What are the risk factors for euglycemic (normal blood glucose level) Diabetic Ketoacidosis (DKA)?

From the Guidelines

Euglycemic diabetic ketoacidosis (DKA) is primarily associated with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with diabetes, particularly those with type 1 diabetes or insulin-deficient type 2 diabetes, with a risk 5-17 times higher than those not treated with SGLT inhibitors 1. The key risk factors for euglycemic DKA include:

• Very-low-carbohydrate diets
• Prolonged fasting
• Dehydration
• Excessive alcohol intake
• Other common precipitating factors, such as recent surgery or acute illness To prevent euglycemic DKA, patients on SGLT2 inhibitors should:

• Temporarily discontinue the medication during periods of illness, fasting, or before surgery
• Monitor ketone levels, especially when blood glucose is <250 mg/dL and symptoms of DKA are present, as up to a third of people treated with SGLT2 inhibitors who developed DKA present with glucose levels <200 mg/dL (11.1 mmol/L) 1
• Maintain adequate hydration and carbohydrate intake It is essential to note that normal blood glucose levels do not rule out DKA in patients taking SGLT2 inhibitors, and diagnosis requires checking for ketones and assessing acid-base status, even when glucose levels are near normal 1. The mechanism behind euglycemic DKA involves SGLT2 inhibitors promoting urinary glucose excretion, which can lead to ketosis without significant hyperglycemia, allowing ketone production to continue even when blood glucose levels are not markedly elevated 1.

From the FDA Drug Label

In patients with type 1 diabetes mellitus, dapagliflozin significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL).

The risk factors for euglycemic Diabetic Ketoacidosis (DKA) include:

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus
• Pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery)
• Precipitating conditions such as:
  • Under-insulinization due to insulin dose reduction or missed insulin doses
  • Acute febrile illness
  • Reduced caloric intake
  • Ketogenic diet
  • Surgery
  • Volume depletion
  • Alcohol abuse 2

From the Research

Risk Factors for Euglycemic Diabetic Ketoacidosis (DKA)

The risk factors for euglycemic DKA include:

• Recent use of insulin 3
• Decreased caloric intake 3
• Heavy alcohol consumption 3
• Chronic liver disease 3
• Glycogen storage disorders 3
• DKA in pregnancy 3
• Use of sodium glucose cotransporter 2 (SGLT2) inhibitors 3, 4, 5, 6
• Perioperative fasting 4
• Pancreatic etiology 4
• Low carbohydrate or ketogenic diet 4, 7
• Obesity 4
• Malignancy 4
• Severe carbohydrate restriction 7
• Fasting 5
• Surgery 5
• Acute infection 5
• Insulin deprivation (endogenous or exogenous) 5

Precipitants of Euglycemic DKA

Precipitants of euglycemic DKA include:

• Nausea, abdominal pain, and vomiting 5
• Low pH and high β-hydroxybutyrates 5
• Avoidance of euDKA risk states in SGLT2i users 5

Diagnostic Challenges

Diagnostic challenges of euglycemic DKA include:

• Absence of hallmark hyperglycemia seen in diabetic ketoacidosis (DKA) 6
• Pseudonormoglycemia 3
• High anion-gap metabolic acidosis 7
• Elevated insulin levels 7
• High ketone levels in urine and blood 7