Case Presentation: A 55-year-old man with poorly-controlled type II diabetes and coronary artery bypass graft one month previously presented with a three-day history of dyspnea, nausea, vomiting, and constipation. He had been started on empagliflozin/metformin HCl after his bypass. On presentation, his vital signs were remarkable for tachycardia. His exam was notable for mild left lower quadrant abdominal tenderness. Initial labs demonstrated a leukocytosis of 15.2, blood glucose of 89 mg/dL, bicarbonate of 24 mg/dL, anion gap of 18 mEq/L with lactate of 2.2 mMol/L. Venous blood gas significant for pH of 7.36 with carbon dioxide of 45 mmHg. Urinalysis was acellular with 1+ ketones. CT of the abdomen and thorax were unremarkable. A presumptive diagnosis of diabetic ketoacidosis (DKA) was made, and the patient was treated with intravenous fluids and subcutaneous insulin. Beta-hydroxybutyrate subsequently returned at 4.01 mmol/L. Three days later he was discharged on metformin IR with empagliflozin removed from his home medication list.
Discussion: This case demonstrates the importance of recognizing euglycemic DKA as a rare side effect of SGLT2 inhibitors like empagliflozin. SGLT2 inhibitors stimulate glucagon secretion, while also reducing insulin secretion by increasing urinary glucose excretion; this increased glucagon to insulin ratio may lead to ketoacidosis. Decreased gluconeogenesis and increased glucosuria contribute to euglycemia. The metformin prescribed a month prior to presentation likely caused intermittent vomiting, decreased intake, and a subsequent state of starvation, precipitating DKA. Given the patient’s euglycemia and normal pH in the setting of recent vomiting, the patient’s elevated anion gap was critical to making the diagnosis, which prompted the confirmatory beta-hydroxybutyrate test. Recognizing euglycemic DKA in the context of a normal pH is essential to initiating appropriate therapy with insulin and fluids without delay.
Conclusions: The traditional markers of DKA may not be reliable in a patient with euglycemic DKA. A high index of suspicion for this diagnosis is required in all patients on SGLT2 inhibitors as patients may be neither hyperglycemic nor acidemic, but attention to the anion gap may reveal the diagnosis.