Newer Perspectives of Mechanisms for Euglycemic Diabetic Ketoacidosis

Abstract

Euglycemic diabetic ketoacidosis (EDKA) was considered a rare condition with its specific definition and precipitating factors. However, with the wide use of sodium glucose cotransporter 2 (SGLT-2) inhibitors, the newest class of antidiabetic agents, EDKA has come back into the spotlight. Relevant cases are increasingly being reported along with insights into the mechanism of EDKA. It seems increasingly clear that EDKA is more common than we used to believe. The SGLT-2 inhibitor-associated EDKA also indicates a necessary review of our previous understanding of “diabetic” ketoacidosis, since the SGLT-2 inhibitor predisposes patients to DKA in a “starvation” way. Actually, there are growing reports about starvation-induced ketoacidosis as well. The previously “exclusive” nomenclature and cognition of these entities need to be reexamined. That the hormonal interactions in DKA may differ from the severity of insulin deficiency also may have served in the scenario of EDKA. The SGLT-2 inhibitors are newly approved in China. The main purpose of this work is to have a better understanding of the situation and update our knowledge with a focus on the pathogenesis of EDKA.

Regular performance feedback may be key to maintain good quality DKA management: results from a five-year study

“…Lately, there is an increased frequency of euglycemic ketoacidosis associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors. Such patients with SGLT2 inhibitor associated euglycaemic ketoacidosis are more susceptible to hypoglycemia with DKA treatment further to a complex drug-associated mechanism 40. However, there is limited literature studying the prevalence and associated risk factors of hypoglycemia resulting from DKA treatment.…”

Modeling Ketogenesis for Use in Pediatric Diabetes Simulation

“…If additional scenarios are created where the presence of counter-regulatory hormones (via stress, illness, and exercise) or medications like SGLT inhibitors would accelerate ketogenesis, we will need to consider adding a similar type of interpolated function to modulate ketone output accordingly. [27][28][29] Selecting urine ketones instead of blood ketones for the simulation's output is another possible limitation given the newest sick day guidelines' preference for blood ketone monitoring over urine ketone monitoring. 30 Utilization of blood ketone measurement for the management of sick days and DKA has copious benefits-primarily that blood ketone measurements detect β-hydroxybutyrate rapidly, while urine ketone measurements detect acetoacetate that reflects an average of urine ketone concentration from the last void.…”

Cetoacidosis por estrés: caso clínico en paciente con atrofia muscular espinal

“…El consumo de etanol y los estados de estrés se asocian a una activación de hormonas de contrarregulación, inhibición de insulina, más un estado de ayuno (activación de gluconeogénesis). El uso de inhibidores SGLT2 provoca pérdida masiva de glucosa en la orina, lo que disminuye la secreción de insulina, aumenta las hormonas de contrarregulación, activa la gluconeogénesis y produce movilización de ácidos grasos para obtener energía 16 . Estas condiciones favorecen cetogénesis.…”

“…Ingresa al servicio de urgencia somnolienta, normotensa 115/78 mmHg, taquicárdica 140 lpm, polipneica 30 rpm, afebril. Se realizan exámenes de ingreso destacando en niveles plasmáticos: 16,4 mmHg; EB -26 mmol/L; delta ratio 1,05; gap de aniones 31 mEq/L; creatinina 0,37 mg/dL; BUN 38 mg/dL; sodio 147 mEq/L; potasio 3,7 mEq/L; cloro 112 mEq/L; lactato 1,2 mmol/L; glucosa 108 mg/dL; albúmina 4,2 g/dL; CK total 243 U/L; cetonemia +++, cetonuria +, osmolalidad plasmática medida 322 mOsm/kg, osmolalidad calculada 314 mOsm/ kg, estudios toxicológicos negativo, niveles de salicilato < 3 µg/mL, niveles acetoaminofeno < 1,2 µg/ mL. Además, tomografía computada de abdomen y pelvis (por antecedente de dolor abdominal), que mostraba nefrolitiasis bilateral y atrofia muscular toracoabdominal, sin otros hallazgos.…”