From the Guidelines
Euglycemic diabetic ketoacidosis (DKA) is a complex condition characterized by ketoacidosis without significant hyperglycemia, resulting from insulin deficiency and elevated counter-regulatory hormones, as described in the pathogenesis of hyperglycemic crises in diabetes 1. The pathophysiology of euglycemic DKA involves a reduction in the net effective action of circulating insulin coupled with a concomitant elevation of counterregulatory hormones, such as glucagon, catecholamines, cortisol, and growth hormone, leading to increased hepatic and renal glucose production and impaired glucose utilization in peripheral tissues. Some key factors that contribute to the development of euglycemic DKA include:
- Insulin deficiency combined with elevated counter-regulatory hormones, leading to increased lipolysis and ketone body production
- SGLT2 inhibitor medications, which cause urinary glucose excretion, preventing hyperglycemia while not stopping ketogenesis
- Reduced carbohydrate intake or starvation, which decreases available glucose
- Pregnancy, which increases insulin resistance and accelerates ketone production
- Alcohol consumption, which inhibits gluconeogenesis
- Partial insulin treatment, which may control glucose but be insufficient to suppress ketogenesis The management of euglycemic DKA should focus on stopping SGLT2 inhibitors (if applicable), administering IV insulin and dextrose to maintain glucose levels between 150-200 mg/dL, correcting fluid deficits, and addressing electrolyte imbalances, particularly potassium, as these interventions can help mitigate morbidity, mortality, and improve quality of life 1.
From the Research
Pathophysiology of Euglycemic DKA
The pathophysiology of euglycemic diabetic ketoacidosis (DKA) involves a complex interplay of factors, including:
- Relative or absolute carbohydrate deficit 2
- Milder degree of insulin deficiency or resistance 2
- Increased glucagon/insulin ratio 2
- Enhanced lipolysis and ketone body reabsorption 3
- Imbalance in glucagon/insulin levels due to stimulation of pancreatic alpha cells and inhibition of beta cells by sodium-glucose cotransporter-2 inhibitors (SGLT2i) 3
Causes of Euglycemic DKA
Euglycemic DKA can occur in patients with type 1 or type 2 diabetes mellitus, and can be caused by various factors, including:
- Sodium/glucose cotransporter-2 inhibitors (SGLT2i) 2, 4, 3, 5
- Pregnancy 2, 4, 6
- Fasting 2, 6
- Bariatric surgery 2
- Gastroparesis 2
- Insulin pump failure 2
- Cocaine intoxication 2
- Chronic liver disease 2, 4, 6
- Glycogen storage disease 2, 4
- Low carbohydrate or ketogenic diet 3
- Obesity 3
- Malignancy 3
- Perioperative fasting 3
- Pancreatic etiology 3
Diagnostic Challenges
Euglycemic DKA can be challenging to diagnose due to the absence of hyperglycemia, and can be misdiagnosed as other conditions 4, 6, 5. The diagnostic workup includes:
- Arterial blood gas for metabolic acidosis 2
- Serum ketones 2, 6
- Exclusion of other causes of high anion gap metabolic acidosis 2
- Venous blood gas for serum pH, bicarbonate, and ketones 6
Treatment
The treatment of euglycemic DKA is similar to that of DKA, and includes:
- Correction of dehydration, electrolytes deficit, and insulin replacement 2
- Use of dextrose-containing fluids to accompany intravenous insulin and correct metabolic acidosis, ketonemia, and prevent hypoglycemia 2
- Monitoring of anion gap and ketones to guide insulin and fluid management 5
- Slower transition to subcutaneous insulin to prevent relapse 5