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Research paper
Published online: 2021-05-27
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Study of Epalrestat in Diabetic Distal Symmetric Polyneuropathy and correlation of its therapeutic efficacy with erythrocyte sorbitol levels : A step towards Precision Medicine

RUJUL Jain, SK Singh
DOI: 10.5603/DK.a2021.0038

open access

Ahead of print
Original articles (submitted)
Published online: 2021-05-27

Abstract

Aims : Diabetic Distal Symmetric Polyneuropathy (DSPN), despite being the most common and a disabling diabetic complication, remains difficult to treat. It has led to rekindle our interest in Epalrestat which has the potential to alter the natural history of the disease. The present study was designed to evaluate the efficacy of Epalrestat in DSPN and to corelate its therapeutic efficacy with baseline erythrocyte sorbitol levels. Methods : 100 patients with duration of diabetes more than five years and Diabetic Neuropathy Symptom Score (DNSS) ≥ 1 were included. They were divided into two groups of 50 patients each : Group 1 (received Tablet Epalrestat 150 mg once a day), Group 2 (received placebo). Baseline Diabetic Neuropathy Symptom Score (score out of 4), Numeric Pain Intensity Scale (score out of 10), Monofilament score (score out of 10), Vibration Perception Threshold (VPT) by Sensitometer and erthyrocyte sorbitol levels (by ELISA) were recorded. Same parameters were repeated at three months follow up visit. Results : Epalrestat was overall more effective than placebo in improving the symptoms as well as in improving the quantitative sensory nerve function measured by sensitometer The improvement in all the parameters positively correlated with baseline erythrocyte sorbitol levels. Conclusions : Epalrestat offers a ray of hope in the treatment of DSPN patients who have high baseline erythrocyte sorbitol levels and thus can be a useful tool in predicting the response to drug.

Abstract

Aims : Diabetic Distal Symmetric Polyneuropathy (DSPN), despite being the most common and a disabling diabetic complication, remains difficult to treat. It has led to rekindle our interest in Epalrestat which has the potential to alter the natural history of the disease. The present study was designed to evaluate the efficacy of Epalrestat in DSPN and to corelate its therapeutic efficacy with baseline erythrocyte sorbitol levels. Methods : 100 patients with duration of diabetes more than five years and Diabetic Neuropathy Symptom Score (DNSS) ≥ 1 were included. They were divided into two groups of 50 patients each : Group 1 (received Tablet Epalrestat 150 mg once a day), Group 2 (received placebo). Baseline Diabetic Neuropathy Symptom Score (score out of 4), Numeric Pain Intensity Scale (score out of 10), Monofilament score (score out of 10), Vibration Perception Threshold (VPT) by Sensitometer and erthyrocyte sorbitol levels (by ELISA) were recorded. Same parameters were repeated at three months follow up visit. Results : Epalrestat was overall more effective than placebo in improving the symptoms as well as in improving the quantitative sensory nerve function measured by sensitometer The improvement in all the parameters positively correlated with baseline erythrocyte sorbitol levels. Conclusions : Epalrestat offers a ray of hope in the treatment of DSPN patients who have high baseline erythrocyte sorbitol levels and thus can be a useful tool in predicting the response to drug.

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Keywords

Diabetic peripheral neuropathy, Epalrestat, Sorbitol, Vibration perception threshold.

About this article
Title

Study of Epalrestat in Diabetic Distal Symmetric Polyneuropathy and correlation of its therapeutic efficacy with erythrocyte sorbitol levels : A step towards Precision Medicine

Journal

Clinical Diabetology

Issue

Ahead of print

Article type

Research paper

Published online

2021-05-27

DOI

10.5603/DK.a2021.0038

Keywords

Diabetic peripheral neuropathy
Epalrestat
Sorbitol
Vibration perception threshold.

Authors

RUJUL Jain
SK Singh

References (10)
  1. Edwards JL, Vincent AM, Cheng HT, et al. Diabetic neuropathy: mechanisms to management. Pharmacol Ther. 2008; 120(1): 1–34.
  2. Argoff CE, Cole BE, Fishbain DA, et al. Diabetic peripheral neuropathic pain: clinical and quality-of-life issues. Mayo Clin Proc. 2006; 81(4 Suppl): S3–11.
  3. Oates PJ. Aldose reductase, still a compelling target for diabetic neuropathy. Curr Drug Targets. 2008; 9(1): 14–36.
  4. Okayama N, Omi H, Okouchi M, et al. Mechanisms of inhibitory activity of the aldose reductase inhibitor, epalrestat, on high glucose-mediated endothelial injury: neutrophil-endothelial cell adhesion and surface expression of endothelial adhesion molecules. J Diabetes Complications. 2002; 16(5): 321–326.
  5. Hotta N, Akanuma Y, Kawamori R, et al. Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications Trial. Diabetes Care. 2006; 29(7): 1538–1544.
  6. Chalk C, Benstead TJ, Moore F. Aldose reductase inhibitors for the treatment of diabetic polyneuropathy. Cochrane Database Syst Rev. 2007(4): CD004572.
  7. Maccari R, Ottanà R. Targeting aldose reductase for the treatment of diabetes complications and inflammatory diseases: new insights and future directions. J Med Chem. 2015; 58(5): 2047–2067.
  8. Sharma SR, Sharma N. Epalrestat, an aldose reductase inhibitor, in diabetic neuropathy: an Indian perspective. Ann Indian Acad Neurol. 2008; 11(4): 231–235.
  9. Ando H, Takamura T, Nagai Y, et al. Kanazawa University Multicenter Diabetes Study Group. Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathy. J Diabetes Complications. 2006; 20(6): 367–370.
  10. Meijer JWG, Smit AJ, Sonderen EV, et al. Symptom scoring systems to diagnose distal polyneuropathy in diabetes: the Diabetic Neuropathy Symptom score. Diabet Med. 2002; 19(11): 962–965.

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