Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathy.
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.
Ando
Hitoshi
H
Department of Diabetes and Digestive Disease, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
Takamura
Toshinari
T
Nagai
Yukihiro
Y
Kaneko
Shuichi
S
D000368:Aged; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010525:Peripheral Nerves / Q000187:drug effects; D011379:Prognosis; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013012:Sorbitol / Q000032:analysis*; D053778:Thiazolidines / Q000627:therapeutic use*; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D053778:Thiazolidines; C038131:epalrestat; D013012:Sorbitol; D012236:Rhodanine; D000449:Aldehyde Reductase