scholarly journals A Case of Euglycemic Diabetic Ketoacidosis Following Canagliflozin Therapy

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A358-A358
Author(s):  
Kubra M Tuna ◽  
Randa Abdelmasih ◽  
Ramy Abdelmaseih ◽  
Mrhaf Alsamman ◽  
Joseph Robbins

Abstract Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM). In general, DKA characterized by blood sugar over 250 mg/dL, anion-gap metabolic acidosis, and increased plasma or urine ketones. Approximately 2–3% of DKA patients can present with normal blood glucose levels (less than 250 mg/dl) which called euglycemic DKA. Some of the etiologies of euglycemic DKA include recent use of insulin, low caloric intake, alcoholism, chronic liver disease, and pregnancy. Very rarely, SGLT2 inhibitor use may be responsible for euglycemic DKA. Case Presentation: Here we present a case of 44 years old female with a past medical history of DM type 2 who presented with acute onset of nausea and vomiting. Initial laboratory findings were remarkable for anion gap metabolic acidosis with a blood glucose level of 201 mg/dl. The patient was on long-acting insulin along with Canagliflozin and Metformin therapy over years and reported being compliant with medications. She was treated with intravenous insulin therapy which resolved acidosis as well as symptoms. The patient was discharged with recommendations of discontinuation of Canagliflozin. Discussion: SGLT2 inhibitors are the novel class of oral antidiabetic drugs which widely used due to their favorable cardiovascular and renal outcomes independent of glycemic control. However, their side effects remain a concern. DKA is a rare but serious side effect of SGLT2 inhibitors with an incidence rate of 9.4% in type 1 DM and less than 0.2% in type 2 DM. Patients typically present with euglycemia or low-grade hyperglycemia which results in a diagnostic challenge for treating physicians. SGLT2 inhibitors increase urinary glucose excretion with a subsequent decrease in circulating insulin and an increase in glucagon, rendering a metabolic shift from glucose to fatty acid utilization. During times of intercurrent illness (decreased oral intake, sepsis) or metabolic stress (surgery), decreased carbohydrate intake coupled with the aforementioned changes will result in decreased insulin secretion and increased counter-regulatory hormones including adrenaline and cortisol, promoting lipolysis, fatty acid oxidation, and ketone production by the liver which ultimately leading to euglycemic DKA. Conclusion: SGLT2 inhibitors induced euglycemic DKA treatment is identical to classic DKA with consideration of the lack of hyperglycemia. Appropriate patient counseling to ensure safe SGLT2 inhibitor therapy is crucial, including appropriate holding parameters during concomitant volume-depleting illnesses and decreased oral intake. Timely diagnosis of euglycemic DKA, and recognitions of other rare but lethal side effects to decrease overall morbidity and mortality.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sindhura Inkollu ◽  
Sindhuja Korem ◽  
Sudha Ganne

Abstract Background: Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newer class of antihyperglycemics that cause reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. Common side effects include yeast and urinary tract infections. The US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors. The mechanisms by which SGLT2 inhibitors cause euglycemic DKA are unclear. SGLT2 inhibitors may lead to a decrease in either endogenous or exogenous insulin and an increase in glucagon production.1 This insulin deficiency or resistance may be mild in Type 2 diabetics, however, preventing the profound spike in blood glucose seen in traditional DKA. Here, we report a case of euglycemic DKA in a patient on Canagliflozin who presented initially with hypoglycemia. Clinical case: A 70 year old female presented with altered mental status for 1 day duration. Her past medical history is significant for type 2 Diabetes Mellitus, being managed on Canagliflozin, Glimepiride and Janumet. One week prior to admission she had lumbar spinal fusion surgery. Since then she has been feeling weak and tired with poor oral intake, but continued to use her medications. Initial laboratory findings showed blood glucose of 68 (70-100 mg/dl) without any acidosis. Her altered mental status was attributed to higher opioid doses which she received prior. Oral hypoglycemic agents have been held. On 2nd day of hospitalization, patient became more lethargic and complained of nausea. Laboratory testing revealed a serum glucose of 250mg/dL, serum bicarbonate of 13 (21–31mmol/L), and Anion gap of 25 (3.6–11.0mmol/L). With the suspicion of DKA, a beta-hydroxy butyrate level was obtained which was elevated at 90.10 (0 – 4.16 mg/dL). Venous blood gas analysis was significant for pH 7.23 (7.31-7.41) and pCO2 – 28 (41-51 mmHg). Urinalysis showed ketosis and glucosuria. Patient was diagnosed as euglycemic diabetic ketoacidosis from Canagliflozin in presence of precipitating factors - stress and poor intake. Patient was treated with insulin drip and intravenous fluids with reduction in anion gap and correction of acidosis within 24hrs. There was a gradual improvement in her mental status. She was discharged on subcutaneous insulin, and all other diabetic medications were stopped. Conclusion: Our case highlights the importance of being vigilant in a patient on Canagliflozin, euglycemic DKA can occur even if they present initially with hypoglycemia and no acidosis. Reference: 1. Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016;7(2):135-138.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A380-A381
Author(s):  
Joi C Hester ◽  
Stacy Zimmerman ◽  
Teresa Allison Nimmo ◽  
Wesley Cunningham ◽  
Joshua Liu ◽  
...  

Abstract Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are cardiorenal protective agents increasingly used in patients with diabetes. Cases of euglycemic diabetic ketoacidosis (euDKA) have been reported particularly among patients with type 1 diabetes. Our case is an example that highlights the role SGLT-2 inhibitors play in the development of euDKA in a patient with type 2 diabetes with confounding factors of strict adherence to a ketogenic diet and ankle fracture. A 72-year-old female with a history of type 2 diabetes presented to the emergency department (ED) with right ankle pain and obvious deformity after a mechanical fall. Radiography of the right lower extremity confirmed distal fracture of the tibia and fibula. After reduction of her fracture in the ED, she was admitted in anticipation of an open reduction internal fixation. Her diabetes was controlled on empagliflozin monotherapy and adhering to a ketogenic diet. She monitored her blood ketones daily at home and reported values in the 3–4 mmol/L range. On admission, her basic metabolic panel (BMP) revealed a blood glucose of 148 mg/dL, bicarbonate of 20 mEq/L, anion gap of 18 mEq/L, Cr of 1.3 mg/dl, and eGFR of 40 mL/min. Her beta-hydroxybutyrate (BHB) was 5.09 mmol/L. The initial assessment was presumed starvation ketosis. On hospital day three, she complained of continued nausea, polydipsia, and abdominal pain. Chart review revealed nocturia with approximately 3–4 voids per night. Repeat BMP showed a blood glucose of 152 mg/dL, bicarbonate of 16 mEq/L, anion gap still at 18 mEq/L, Cr 1.4 mg/dl, and eGFR of 37 mL/min. Since admission, all of her blood glucose levels ranged between 118–178 mg/dL. She denied dyspnea but exhibited Kussmaul respirations on physical exam. Repeat labs revealed a BHB of 8.92 mmol/L, and arterial blood gas (ABG) showed pH 7.2, pCO2 23, pO2 100, bicarbonate 8.6 mEq/L, consistent with high-anion gap metabolic acidosis, confirming the diagnosis of euDKA. Her empagliflozin had been held since admission, but she had not received any insulin up to this point due to euglycemia. She was immediately started on a weight-based dose of 12 units of insulin glargine with subsequent improvement of her BHB and anion gap. This patient’s use of an SGLT2-inhibitor in combination with her being on a ketogenic diet, contributed to a nonregulated state of ketone production leading to euDKA in the perioperative period. As SGLT2-inhibitors become more readily available, it is important to educate physicians and patients about the risk of euDKA during fasting, ketogenic diets, and the perioperative period.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A385-A386
Author(s):  
Shyamsunder Vachhani ◽  
Gautam Das

Abstract Introduction: Dapagliflozin is one of the novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in the treatment of patients with type 2 diabetes. Diabetes Ketoacidosis (DKA) is defined by the triad of hyperglycaemia, anion-gap acidosis, and increased plasma ketones. Euglycemic DKA is an uncommon form of ketoacidosis which is characterized by metabolic acidosis with a pH <7.3 and a serum bicarbonate of <18mEq/L, ketosis, and a blood glucose level of <200 mg/dl. This can be caused by SGLT2 inhibitors. Euglycemic diabetes ketoacidosis is a rare complication that occurs in patient taking SGLT2 inhibitors. Here we describe a patient with euglycemic DKA. The incidence of DKA associated with dapagliflozin has been reported to be < 0.1%. Case Presentation: This 55 years old gentleman has past medical history of obesity, type 2 diabetes (since age of 27 yrs.), hypercholesterolemia, hypertension and osteoarthritis. He recently suffered from myocardial infarction discharged 2 days back and presented to emergency department with central chest pain radiating to both arms in the morning. ECG reported as normal and venous blood gas showed pH- 7.10, pCo2- 3.84, pO2- 5.54, glucose- 10, lactate-1.8, bicarbonate- 8.5, base excess 19.2, anion gap 25. And dapagliflozin was stopped as a part of discharge planning and followed up in our diabetes clinic. Urine dipstick revealed Glucose +2, ketone +4, pH 5. He was diagnosed to be suffering from euglycemic diabetic ketoacidosis & treated as per protocol. When he recovered from DKA his insulin was optimised and dapagliflozin was stopped as a part of discharge planning and was followed up in our diabetes clinic. Discussion: In patients on dapagliflozin, cases of euglycemic diabetes ketoacidosis are increasingly being reported. Diagnosis of euglycemic diabetes ketoacidosis can be easily missed in the emergency department due to absence of marked hyperglycemia, often leading to delayed diagnosis and treatment. Mechanism of action of dapagliflozin is by selectively inhibiting the transporter protein SGLT2 in the renal proximal, which prevents glucose reabsorption and subsequently induces the elimination of filtered glucose via urine, the process is known as ‘glycuresis’ which reduces the blood glucose levels. SGLT-2 inhibitors should be initiated by a clinician cautiously and only after adequately weighing the risks and benefits of treatment. It is advisable to do urine test on patient taking dapagliflozin on admission which will help diagnose euglycemic DKA early. To prevent this potentially dangerous complication, patients taking SGLT2 inhibitors who become ill should discontinue the medication, undergo ketone evaluation, and start basal insulin, if ketones are positive. In addition, patients should be educated to stop their SGLT2 inhibitor at least 1 week prior to elective procedures.


2021 ◽  
Author(s):  
Michael Colacci ◽  
John Fralick ◽  
Ayodele Odutayo ◽  
Michael Fralick

Importance: The risk of diabetic ketoacidosis (DKA) with sodium-glucose cotransporter-2 (SGLT2) inhibitors is unclear. Objective: To examine the risk of DKA with SGLT2 inhibitors in both observational studies and large clinical trials. Data Sources: Searches of PubMed, EMBASE and CENTRAL (inception to 15 April 2019) without language restrictions; conference proceedings; and reference lists. Study Selection: Randomized controlled trials and observational studies that quantified the rate of diabetic ketoacidosis with an SGLT2 inhibitor in comparison to another diabetes medication or placebo. Data Extraction and Synthesis: Two independent investigators abstracted study data and assessed the quality of evidence. Data were pooled using random effects models with the Hartung-Knapp-Sidik-Jonkman method. Main Outcome and Measures: Absolute event rates and hazard ratios for diabetic ketoacidosis were extracted from each study. Results: Seven randomized trials encompassing 42,375 participants and five cohort studies encompassing 318,636 participants were selected. Among the 7 randomized controlled trials, the absolute rate of DKA among patients randomized to an SGLT2 inhibitor ranged from 0.6 to 2.2 events per 1000 person years. Four randomized trials were included in the meta-analysis, and compared to placebo or comparator medication, SGLT2 inhibitors had a 2.4-fold higher risk of DKA (Relative Risk [RR] = 2.46 [95% CI, 1.16-5.21]; I2 = 0%; P = 0.54). Among the 5 observational studies, the absolute rate of DKA associated with SGLT2 inhibitor use ranged from 0.6 to 4.9 per 1000 person years and a 1.7-fold higher rate of DKA compared to another diabetes medication (RR = 1.74 [95% CI, 1.01-2.93]; I2 = 45%; P = 0.12). Conclusions and Relevance: In adults with type 2 diabetes, SGLT2 inhibitors increase the risk of DKA in both observational studies and large randomized clinical trials. Registration: CRD42019146855 Funding Source: None


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lavrynenko O ◽  
◽  
Santos H ◽  
Garza A ◽  
Qazi R ◽  
...  

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) >250mg/dl; anion gap metabolic acidosis (pH <7.30 and bicarbonate <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.


Author(s):  
Prashanth Rawla ◽  
Anantha R Vellipuram ◽  
Sathyajit S Bandaru ◽  
Jeffrey Pradeep Raj

Summary Euglycemic diabetic ketoacidosis (EDKA) is a clinical triad comprising increased anion gap metabolic acidosis, ketonemia or ketonuria and normal blood glucose levels <200 mg/dL. This condition is a diagnostic challenge as euglycemia masquerades the underlying diabetic ketoacidosis. Thus, a high clinical suspicion is warranted, and other diagnosis ruled out. Here, we present two patients on regular insulin treatment who were admitted with a diagnosis of EDKA. The first patient had insulin pump failure and the second patient had urinary tract infection and nausea, thereby resulting in starvation. Both of them were aggressively treated with intravenous fluids and insulin drip as per the protocol for the blood glucose levels till the anion gap normalized, and the metabolic acidosis reversed. This case series summarizes, in brief, the etiology, pathophysiology and treatment of EDKA. Learning points: Euglycemic diabetic ketoacidosis is rare. Consider ketosis in patients with DKA even if their serum glucose levels are normal. High clinical suspicion is required to diagnose EDKA as normal blood sugar levels masquerade the underlying DKA and cause a diagnostic and therapeutic dilemma. Blood pH and blood or urine ketones should be checked in ill patients with diabetes regardless of blood glucose levels.


2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Asma Abu-Abed Abdin ◽  
Muhammad Hamza ◽  
Muhammad S. Khan ◽  
Awab Ahmed

Diabetic ketoacidosis (DKA) is characterized by elevated anion gap metabolic acidosis, hyperglycemia, and elevated ketones in urine and blood. Hyperglycemia is a key component of DKA; however, a subset of DKA patients can present with near-normal blood glucose, an entity described as “euglycemic DKA.” This rare phenomenon is thought to be due to starvation and food restriction in insulin dependent diabetic patients. Cocaine abuse is considered a trigger for development of DKA. Cocaine also has anorexic effects. We describe an interesting case of euglycemic DKA in a middle-aged diabetic female presenting with elevated anion gap metabolic acidosis, with near-normal blood glucose, in the settings of noncompliance to insulin and cocaine abuse. We have postulated that cocaine abuse was implicated in the pathophysiology of euglycemic DKA in this case. This case highlights complex physiological interplay between type-1 diabetes, noncompliance to insulin, and cocaine abuse leading to DKA, with starvation physiology causing development of euglycemic DKA.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A382-A383
Author(s):  
Maram Khalifa ◽  
Hassaan Aftab ◽  
Vitaly Kantorovich

Abstract Background: With mounting evidence demonstrating improved cardiovascular and renal outcomes with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, this class of newest antidiabetic agents is rapidly gaining favor. SGLT2 inhibition lowers the renal threshold for glucose excretion, resulting in renal glycosuria, a shift in substrate utilization from carbohydrate to fat oxidation and hyperglucagonemia and thus poses the risk of developing euglycemic DKA as a rare but serious adverse effect. Clinical Cases: the first case is A 36-year-old female was diagnosed with type 2 DM with an HbA1c of 10% and was started on multi-agent antihyperglycemic therapy including metformin 500 mg BID, extended release exenatide 2 mg once a week and empagliflozin 25 mg once daily which were all initiated simultaneously. 2 days after starting regimen, she complained of nausea, vomiting and was unable to tolerate oral diet and fluids by day 4 which potentially predisposed to starvation ketoacidosis. She presented to the ED with normal vitals, grossly normal physical exam and labs were significant for beta-hydroxybutyrate of over 7 mmol/L (ref range &lt;0.28), bicarbonate of 10 mmol/L (22 - 33), anion gap 25 (7 - 17), arterial pH 7.16 (7.33 - 7.43), serum glucose 111 (7.33 - 7.43). GAD-65 antibody titer was &lt;5 IU/mL (&lt; 5). She was diagnosed with euglycemic DKA, transferred to ICU and started on DKA protocol to which she responded very well. Second patient is A 65 Years old male with past medical history of CAD, HTN, HDL, history of PE/DVT and Type 2 DM was on insulin and jardiance, started ketodiet while continuing taking the jardiance and stopped taking his insulin because his sugars were controlled presented to the ED with abdominal pain, nausea and vomiting, had relatively normal vitals and benign physical exam, labs showed Bicarbonate of 9 mmol/L (22 - 33), anion gap of 31 (7 - 17), venous pH of 7.07 (7.33 - 7.43) glucose was 189 (7.33 - 7.43), beta-hydroxybutyrate of over 7.7 mmol/L (ref range &lt;0.28), patient was admitted to the ICU and started on insulin on DKA protocol Conclusion: SGLT2 inhibitors may be associated with DKA due to their ketogenic effects secondary to enhanced lipolysis and increased glucagon to insulin ratio. although not expected, euglycemic DKA could be much more present in cases where there is predisposition to increase ketones generation w/without appropriate clearance eg. starvation, ketotic diet, AKI, etc. These should be monitored for and the patient needs to be educated about accordingly to prevent both adverse outcomes and potential decrease in drug use if not strongly indicated. also,It would be prudent for prescribing clinicians to advise patients to withhold potentially harming medications temporarily if they cannot maintain adequate oral intake.


2020 ◽  
pp. 1-2
Author(s):  
Ajay Budhwar ◽  
Parul Malhotra

We describe a case report of a patient who presented with euglycemic diabetic ketoacidosis (euDKA), six days after starting treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitor, Canagliflozin. ‘Euglycemic diabetic ketoacidosis’ or ‘DKA with lower-than-anticipated glucose levels’ (as recommended by AACE/ACE) is a rare, challenging and easy to miss the diagnosis A 41-year-old male with a history of type 2 Diabetes Mellitus presented with uncontrolled hyperglycemia. Canagliflozin (SGLT2 inhibitor) was added to his anti-diabetic regimen of Metformin and Sitagliptin. Six days later, he presented with symptoms of diabetic ketoacidosis with normal blood glucose of 131mg/dl. The patient was further investigated with arterial blood gas analysis and serum ketone studies, keeping in view of the potential of euglycemic diabetic ketoacidosis (euDKA) with SGLT2 inhibitor use. The clinical picture and lab values of the patient were consistent with diabetic ketoacidosis(DKA), although it is rare in type 2 DM. Blood glucose was in the normal range which could have delayed the diagnosis if the physician was not vigilant. If one had only focused on the blood glucose, then this potentially fatal condition could have been missed. However, when other causes of anion gap metabolic acidosis were excluded and the lab values of urine ketones, elevated beta-hydroxybutyrate, reduced bicarbonate, and normal lactate interpreted, it leads to the diagnosis of SGLT2 inhibitor-associated euglycemic DKA. We performed a literature review of this topic and discuss the history of euglycemic diabetic ketoacidosis, risk factors, pathophysiology, diagnosis, management, and prevention of SGLT2 inhibitor-induced euDKA.


2020 ◽  
Vol 2020 ◽  
pp. 1-3 ◽  
Author(s):  
Samantha Steinmetz-Wood ◽  
Matthew Gilbert ◽  
Katherine Menson

Results from major clinical trials have shown significant cardiorenal-protective benefits of SGLT2 inhibitors in patients with type 2 diabetes (T2DM), leading to increased popularity. A rare but serious side effect of SGLT2 inhibitors is euglycemic diabetic ketoacidosis (EDKA), which presents more covertly but has been described. Identification and report of modifiable risk factors would be an important step in helping clinicians appropriately counsel patients. In this case report, we present DKA in a patient on an SGLT2 inhibitor and ketogenic diet (KD). A 47-year-old male with a history of poorly controlled T2DM on metformin and empagliflozin presented to the emergency department (ED) with several days of pharyngitis, dyspnea, emesis, abdominal pain, and anorexia. Of note, one month prior to this event, he presented to the ED with malaise and was found to have an anion gap of 21, a bicarbonate level of 13 mmol/L, a pH level of 7.22, 3+ ketonuria, and a glucose level of 7 mmol/L (127 mg/dl). Additional workup was negative, and findings were attributed to his KD. His use of empagliflozin was not identified on his medication list. At second presentation, the patient was tachypneic and tachycardic and had mild abdominal tenderness. Labs revealed anion gap 28, bicarbonate 5 mmol/l, pH 6.94, 3+ ketonuria, glucose 14.9 mmol/L (269 mg/dl), and beta-hydroxybutyrate 8.9 mmol/L. The patient was diagnosed with DKA and was treated accordingly. With closure of anion gap, the patient was transitioned to insulin and metformin, and his empagliflozin was discontinued indefinitely. Before prescribing this medication class, physicians should inquire about low-carbohydrate diets given the higher risk for DKA, though knowledge of this risk is still not widespread.


Sign in / Sign up

Export Citation Format

Share Document