Diabetic neuropathy: pathogenesis and therapy

Diabetic neuropathies are complex, heterogeneous disorders that encompass a wide range of abnormalities affecting both peripheral and autonomic nervous systems, causing considerable morbidity and mortality. Treatment should be based upon the underlying etiology and not symptoms alone, although symptomatic therapy is needed. Neuropathies may be focal or diffuse, proximal or distal, and involve somatic and autonomic nerves. Focal syndromes are classified as (1) entrapment syndromes or (2) mononeuropathies. Entrapment syndromes are treated by means of relieving compression within confined spaces. Mononeuropathies are due to a vascular insult and resolve spontaneously. They are best treated by supportive therapy. Proximal neuropathies are usually due to an inflammatory, vasculitic, or autoimmune condition and are best treated with specific therapies for the underlying disorder based on biopsy findings. Therapies for distal polyneuropathies include metabolic treatments (e.g., aldose reductase inhibitors, aminoguanidine, gamma-linolenic acid), autoimmune therapies, and nerve growth factors. No definitive treatment is available for painful diabetic neuropathy. Several medications have been used, among them tricyclic antidepressants, antiepileptic drugs, phenothiazines, calcitonin, local anesthetics, nonsteroidal anti-inflammatory drugs, and dextromethorphan. Nonpharmacologic therapies include surgical sympathectomy, spinal cord blockade, electrical spinal cord stimulation, and prostaglandin.