Euglycemic diabetic ketoacidosis (EuDKA) is an uncommon diabetic complication. Just like diabetic ketoacidosis (DKA), EuDKA is a medical emergency. EuDKA is primarily related to the imbalance between insulin and counter-regulatory hormones, with an elevated insulin/glucagon ratio, and is characterized by blood glucose near normal (blood glucose less than 250 mg/dL) in the background of DKA. There are many factors associated with EuDKA, but the overall mechanism is based on a relative state of carbohydrate deficit, resulting in ketosis while maintaining near-normal glucose levels. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new oral antidiabetic medication category that can precipitate EuDKA. EuDKA is more common in patients with diabetes mellitus on SGLT2 inhibitors with lower mass index and decreased glycogen store which can be triggered by surgery, infection, trauma, a major illness or reduced food intake and persistent vomiting, gastroparesis, dehydration, and reduced insulin dosages. This is a case of a 34-year-old male, Filipino, diagnosed with type 2 diabetes mellitus, who was maintained on dapagliflozin + metformin 5mg/1000mg taken twice a day with good compliance and was admitted with EuDKA precipitated by decreased food intake and managed with intravenous insulin. Throughout admission, the blood glucose levels did not exceed 250mg/dL. His clinical condition improved through insulin therapy, administration of sodium bicarbonate, and intravenous hydration. EuDKA is an uncommon diabetic complication. High clinical suspicion is required to avoid delay in diagnosis and management since normal blood sugar levels masquerade the underlying DKA. Nevertheless, the cornerstone for the management of DKA and EuDKA remains the same: intravenous hydration and insulin therapy.

OBJECTIVE: Hyperglycemia in patients with type 2 diabetes mellitus is frequently encountered in the hospital setting. The recent guidelines for the management of inpatient hyperglycemia have included the use of dipeptidyl peptidase 4 inhibitors as an alternative to standard insulin therapy in select patients. This raises the question of the inpatient use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), which have gained increasing popularity in the outpatient setting because of beneficial cardiovascular and renal outcomes. This article describes the risks associated with the use of SGLT2i for the management of inpatient hyperglycemia.
METHODS: A literature review was performed using PubMed and Google Scholar for studies assessing the inpatient use of SGLT2i. Search terms included \"SGLT2 inhibitors,\" \"euglycemic DKA,\" \"inpatient hyperglycemia,\" \"DPP4 inhibitors,\" \"hypovolemia,\" and \"urinary tract infections.\" Studies not written in English were excluded. Forty-eight articles were included.
RESULTS: Review of the literature showed significant safety concerns with the use of SGLT2i for the inpatient management of hyperglycemia. Hospitalized patients treated with SGLT2i were at increased risk of diabetic ketoacidosis, euglycemic diabetic ketoacidosis, hypovolemia, and urinary tract infections. When compared head-to-head, SGLT2i were not more effective for inpatient glycemic control than dipeptidyl peptidase 4 inhibitors and did not reduce insulin requirements when used in combination with insulin. Although SGLT2i can be considered for the treatment of congestive heart failure, they should be started close to or at the time of discharge.
CONCLUSIONS: Although SGLT2i are a preferred pharmacotherapy class for the outpatient management of type 2 diabetes mellitus, there are considerable safety concerns when using them in a hospital setting, and avoidance is recommended.

A subclass of diabetic ketoacidosis (DKA) is euglycemic DKA, characterized by the same traits of ketoacidosis and low bicarbonate levels. However, the condition differs from classic DKA because of its normoglycemic levels. Euglycemic DKA was once thought to be incredibly rare, but its incidence has been on the rise with the widespread use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors and other newer anti-diabetic medications. The disorder is not fully understood and is often missed when presenting because of the non-elevated blood sugars. Common triggers for euglycemic DKA include infection, fasting, pregnancy, and medications such as SGLT2 inhibitors. This case report involves a patient with type 2 diabetes mellitus on sitagliptin that presented to the emergency department with shortness of breath, cough, nausea, vomiting, and abdominal pain and tested influenza positive with blood glucose levels of 209 mg/dl. He was started on IV fluids and subcutaneous insulin but developed worsening acidosis. The following day, he was transferred to the ICU for DKA protocol and diagnosed with euglycemic DKA.

While rare, serious adverse effects including euglycemic diabetic ketoacidosis (EDKA) have been associated with sodium-glucose cotransporter-2 inhibitor (SGLT2i) use. We present an interesting case of SGLT2i-induced EDKA occurring two years after initiation of therapy. Most patients with EDKA recover with prompt recognition and treatment. Patient education about identifying early signs remains a cornerstone of early identification and response to SGLT2i-induced EDKA.

Euglycemic diabetic ketoacidosis (DKA), a side effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors, is a triad of high metabolic anion gap acidosis, raised serum and urine ketones, and serum glucose <250 mg/dl. SGLT2 inhibitors cause a carbohydrate deficit by glucosuria, which leads to an increased glucagon/insulin ratio, the metabolic shift from glucose to lipid utilization causing ketogenesis, and hence euglycemic DKA. Additional factors like the ketogenic diet, illness, surgery, and pregnancy contribute to precipitating these episodes. Keywords search included \"Euglycemic DKA and SGLT2 inhibitors\" in PubMed and Google Scholar, to compile data from existing articles that provide information on the withholding and restarting period of the drug after a euglycemic DKA episode. SGLT2 inhibitors, used in the treatment of type 2 DM, have an average half-life of 11-13 hours, so most articles suggested withholding the drug three days before any elective surgery but some articles suggested a longer withholding period based on other precipitating factors contributing to euglycemic DKA. Hence, we came up with patient inclusion criteria and concomitant therapies review that we need to consider in making this decision. In addition, a multidisciplinary approach is required when laying out guidelines for restarting the drug to have a unanimous approach. After reviewing the existing literature, it is clear that concrete guidelines are required to decide on drug withholding and restarting periods after a euglycemic DKA episode, as they vary among different institutions and different specialties. We believe it is crucial to consider patient inclusion criteria and concomitant therapies in forming those guidelines.

BACKGROUND: Euglycemic diabetic ketoacidosis (DKA) is a potentially life-threatening adverse condition associated with use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). This risk is further pronounced in the perioperative period. There is no consensus for when SGLT2i should be held preoperatively, and recommendations from various organizations have evolved from 1 day to 3 to 4 days in the latest American Diabetes Association guidelines. Further study of patients with perioperative euglycemic DKA is required to help clarify the optimal timing of preoperative discontinuation of SGLT2i agents.
METHODS: In this retrospective, single-centre case series we examined 4 patients who developed postoperative euglycemic DKA after coronary artery bypass grafting, 3 of whom underwent semiurgent surgery. We characterized their clinical course, predisposing factors and treatment characteristics.
RESULTS: The SGLT2i were held for 1 to 5 days preoperatively, with times since last dose before surgery being 54, 79, 80 and 151 hours. Surgery was semiurgent for 3 patients, and elective for 1 patient. Three patients were diagnosed with euglycemic DKA within 24 hours after surgery. The fourth patient developed euglycemic DKA on postoperative day 3 in the context of significant hypovolemia and exhibited potential signs of protracted SGLT2i action at 7 days since the last dose.
CONCLUSIONS: The duration of SGLT2i action and risk for DKA is variable and complex. Providers should hold SGLT2i at least 3 days before elective major surgery, with potentially longer times in high-risk patients. Careful vigilance should be used for perioperative DKA development in all patients recently exposed to SGLT2i.

OBJECTIVE: To identify clinical characteristics and factors associated with the development of euglycemic diabetic ketoacidosis (eDKA), and develop suitable strategies to reduce such events.
METHODS: Electronic health record (EHR) data were extracted to identify all patients between December 1, 2013, and March 30, 2021, who underwent surgical procedures and had been prescribed a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before these procedures. The resulting list was streamlined to a subset of patients who either had diabetic ketoacidosis (DKA) listed as a hospital diagnosis, postoperative serum bicarbonate ≤ 16 mmol/L, or postoperative serum pH ≤ 7.20. Clinical documentation and laboratory data were reviewed to determine the patients with eDKA.
RESULTS: A total of 2183 procedures conducted on 1307 patients, met the inclusion criteria with the majority (1726, 79.1%) being nonemergent patients. Among 1307 patients, 625 (47.8%) were prescribed empagliflozin, 447 (34.2%) canagliflozin, 214 (16.4%) dapagliflozin, and 21 (1.6%) ertugliflozin, respectively. A total of 8 incidences pertaining to eDKA were noted for 8 unique patients; 5 had undergone emergency surgery whereas 3 had undergone nonemergent procedures. In the 3 nonemergent cases, only 1 patient had received counseling to stop the SGLT2i 3 days before the procedure. In perioperative patients who were prescribed an SGLT2i over 6 years, the incidence of eDKA was 0.17% and 1.1% for nonemergent and emergent procedures, respectively.
CONCLUSIONS: Euglycemic DKA was rare in patients undergoing nonemergent procedures, likely because of preoperative instructions to stop their SGLT2i 3 days before the procedure. Euglycemic DKA was more likely to occur in patients undergoing emergency surgery when the SGLT2i could not be prophylactically stopped.

Diabetic ketoacidosis (DKA) is a well-known, serious complication that many patients with type 1 and 2 diabetes face due to either a relative or absolute insulin deficiency. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have gained increased popularity due to their diabetic, cardiovascular, and renal benefits. An associated complication of SGLT2 inhibitors is euglycemic DKA. A 56-year-old male with a history of type 2 diabetes mellitus and peripheral neuropathy presented with right foot pain secondary to a diabetic foot ulcer. The ulcer was present for one year, but the patient noticed increased pain and purulent discharge over the three days prior to presentation. While being treated inpatient for the foot ulcers, the patient repeatedly refused to receive standard hospital diabetes management of insulin injections. He instead insisted to take his home medications against medical advice, which were metformin and Glyxambi® (empagliflozin/linagliptin, Boehringer Ingelheim, Ingelheim am Rhein, Germany). His diabetic foot ulcer was medically managed with IV antibiotics.  On day 4 of admission, his anion gap increased to 23 mEq/L, and serum bicarbonate (CO2) decreased to 8 mEq/L, raising concerns of diabetic ketoacidosis. His glucose was 141 mg/dL, his beta-hydroxybutyrate was high at 5.5 mmol/L. An arterial blood gas (ABG) test demonstrated anion gap metabolic acidosis with secondary respiratory alkalosis. A urinalysis demonstrated glucose 1000 mg/dL and ketones of 150 mg/dL. The patient was diagnosed with euglycemic DKA. Due to the patient having normal glucose levels, an insulin drip and a 5% dextrose with 0.45% normal saline drip were started. Basic metabolic profiles were ordered every four hours, with glucose checks every hour. Once the anion gap was closed and his urinary ketones disappeared, the patient transitioned to subcutaneous insulin. He was able to be discharged home with basal subcutaneous insulin and metformin with instructions to avoid SGLT2 inhibitors in the future.  Unfortunately, there are currently no guidelines from endocrinology or internal medicine societies regarding the management of euglycemic DKA. As the typical DKA diagnostic criteria of elevated blood glucose level are not present, it is easy to overlook euglycemic DKA. As these SGLT2 inhibitors become more prevalent, careful monitoring of all potential side effects as well as the contraindications are prudent to successful management of complex disease states.

OBJECTIVE: Diabetic ketoacidosis (DKA) during pregnancy is a life-threatening emergency for both the mother and the fetus. The pathophysiology of DKA in pregnancy has its own characteristics due to multiple factors, such as insulin resistance, accelerated starvation and respiratory alkalosis, thus creating ketosis-prone state, with DKA occurring at milder degrees of hyperglycemia, even in normoglycemic levels, which can result in delayed diagnosis and treatment with potential for adverse metabolic consequences.
METHODS: In this article, we presented 8 clinical cases of DKA during pregnancy. We discuss the spectrum of the clinical picture, the entity of euglycemic DKA vs hyperglycemic DKA, the period of pregnancy in appearance of episode of DKA and triggers of DKA.
CONCLUSIONS: The treatment of DKA in pregnant women must be started immediately and must be accentuated on intravenous fluids, insulin and electrolyte replacement. DKA in pregnancy may be euglycemic. Prevention, early recognition, immediate hospitalization, and aggressive management remain the cornerstones in DKA management in pregnancy.

A 48-year-old male patient with Type 2 diabetes mellitus(T2D), on insulin replacement therapy, glipizide, and dapagliflozin presented with generalized weakness with weight loss of 40 pounds in 6 months ever since he was started on dapagliflozin. He was hemodynamically stable on arrival with a finger stick glucose of 121 gm%. Physical examination was unremarkable except for dry mucus membranes. His laboratory results on arrival are shown in Table 1. His serum osmolar gap was within the normal range. He was treated insulin drip per DKA protocol and gap was closed, the patient was clinically and biochemically back to baseline, and he was discharged home. Delayed diagnosis of normoglycemic diabetic ketoacidosis (DKA) in adults with diabetes treated with multiple antidiabetic drugs (eg, sodium-glucose cotransporter-2 [SGLT-2] inhibitors) can potentially increase morbidity and mortality. Patient education in terms of symptoms and signs, physician awareness of early recognition of ketoacidosis in the setting of paradoxically normal or near-normal blood glucose levels in these patients is the primary focus of this case study. This is paradoxical DKA because theoretically patient is not meeting one of the criteria for DKA which include triad of hyperglycemia, Ketoacidosis with widened anion gap, Ketonemia. This is a short case report of presumed SGLT-2 inhibitor euglycemic diabetic ketoacidosis. The main teaching point is recognition and early diagnosis of this issue when multiple diabetic medications are present with the absence of hyperglycemia. This is, by current definition, not DKA because theoretically, the patient does not meet one of the criteria for DKA as the patient was apparently not hyperglycemic, albeit with, ketoacidosis and widened anion gap. (ketonemia).