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Ganglioside treatment in diabetic peripheral neuropathy: A multicenter trial

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Summary

Ganglioside treatment was evaluated with a multicenter, randomized, double-blind, controlled, cross-overvs placebo trial in 140 insulin-treated diabetic subjects with peripheral neuropathy. The patients entered the study when they showed an impairment in at least two of the electroneurographic parameters, and were assigned to two protocols according to the presence and severity of their neurological symptoms. Ninety-seven diabetic subjects with no or mild symptoms were assigned to protocol I, whereas 43 symptomatic patients were assigned to protocol II. The treatment periods lasted 6 weeks with an intermediate washout period of 4 weeks. The treatment consisted in the daily i.m. administration of 20 mg gangliosides or of placebo. Electroneurographic parameters were recorded at the beginning and at the end of each treatment period, whereas clinical and metabolic data (mean daily plasma glucose, glycosuria and glycosylated hemoglobin) were evaluated every three weeks in protocol I and every two weeks in protocol II. No change in the metabolic parameters was observed throughout the trial period. However, the treatment induced a statistically significant improvement of paresthesias (protocol II) and of some electrophysiological parameters; in particular, ganglioside treatment improved MCV of peroneal nerve (p<0.03) in patients of protocol I, MCV of ulnar nerve (p<0.002) and SCV of median nerve (p<0.06) in patients of protocol II. Furthermore, 22 subjects of protocol II showed a ‘drug preference’ while 10 preferred placebo and 9 had no preference. In conclusion, ganglioside treatment seems to have a positive effect on diabetic peripheral neuropathy, improving both some symptoms and some electrophysiological parameters.

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References

  1. Bassi S., Albizzati M. G., Calloni E., Frattola L.: Electromyographic study of diabetic and alcoholic polyneuropathic patients treated with gangliosides — Muscle and Nerve5, 351, 1982.

    Article  PubMed  CAS  Google Scholar 

  2. Bergamini L., Troni W., Lacquaniti F.: Le neuropatie diabetiche — Omnia med. ther. (Arch.)13, 1, 1980.

    Google Scholar 

  3. Campbell I. W., Fraser D. M., Ewing D. J., Baldwa V. S., Harrower A. B. D., Murray A., Neilson J. M. M., Clarke B. F.: Peripheral and autonomic nerve function in diabetic ketoacidosis — Lancetii, 167, 1976.

    Article  Google Scholar 

  4. Canal N., Comi G., Saibene V., Musch B., Pozza G.: The relationship between peripheral and autonomic neuropathy in insulin dependent diabetes: a clinical and instrumental evaluation. In:Canal N., Pozza G. (Eds): Peripheral neuropathies. Elsevier-North Holland, Biochemical Press, Amsterdam - New York, 1978; p. 247.

    Google Scholar 

  5. Ceccarelli B., Aporti F., Finesso M.: Effects of brain gangliosides on functional recovery in experimental regeneration and reinnervation. In:Porcellati G., Ceccarelli B., Tettamanti G. (Eds): Gangliosides function. Plenum Press, New York and London, 1976; p. 275.

    Google Scholar 

  6. Chochinov R. H., Ullyot G. L. E., Moorhouse J. A.: Sensory perception thresholds in patients with juvenile diabetes and their close relatives — New Engl. J. Med.286, 1233, 1972.

    Article  PubMed  CAS  Google Scholar 

  7. Clements R. S. Jr., Vourganti B., Kuba T., Oh S. J., Darnell B.: Dietary myoinositol intake and peripheral nerve function in diabetic neuropathy — Metabolism28, 477, 1979.

    Article  PubMed  Google Scholar 

  8. Crepaldi G., Bellavere F., Cardone C., Bosello G., Fedele D.: Short and long-term continuous subcutaneous insulin infusion system treatment in patients with diabetic autonomic neuropathy — Diabetologia23, 162, 1982; abstract # 66.

    Google Scholar 

  9. Cuatrecasas P.: Gangliosides and membrane receptors for cholera toxin — Biochemistry (Wash.)12, 3558, 1973.

    CAS  Google Scholar 

  10. Culebras A., Alio J., Herrera J. L.: Effect of aldose reductase inhibitor on diabetic peripheral neuropathy — Arch. Neurol. (Chic.)38, 133, 1981.

    CAS  Google Scholar 

  11. Daly J. W.: The effect of gangliosides on activity of adenylate cyclase and phosphodiesterase from rat cerebral cortex. In:Rapport M. M., Gorio A. (Eds): Gangliosides in neurological and neuromuscular function, development and repair. Raven Press, New York, 1981; p. 55.

    Google Scholar 

  12. Fedele D., Bellavere F., Cardone C., Ferri M., Crepaldi G.: Short- and long-term continuous subcutaneous insulin infusion (CSII) in patients with diabetic autonomic neuropathy (DAN). In:Alberti K. G. M. M., Ogada T., Aluoch J. A., Mingola E. N. (Eds): 11th Congress IDF, Nairobi, November 10–17, 1982. Excerpta Medica Foundation. Amsterdam-Oxford-Princeton, 1982; p. 36, abstract # 77.

  13. Fedele D., Marchiori E., Brugnolo R., Zangaglia O., Valerio G.: La determinazione dell’emoglobina glicosilata (HbG): valutazione critica di un micrometodo commerciale — G. ital. Chim. clin.6, 237, 1981.

    CAS  Google Scholar 

  14. Fedele D., Negrin P., Fardin P., Tiengo A.: Motor conduction velocity (MCV) in insulin-dependent and in non-insulin-dependent diabetics with and without clinical peripheral neuropathy — Diabète et Métab.6, 189, 1980.

    CAS  Google Scholar 

  15. Ferrari G., Fabris M., Gorio A.: Gangliosides enhance neurite outgrowth in PC 12 cells — Develop. Brain. Res.8, 215, 1983.

    Article  CAS  Google Scholar 

  16. Fishman P. H., Brady R. O.: Biosynthesis and function of gangliosides — Science194, 906, 1976.

    Article  PubMed  CAS  Google Scholar 

  17. Fleiss J. L.: Statistical methods for rates and proportions. J. Wiley & Sons, New York, 1973.

    Google Scholar 

  18. Fraser D. M., Campbell I. W., Ewing D. J., Murray A., Neilson J. M. M., Clarke B. F.: Peripheral and autonomic nerve function in newly diagnosed diabetes mellitus — Diabetes26, 546, 1977.

    Article  PubMed  CAS  Google Scholar 

  19. Gabbay K. H., Spack N., Loo S., Hirsch H., Ackil A. A.: Aldose reductase inhibition: studies with alrestatin — Metabolism28 (Suppl. 1), 471, 1979.

    Article  PubMed  CAS  Google Scholar 

  20. Gart J. S.: An exact test for comparing matched proportions in cross-over designs — Biometrika5, 75, 1969.

    Article  Google Scholar 

  21. Gorio A., Aporti F., Norido F.: Ganglioside treatment in experimental diabetic neuropathy. In:Rapport M. M., Gorio A. (Eds): Gangliosides in neurological and neuromuscular function, development and repair. Raven Press, New York, 1981; p. 259.

    Google Scholar 

  22. Gorio A., Carmignoto G., Facci L., Finesso M.: Motor nerve sprouting induced by ganglioside treatment. Possible implications for gangliosides on neuronal growth — Brain Res.197, 236, 1980.

    Article  PubMed  CAS  Google Scholar 

  23. Gorio A., Carmignoto G., Ferrari G.: Axon sprouting stimulated by gangliosides. A new model for elongation and sprouting. In:Rapport M. M., Gorio A. (Eds): Gangliosides in neurological and neuromuscular function, development and repair. Raven Press, New York, 1981; p. 177.

    Google Scholar 

  24. Gorio A., Carmicnoto G., Ferrari G., Norido F., Bubini R., Zanoni R.: Pharmacological aspects of experimental peripheral neuropathy. In:Refsum S., Bolis C. L., Portera-Sanchez A. (Eds): International conference on peripheral neurophaties. Excerpta Medica, Amsterdam-Oxford-Princeton, 1982; p. 29.

    Google Scholar 

  25. Gorio A., Di Gianberardino L., Norido F., Schiavinato A., Vitadello M.: In diabetic neuropathy changes of conduction velocity precede alteration in axonal transport. Implications for the pharmacological effect of gangliosides. ISN meeting, Vancouver, 1983.

  26. Gorio A., Marini P., Zanoni R.: Muscle reinnervation III. Motoneuron sprouting capacity, enhancement by exogenous gangliosides — Neuroscience8, 417, 1983.

    Article  PubMed  CAS  Google Scholar 

  27. Graf R. J., Halter J. B., Halar E., Porte D. Jr.: Nerve conduction abnormalities in untreated maturity-onset diabetes: relation to levels of fasting plasma glucose and glycosylated hemoglobin — Ann. intern. Med.90, 298, 1979.

    PubMed  CAS  Google Scholar 

  28. Graf R. J., Halter J. B., Pfeifer M. A., Halar E., Brozovich F., Porte D. Jr.: Glycemic control nerve conduction abnormalities in non-insulin-dependent diabetic subjects — Ann. intern. Med.94, 307, 1981.

    PubMed  CAS  Google Scholar 

  29. Greene D. A., De Jesus P. V., Winegrad A. I.: Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes — J. clin. Invest.55, 1326, 1975.

    Article  PubMed  CAS  Google Scholar 

  30. Huggett A. S. F., Nixon D. A.: Use of glucose-oxidase peroxidase and o-dianisine in the determination of blood and urine glucose — Lancetii, 368, 1957.

    Article  Google Scholar 

  31. Judzerwitsch R. G., Jaspan J. B., Polonsky K. S., Weinberg C. R., Halter J. B., Halar E., Pfeifer M. A., Vukadinovic C., Bernstein L., Schneider M., Liang K. Y., Gabbay K. H., Rubenstein A. H., Porte D. Jr.: Aldose reductase inhibition improves nerve conduction velocity in diabetic patients — New Engl. J. Med.308, 119, 1983.

    Article  Google Scholar 

  32. Kynoch P. A. M., Lehman M.: Rapid estimation (2 1/2 hours) of glycosylated hemoglobin for routine purposes — Lancetii, 16, 1977.

    Article  Google Scholar 

  33. Leon A., Facci L., Toffano G., Sonnino S., Tettamanti G.: Activation of (Na+-K+) ATPase by nonmolar concentrations of GM1 ganglioside — J. Neurochem.37, 350, 1981.

    Article  PubMed  CAS  Google Scholar 

  34. Levin E. R., Hanscom T. A., Fisher M., Lauvstad W. A., Lui A., Ryan A., Glokner D., Levin S. R.: The influence of pyridoxine in diabetic peripheral neuropathy — Diabetes Care4, 606, 1981.

    Article  PubMed  CAS  Google Scholar 

  35. Mingione A., Monteleone M., Paruzzi G., Soragni O., Cristiani G., Moretti C., Mega W., Scanabissi F.: Research in the use of cerebral gangliosides in neurolysis of the upper limb — Clin. Neurophysiol.19, 353, 1979.

    CAS  Google Scholar 

  36. Noël P.: Sensory nerve conduction in the upper limbs at various stages of diabetic neuropathy — J. Neurol. Neurosurg. Psychiat.36, 786, 1973.

    PubMed  Google Scholar 

  37. Norido F., Canella R., Aporti F.: Acceleration of nerve regeneration by gangliosides estimated by the somatosensory evoked potentials — Experientia (Basel)37, 301, 1981.

    CAS  Google Scholar 

  38. Norido F., Canella R., Gorio A.: Ganglioside treatment on neuropathy in diabetic mice — Muscle and Nerve5, 107, 1982.

    Article  PubMed  CAS  Google Scholar 

  39. Obata K., Oide M., Handa S.: Effects of glycolipids onin vitro development of neuromuscular function — Nature (Lond.)266, 369, 1977.

    Article  CAS  Google Scholar 

  40. Pietri A., Ehle A. L., Raskin P.: Changes in nerve conduction velocity after six weeks of glucoregulation with portable insulin pumps — Diabetes29, 668, 1980.

    Article  PubMed  CAS  Google Scholar 

  41. Porte D. Jr., Graf R. J., Halter J. B., Pfelifer M. A., Halar E.: Diabetic neuropathy and plasma glucose control — Amer. J. Med.70, 195, 1981.

    Article  PubMed  Google Scholar 

  42. Pozza G., Saibene V., Comi G., Canal N.: The effect of ganglioside administration in human diabetic peripheral neuropathy. In:Rapport M. M., Gorio A. (Eds): Gangliosides in neurological and neuromuscular function, development and repair. Raven Press, New York, 1981; p. 253.

    Google Scholar 

  43. Purpura D. P.: Pathobiology of cortical neurons in metabolic and unclassified amentias. In:Katzman R. (Ed.): Congenital and acquired cognitive disorders. Raven Press, New York, 1979; p. 43.

    Google Scholar 

  44. Purpura D. P., Baker H. J.: Meganeurites and other aberrant processes of neurons in feline GMI gangliosidoses: a Golgi study — Brain Res.143, 13, 1978.

    Article  PubMed  CAS  Google Scholar 

  45. Saibene V., Brambilla L., Bertoletti A., Bolognani L., Pozza G.: Chromatographic and colorimetric detection of glycosylated hemoglobins: a comparative analysis of two different methods — Clin. chim. Acta93, 199, 1979.

    Article  PubMed  CAS  Google Scholar 

  46. Sidenius P., Jakobsen J.: Reversibility and preventability of the decrease in slow axonal transport velocity in experimental diabetes — Diabetes31, 689, 1982.

    PubMed  CAS  Google Scholar 

  47. Tong H. I.: Influence of neurotrophic vitamins on the nerve conduction velocity in diabetic neuropathy — Ann. Acad. Med. (Singapore)9, 65, 1980.

    CAS  Google Scholar 

  48. Troni W.: Analysis of conduction velocity in the H pathway. Part 2 and electrophysiological study in diabetic polyneuropathy — J. Neurol. Sci.51, 235, 1981.

    Article  PubMed  CAS  Google Scholar 

  49. Ward J. B. D., Barnes C. G., Fisher D. J., Jessop D. J., Baker R. W. R.: Improvement in nerve conduction following treatment in newly diagnosed diabetics — Lanceti, 428, 1971.

    Article  Google Scholar 

  50. Whitehouse F. W.: Two minutes with diabetes — Med. Tms. (N.Y.)108, 132, 1980.

    CAS  Google Scholar 

  51. Who: Peripheral neuropathies. Who Tech. Rep. Ser. No. 654: 77, Geneva, 1980; p. 27.

  52. Willinger M., Schachner M.: GM1 ganglioside as a marker for neuronal differentiation in mouse cerebellum — Develop. Biol.74, 101, 1980.

    Article  PubMed  CAS  Google Scholar 

  53. Winer D. J.: Statistical principles in experimental design. 2nd ed. McGrow-Hill, New York, 1971.

    Google Scholar 

  54. Yagihashi S., Tokui A., Kashiwamura H., Takagi S., Iamamura K.:In vivo effect of methylcobalamin on the peripheral nerve structure in streptozotocin diabetic rats — Hormone metab. Res.14, 10, 1982.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Istituto di Medicina Clinica Cattedra di Patologia Medica, Università di Padova, Via Giustiniani, 2 - 35100, Padova, Italy

    Gaetano Crepaldi, Domenico Fedele & Antonio Tiengo

  2. Clinica delle Malattie Nervose e Mentali, Università di Padova, Italy

    Leontino Battistin & Paolo Negrin

  3. Clinica Medica Generale e Terapia Medica VIII, Università di Milano, Italy

    Guido Pozza

  4. Clinica delle Malattie Nervose e Mentali, Università di Milano, Italy

    Nicola Canal & Gian Carlo Comi

  5. Istituto di Medicina Interna, Università di Torino, Italy

    Gianfranco Lenti & Gianfranco Pagano

  6. Clinica delle Malattie Nervose e Mentali, Università di Torino, Italy

    Ludovico Bergamini & Walter Troni

  7. Reparto di Endocrinologia, Ospedale Generale Umberto I Mestre, Italy

    Francesco Frigato

  8. Reparto di Neurologia, Ospedale Generale Umberto I Mestre, Italy

    Cesare Ravenna & Corrado Mezzina

  9. Servizio Ricerca Clinica Fidia/Abano Terme, Italy

    Roberta Gallato, Danilo Massari, Marino Massarotti & Rita Matano

  10. Istituto di Statistica, Università di Padova, Italy

    Francesco Grigoletto

  11. Division of Biostatistics, University of Rochester/N.Y., USA

    Hank Davis

  12. Bio/Basics International, New Jersey, USA

    Monroe Klein

Authors
  1. Gaetano Crepaldi
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  2. Domenico Fedele
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  3. Antonio Tiengo
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  6. Guido Pozza
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  7. Nicola Canal
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  8. Gian Carlo Comi
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  14. Cesare Ravenna
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  21. Hank Davis
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  22. Monroe Klein
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Crepaldi, G., Fedele, D., Tiengo, A. et al. Ganglioside treatment in diabetic peripheral neuropathy: A multicenter trial. Acta diabet. lat 20, 265–276 (1983). https://doi.org/10.1007/BF02581271

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