SGLT2 inhibitors have a unique risk of euglycemic diabetic ketoacidosis. During which circumstances is this risk heightened?

• A. Illness, dehydration, or low insulin levels
• B. Regular exercise
• C. Sleep deprivation
• D. Dehydration alone without illness

Answer: (A)

SGLT2 inhibitors can trigger ketoacidosis without high blood glucose because they cause glucose to be lost in the urine, which lowers blood sugar while still allowing fat breakdown and ketone production to rise. The risk is greatest in states that promote ketogenesis or reduce insulin activity: illness, dehydration, or low insulin levels.

Illness raises stress hormones (glucagon, cortisol, catecholamines) and often reduces oral intake, both of which push the body toward producing ketones. Dehydration worsens the situation by concentrating ketones and reducing renal clearance, further tipping the balance toward ketoacidosis. When insulin levels are low or relative insulin deficiency exists, the normal suppression of fat breakdown is lost, increasing ketone formation even if glucose isn’t markedly elevated. This combination explains why euglycemic DKA can occur with SGLT2 inhibitors.

Regular exercise and sleep deprivation can affect metabolism but do not create the same strongest combination of factors (illness, dehydration, and low insulin) that heighten this specific risk. Dehydration alone without another trigger isn’t as reliably risky as the trio mentioned.