A 58-year-old man with a 10-year history of type 2 diabetes mellitus is brought to the emergency department by his wife due to severe nausea, vomiting, and generalized weakness for the past 48 hours. He recently had a viral upper respiratory infection and has had poor oral intake. His medications include metformin, empagliflozin, and lisinopril. Vital signs show a blood pressure of mmHg, heart rate of /min, and respiratory rate of /min. Physical examination reveals dry mucous membranes.
Laboratory studies show:
| Laboratory Test | Result | Reference Range |
|---|---|---|
| Serum sodium | mEq/L | mEq/L |
| Serum potassium | mEq/L | mEq/L |
| Serum chloride | mEq/L | mEq/L |
| Serum bicarbonate | mEq/L | mEq/L |
| Blood urea nitrogen | mg/dL | mg/dL |
| Serum creatinine | mg/dL | mg/dL |
| Serum glucose | mg/dL | mg/dL |
| Serum ketones | Positive | Negative |
Arterial blood gas analysis reveals a pH of .
Which of the following is the most direct underlying metabolic mechanism precipitating this patient's primary acid-base disturbance?
- Increased ratio of circulating glucagon to insulinCevap
- BInhibition of mitochondrial glycerophosphate dehydrogenase
- CComplete cessation of endogenous pancreatic insulin secretion
- DDecreased renal tubular excretion of unmeasured organic anions
- EDecreased aldosterone synthesis resulting in impaired distal tubular acid secretion
Cevap
Increased ratio of circulating glucagon to insulin
The patient presents with a high anion-gap metabolic acidosis ( mEq/L) and positive serum ketones, diagnostic of diabetic ketoacidosis (DKA). However, his blood glucose is unexpectedly low for standard DKA presentation ( mg/dL). This presentation is characteristic of euglycemic DKA, a known, life-threatening adverse effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors like empagliflozin. SGLT2 inhibitors block proximal tubular glucose reabsorption, resulting in massive, continuous glycosuria. This artificially lowers serum glucose, which in turn decreases pancreatic beta-cell insulin secretion and strongly stimulates alpha-cell glucagon release. The resulting high glucagon-to-insulin ratio promotes severe lipolysis, releasing free fatty acids that undergo hepatic oxidation into ketone bodies. The physiologic stress of his recent viral infection and subsequent poor oral intake further exacerbated this dangerous glucagon-heavy metabolic state.
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Anahtar Kavram
Sodium-glucose cotransporter-2 (SGLT2) inhibitors can precipitate euglycemic diabetic ketoacidosis by inducing profound glycosuria, creating a state of relative insulin deficiency and marked glucagon excess that drives ketogenesis.