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

In the experimental rat model of diabetes a slowing of nerve conduction velocity and a resistance to ischemic conduction failure have been found as an indication of polyneuropathy. The same electrophysiological abnormalities have been demonstrated in a model in which healthy rats are kept under hypoxic conditions (10% O2) for a 10-week period. Two factors are held responsible for the development of diabetic polyneuropathy: metabolic deterioration and hypoxia. However, until now the relative roles of metabolic deterioration and hypoxia in the development of polyneuropathy have not been settled. To test both explanations further with more sophisticated electrophysiological techniques, the H-reflex (motor and sensory NVC) and the stimulated SF-EMG (measures terminal nerve branch and neuromuscular transmission) were measured in 3 groups of 10 rats, a healthy control group, a diabetic group, and a hypoxic group, every 5 weeks, for 6 months. In the control rats an age-related increase in motor and sensory conduction velocity was found, whereas in the diabetic rats as well as in the hypoxic rats a marked decrease in sensory and a slight decrease in motor nerve conduction velocity was observed. The jitter measured in the stimulated SF-EMG was significantly increased in both the diabetic and the hypoxic group. The results of the present study support the possible role of hypoxia, in addition to metabolic factors, in the development of experimental diabetic neuropathy.
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PMID:Hypoxic neuropathy versus diabetic neuropathy. An electrophysiological study in rats. 150 76

The concentration and distribution of labile elements in nerve cells is tightly regulated by multiple membrane transport processes and by binding to lipids and proteins. The multifaceted nature of elemental regulation provides numerous sites at which toxicants or disease processes might act to disrupt this regulation. Such disruption can affect cytoskeletal integrity, macromolecular synthesis, energy production, osmoregulation and other cellular processes. The possible role of perturbed elemental homeostasis in the mechanism of nerve injury caused by certain chemicals (e.g., acrylamide, 2,5-hexanedione) and neuropathic diseases (e.g., diabetes) has not been determined. To investigate this possibility, we have used electron probe x-ray micro-analysis (EPMA) to measure the distribution of elements and water in cellular compartments of myelinated axons (axoplasm, mitochondria) and glial cells (cytoplasm, myelin) in normal rat central and peripheral nervous systems. Results indicate that each compartment exhibits a characteristic composition of elements and water which might reflect function of that anatomical region or organelle. Injury-induced changes in elemental content of PNS axons and Schwann cells have been identified using several neurotoxic models (i.e., acrylamide, axotomy, diabetic neuropathy). Each type of injury initiated early alterations in element and water composition of both axons and glial cells. Compositional changes were specific and developed sequentially instead of simultaneously. Results of these studies suggest that, rather than being an epiphenomenon, altered elemental regulation might represent a primary component of many neurotoxic mechanisms.
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PMID:Perturbation of axonal elemental composition and water content: implication for neurotoxic mechanisms. 150 12

The cornea was thought to be not for a long time saved from the havoc of the diabetes. Last time a series of authors talk about a diabetic keratopathy. For the beginning the cornea endothelium was involved (changes of density and form of the cells) and last time the cornea epithelium was involved, some authors making a correlation between the diabetic neuropathy and keratopathy that consider a special entity, the diabetic keratopathy. We kept under the observation a group of diabetic patients who were hospitalized at our clinic of ambulatory examined for various complications of diabetes, in order to discover if it exist a relationship between the two affection, neuropathy and keratopathy. The number of the diabetic neuropathies is more less (13.3%) than that of the diabetic retinopathies or nephropathies. The keratopathies were observed for 6.6% (much inferior to other statistics). Half of the cases of keratopathies have presented either symptom of neuropathies or any other neurological charge; though for the first time it could be done the relationship between the two affections, the examination of the patients often pleads for coincidences; it's why we wonder if it really exist a diabetic keratopathy or a keratopathy at the diabetic patient.
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PMID:[Does diabetic keratitis exist?]. 152 43

Diabetic neuropathies form a group of diverse conditions, which can be distinguished between those which recover (acute painful neuropathies, radiculopathies, mononeuropathies) and those which progress (sensory and autonomic neuropathies). These two main groups can be distinguished in several ways: sensory and autonomic neuropathies are classic diabetic complications progressing gradually in patients with long-standing diabetes who often have other specific complications, while the reversible neuropathies do not have these features. The latter are characterised by their occurrence at any stage of diabetes, often at diagnosis, they may be precipitated on starting insulin treatment, and they are more common in men; they can occur at any age, though more often in older patients, and are unrelated to other diabetic complications. The two groups of neuropathies also show differences in nerve structural abnormalities and with regard to distinctive blood flow responses. The underlying mechanisms responsible for these very different forms of neuropathy remain speculative, but evidence for an immunological basis for the development of severe symptomatic autonomic neuropathy is presented.
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PMID:Clinical observations and experiments in diabetic neuropathy. 154 77

Since 1981 a number of aldose reductase inhibitors (ARIs) have been extensively investigated in clinical trials for the treatment or prevention of diabetic complications. In general, the results from these trials have varied from no effect to improvement. In part, the inconclusive results are due to differences in the study designs. Investigation of some ARIs has been discontinued because of lack of efficacy (ponalrestat) or major toxicity (sorbinil). Of the ARIs that have been evaluated, only tolrestat is currently undergoing clinical investigation. Although the most recent studies have shown promising results, the role of ARIs in the treatment or prevention of secondary complications of diabetic neuropathy will be determined in ongoing or future clinical trials.
J Diabetes Complications
PMID:Recent clinical experience with aldose reductase inhibitors. 156 57

Tolrestat is an aldose reductase inhibitor that is undergoing extensive clinical investigation for the treatment of diabetic complications including polyneuropathy. As part of a larger European trial, we report here the results from a single clinical center on the efficacy of tolrestat in patients with confirmed diabetic neuropathy. The trial was conducted in two phases: a 6-month double-blind, placebo-controlled phase, and a 6-month open-label phase in which most patients were treated with tolrestat. Following the double-blind phase, motor and sensory nerve conduction velocity had significantly deteriorated in the placebo group, which did not occur during treatment with tolrestat. Deterioration of vibration threshold also occurred during placebo treatment and did not occur with tolrestat. During the open-label phase, motor nerve condition velocity and vibration threshold improved with tolrestat. Moreover, the deterioration of motor nerve conduction velocity and vibration threshold that had occurred in patients initially treated with placebo, was stopped during open-label treatment with tolrestat.
J Diabetes Complications
PMID:Long-term effects of tolrestat on symptomatic diabetic sensory polyneuropathy. 156 58

Aldose reductase inhibitors improve nerve biochemistry, function, and structure in diabetic animals and increase nerve conduction in diabetic patients. Nevertheless, it has been difficult to demonstrate a benefit from these agents in patients with clinically overt diabetic neuropathy. Direct measurement of the nerve tissue penetration and biochemical and biological potency of these compounds is essential to fully understand and evaluate their effectiveness. Human sural nerve biopsies obtained from diabetic neuropathic patients undergoing treatment with an aldose reductase inhibitor revealed a reduction in intermediates of the polyol pathway. Specific morphologic lesions that correlate with the degree of clinical and electrophysiologic impairment also were identified. Morphologic evaluation of sural nerve biopsies obtained after aldose reductase inhibitor treatment suggests that these biochemically effective compounds ameliorate clinically relevant structural lesions in patients with diabetic neuropathy.
J Diabetes Complications
PMID:Effects of aldose reductase inhibitors on the progression of nerve fiber damage in diabetic neuropathy. 156 56

Although neuropathy has long been recognized as a complication of diabetes, the impact of this condition has not been adequately established. The prevalence of diabetic neuropathy is virtually unknown because the published studies differ considerably with regard to definition, method of assessment, and patient selection. Furthermore, the determination of prevalence has been hampered by the fact that there is no generally accepted classification of the variety of manifestations of diabetic neuropathy. The introduction of new sensitive diagnostic methods aids in the detection of less severe stages of neuropathy, as compared with clinically based assessment, and renders the disease more prevalent. The prevalence of diabetic neuropathy in the few reported population-based studies was approximately 30%. We have evaluated the prevalence of cardiovascular autonomic neuropathy in a group of approximately 1000 diabetic patients randomly included from 21 hospitals in Germany, Austria, and Switzerland. The results of this study and those of a prospective study on the natural history of neural dysfunction during the first 5 years after diagnosis of type 1 diabetes will be presented.
J Diabetes Complications
PMID:The epidemiology of diabetic neuropathy. Diabetic Cardiovascular Autonomic Neuropathy Multicenter Study Group. 156 59

Conventional electrophysiologic measurements such as nerve conduction velocity, compound action potential, and neuropathic symptom scores have been used to assess the severity of diabetic neuropathy and have been the major efficacy end points following pharmacologic intervention trials. Unfortunately, these measurements are not particularly sensitive and their reproducibility is, at best, good. Detailed morphometric analysis of sural nerve biopsies has evolved as a sensitive and highly reproducible method for assessing the severity and progression of diabetic peripheral neuropathy. In this study we demonstrate highly significant correlations between morphometric parameters of diabetic sural nerves and electrophysiologic and sensory score measurements of the same sural nerve. These data suggest that detailed morphometric examination is a more sensitive and reproducible method for assessing the severity of diabetic neuropathy, and that quantitative morphometric parameters provide sensitive indicators of electrophysiologic and clinically meaningful nerve damage. Morphometric analysis of sural nerve biopsies therefore constitutes a rational basis for sensitive efficacy end points in the design of future therapeutic clinical trials.
J Diabetes Complications
PMID:Structure-function interactions in the therapeutic response of diabetic neuropathy. 156 61

Rational treatment of diabetic polyneuropathy depends upon establishing its cause, which is at present unknown. A number of animal models of diabetes have been examined and although abnormalities are detectable in the peripheral nervous system they do not duplicate the degenerative neuropathy encountered in the human. The relevance of these abnormalities is therefore uncertain, although they may reflect the earlier changes in man. For human neuropathy, it is likely that vascular lesions or an abnormal susceptibility to mechanical injury are responsible for focal neuropathies. The evidence that ischaemia and hypoxia are responsible for the diffuse sensory neuropathy and autonomic polyneuropathy is still equivocal and it is often difficult to establish whether the vascular changes are primary or secondary. Metabolic explanations, such as sorbitol accumulation in nerve, have not so far been adequately validated by responses to treatment. The manifestations of diabetic neuropathy are complex and a single explanation should not be sought.
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PMID:Diabetic neuropathy: models, mechanisms and mayhem. 156 4


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