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Peripheral Diabetic Neuropathy

Current Recommendations and Future Prospects for its Prevention and Management

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Summary

One-third of diabetic patients are affected by peripheral neuropathy (PDN) in which the main aetiopathogenetic mechanism seems to be the high blood and nerve glucose content. The results of some long term trials, such as the Diabetes Control and Complications Trial (DCCT) and Stockholm studies, showed clearly that the maintenance of near-normal blood glucose levels and haemoglobin (Hb)A1C below 7.5% with intensive insulin treatment represents the best approach to primary and secondary prevention of the late diabetic complications, including PDN.

After 5 years of such treatment DCCT reported that the development of clinical PDN was reduced by 64%. On the other hand, various and important problems still exist in identifying an efficacious aetiological therapy for PDN. In fact, while on the basis of current knowledge we have 2 possibilities for treatment of the pain, optimisation of glycaemic and HbA1C values and correct use of tricyclic antidepressants, none of the various substances tested has proven to be efficacious for PDN. Gangliosides, aldose-reductase inhibitors, including tolrestat, γ-linolenic acid, levacecarnine (acetyl-L-carnitine) and antioxidants, were all shown to be of poor efficacy and often with significant adverse effects.

The maintenance of near-normal glycaemic equilibrium seems currently to be the best way not only to prevent PDN but also to treat it. In the near future more long term trials, with very clear inclusion and exclusion criteria for recruitment, are needed to assist in identifying an efficacious treatment for PDN.

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References

  1. Consensus statement: report and recommendations of the San Antonio Conference on Diabetic Neuropathy [editorial]. Diabetes 1988; 37(7): 1000–4

    Google Scholar 

  2. Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973. Diabetes Care 1978; 1: 168–88, 252–63

    Google Scholar 

  3. Fedele D, Comi GC, Coscelli C, et al. A multicenter study on the prevalence of diabetic neuropathy in italy. Diabetes Care 1997; 20: 830–7

    Article  Google Scholar 

  4. American Diabetes Association. Diabetes 1996: vital statistics. Alexandria: ADA, 1996: 1–102

    Google Scholar 

  5. Nathan DM. The pathophysiology of diabetic complications: how much does the glucose hypothesis explain? Ann Intern Med 1996; 124 (1 Pt 2):86–9

    PubMed  CAS  Google Scholar 

  6. Yagihashi S. Pathology and pathogenetic mechanisms of diabetic neuropathy. Diab Metab Rev 1995; 11(3): 193–225

    Article  CAS  Google Scholar 

  7. Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med 1995; 122(8): 561–8

    Google Scholar 

  8. Reichard P, Nilsson BY, Rosenquisit U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 1993; 329: 304–9

    Article  PubMed  CAS  Google Scholar 

  9. Greene DA, Lattimer-Greene S, Sima AAF. Pathogenesis of diabetic neuropathy: role of altered phosphoinositide metabolism. Crit Rev Neurobiol 1989; 5: 143–219

    PubMed  CAS  Google Scholar 

  10. Jamal GA. Pathogenesis of diabetic neuropathy: the role of the ω-6-essential fatty acids and their eicosanoid derivatives. Diabetic Med 1990; 7: 574–9

    Article  PubMed  CAS  Google Scholar 

  11. Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996; 19: 257–67

    Article  PubMed  CAS  Google Scholar 

  12. Thomas PK. Growth factors and diabetic neuropathy. Diabetic Med 1994; 11: 732–9

    Article  PubMed  CAS  Google Scholar 

  13. Dyck PJ. Hypoxic neuropathy: does hypoxia play a role in diabetic neuropathy? Neurology 1989; 39: 111–8

    Article  PubMed  CAS  Google Scholar 

  14. Morley GK, Mooradian AD, Levine AS, et al. Mechanism of pain in diabetic peripheral neuropathy: effect of glucose on pain perception in humans. Am J Med 1984; 77: 79–82

    Article  PubMed  CAS  Google Scholar 

  15. Young RJ, Clarke BF. Pain relief in diabetic neuropathy: the effectiveness of imipramine and related drugs. Diabetic Med 1985; 2: 363–6

    Article  PubMed  CAS  Google Scholar 

  16. Rull JA, Quibrera R, Gonzales-Millan H, et al. Symptomatic treatment of peripheral diabetic neuropathy with carbamazepine (tegretol): double blind cross-over trial. Diabetologia 1969; 5: 215–8

    Article  PubMed  CAS  Google Scholar 

  17. Davis JL, Lewis SB, Gerich JE, et al. Peripheral diabetic neuropathy treated with amitriptyline and fluphenazine. JAMA 1977; 238: 2291–2

    Article  PubMed  CAS  Google Scholar 

  18. Max MB, Lynch SA, Muir J, et al. Effects of desipramine, amitriptyline and fluoxetine on pain in diabetic neuropathy. N Engl J Med 1992; 326: 1250–6

    Article  PubMed  CAS  Google Scholar 

  19. Dejgard A, Petersen P, Kastrup J. Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet 1988; 1: 9–11

    Article  PubMed  CAS  Google Scholar 

  20. Stracke H, Meyer U, Schumacher HE, et al. Mexiletine in the treatment of diabetic neuropathy. Diabetes Care 1992; 11: 1550–5

    Article  Google Scholar 

  21. Capsaicin Study Group. Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Diabetes Care 1992; 15: 159–65

    Article  Google Scholar 

  22. Levy DM, Abraham RR, Tomlinson DR. Topical capsaicin in the treatment of painful neuropathy [letter]. N Engl J Med 1991; 324: 776

    Article  PubMed  CAS  Google Scholar 

  23. Solders G, Tyden G, Persson A, et al. Improvement in diabetic neuropathy 4 years after successful pancreatic and renal transplantation. Diabetologia 1991; 34 Suppl. 1: S125–7

    Article  PubMed  Google Scholar 

  24. Handelsman DJ, Turtle JR. Clinical trial of an aldose reductase inhibitor in diabetic neuropathy. Diabetes 1981; 30: 459–64

    Article  PubMed  CAS  Google Scholar 

  25. Fagius J, Brattberg A, Jameson S, et al. Limited benefit of treatment of diabetic polyneuropathy with an aldose-reductase inhibitor: a 24-week controlled trial. Diabetologia 1985; 28: 323–9

    Article  PubMed  CAS  Google Scholar 

  26. Greene DA. Effects of aldose reductase inhibitors on the progression of nerve fibre damage in diabetic neuropathy. J Diabetes Complications 1992; 6: 35–8

    Article  PubMed  CAS  Google Scholar 

  27. Boulton AJM, Levin S, Comstock J. A multicentre trial of the aldose-reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy. Diabetologia 1990; 33: 431–7

    Article  PubMed  CAS  Google Scholar 

  28. Giugliano D, Marfella R, Quatraro A, et al. Tolrestat for mild diabetic neuropathy: a 52-week, randomized, placebo-controlled trial. Ann Intern Med 1993; 118: 7–11

    PubMed  CAS  Google Scholar 

  29. Giugliano D, Acampora R, Marfella R, et al. Tolrestat in the primary prevention of diabetic neuropathy. Diabetes Care 1995; 18: 536–41

    Article  PubMed  CAS  Google Scholar 

  30. Coscelli C, Cucinotta D, Santeusanio F, et al. Safety of tolrestat in diabetic neuropathy: the Italian multicentre surveillance study. Clin Drug Invest 1995; 10: 235–41

    Article  CAS  Google Scholar 

  31. Nicolucci A, Carinci F, Graepel JG, et al. The efficacy of tolrestat in the treatment of diabetic peripheral neuropathy: a meta-analysis of individual patient data. Diabetes Care 1996; 19: 1091–6

    Article  PubMed  CAS  Google Scholar 

  32. Wyeth-Recordati Pharmaceuticals. Unpublished study, protocol no. 709A-902-IT

  33. Ledeen RW, Yu K, Rapport MM, Swanki K, editors. Ganglioside structure, function and biomédical potential. Adv Exper Med Biol, Vol. 174, Plenum Press. New York, 1984

  34. Abraham RR, Levy DM, Abraham RM. Changes in thermal sensation in diabetic patients after treatment with gangliosides. Diab Res Clin Pract 1988; 7: 129–35

    CAS  Google Scholar 

  35. Fedele D, Crepaldi G, Battistin L. Multicenter trial on gangliosides in diabetic peripheral neuropathy. Adv Exp Med Biol 1984; 174: 601–6

    Article  PubMed  CAS  Google Scholar 

  36. Cameron NE, Cotter MA, Robertson S. Angiotensin converting enzyme inhibition prevents development of muscle and nerve dysfunction and stimulates angiogenesis in streptozotocin-diabetic rats. Diabetologia 1992; 35: 12–8

    Article  PubMed  CAS  Google Scholar 

  37. Jamal GA, Carmichael H. The effect of γ-linoleic acid on human diabetic peripheral neuropathy: a double-blind placebo controlled trial. Diabetic Med 1990; 7: 319–23

    Article  PubMed  CAS  Google Scholar 

  38. γ-Linolenic Acid Multicenter Trial Group. Treatment of diabetic neuropathy with γ-linolenic acid. Diabetes Care 1993; 16: 8–15

    Article  Google Scholar 

  39. Ido Y, McHowat J, Chang KC, et al. Neuronal dysfunction and metabolic imbalances in diabetic rats: prevention by acetyl-L-carnitine. Diabetes 1994; 43: 1469–77

    Article  PubMed  CAS  Google Scholar 

  40. Quatraro A, Roca P, Donzella C, et al. Acety-L-carnitine for symptomatic diabetic neuropathy [letter]. Diabetologia 1995; 38: 123

    Article  PubMed  CAS  Google Scholar 

  41. Sigma-Tau Pharmaceuticals. Unpublished study, protocol no. DRN 20032891/ALC-ST200

  42. Kihara M, Schmelzer JD, Poduslo JF, et al. Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals. Proc Natl Acad Sci USA 1991; 88: 6107–11

    Article  PubMed  CAS  Google Scholar 

  43. Van Dam PS, Van Asbeck BS, Erkelens DW, et al. The role of oxidative stress in neuropathy and other diabetic complications. Diab Metab Rev 1995; 11: 181–92

    Article  Google Scholar 

  44. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant α-lipoic acid: a 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995; 38: 1425–33

    Article  PubMed  CAS  Google Scholar 

  45. Anand P, Terenghi G, Warner G, et al. The role of endogenous nerve growth factor in human diabetic neuropathy. Nature Med 1996; 2: 703–7

    Article  PubMed  CAS  Google Scholar 

  46. Dyck PJ. Nerve growth factor and diabetic neuropathy. Lancet 1996; 348: 1044–5

    Article  PubMed  CAS  Google Scholar 

  47. Pfeifer MA, Schumer MP. Clinical trials of diabetic neuropathy: past, present and future. Diabetes 1995; 44: 1355–61

    Article  PubMed  CAS  Google Scholar 

Download references

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Fedele, D., Giugliano, D. Peripheral Diabetic Neuropathy. Drugs 54, 414–421 (1997). https://doi.org/10.2165/00003495-199754030-00004

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