Abstract
It has been more than 30 years since the first aldose reductase inhibitor (ARI) was tested in diabetic and galactosemic rats and found to control the polyol accumulation. Since then, a considerable number of ARIs have been tested in experimental and human diabetes. Despite the initial encouraging results from tests that were conducted for the past 20 years, ARIs have not been established for the treatment of diabetic neuropathy yet. The main reasons for this are inconsistent results and the unacceptable high rate of side-effects associated with the initially tested compounds. The lack of well-defined end points and the inability to produce an inhibitor that achieves satisfactory tissue penetration and enzyme inhibition are other major contributing factors for this failure. This chapter focuses on the clinical trials that have examined the effect of all tested ARIs on human diabetic neuropathy.
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References
Dvornik D, Simard-Duquesne N, Krami M, et al. Polyol accumulation in galactosemic and diabetic rats: control by an aldose reductase inhibitor. Science 1973;182:1146–1148.
Tomlinson DR, Willars GB, Carrington AL. Aldose reductase inhibitors and diabetic complications. Pharmacol Ther 1992;54:151–194.
Pfeifer MA, Schumer MP, Gelber DA. Aldose reductase inhibitors: the end of an era or the need for different trial designs? Diabetes 1997;46(Suppl 2):S82–S89.
Dyck PJ, O’Brian PC. Meaningful degrees of prevention or improvement of nerve conduction in controlled clinical trials of diabetic neuropathy. Diabetes Care 1989; 12: 649–652.
Culebras A, Alio J, Herrera JL, Lopez-Fraile IP. Effect of an aldose reductase inhibitor on diabetic peripheral neuropathy. Arch Neurol 1981;38:133–134.
Handelsman DJ, Turtle JR. Clinical trial of an aldose reductase inhibitor in diabetic neuropathy. Diabetes 1981;30:459–464.
Fagius J, Jameson S. Effects of aldose reductase inhibitor treatment in diabetic polyneuropathy—a clinical and neurophysiological study. J Neurol Neurosurg Psychiatr 1981;44: 991–1001.
Judzewitsch RG, Jaspan JB, Polonsky KS, et al. Aldose reductase inhibition improves nerve conduction velocity in diabetic patients. N Engl J Med 1983;308:119–125.
Jaspan J, Maselli R, Herold K, Bartkus C. Treatment of severely painful diabetic neuropathy with an aldose reductase inhibitor: relief of pain and improved somatic and autonomic nerve function. Lancet 1983;ii:758–762.
Young RJ, Ewing DJ, Clarke BF. A controlled trial of sorbinil, an aldose reductase inhibitor, in chronic painful diabetic neuropathy. Diabetes 1983;32:938–942.
Lewin IG, O’Brien AD, Morgan MH, Corrall RJM. Clinical and neurophysiological studies with the aldose reductase inhibitor, sorbinil, in symptomatic diabetic neuropathy. Diabetologia 1984;26:445–448.
Fagius J, Brattberg A, Jameson S, Berne C. Limited benefit of treatment of diabetic neuropathy with an aldose reductase inhibitor: a 24-week controlled trial. Diabetologia 1985;28:323–329.
O’Hare JP, Morgan MH, Alden P, Chissel S, O’Brien AD, Corrall RJM. Aldose reductase inhibition in diabetic neuropathy: Clinical and neurophysiological studies of one year’s treatment with sorbinil. Diabet Med 1988;5:537–542.
Guy RJC, Gilbey SG, Sheehy M, Asselman P, Watkins P. Diabetic neuropathy in the upper limb and the effect of twelve months sorbinil treatment. Diabetologia 1988;31: 214–220.
Consensus Statement. Report and Recommendations of the San Antonio Conference on Diabetic Neuropathy. Diabetes 1988;37:1000–1004.
Sima AAF, Brill V, Nathaniel T, et al. Regeneration and repair of myelinated fibres in sural nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil. N Engl J Med 1988;319:548–555.
Dyck PJ, Zimmerman BR, Vilen TH, et al. Nerve glucose, fructose, sorbitol, myo-inositol, and fiber degeneration and regeneration in diabetic neuropathy. N Engl J Med 1988;319: 542–548.
Gill JS, Williams G, Ghatei MA, Hetreed AH, Mather HM, Bloom SR. Effect of the aldose reductase inhibitor, ponalrestat, on diabetic neuropathy. Diabete Metab 1990; 16:296–302.
Price DE, Alani SM, Wales JK. Effect of aldose reductase inhibition on resistance to ischemic conduction block in diabetic subjects. Diabetes Care 1991;14:411–413.
Ziegler D, Mayer P, Rathmann W, Gries FA. One-year treatment with the aldose reductase inhibitor, ponalrestat, in diabetic neuropathy. Diabetes Res Clin Pract 1991;14:63–73.
Krentz AJ, Honigsberger L, Ellis SH, Hardman M, Nattrass M. A 12-month randomized controlled study of the aldose reductase inhibitor ponalrestat in patients with chronic symptomatic diabetic neuropathy. Diabet Med 1992;9:463–468.
Boulton AJM, Levin S, Comstock J. A multicentre trial of the aldose reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy. Diabetologia 1990;33: 431–437.
Macleod AF, Boulton AJM, Owens DR, et al. A multicentre trial of the aldose reductase inhibitor tolrestat in patients with symptomatic diabetic peripheral neuropathy. Diabete Metab 1992; 18:14–20.
Santiago JV, Sonksen PH, Boulton AJM, et al. Withdrawal of the aldose reductase inhibitor tolrestat in patients with diabetic neuropathy: Effect on nerve function. J Diab Comp 1993;7:170–178.
Sima AAF, Greene DA, Brown MB, et al. Effect of hyperglycemia and the aldose inhibitor tolrestat on sural nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy. J Diab Comp 1993;7:157–169.
Giugliano D, Marfella R, Quatraro A, et al. Tolrestat for mild diabetic neuropathy. A 52week, randomized, placebo controlled trial. Ann Int Med 1993;118:7–11.
Giugliano D, Acampora R, Marfella R, et al. Tolrestat in the primary prevention of diabetic neuropathy. Diabetes Care 1995;18:536–541.
Didangelos TP, Karamitsos DT, Athyros VG, Kourtoglou GI. Effect of aldose reductase inhibition on cardiovascular reflex tests in patients with definite diabetic autonomic neuropathy over a period of 2 years. J Diab Comp 1998;12:201–207.
Greene DA, Arezzo J, Brown M. Effects of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy. Neurology 1999;53:580–591.
Hotta N, Toyota T, Matsuoka K, et al. Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study. Diabetes Care 2001;24:1776–1782.
Johnson BF, Nesto RW, Pfeifer MA, et al. Cardiac abnormalities in diabetic patients with neuropathy: effects of aldose reductase inhibitor administration. Diabetes Care 2004;27: 448–454.
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© 2007 Humana Press Inc., Totowa, NJ
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Veves, A. (2007). Aldose Reductase Inhibitors for the Treatment of Diabetic Neuropathy. In: Veves, A., Malik, R.A. (eds) Diabetic Neuropathy. Clinical Diabetes. Humana Press. https://doi.org/10.1007/978-1-59745-311-0_18
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DOI: https://doi.org/10.1007/978-1-59745-311-0_18
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