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Aldose Reductase Inhibitors for the Treatment of Diabetic Neuropathy

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Diabetic Neuropathy

Part of the book series: Clinical Diabetes ((CLD))

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

  1. 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.

    Article  PubMed  CAS  Google Scholar 

  2. Tomlinson DR, Willars GB, Carrington AL. Aldose reductase inhibitors and diabetic complications. Pharmacol Ther 1992;54:151–194.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    PubMed  CAS  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    PubMed  CAS  Google Scholar 

  6. Handelsman DJ, Turtle JR. Clinical trial of an aldose reductase inhibitor in diabetic neuropathy. Diabetes 1981;30:459–464.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. Consensus Statement. Report and Recommendations of the San Antonio Conference on Diabetic Neuropathy. Diabetes 1988;37:1000–1004.

    Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. 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.

    PubMed  CAS  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    PubMed  CAS  Google Scholar 

  24. 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.

    Article  CAS  Google Scholar 

  25. 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.

    Article  CAS  Google Scholar 

  26. 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.

    PubMed  CAS  Google Scholar 

  27. Giugliano D, Acampora R, Marfella R, et al. Tolrestat in the primary prevention of diabetic neuropathy. Diabetes Care 1995;18:536–541.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Article  CAS  Google Scholar 

  29. Greene DA, Arezzo J, Brown M. Effects of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy. Neurology 1999;53:580–591.

    PubMed  CAS  Google Scholar 

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

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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

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-626-9

  • Online ISBN: 978-1-59745-311-0

  • eBook Packages: MedicineMedicine (R0)

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