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

Diabetic neuropathy is a common complication of diabetes mellitus patients. It is a wide range of abnormalities affecting proximal and distal peripheral sensory and motor nerves. Although plasma hyperosmolality is a common finding in diabetes mellitus, the effects of hyperosmolality on conduction of various sensory signal components have not been addressed in detail. Here we show that in rat dorsal root ganglion (DRG) preparations from normal rats, hyperosmolar solutions (360 mmol/kg, containing increased glucose, sucrose, NaCl, or mannitol) produce a selective block of signal propagation in myelinated sensory A-fibers. In compound action potential (CAP) recordings with suction electrodes, peak A-fiber CAP amplitude was selectively decreased (20%), while the C-fiber peak remained intact or was slightly increased. Hyperosmolar solutions had smaller effects on conduction velocity (CV) of both A- and C-fibers (approximately 5% decrease). Hyperosmolality-induced CAP changes could not be observed during recordings from isolated spinal nerves but were evident during recordings from desheathed spinal nerves. In intracellular recordings, hyperosmolar solutions produced a block of spinal nerve-evoked action potential invasion into the somata of some A-fiber neurons. Removal of extracellular calcium completely prevented the hyperosmolality-induced CAP decreases. Based on these data, we propose that the decreased CAP amplitudes recorded in human patients and in animal models of diabetes are in part due to the effects of hyperosmolality and would depend on the extracellular osmolality at the time of sensory testing. We also hypothesize that hyperosmolality may contribute to both the sensory abnormalities (paresthesias) and the chronic pain symptoms of diabetic neuropathy.
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PMID:Hyperosmolar solutions selectively block action potentials in rat myelinated sensory fibers: implications for diabetic neuropathy. 1367 99

A clinical state of peripheral and autonomic nerve damage in the abnormal environment of diabetes mellitus leads to syndromes of diabetic neuropathy. Diabetic neuropathy is a complication that affects most patients with longstanding diabetes mellitus, deteriorating their quality of life. The pathogenesis of diabetic neuropathy is multifactorial. The goals of treating diabetic neuropathy are to prevent the progression and reduce the symptoms. Smooth diabetes control without the risk of hypoglycaemia is most important to prevent progression. Early treatment is suggested, because of advanced marked nerve fiber loss. Treatments are supported by several investigations in diabetic patients: aldose reductase inhibition, prevention of protein glycation, improvement of nerve and administration of neurotrophic factors. Many other medications like amitriptiline, gabapentin, and carbamazepine have been used successfully in the treatment of painful diabetic neuropathy. To reduce the symptoms, studies have also shown analgesics to be effective.
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PMID:[Therapy of diabetic neuropathy]. 1457 19

Diabetic neuropathy is associated with changes in the extracellular matrix of the perineurium, including thickening of the basement membrane of the perineurial cells. Peripheral vascular disease (PVD) is a common vascular condition that can occur in the absence or presence of diabetes. Thickening of the vascular basement membrane of the vasa nervorum is associated with both diabetes and nondiabetic peripheral vascular disease. However, perineurial cell basement membrane (PCBM) thickening in the nondiabetic PVD state has not, until now, been investigated. In this study, 36 nerve fascicles were examined from three patient groups: a diabetic group, a nondiabetic PVD group, and a group free of both PVD and diabetes (control group). PCBM thickness, fascicle size, and myelinated nerve fibre (MNF) density were measured in all three groups. Endoneurial blood vessels were also observed for evidence of morphological changes. The results showed that the thickness of the PCBM is significantly greater in the diabetic group in comparison with both the control and the nondiabetic PVD group, and this increase in thickness is linearly related to fascicle size. The thickness of the PCBM was not significantly different between the nondiabetic PVD and control groups. Although both the nondiabetic PVD and diabetic groups showed a loss of myelinated nerve fibres in comparison with the control group, this loss was statistically greater in the diabetic group. The endoneurial blood vessels of both the diabetic and nondiabetic PVD groups showed evidence of endothelial cell hyperplasia, hypertrophy, and basement membrane reduplication.
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PMID:Perineurial cell basement membrane thickening and myelinated nerve fibre loss in diabetic and nondiabetic peripheral nerve. 1470 18

1. Diabetic neuropathy is one of the most frequent complications of diabetes mellitus. However, the mechanisms underlying these disorders are not yet well defined and it has been reported that currently available analgesics have hardly any ameliorating effect on painful diabetic neuropathy. 2. The purpose of the present study was to evaluate the antinociceptive effect of oxcarbazepine (OCBZ), a keto derivative of carbamazepine (CBZ), in animal models generally used in pain research and in rats and mice with streptozotocin (STZ)-induced diabetes. In addition, we compared the effect of OCBZ with those of CBZ, mexiletine and morphine. 3. Diabetes was induced by injection of STZ at a dose of 300 mg/kg (i.p.) in mice and 50 mg/kg (i.v.) in rats. Experiments were conducted 2 weeks after STZ injection and those animals with a serum glucose level above 400 mg/dL were used for data analysis. Antinociceptive effects of the drugs were evaluated by the paw withdrawal test (normal, STZ-induced diabetic and carrageenin-injected rats), tail-flick test (normal and STZ-induced diabetic mice) and nociceptive behaviour (formalin-injected mice). 4. In the present study, diabetic mice showed thermal hyperalgesia and diabetic rats exhibited mechanical hyperalgesia. From these results, the STZ-induced diabetic animals used in the present study were found to be suitable for research on painful diabetic neuropathy. In STZ-induced diabetic animals, the antinociceptive effects of OCBZ, CBZ and mexiletine were facilitated, whereas the effect of morphine was attenuated, compared with effects in normal animals. 5. Oxcarbazepine inhibited the formalin-induced biphasic pain responses and increased the nociceptive threshold in the case of carrageenin-induced hyperalgesia. In view of these results, inhibition of substance P-mediated pain transmission may be involved in the antinociceptive action of OCBZ. 6. These results indicate that OCBZ has an analgesic action and is a possible therapeutic agent for the treatment of neuropathic pain, such as occurs in painful diabetic neuropathy.
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PMID:Oxcarbazepine antinociception in animals with inflammatory pain or painful diabetic neuropathy. 1475 85

Diabetic neuropathy (DN) represents a major complication of type 1 diabetes mellitus (T1DM) but there is considerable uncertainty as to its incidence, prevalence, diagnosis and prognosis in pediatric population. Generally, DN is classified as polyneuropathy, focal neuropathy and autonomic neuropathy. The latter seems to be detectable even in asymptomatic children and adolescents with diabetes and is associated with the most serious consequences, such as hypoglycemia unawareness and cardiovascular dysfunction. A near-normal control of blood glucose in the early years after onset of diabetes may delay the development of clinically significant nerve impairment and, therefore, children and adolescents with diabetes represent a critical target for primary prevention of this complication. The aim of this review is to focus on the main clinical, epidemiological and prognostic aspects of DN in children and adolescents with T1DM. Etiopathogenetic theories and diagnostic tools are also reviewed from in a pediatric perspective.
Pediatr Diabetes 2004 Mar
PMID:Diabetic neuropathy in children and adolescents. 1504 90

Diabetic neuropathy is a common form of peripheral neuropathy, yet the mechanisms responsible for pain in this disease are poorly understood. Alterations in the expression and function of voltage-gated tetrodotoxin-resistant (TTX-R) sodium channels have been implicated in animal models of neuropathic pain, including models of diabetic neuropathy. We investigated the expression and function of TTX-sensitive (TTX-S) and TTX-R sodium channels in dorsal root ganglion (DRG) neurons and the responses to thermal hyperalgesia and mechanical allodynia in streptozotocin-treated rats between 4-8 weeks after onset of diabetes. Diabetic rats demonstrated a significant reduction in the threshold for escape from innocuous mechanical pressure (allodynia) and a reduction in the latency to withdrawal from a noxious thermal stimulus (hyperalgesia). Both TTX-S and TTX-R sodium currents increased significantly in small DRG neurons isolated from diabetic rats. The voltage-dependent activation and steady-state inactivation curves for these currents were shifted negatively. TTX-S currents induced by fast or slow voltage ramps increased markedly in neurons from diabetic rats. Immunoblots and immunofluorescence staining demonstrated significant increases in the expression of Na(v)1.3 (TTX-S) and Na(v) 1.7 (TTX-S) and decreases in the expression of Na(v) 1.6 (TTX-S) and Na(v)1.8 (TTX-R) in diabetic rats. The level of serine/threonine phosphorylation of Na(v) 1.6 and In Na(v)1.8 increased in response to diabetes. addition, increased tyrosine phosphorylation of Na(v)1.6 and Na(v)1.7 was observed in DRGs from diabetic rats. These results suggest that both TTX-S and TTX-R sodium channels play important roles and that differential phosphorylation of sodium channels involving both serine/threonine and tyrosine sites contributes to painful diabetic neuropathy.
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PMID:Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat. 1512 45

Diabetic neuropathy is a common complication of type 1 and 2 diabetes mellitus. Chronic hyperglycaemia and/or insulin deficiency in the peripheral nerve lead to metabolic and vascular disturbances, responsible for the functional alterations and the characteristic histological abnormalities observed in the nerve fibre. Recently, genetic factors have been described, suggestive of a predisposition and/or a protective effect for diabetic neuropathy in certain patients. The search for these genetic factors through the study of polymorphism of gene involved in the various metabolic and vascular pathways, is currently increasing, but with contradictory results. The main studies and data are reviewed in this Article. The identification of candidate-genes should allowed, in the future, to better identify and manage diabetic patients at-risk for peripheral neuropathy.
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PMID:[Genetics of diabetic complications: peripheral neuropathy]. 1516 18

Diabetic neuropathy is characterized by slowing of conduction velocity and axonal atrophy. Both of these cardinal features of neuropathy might be linked to impaired neurofilament investment of axons. Since neurofilaments form the critical structural latticework of axons, their importance in neuropathy is of interest. We tested directly the relationship of neurofilaments to diabetic neuropathy by superimposing streptozotocin-generated diabetes on a unique but viable transgenic mouse described by Eyer and Peterson. These mice express a fusion protein in which the carboxyl terminus of the high molecular weight neurofilament protein (Nf-H) was replaced by beta-galactosidase, in turn blocking normal neurofilament export and rendering axons completely lacking neurofilaments. Despite similar levels of hyperglycaemia, diabetic mice lacking neurofilaments developed progressive slowing of conduction velocity in their motor and sensory fibres between 4 and 8 weeks after the onset of diabetes (P < 0.05), unlike diabetic mice with normal neurofilaments, who developed only mild evidence of neuropathy over the same time-frame. Diabetic mice without neurofilaments, but not those with neurofilaments, had a progressive decline in the amplitude of the caudal nerve compound action potential and there were trends toward increased axonal atrophy in diabetics lacking neurofilaments. Single daily doses of insulin that restored normoglycaemia (0.1 IU subcutaneous insulin daily 5 of 7 days weekly for 4 weeks) reversed conduction slowing and restored sensory axon calibre. Our findings indicate that abnormalities in neurofilament export or transport alone cannot account for features of diabetic neuropathy. Instead, neurofilaments may allow axons to better resist the ravages of diabetes. Our findings also confirm the impact of insulin on reversing the phenotype.
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PMID:Accelerated diabetic neuropathy in axons without neurofilaments. 1528 71

Diabetic neuropathy (DN) is a common complication of diabetes that often is associated with considerable morbidity and mortality. The epidemiology and natural history of DN is clouded with uncertainty because of confusion regarding the definition and measurement of this disorder. The recent resurgence of interest in the vascular hypothesis, oxidative stress, the neurotrophic hypothesis,and the possibility of the role of autoimmunity has opened up new avenues of investigation for therapeutic intervention. The ability to manage successfully the many different manifestations of diabetic neuropathy depends ultimately on success in uncovering the pathogenic processes underlying this disorder.
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PMID:Diabetic neuropathies. 1530 87

Diabetic neuropathy is one of the most frequent peripheral neuropathies associated with hyperalgesia and hyperesthesia. Besides alteration in the levels of neurotransmitter, alteration in the neuronal nitric oxide synthase (nNOS) is a key factor in the pathogenesis of diabetic neuropathy. The present study was aimed at evaluating the role of PDE-5 inhibitor on nociception in streptozotocin-induced diabetes in animal models of nociception (writhing assay in mice and paw hyperalgesia test in rats). Diabetic animals showed a significant decrease in pain threshold as compared to non-diabetic animals in both tests, indicating diabetes induced hyperalgesia in mice and rats. The PDE-5 inhibitor, sildenafil, significantly increased the pain threshold in both diabetic and non-diabetic animals. However, L-NAME, a non-specific NOS inhibitor and methylene blue (MB), a guanylate cyclase inhibitor blocked the antinociceptive effect. The per se administration of L-NAME or MB augmented the hyperalgesic response in diabetic animals with little or no effect in non-diabetic animals, indicating the alteration of NO-cGMP pathway in diabetes. The results in the present study demonstrate that the decreased nNOS-cGMP system may play a crucial role in the pathogenesis of diabetic neuropathy.
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PMID:Modulatory effect of the PDE-5 inhibitor sildenafil in diabetic neuropathy. 1545 68


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