Summary
Insulin neuritis, or painful neuropathy following rapid improvement in glycaemic control, is well recognised but its aetiology is unclear. An understanding of the processes involved in the genesis of acute painful neuropathy of rapid glycaemic control may give an insight into the early pathogenetic factors leading to diabetic nerve damage in general. We have identified five subjects with insulin neuritis including one who developed severe autonomic neuropathy following treatment with insulin. Subjects underwent: 1) assessment of neuropathic symptom and deficit scores; 2) quantitative sensory and electro-physiological studies and 3) sural nerve epineurial vessel photography and fluorescein angiography in vivo. The sural nerve photographs were independently graded by an ophthalmologist. All subjects with insulin neuritis presented with severe sensory symptoms but clinical examination and electrophysiological tests were normal except in the subject with the severe autonomic neuropathy in whom all the tests were abnormal. On nerve photography, there was an abundance of epineurial nutrient vessels although these showed severe abnormalities including arteriolar attenuation, tortuosity and arterio-venous shunting in all subjects. Proliferating neural ‘new vessels’ which bear striking similarities to those found in the retina and that were more leaky to fluorescein than normal vessels, were observed in three subjects. Venous distension and/or tortuosity was also observed in three subjects and this was most marked in the subject with severe autonomic neuropathy. This study shows that epineurial nutrient vessel anatomy is abnormal in subjects with acute painful neuropathy of rapid glycaemic control, a condition previously thought to be purely metabolic in origin. The presence of epineurial arterio-venous shunting and a fine network of vessels resembling the new vessels of the retina, may lead to a ‘steal’ effect rendering the endoneurium ischaemic. This process may be important in the genesis of neuropathic pain, and further supports the importance of vascular factors in the pathogenesis of diabetic neuropathy.
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Abbreviations
- NIDDM:
-
Non-insulin-dependent diabetes mellitus
- IDDM:
-
insulin-dependent diabetes mellitus
References
Thomas PK, Eliasson SG (1984) Diabetic neuropathy. In: Dyck PJ, Thomas PK, Lambert EH, Bunge E (eds) Peripheral neuropathy, 2nd edn, vol 2. Saunders, Philadelphia, pp 1773–1810
Greene D, Lattimer SA, Sima AAF (1987) Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engl J Med 316: 599–606
Tomlinson DR (1992) The pharmacology of diabetic neuropathy. Diab Metab Rev 8: 67–84
Tesfaye S, Malik R, Ward JD (1994) Vascular factors in diabetic neuropathy. Diabetologia 37: 847–854
Cameron NE, Cotter MA (1994) The relationship of vascular changes to metabolic factors in diabetes mellitus and their role in the development of peripheral nerve complications. Diab Metab Rev 10: 189–224
Boulton AJM (1993) Causes of neuropathic pain. Diabet Med 10 [Suppl 2]:87S-88S
Ward JD (1989) Diabetic neuropathy. Br Med Bull 45(1):111–126
Caravati CM (1933) Insulin neuritis: a case report. Va Med Mon 59: 745–746
Jordan WR (1936) Neuritic manifestations in diabetes mellitus. Arch Intern Med 57: 308–366
Rudy A, Epstein SH (1945) Review of 100 cases of ‘diabetic neuropathy’ followed from 1 to 10 years. J Clin Endocrinol Metab 5: 92–98
Martin MM (1953) Diabetic neuropathy. Brain 76: 594–624
Ellenberg M (1958) Diabetic neuropathy precipitating after institution of diabetic control. Am J Med Sci 236: 466–471
Krentz AJ (1989) Acute symptomatic diabetic neuropathy associated with normalisation of haemoglobin A1. J Roy Soc Med 82: 767–768
Llewelyn JG, Thomas PK, Fonseca V, King RHM, Dan-dona P (1986) Acute painful diabetic neuropathy precipitated by strict glycaemic control. Acta Neuropathol (Berl) 72: 157–163
Ward JD (1990) Clinical features of diabetic peripheral neuropathies. In: Ward JD, Goto Y (eds) Diabetic neuropathy. Wiley, Chichester, pp 281–296
Tesfaye S, Harris N, Jakubowski J et al. (1993) Impaired blood flow and arterio-venous shunting in human diabetic neuropathy: a novel technique of nerve photography and fluorescein angiography. Diabetologia 36: 1266–1274
Newrick PG, Wilson AJ, Jakubowski J, Boulton AJM, Ward JD (1986) Sural nerve oxygen tension in diabetes. BMJ 293: 1053–1054
Malik RA, Tesfaye S, Thompson SD et al. (1993) Endoneurial localisation of microvascular damage in human diabetic neuropathy. Diabetologia 36: 454–459
Britland ST, Young RJ, Sharma AK, Clarke BF (1990) Relationship of endoneurial capillary abnormalities to type and severity of diabetic polyneuropathy. Diabetes 39: 909–913
Dyck PJ, Lais A, Karnes JL, O'Brien P, Rizza R (1986) Fibre loss is primary and multifocal in sural nerves in diabetic polyneuropathy. Ann Neurol 19: 425–439
Malik RA, Tesfaye S, Thompson SD et al. (1994) Trans-perineurial capillary abnormalities in the sural nerves of patients with diabetic neuropathy. Microvascular Res 48: 236–245
Cameron NE, Cotter MA, Low PA (1991) Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits. Am J Physiol 261:E1-E8
Low PA, Tuck RR, Dyck PJ, Schmelzer JD, Yao JK (1984) Prevention of some electrophysiologic and biochemical abnormalities with oxygen supplementation in experimental diabetic neuropathy. Proc Natl Acad Sci USA 81: 6894–6898
Cameron NE, Cotter MA, Robertson S (1992) Angiotensin converting enzyme inhibition prevents the development of muscle and nerve dysfunction and stimulates angiogenesis in streptozotocin-diabetic rats. Diabetologia 35: 12–18
Hotta N, Kakuta H, Fukasawa H et al. (1992) Effect of niceritrol on streptozotocin-induced diabetic neuropathy in rats. Diabetes 41: 587–591
Dandona P, Bolger J, Boag F, Abrams JD (1985) Rapidly progressive retinopathy following strict diabetic control. BMJ 290: 895–896
Van Ballegooie E, Hooymans JMM, Timmerman Z et al. (1984) Rapid deterioration of diabetic retinopathy during treatment with continuous subcutaneous insulin infusion. Diabetes Care 7: 232–235
O'Brien IAD, O'Hare P, Corrall RJM (1986) Heart rate variability in healthy subjects: effect of age and derivation of normal ranges for tests of autonomic function. Br Heart J 55: 348–354
Tesfaye S, Harris N, Wilson RM, Ward JD (1992) Exercise induced conduction velocity increment: a marker of impaired nerve blood flow in diabetic neuropathy. Diabetologia 35: 155–159
Archer AG, Watkins PJ, Thomas PK, Sharma AK, Payan J (1983) The natural history of acute painful neuropathy in diabetes mellitus. J Neurol Neurosurg Psychiatry 26: 491–499
Patel V, Rassam S, Newsom R, Wiek J, Kohner E (1992) Retinal blood flow in diabetic retinopathy. BMJ 305: 678–683
Pirart J (1978) Diabetes mellitus and its degenerative complications: a prospective study of 4400 patients observed between 1947 and 1973. Diabetes Care 1: 168–188, 252-263
Kihara M, Zollman PJ, Smithson IL, Lagerlund TD, Low PA (1994) Hypoxic effect of exogenous insulin on normal and diabetic peripheral nerve. Am J Physiol 266:E980-E985
Reja A, Tesfaye S, Harris ND, Ward JD (1995) Is ACE inhibition with lisinopril helpful in diabetic neuropathy? Diabet Med 12: 307–309
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Tesfaye, S., Malik, R., Harris, N. et al. Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis). Diabetologia 39, 329–335 (1996). https://doi.org/10.1007/BF00418349
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DOI: https://doi.org/10.1007/BF00418349