A 64- year- old woman with past medical history of type 1 diabetes mellitus (DM), managed with 22 units of daily subcutaneous long acting insulin, and 50 mg of daily oral canagliflozin, presented to the hospital with new onset nausea and vomiting. Physical examination was notable for Heart rate 120, Blood pressure 110/85 mm of Hg, and dry mucus membranes. Laboratory data revealed serum Sodium, Potassium, Bicarbonate and Anion gap to be 135, 5.3, 14 and 23 mEq/L, respectively. The serum creatinine was 0.7 mg/dL with serum glucose 244 mg/dL. Initially, patient was managed conservatively with intravenous (IV) isotonic fluids and antiemetic. The working diagnosis was dehydration due to infectious gastroenteritis. After eight hours, patient’s symptoms worsened, and subsequent laboratory work showed serum bicarbonate 10 mEq/L, glucose 234 mg/dL, beta-hydroxybutyrate 8.19 mmol/L, with arterial blood gas significant for pH 7.06, PCO2 25. Urinalysis showed elevated glucose (>1g/dL) and ketones (>80mg/dL). Diabetic ketoacidosis (DKA) was suspected and aggressive intravenous fluids and insulin were instituted. With above treatment, patient’s symptoms gradually improved, and anion gap closed. She was able to tolerate oral diet within 24 hours of hospital stay and was discharged home after 48 hours.
Discussion: DKA is a well-defined complication of type 1 DM, and is traditionally described by hyperglycemia, high anion gap metabolic acidosis and increased plasma ketones. Sodium glucose cotransporter 2 (SGLT2) inhibitors are oral hypoglycemic agents indicated for type 2 DM targeting reabsorption of glucose at proximal renal tubules. Due to insulin independent glucose lowering effect, their off label use in type 1 DM is also increasing. SGLT2 inhibitor induced increased glucagon levels and glycosuria leads to increased ketone production and low blood glucose levels resulting in euglycemic DKA. The absence of hyperglycemia results in delayed recognition of the DKA leading to unnecessary testing and treatment. Canagliflozin is usually started at 100 mg oral daily dose and then increased up to 300 mg daily. To our knowledge, most of the reported DKA cases with canagliflozin occurred at daily dose range of 100-300 mg, while our patient was taking reduced dose of 50mg daily. The concomitant mild infection could be potential contributor, however, the rapid correction of symptoms and metabolic derangements with IV fluids and insulin indicates that DKA was the culprit.
Conclusions: Patients with history of diabetes mellitus who are taking SGLT2 inhibitors and presenting with symptoms suggestive of DKA, should be quickly evaluated for this life threatening complication, as it could be easily missed with normal blood glucose levels. This effect is dose independent and can occur at any time after initiation of therapy.