A patient with poorly controlled diabetes mellitus develops an early posterior subcapsular cataract. Which biochemical pathway contributes most directly to lens opacification in this setting?

• A Non-enzymatic conversion of glucose to galactose within lens fibers
• B Accelerated glycolysis generating excess methylglyoxal in the lens cortex
• C Increased pentose phosphate flux depleting glutathione in lens epithelium
• D Sorbitol (polyol) pathway via aldose reductase, with osmotic swelling because sorbitol cannot exit the fiber cell ✓

Explanation

Hyperglycemia increases glucose flux through aldose reductase, which reduces glucose to sorbitol. Lens fibers lack or have very low sorbitol dehydrogenase activity, so sorbitol accumulates, is osmotically active, draws water in, and disrupts fiber integrity, producing cataract. Galactosemia produces cataract through the same polyol route with galactitol, not through galactose formation from glucose. The pentose phosphate pathway actually protects the lens by supplying NADPH for glutathione reduction.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.