What is euglycemic diabetic ketoacidosis?
Euglycemic diabetic ketoacidosis (DKA) is an acute life-threatening metabolic emergency characterized by ketoacidosis and relatively lower blood glucose (less than 11 mmol/L). The absence of hyperglycemia is a conundrum for physicians in the emergency department and intensive care units; it may delay diagnosis and treatment causing worse outcomes.
What is EDKA in diabetic ketoacidosis?
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.
What is diabetic ketoacidosis (DKA)?
Diabetic ketoacidosis (DKA) is widely known as a life-threatening acute complication of diabetes mellitus (DM). It mainly occurs in patients with type 1 DM; however, any acute illness like infection, trauma or acute coronary syndrome may also trigger DKA in type 2 DM.
What is the difference between euDKA and DKA?
As opposed to EuDKA (where blood glucose levels are normal or mildly elevated), typical DKA in Type 1 and 2 DM presents with marked hyperglycemia (usually 350–800 mg/dL) and associated with increased endogenous glucose production. Nevertheless, there is a reduction in tissue glucose disposal in the vicinity of insulin resistance.
What causes euglycemic DKA?
The three common causes of euglycemic DKA are SGLT-2 inhibitors, pregnancy and prolonged fasting.
What medication causes euglycemic DKA?
DKA is characterized by hyperglycemia, acidosis, and ketonemia, and sodium glucose transporter 2 inhibitors (SGLT2i) represent a new diabetes medication that has been associated with euglycemic DKA (eu-DKA).
How do you manage euglycemic ketoacidosis?
The mainstay of treatment involves rapid correction of dehydration using intravenous fluids (13). The second most important step in the management is the use of insulin drip along with a dextrose containing solution until the anion gap, and bicarbonate levels normalize (14).
What is euglycemic range?
Glycemic Indices Mean, standard deviation (SD) and time spent in euglycemia (70–180 mg/dL), in hyperglycemia (>180 mg/dL) and in hypoglycemia (<70 mg/dL) were calculated from CGM data.
How long does it take to recover from diabetic ketoacidosis?
How long does it take to recover from diabetic ketoacidosis? Finally, some good news! Once you're safely admitted to the hospital for DKA, recovery is usually complete in one to three days.
What are euglycemic drugs?
Canagliflozin, dapagliflozin, and empagliflozin are the most widely used medications in this class. These medications lower serum glucose levels by the novel mechanism of increasing glucose clearance in the urine, making them unlikely to cause hypoglycemia.
How do you differentiate euglycemic DKA from starvation ketosis?
However, unlike starvation ketosis, euglycemic DKA is a distinct clinical entity resulting from severe insulin deficiency, and can be differentiated from the former by the presence of a precipitating clinical illness,2 a bicarbonate concentration lower than 18 mmol/L,2 and as we have seen, very rapid resolution of ...
Can you have DKA without hyperglycemia?
Hyperglycemia is a key diagnostic criterion of DKA; however, in some rare cases, normal glucose levels can be present.
Does alcohol cause ketoacidosis?
Causes. Alcoholic ketoacidosis is caused by very heavy alcohol use. It most often occurs in a malnourished person who drinks large amounts of alcohol every day.
What does euglycemic mean?
: a normal level of sugar in the blood.
Can you have ketones and normal blood sugar?
5 – Can you get ketones with a normal or low blood sugar? Ketones can also be present when your blood sugar is normal or low.
Why do patients in DKA have increased urine formation?
As an excessive amount of glucose enters the renal tubules, it draws a large amount of water that ends up producing a significant amount of urine. This is known as osmotic diuresis and leads to volume depletion and dehydration in the patient.
How do SGLT2 inhibitors cause euglycemic DKA?
The proposed mechanism of SGLT2 inhibitor–associated euglycemic diabetic ketoacidosis implicates glucosuria leading to decreased plasma glucose levels and decreased insulin release (Fig 1). Carbohydrate deficit, insulinopenia, and increased glucagon release lead to upregulation of lipolysis and ketogenesis.
Which diabetes medication causes DKA?
Sodium–glucose cotransporter-2 (SGLT2) inhibitors, a class of drug used to treat type 2 diabetes, may lead to ketoacidosis in the early periods of drug therapy. The class comprises three drugs: canagliflozin, dapagliflozin, and empagliflozin.
How do SGLT2 inhibitors cause DKA?
Hence, SGLT2 inhibitors render the body susceptible to acidemia by ketogenesis and continue to produce glycosuria, thereby causing near normal or less abnormally elevated glucose levels than usually seen in DKA [11].
How does Jardiance cause DKA?
Jardiance causes your body to make more ketones. A buildup of ketones in the body can cause the blood to be too acidic. Symptoms of ketoacidosis can include: high blood sugar levels.
What causes eu-dka?
Other causes associated with eu-DKA include pregnancy, decreased caloric intake, heavy alcohol use, insulin use prior to hospital admission, cocaine abuse, pancreatitis, sepsis, chronic liver disease and liver cirrhosis. Patients with eu-DKA as well as with DKA need immediate referral for emergency evaluation and treatment.
What is the treatment for eu-DKA?
The treatment includes rapid correction of dehydration, correction electrolyte abnormalities, and use of insulin drip until the anion gap, and bicarbonate levels normalize.
What is a DKA?
Diabetic ketoacidosis (DKA) is defined as a clinical triad comprising metabolic acidosis, hyperglycemia and increased ketone bodies in the blood and urine. Hyperglycemia is usually the hallmark for the diagnosis of DKA (1). However, there is a subset of patients in whom the serum glucose levels are within the normal limits, ...
What is EDKA in diabetes?
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.
Why do diabetics get EDKA?
The underlying mechanism of EDKA is either due to decreased hepatic production of glucose during fasting state or enhanced urinary excretion of glucose induced by an excess of counter-regulatory hormones, the former being the most common reason. Thus, when a diabetic patient is exposed to any triggering factor for DKA and is fasting or starving while continuing the insulin treatment regularly, the liver will be in a state of glycogen depletion, thereby producing a lesser amount of glucose. On the other hand, there will be lipolysis and fatty acid production, which finally leads to excessive ketone body production (3). Some of the common causes of EDKA that have been reported in literature so far are low caloric intake, fasting or starvation (5), pregnancy (6), pancreatitis (7), cocaine intoxication, prolonged vomiting or diarrhea (8), insulin pump use (9) and of late use of SGLT2 inhibitors like empagliflozin, canagliflozin and so forth (10).
Is euglycemic ketoacidosis rare?
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.
Does fasting cause euglycemic ketoacidosis?
Burge et alhad reported in their study that short-term fasting is a well-known mechanism of developing euglycemic ketoacidosis when there is insulin deficiency in type I diabetic patients (11). They also subsequently went ahead to describe how dehydration can accelerate the development of DKA during periods of insulin deficiency. Dehydration usually promotes the development of hyperglycemia. However, it is interesting to note its differential role in EDKA. Fasting primarily increases the secretion of counter-regulatory hormones especially the glucagon, which depletes the glycogen stores in the liver. Dehydration acts as a stimulus for further glucagon secretion, which results in lipolysis and ketone body production in the background of decreased glucose production leading to EDKA. During insulin deficiency, dehydration also increases the secretion of other counter-regulatory hormones like catecholamines and cortisol, which further worsens EDKA (12). In the case of our second patient, urinary tract infection in conjunction with nausea due to the infection caused a decreased calorie intake and led to ketoacidosis with euglycemia. This is a classic presentation of EDKA.
What is euglycemic DKA?
Euglycemic DKA is an uncommon and likely under-diagnosed phenomenon, best defined as DKA with a lower than expected blood glucose (less than 250 mg/dL according to the American Diabetes Association). 4–6
What is the treatment for euglycemic DKA?
Euglycemic DKA treatment is the same as traditional DKA, and includes hydration, insulin, and supportive care. Patients with euglycemic DKA may also need a dextrose infusion given the lower glucose levels.
Can SGLT2 cause ketoacidosis?
In 2015 the FDA issued a warning, however, that SGLT2 inhibitors may cause ketoacidosis , urinary tract infections, and urosepsis. 4 Since then, multiple case reports have been published showing an association between SGLT2 inhibitors and the development of euglycemic DKA.
Is DKA defined by absolute blood glucose?
DKA is not defined by an absolute blood glucose.
Is SGLT2 a type 1 drug?
The FDA has approved these three SG LT2 inhibitors for Type 2 diabetics, and at times, they are prescribed off-label for Type 1. The mechanism involves decreasing glucose reabsorption in the nephron’s proximal tubule (via inhibition of the sodium-glucose linked cotransporter-2 protein). This results in increased urinary excretion of glucose that is independent of the body’s insulin secretion. 1
Can SGLT2 cause euglycemic DKA?
The mechanisms by which SGLT2 inhibitors cause or predispose to euglycemic DKA are unclear and likely complex . SGLT2 inhibitors may lead to a decrease in either endogenous or exogenous insulin, and an increase in glucagon production. 8 This insulin deficiency or resistance may be mild in Type 2 diabetics, however, preventing the profound spike in blood glucose seen in traditional DKA. 7
What is DKA in diabetes?
Background: Diabetic ketoacidosis (DKA) is traditionally defined as a triad of hyperglycemia (>250mg/dL), anion gap acidosis, and increased plasma ketones. There is another entity that providers must be aware of known as euglycemic DKA (euDKA), which is essentially DKA without the hyperglycemia (Serum glucose <200 mg/dL). Euglycemic DKA is a rare entity that mostly occurs in patients with type 1 diabetes, but can possibly occur in type 2 diabetes as well. The exact mechanism of euDKA is not entirely known, but has been associated with partial treatment of diabetes, carbohydrate food restriction, alcohol intake, and inhibition of gluconeogenesis. euDKA, can also be associated with sodium-glucose cotransporter 2 (SGLT-2) inhibitor medications. These medications first came onto the market in 2013 and are FDA approved for the treatment of type 2 diabetes, however many physicians use them off-label for type I diabetes due to their ability to improve average glucose levels, reduce glycemic variability without increasing hypoglycemia, and finally promote weight loss. Does euDKA Exist even in Patients not Using SGLT-2 Inhibitors? The short answer is YES. Munro JF et al [5] reviewed a case series of 37 episodes of euDKA in a publication from 1973. Although, dated and not robust evidence some take home messages can be derived: All but one episode was in insulin dependent diabetics Vomiting was the most frequent symptom of euDKA in 32% of patients Management in most cases consisted of: Intravenous fluids and electrolyte replacement. No deaths occurred in this case series What are the Names of the SGLT-2 Inhibitors? Ipragliflozin (Suglat) – Approved in Japan Dapagliflozin (Farxiga) – 1st SGLT2 Inhibitor Approved; Approved in US Luseogliflozin (Lusefi) – Approved in Japan Tofo Continue reading >>
What is euglycemic diabetic ketoacidosis?
Euglycemic diabetic ketoacidosis is a post market warning in patients with type 1 diabetes and type 2 diabetes treated with SGLT-2 inhibitors . We report a case of a 39-year-old obese female with presumed type 2 diabetes for seven years who presented to the emergency department with three days of nausea, vomiting, and abdominal pain. Due to previous total non-adherence with a prescribed insulin regimen, she was recently started on canagliflozin and liraglutide. The diagnosis of euDKA was missed in the initial evaluation as the blood glucose level was only 167 mg/dL. Further work up showed severe metabolic acidosis with an anion gap of 25 and positive ketones in the urine. She was treated successfully with dextrose water 5%/half normal saline and an insulin drip. As part of the work up, she tested positive for glutamic acid decarboxylase autoantibodies. Given the increasing utilization of SGLT-2 inhibitors and the fact that patients can present with near-normal glycemia, the diagnosis can be missed. Vigilance with the use of SGLT-2 inhibitors is necessary to decrease morbidity and potentially mortality particularly in patients with long-standing type 2 diabetes associated with marked β-cell insufficiency, type 1 diabetes mellitus, or latent autoimmune diabetes of adult onset. Continue reading >>
What is DKA in medicine?
Food and Drug Administration (FDA) issued a Drug Safety Communication that warns of an increased risk of diabetic ketoacidosis (DKA) with uncharacteristically mild to moderate glucose elevations (euglycemic D KA [euDKA]) associated with the use of all the approved sodium–glucose cotransporter 2 (SGLT2) inhibitors (1). This Communication was based on 20 clinical cases requiring hospitalization captured between March 2013 and June 2014 in the FDA Adverse Event Reporting System database. The scarce clinical data provided suggested that most of the DKA cases were reported in patients with type 2 diabetes (T2D), for whom this class of agents is indicated; most likely, however, they were insulin-treated patients, some with type 1 diabetes (T1D). The FDA also identified potential triggering factors such as intercurrent illness, reduced food and fluid intake, reduced insulin doses, and history of alcohol intake. The following month, at the request of the European Commission, the European Medicines Agency (EMA) announced on 12 June 2015 that the Pharmacovigilance Risk Assessment Committee has started a review of all of the three approved SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to evaluate the risk of DKA in T2D (2). The EMA announcement claimed that as of May 2015 a total of 101 cases of DKA have been reported worldwide in EudraVigilance in T2D patients treated with SGLT2 inhibitors, with an estimated exposure over 0.5 million patient-years. No clinical details were provided except for the mention that “all cases were serious and some required hospitalisation. Although [DKA] is usually accompanied by high blood sugar levels, in a number of these reports blood sugar levels were only moderately increased” (2). Wit Continue reading >>
How many people in Canada have diabetes?
More than 10 million Canadians are currently living with diabetes.1 Of those, 90% have type 2 diabetes mellitus (T2DM).1 Recently launched oral medications known as sodium-glucose cotransporter-2 (SGLT2) inhibitors were approved by the US Food and Drug Administration (FDA) in 2013 for treating T2DM.2 Approval by Health Canada was granted in 2014.3 Treatment with SGLT2 inhibitors (canagliflozin, dapagliflozin, or empagliflozin) has been shown to improve weight loss and glycemic control and to provide cardiovascular protection.4 Given the favourable clinical profile of SGLT2 inhibitors, health care providers are increasingly prescribing these antihyperglycemic agents. However, recent FDA and Health Canada warnings have cautioned about the possibility of patients developing ketoacidosis with their use.5,6 More important, most cases of ketoacidosis occurred in settings of mildly elevated or normal blood glucose levels (ie, euglycemic diabetic ketoacidosis [DKA]).6 We report a case of ketoacidosis in a patient with T2DM, taking canagliflozin, presenting with a serum glucose level of 11.9 mmol/L. A 51-year-old man with a known history of T2DM and hypertension presented to the emergency department with a 1-week history of malaise, cough, and intermittent shortness of breath. Over the preceding 2 days, he admitted to a history of decreased oral intake and fever, and he had abstained from taking his antihyperglycemic medications (canagliflozin and linagliptin-metformin). He reported 3 episodes of clear emesis the day of his presentation in the emergency department. He denied any other symptoms, sick contacts, or travel history. He reported no substance use, alcohol consumption, or other ingestions. He was not vaccinated against the flu. He was not taking insulin. Vital signs at Continue reading >>
What is a DKA?
Background: Diabetic ketoacidosis (DKA) is traditionally defined as a triad of hyperglycemia (>250mg/dL), anion gap acidosis, and increased plasma ketones.
What is eudka associated with?
The exact mechanism of euDKA is not entirely known, but has been associated with partial treatment of diabetes, carbohydrate food restriction, alcohol intake, and inhibition of gluconeogenesis. euDKA, can also be associated with sodium-glucose cotransporter 2 (SGLT-2) inhibitor medications. These medications first came onto ...
What is the most common symptom of eudka?
Vomiting was the most frequent symptom of euDKA in 32% of patients
Can eudka be missed?
Discussion: euDKA could be completely missed if just looking at the serum blood glucose alone. This could lead to worse outcomes for patients not started on treatment. The exact incidence of euDKA in patients taking SGLT-2 inhibitors is really unknown, as this entity may be under reported or even completely missed.
What is euglycemic DKA?
Euglycemic DKA (EDKA) is a clinical syndrome occurring both in type 1 (T1DM) or type 2 (T2DM) diabetes mellitus characterized by euglycemia ( blood glucose less than 250 mg/dL) in the presence of severe metabolic acidosis (arterial pH less than 7.3, serum bicarbonate less than 18 mEq/L) and ketonemia. DKA is one of the most severe and life-threatening complications of diabetes mellitus and can be seen in a variety of conditions. However, the incidence of EDKA has grown with the introduction of sodium-glucose transporter 2 (SGLT2) inhibitors. [1] It also presents a diagnostic challenge for physicians due to the variety of etiologies and normal blood glucose levels, often resulting in delayed diagnosis. [2] [3]
How many DKA patients are euglycemic?
Approximately 2.6% to 3.2% of DKA admissions are euglycemic. [7] [12] DKA-associated with SGLT2 inhibitors has rates ranging from 0.16 to 0.76 events per 1000 patient-years in patients with type 2 diabetes. Blau et al. estimate the SGLT2 inhibitors increase the risk of DKA in T2D patients by 7-fold. [13] Erondu et al. estimate an overall incidence of DKA from SGLT2 inhibitor use of approximately 0.1%. [14] Data on patients with type 1 diabetes who presented with DKA associated with SGLT2 inhibitors showed rates varying from 5 to 12%; however, euglycemia was not present in all cases. [8] Data associated with other causes of euglycemic DKA is scarce.
What is EDKA in medical terms?
Continuing Education Activity. Euglycemic diabetic ketoacidosis (EDKA) is an uncommon diabetic complication associated with several risk factors such as fasting, surgery, pregnancy, and now the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. EDKA is primarily related to an imbalance between insulin and counter-regulatory hormones, ...
Why do diabetics get EDKA?
The overall mechanism is based on a general state of starvation, resulting in ketosis while maintaining normoglycemia. Therefore, conditions like anorexia, gastroparesis, fasting, use of a ketogenic diet, and alcohol use disorder can lead to states of carbohydrate starvation and resultant ketosis. Additional triggers for EDKA include pregnancy, pancreatitis, glycogen storage disorders, surgery, infection, cocaine toxicity, cirrhosis, and insulin pump use. [4] [5] T1DM who underwent bariatric surgery patients experience DKA in over 20% of postoperative cases and may be especially prone to EDKA. [6]
Why do diabetics not recognize DKA?
Often the insulin-using diabetic patients do not recognize their symptoms as DKA because serum glucose is not elevated and may maintain or decrease their insulin dose. [1] . If insulin dosing is adequate for glucose levels, it will prevent gluconeogenesis, resulting in euglycemia.
What tests are needed for a diabetic patient?
An ill-feeling patient with diabetes with symptoms such as malaise, dyspnea, nausea, or vomiting should undergo screening with serum pH and blood or urine ketone testing . [3] [26]
Why is pregnancy a risk factor for EDKA?
Pregnancy is a risk factor for EDKA because of the physiologic state of hypoinsulinemia and increased starvation. Increased levels of cortisol and placental lactogen result in insulin resistance, and episodes of vomiting or fasting can lead to exaggerated starvation ketosis. [24] .
Pathophysiology
The mechanism behind EDKA involves a general state of starvation that results in ketosis while normoglycemia is maintained. 1 Simply put, EDKA is DKA in which normal glucose concentrations are present. Diabetic patients, especially those on insulin, may not recognize symptoms as DKA because the serum glucose is not elevated.
EDKA Precipitating Factors
SGLT2i: In the United States, SGLT2i (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) are currently approved to treat only T2DM, not T1DM. SGLT2i have demonstrated additional benefits for cardiovascular disease, chronic kidney disease, and heart failure.
Treatment
TABLE 2 outlines a stepwise approach to the management of EDKA. 2,7,9,28-31
Conclusion
EDKA is a high-risk yet obscure condition that can be challenging to diagnose and manage. As therapeutics experts, pharmacists are well suited to collaborate with other members of the healthcare team, as well as the patient, to identify risk factors for EDKA and to help appropriately manage this complex condition.
What is the eudka characterized by?
EuDKA is characterized by metabolic acidosis and ketosis in the presence of normal or moderately increased blood glucose levels.In most cases, blood glucose values remain less than 250 mg/dl.
How does SGLT2is affect blood glucose levels?
SGLT2is lowers blood glucose levels modestly by inhibiting glucose reabsorption in the proximal tubule leading to urinary glucose excretion. A decrease in blood glucose, in turn, reduces insulin secretion from β‐cells of the pancreas and stimulates the secretion of glucagon from pancreatic α‐cells.
Can Eudka be diagnosed with hyperglycemia?
The patient with EuDKA may not present with typical clinical signs and symptoms of DKA like dehydration because of the absence of marked hyperglycemia. Because of their atypical presentation, there is an increased probability of missing the diagnosis. Any diabetic patient taking SGLT2i presenting with symptoms like abdominal pain, nausea, vomiting, or fatigue should raise the suspicion of EuDKA. To diagnose EuDKA, keep in mind that the predominant ketone body is β-hydroxybutyrate i.e measured in blood, so measuring only urinary ketone body (acetoacetate ) may be deceiving as it is much less sensitive. Once the diagnosis is confirmed, it is advisable to stop SGLT2i immediately and manage the patient with hydration and insulin therapy, correction of electrolytes with the same protocol followed for DKA.
Which organs reabsorb ketone bodies?
The role of kidneys. The kidney tubules have a large capacity to reabsorb and use ketone bodies. The reabsorption of ketones in proximal tubules occurs via sodium-dependent monocarboxylate transporters (SMCT1 and SMCT2) which is dependent on sodium gradient (lumen to proximal tubule).
Is SGLT2 a ketoacidosis?
SGLT2 Inhibitor-induced Euglycemic Diabetic Ketoacidosis. Sodium-glucose co-transporter 2 inhibitors (SGLT2is) have emerged as a breakthrough therapy for the treatment of diabetes mellitus (DM) reducing key cardiovascular and kidney endpoints. These effects appear to be independent of their effects on blood pressure and glucose.
Can SGLT2I cause Eudka?
At-risk patients . Fortunately, not all the patients taking SGLT2i’s develop EuDKA. In a majority of patients, it is precipitated by a reduction or discontinuation of insulin, following starvation or low carbohydrate diet, urosepsis, dehydration, severe acute illness, heavy physical exercise, or excessive alcohol intake.
Is DKA normal in type 1 diabetes?
As opposed to EuDKA (where blood glucose levels are normal or mildly elevated), typical DKA in Type 1 and 2 DM presents with marked hyperglycemia (usually 350–800 mg/dL) and associated with increased endogenous glucose production. Nevertheless, there is a reduction in tissue glucose disposal in the vicinity of insulin resistance. In EuDKA, insulin deficiency is milder and there is rather an improvement in insulin resistance.
