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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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.
Bergamini L., Troni W., Lacquaniti F.: Le neuropatie diabetiche — Omnia med. ther. (Arch.)13, 1, 1980.
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.
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.
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.
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.
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.
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.
Cuatrecasas P.: Gangliosides and membrane receptors for cholera toxin — Biochemistry (Wash.)12, 3558, 1973.
Culebras A., Alio J., Herrera J. L.: Effect of aldose reductase inhibitor on diabetic peripheral neuropathy — Arch. Neurol. (Chic.)38, 133, 1981.
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.
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.
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.
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.
Ferrari G., Fabris M., Gorio A.: Gangliosides enhance neurite outgrowth in PC 12 cells — Develop. Brain. Res.8, 215, 1983.
Fishman P. H., Brady R. O.: Biosynthesis and function of gangliosides — Science194, 906, 1976.
Fleiss J. L.: Statistical methods for rates and proportions. J. Wiley & Sons, New York, 1973.
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.
Gabbay K. H., Spack N., Loo S., Hirsch H., Ackil A. A.: Aldose reductase inhibition: studies with alrestatin — Metabolism28 (Suppl. 1), 471, 1979.
Gart J. S.: An exact test for comparing matched proportions in cross-over designs — Biometrika5, 75, 1969.
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.
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.
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.
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.
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.
Gorio A., Marini P., Zanoni R.: Muscle reinnervation III. Motoneuron sprouting capacity, enhancement by exogenous gangliosides — Neuroscience8, 417, 1983.
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.
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.
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.
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.
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.
Kynoch P. A. M., Lehman M.: Rapid estimation (2 1/2 hours) of glycosylated hemoglobin for routine purposes — Lancetii, 16, 1977.
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.
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.
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.
Noël P.: Sensory nerve conduction in the upper limbs at various stages of diabetic neuropathy — J. Neurol. Neurosurg. Psychiat.36, 786, 1973.
Norido F., Canella R., Aporti F.: Acceleration of nerve regeneration by gangliosides estimated by the somatosensory evoked potentials — Experientia (Basel)37, 301, 1981.
Norido F., Canella R., Gorio A.: Ganglioside treatment on neuropathy in diabetic mice — Muscle and Nerve5, 107, 1982.
Obata K., Oide M., Handa S.: Effects of glycolipids onin vitro development of neuromuscular function — Nature (Lond.)266, 369, 1977.
Pietri A., Ehle A. L., Raskin P.: Changes in nerve conduction velocity after six weeks of glucoregulation with portable insulin pumps — Diabetes29, 668, 1980.
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.
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.
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.
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.
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.
Sidenius P., Jakobsen J.: Reversibility and preventability of the decrease in slow axonal transport velocity in experimental diabetes — Diabetes31, 689, 1982.
Tong H. I.: Influence of neurotrophic vitamins on the nerve conduction velocity in diabetic neuropathy — Ann. Acad. Med. (Singapore)9, 65, 1980.
Troni W.: Analysis of conduction velocity in the H pathway. Part 2 and electrophysiological study in diabetic polyneuropathy — J. Neurol. Sci.51, 235, 1981.
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.
Whitehouse F. W.: Two minutes with diabetes — Med. Tms. (N.Y.)108, 132, 1980.
Who: Peripheral neuropathies. Who Tech. Rep. Ser. No. 654: 77, Geneva, 1980; p. 27.
Willinger M., Schachner M.: GM1 ganglioside as a marker for neuronal differentiation in mouse cerebellum — Develop. Biol.74, 101, 1980.
Winer D. J.: Statistical principles in experimental design. 2nd ed. McGrow-Hill, New York, 1971.
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.
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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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DOI: https://doi.org/10.1007/BF02581271