Diabetic neuropathy: scope of the syndrome

Diabetic neuropathy is a common complication of diabetes that may be disabling and even contribute to mortality. Diabetic peripheral neuropathy encompasses a group of clinical and subclinical syndromes, each characterized by diffuse or focal damage to peripheral somatic or autonomic nerve fibers. None of these syndromes is pathognomonic for diabetes, and they may occur idiopathically or in association with other disorders in nondiabetic persons. Distal symmetric sensorimotor polyneuropathy is the most common form of peripheral neuropathy and is the leading cause of lower limb amputation. The characteristic slowing of sensory and motor nerve conduction velocities and advancing distal symmetric sensorimotor deficits are ascribed to an underlying insidious, chronically progressive, length-dependent, distal axonopathy of the dying-back type primarily, but not exclusively, affecting sensory nerve fibers. The cumulative prevalence of clinical diabetic neuropathy parallels the degree and duration of antecedent hyperglycemia, and the Diabetes Control and Complications Trial definitively established an important role of improved metabolic control in the primary prevention of clinical neuropathy. Improved blood glucose control substantially reduces the risk of developing diabetic polyneuropathy in type 1 diabetes mellitus, thereby strongly implicating hyperglycemia as the important causative factor in this degenerative disease process. Studies in experimental animal models reveal several glucose-related metabolic mechanisms that could initiate neurochemical, neurotrophic, and/or neurovascular defects culminating in a peripheral sensorimotor and autonomic neuropathy. Other than improved blood glucose control, therapy for diabetic neuropathy remains palliative and supportive, although this is expected to change radically as new insights into the pathogenetic mechanisms of diabetic neuropathy give rise to specific new mechanism-based therapies.