Are ketones elevated in euglycemic (normal blood sugar level) Diabetic Ketoacidosis (DKA)?

From the Guidelines

Yes, ketones are elevated in euglycemic diabetic ketoacidosis (DKA). Euglycemic DKA is characterized by the presence of metabolic acidosis and increased ketone bodies despite normal or only mildly elevated blood glucose levels (typically less than 250 mg/dL) 1. This condition most commonly occurs in patients with type 1 diabetes who are taking SGLT-2 inhibitors like empagliflozin, dapagliflozin, or canagliflozin. Other risk factors include pregnancy, reduced caloric intake, alcohol consumption, and insulin dose reduction. The pathophysiology involves continued ketogenesis despite relatively normal glucose levels, as SGLT-2 inhibitors promote urinary glucose excretion while not preventing the hormonal changes that lead to ketone production.

Key Points to Consider

• When diagnosing euglycemic DKA, clinicians should measure serum ketones (beta-hydroxybutyrate) rather than relying solely on urine ketones, as serum measurements are more sensitive and specific 1.
• Treatment follows standard DKA protocols with intravenous fluids, insulin therapy, and electrolyte replacement, though patients may require more careful glucose monitoring to prevent hypoglycemia during treatment 1.
• The management goals include restoration of circulatory volume and tissue perfusion, resolution of hyperglycemia, and correction of electrolyte imbalance and acidosis 1.
• Ketones are typically elevated in euglycemic DKA, and their measurement is crucial for diagnosing and monitoring the condition. Some key considerations for treatment include:
• Providing adequate fluid replacement
• Frequent bedside testing
• Appropriate treatment of any concurrent infections
• Appropriate follow-up to avoid recurrent DKA 1. It is essential to individualize treatment based on a careful clinical and laboratory assessment, as there is considerable variability in the presentation of DKA and hyperosmolar hyperglycemic states 1.

From the Research

Definition and Characteristics of Euglycemic DKA

• Euglycemic diabetic ketoacidosis (EDKA) is a clinical triad comprising increased anion gap metabolic acidosis, ketonemia or ketonuria, and normal blood glucose levels <200 mg/dL 2.
• EDKA is characterized by milder degrees of hyperglycemia with blood glucose level < 200 mg/dL, which can result in delayed diagnosis and treatment with potential for adverse metabolic consequences 3.
• The condition is a diagnostic challenge as euglycemia masquerades the underlying diabetic ketoacidosis, requiring a high clinical suspicion and ruling out other diagnoses 2.

Etiologies of Euglycemic DKA

• Possible etiologies of euglycemic DKA include recent use of insulin, decreased caloric intake, heavy alcohol consumption, chronic liver disease, glycogen storage disorders, and the use of sodium glucose cotransporter 2 (SGLT2) inhibitors 4, 3, 5.
• Other causes associated with EDKA include pregnancy, decreased caloric intake, heavy alcohol use, insulin use prior to hospital admission, cocaine abuse, pancreatitis, sepsis, chronic liver disease, and liver cirrhosis 3.
• SGLT-2 inhibitors can cause a low level of ambient ketones, and any additional ketone formation predisposes to ketoacidosis, while the agent's glycosuric effect limits hyperglycemia 5.

Diagnosis and Management of Euglycemic DKA

• Diagnosis of EDKA involves laboratory assessment, including venous blood gas for serum pH, bicarbonate, and ketones 6.
• Management includes rapid correction of dehydration, correction of electrolyte abnormalities, and use of insulin drip until the anion gap and bicarbonate levels normalize 3.
• Increased glucose administration using higher percentages of dextrose (10 or 20%) may be required to facilitate the concomitant administration of the relatively large amounts of insulin needed to correct the severe acidosis in these patients 3.
• The immediate use of a glucose-containing intravenous fluid can induce endogenous insulin secretion and stop ketogenesis in euglycemic DKA 5.