Effects of aldose reductase inhibitors on the progression of nerve fiber damage in diabetic neuropathy.
Aldose reductase inhibitors improve nerve biochemistry, function, and structure in diabetic animals and increase nerve conduction in diabetic patients. Nevertheless, it has been difficult to demonstrate a benefit from these agents in patients with clinically overt diabetic neuropathy. Direct measurement of the nerve tissue penetration and biochemical and biological potency of these compounds is essential to fully understand and evaluate their effectiveness. Human sural nerve biopsies obtained from diabetic neuropathic patients undergoing treatment with an aldose reductase inhibitor revealed a reduction in intermediates of the polyol pathway. Specific morphologic lesions that correlate with the degree of clinical and electrophysiologic impairment also were identified. Morphologic evaluation of sural nerve biopsies obtained after aldose reductase inhibitor treatment suggests that these biochemically effective compounds ameliorate clinically relevant structural lesions in patients with diabetic neuropathy.
Greene
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DA
Michigan Diabetes Research and Training Center, University of Michigan, Ann Arbor 48109.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D003929:Diabetic Neuropathies / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004311:Double-Blind Method; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D009281:Naphthalenes / Q000627:therapeutic use*; D009416:Nerve Regeneration; D010793:Phthalazines / Q000627:therapeutic use*; D013497:Sural Nerve / Q000473:pathology / Q000503:physiopathology
D007093:Imidazoles; D048289:Imidazolidines; D009281:Naphthalenes; D010793:Phthalazines; C040550:tolrestat; C042829:ponalrestat; D000449:Aldehyde Reductase; C026411:sorbinil