Effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy. The Tolrestat Study Group.

Abstract:

:Tolrestat is a well tolerated nonhydantoin aldose reductase inhibitor that has been reported to improve nerve conduction in diabetic animals and humans. Its effects on nerve biochemistry and structure have not been studied in patients with diabetic neuropathy. Patients with advanced diabetic neuropathy treated with long-term open-label tolrestat were randomly assigned to continuation on drug treatment or to placebo-controlled drug withdrawal for 12 months. At the end of this period, sural nerve biopsies were obtained for measurement of glucose, sorbitol, and fructose content, and for detailed morphometric analysis. Tolrestat ameliorated the glucose-mediated increase in sorbitol and fructose in sural nerve tissue. No statistically significant differences in nerve morphometry emerged between the two groups; however, both treatment groups exhibited increased nerve-fiber regeneration and normalization of axo-glial dysfunction and segmental demyelination following long-term tolrestat treatment. These findings are similar to those previously reported in a placebo-controlled sequential nerve biopsy study with the aldose reductase inhibitor sorbinil. Thus tolrestat is a biochemically effective aldose reductase inhibitor in human diabetic nerve with potential therapeutic efficacy for diabetic neuropathy.

authors

Sima AA,Greene DA,Brown MB,Hohman TC,Hicks D,Graepel GJ,Bochenek WJ,Beg M,Gonen B

doi

10.1016/1056-8727(93)90041-v

subject

Has Abstract

pub_date

1993-07-01 00:00:00

pages

157-69

issue

3

eissn

1056-8727

issn

1873-460X

pii

1056-8727(93)90041-V

journal_volume

7

pub_type

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