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

Neuropathy is a common complication of Type 1 and Type 2 diabetes. In the peripheral nerve, persistent hyperglycaemia leads to metabolic and vascular disorders responsible for nerve fibre abnormalities. Genetic predisposition has been mentioned more recently. Among metabolic factors, an increase of the polyol pathway, a linoleic acid metabolism abnormality, a decrease of carnitine level, an increase of protein glycation, nerve growth factor abnormalities, and high production of oxygen free radicals can be involved. These factors could account for nerve membrane phospholipid pattern disorder, a decrease of Na/K ATPase activity and disequilibrium in prostaglandin production. Vascular factors involve a decrease in nitric oxide production, an abnormality of eicosanoid production, and an increase in the oxidative pathway, inducing vasoconstriction of endoneural microvascularisation and nerve hypoxia. Strong interactions exist between metabolic and vascular factors, making it difficult to distinguish between them. Moreover, a restriction polymorphism in the first intron of the Na/K ATPase ATP1 A1 gene is associated with low enzymatic activity and a relative risk of neuropathy of 6.5. Electromyography determines the myelinisation state of large nerve fibres and the number of functional axons. However, it cannot detect damage to small fibres, and the study of sensitive nerves is difficult. Electromyography is not a systematic examination and should be preceded by a clinical examination of sensitivity.
Diabetes Metab 1998 Nov
PMID:[Physiopathology of diabetic neuropathies. Functional exploration of peripheral involvement]. 988 Dec 36

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

Recent evidence from animal models of diabetes and human diabetic subjects suggests that the reduced availability of neurotrophic factors may contribute to the pathogenesis of diabetic peripheral neuropathy (DPN). Of these proteins, nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin (NT-3) and NT-4/5 appear to be important for the development and maintenance of peripheral neurons, but others, including insulin-like growth factors (IGFs), may also be involved. Studies with NGF, NT-3, IGF-I and IGF-II both in vitro and in animal models of neuropathies (including DPN) suggest that these factors ameliorate nerve degeneration. Recombinant human NGF is the first neurotrophic factor to enter clinical trials for DPN and is currently being tested in two phase III studies.
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PMID:Neurotrophic factors and diabetic peripheral neuropathy. 1002 26

Diabetic peripheral neuropathies are a variety of syndromes which affect sensory, autonomic and motor nerve function. The commonest form, distal symmetric sensory polyneuropathy, is a major risk factor for foot ulceration, which may eventually lead to lower limb amputation. By 2010, it is estimated that globally 220 million people will have diabetes, and epidemiological studies estimate that more than 50% of diabetic patients with a 25-year history will develop diabetic peripheral neuropathies. In 1986, the USA expenditure for care of these neuropathies was estimated at $240 million, and, as the incidence of diabetes is predicted to increase, this cost is likely to escalate. Risk factors associated with diabetic peripheral neuropathy need to be identified so that interventions can be devised. Recombinant nerve growth factor, a putative treatment for diabetic peripheral neuropathies, is currently being evaluated in phase III trials for this indication.
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PMID:Diabetic peripheral neuropathies: their cost to patient and society and the value of knowledge of risk factors for development of interventions. 1002 27

Heterogeneous myocardial sympathetic denervation complicating diabetes has been invoked as a factor contributing to sudden unexplained cardiac death. In subjects with diabetic autonomic neuropathy (DAN), distal left ventricular (LV) denervation contrasts with preservation of islands of proximal innervation, which exhibit impaired vascular responsiveness. The aims of this study were to determine whether this heterogeneous pattern of myocardial sympathetic denervation occurs in a rat model of diabetes and to explore a potential association with regional fluctuations in myocardial nerve growth factor (NGF) protein. Myocardial sympathetic denervation was characterized scintigraphically using the sympathetic neurotransmitter analog C-11 hydroxyephedrine ([11C]HED) and compared with regional changes in myocardial NGF protein abundance and norepinephrine content after 6 and 9 months in nondiabetic (ND) and streptozotocin-induced diabetic (STZ-D) rats. In ND rats, no difference in [11C]HED retention or norepinephrine content was detected in the proximal versus distal myocardium. After 6 months, compared with ND rats, myocardial [11C]HED retention had declined in the proximal segments of STZ-D rats by only 9% (NS) compared with a 33% decrease in the distal myocardium (P < 0.05). Myocardial norepinephrine content was similar in both ND and STZ-D rats. At 6 months, LV myocardial NGF protein content in STZ-D rats decreased by 52% in the proximal myocardial segments (P < 0.01 vs. ND rats) and by 82% distally (P < 0.01 vs. ND rats, P < 0.05 vs. proximal segments). By 9 months, [11C]HED retention had declined in both the proximal and distal myocardial segments of the STZ-D rats by 42% (P < 0.01 vs. ND rats), and LV norepinephrine content and NGF protein were decreased in parallel. Therefore, 6 months of STZ-induced diabetes results in heterogeneous cardiac sympathetic denervation in the rat, with maximal denervation occurring distally, and is associated with a proximal-to-distal gradient of LV NGF protein depletion. It is tempting to speculate that regional fluctuations of NGF protein in the diabetic myocardium contribute to heterogeneous cardiac sympathetic denervation complicating diabetes.
Diabetes 1999 Mar
PMID:Heterogeneous cardiac sympathetic denervation and decreased myocardial nerve growth factor in streptozotocin-induced diabetic rats: implications for cardiac sympathetic dysinnervation complicating diabetes. 1007 63

Painful sensory syndromes and the anesthetic foot result in much clinical morbidity and patient unhappiness in diabetes. As yet, a satisfactory and fundamental therapy is not available to us to help patients. Effective blood glucose control and vigilant screening programs for foot problems are all we have to offer. Clinical observation of neuropathic syndromes and measures of nerve function have not led to significant understanding of pathogenesis. The primary source of understanding of pathways to nerve damage come from animal studies, despite the fears that the model in diabetes in no way reflects the human situation. Therapeutic hope at the moment from such animal work must focus on the interference of pathways known to lead to neural blood-flow abnormalities and a variety of metabolic abnormalities, as well as the possibility that addition of nerve growth factor will assist repair and regeneration. The understanding of these multiple pathways in the animal model underlines the likely enormous complexity in the final picture of understanding in diabetic neuropathy. Modern imaging techniques such as magnetic resonance imaging should, in the future, allow more significant investigation of the human subject.
Diabetes Care 1999 Mar
PMID:Improving prognosis in type 2 diabetes. Diabetic neuropathy is in trouble. 1009 6

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

The study investigated the role of nerve growth factor (NGF) in the regeneration of noradrenergic nerves of the right atria from control and 8-week diabetic rats, after lesion caused by a single injection of 6-hydroxydopamine (6-OHDA, 100 mg/kg ip). This treatment caused a profound depletion of tissue noradrenaline (NA) of the right atria from both control and diabetic groups, followed by a progressive repletion that was not complete at 49 days. Immunoreactivity for the NGF receptors trkA and p75(NTR) was decreased and increased, respectively, between days 3 and 28 in right atria from diabetic rats and returned to pretreatment levels at day 49. Receptor levels were not significantly altered in controls. In contrast to tissue NA, at day 14 functional responses to electrical nerve stimulation of the right atria had completely returned to the pretreatment state in diabetic rats and were very close to normal in nondiabetic rats. NGF treatment (1 mg/kg, three times/week, for 2 weeks) increased tissue NA only in control rats; the pattern was similar after 6-OHDA. These findings are consistent with the hypothesis that NGF normally plays a role in the regulation of autonomic sympathetic nerves in the adult rat atrium and that mature and uninjured sympathetic neurons remain responsive to NGF. In injured noradrenergic neurons, NGF promotes regeneration in nondiabetic rats. The ability of NGF to promote regeneration of noradrenergic nerves is lost in diabetes and this may relate to the loss of trkA receptor on prejunctional nerve terminals after denervation.
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PMID:The regeneration of peripheral noradrenergic nerves after chemical sympathectomy in diabetic rats: effects of nerve growth factor. 1022 15

A large number of neurotrophic factors that exert effects on specific neuronal populations in the peripheral nervous system have been discovered. Some of these factors may prove useful for the treatment of diabetic peripheral neuropathy. Among the most promising are members of the neurotrophin gene family (nerve growth factor [NGF], brain-derived neurotrophic factor, neurotrophin [NT]-3, and NT-4/5), insulin-like growth factor (IGF)-I and IGF-II, and glial cell-derived neurotrophic factor. Of these, NGF and the IGFs have been tested most extensively in animal models of diabetic neuropathy, with encouraging results. Recombinant human nerve growth factor (rhNGF) has been tested in phase II clinical trials for treatment of patients with diabetes, and the results have been encouraging. Phase III trials of rhNGF have been completed, and clinical trials of other neurotrophic factors are likely to be conducted in the next few years.
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PMID:Neurotrophic factors in the therapy of diabetic neuropathy. 1048 43

To address the role of nerve growth factor (NGF) in diabetes mellitus (DM)-induced cardiac autonomic neuropathy, we quantitated and compared the expression of NGF mRNA in the cardiac and the skeletal muscle in experimental DM mice with the RT-PCR-HPLC method, which we have developed previously, using a NGF deletion mutant RNA as an internal standard. DM was induced in ICR mice via intraperitoneal injection of streptozotocin. RT-PCR was performed using total RNA extracted from left ventricle and soleus muscle, and the levels of NGF mRNA were quantitated by HPLC analysis. NGF mRNA content of the cardiac muscle was 17-fold higher than the skeletal muscles in control mice. NGF mRNA content of the cardiac muscle in diabetic mice at 6 weeks was 4.0-fold higher than that in the control mice, while that of the skeletal muscle in diabetic mice was not different from the controls. These results indicated that the DM-induced increase in NGF mRNA content was higher in cardiac muscle than skeletal muscle, and that NGF might play an important role in cardiac autonomic neuropathy.
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PMID:Comparison of nerve growth factor mRNA expression in cardiac and skeletal muscle in streptozotocin-induced diabetic mice. 1059 85


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