesis. As a result of decreased blood glucose levels, pancreatic α cells are stimulated to increase glucagon secretion, further promoting lipolysis and ketogenesis. It was concluded that clinicians should maintain a high index of suspicion of euglycemic diabetic ketoacidosis in patients using SGLT2 so that appropriate therapy can be provided in a timely manner. The present work aims to present bibliographic research on the mechanism of SGLT2 in severe euglycemic metabolic ketoacidosis as well as clinical and therapeutic approaches.