A 55-year-old woman with type 2 diabetes on empagliflozin for three weeks presents with nausea, vomiting, and abdominal pain. Blood glucose is 168 mg/dL, pH 7.24, bicarbonate 14 mEq/L, and urine ketones are strongly positive. Which mechanism best explains this presentation?
- A SGLT2 inhibition causes direct pancreatic beta-cell glucotoxicity
- B SGLT2 inhibition blocks renal tubular reabsorption of bicarbonate
- C Increased glucagon-to-insulin ratio promotes hepatic ketogenesis ✓
- D Empaglipflozin directly uncouples mitochondrial oxidative phosphorylation
Correct answer: C. Increased glucagon-to-insulin ratio promotes hepatic ketogenesis
Explanation
SGLT2 inhibitors cause glucosuria, lowering insulin and raising glucagon. The resulting high glucagon-to-insulin ratio promotes lipolysis and hepatic ketogenesis, producing euglycemic DKA. Blood glucose may be only mildly elevated. The drug does not cause bicarbonate wasting or mitochondrial uncoupling. Beta-cell glucotoxicity is not an acute mechanism.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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