An Unusual Case of Metabolic Acidosis- Mind the Gap!

Background: Euglycemic diabetic ketoacidosis (EDKA) is a rare, life-threatening condition characterized by acidosis, elevated ketone levels, and a high anion gap (AG) in the presence of normal blood glucose. We present a unique case of EDKA in a non-diabetic patient linked to sodium-glucose cotransporter-2 (SGLT2) inhibitor use. Case Presentation: A 64-year-old female with a history of chronic hypercapnic respiratory failure, Charcot-Marie-Tooth disease, hypertension, depression, and chronic diastolic congestive heart failure was admitted for progressively worsening confusion, left-sided weakness, facial numbness, dyspnea, generalized weakness and feeling ill for 24 hours duration. Physical exam revealed afebrile, confused patient with bilateral lower extremity weakness. At home she was on Dapagliflozin, Metoprolol, Sacubitril-Valsartan, and Spironolactone. Laboratory results showed a glucose level of99 mg/dl, a bicarbonate level of 13 mmol/l, an AG of 18mEq/l, delta gap of 6mEq/l, arterial pH of 7.08, and PCO2 of 36. Urinalysis revealed leukocytes, positive nitrate, high glucose (>1000 mmol/l), ketones (>80 mmol/l), and beta-hydroxybutyrate (6.7 mmol/l). Computed tomography (CT) brain scan showed no intracranial hemorrhage. EDKA was diagnosed, and her treatment included intravenous dextrose, insulin, and broad-spectrum antibiotics for a urinary tract infection. She responded well to treatment, with resolution of her metabolic acidosis. Conclusion: The incidence of EDKA due to SGLT2 inhibitors is approximately 0.1%. Timely diagnosis can be challenging due to normal glucose levels. We know that SGLT2 inhibitors enhance glycosuria, promoting ketone body production through lipolysis. Elevated glucagon and reduced glucose levels contribute to hepatic ketone production. Increasing glucagon levels and low glucose levels promote the production of ketones, and this glucagon-insulin imbalance leads to the development of EDKA. Differential diagnoses for high anion gap metabolic acidosis (HAGMA) include methanol, uremia, diabetic ketoacidosis, propylene glycol, isoniazid, iron overdose, lactic acidosis, ethylene glycol, and salicylate toxicity. Initial laboratory assessments should include basic electrolytes, glucose, calcium, magnesium, creatinine, blood urea nitrogen, serum and urine ketones, beta-hydroxybutyric acid, arterial or venous blood gas analysis, lactic acid, and complete blood count, among others. Blood cultures, urine analysis, and chest radiographs are needed to rule out any infection. High-calorie glucose infusion and tight glycemic control are key elements in ameliorating intractable metabolic acidosis brought about by SGLT2 inhibitor-induced EDKA. Remember to always mind the gap in patients with HAGMA! Healthcare providers should remain diligent, considering EDKA, especially with normal glucose levels. Patients need to be educated about the risks associated with SGLT2 inhibitors, fostering open communication and shared decision-making for safer medication management.