A 55-year-old man with poorly controlled type 2 diabetes develops bilateral posterior subcapsular lens opacities over months. Lens fiber cells lack insulin-regulated GLUT4 and take up glucose freely. Which metabolic pathway operating in the lens explains cataract formation under hyperglycemia?
- A Accumulation of sorbitol from aldose reductase activity, causing osmotic swelling of lens fibers ✓
- B Excessive glycogen deposition from upregulated glycogen synthase
- C Nonenzymatic conversion of glucose to methylglyoxal, which polymerizes crystallins exclusively
- D Accelerated pentose phosphate flux generating excess ribulose-5-phosphate in the lens
Correct answer: A. Accumulation of sorbitol from aldose reductase activity, causing osmotic swelling of lens fibers
Explanation
In hyperglycemia, aldose reductase reduces surplus glucose to sorbitol using NADPH. Lens fibers lack significant sorbitol dehydrogenase and are impermeable to sorbitol, so it accumulates, draws water in osmotically, and disrupts fiber architecture, producing cataract. While nonenzymatic glycation also contributes to diabetic cataract, the classic osmotic mechanism tested here is sorbitol accumulation. Pentose phosphate flux changes do not explain lens opacification.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.