A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 55-year-old male is hospitalized for acute heart failure. The patient has a 20-year history of alcoholism and was diagnosed with diabetes mellitus type 2 (DM2) 5 years ago. Physical examination reveals ascites and engorged paraumbilical veins as well as 3+ pitting edema around both ankles. Liver function tests show elevations in gamma glutamyl transferase and aspartate transaminase (AST). Of the following medication, which most likely contributed to this patient's presentation?
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A
GlargineIncorrect. Insulin glargine is generally safe in heart failure and does not cause the fluid retention typical of TZDs.
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B
GlipizideIncorrect. Sulfonylureas like glipizide cause hypoglycemia and weight gain but are not classically associated with fluid retention or precipitating heart failure.
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C
MetforminIncorrect. Metformin should be avoided in unstable CHF (lactic acidosis risk) but does not directly cause fluid retention or worsening heart failure.
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D
PioglitazoneCorrect. Pioglitazone (a TZD/PPAR-γ agonist) causes sodium and fluid retention via renal ENaC activation, precipitating or worsening heart failure.
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E
AcarboseIncorrect. Acarbose is an α-glucosidase inhibitor that causes GI side effects (flatulence, diarrhea) but does not cause fluid retention or precipitate heart failure.
↑ Tap an answer to reveal the reasoning
Answer: D. Thiazolidinediones (TZDs) — pioglitazone and rosiglitazone — are PPAR-γ agonists that improve insulin sensitivity. Their major adverse effects include fluid retention/edema, weight gain, and worsening congestive heart failure, plus a black-box warning against use in NYHA Class III or IV heart failure. This patient's acute heart failure presentation (ascites, paraumbilical varices, 3+ pitting edema, AST elevation) in a known diabetic on pioglitazone is the textbook adverse-event scenario.
PPAR-γ activation increases renal sodium reabsorption (via the ENaC channel in collecting duct), causing fluid retention that can precipitate or worsen heart failure — especially in patients with underlying cardiac dysfunction. Although this patient also has alcoholic liver disease (elevated GGT and AST out of proportion to ALT, ascites, paraumbilical varices), the pitting edema and acute decompensation point specifically to pioglitazone-induced fluid overload superimposed on his underlying disease.
Clinical pearl: avoid TZDs in patients with CHF, monitor for edema and weight gain, and recognize the additional risks of bladder cancer (pioglitazone) and bone fractures with chronic use.
**Why each option:**
**A.** Insulin glargine is generally safe in heart failure and does not cause the fluid retention typical of TZDs.
**B.** Sulfonylureas like glipizide cause hypoglycemia and weight gain but are not classically associated with fluid retention or precipitating heart failure.
**C.** Metformin should be avoided in unstable CHF (lactic acidosis risk) but does not directly cause fluid retention or worsening heart failure.
**D.** Correct. Pioglitazone (a TZD/PPAR-γ agonist) causes sodium and fluid retention via renal ENaC activation, precipitating or worsening heart failure.