Severe euglycemic diabetic ketoacidosis of multifactorial etiology in a type 2 diabetic patient treated with empagliflozin: case report and literature review

Abstract

Background Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are a relatively novel class of oral medications for the treatment of Type 2 DM with a generally acceptable safety profile. However, these agents have been associated with rare events of a serious and potentially life-threatening complication named euglycemic diabetic ketoacidosis (euDKA). euDKA is not identical with the typical diabetic ketoacidosis, as it often presents with serious metabolic acidosis but only mild to moderate glucose and anion gap elevation. Case presentation We report a case of a 51-year old female with Type 2 DM treated with an SGLT-2 inhibitor, developing severe metabolic acidosis with only mild blood glucose elevation after a routine surgery. A careful evaluation of involved factors led to the diagnosis of euDKA, followed by cautious application of simple therapeutic measures that resulted in complete restoration of acidosis and glycemic control in less than 48-h. Conclusions Euglycemic ketoacidosis is a rare but rather serious complication of SGLT-2 inhibitors use, often with a multifactorial etiology. Its atypical presentation requires a high level of awareness by physicians as early recognition of this complication can quickly and safely restore acid-base balance.

Euglycemic Diabetic Ketoacidosis and Sodium-Glucose Cotransporter-2 Inhibitors: A Focused Review of Pathophysiology, Risk Factors, and Triggers

“…The majority of the authors reported EDKA in middle-aged women with long-standing T2DM, body mass index between 35 and 40 kg/m 2 , and who had been on multiple doses of SGLT2i for at least more than three months [34][35][36]. The common presenting complaints were fatigue, abdominal pain, shortness of breath, reduced food intake, nausea, and vomiting.…”

“…On examination, they were tachypneic, with tachycardia, blood glucose less than 200 mg/dL, blood pH <7.3 (7.08-7.2), increased anion gap, and increased blood ketones, such as beta-hydroxybutyrate and serum acetone. Sampani et al reported increased ketones in the urine as well [ 34 ]. The precipitating factors, signs and symptoms, and diagnostic criteria are depicted in Figure 3 [ 2 , 7 - 10 , 20 - 32 , 34 ].…”

Sodium–glucose cotransporter 2 inhibitor-induced euglycemic diabetic ketoacidosis in a patient with coronavirus disease 2019: a case report

“…DKA is a serious complication of diabetes that is commonly observed in both T1DM and T2DM patients, especially under extreme physical stress such as trauma, surgery, or infection [ 2 , 8 , 9 ]. Persistent acidosis may be commonly seen after resolution of DKA due to hyperchloremic acidosis from resuscitation with fluids containing zero strong ion difference.…”

“…Fasting beta hydroxybutyrate (β-HB) levels are doubled after empagliflozin administration, as reported by Ferranini et al . [ 2 , 10 ], as there is a rise of β-HB due to overproduction and, hence, both clearance rate and fractional excretion of β-HB are increased [ 2 , 11 ].…”

“…in 1973. The report described 37 cases with a glucose concentration at presentation of less than 16.7 mmol/L (300 mg/dL) in individuals with type 1 diabetes mellitus (T1DM) [ 1 , 2 ]. According to the Joint British Diabetes Societies Inpatient Care Group: The Management of Diabetic Ketoacidosis in Adults, criteria for diagnosis of diabetic ketoacidosis (DKA) require ketonemia ≥ 3 mmol/L or significant ketonuria (more than 2+ on standard urine sticks), capillary blood glucose > 11 mmol/L, serum bicarbonate (HCO 3− ) < 15 mmol/L, and/or venous pH < 7.3 [ 3 ].…”