Causes of Euglycemic Diabetic Ketoacidosis

Primary Pathophysiologic Mechanism

Euglycemic diabetic ketoacidosis (euglycemic DKA) is caused by insulin deficiency in the presence of factors that maintain relatively normal blood glucose levels, most commonly SGLT2 inhibitor use, reduced food intake, pregnancy, alcohol consumption, and liver failure 1
The American College of Endocrinology recommends recognizing that euglycemic DKA requires absolute or relative insulin deficiency combined with conditions that prevent hyperglycemia from developing 2
Insulin deficiency leads to unrestrained lipolysis and hepatic ketone production, resulting in metabolic acidosis 3, 2

SGLT2 inhibitors are now the leading cause of euglycemic DKA, particularly as their use expands beyond diabetes to heart failure and chronic kidney disease, according to the American Heart Association 4, 5
The mechanism involves multiple pathways, including reduction in insulin doses due to improved glycemic control, increased glucagon levels leading to enhanced lipolysis and ketone production, and decreased renal clearance of ketones 5, 3
Risk is present in both diabetic and non-diabetic patients taking SGLT2 inhibitors, with non-diabetic patients on these medications for heart failure being particularly vulnerable when they experience decreased oral intake, fasting, or acute illness 5

The American Diabetes Association identifies key risk factors that predispose to euglycemic DKA, including SGLT2 inhibitor therapy, acute febrile illness, reduced caloric intake due to illness or surgery, dehydration, excessive alcohol intake, and presence of autoimmunity in patients thought to have type 2 diabetes 1, 2
Pregnancy, particularly in patients with type 1 diabetes, carries significant risk for euglycemic DKA, with up to 2% of pregnancies with pregestational diabetes being complicated by DKA 1
Heavy alcohol consumption or alcohol abuse promotes euglycemic DKA through impaired gluconeogenesis leading to relative hypoglycemia, enhanced ketogenesis from alcohol metabolism, and often combined with reduced food intake 1, 2
Liver failure or chronic liver disease impairs hepatic glucose production while ketogenesis continues, maintaining lower glucose levels despite ongoing ketoacidosis 1

Check blood or urine ketones in any ill diabetic patient regardless of blood glucose level, particularly those on SGLT2 inhibitors, pregnant patients, or those with reduced oral intake, as recommended by the American Association of Clinical Endocrinologists 1