What is Euglycemic Diabetic Ketoacidosis?

Euglycemic diabetic ketoacidosis (DKA, also known as EDKA) is a serious health condition that can occur in both type 1 and type 2 diabetes. In simple terms, it is a state where your blood sugar levels aren’t too high (less than 250 mg/dL), but your body is still very acidic (arterial pH less than 7.3 and serum bicarbonate less than 18 mEq/L) and has high levels of ketones. Ketones are chemicals your body makes when it breaks down fat for energy, which happens when there isn’t enough insulin to use blood sugar for energy.

DKA is among the most severe and life-threatening complications of diabetes and can be triggered by different conditions. Interestingly, the occurrence of EDKA has increased with the use of a certain type of diabetes medicine called sodium-glucose transporter 2 (SGLT2) inhibitors.

One tricky part about EDKA is that it can often be hard to diagnose since the causes can vary and the blood sugar levels remain normal. This often leads to a delay in diagnosing the condition.

What Causes Euglycemic Diabetic Ketoacidosis?

Several factors can trigger a condition known as EDKA in people with diabetes. In general, EDKA is caused by a state similar to starvation, leading to a condition called ketosis while keeping blood sugar levels normal. Factors that can cause this “starvation-like” state and thus increase the chances of EDKA include not eating enough (anorexia), delayed emptying of the stomach (gastroparesis), fasting, following a diet that’s high in fat and low in carbs (ketogenic diet), and alcohol use disorder. Other factors that can contribute to developing EDKA include pregnancy, pancreatitis, disorders that affect the body’s ability to store glucose (glycogen), surgery, infections, the toxic effects of cocaine, cirrhosis, and the use of an insulin pump.

People with type 1 diabetes who have had weight loss surgery (bariatric surgery) can also have an increased risk of EDKA. In fact, some studies suggest that over 20% of these patients experience EDKA after their surgery.

Another potential cause of EDKA comes from a newer class of drugs used to manage blood sugar in people with diabetes. These medications, known as SGLT2 inhibitors, include drugs like canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. EDKA could be more likely in people with diabetes who take these medications and have a lower body mass and less glycogen, which is stored glucose that your body uses for energy.

Furthermore, certain events can trigger episodes of EDKA. These include surgery, infections, injuries, severe illness, not eating enough, continuous vomiting, delayed stomach emptying, dehydration, and decreased insulin dosages.

Rarely, a person with a condition called diabetic ketoacidosis (DKA) might receive enough extra insulin to reduce their blood sugar levels under 250 mg/dL, which might lead to EDKA.

Risk Factors and Frequency for Euglycemic Diabetic Ketoacidosis

About 2.6% to 3.2% of admissions for a condition called DKA (Diabetic Ketoacidosis) show normal blood sugar levels, also known as euglycemia. It’s also found that using medications called SGLT2 inhibitors can cause DKA in people with type 2 diabetes. The rate of these cases ranges from 0.16 to 0.76 incidents per 1000 patient-years. It is estimated that people with type 2 diabetes who take these drugs are seven times more likely to develop DKA.

About 2.6% to 3.2% of DKA hospital admissions have normal blood sugar levels.
The rate of DKA incidents related to the use of SGLT2 inhibitors in type 2 diabetes patients ranges from 0.16 to 0.76 cases per 1000 patient-years.
Using SGLT2 inhibitors can increase the risk of developing DKA by a factor of seven in patients with type 2 diabetes.
The overall frequency of DKA related to the use of SGLT2 inhibitors is around 0.1%.
In patients with type 1 diabetes taking SGLT2 inhibitors, the chances of DKA can vary between 5% to 12%, but normal blood sugar levels are not always present.
SGLT2 inhibitors are not approved for use in patients with type 1 diabetes.

More information on DKA caused by other factors apart from these drugs in patients with normal blood sugar levels is limited and difficult to obtain.

Signs and Symptoms of Euglycemic Diabetic Ketoacidosis

Euglycemic diabetic ketoacidosis (EDKA) is a condition similar to hyperglycemic DKA, but the symptoms can vary from person to person. Common symptoms are usually nausea, vomiting, difficulties breathing, feeling unwell and tiredness, loss of appetite, fatigue, and abdominal pain. It’s important to note that patients may not feel excessively thirsty or urinate too much, as these are symptoms associated with high blood sugar levels, which these patients may not have. The onset of symptoms might take longer, as the condition requires a gradual process of starvation to induce ketosis and dehydration.

Other factors like infections, stressors like pregnancy, surgery, pancreatitis, alcohol use, or fasting could trigger EDKA. However, not every patient will have these contributing factors.

Nausea
Vomiting
Difficulty breathing
General feeling of fatigue and discomfort
Loss of appetite
Abdominal pain

Patients might also suffer from symptoms like rapid and deep breathing (Kussmaul respiration), which is a way the body tries to compensate for severe metabolic acidosis. Patients may have an unusual fruity smell on their breath due to the release of a substance called acetone.

Faster than normal heart rate (tachycardia), low blood pressure (hypotension), altered state of consciousness, increased skin elasticity (indicated by the skin returning slowly to its normal shape when pinched), and delay in the restoration of color to the skin on being pressed (delayed capillary refill) are all signs of total body fluid loss, indicating severe dehydration.

In severe cases, this kind of body fluid loss and metabolic imbalance can lead to serious conditions like hypovolemic shock, extreme fatigue, respiratory failure, coma, and even death.

Testing for Euglycemic Diabetic Ketoacidosis

If a patient with diabetes is feeling unwell, with symptoms such as general discomfort (malaise), breathing difficulty (dyspnea), feeling sick (nausea), or vomiting, they should undergo a blood test that includes a measurement of blood acidity (serum pH) and the quantity of certain chemicals in their blood or urine (ketone testing).

Initial tests for a condition known as Euglycemic Diabetic Ketoacidosis (EDKA) include the checking of basic electrolytes, blood sugar (glucose), calcium, magnesium, creatinine (a waste product that your kidneys should filter out), urine ketones (chemicals your body produces when it breaks down fat), beta-hydroxybutyric acid (a type of ketone), and lactic acid among other things. They may also conduct a chest radiograph (an X-ray of your chest) and an EKG (a test that records your heart’s electrical activity). Urine screening is helpful as it can detect ketones but not beta-hydroxybutyrate. The typical level of beta-hydroxybutyrate in blood is less than 0.5 mmol/L; however, in EDKA, it’s regularly more than 3 mmol/L.

If there is a possibility of an infection, your doctor may order a CBC (complete blood count) and blood cultures. They may also want to check the concentration of certain substances in your blood (serum osmolality) and toxic alcohols to clear out the possibility of toxic alcohol consumption. Also, they will keep a close eye on your anion gap (a measure of acid balance in your body) to guide diagnosis, treatment, and management.

Typically, a patient with EDKA will have normal blood sugar (less than 250 mg/dL) despite their body’s acidic state (pH less than 7.3), and a lower level of bicarbonate in their blood (a chemical that helps maintain pH balance). To diagnose EDKA, both serum and urine ketones need to be high. Lactic acid could also be high, but it should not be the sole cause for the increase in anion gap. There might be an increase in white blood cells (leukocytosis) but this could be due to infection, stress or other reasons.

Potassium levels vary, but your doctor will be sure to check them before starting treatment since overall body potassium is typically low in EDKA. In conditions of poor nutrition, there can be low magnesium and phosphate levels due to reduced intake and increased losses. Mild low sodium levels may also be present but is generally less severe than the “pseudo-hyponatremia” seen in states with exceedingly high blood sugar.

Treatment Options for Euglycemic Diabetic Ketoacidosis

When a patient comes in severely dehydrated, which is often the case, the first step is to rehydrate them. This process involves giving them fluids, like isotonic saline or a lactated ringers solution, administered through an IV. These fluids help replace water and electrolytes (minerals) in your body that are necessary for key functions. The American Diabetes Association suggests starting with a high rate of fluid during the first 1 to 2 hours.

Next, assuming the patient’s potassium levels are greater than 3.3 mEq/L, doctors will start an insulin infusion. Insulin helps with the regulation of sugar in the blood. As the patient’s blood sugar level will typically be less than 250 mg/dL, sugar (dextrose 5%) is added to the fluids that are being given to prevent too low blood sugar (hypoglycemia) and speed up the process of ketosis clearance. Ketosis is a metabolic state where the body, lacking glucose, burns fat for fuel, producing acids as a waste product. If ketosis persists, doctors might increase the amount of dextrose to 10%.

Close monitoring of potassium is crucial because the body’s total potassium might be depleted. Potassium is an essential mineral that helps nerves and muscles communicate. As such, it may become necessary to give additional potassium and other electrolytes via an IV. Blood sugar levels should be checked every hour and electrolytes roughly every four hours, which is the standard for treating DKA (Diabetic Ketoacidosis, a severe complication of diabetes).

If the patient is on SGLT2 inhibitors (a type of diabetes medication), it is crucial to stop this medication as soon as the diagnosis is made and keep it paused until the patient recovers from the acute illness. Infusions of sodium bicarbonate, a treatment sometimes used to correct the acidity of the blood, are not indicated for this condition. It’s worth noting that even their use in cases of severe acidemia (excessively acidic blood) where the pH level is less than 6.9 is contentious.

Because these patients need attentive heart, and lab monitoring along with frequent adjustments of insulin infusion, they will typically need to be admitted to intensive care (ICU). The IV fluid treatment should continue until the anion gap (a measure of acid in the blood) has closed and the acidosis has resolved. Acidosis is a high level of acid in the blood, which can cause harmful effects if not treated.

When a patient has a medical condition known as anion gap metabolic acidosis, doctors have to consider many possibilities. Some of the issues that could cause this condition are infections like pneumonia, infections of the urinary tract, and presence of bacteria in the blood. These need to be checked and ruled out in the early stage of diagnosis. For patients who complain about stomach pain, possible causes like infections in the abdominal area and pancreatitis need to be considered.

Ingestion of toxic alcohol (like methanol or ethylene glycol), or paraldehyde
Overdose of salicylate
Lactic acidosis (a build-up of lactic acid in the bloodstream)
Starvation ketosis (where the body burns fat because not enough food is available)
Pregnancy

Another factor to note is that the patient could have recently used insulin, which may cause a normal sugar level presentation. This condition can look a lot like something called alcoholic ketoacidosis, but with two major differences: Patients with this condition have diabetes, and those with alcoholic ketoacidosis often drink alcohol excessively and usually have low blood sugar levels. The latter group can be treated successfully with fluids and glucose, without needing insulin.

What to expect with Euglycemic Diabetic Ketoacidosis

Most patients with EDKA, a serious health condition, usually improve with quick detection and proper treatment. However, a delayed diagnosis and inadequate treatment, notably rehydration without the provision of dextrose/insulin, can result in persistent acidosis (a build-up of acid in the body), vomiting, and an extended stay in the hospital.

Prognosis, or the expected outcome, is generally worse for small children and pregnant women. In severe and rare cases, patients can suffer from respiratory failure (inability to breathe adequately), hypovolemic shock (a severe drop in blood volume), fall into a coma, or even succumb to the illness. Deaths from EDKA are rare, but pregnant women face a higher risk of mortality compared to the general population.

Possible Complications When Diagnosed with Euglycemic Diabetic Ketoacidosis

Euglycemic DKA (a type of diabetic ketoacidosis where blood sugar levels are not high) can cause numerous unpleasant and dangerous health issues in patients. These conditions could include persistent vomiting, dehydration, low blood sugar (hypoglycemia), hypovolemic shock (a severe fluid loss that makes the heart unable to pump enough blood to your body), breathing failure, brain swelling (cerebral edema), unconsciousness, seizures, infections, and blood clots. Extra severe consequences might be heart attacks or even death. For pregnant women, Euglycemic DKA raises the risk of death for both the mother and the baby (up to 9%).

Here’s a summary of potential health issues:

Persistent vomiting
Dehydration
Low blood sugar (Hypoglycemia)
Hypovolemic shock
Respiratory failure
Brain swelling (Cerebral edema)
Unconsciousness (Coma)
Seizures
Infections
Blood clots (Thrombosis)
Heart attacks (Myocardial infarction)
Potential death

Remember, Euglycemic DKA also increases the risk of death for pregnant women and their babies.

Preventing Euglycemic Diabetic Ketoacidosis

People with diabetes, particularly during times of illness or when experiencing feelings of nausea, should be very careful to regularly check their capillary or urine ketone levels. This can help them detect a condition called Euglycemic Diabetic Ketoacidosis, or EDKA, early on before it becomes serious.

Even though a group of drugs known as SGLT2 inhibitors have been found to have additional positive effects on heart and kidney health, they are not advised for use in managing patients with Type 1 Diabetes Mellitus (T1DM). This is because there is a high risk that these patients could develop EDKA when they are taking these medications.

Frequently asked questions

Euglycemic Diabetic Ketoacidosis (EDKA) is a serious health condition that occurs when blood sugar levels are not too high (less than 250 mg/dL), but the body is still very acidic (arterial pH less than 7.3 and serum bicarbonate less than 18 mEq/L) and has high levels of ketones. It can occur in both type 1 and type 2 diabetes.

About 2.6% to 3.2% of admissions for a condition called DKA (Diabetic Ketoacidosis) show normal blood sugar levels, also known as euglycemia.

The signs and symptoms of Euglycemic Diabetic Ketoacidosis (EDKA) include: - Nausea - Vomiting - Difficulty breathing - General feeling of fatigue and discomfort - Loss of appetite - Abdominal pain Patients with EDKA may also experience additional symptoms such as: - Rapid and deep breathing (Kussmaul respiration) - Unusual fruity smell on breath due to the release of acetone - Faster than normal heart rate (tachycardia) - Low blood pressure (hypotension) - Altered state of consciousness - Increased skin elasticity (indicated by slow return to normal shape when pinched) - Delayed capillary refill (delay in restoration of color to skin when pressed) In severe cases, EDKA can lead to serious conditions including: - Hypovolemic shock - Extreme fatigue - Respiratory failure - Coma - Death It's important to note that not all patients with EDKA will have the same symptoms, as they can vary from person to person. Additionally, patients with EDKA may not experience excessive thirst or increased urination, which are commonly associated with high blood sugar levels. The onset of symptoms in EDKA may also be slower compared to hyperglycemic DKA, as it requires a gradual process of starvation to induce ketosis and dehydration.

Euglycemic Diabetic Ketoacidosis (EDKA) can be caused by several factors, including not eating enough (anorexia), delayed emptying of the stomach (gastroparesis), fasting, following a diet that's high in fat and low in carbs (ketogenic diet), alcohol use disorder, pregnancy, pancreatitis, disorders that affect the body's ability to store glucose (glycogen), surgery, infections, the toxic effects of cocaine, cirrhosis, the use of an insulin pump, weight loss surgery in people with type 1 diabetes, and the use of certain medications called SGLT2 inhibitors.

The doctor needs to rule out the following conditions when diagnosing Euglycemic Diabetic Ketoacidosis: 1. Ingestion of toxic alcohol (like methanol or ethylene glycol), or paraldehyde 2. Overdose of salicylate 3. Lactic acidosis (a build-up of lactic acid in the bloodstream) 4. Starvation ketosis (where the body burns fat because not enough food is available) 5. Pregnancy

The types of tests needed for Euglycemic Diabetic Ketoacidosis (EDKA) include: - Blood test to measure blood acidity (serum pH) - Blood test to measure the quantity of certain chemicals in the blood or urine (ketone testing) - Checking of basic electrolytes, blood sugar (glucose), calcium, magnesium, creatinine, urine ketones, beta-hydroxybutyric acid, and lactic acid - Chest radiograph (X-ray of the chest) - EKG (test that records heart's electrical activity) - CBC (complete blood count) and blood cultures if there is a possibility of infection - Serum osmolality and toxic alcohol testing to rule out toxic alcohol consumption - Monitoring of anion gap to guide diagnosis, treatment, and management - Checking potassium levels before starting treatment, as overall body potassium is typically low in EDKA - Monitoring blood sugar levels and electrolytes every hour and every four hours, respectively, during treatment - Close monitoring of potassium levels and possible administration of additional potassium and electrolytes via IV - Stopping SGLT2 inhibitors medication if the patient is on it - Admitting the patient to intensive care (ICU) for attentive monitoring and adjustment of insulin infusion - Continuing IV fluid treatment until the anion gap has closed and the acidosis has resolved.

Euglycemic Diabetic Ketoacidosis is treated by rehydrating the patient with fluids administered through an IV, such as isotonic saline or a lactated ringers solution. Insulin infusion is started if the patient's potassium levels are greater than 3.3 mEq/L. Sugar (dextrose 5%) is added to the fluids to prevent low blood sugar and speed up the process of ketosis clearance. Close monitoring of potassium and electrolytes is crucial, and additional potassium and electrolytes may be given via an IV if necessary. The patient should be admitted to intensive care for attentive monitoring and frequent adjustments of insulin infusion. The IV fluid treatment should continue until the anion gap has closed and the acidosis has resolved. Sodium bicarbonate infusions are not indicated for this condition.

The side effects when treating Euglycemic Diabetic Ketoacidosis include: - Persistent vomiting - Dehydration - Low blood sugar (Hypoglycemia) - Hypovolemic shock - Respiratory failure - Brain swelling (Cerebral edema) - Unconsciousness (Coma) - Seizures - Infections - Blood clots (Thrombosis) - Heart attacks (Myocardial infarction) - Potential death It is important to note that for pregnant women, Euglycemic DKA raises the risk of death for both the mother and the baby (up to 9%).

The prognosis for Euglycemic Diabetic Ketoacidosis (EDKA) is generally good with quick detection and proper treatment. However, a delayed diagnosis and inadequate treatment can lead to persistent acidosis, vomiting, and an extended hospital stay. In severe cases, patients can suffer from respiratory failure, hypovolemic shock, coma, or even death. Pregnant women face a higher risk of mortality compared to the general population.

An endocrinologist or a diabetes specialist.