Review Author: JC Alvarenga, MD
Introduction:
What is euglycemic diabetic acidosis (euDKA)? euDKA is defined as diabetic ketoacidosis with a glucose level <250. Patients will present with ketoacidosis (pH < 7.3 or Bicarb < 18), with near-normal or mild hyperglycemia.
What is the issue? The problem with euDKA is that it is often missed due to normal or mildly elevated levels of glucose which can mask the underlying DKA and lead to worse outcomes for patients if missed.
Pathophysiology euDKA:
The pathophysiology of DKA is well known and is characterized by a deficiency of insulin with an excess of counterregulatory hormones (which include Glucagon, corticosteroids, catecholamines, or growth hormone). It is the hormonal imbalances that cause hyperglycemia, which further increases glycogenolysis, hepatic gluconeogenesis, and ketogenesis.
A: Pathophysiology of DKA. B: Pathophysiology of euDKA
euDKA carbohydrate deficiency plays a critical role in its pathophysiology. The counterregulatory hormone production is unabated, causing an increase in the glucagon:insulin ratio and triggering ketogenesis without significant effect or change on hepatic gluconeogenesis and peripheral glucose utilization.
The three most common causes of euDKA are use of SGLT-2 inhibitors, pregnancy, and fasting.
Diagnosis:
euDKA is a diagnosis of exclusion as other forms of ketoacidosis may present with similar presentations. Certain labs must be conducted to differentiate between euDKA and other forms of ketoacidosis. Other forms of ketoacidosis include: Alcoholic Ketoacidosis, Chronic Liver Disease, Starvation Ketosis,
To help differentiate euDKA from alcoholic ketoacidosis, a history of chronic alcoholism, binge alcohol consumption, lack of diabetic history, and HYPOGLYCEMIA will be apparent. Starvation ketosis will differentiate in that the patient also lacks a history of diabetes, has no concurrent illness, has HYPOGLYCEMIA, and a bicarb levels will usually be above 18. As for sepsis, there will be an absence of ketones on lab work up.
Treatment:
Treatment is based on the principles of DKA:
- Insulin to correct metabolic acidosis and anion gap, correction of electrolytes and dehydration
- Dextrose (10% or 5%) must be used with insulin until the acidosis and anion gap has been corrected
- Resolution of DKA
o pH > 7.3 unts
o Bicarb > 15 mmol/L
o Blood Ketone > 0.6 mmol/L
Prevention of euDKA:
Patients who are prescribed SGLT-2 inhibitors must be aware of the risk factors of DKA and explained the symptoms to look out for. Patient education and lifestyle modification should also be taught to help prevent euDKA.
Conclusion:
In conclusion, euDKA is a diagnosis that can be easily missed. If you have a patient presenting with metabolic acidosis in the absence of hyperglycemia and a history of DM, that is either on a SGLT-2i, pregnant, fasting, or has recent illness, it is important to keep in your differentials. Also knowing how to differentiate between euDKA and other causes of ketosis is important, as euDKA is a diagnosis of exclusion.
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References:
Nasa P, Chaudhary S, Shrivastava PK, Singh A. Euglycemic diabetic ketoacidosis: A missed diagnosis. World J Diabetes. 2021 May 15;12(5):514-523. doi: 10.4239/wjd.v12.i5.514. PMID: 33995841; PMCID: PMC8107974.