From the Guidelines
A beta-hydroxybutyrate level above 3.0 mmol/L is concerning for euglycemic ketoacidosis, especially when accompanied by an anion gap metabolic acidosis and relatively normal blood glucose levels. This condition requires immediate medical attention despite the absence of significant hyperglycemia. The diagnosis and management of euglycemic ketoacidosis involve specific measurement of b-hydroxybutyrate in blood, as recommended by recent guidelines 1. Key points to consider in the diagnosis and management of euglycemic ketoacidosis include:
- Individuals prone to ketosis, such as those with type 1 diabetes or treated with sodium-glucose transport protein 2 inhibitors, should measure ketones in urine or blood if they have unexplained hyperglycemia or symptoms of ketosis 1
- Blood ketone determinations that rely on the nitroprusside reaction should not be used to monitor treatment of ketoacidosis, highlighting the importance of accurate measurement of b-hydroxybutyrate levels 1
- Treatment involves intravenous fluids, insulin therapy, and careful monitoring of electrolytes, particularly potassium. Euglycemic ketoacidosis is most commonly seen in patients taking SGLT2 inhibitors, during pregnancy, with reduced caloric intake, alcohol use, or in patients with type 1 diabetes. The pathophysiology involves continued ketogenesis despite normal glucose levels, often because SGLT2 inhibitors promote urinary glucose excretion while not suppressing lipolysis and ketone production. Clinicians should maintain a high index of suspicion for euglycemic ketoacidosis in at-risk patients presenting with unexplained acidosis, even when glucose levels appear reassuringly normal.
From the Research
Euglycemic Ketoacidosis and Hydroxybutyrate Levels
- The level of hydroxybutyrate that is concerning for euglycemic ketoacidosis is not explicitly stated in most studies, but one case report mentions a ß-hydroxybutyrate concentration of 5150 μmol/L in a patient with euglycemic ketoacidosis 2.
- However, a study on the utility of plasma beta-hydroxybutyrate to define resolution of diabetic ketoacidosis suggests that a plasma BOHB value of <1.5 mmol/L can be used to define resolution of DKA, implying that higher levels may be concerning 3.
- It is essential to note that the diagnosis of euglycemic ketoacidosis is challenging and requires careful evaluation of clinical presentation, laboratory results, and other factors 4, 5.
Risk Factors and Clinical Presentation
- Euglycemic ketoacidosis can occur in patients with or without diabetes, particularly those taking sodium-glucose cotransporter 2 (SGLT-2) inhibitors 6, 2, 5.
- Decreased oral intake, acute illness, fasting, or a perioperative state can increase the risk of euglycemic ketoacidosis in patients taking SGLT-2 inhibitors 5.
- Clinical presentation may include nausea, vomiting, malaise, or metabolic acidosis, and patients should be promptly evaluated for the presence of urine and/or serum ketones 6.