Diabetic ketoacidosis (DKA) is a severe metabolic complication of diabetes that traditionally signals a profound lack of insulin, marked by dangerously high blood sugar levels, a buildup of acidic substances, and dehydration. DKA is typically diagnosed when blood glucose measurements exceed 250 mg/dL. However, a challenging variant exists where the characteristic high blood sugar is absent, creating a diagnostic dilemma. This condition, Euglycemic Diabetic Ketoacidosis (EDKA), is a serious life-threatening event that can be easily missed because the classic warning sign of hyperglycemia is not present.
Defining Euglycemic DKA
Euglycemic Diabetic Ketoacidosis is defined by a triad of clinical findings: a high level of ketones in the blood or urine, a state of metabolic acidosis, and a blood glucose level that is normal or only mildly elevated, typically remaining below 250 mg/dL. The term “euglycemic” means “normal blood sugar,” which contrasts sharply with the expectation of DKA.
The underlying mechanism of EDKA involves a severe imbalance between key hormones, specifically a relative or absolute deficiency of insulin coupled with an excess of counter-regulatory hormones like glucagon. When insulin’s action is severely limited, the body mistakenly thinks it is starving, even if blood sugar is adequate. This perceived starvation state forces the body to switch its primary fuel source from glucose to fat. The liver rapidly breaks down fatty acids, a process called lipolysis, which generates an excessive amount of acidic byproducts known as ketone bodies. This overwhelming production of ketones leads to a drop in the blood’s pH, causing the life-threatening metabolic acidosis that defines the condition.
Primary Triggers and Risk Factors
The most significant and increasingly common trigger for EDKA is the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors, which include drugs like dapagliflozin and empagliflozin. These drugs work by causing the kidneys to excrete excess glucose into the urine, which lowers blood sugar. This mechanism can inadvertently promote the conditions for EDKA.
By forcing glucose out of the body, SGLT2 inhibitors create a state of perceived carbohydrate deprivation, which lowers insulin levels and increases the ratio of glucagon to insulin. This hormonal shift is the primary driver of ketogenesis. The resulting glucose loss through the urine also contributes to dehydration and volume depletion, which can further stimulate counter-regulatory hormones and worsen the ketoacidosis.
Other Triggers
A variety of other physiological stressors and lifestyle factors can also precipitate EDKA, especially in diabetic patients with reduced insulin reserves. Any condition that leads to reduced carbohydrate intake or increased metabolic demand can be a trigger. These factors include:
- Prolonged fasting (e.g., before surgery or due to a restrictive diet like a very low-carbohydrate or ketogenic regimen).
- Acute illness or infection (e.g., pneumonia or a urinary tract infection).
- Reduced insulin dosage or pump malfunction in patients with type 1 diabetes.
- Pregnancy and acute alcohol consumption.
Recognising the Symptoms
Recognizing the clinical signs of EDKA can be challenging because the classic symptoms of high blood sugar are often absent, leading to delayed diagnosis. Patients may not experience the excessive thirst (polydipsia) or frequent urination (polyuria) that typically prompt emergency care.
The symptoms that manifest are primarily related to the metabolic acidosis and the accompanying dehydration. Patients frequently report severe nausea, persistent vomiting, and intense abdominal pain. Generalized malaise, profound fatigue, and lethargy are common, reflecting the body’s inability to use energy efficiently. A distinct physical sign is Kussmaul breathing, characterized by deep, labored, and rapid respirations, as the body attempts to expel carbon dioxide to compensate for the high acid load in the blood. Since the blood sugar is not high, it is imperative for patients with diabetes who experience these symptoms to check for ketones, even if their glucose reading is normal.
Emergency Treatment and Management
EDKA is a medical emergency that requires immediate hospitalization and a specialized treatment approach. The primary goals of management are to correct the profound dehydration, halt the excessive production of ketones, and resolve the metabolic acidosis. This process begins with aggressive fluid resuscitation using intravenous (IV) solutions, often isotonic saline, to restore the body’s volume status and improve kidney function.
Once dehydration is addressed and a safe potassium level is confirmed, an insulin infusion is initiated to suppress lipolysis and stop the liver from producing further ketones. This step is non-negotiable. A crucial difference from standard DKA management is the necessity of administering dextrose simultaneously with the insulin infusion. Since the blood glucose level is already normal or low, IV fluids containing dextrose, such as 5% or 10% dextrose in water, must be used to prevent hypoglycemia while the insulin infusion works to clear the ketones. SGLT2 inhibitors must be discontinued immediately upon diagnosis and held until the patient has fully recovered.