Diabetic neuropathy: mechanisms and future treatment options
- Professor P K Thomas, University Department of Clinical Neurosciences, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK. Telephone 0044 171 794 0500; fax 0044 171 431 1577.
There is no single diabetic neuropathy. A wide variety of syndromes involving the peripheral nerves may be encountered in patients with diabetes mellitus, implying a correspondingly diverse range of underlying causative mechanisms. The classification of the diabetic neuropathies is not yet finalised and has required successive modifications in the light of accumulating knowledge. The scheme favoured by myself is given in the table. This broadly categorises the manifestations into (1) rapidly reversible phenomena, (2) generalised polyneuropathies, (3) focal and multifocal neuropathies, and (4) superimposed chronic inflammatory demyelinating polyneuropathy.
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Classification of the diabetic neuropathies
Pathogenesis
HYPERGLYCAEMIC NEUROPATHY
Patients with severe uncontrolled hyperglycaemia may complain of uncomfortable sensory symptoms, mainly in the lower limbs. They also show reduced nerve conduction velocity and increased resistance to ischaemic conduction failure. These phenomena have little clinical importance. They are rapidly corrected by the establishment of diabetic control and are thus presumably related directly to hyperglycaemia or to a metabolic abnormality correlated with it. Possible mechanisms have been discussed by Watkins and Thomas.1 The increased resistance to ischaemic conduction failure may be related to a switch to anaerobic glycolysis in diabetic nerve. The positive sensory symptoms could be related to hypoxia, which is known to be present in human diabetic neuropathy. Experimentally, hyperglycaemic but not normoglycaemic hypoxia gives rise to alterations in fast K+conductance and afterpotentials in axons, related to axoplasmic acidification. This might lead to the generation of ectopic impulses and contribute to the occurrence of positive symptoms.
DISTAL SENSORY/AUTONOMIC POLYNEUROPATHY
The commonest type of diabetic neuropathy is a distal symmetric predominantly sensory polyneuropathy and there are indications that small fibre sensory modalities are affected earlier. Minor distal motor involvement may coexist. Severe autonomic neuropathy is virtually only encountered in type I diabetic patients, but less prominent accompanying autonomic involvement is frequent both in type I and type …
