The relationship between the effect of
aldose reductase inhibitors (ARIs) on the activation of the
polyol pathway and on
diabetic neuropathy has not been fully established. To address this issue, we investigated the effect of
epalrestat (150 mg/day), an ARI, on erythrocyte
sorbitol levels as an index of
polyol activation and on nerve function test results in 43 patients with diabetic peripheral
polyneuropathy. After 6 months of
epalrestat administration, erythrocyte
sorbitol levels did not decrease in patients as a whole. However, a decrease in erythrocyte
sorbitol levels during
epalrestat administration was significantly correlated with baseline erythrocyte
sorbitol levels (rho=-.47, P<.01): The higher the level at baseline, the greater the decrease after
epalrestat treatment. Moreover, the mean
sorbitol level during
epalrestat treatment was associated with the beneficial effect of
epalrestat on vibration sensitivity as measured with a C-128 tuning fork (rho=-.66, P<.01) and/or a pallesthesiometer TM-31A (rho=.53, P<.05). On the other hand, erythrocyte
sorbitol levels did not reflect the prognosis of nerve conduction velocity. These findings at least partly suggest a causal relationship between
polyol activation and the development of
diabetic neuropathy.
Aldose reductase inhibitor treatment may be clinically useful in the control of
polyol activation, especially in patients with excessive accumulation of
sorbitol.