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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most common form of diabetic neuropathy is chronic, distal symmetrical sensorimotor, or predominantly sensory neuropathy; the latter is invariably associated with some degree of autonomic dysfunction. There are, however, other neuropathic patterns in diabetes mellitus that are uncommon but are important to recognize, since they may mimic many other non-neurologic diseases. This article discusses a variety of forms of mononeuropathies and diabetic proximal motor neuropathy, commonly known as diabetic amyotropy.
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PMID:Diabetic neuropathy. 922 53

Oxidative stress is present in the diabetic state. Our work has focused on its presence in peripheral nerves. Antioxidant enzymes are reduced in peripheral nerves and are further reduced in diabetic nerves. That lipid peroxidation will cause neuropathy is supported by evidence of the development of neuropathy de novo when normal nerves are rendered alpha-tocopherol deficient and by the augmentation of the conduction deficit in diabetic nerves subjected to this insult. Oxidative stress appears to be primarily due to the processes of nerve ischemia and hyperglycemia auto-oxidation. The indexes of oxidative stress include an increase in nerve, dorsal root, and sympathetic ganglia lipid hydroperoxides and conjugated dienes. The most reliable and sensitive index, however, is a reduction in reduced glutathione. Experimental diabetic neuropathy results in myelinopathy of dorsal roots and a vacuolar neuropathy of dorsal root ganglion. The vacuoles are mitochondrial; we posit that lipid peroxidation causes mitochondrial DNA mutations that increase reduced oxygen species, causing further damage to mitochondrial respiratory chain and function and resulting in a sensory neuropathy. Alpha-lipoic acid is a potent antioxidant that prevents lipid peroxidation in vitro and in vivo. We evaluated the efficacy of the drug in doses of 20, 50, and 100 mg/kg administered intraperitoneally in preventing the biochemical, electrophysiological, and nerve blood flow deficits in the peripheral nerves of experimental diabetic neuropathy. Alpha-lipoic acid dose- and time-dependently prevented the deficits in nerve conduction and nerve blood flow and biochemical abnormalities (reductions in reduced glutathione and lipid peroxidation). The nerve blood flow deficit was 50% (P < 0.001). Supplementation dose-dependently prevented the deficit; at the highest concentration, nerve blood flow was not different from that of control nerves. Digital nerve conduction underwent a dose-dependent improvement at 1 month (P < 0.05). By 3 months, all treated groups had lost their deficit. The antioxidant drug is potentially efficacious for human diabetic sensory neuropathy.
Diabetes 1997 Sep
PMID:The roles of oxidative stress and antioxidant treatment in experimental diabetic neuropathy. 928 97

Diabetic peripheral neuropathy is a common, painful, and disabling condition that is known to occur by two mechanisms: hyperglycemia and arterial blood flow occlusion. Pentoxifylline (Trental) functions by improving erythrocyte flexibility in blood vessels, which could increase the delivery of oxygen to occluded nerve vessels. This 1-year clinical trial was aimed at ascertaining the effects of pentoxifylline on diabetic sensory neuropathy. Fifty patients with type I or II diabetes were evaluated in a randomized, double-blind, parallel group and placebo-controlled study. Pentoxifylline effectiveness was evaluated by measuring glycated hemoglobin, blood pressure and current perception threshold (CPT). The CPT results showed no statistically significant effect of pentoxifylline on mean nerve sensory perception thresholds in ankle and toe at 5, 250 and 2000 Hz. There were no significant changes in glycated hemoglobin or in systolic and diastolic blood pressure during the trial. Thus, glycated hemoglobin and blood pressure did not explain the lack of pentoxifylline effect on diabetic neuropathy. In conclusion, pentoxifylline appears not to add benefits to the clinical treatment of diabetic sensory neuropathy of the lower extremity.
J Diabetes Complications
PMID:The effect of pentoxifylline on current perception thresholds in patients with diabetic sensory neuropathy. 933 9

A multiplicity of peripheral nerve syndromes may develop in patients with diabetes mellitus, the commonest of which is a chronic symmetric sensory polyneuropathy, often associated with autonomic neuropathy. Once established, it is largely irreversible. Acute painful diabetic sensory neuropathy is a separate entity with a favorable prognosis. It now seems likely that chronic inflammatory demyelinating polyneuropathy occurs with greater frequency in diabetic subjects than in the general population and is one explanation for the occurrence of a predominantly motor polyneuropathy. Focal and multifocal peripheral nerve lesions are seen mainly in older diabetic patients and comprise cranial, thoracoabdominal and limb nerve lesions, the last including proximal lower limb diabetic motor neuropathy (diabetic amyotrophy). With this wide array of disorders and the frequency of diabetes, it is important to distinguish those that are directly or indirectly related to diabetes from those that have a coincidental relationship.
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PMID:Clinical features and investigation of diabetic somatic peripheral neuropathy. 935 78

To evaluate the role of nitric oxide synthase (nNOS) in the pathogenesis of diabetic neuropathy, we investigated nociception and nNOS expression in dorsal root ganglion (DRG) of rats with streptozocin-induced diabetes. Paw withdrawal threshold to noxious mechanical stimuli was decreased in both L-NAME-treated and diabetic rats. The number of NADPH-diaphorase positive neurons was significantly decreased in untreated diabetic compared with control rats. Decreased expression of nNOS protein was confirmed by immunoblotting. Insulin treatment completely prevented decreases in withdrawal threshold and nNOS expression. Cyclic GMP content paralleled nNOS expression in experimental animals. These results suggest that decreased nNOS-cGMP system in DRG may play a role in the pathogenesis of diabetic sensory neuropathy.
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PMID:Hyperalgesia and decreased neuronal nitric oxide synthase in diabetic rats. 950 63

Neurotrophin-3 (NT-3) acts as a target-derived neurotrophic factor for large calibre sensory neurones and plays a role in the maintenance of the adult phenotype of proprioceptive and mechanoreceptive fibres. Large fibre sensory neuropathy is common in diabetes mellitus and the aim of this study was to determine whether endogenous NT-3-dependent neurotrophic support was sub-optimal in the streptozotocin-diabetic rat. NT-3 gene expression was analysed by Northern blotting and ELISA in hindlimb skeletal muscle and found to be decreased by up to 70% (p < 0.05) in rats with 4-6 weeks of diabetes compared to aged-matched controls. Treatment of other diabetic rats with insulin prevented development of deficits of both NT-3 protein and of its mRNA. The deficits in target tissue production of NT-3 were coincident with significant decreases in its anterograde and retrograde axonal transport in sciatic nerve at 6 weeks of diabetes. The mRNA expression in lumbar dorsal root ganglia of the specific receptor for NT-3, trkC, was also down-regulated at 12 weeks of diabetes by 50% (p < 0.05). The observed decreases in NT-3 target tissue production and related axonal transport suggest that large calibre sensory neurones expressing trkC may be receiving sub-optimal neurotrophic support in experimental diabetes.
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PMID:Target tissue production and axonal transport of neurotrophin-3 are reduced in streptozotocin-diabetic rats. 954 Nov 70

Since the discovery of nerve growth factor (NGF), its role in the physiology/pathophysiology of nerve function has been under intense investigation. More recently, the potential of recombinant human NGF (rhNGF) as a putative treatment for peripheral neuropathies, in particular diabetic polyneuropathy and HIV-associated sensory neuropathy, is being explored. In animal models of diabetes, depletion of endogenous NGF levels has been demonstrated in foot skin and skeletal muscle; these levels reduce further with increasing disease duration. Preclinical studies in animal models of diabetes have shown that administration of NGF can reverse or alleviate impairment in nerve function.
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PMID:Biological actions of nerve growth factor in the peripheral nervous system. 1002 24

The aim of this study was to determine phenotypie characteristics of patients with early onset cerebellar ataxia (EOCA) with preserved tendon reflexes. The series comprises 25 patients, representing 10% of all ataxic patients who have been genetically studied in our laboratory since 1990. There were 11 males and 14 females. Fourteen patients were homozygous for the GAA expansion on chromosome 9q13 (group 1) and therefore a diagnosis of Friedreich's ataxia with retained reflexes (FARR) was given. The remaining 11 patients had two normal non-expanded alleles (group 2) and a working diagnosis of EOCA with retained reflexes (EOCARR) was established. Mean ages of onset were 13.7 +/- 5.9 years (3-25) for group 1 and 10.3 +/- 7.3 for group 2; the difference was not significant. Frequencies of symptoms and signs were also comparable for both groups the only significant differences being the higher frequency of nystagmus, cardiomyopathy and sensory neuropathy in group 1 patients. There was a tendency for FARR patients to have higher frequencies of hypopallesthesia in the lower limbs and skeletal deformities. In none of the cases diabetes mellitus was observed. We conclude that differentiation of FARR and EOCARR may be suspected by classical clinical and electrophysiological data and confirmed by analysis of the GAA repeat.
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PMID:Early onset cerebellar ataxia and preservation of tendon reflexes: clinical phenotypes associated with GAA trinucleotide repeat expanded and non-expanded genotypes. 1019 66

Vascular alterations of peripheral nerves occuring after mechanical injury or in metabolic disorders are well described. It is thought that vascular endothelial growth factor (VEGF), a potent growth factor for angiogenesis, also plays an important role for regeneration of nervous tissue. We used a rat model of type I diabetes (streptozotozin-induced) with sensory neuropathy and with chronic hyperglycemia over 12 weeks. A monoclonal antibody to VEGF was used for immunohistochemistry of sciatic nerves and dorsal root ganglia (DRG). Intense VEGF staining was detected in cell bodies and nerve fibers of animals with chronic diabetes. Healthy control groups expressed no or very little VEGF and animals treated with insulin to prevent neuropathy and severe hyperglycemia showed significantly lower immunostaining for VEGF. After application of nerve growth factor (NGF), which is known to improve axonal and Schwann cell regeneration, a markedly decreased expression of VEGF was seen in diabetic animals. In contrast, enhanced VEGF staining was noted in NGF-treated healthy controls of the same age and body weight as the diabetic rats. Similar findings were made in diabetic animals treated with both, insulin and NGF. We conclude that functional alteration of peripheral nerves causes up-regulation of VEGF in Schwann cells and neurons. With functional restitution of nervous tissue, i.e. under insulin and/or NGF treatment VEGF expression decreases significantly. Additionally, NGF may stimulate VEGF in normal controls. The production of VEGF may play a role in complete nerve regeneration and its regulation may reflect the functional state of peripheral nerves.
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PMID:Vascular endothelial growth factor expression in peripheral nerves and dorsal root ganglia in diabetic neuropathy in rats. 1021 80

Foot disease is a common complication of diabetes that can have tragic consequences. Tight glucose control can reduce microvascular diabetic complications, including peripheral sensory neuropathy and thus development of foot ulcers. Patient education is essential for risk-factor reduction and early recognition of foot complications. Awareness and training of healthcare providers in diagnosing and treating diabetic foot disease are paramount and may begin with such simple measures as adding a wall poster or chart reminder to conduct foot examinations in all diabetic patients at every office visit.
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PMID:Preventing diabetic foot complications. Tight glucose control and patient education are the keys. 1041 76


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