Hearing impairment and ocular complications in Zucker diabetic fatty rats: a cross-sectional study across disease progression

Diabetic retinopathy is a well-recognized microvascular complication of diabetes mellitus; however, diabetes-associated auditory dysfunction remains less well characterized, particularly with respect to its longitudinal progression. In this study, we performed a cross-sectional assessment of ocular and auditory function in Zucker diabetic fatty (ZDF) rats and examined their relationships with chronic hyperglycemia. Forty male ZDF (fa/fa) rats and thirty-two age-matched control rats (fa/-) were evaluated at 12, 20, 28, and 36 weeks of age. Ocular changes were assessed using slit-lamp microscopy and fluorescein fundus angiography, while auditory function was evaluated using auditory brainstem response (ABR) testing across frequencies from 4 to 32 kHz. Fasting blood glucose levels were monitored throughout the study. ZDF rats developed sustained hyperglycemia from 12 weeks of age onward. Elevated ABR thresholds were first observed at high frequencies (32 kHz) at 12 weeks, followed by progressive involvement of mid frequencies (16 and 24 kHz) at 20 weeks and all tested frequencies (4-32 kHz) at 28-36 weeks. Retinal vascular leakage and cataract formation increased with disease duration. Fasting blood glucose levels showed strong positive associations with ABR thresholds across all frequencies (r = 0.72-0.85, P < 0.01) and with cataract severity. These findings show that chronic hyperglycemia in ZDF rats is accompanied by progressive auditory and ocular dysfunction, providing longitudinal functional evidence of multisystem sensory impairment in a diabetic animal model.