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Euglycemic Ketoacidosis - Causes & Treatment

Euglycemic ketoacidosis is a rare but dangerous metabolic condition characterized by elevated ketone bodies and acidosis despite normal blood sugar levels.

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Things worth knowing about "Euglycemic Ketoacidosis"

Euglycemic ketoacidosis is a rare but dangerous metabolic condition characterized by elevated ketone bodies and acidosis despite normal blood sugar levels.

What is Euglycemic Ketoacidosis?

Euglycemic ketoacidosis (also abbreviated as euDKA) is a rare but potentially life-threatening variant of diabetic ketoacidosis (DKA). Unlike classic DKA, blood glucose levels in euglycemic ketoacidosis remain normal or only mildly elevated (typically below 250 mg/dL or 13.9 mmol/L). At the same time, the concentration of ketone bodies in the blood is elevated, and a metabolic acidosis (acidification of the blood) is present. Because blood sugar is not significantly elevated, the condition is frequently overlooked or diagnosed with delay.

Causes

Euglycemic ketoacidosis can be triggered by a variety of factors:

SGLT-2 inhibitors: The most common cause in recent years is the use of so-called SGLT-2 inhibitors (e.g., empagliflozin, dapagliflozin, canagliflozin), a class of diabetes medications. These drugs promote the excretion of glucose through the kidneys and can thereby favour ketone body production without significantly raising blood sugar.
Fasting or severely reduced carbohydrate intake: Insufficient caloric intake, particularly before surgery or during dietary changes, can increase ketone production.
Alcohol consumption: Excessive alcohol intake can impair hepatic glucose production and simultaneously promote ketone formation.
Insulin deficiency or reduced insulin dose: Especially in type 1 diabetes, but also in type 2 diabetes, an insufficient insulin supply can stimulate ketone production.
Pregnancy: During pregnancy, there is an increased susceptibility to ketone formation, particularly with inadequate food intake.
Intercurrent illness: Infections, surgical procedures, or other physical stressors can act as triggers.

Symptoms

The symptoms of euglycemic ketoacidosis are often non-specific and can easily be confused with other conditions. Typical complaints include:

Nausea and vomiting
Abdominal pain
General malaise and weakness
Rapid or deep breathing pattern (Kussmaul breathing)
Confusion or drowsiness
Noticeably sweet or fruity breath odor (caused by acetone)

Because blood sugar is not significantly elevated, classic signs of hyperglycemia such as excessive thirst or frequent urination are often absent.

Diagnosis

The diagnosis of euglycemic ketoacidosis requires a high degree of clinical vigilance. The following diagnostic measures are essential:

Blood gas analysis: Evidence of metabolic acidosis (pH < 7.3, bicarbonate < 15 mmol/L)
Ketone measurement: Elevated beta-hydroxybutyrate levels in the blood (> 3 mmol/L) or ketonuria in the urine
Blood glucose measurement: Normal or only mildly elevated blood glucose (below 250 mg/dL)
Laboratory values: Electrolytes, renal function, complete blood count, and inflammatory markers
Medical history: Targeted inquiry about medications (especially SGLT-2 inhibitors), dietary habits, and pre-existing conditions

Treatment

Treatment of euglycemic ketoacidosis is carried out in a hospital setting and involves several pillars:

Discontinuation of the SGLT-2 inhibitor: In medication-induced euDKA, the causative drug must be stopped immediately.
Insulin administration: Insulin is essential to halt ketone body production. Because blood glucose is not elevated, glucose must be infused simultaneously to prevent hypoglycemia.
Fluid replacement: Correction of fluid deficits through intravenous infusions.
Electrolyte correction: Particular attention must be paid to potassium, which can drop under insulin therapy and must be supplemented accordingly.
Treatment of the underlying cause: Infections or other triggers are treated specifically.

Prevention and Patient Guidance

Patients taking SGLT-2 inhibitors should be informed about the risk of euglycemic ketoacidosis. The following precautions are recommended:

Discontinue the SGLT-2 inhibitor before planned surgery or prolonged fasting periods in a timely manner (usually 3–4 days in advance, following medical advice).
Contact a physician in case of illness, significantly reduced food intake, or intense physical exertion.
Check ketone levels at home with a monitoring device if symptoms occur.
Never drastically reduce the insulin dose without medical supervision.

References

Rawla P. et al. - Euglycemic Diabetic Ketoacidosis: A Review. Medical Science Monitor, 2017. PubMed PMID: 28223411.
European Medicines Agency (EMA) - SGLT2 inhibitors: information on potential risk of diabetic ketoacidosis. EMA/230698/2015.
Pasquel F.J., Umpierrez G.E. - Hyperosmolar Hyperglycemic State: A Historic Review of the Clinical Presentation, Diagnosis, and Treatment. Diabetes Care, 2014. DOI: 10.2337/dc14-0984.

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