Euglycemic Diabetic Ketoacidosis Research Articles

SGLT-2 inhibitors for treatment of heart failure in patients with and without type 2 diabetes: A practical approach for routine clinical practice

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i), initially studied and approved for the treatment of diabetes, are now becoming a promising class of agents to treat heart failure (HF) and chronic kidney disease (CKD), even in patients without diabetes. While the potential benefits in several diseases (usually treated by different medical specialties) is amplifying the interest in these drugs, their use in frail patients with multiple pathologies and on polypharmacy can be complex, requiring a composite multidisciplinary approach. Following a brief overview of the evidence supporting the benefits of SGLT-2i in patients with HF or CKD, we herein provide guidance for prescribing SGLT-2i in daily practice using a multidisciplinary approach. A shared treatment algorithm is presented for initiating an SGLT-2i in patients already being treated for diabetes and HF. Tools to prevent hypoglycemia, blood pressure drop, genital infections, euglycemic diabetic ketoacidosis and eGFR dip are also provided. It is hoped that this practical, multidisciplinary guidance for initiating SGLT-2i in patients with HF and/or CKD, whatever therapy they are currently on, can help to offer SGLT-2i to the largest population of patients possible to provide the most therapeutic benefit.

Euglycemic diabetic ketoacidosis associated with SGLT2 inhibitors: A systematic review and quantitative analysis.

Background:Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) rarely cause euglycemic diabetic ketoacidosis (euDKA) in diabetic patients. The aim was to identify demographic, clinical, and predisposing factors for euDKA from published case reports.Methods:A systematic review of published case reports of euDKA in patients receiving SGLT2 inhibitors and meta-analysis of clinical trials to quantify the risk ratio (RR) of DKA in patients receiving SGLT2 inhibitors. PubMed and EMBASE databases were searched for the case reports of and clinical trials from January 2010 to August 2020. Studies published in English language were included and other languages were excluded. Data related to patients’ demography, clinical presentation, drug and dose of SGLT2 inhibitors, and concomitant medication were extracted. Incidence of diabetic ketoacidosis (DKA) extracted from clinical trials. Data related to demographic, clinical, and other parameters presented as ratios and proportions and incidence of DKA in RR using Review Manager 5.3.Results:Forty-seven of 160 reports with an aggregate of 77 patients were included in the analysis. The majority of the patients were females (67.53%), with T2DM and with gastrointestinal symptoms (58%). Surgery was the most common precipitating factor (n/N = 15/77). Canagliflozin (n/N = 34/77) was the commonest SGLT2 inhibitor reported along with metformin as the concomitant medication (63.6%). The pooled RR of DKA was 3.70 (95%CI 2.58, 5.29) and I2 = 0%.Conclusion:euDKA is commonly seen in middle-aged female, T2DM patients taking SGLT2 inhibitors along with metformin. The risk of DKA in patients receiving SGLT2 inhibitors increases by 3.7 times than the other medication.

A Case of SGLT-2i Induced Euglycemic Diabetic Ketoacidosis in the Setting of Gastrointestinal Stress

Euglycemic DKA (euDKA) is a rare, uncommon variant of DKA, characterized by the imbalance between insulin and counterregulatory hormones. Lately, the use of SGLT2 inhibitors is known to incite euDKA, which is often missed on initial presentation. In this case, we present a scenario of a 61-year-old African American male with a history of hypertension, CAD s/p CABG, and type 2 diabetes mellitus on SGLT2i (empagliflozin) with a clinical picture of normoglycemic DKA process. With a pH of 7.14, bicarbonate of 8 mEq/L, anion gap (AG) of 17mEq/L, ketoacidosis, and glucosuria, the patient met criteria for euDKA; however, the initial clinical diagnosis of euDKA was overlooked by the possibility of an underlying infectious gastroenteritis, given his recent history of travel with passengers with similar presentation, causing a delay in euDKA management. The management of euDKA is like that of a typical DKA, inculcating aggressive fluid resuscitation and insulin, followed by a permanent discontinuation of SGLT2i. Thus, this case highlights the importance of understanding SGLT2i induced euDKA and its early diagnostic and timely management to prevent further complications.

Euglycemic Diabetic Ketoacidosis in a Diabetic Patient Treated with SGLT2 Inhibitor

Abstract Diabetic ketoacidosis (DKA) is a life - threatening complication and must be diagnosed and treated promptly and aggressively. The classic triad of DKA is: Hyperglycemia (blood glucose (BG) > 250 mg/dl: Anion gap metabolic acidosis (pH < 7.30 and bicarbonate < 18 mEq/L): And ketonemia. With Food and Drug Administration (FDA) approval of the sodium - glucose transporter 2 inhibitors (SGLT2i), DKA can occur with BG levels below 200 mg/dl and has been defined as euglycemic DKA (EuDKA). Due to the absence of hyperglycemia, the diagnosis of EuDKA is challenging and often delayed. This 60-year-old diabetic male, treated with empagliflozin and pioglitazone, presented with diarrhea and abdominal pain which started 20 days ago. He was admitted with dehydration and diagnosis of colitis. On admission laboratory evaluation revealed metabolic acidosis with elevated anion gap of 18mEq/L, bicarbonate of 19 mEq/L, and BG of 146 mg/dL. There was no history of ingestion of alcohol, salicylates, methanol, ethylene glycol and nothing to suggest lactic acidosis. The plasma creatinine was 0.79 mg/dl. On the following day, he developed an increase in the anion gap to 22 mEq/L and further decrease in bicarbonate to 13 mEq/L, and serum ketones were detected. The patient was treated for EuDKA in ICU with intravenous insulin, dextrose (to prevent hypoglycemia), and normal saline with resolution of his symptoms and EuDKA in 3 days. With the widespread use of SGLT2i, physicians need to have a high suspicion of EuDKA in patients who present with an unexplained anion gap acidosis without or only modest elevation in BG concentration.

Safety of SGLT2 Inhibitors: A Pharmacovigilance Study from 2013 to 2021 Based on FAERS.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2is) are widely used in clinical practice for their demonstrated cardiorenal benefits, but multiple adverse events (AEs) have been reported. We aimed to describe the distribution of SGLT2i-related AEs in different systems and identify important medical event (IME) signals for SGLT2i. Methods: Data from the first quarter (Q1) of 2013–2021 Q2 in FAERS were selected to conduct disproportionality analysis. The definition of AEs and IMEs relied on the system organ classes (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA-version 24.0). Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to estimate the association between SGLT2is and IMEs. Results: A total of 57,818 records related to SGLT2i, with 22,537 SGLT2i-IME pairs. Most SGLT2i-related IMEs occurred in monotherapy (N = 21,408, 94.99%). Significant signals emerged at the following SOCs: “metabolism and nutrition disorders” (N = 9,103; IC025 = 4.26), “renal and urinary disorders” (3886; 1.20), “infections and infestations” (3457; 0.85). The common strong signals were observed in diabetic ketoacidosis, ketoacidosis, euglycaemic diabetic ketoacidosis and Fournier’s gangrene. Unexpected safety signals such as cellulitis, osteomyelitis, cerebral infarction and nephrolithiasis were detected. Conclusion: Our pharmacovigilance analysis showed that a high frequency was reported for IMEs triggered by SGLT2i monotherapy. Different SGLT2is caused different types and the association strengths of IMEs, while they also shared some specific PTs. Most of the results are generally consistent with previous studies, and more pharmacoepidemiological studies are needed to validate for unexpected AEs. Based on risk-benefit considerations, clinicians should be well informed about important medical events that may be aggravated by SGLT2is.

Abstract #1085426: Clinical Characteristics and Outcomes of Ketogenic Diet or Very Low Carbohydrate Diet Induced Euglycemic Diabetic Ketoacidosis in Patients on Sodium-Glucose Co-Transporter-2 Inhibitors

Euglycemic diabetic ketoacidosis (EDKA) linked to Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT-2i) use in diabetics is increasingly noticed. The underlying mechanism is primarily increased lipolysis and ketone body reabsorption. A ketogenic diet or very low-carbohydrate diet (VLCD) commonly adopted by diabetic patients also enhances body ketosis by breaking down fats into energy sources. However, this diet in SGLT-2i users was observed to trigger EDKA. We aim to understand the patient-specific factors and review the literature of this cohort of patients. Several databases were carefully analyzed to distinguish patient-specific risk factors and clinical characteristics of ketogenic diet-induced EDKA in patients on SGLT-2i. The patient’s symptoms, clinical profile, laboratory results, and safety of dietary changes in SLGT-2i were reviewed. A total of 13 case reports identifying 14 patients on a ketogenic diet and SGLT-2i diagnosed with EDKA were thoroughly reviewed. There were found to be more females (8/14) than males (6/14); median age was 51.02 ± 11.26. Of the 14 patients, 12 (85%) were associated with Type-2 DM, 1 (7%). Duration of treatment with an SGLT2 inhibitor before EKA onset varies from 1 to 365 days. Duration of consuming a ketogenic diet or VLCD before EDKA onset varies from 1 to 90days, with over 90% of patients hospitalized in < 4 weeks after starting the diet. At presentation, average blood glucose was 167.50 ± 41.80, pH 7.10 ± 0.10, HCO3 8.1 ± 3.0 mmol/L, potassium 4.2 ± 1.1, anion-gap 23.6 ± 3.5 mmol/L, and the average HbA1C was 10 ± 2.4. Hospital stay ranged from 1 to 15 days. None of the patients were reinitiated on SGLT-2i, and 2/4 of patients reported were back on the Ketogenic diet or VLCD upon patient questioning. Despite the popularity of the ketogenic diet and VLCD for weight loss, their use in diabetics taking SGLT-2i is associated with EDKA. Physicians should educate their patients with diabetes taking SGLT-2i about the risk of EDKA. In addition, patients should be counseled on the importance of including their physician in any decisions relating to significant changes in diet or exercise routines. Further research is needed to address if SGLT-2i’s are permanently discontinued in patients with diabetes on SGLT-2i’s and the ketogenic diet that developed EDKA.

Euglycemic Diabetic Ketoacidosis, diagnostic challenge in resource limited countries: Case series

Official Journal of the Endocrine Society of Sri Lanka. The Sri Lanka Journal of Diabetes Endocrinology and Metabolism (SJDEM) publishes original research articles, reviews, and other special features related to diabetes, endocrinology and metabolism in humans and human tissue.

CONSIDERATIONS FOR SODIUM-GLUCOSE TRANSPORTER 2 INHIBITOR THERAPY RESULTING IN EUGLYCEMIC DIABETIC KETOACIDOSIS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Sodium-glucose transporter 2 inhibitors (SGLT2i) have recently become an increasingly popular treatment choice for type 2 diabetics. A rare complication of SGLT2i use is euglycemic diabetic ketoacidosis (EDKA), during which life threatening severe metabolic acidosis and ketonemia arises in the setting of glucose levels of <250 mg/dL. CASE PRESENTATION: A 40-year-old male with a history of presumed type 2 diabetes mellitus (DM-2) which was diagnosed six years prior was transferred to our intensive care unit with persistent diabetic ketoacidosis (DKA). Past medical history was positive for prior episodes of DKA. His diabetic medications included glimepiride, dapagliflozin, metformin, and degludec insulin. He presented with a one day history of vomiting and polydipsia. Despite five liters of intravenous (IV) fluids, IV bicarbonate, and IV insulin, he persisted with a high anion gap metabolic acidosis (HAGMA). Lab work revealed an anion gap of 32, an osmolar gap of 26 with a normal lactic acid, and blood glucose of 148 mg/dL [Figure 1]. Arterial blood gas (ABG) revealed a pH of 7.046 and bicarbonate of 3.2. He was treated with an IV bicarbonate drip, IV insulin drip, and high volume IV fluids. He also underwent monitoring with serial ABGs, frequent blood glucose checks, and basic metabolic panels. The HAGMA gradually resolved over the next 48 hours. Additional serology revealed a positive glutamic acid decarboxylase (GAD) antibody; indicative of latent autoimmune DM in adults (LADA). After improvement his glimepiride, dapagliflozin, and metformin were discontinued. He was ultimately transitioned from an IV insulin drip to a basal/bolus insulin regimen at discharge. DISCUSSION: SGLT2i medications enhance excretion and block reabsorption of filtered glucose from the proximal convoluted tubule, resulting in a state of glucose starvation thereby increasing the glucagon/insulin ratio [1]. The HAGMA seen in EDKA is thought to result from increased lipolysis due to the glucagon/insulin imbalance, ultimately leading to ketoacidosis [2]. The mechanism of ketone production in EDKA is similar to DKA; acetoacetic acid reduces to beta-hydroxybutyric acid [2]. EDKA is a rare but known complication in type 2 diabetics who are prescribed SGLT2i therapies. Use of SGLT2i is not recommended in those with autoimmune diabetes by the Food and Drug Administration as ketone-associated complications can be as high as 9% [3]. LADA is an anti-islet cell autoimmune adult-onset DM. In our patient, he was initially misdiagnosed with DM-2; however, his blood work revealed that he had LADA. CONCLUSIONS: As SGLT2i usage becomes increasingly more common, providers should be cognizant of the patient's diabetic history and ensure the correct etiology of their patient's diabetes. Additionally, critical care providers should remain vigilant of the phenomenon of EDKA and its predisposing risk factors. REFERENCE #1: Pfützner A, Klonoff D, Heinemann L, Ejskjaer N, Pickup J. Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapy-an emerging problem and solutions offered by diabetes technology. Endocrine. 2017 Apr;56(1):212-216. doi: 10.1007/s12020-017-1264-y. Epub 2017 Mar 17. PMID: 28303514. REFERENCE #2: Plewa MC, Bryant M, King-Thiele R. Euglycemic Diabetic Ketoacidosis. 2021 Feb 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 32119457. REFERENCE #3: Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015 Sep;38(9):1687-93. doi: 10.2337/dc15-0843. Epub 2015 Jun 15. PMID: 26078479; PMCID: PMC4542270. DISCLOSURES: No relevant relationships by Jonathan Ross Ang, source=Web Response No relevant relationships by Parth Patel, source=Web Response No relevant relationships by Tarang Patel, source=Web Response No relevant relationships by Shaili Patel, source=Web Response No relevant relationships by SACHIN PATIL, source=Web Response

EUGLYCEMIC DIABETIC KETOACIDOSIS MASQUERADING AS TOXIC ALCOHOL INGESTION

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: First reported in 1973, euglycemic diabetic ketoacidosis (euDKA) historically accounted for 0.8-1.1% of diabetic ketoacidosis (DKA) cases [1]. Without hyperglycemia, the anion gap metabolic acidosis (AGMA) of euDKA may be attributed to other causes. We present a case of euDKA that was mistaken for toxic alcohol poisoning. CASE PRESENTATION: A 53-year-old woman with type 2 diabetes (T2D), for which she reported taking metformin and glyburide, presented with abdominal pain and nausea. She also reported drinking "vodka" given by a stranger the day prior. Labs included bicarbonate 12 mEq/L, anion gap (AG) 18, lactate 1.7 mmol/L, lipase 735 U/L, and urinalysis with 2+ glucose and 3+ ketones. CT confirmed pancreatitis. Correctional insulin was ordered but not given due to blood sugar of 121-225 mg/dL. Repeat labs overnight revealed bicarbonate <5, AG >18, and arterial pH 7.09. After toxicology consult, she was given IV fomepizole and transferred to the ICU for urgent hemodialysis (HD) for possible toxic alcohol poisoning. Just prior to placing HD access, records obtained revealed that she was prescribed empagliflozin. Ultimately, a toxic alcohol panel was negative and beta-hydroxybutyrate was elevated at 0.86 mmol/L. She was treated with infusions of crystalloid, insulin, and dextrose. Her ketosis resolved in 9 days, and she was discharged on insulin and metformin. DISCUSSION: Previously seen with low caloric intake, alcohol or cocaine use, liver disease, or pregnancy, euDKA has recently been linked to sodium glucose cotransporter 2 inhibitor (SGLT2I) use [2]. Since FDA approval in 2013, SGLT2I use has steadily risen as data on cardiovascular and renal benefits accumulate. SGLT2Is act independent of insulin by blocking proximal tubule reabsorption of glucose. This can lead to euglycemia despite insulin deficiency and the potential for an acute insult, like pancreatitis, to trigger euDKA. Along with lack of insulin, SGLT2I-related euDKA may be mediated by volume depletion, counterregulatory hormones, and enhanced lipolysis and fatty acid oxidation [3]. Notably, pancreatitis can trigger euDKA without SGLT2I use [2]. Though the initial ketonuria and lack of inebriation were, in retrospect, clues to the presence of DKA in this case, the report of a suspicious ingestion led to a presumptive diagnosis of toxic alcohol poisoning. Indeed, untreated toxic alcohol poisoning can lead to major disability or death, and prompt empiric treatment is vital if clinical suspicion exists. CONCLUSIONS: The rapid diagnosis of AGMA remains a challenge in intensive care. As SGLT2I use continues to grow, providers will increasingly encounter euDKA. Importantly, euglycemia does not exclude DKA, and euDKA must be routinely considered in the differential of unexplained severe AGMA to prevent adverse outcomes from delays in treatment. REFERENCE #1: Jenkins et al. Euglycaemic diabetic ketoacidosis: does it exist? Acta Diabetol 1993;30:251-3. REFERENCE #2: Bonora et al. Euglycemic Ketoacidosis. Review Curr Diab Rep 2020 May 19;20:25. REFERENCE #3: Qiu et al. Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectives. Diabetes Metab Res Rev 2017 Jul;33(5). DISCLOSURES: No relevant relationships by Christos Argyropoulos, source=Web Response No relevant relationships by Matt Bouchonville, source=Web Response No relevant relationships by Mitchell Byrd, source=Web Response No relevant relationships by Melissa Fang, source=Web Response No relevant relationships by Umair Khan, source=Web Response No relevant relationships by Joao Teixeira, source=Web Response

Perioperative Management of Long-term Antidiabetic Therapy in Patients with Diabetes Mellitus

Drug therapy, as well as diabetes technology, e.g. insulin pumps or sensor glucose measurement, have developed enormously in recent years. Their use differs according to the type of diabetes, secondary or concomitant diseases, and individual factors and target values. In the perioperative phase, diabetic patients are generally at increased risk of complications, including a derailment of glucose metabolism, an increased rate of cardiovascular events, worsening of preexisting renal insufficiency, and increased incidence of wound infections. In addition, drug class-specific side effects of antidiabetic therapy may occur. The prevalence of diabetes patients in anesthesiology is high and will continue to increase. In Germany, more than 8 million people are estimated to live with diabetes mellitus. The rate of new cases is about 600 000 per year. The distinction between type 1 and type 2 diabetes mellitus is essential. Diabetes therapy is becoming increasingly individualized; combination therapies are becoming more common. Therefore, the management of long-term medication should also be individualized. Substance-specific side effects or adverse effects, especially of oral antidiabetic agents, must be considered in the care of patients, e.g. euglycemic diabetic ketoacidosis under SGLT-2 inhibitors is a relevant problem. Insulin therapy is also evolving; knowledge of new preparations and of insulin pump therapy facilitates perioperative management. Both hypoglycemia and hyperglycemia, possibly with ketoacidosis, must be avoided. The purpose of this article is to provide an overview of the management of long-term medication in patients with diabetes mellitus.

IJU this issue

This issue contains two Review Articles, 11 Original Articles, three Urological Notes and five Editorial Comments. The number of people with diabetes rose rapidly. The prevalence in Japan is estimated to be approximately 10%. Sodium–glucose-linked transport protein 2 (SGLT2) inhibitors are newly developed drugs, used for the treatment of type 2 diabetes mellitus, that act on the proximal convoluted tubules of the nephrons to prevent resorption of glucose from the filtrate. In this issue Chandrashekar et al. (Brisbane, Australia) reviewed the urological implications of these drugs. Increased glycosuria is thought to result in genital infections and urinary tract infections. Genital infections in males, which can be increased by up to fivefold, include balanitis and balanoposthitis. SGLT2 inhibitors might also cause Fournier’s gangrene. Unexpectedly, one large-scale study failed to show the increased risk for severe and non-severe urinary tract infection events among cases treated with SGLT2 inhibitor, compared with those among cases treated with dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 agonists. Pollakiuria and nocturia, which might have impacts on quality of life, were the most prevalent lower urinary tract symptoms after initiation of SGLT2 inhibitors. Notably, the authors recommended that SGLT2 inhibitors should be ceased perioperatively, because perioperative use increases the risk of euglycemic diabetic ketoacidosis. Three original articles and one urological note on renal cell carcinoma (RCC) appear in this issue. Ishiyama et al. (Tokyo, Japan) reviewed their 23 patients who underwent extracorporeal circulation-assisted surgery with or without using deep hypothermic circulatory arrest (DHCA). They found that surgical time, estimated blood loss, perioperative complication rate, 90-day mortality rate and hospital stay days were similar between these two groups. In addition, oncological outcomes (cancer-specific and overall survival) did not differ between groups. They concluded that the use of DHCA did not result in inferior perioperative outcomes. Although DHCA often requires longer operative time and are thought to be related with platelet dysfunction and coagulopathy, the authors successfully showed the safety and usefulness of DHCA. Wakita et al. (Kobe, Japan) reported on the surgical outcomes of the complex tumors of the kidney treated with robot-assisted partial nephrectomy (RAPN). They retrospectively analyzed 348 patients who underwent RAPN at a single center; 299 had non-complex tumors (RENAL score <10) and 49 had complex tumors (RENAL score ≥10). Although more perioperative complications and lower postoperative renal function with longer ischemia time and console time were observed in the complex tumors group, positive surgical margin rate and recurrence-free survival did not differ between groups. They concluded that RAPN for complex renal tumors is safe, with no difference in oncological outcomes despite more complications and decreased renal function. For the complex tumors, radical nephrectomy or open partial nephrectomy tend to be carried out, even in this era. The authors clearly showed the effectiveness and safety, along with limitation, of RAPN for the complex tumors. Several risk factors for recurrence or survival in pT3a RCC patients have been proposed. In this issue Ohsugi et al. (Hirakata, Japan) performed a retrospective study assessing the predictors of postoperative recurrence in non-metastatic patients with pT3a RCC. Analyzing 114 patients, they identified three predictors for recurrence-free survival on multivariate analysis, perinephric fat invasion, sarcomatoid or rhabdoid features and necrosis. They found that high-risk pT3a cases with two or three of these predictors had poor prognosis, and that the recurrence-free survival was similar between high-risk pT3a cases and those with pT3b or greater. Previously, the impact of perinephric fat invasion on cancer-specific survival was analyzed using 2998 patients from the RCC registry of The Cancer Registration Committee of JUA.1 Perinephric fat invasion was associated with advanced age and aggressive pathological features, and was an independent prognostic factor in non-metastatic RCC especially in larger tumors. Nivolumab plus ipilimumab is widely used for the first-line therapy for advanced RCC. Ishihara et al. (Tokyo, Japan) reviewed their 16 advanced RCC cases without prior nephrectomy. They found that tumor response between primary and metastatic lesions was generally parallel. Interestingly, the magnitude of tumor response ranged more widely in metastatic lesions than in primary lesions. As unresectable RCC is not rare, this study provides us useful clinical information on decision-making. None declared.

Sodium-Glucose Cotransporter-2 Inhibitor–Associated Euglycemic Diabetic Ketoacidosis After Orthotopic Heart Transplant in a Prediabetic Patient: A Case Report

Postoperative euglycemic diabetic ketoacidosis (euDKA) associated with sodium-glucose cotransporter-2 (SGLT2) inhibitor use has been well-documented and carries a Food and Drug Administration recommendation to hold SGLT2 inhibitors 3 to 4 days before a planned surgical procedure. Unfortunately, many surgical procedures, such as orthotopic heart transplant (OHT), are unplanned and unpredictable. With the increasing use of SGLT2 inhibitors in diabetic and non-diabetic heart failure patients, new challenges in patient management and perioperative risk have arisen. We report a case in which SGLT2 inhibitor-associated euDKA complicated the postoperative course of a prediabetic patient who had undergone OHT.

Awareness of euglycaemic diabetic ketoacidosis during pregnancy prevents recurrence of devastating outcomes: a case report of two pregnancies in one patient

BackgroundEuglycaemic diabetic ketoacidosis (DKA) during pregnancy is a life-threatening obstetric emergency. It requires early identification and prompt action. Obstetricians’ knowledge about symptoms, diagnostic pitfalls and management during pregnancy and delivery need to be improved. We report a case of a young diabetic woman developing severe euglycaemic DKA in two consecutive pregnancies; the first pregnancy resulted in the most deviating outcome (i.e., intrauterine death), while the second pregnancy resulted in the delivery of a healthy newborn. Thus, the novelty of the case presented here is the possibility to demonstrate how the management of DKA in pregnancy can dramatically change outcomes.Case presentationWe report a case of a young diabetic woman in whom DKA was concealed by hyperemesis and oesophageal reflux. This woman presented to our delivery unit with severe euglycaemic DKA during her first pregnancy. While the mother’s condition could be successfully stabilized, the foetus died shortly after admission. Two years later, the same woman presented with similar problems. Repeated episodes of mild euglycaemic DKA could be successfully managed with consequent interdisciplinary treatment and close observation, leading to a good pregnancy outcome, i.e., the birth of a healthy child.ConclusionAwareness of euglycaemic DKA needs to be increased to reduce the risk of severe complications during pregnancies in diabetic women. This case report demonstrates that increased awareness of DKA with immediate recognition and a successful multidisciplinary approach are mandatory for an positive pregnancy outcomes.

Sodium-Glucose Co-transporter 2 Inhibitor-Associated Euglycemic Diabetic Ketoacidosis After Bariatric Surgery: A Case and Literature Review

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce cardiovascular, kidney, and overall mortality. SGLT2i are also associated with a rare adverse event, euglycemic diabetic ketoacidosis (EDKA). This report describes a case of EDKA one day after bariatric surgery in a 51-year-old female with type 2 diabetes mellitus managed with the SGLT2i, canagliflozin. She was following a ketogenic diet for three weeks prior to surgery. The patient made a steady recovery with rapid anion gap closure followed by prolonged non-anion gap metabolic acidosis. Her medical record was tagged with a life-threatening reaction to SGLT2i. The risk of EDKA from SGLT2i may be increased by a low carbohydrate diet or postoperative status. Our case was complicated by hypokalemia, exemplifying the need for aggressive electrolyte management. Further guidance is needed to manage risk factors provoking EDKA and the use of SGLT2i therapy after an episode of EDKA.

Euglycemic Diabetic Ketoacidosis in Type 1 Diabetes on Insulin Pump, with Acute Appendicitis: A Case Report.

IntroductionRecently, euglycemic diabetic ketoacidosis has been an increasing topic of discussion within emergency medicine literature. Euglycemic diabetic ketoacidosis can easily be missed, as a normal point-of-care glucose often mistakenly precludes the work-up of diabetic ketoacidosis.Case ReportA 16-year-old female with a past medical history of type 1 diabetes presented to the emergency department with altered mental status, vomiting, and abdominal pain. She was diagnosed with euglycemic diabetic ketoacidosis.ConclusionReported cases of euglycemic diabetic ketoacidosis are most frequently attributed to sodium glucose cotransporter-2 inhibitors, but other potential causes have been discussed in the literature. In this patient, a starvation state with continued insulin use in the setting of acute appendicitis led to her condition.

Euglycemic diabetic ketoacidosis - a rare side effect of sodium-glucose co-transporter-2 inhibitor in a patient of type 2 diabetes mellitus with left ventricular dysfunction: a case report

A 42 year old female with type 2 diabetes mellitus (T2DM), presented with angina on exertion and left ventricular (LV) dysfunction (global LV ejection fraction (EF)=26%). Patient was subjected to coronary angiography which revealed triple vessel disease. Patient was started on usual standard of care heart failure (HF) medications, including sodium-glucose co-transporter-2 (SGLT-2) inhibitor dapagliflozin which is promising new class of drug for treating T2DM and HF. Patient was advised myocardial revascularization in form of percutaneous transluminal coronary angioplasty (PTCA). Post angioplasty patient developed metabolic acidosis (high anion gap with normal lactate and increased ketone levels). Patient was diagnosed as case of euglycemic diabetic ketoacidosis (DKA) and patient was treated by volume resuscitation and insulin infusion.

Euglycemic Diabetic Ketoacidosis in a Diabetic Patient Treated with SGLT2 Inhibitor

Diabetic Ketoacidosis (DKA) is a life - threatening complication and must be diagnosed and treated promptly and aggressively. The classic triad of DKA is hyperglycemia (Blood Glucose (BG) &gt;250mg/dl; anion gap metabolic acidosis (pH &lt;7.30 and bicarbonate &lt;18mEq/L); and ketonemia. With Food and Drug Administration (FDA) approval of the sodium - glucose transporter 2 inhibitors (SGLT2i), DKA can occur with BG levels below 200mg/dl and has been defined as Euglycemic DKA (EuDKA). Due to the absence of hyperglycemia, the diagnosis of EuDKA is challenging and often delayed. This 60-year-old diabetic male, treated with Empagliflozin and pioglitazone, presented with diarrhea and abdominal pain, which started 20 days ago. He was admitted with dehydration and diagnosis of colitis. On admission laboratory evaluation revealed metabolic acidosis with elevated anion gap of 18mEq/L, bicarbonate of 19mEq/L, and BG of 146mg/dL. There was no history of ingestion of alcohol, salicylates, methanol, ethylene glycol and nothing to suggest lactic acidosis. The plasma creatinine was 0.79mg/dl. On the following day, he developed an increase in the anion gap to 22mEq/L and further decrease in bicarbonate to 13mEq/L, and serum ketones were detected. The patient was treated for EuDKA in ICU with intravenous insulin, dextrose (to prevent hypoglycemia), and normal saline with resolution of his symptoms and EuDKA in 3 days. With the widespread use of SGLT2i, physicians need to have a high suspicion of EuDKA in patients who present with an unexplained anion gap acidosis without or only modest elevation in BG concentration.

Sodium-Glucose Transporter Inhibition in Adult and Pediatric Patients with Type 1 Diabetes Mellitus.

Adjunctive therapies to insulin for treatment of type 1 diabetes mellitus (T1D) have gained popularity in efforts to achieve glycemic targets, and sodium-glucose transporter (SGLT) inhibitors are an appealing option due to associated weight loss, low risk of hypoglycemia, and improved cardiorenal outcomes seen in persons with type 2 diabetes mellitus. The increased risk of diabetic ketoacidosis (DKA), including euglycemic DKA, has led many to be wary of their use in T1D, especially given limited pediatric data and data regarding cardiorenal protection in this population. The phase 3 trials of these agents in T1D have yielded lower HbA1c, decreased total daily insulin dose, and small but significant weight loss with no increase in hypoglycemia. These trials also reported increased risks of genital mycotic infection and DKA. SGLT inhibitors have been approved as adjunctive therapy to insulin in adults with T1D in Europe and Japan, but the United States Food and Drug Administration has rejected similar applications. Although approaches to mitigate the risk of DKA have been developed, no randomized trials using such tools have been conducted. More research is needed to minimize the risk of DKA and to better evaluate the cardiorenal impact of these agents in persons with T1D.

Sodium glucose-linked transport protein 2 inhibitors: An overview of genitourinary and perioperative implications.

Sodium glucose-linked transport protein 2 inhibitors are relatively novel drugs, used for the treatment of type 2 diabetes mellitus. Their use since Pharmaceutical Benefits Schemeapproval in Australia has increased drastically, possibly due to the low risk of hypoglycemic events and their advertised cardiovascular mortality benefits. However, as with any novel drug, adverse effects regarding their use require medical practitioner awareness for optimal patient outcomes. This paper aims to cover the major urological implications, including those pertinent perioperatively, that concern this class of drugs. There is a clear risk of developing genital mycotic infections with the use of sodium glucose-linked transport protein 2 inhibitors, including serious infections such as Fournier's gangrene. Evidence for developing urinary tract infections has been mixed. Sodium glucose-linked transport protein 2 inhibitor-induced lower urinary tract symptoms may have impacts on quality of life via pollakiuria and nocturia, of which there are increased reports. Perioperative use increases the risk of euglycemic diabetic ketoacidosis. It is recommended that sodium glucose-linked transport protein 2 inhibitors be ceased perioperatively.

Abstract #1000943: Hidden In Plain Sight: The Complexity of Euglycemic DKA Induced by Severe Alcoholic Pancreatitis

The diagnostic challenge of euglycemic diabetic ketoacidosis (EDKA) is attributed to its relatively uncommon presentation and similarity to other forms of ketoacidosis. Often unrecognized at initial presentation, appropriate treatment for this life-threatening complication is delayed and potentially fatal. To emphasize EDKA as a differential diagnosis in severe metabolic derangement and highlight the complexity of ketoacidosis with alcoholic pancreatic injury, we describe a case of EDKA with severe acute pancreatitis in a patient without known diabetes.