Diabetic neuropathies: features and mechanisms.
Diabetic neuropathies include both focal neuropathies and diffuse polyneuropathy. Polyneuropathy, the most common of the diabetic neuropathies excluding focal entrapment, has not yet been explained by a single disease mechanism despite intensive investigation. A number of abnormalities appear to cascade into a 'vicious cycle' of progressive microvascular disease associated with motor, sensory and autonomic fiber loss. These abnormalities include excessive polyol (sugar alcohol) flux through the aldose reductase pathway, functional and structural alterations of nerve microvessels, nerve and ganglia hypoxia, oxidative stress, nonspecific glycosylation of axon and microvessel proteins, and impairment in the elaboration of trophic factors critical for peripheral nerves and their ganglia. While an initiating role for nerve ischemia in the development of polyneuropathy has been proposed, the evidence for it can be questioned. The role of sensory and autonomic ganglia in the development of polyneuropathy has had relatively less attention despite the possibility that they may be vulnerable to a variety of insults, particularly neurotrophin deficiency. Superimposed on the deficits of polyneuropathy is the failure of diabetic nerves to regenerate as effectively as nondiabetics. Polyneuropathy has not yet yielded to specific forms of treatment but a variety of new trials addressing plausible hypotheses have been initiated. This review will summarize some of the clinical, pathological and experimental work applied toward understanding human diabetic neuropathy and will emphasize ideas on pathogenesis.
Zochodne
D W
DW
Department of Clinical Neurosciences, University of Calgary, Alberta. dzochodn@acs.ucalgary.ca
D000818:Animals; D001341:Autonomic Nervous System / Q000473:pathology / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000145:classification / Q000473:pathology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000145:classification / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008959:Models, Neurological; D010523:Peripheral Nervous System Diseases / Q000145:classification / Q000473:pathology / Q000503:physiopathology