Fatema Jawad  ( Sughrabai MilIwailla Hospital, Karachi. )

Diabetic neuropathy, a troublesome com­plication of Diabetes Mellitus is encountered in an incidence of 5 to 50 percent of cases.¹ According to the distribution it is classed as symmetric distal polyneuropathy, symmetric proximal motor neuropathy and focal asymmetric neuropathy^2-4. In most cases the sensory, motor and autonomic nerves are involved. The small fibre type neuropathy manifests as pain and parasthesias in the lower extremities with less involvement of reflexes, position and vibration sensation. Autonomic sensation is usually present. In the large fibre type symmetric polyneuropathy there is loss of ankle reflexes decreased position and vibration sense and sensory ataxia. The cause for selective nerve fibre involve­ment is not known. The element of pain manifests itself due to acute axonal degeneration involving fibres of all sizes⁵, and is associated with profound weight loss and depression. The cause of the pain is attributed to regeneration of small and unmye­linated fibres causing spontaneous nerve impu­lses,^6-7  or hypoglycaemia causing increased pain intensity⁸. A motor neuropathy may result from re­peated episodes of hypoglycaemia due to spinal motor neuron loss⁹. Weakness and wasting of hand muscles and foot drop preceded by paraesthesias are usually observed. Focal neuropathy may affect any cranial or peripheral nerve. The most commonly involved nerves are median, ulnar, common peroneal and femoral with the cranial nerves being the ill, VI and IV in frequency. Painful diabetic thoraco­abdominal neuropathy is another focal involve­ment seen in the fifth or sixth decade^10,11,12. Weight loss, is significant and provides a suspicion of malignancy. Hyperesthesia and hypaesthesia in the appropriate thoracic segment is suggestive of the diagnosis. Autonomic neuropathy is encountered in 20 to 40 percent of the diabetics.^13-16 The cardiovascular and genitourinary systems have been largely assessed. The most commonly obser­ved cardiovascular abnormalities are postural hypotension, resting tachycardia and painless myocardial infarction.¹⁶ Orthostatic hypotension involves both systolic and diastolic valves and as there is a blunted catecholamine response in these cases, the compensatory tachycardia is lacking. It has also been observed that blood pressure does not rise progressively during the early morning hours in Type I diabetics due to dysfunction of the autonomic nervous system. Silent or less painful infarction was observed in 42 percent 9f diabetics in comparison to 6 to 15 percent of the non-diabetics¹⁷. This is attributed to lesions in the afferent fibres running through the cardiac sympathetic nerves which carry the pain impu­lses^18-20. Despite recent advances, the exact patho­genesis of diabetic peripheral neuropathy remains unknown. Many theories have been proposed. Insulin deficiency may cause metabolic deran­gements but they fail to explain the development of a structural neuropathy. The sorbitol accumu­lation hypothesis is the most popular theory. Elevated glucose levels lead to saturation of hexokinase and collection of sorbitol causing direct toxicity by tissue swelling by osmotic effect²¹. Myoinositol, a precursor of polyphospho­inositides, an important element of nerve cellular functions, has been considered to play a role in diabetic neuropathy. Insulin deficiency and, hyperglycaemia cause reduced myoinositol con­centration correlating with reduced nerve con­duction velocity²². The hypoxia hypothesis²³ proposes that the diabetic state causes capillary abnormalities leading to decreased blood and oxygen delivery to nerves and consequent slowing of nerve con­duction. + To maintain normal blood glucose and lipids level in conjunction with ideal body weight has been the aim of treatment of Diabetes Mellitus. A relationship between the duration of Diabetes and development of neuropathies before therapy, with improvement of motor nerve conduction velocity after therapy, is flow well estab­lished^24-26. The improvement becomes evident until after six months of treatment. Lately aldose reductase inhibitors have been tried as therapy for diabetic neuropathy. These act on the nerve metabolism and a favour­able though small response has been achieved.^27,28 The substances used are Alrestatin, Sorbinil, toirestat which have been given multicentre trials but none have been approved for clinical use. Dietary myoinositol supplementation has given inconclusive and contradictory results. Vitamins, especially of the B group, do not show enough evidence to justify their use in diabetic neuropathy. Pyridoxine, used for over three months in a daily dose of 150 mg, proved to be ineffective in allevia­ting the symptoms of diabetic neuropathy.²⁹ Phenytoin commonly used in painful neuropathy.³⁰ should be avoided due to its inhibitory effect on insulin secretion. Carbamaze­pine has proved to be helpful after being tried in three controlled double blind studies^31-33 but should be reserved for refractory cases due to its potential toxicity. Patients with orthostatic hypotension should be instructed to sleep with head up tilt, use elastic stockings, increase salt in diet and to minimize sudden changes of posture. Drugs which have been suggested are Fluorohydrocortisone³⁴, indomethacin³⁵, a combination of . diphenhy­dramine and cimetidine³⁶ dihydroergotamine³⁷, metoclopramide,³⁸ and pindolol.³⁹ Bladder complications due to autonornic neuropathy can be very troublesome. Voidance every three hours with iritermittent catheteriza­tion is helpful. Cholinergic drugs as bethanechol may assist in triggering detrusor function. Urinary tract infection requires appropriate antibiotics and bladder neck resection is considered when all conservative measures fail. Male impotency re­quiiès psychological counselling before a penile prosthesis is considered.⁴⁰ Dysphagia or heart-burns due to oesophageal dysfunction may be managed with domperidone⁴¹ or bethanechol⁴². Metoclopramide relieves delayed gastric emptying in a dose of 10 mg before each meal and at bed time.⁴³ Diarrhoea may be treated with tetracyc­line although it resolves spontaneously. Patients with diabetic neuropathy should be encouraged to stop the use of tobacco and alcohol. Drugs known to aggravate peripheral neuropathies as isoniazid, nitrofurantoin, hydralizine and dapsone should be avoided.

1. Thomas, P.K. and Eliasson, S.G. Peripheral neuropathy. Edited by Dyck, P.J. , Thomas, P.K., Lambert, E.H. Bunge, R.W.B. Philadelphia Saunders, 1984; p. 1773.
2. Brown, M.J. and Asbury, A.K. Diabetic neuro­pathy. Ann. Neurol., 1984; 15:2.
3. Evans, R.W. and Harati, Y. What’s new; review of clinical presentations, pathophysiology, and treatment of diabetic neuropathies. Tex. Med., 1983;79 :50.
4. Dyck, P3., Jarnes, J. and Obrien, P.C. Diagnosis, staging asid classification of diabetic neuropathy and association with other complications. Edited by Dyck, P.J. , Thomas, P.K., Asbury A.K., winegrad, Al., Porte, D. Philadelphia, Saunders, 1987;p. 36.
5. Archer, A.G., Watkins, P3., Thomas, P.K., Sharma, A.K. and Payan, 3. The natwral history of acute painful neuropathy in diabetes mellitus. J. Neurol. Neurosurg. Psychiatry, 1983; 46:491.
6. Burchiel,K.J., Russel, L.C., Lee, R.P. and Sima, A.A. Spontaneous activity of primary afferent neurons in diabetic BB/Wistar rats; a possible mechanism of chronic neuropathic pain. Diabetes, 1985;34 :1210.
7. Liewelyn, T.G., Thomas, P.K., Fonseca, V., King, RH. and Dandona, P. Acute painful diabetic neuropathy precipitated by strict gly­caemic control. Acta Neuropathol (Berl), 1986;72 157.
8. Morley, G.K., Mooradian, A.D., Levine, A.L. and Morley, J.E. Mechanism of pain in diabetic peripheral neuropathy; effect of glucose on pain perception in humans. Am. J. Med., 1984;77 : 79.
9. Jaspan, J.B., woilman, RI., Bernstein, L. and Rubensteun, A.H. Hypoglycaemic peripheral neuropathy in association with insulinoma; implication of glucopenia rather than hyperin­ sulinism; case report and literature reviw. Medi­cine (Baltimore), 1982;61 : 33.
10. Ellenbeng, M. Diabetic truncal mononeuropathy a new clinical syndrome. Diabetes Care, 1978;1: 10.
11. Longstreth, G.F. and Newcomer, A.D. Abdo­minal pain ctused by diabetic radiculopathy. Ann. Intern. Med., 1977; 86: 166.
12. Boulton, A.J., Angus, E., Ayyar, D.R. and Weiss, D.R. Diabetic thoracic polyradiculopathy presenting as abdominal swelling. Br. Med. J. (Clin Res), 1984; 189 : 798.
13. Niakan, F., Harati, H. and Comstock, J.P. Dia­betic autonomic neuropathy. Metabolism, 1986;35 : 224.
14. McLead, T.G. and Tuck, R.R. Disorders of the autonomic nervous system. I. Pathophysiology and clinical features. Ann. Neurol., 1987; 21:419.
15. McLead, T.G. and Tuck, R.R. Disorders of the autonomic nervous system. 11. investigation and treatment. Ann. Neurol., 1987;21 :519.
16. Ewing, D.J. and Clarke, Bi. Diabetic autonomic neuropathy; present insights and future pros­pects. Diabetes Care, 1986; 9: 648.
17. Nesto, R.W. and Phillips, R.T. Asymptomatic myocardial ischaemia in diabetic patients. Am. J. Med., 1986; 80 (Suppl. 4C) : 40.
18. Faerman, I., Faccio, E., Mllei, R. et. al. Autono­mic neuropathy and painless myocardial infarc­tion in diabetic patients: histologic evidence of their relationship. Diabetes, 1977; 26 : 1147.
19. Campbell, I. W., Ewing, D.J. and Clarke, B.F. Painful myocardial infarction in severe diabetic autonomic neuropathy. Acta Diabetol. Lat., 1978; 15: 201.
20. Bradley, R.F. and Schonfeld, A. Diminished pain in diabetic patients with acute myocardial in­farction. Geriatrics, 1962; 17 : 322.
21. Eaton, R.P. Aldose reductase inhibition and the diabetic syndrome of limited joint mobility; implications for altered collagen hydration. Metabolism, 1986; 35 :119.
22. Greene, D.A., Lewis, R.A., Lattimer, S.A. and Brown, M.J. Selective effect, of myo-inositol administration on sciatic and tibial motor nerve conduction parameters in the Streptozocin­diabetic rat. Diabetes, 1982; 31: 573.
23. Low, P.A. Recent advances in the pathogenesis of diabetic neuropathy. Muscle Nerve, 1987; 10 :121.
24. Daube, J.R. Electrophysiologic testing, in diabe­tic neuropathy. Edited by Dyck, P3., Thomas, P.K., Asbury, A.K. , Winegrad, A.I., Porte, D. Philadelphia, Saunders, 1987; p. 162.
25. Fraser, D.M., Campbell, I.W., Ewing, D.J., Murray, A., Neilson, J.M. and Clarke, B.F. Peripheral and autonomic nerve function in newly diagnosed diabetes mellitus. Diabetes, 1977; 26 :546.
26. Horowitz, S.H. and Ginsberg-Fellner, F. lschae­mia and sensory nerve conduction in diabetes mellitus. Neurology, 1979 ;29 :695.
27. Judzewitsch, R.G., Jaspan, J.B., Polonsky, K.S., Weinberg, C.R., Halter, J.B., Halas, E., Pfeifer, M.A., Verkadinovic, C., Bernstein, L., Schneider, M., Liang, K., Gabbay, K.H., Rubenstein, A.H. and Porte, D.Jr. Aldose reductase inhibition improves nerve conduction velocity in diabetic patients. N. Engl. J. Med., 1983; 308 : 119.
28. Fagius, J. and Jameson, S. Effects of aldose reductase inhibitor treatment in diabetic polyne­uropathy — a clinical and neurophysiological study. J. Neurol. Neurosurg. Psychiatry, 1981 ;44:991.
29. Jones, C.L. and Gonsalez, V. Pyridoxine defi­ciency; a new factor in diabetic neuropathy. J. Mn. Podiatry Assoc., 1978;68 : 646.
30. Ellenberg, M. Treatment of diabetic neuropathy with diphenylhydantoin. N.Y. J.Med., 1968; 68 : 2653.
31. Rull, J.A., Quibrera, R., Gonsalez-Millan, H., Lozano-Castane, D.A. Symptomatic treatment of peripheral diabetic neuropathy with carbamaze­pine (Tegretol); double blind crossover study. Diabetologia, 1969;5 :215.
32. Wilton, T.D. Tegretol in the treatment of diabetic neuropathy. S. Air. Med. J., 1974; 48 :869.
33. Chakrabarti, A.K. and Samantaray, S.K. Diabetic peripheral neuropathy; nerve conduction studies, before, during and after carbamazepine therapy. Aust. N.Z. J. Med., 1976; 6 : 565.
34. Campbell, I.W., Ewing, D.J. and Clarke, B.F. 9-alphafluorohydrocortisone in the treatment of postural hypotension in diabetic autonomic neuropathy. Diabetes, 1975; 24: 381.
35. Sutdiffe, R.L. G. Indomethacin treatment of postural hypotension, Letter. Br. Med. J., 1980; 280 : 1229.
36. Stacpoole, P.W. and Robertson, D. Combination Hi and H2 receptor antagonist therapy in dia­betic autonomic neuropathy. South. Med. 1982; 75 : 634.
37. Jennings, G., Esler, M. and Holmes, R. Treatment of orthostatic hypotension with dihydroergota­mine. Br. Med. J., 1979; 2 : 307.
38. Kuchel, 0., Buu, N.T., Gutkowska, J. and Genest, J. Treatment of severe orthostatic hypo­tension by metoclopramide. Ann. Intern. Med., i980;93 :841.
39. Boesen, F., Anderseon, E.B., Kanstrup, L.L., Hesse, B. and Christensen, NJ. Treatment of diabetic orthostatic hypotension with pindolol. Acta Neurol. Scand., 1982;66 :386.
40. Scott, F.B. , Fishman, I.J. and light, J.K. An inflatable penile prosthesis for treatment of diabetic impotence. Ann. Intern. Med., 1980;92 (Pt.2) : 340.
41. Madderm, G.T., Horowitz, M. and Jamieson, G.G. The effect of domperidone on oesophageal emptying in diabetic autonomic neuropathy. Bi. J. ClAn. Pharmacol., 1985; 19 :441.
42. Stewart, I.M., Hosking, D.J., Preston, Bi. and Atkinson, M. Oesophageal motor changes in diabetes mellitus. Thorax, 1976; 31 : 278.
43. Brownlee, M. and Kroopf, S.S. Metoclopramide for gastroparesis diabeticorum. N. Engi. 5. Med., 1974;291 : 1257.