Letter to the Editor
Euglycemic diabetic ketoacidosis associated with sodium-glucose cotransporter type 2 inhibitors
Cetoacidosis diabética euglucémica asociada a los inhibidores del cotransportador sodio-glucosa tipo 2
Íñigo Isern de Val
, Héctor Mercado Castillo, María del Carmen Díaz Melé
Corresponding author
Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
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Ultrasound image of the right eye, showing dense intermediate uveitis (*). B. 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Its approach involves correction of acid-base and electrolyte imbalances together with intensive insulin therapy. In some cases, also dialysis. The present case highlights the importance of considering EDKA as a possible side effect in patients receiving this medication, especially in situations of metabolic stress. Disclosure of the presence of this entity may be crucial to avoid diagnostic delay.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The following is a case report of a 42-year-old female patient with hypertension, hypercholesterolaemia, obesity and type 2 diabetes mellitus, treated with metformin and empagliflozin, an SGLT-2i. She underwent gastric bypass surgery seven days before the episode, with no immediate complications. The patient was discharged after four days to continue her recovery.</p><p id="par0015" class="elsevierStylePara elsevierViewall">However, the next day, the patient started with abdominal pain, polyuria and general malaise, along with disorientation. She went to the emergency department, where severe metabolic acidosis was observed with a pH of 6.95 and a bicarbonate (HCO3) of 7.1 mmol/L, although lactate levels were in the normal range (1.2 mmol/L). In addition, she had leukocytosis of 20,000/mm<span class="elsevierStyleSup">3</span>, with normal blood glucose levels.</p><p id="par0020" class="elsevierStylePara elsevierViewall">To rule out postoperative complications, an abdominopelvic computed tomography (CT) scan was performed, with no significant findings. Despite a total of 250 mmol of sodium bicarbonate, there was no improvement. Due to muscle exhaustion, tachypnoea and shallow breathing, the patient was intubated and connected to invasive mechanical ventilation. The patient was subsequently transferred to Intensive Care Medicine (ICM).</p><p id="par0025" class="elsevierStylePara elsevierViewall">A repeat contrast-enhanced chest-abdomen-pelvis CT scan was performed with no further complications. Toxicological tests, including metformin and paracetamol, were also performed. Despite these measures, the patient continued to present with severe acidosis, hypernatremia and hypokalaemia, with lactate in range, elevated anion GAP of 39 mmol/L. As a result, she was urgently dialysed. The clinical suspicion was confirmed by the presence of glycosuria and ketonuria.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The clinical signs were consistent with EDKA, as a consequence of empagliflozin (SGLT2i) administration and surgical metabolic stress, as well as decreased intake.</p><p id="par0035" class="elsevierStylePara elsevierViewall">She was started on rapid intravenous insulin at 6 IU/h and 5% glucose IV hydration therapy was implemented. A progressive correction of acid-base balance and electrolyte imbalances was observed through adequate intake. Despite this, ketone bodies in the urine persisted, so intensive insulin therapy was continued.</p><p id="par0040" class="elsevierStylePara elsevierViewall">On the fourth day of hospitalisation, the weaning process was started and the patient was extubated without complications. An oral diet was started, which was well tolerated, and the patient was discharged from the Intensive Care Unit (ICU).</p><p id="par0045" class="elsevierStylePara elsevierViewall">EDKA is rare but is on the rise since the approval of SGLT2i in 2013. These drugs, empagliflozin, canagliflozin and dapagliflozin, are used in the treatment of both diabetes and heart failure.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> Although most patients who receive them do not develop complications, EDKA is considered a serious side effect, and its aetiology is multifactorial.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> It requires precipitating factors such as acute illness, surgery, fasting, dehydration, reduced intake, among others. Ultimately, any condition that significantly increases ketosis.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">SGLT2i reduces plasma glucose by inhibiting the sodium-glucose cotransporter-2 in the proximal renal tubule, leading to the elimination of 50–80 g of glucose per day. Insulin secretion decreases and glucagon release increases, promoting lipolysis and ketogenesis. In addition, the reabsorption of ketone bodies in the renal tubular system is increased.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4,5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">EDKA, characterised by blood glucose levels in the normal range, may go unrecognised, delaying diagnosis and treatment. Significant ketoacidosis with normal lactate, highly increased anion GAP, normal or near-normal blood glucose and ketone bodies in blood and urine are some of its signs. It may progress to severe ketoacidosis with encephalopathy and coma.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Although there are no specific guidelines, the treatment of EDKA is based on volume replacement and insulin therapy, ensuring adequate potassium and glucose levels by administering glucose saline. Sodium bicarbonate replacement is an option in cases of severe acidosis. The prognosis is favourable when treatment is initiated, however, diagnostic delay can be fatal.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Given the increasing use of SGLT2i due to its benefits in diabetes mellitus and its cardiovascular and renal effects, it is essential to increase diagnostic suspicion and awareness of EDKA. Dissemination of this clinical entity will contribute to early detection and treatment, especially in the emergency and intensive care settings.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0070" class="elsevierStylePara elsevierViewall">This work has not involved experiments. Medical records were accessed with appropriate permission. Individuals' privacy rights were safeguarded.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0075" class="elsevierStylePara elsevierViewall">This work has not received any funding.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Euglycemic diabetic ketoacidosis associated with the use of a sodium–glucose cotransporter-2 inhibitor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L. 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