Euglycemic diabetic ketoacidosis (EDKA) is a scary condition that can happen to anyone with diabetes, but it’s especially concerning for those taking SGLT-2 inhibitors.
Unlike traditional diabetic ketoacidosis (DKA), your blood sugar doesn’t have to be sky high for ketoacidosis to develop. In fact, your levels can be perfectly normal.
I’m going to explain what EDKA is, why it happens, what the symptoms are and how to recognize and treat it. I hope by understanding this condition, you’ll be able to catch it early on.
Key Takeaways
- Euglycemic diabetic ketoacidosis (EDKA) is marked by metabolic acidosis and ketonemia with blood glucose levels below 250 mg/dL, often misdiagnosed due to its subtle presentation.
- SGLT-2 inhibitors significantly increase the risk of EDKA by promoting ketone production, emphasizing the need for careful monitoring and patient education.
- Timely recognition and comprehensive management of EDKA, including fluid resuscitation and insulin therapy, are crucial to prevent severe complications and improve patient outcomes.
What is Euglycemic Diabetic Ketoacidosis?
EDKA is a condition where you have severe metabolic acidosis with ketones in your urine and/or blood, but your blood glucose is below 250 mg/dL.
That’s right, your blood sugar doesn’t have to be high like it is with traditional diabetic ketoacidosis (DKA). If you’re taking a SGLT-2 inhibitor, you might not even suspect ketoacidosis because your blood sugar is normal.
EDKA is often misdiagnosed as other non-ketotic conditions because the symptoms are so non-specific and your blood sugar is normal. This leads to delayed and incorrect treatment.
EDKA makes up only about 3.2% of all cases of DKA, but it’s on the rise as more people are prescribed SGLT-2 inhibitors. In the hospital, we’re seeing more cases of EDKA and I want you to be aware of it too.
If you’re hospitalized with a severe illness, your doctor may not automatically test your ketones, so make sure to ask!
Traditional markers like an anion gap may not be present with EDKA, so it’s important to get a serum or urine ketone test.
Additionally, EDKA can occur if you have classic DKA that’s only partially treated.
Causes and Risk Factors of EDKA
Several things can increase your risk for developing euglycemic diabetic ketoacidosis (EDKA). If you take a SGLT-2 inhibitor and are preparing for surgery, you are at higher risk. Other risk factors include:
- Low glycogen stores (not eating or drinking, fasting)
- Pregnancy
- Infections
- Missing insulin doses
- Dehydration
- Low carbohydrate diet
- Pregnancy
- Insulin pump failure (if you use an insulin pump)
SGLT-2 inhibitors and EDKA
SGLT-2 inhibitors increase your risk of EDKA by 150 fold! These medications make you pee out your glucose, which changes your metabolic profile.
It doesn’t seem to matter how long you’ve been on these medications, your risk of EDKA is high.
These medications can cause your glucagon levels to increase, making you more prone to ketosis. Add in decreased insulin sensitivity and higher glucose production from your liver and you have a recipe for disaster. DKA rates with SGLT-2 inhibitors are about 0.1%.
These medications do have benefits for your heart and kidneys, but they’re not without risk.
Other Contributing Factors
In addition to SGLT-2 inhibitors, several other things increase your risk for developing EDKA. If you have type 1 diabetes, you are at higher risk if you are eating a ketogenic diet (high fat, low carbohydrate).
This is because you are not getting enough carbohydrates to provide fuel for your body. It can also be caused by certain medical situations, such as:
- Prolonged fasting
- Severe infections
- Pancreatitis
- Trauma
Insulin resistance is also a contributing factor for ketoacidosis. If you are overweight or obese, you are at higher risk for ketoacidosis, especially if you take a SGLT-2 inhibitor.
Pathophysiology of EDKA
Euglycemic diabetic ketoacidosis (EDKA) occurs when you have an insulin deficiency and your body is producing high levels of counter-regulatory hormones, such as glucagon.
Glucagon causes fat to be broken down, which leads to increased ketone production when you are not making enough insulin.
Starvation ketoacidosis can occur when your body is breaking down fat for fuel.
Ketones can cause metabolic acidosis, even if your blood sugars are normal, because your body is producing acid as a byproduct of fat metabolism.
Lactic acid can also contribute to an elevated anion gap, so this must be evaluated when you are diagnosed with EDKA.
Symptoms of EDKA
Symptoms of EDKA are similar to those of DKA, but they can be missed because your blood sugars are not typically high. You may experience:
- Nausea and vomiting
- Fatigue
- Abdominal pain
- Shortness of breath
EDKA symptoms can develop more slowly than DKA, so it is often missed. If you take a SGLT-2 inhibitor, you are at higher risk for EDKA and should be evaluated promptly if you develop any symptoms.
Because your blood sugars are normal, you may not have polyuria (excessive urine production) or changes in mental status that would alert your healthcare provider to evaluate you for ketoacidosis.
Kussmaul respirations (deep, shallow breathing) can also be present.
Clinical Presentation of EDKA
Patients with euglycemic DKA often present with nausea and vomiting, fatigue, abdominal pain and shortness of breath.
Unlike typical DKA, the symptoms of EDKA develop over a period of days, rather than hours, which can make the diagnosis more challenging.
Because patients with this often have “normal” blood sugars, they may not exhibit increased thirst and frequency of urination, and changes in mental status are often subtle.
This can lead to delays in recognition of severity of illness. You may notice Kussmaul respirations in these patients, which is a clue to the presence of respiratory failure.
How is EDKA Diagnosed ?
The diagnosis of EDKA should be suspected in any patient with metabolic acidosis and ketonuria or ketonemia, even if blood sugars are “normal”.
In fact, the presence of metabolic acidosis and ketonuria or ketonemia in a patient with type 2 diabetes should prompt a measurement of serum beta-hydroxybutyrate levels.
A level > 3 mmol/L is confirmatory for EDKA.
- Serum pH and Ketones: Even if your blood sugar is normal, if your metabolic acidosis and ketones are high, EDKA should be suspected.
- Beta-Hydroxybutyrate Levels: A beta-hydroxybutyrate level over 3 mmol/L is diagnostic for EDKA.
- Anion Gap Metabolic Acidosis: This tells doctors if you have lactic acidosis, which can be caused by sepsis or kidney failure. A low pH of 7.3 or less indicates significant metabolic acidosis.
The presence of an anion gap metabolic acidosis is also supportive of the diagnosis, and other causes of anion gap metabolic acidosis, such as lactic acidosis, should be considered and ruled out.
This includes patients with sepsis and renal failure. The severity of acidosis in EDKA is evident by a pH < 7.3.
Treatment Strategies for EDKA
Treatment for EDKA is serious and needs to be taken very seriously. Here you can do :
Fluid Replacement: You will need 6 to 9 liters of fluids, usually given through an IV at a rate of 1 to 1.5 L/hr. Isotonic saline or lactated Ringer’s solution is used.
Insulin Infusion: You’ll require insulin, beginning with 0.05 to 0.1 U/kg/hour.
Don’t stop the insulin too soon. Once you are hydrated, you will need to be on a combination of dextrose and insulin to keep your blood sugar stable and prevent hypoglycemia.
Note : Always consult your doctor or healthcare provider if you experience these health issues.
Insulin Therapy and Fluid Management
Hypoglycemia is a concern in patients with EDKA, rather than hyperglycemia. I V insulin should be continued until the patient is adequately hydrated, at which time dextroose and insulin should be added to fluids.
This is in contrast to DKA patients with hyperglycemia, in whom insulin can be held for 2-3 hours before being restarted.
Basal insulin can be added 2-3 hours before discontinuing insulin infusion. The dose should be based on weight or the previous insulin infusion rate.
Adding 5% dextrose to fluids is also important to prevent hypoglycemia during recovery.
Fluid resuscitation is the first priority in patients with severe dehydration.
This is usually accomplished with isotonic saline or lactated Ringer’s solution, followed by addition of dextrose and an insulin drip.
Monitoring and Adjustments
Hypoglycemia is a concern in patients with EDKA, so all fluids should include 5% dextrose.
Subcutaneous insulin should be started 2-3 hours before discontinuing insulin infusion.
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Complications and Prognosis
EDKA can lead to serious complications, such as prolonged vomiting, severe dehydration and life-threatening conditions like hypovolemic shock or respiratory failure.
Chronic kidney disease increases your risk and pregnant or young women may do worse.
As with any serious illness, outlook and prognosis depend on several factors, including your overall health, age and underlying conditions.
It is a warning sign of poor health and a need for better management of your diabetes.
However, with recognition and treatment, EDKA is reversible and your health can be restored.
Final Thoughts
Euglycemic diabetic ketoacidosis is a sneaky condition that’s gaining recognition as a significant clinical challenge.
We need to be aware of it and vigilant in our hospitals. Early recognition, accurate diagnosis and treatment are important for managing EDKA and preventing severe consequences.
EDKA is on the rise, and we need to continue educating ourselves about this condition, especially with the SGLT-2 inhibitors.
Once you understand the pathophysiology, clinical features and treatment of EDKA, you’ll be better equipped to recognize and treat it. It’s not a rare condition, and we need to be aware of it to prevent further harm to our patients.
FAQs
What’s the main difference between EDKA and DKA?
EDKA is different from DKA in that it occurs at normal or near normal blood sugars, whereas DKA occurs at high blood sugars in both type 1 and type 2 diabetes.
Why is EDKA misdiagnosed?
EDKA is misdiagnosed because of the lack of hyperglycemia, so clinicians miss ketosis and metabolic acidosis and DKA occurs even when blood sugars are relatively low. This leads to a mis understanding of the patient’s condition.
How do SGLT-2 inhibitors cause EDKA?
SGLT-2 inhibitors cause EDKA by increasing glucose elimination through the kidneys and elevating glucagon levels which in turn increase ketone production.
This can increase the risk of DKA in some patients.
What can patients do to prevent EDKA?
Patients must learn to recognize symptoms to prevent EDKA. They must check their blood sugars and ketones regularly, follow ‘sick day rules’ which is to drink plenty of fluids and carbohydrates and seek medical attention when needed.
References
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- Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: A predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care 2015;38:1638-42.
- Perry RJ, Rabin-Court A, Song JD, et al. Dehydration and insulinopenia are necessary and sufficient for euglycemic ketoacidosis in SGLT2 inhibitor-treated rats. Nat Commun. 2019;10(1):548.
- Svart MV, Voss TS, Bayat M, et al. Rare presentations of ketoacidosis: diabetic ketoalkalosis and ketoacidosis secondary to fasting and muscular dystrophy. Clin Diabetes. 2015;33(1):37-39.
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