Skip to main content
SpringerLink
Log in

Treatment of diabetic autonomic neuropathy with an aldose reductase inhibitor

  • Original Communications
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

To evaluate the effects of the aldose reductase inhibitor Ponalrestat (Statil) on diabetic autonomic neuropathy, a double-blind placebo controlled trial was carried out on a group of 34 diabetic patients with documented cardiac autonomic neuropathy. After a 4-week, placebo run-in period, patients were randomised for treatment with 600 mg Statil or placebo for another 24 weeks. Moreover, the reliability of the autonomic nerve function tests was investigated by comparing the results at onset and at week 4. Fifteen patients treated with Statil and 12 with placebo completed the study. Neither symptom scores nor cardiovascular reflexes, pupil reflexes and skin vasomotor reflexes improved after Statil therapy, which led us to conclude that Statil is not effective in the treatment of diabetic autonomic neuropathy. Reliability coefficients for cardiovascular reflexes and pupil reflex showed high values, ranging from 60% to 80%. Therefore these methods are recommended in future therapy trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Armstrong FM, Bradbury JE, Ellis SH, Owens DR, Rosen I, Sonksen P, Sundkvist G (1991) A study of peripheral diabetic neuropathy. The application of age-related reference values. Diabetic Med 8:S94-S99

    PubMed  Google Scholar 

  2. Bland M (1990) An introduction to medical statistics. Oxford University Press, Oxford

    Google Scholar 

  3. Boulton AJM, Levin S, Comstock J (1990) A multicentre trial of the aldose reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy. Diabetologia 33:431–437

    PubMed  Google Scholar 

  4. Brown MJ, Asbury AK (1984) Diabetic neuropathy. Ann Neurol 15:2–12

    PubMed  Google Scholar 

  5. Christensen JEJ, Varnek L, Gregersen G (1985) The effect of an aldose reductase inhibitor (sorbinil) on diabetic neuropathy and neural function of the retina: a double-blind study. Acta Neurol Scand 71:164–167

    PubMed  Google Scholar 

  6. Donk AF, Faes TIC, Broere D, Veen EA van der, Bertelsmann FW (1990) Quantitation of skin vasomotor control in normal subjects and in diabetic patients with autonomic neuropathy. J Neurol 237:457–460

    PubMed  Google Scholar 

  7. Dyck PJ, Kratz KM, Lehman KA, Karnes JL, Melton LJ, O'Brien PC, Litchy WJ, Windebank AJ, Smith BE, Low PA, Service FJ, Rizza RA, Zimmerman BR (1991) The Rochester diabetic neuropathy study: design, criteria for types of neuropathy, selection bias and reproducibility of tests. Neurology 41:799–807

    PubMed  Google Scholar 

  8. Ewing DJ, Campbell IW, Burt AA, Clarke BF (1973) Vascular reflexes in diabetic autonomic neuropathy. Lancet II:1354–1356

    Google Scholar 

  9. Ewing DJ, Campbell IW, Murray A, Neilson JMM, Clarke BF (1978) Immediate heart-rate response to standing: simple test for autonomic neuropathy in diabetes. BMJ 1:145–147

    PubMed  Google Scholar 

  10. Fagius J, Jameson S (1981) Effects of aldose reductase inhibitor treatment in diabetic polyneuropathy: a clinical and neurophysiological study. J Neurol Neurosurg Psychiatry 44:991–1001

    PubMed  Google Scholar 

  11. Fagius J, Brattberg A, Jameson S, Berne C (1985) Limited benefit of treatment of diabetic polyneuropathy with an aldose reductase inhibitor: a 24-week controlled trial. Diabetologia 28:323–329

    PubMed  Google Scholar 

  12. Florkowski CM, Rowe BR, Nightingale S, Harvey TC, Barnett AH (1991) Clinical and neurophysiological studies of aldose reductase inhibitor ponalrestat in chronic symptomatic diabetic peripheral neuropathy. Diabetes 40:129–133

    PubMed  Google Scholar 

  13. Gabbay KH (1973) The sorbitol pathway and the complications of diabetes. N Engl J Med 288:831–836

    PubMed  Google Scholar 

  14. Gill JS, Williams G, Ghatei MA, Hetreed AH, Mather HM, Bloom SR (1990) Effect of the aldose reductase inhibitor, ponalrestat, on diabetic neuropathy. Diabete Metab 16:296–302

    PubMed  Google Scholar 

  15. Gillon KRW, Hawthorne JN, Tomlinson DR (1983) Myoinositol and sorbitol metabolism in relation the peripheral nerve function in experimental diabetes in the rat: the effect of aldose reductase inhibition. Diabetologia 25:365–371

    PubMed  Google Scholar 

  16. Greene DA, Lattimer SA (1985) Recent advances in the therapy of diabetic peripheral neuropathy by means of an aldose reductase inhibitor. Am J Med 79:13–17

    Google Scholar 

  17. Greene DA, Lattimer S, Ulbrecht J, Carroll P (1985) Glucose-induced alterations in nerve metabolism: current perspective on the pathogenesis of diabetic neuropathy and future directions for research and therapy. Diabetes Care 8:290–299

    PubMed  Google Scholar 

  18. Judzewitsch RG, Jaspan JB, Polonsky KS, Weinberg CR, Halter JB, Halar E, Pfeifer MA, Vukadinovic C, Bernstein L, Schneider M, Liang K, Gabbay KH, Rubenstein AH, Porte D (1983) Aldose reductase inhibition improves nerve conduction velocity in diabetic patients. N Engl J Med 308:119–125

    PubMed  Google Scholar 

  19. Krentz AJ, Honingsberger L, Nattrass M (1989) Variability of three standard neurophysiological techniques in established symptomatic diabetic polyneuropathy. Diabetes Res 12:135–139

    PubMed  Google Scholar 

  20. Lanting P, Bos JE, Aartsen J, Schuman L, Reichert-Thoen JWM, Heimans JJ (1990) Assessment of pupillary light reflex latency and darkness adapted pupil size in control subjects and in diabetic patients with and without cardiovascular autonomic neuropathy. J Neurol Neurosurg Psychiatry 53:912–914

    PubMed  Google Scholar 

  21. Lewin IG, O'Brien IAD, Morgan MH, Corrall RJM (1984) Clinical and neurophysiological studies with the aldose reductase inhibitor sorbinil, in symptomatic diabetic neuropathy. Diabetologia 26:445–448

    PubMed  Google Scholar 

  22. O'Brien IA, McFadden JP, Corrall RJM (1991) The influence of autonomic neuropathy in mortality in insulin-dependent diabetes. Q J Med 290:495–502

    Google Scholar 

  23. Sima AAF, Bril V, Xathaniel V, Thomas MS, McEwen AJ, Brown MB, Lattimer SA, Greene DA (1988) Regeneration and repair of myelinated fibers in sural nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil. N Engl J Med 319:548–555

    PubMed  Google Scholar 

  24. Smith SA, Smith SE (1987) Assessment of pupillary function in diabetic neuropathy. In: Dyck PJ, Thomas PK, Asburry AK, Winegrad AI, Porte D (eds) Diabetic neuropathy. Saunders, Philadelphia, pp 134–140

    Google Scholar 

  25. Snedecor GW, Cochran WG (1991) Statistical methods. Iowa State University Press, Iowa, pp 102–105

    Google Scholar 

  26. Stribling D, Mirrlees DJ, Harrison HE, Earl DCN (1985) Properties of ICI 128, 436, a novel aldose reductase inhibitor, and its effects on diabetic complications in the rat. Metabolism 34:336–344

    PubMed  Google Scholar 

  27. Sundkvist G, Almer LO, Lilja B (1979) Respiratory influence on heart rate in diabetes mellitus. BMJ 1:924–925

    PubMed  Google Scholar 

  28. Sundkvist G, Lilja B, Rosen J, Agardh CD (1987) Autonomic and peripheral nerve function in early diabetic neuropathy. Acta Med Scand 221:445–453

    PubMed  Google Scholar 

  29. Watkins PJ (1992) Clinical observations and experiments in diabetic neuropathy. Diabetologia 35:2–11

    PubMed  Google Scholar 

  30. Winer BJ (1971) Statistical principles in experimental designs. McGraw-Hill, New York, pp 283–296

    Google Scholar 

  31. Young RJ, Ewing DJ, Clarke BF (1983) A controlled trial of sorbinil, an aldose reductase inhibitor, in chronic painful diabetic neuropathy. Diabetes 32:938–942

    PubMed  Google Scholar 

  32. Ziegler D, Mayer P, Rathmann W, Gries FA (1991) One-year treatment with the aldose reductase inhibitor, ponalrestat, in diabetic neuropathy. Diabetes Res Clin Pract 4:67–75

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Physics, Free University Hospital, P. O. Box 7057, NL-1007, MB Amsterdam, The Netherlands

    T. J. C. Faes

  2. Department of Neurology, Free University Hospital, P. O. Box 7057, NL-1007, MB Amsterdam, The Netherlands

    G. A. Yff, O. De Weerdt, P. Lanting, J. J. Heimans & F. W. Bertelsmann

Authors
  1. T. J. C. Faes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. A. Yff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. De Weerdt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Lanting
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. J. Heimans
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. W. Bertelsmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faes, T.J.C., Yff, G.A., De Weerdt, O. et al. Treatment of diabetic autonomic neuropathy with an aldose reductase inhibitor. J Neurol 240, 156–160 (1993). https://doi.org/10.1007/BF00857521

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00857521

Key words

Search

Navigation