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Diabetic Neuropathy: Models, Mechanisms and Mayhem

Published online by Cambridge University Press:  18 September 2015

P.K. Thomas
P.K. Thomas*
Affiliation:
Royal Free Hospital School of Medicine and Institute of Neurology, London, UK
*
Department of Neurological Science, Royal Free Hospital School of Medicine, Rowland Hill Street, London, England NW3 2PF
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Abstract:

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Rational treatment of diabetic polyneuropathy depends upon establishing its cause, which is at present unknown. A number of animal models of diabetes have been examined and although abnormalities are detectable in the peripheral nervous system they do not duplicate the degenerative neuropathy encountered in the human. The relevance of these abnormalities is therefore uncertain, although they may reflect the earlier changes in man. For human neuropathy, it is likely that vascular lesions or an abnormal susceptibility to mechanical injury are responsible for focal neuropathies. The evidence that ischaemia and hypoxia are responsible for the diffuse sensory neuropathy and autonomic polyneuropathy is still equivocal and it is often difficult to establish whether the vascular changes are primary or secondary. Metabolic explanations, such as sorbitol accumulation in nerve, have not so far been adequately validated by responses to treatment. The manifestations of diabetic neuropathy are complex and a single explanation should not be sought.

Type
Articles
Information
Canadian Journal of Neurological Sciences , Volume 19 , Issue 1 , February 1992 , pp. 1 - 7
Copyright
Copyright © Canadian Neurological Sciences Federation 1992

References

1. Jakobsen, J, Christiansen, JS, Kristoffersen, I, et al. Autonomic and somatosensory function after 2 years of continuous subcutaneous insulin in type 1 diabetes. Diabetes 1988; 37: 452–455.CrossRefGoogle Scholar
2. Kennedy, WR, Navarro, X, Goetz, FC, et al. Effects of pancreatic transplantation on diabetic neuropathy. N Engl J Med 1990; 322: 1031–1037.CrossRefGoogle ScholarPubMed
3. Gregersen, G.Diabetic neuropathy: influence of age, sex, metabolic control, and duration of diabetes on motor conduction velocity. Neurology (Minneap) 1967; 17: 972–980.CrossRefGoogle ScholarPubMed
4. Ward, JD, Barnes, CG, Fisher, DJ, et al. Improvement in nerve conduction following treatment in newly-diagnosed diabetics. Lancet 1971; 1:428–431.CrossRefGoogle ScholarPubMed
5. Steiness, IB.Vibratory perception in diabetics during arrested blood flow to the limb. Acta Med Scand 1959; 163: 195–205.CrossRefGoogle ScholarPubMed
6. Ritchie, JM, A note on the mechanism of resistance to anoxia and ischaemia in pathophysiological mammalian myelinated nerve. J Neurol Neurosurg Psychiatry 1985; 48: 274–277.CrossRefGoogle ScholarPubMed
7. Archer, AG, Watkins, PJ, Thomas, PK, et al. The natural history of acute painful neuropathy in diabetes mellitus. J Neurol Neurosurg Psychiatry 1983; 46: 491–499.CrossRefGoogle ScholarPubMed
8. Subramony, SH, Wilbourn, AJ.Diabetic proximal neuropathy. Clinical and electromyographic studies. J Neurol Sci 1982; 53: 293–301.Google ScholarPubMed
9. Sima, AAF, Lattimer, SA, Yagihashi, S, et al. Axoglial dysjunction. A novel structural lesion responsible for poorly reversible nerve conduction slowing in the spontaneously diabetic BB rat. J Clin Invest 1986; 77: 474–479.CrossRefGoogle Scholar
10. Sima, AAF, Zang, WX, Tze, WJ, et al. Diabetic neuropathy in the streptozotocin diabetic rat and the effect of allogenic islet cell transplantation. Diabetes 1988; 37: 1129–1136.CrossRefGoogle Scholar
11. Pryce, TD.On diabetic neuritis, with a clinical and pathological description of three cases of diabetic pseudo-tabes. Brain 1983; 16: 416–434.CrossRefGoogle Scholar
12. Woltman, HW, Wilder, RM.Diabetes mellitus: pathological changes in the spinal cord and peripheral nerves. Arch Intern Med 1929; 44: 576–603.CrossRefGoogle Scholar
13. Hutchinson, EC, Liversedge, LA.Neuropathy in peripheral vascular disease: its bearing on diabetic neuropathy. Q J Med 1956; 25: 269–274.Google ScholarPubMed
14. Eames, RA, Lange, LS.Clinical and pathological study of ischaemic neuropathy. J Neurol Neurosurg Psychiatry 1967; 30: 215–226.CrossRefGoogle ScholarPubMed
15. Chopra, JS, Hurwitz, LJ.A comparative study of peripheral nerve conduction in diabetes and nondiabetic occlusive peripheral vascular disease. Brain 1969; 92: 83–96.CrossRefGoogle ScholarPubMed
16. Chopra, JS, Hurwitz, LJ.Internodal length of sural nerve fibres in chronic occlusive vascular disease. J Neurol Neurosurg Psychiatry 1967; 30:201–214.CrossRefGoogle ScholarPubMed
17. Fagerberg, SE.Diabetic neuropathy: a clinical and histological study on the significance of vascular affections. Acta Med Scand 1959; 164(Suppl):354.Google Scholar
18. Harriman, D.Ischaemic factor in diabetic neuropathy. In: Proc 4th Internal Cong Neuropathol. Stuttgart, Thieme, 1962; 3: 164.Google Scholar
19. Dolman, CL.The morbid anatomy of diabetic neuropathy. Neurology (Minneap) 1963; 13: 135–142.CrossRefGoogle ScholarPubMed
20. Greenbaum, D, Richardson, PC, Salmon, MV, et al. Pathological observations on six cases of diabetic neuropathy. Brain 1964; 87: 201–204.Google ScholarPubMed
21. Thomas, PK, Lascelles, RG.The pathology of diabetic neuropathy. Q J Med 1966; 35: 485–509.Google Scholar
22. Neary, D, Ochoa, J, Gilliatt, RW.Sub-clinical entrapment neuropathy in man. J Neurol Sci 1975; 24: 283–298.CrossRefGoogle ScholarPubMed
23. Gilliatt, RW, Wilson, TG.A pneumatic-tourniquet test in the carpaltunnel syndrome. Lancet 1962; 2: 11–13.Google Scholar
24. Sunderland, S.The nerve lesion in the carpal tunnel syndrome. J Neurol Neurosurg Psychiatry 1976; 39: 615–626.CrossRefGoogle ScholarPubMed
25. Asbury, AK, Aldredge, H, Hershberg, R, et al. Oculomotor palsy in diabetes mellitus: a clinico-pathological study. Brain 1970; 93: 555–566.CrossRefGoogle ScholarPubMed
26. Fujimura, H, Lacroix, C, Said, G.Vulnerability of nerve fibres to ischaemia: a quantitative study. Brain 1991; 114: 1929–1942.CrossRefGoogle Scholar
27. Raff, M, Sangalang, V, Asbury, AK.Ischemic mononeuropathy multiplex associated with diabetes mellitus. Arch Neurol (Chic) 1968; 18: 487–498.CrossRefGoogle ScholarPubMed
28. Sugimura, K, Dyck, PJ.Multifocal fiber loss in proximal sciatic nerve in symmetric distal diabetic neuropathy. J Neurol Sci 1982; 53: 501–509.CrossRefGoogle ScholarPubMed
29. Johnson, PC, Doll, SC, Cromer, DW.Pathogenesis of diabetic neuropathy. Ann Neurol 1986; 19: 450–457.CrossRefGoogle ScholarPubMed
30. Sima, AAF, Nathaniel, V, Bril, V, et al. Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetics and demonstration of axoglial dysjunction in human diabetic neuropathy. J Clin Invest 1988; 81: 349–364.CrossRefGoogle ScholarPubMed
31. Dyck, PJ, Lais, A, Karnes, JL, et al. Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy. Ann Neurol 1986; 19: 425–439.CrossRefGoogle ScholarPubMed
32. Llewelyn, JG, Thomas, PK, Gilbey, SG, et al. Pattern of myelinated fibre loss in the sural nerve in neuropathy related to type 1 (insulin-dependent) diabetes. Diabetologia 1988; 31: 162–167.CrossRefGoogle ScholarPubMed
33. Hallin, RG.Microneurography in relation to intraneural topography: somatotopic organization of median nerve fascicles in humans. J Neurol Neurosurg Psychiatry 1990; 53: 736–744.CrossRefGoogle ScholarPubMed
34. Dyck, PJ, Hansen, S, Karnes, J, et al. Capillary number and percentage closed in human diabetic sural nerve. Proc Natl Acad Sci USA 1985; 82: 2513–2517.CrossRefGoogle ScholarPubMed
35. Yasuda, H, Dyck, PJ.Abnormalities of endoneurial microvessels and sural nerve pathology in diabetic neuropathy. Neurology 1987; 37: 20–28.CrossRefGoogle ScholarPubMed
36. Powell, HC, Rosoff, J, Myers, RR.Microangiopathy in human diabetic neuropathy. Acta Neuropathol (Berl) 1985; 68: 295–305.Google ScholarPubMed
37. Malik, RA, Newrick, P, Sharma, AK, et al. Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy. Diabetologia 1989; 32:92–102.CrossRefGoogle ScholarPubMed
38. Bradley, J, Thomas, PK, King, RHM, et al. Morphometry of endoneurial capillaries in diabetic sensory and autonomic neuropathy. Diabetologia 1990; 33: 611–618.Google ScholarPubMed
39. Timperley, WR, Boulton, AJM, Davies-Jones, GABet al. Small vessel disease in progressive diabetic neuropathy with good control. J Clin Pathol 1985; 38: 1030–1041.CrossRefGoogle Scholar
40. Vital, C, Leblanc, M, Vallat, JM, et al. Études ultrastructurale du nerf périphérique chez 16 diabétiques sans neuropathie clinique. Comparison avec 16 neuropathies diabétiques et 16 neuropathies non diabétiques. Acta Neuropathol (Berl) 1974; 30: 63–72.Google Scholar
41. Behse, F, Buchthal, F, Carlsen, F.Nerve biopsy and conduction studies in diabetic neuropathy. J Neurol Neurosurg Psychiatry 1977; 40: 1072–1082.CrossRefGoogle ScholarPubMed
42. King, RHM, Llewelyn, JG, Thomas, PK, et al. Diabetic neuropathy: abnormalities of Schwann cell and perineurial basal laminae. Implications for diabetic vasculopathy. Neuropathol Appl Neurobiol 1989; 15: 339–355.CrossRefGoogle ScholarPubMed
43. Korthals, JK, Gieron, MA, Dyck, PJ.Intima of epineurial arterioles is increased in diabetic neuropathy. Neurology 1988; 38: 1582–1586.CrossRefGoogle Scholar
44. Timperley, WR, Ward, JD, Preston, FE, et al. A reassessment of vascular factors in relation to intravascular coagulation. Diabetologia 1976; 12: 237–243.CrossRefGoogle ScholarPubMed
45. Newrick, PG, Wilson, AJ, Jakubowski, J, et al. Sural nerve oxygen tension in diabetes. Br Med J 1986; 293: 1053–1054.Google ScholarPubMed
46. Gaylarde, PM, Fonseca, VA, Llewelyn, JG, et al. Transcutaneous oxygen tension in the legs and feet of diabetics. Diabetes 1988; 37:714–716.CrossRefGoogle Scholar
47. Flynn, MD, Edmonds, ME, Tooke, JE, et al. Direct measurements of capillary blood flow in the diabetic neuropathic foot. Diabetologia 1988; 31: 652–656.CrossRefGoogle ScholarPubMed
48. Rechthand, E, Smith, Q, Latker, C, et al. Altered blood-nerve barrier permeability to small molecules in experimental diabetes mellitus. J Neuropathol Exp Neurol 1987; 46: 302–314.CrossRefGoogle ScholarPubMed
49. Ohi, T, Poduslo, JF, Dyck, PJ.Increased endoneurial albumin in diabetic polyneuropathy. Neurology 1985; 35: 1790–1791.CrossRefGoogle ScholarPubMed
50. Poduslo, JF, Curran, GL, Dyck, PJ.Increase in albumin, IgG, and IgM blood-nerve barrier indices in human diabetic neuropathy. Proc Natl Acad Sci USA 1988; 85: 4879–4883.CrossRefGoogle ScholarPubMed
51. Patel, NJ, Misra, VP, Dandona, P, et al. The effect of non-enzymatic glycation of serum proteins on their permeation into peripheral nerve in normal and streptozotocin-diabetic rats. Diabetologia 1991; 34:78–80.CrossRefGoogle ScholarPubMed
52. Tuck, RR, Schmelzer, JD, Low, PA.Endoneurial blood flow and oxygen tension in the sciatic nerve of rats with experimental diabetic neuropathy. Brain 1984; 107: 935–950.CrossRefGoogle ScholarPubMed
53. Low, PA, Tuck, RR, Dyck, PJ, et al. Prevention of some electrophysiologic and biochemical abnormalities with oxygen supplementation in experimental diabetic neuropathy. Proc Natl Acad Sci USA 1984; 81:6894–6898.CrossRefGoogle ScholarPubMed
54. Sharma, AK, Thomas, PK.Peripheral nerve structure and function in experimental diabetes. J Neurol Sci 1974; 23: 1–15.CrossRefGoogle ScholarPubMed
55. Zochodne, DW, Lam, T Ho.Normal hydrogen clearance but lowered oxygen tension in the sciatic nerve endoneurium of young diabetic animals. Can J Neurol Sci 1991: in press (Proceedings of 26th Canadian Congress of Neurological Science).Google Scholar
56. Appenzeller, O, Parks, RD, MacGee, J.Peripheral neuropathy in chronic disease of the respiratory tract. Am J Med 1968; 44: 873–880.CrossRefGoogle ScholarPubMed
57. Narayan, M, Ferranti, R.Nerve conduction impairment in patients with respiratory insufficiency and severe chronic hypoxemia. Arch Phys Med Rehab 1978; 59: 188–192.Google ScholarPubMed
58. Faden, A, Mendoza, E, Flynn, F.Subclinical neuropathy associated with chronic obstructive pulmonary disease. Possible pathophysiologial role of smoking. Arch Neurol 1976; 38: 639–642.Google Scholar
59. Vila, A, Reymond, F, Paramelle, B, et al. Neuropathies et insufficiantes respiratoire chronique: étude électrophysiologique. Rev Electroencephalogr Neurophysiol Clin 1985; 15: 331–340.CrossRefGoogle Scholar
60. Stoebner, P, Mezin, P, Vila, A, et al. Microangiopathy of endoneurial vessels in hypoxemic chronic obstructive pulmonary disease (COPD). A quantitative ultrastructural study. Acta Neuropathol (Berl) 1989; 78: 388–395.CrossRefGoogle ScholarPubMed
61. McLeod, JG, Pollard, JG.Neuropathies in systemic diseases: hidden and overt. In: Asbury, AK, Gilliatt, RW, eds. Peripheral Nerve Disorders: A Practical Approach. London: Butterworths, 1984: 92–125.Google Scholar
62. Greene, DA, Winegrad, AI.In vitro studies of the substrates for energy production and the effects of insulin on glucose utilization on the neural components of peripheral nerve. Diabetes 1979; 28: 878–887.CrossRefGoogle ScholarPubMed
63. Jacobs, JM, MacFarlane, RM, Cavanagh, JB.Vascular leakage in the dorsal root ganglia of the rat studied with horseradish peroxidase. J Neurol Sci 1976; 29: 95–107.CrossRefGoogle ScholarPubMed
64. Gabbay, KH, Merola, LO, Field, RA.Sorbitol pathway: presence in nerve and cord with substrate accumulation in diabetes. Science 1966; 151:209–210.CrossRefGoogle ScholarPubMed
65. Yue, DK, Hanwell, MA, Satchell, PM, et al. The effects of aldose reductase inhibition on nerve sorbitol and myoinositol in diabetic and galactosemic rats. Metabolism 1984; 33: 1119–1122.CrossRefGoogle ScholarPubMed
66. Judzewitsch, RG, Jaspan, JB, Polonsky, KS, et al. Aldose reductase inhibition improves nerve conduction velocity in diabetic patients. N Engl J Med 1983; 308: 119–125.CrossRefGoogle ScholarPubMed
67. Sima, AAF, Bril, V, Nathaniel, V, et al. Regeneration and repair of myelinated fibers in sural-nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil. N Engl J Med 1988; 319:548–555.CrossRefGoogle ScholarPubMed
68. Das, PK, Bray, GM, Aguayo, AJ, et al. Decreased ouabain-sensitive sodium-potassium ATPase activity in sciatic nerves of rats with streptozotocin-induced diabetes. Exp Neurol 1976; 53: 285–288.CrossRefGoogle Scholar
69. Greene, DA, Lattimer, SA, Sima, AAF.Sorbitol, phosphoinositides, and sodium-potassium ATPase in the pathogenesis of diabetic complications. N Engl J Med 1987; 316: 599–606.Google ScholarPubMed
70. Lambourne, JE, Tomlinson, DR, Brown, AM, et al. Opposite effects of diabetes and galactosaemia on adenosine triphosphatase activity in rat nervous tissue. Diabetologia 1987; 30: 360–362.CrossRefGoogle ScholarPubMed
71. Llewelyn, JG, Patel, NJ, Thomas, PK, et al. Sodium, potassium adenosine triphosphatase activity in peripheral nerve tissue of galactosaemic rats. Effects of aldose reductase inhibition. Diabetologia 1987; 30: 971–972.CrossRefGoogle ScholarPubMed
72. Dyck, PJ, Zimmerman, BR, Vilen, TH, et al. Nerve glucose, fructose, sorbitol, myo-inositol, and fiber degeneration and regeneration in diabetic neuropathy. N Engl J Med 1988; 319: 542–548.CrossRefGoogle ScholarPubMed
73. Thomas, PK, Wright, DW, Tzebelikos, E.Amino acid uptake by dorsal root ganglia from streptozotocin-diabetic rats. J Neurol Neurosurg Psychiatry 1984; 47: 912–916.CrossRefGoogle ScholarPubMed
74. Jakobsen, J, Sidenius, P.Decreased axonal transport of structural proteins in streptozotocin diabetic rats. J Clin Invest 1980; 66: 292–297.CrossRefGoogle ScholarPubMed
75. Sharma, AK, Britland, ST, Young, RJ, et al. Morphological abnormalities in the sural nerve of patients with and without clinical syndromes of diabetic neuropathy. In: Ward, J, Goto, Y, eds. Diabetic Neuropathy. Chichester: John Wiley, 1990: 29–45.Google Scholar
76. Sugimura, K, Dyck, PJ.Sural nerve myelin thickness and axis cylinder caliber in human diabetes. Neurology (NY) 1981; 31: 1087–1091.Google ScholarPubMed
77. Llewelyn, JG, Gilbey, SG, Thomas, PK, et al. Sural nerve morphometry in diabetic autonomic and painful sensory neuropathy: a clinicopathological study. Brain 1991; 114: 867–892.Google ScholarPubMed
78. Brownlee, M, Cerami, M, Vlassara, H.Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988; 318: 1315–1321.Google ScholarPubMed
79. Said, G, Slama, G, Selva, J.Progressive centripetal degeneration of axons in small fibre type diabetic polyneuropathy. A clinical and pathological study. Brain 1983; 106: 791–807.CrossRefGoogle Scholar
80. Waldbillig, RJ, LeRoith, D.Insulin receptors in the peripheral nervous system: a structural and functional analysis. Brain Res 1987; 409: 215–220.CrossRefGoogle ScholarPubMed
81. Llewelyn, JG, Patel, NJ, Thomas, PK, et al. Insulin receptors in sensory and sympathetic ganglia and in peripheral nerve. J Neurol 1988; 235: S16.Google Scholar
82. Duchen, LW, Anjorin, A, Watkins, PJ, et al. Pathology of autonomic neuropathy in diabetes. Ann Intern Med 1980; 92: 301–303.CrossRefGoogle ScholarPubMed
83. Brown, FM, Brink, SJ, Freeman, R, et al. Anti-sympathetic nervous system antibodies. Diminished catecholamines with orthostasis. Diabetes 1989; 38:938–941.CrossRefGoogle ScholarPubMed