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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A unifying metabolic hypothesis completely accounting for the development of one or more of the chronic complications of diabetes on the basis of a single aspect of disturbed glucose metabolism resulting from insulin deficiency and/or hyperglycemia has been sought by clinical and basic scientists for decades. A growing body of loosely related but internally consistent scientific data obtained from cultured cells, incubated tissue preparations, animal models, and man implicate sorbitol- and glucose-induced myo-inositol depletion and altered phosphoinositide metabolism in a series of secondary biochemical, functional, and architectural abnormalities in the PNS in diabetes. These early metabolically based functional and structural changes simulate those that characterize human diabetic neuropathy. Can abnormal phosphoinositide metabolism in diabetic nerve thereby by itself explain the development of chronic diabetic neuropathy with all of its clinical complexity and heterogeneity? Almost certainly not. Even if the entire contribution of hyperglycemia to the development of diabetic neuropathy were mediated by secondary abnormalities in phosphoinositide metabolism, other factors must also play a role. Witness the differences in the histopathological picture of neuropathy in patients with IDDM and NIDDM despite similar durations and severity of diabetes, the apparent influence of age and gender on the appearance of early neuropathy in patients with IDDM, and the association of alcohol consumption with diabetic neuropathy. While early metabolic and functional disturbances in diabetic nerve such as impaired (Na,K)-ATPase function and paranodal swelling are empirically attributable to abnormal myo-inositol and phosphoinositide metabolism, more advanced abnormalities such as axo-glial dysjunction may reflect superimposed independent biochemical and/or hormonal defects (although, as mentioned previously, aldose reductase inhibition decreases axo-glial dysjunction in diabetic humans). The PNS has only a limited repertoire of responses to a variety of insults, so that Wallerian degeneration, axonal atrophy, impaired axonal transport, and dystrophic changes in diabetic neuropathy may represent multiple factors. On the other hand, the increasingly recognized importance of the phosphoinositide cascade in neuromodulation may attribute a progressively wider range of disturbances in the diabetic PNS to myo-inositol depletion and associated defects in phosphoinositide metabolism. Thus, while all effects of aldose reductase inhibitors in the PNS of diabetic rats have been reproduced by myo-inositol supplementation when this alternative intervention has been tested, the exact role of phosphoinositide metabolism in most of these responses is not well understood.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathogenesis of diabetic neuropathy: role of altered phosphoinositide metabolism. 256 4

Extensive multiple neuropathies were observed in four patients after prolonged stay in intensive care units. Date of onset of the multiple disorders was difficult to determine due to disturbed consciousness of all patients during the first few weeks of intensive care: it was probably between the 10th and 30th days. Electrophysiological examinations in the 4 patients, and ultrastructural study of musculocutaneous nerve of leg in 2 cases, suggested an acute axonal lesion. All patients survived the causal affection which had justified prolonged intensive care, 3 recovering from the multiple neuropathy within 3 to 4 months, the last patient having marked neuromuscular sequelae. Several factors can be incriminated at the origin of this multiple neuropathy. Whereas retrospective studies allowed exclusion of a toxic, infectious or drug-related cause, severe nutritional deficiencies existed; proteins in all cases and vitamins in one patient despite enteral re-nutrition judged as satisfactory. Additionally, a role for a previous lesion of peripheral nerves from chronic hypoxia was possible in 2 cases as well as for a non-insulin dependent diabetes in one of these two patients. A rarely reported but probably not exceptional complication, diagnosis is assisted by early electrophysiologic exploration. Correction of nutritional disorders may require parenteral feeding exclusively, this possibly accelerating neurologic recovery, as proposed in the several rare studies reported in the literature.
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PMID:[Polyneuropathies during prolonged stays in resuscitation]. 332 11

Altered sorbitol and myo-inositol metabolism, (Na,K)-ATPase function, electrochemical sodium gradients, axonal swelling, and distortion and disruption of the node of Ranvier ("axo-glial dysjunction") directly implicate hyperglycemia in the pathogenesis of neuropathy in diabetic rats, but the relevance of this sequence to clinical neuropathy in heterogeneous groups of diabetic patients remains to be established. Fascicular sural nerve morphometry in 11 patients with neuropathy complicating insulin-dependent diabetes revealed a pattern of interrelated structural changes strikingly similar to that of the diabetic rat when compared to age-matched controls. 17 older non-insulin-dependent diabetic patients with comparable duration and severity of hyperglycemia and severity of neuropathy, displayed similar nerve fiber loss, paranodal demyelination, paranodal remyelination and segmental demyelination compared to age-matched controls, but axo-glial dysjunction was replaced by Wallerian degeneration as the primary manifestation of fiber damage, and fiber loss occurred in a spatial pattern consistent with an ischemic component. The mechanistic model developed from the diabetic rat does indeed appear to apply to human diabetic neuropathy, but superimposed hormonal, metabolic, vascular, and/or age-related effects alter the morphologic expression of the neuropathy in non-insulin dependent diabetes.
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PMID:Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demonstration of axo-glial dysjunction in human diabetic neuropathy. 333 24

The clinical and electro-neurographic examinations were carried out in 54 patients aged 21-67 years (mean = 41.8) with IDDM of at least 10-year duration, and 25 subjects aged 19-62 years (mean = 39.0) as a control group. The aim of the study was the determination of: 1) the frequency of polyneuropathy appearance in patients with IDDM of at least 10-year duration; 2) the usefulness of electroneurography for detection of subclinical impairment of peripheral nervous system in diabetics; 3) the characterization of electro-neurographic abnormalities in diabetic neuropathy; 4) the influence of diabetes duration and metabolic control on severity of peripheral nerves affection; 5) the relationship between polyneuropathy and retinopathy, nephropathy and cataract occurrence in diabetic patients. Polyneuropathy was diagnosed--clinically in 67% of patients, electro-neurographically in 85% of patients. The neurographic study proved high sensitivity for detection of subclinical affection of peripheral nerves in diabetics. The electro-neurographic abnormalities appeared more frequently and were more considerable in the group of patients with clinical polyneuropathy. Frequency of the sensory and motor nerve fibres involvement was similar. The electroneurographical abnormalities corresponded with the features of mixed--axonal and demyelinating type of neuropathy. It was disclosed that the degree of neurographical changes did not depend on duration and severity of hyperglycemia in late period of the disease. A moderate relationship between occurrence of polyneuropathy and retinopathy, nephropathy as well as diabetic cataract was revealed.
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PMID:[Clinical and electroneurographic changes in the peripheral nervous system of patients with chronic insulin-dependent diabetes (IDDM)]. 750 45

Although the detailed pathogenesis of diabetic polyneuropathy is not known, several mechanisms appear to be involved and may occur sequentially. Hence, the early and much researched activation of the polyol-pathway appears to secondarily affect nonenzymatic glycation, perturbation of vasoactive substances, the immune system and neurotrophism. These metabolic abnormalities may be differentially expressed in the neuropathy occurring in insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) diabetes. This notion is supported by differences in the structural abnormalities of the neuropathies in the two types of diabetes. Distinct and characteristic nodal changes occur in IDDM but not in NIDDM neuropathy, which also shows a milder axonal atrophy. On the other hand, nerve fiber loss which characterizes diabetic neuropathy tends to be focal in the older NIDDM patients, suggesting a more prominent vascular genesis. A further characteristic feature of diabetic neuropathy is blunted fiber regeneration, which probably is consequent to impairments of the necessary immune response and local synthesis of neurotrophic factors. Nerve biopsies from diabetic patients, although not necessary for diagnosis, provide valuable tissue for biochemical and molecular analysis of underlying mechanisms, the detailed elucidation of which will facilitate the design of targeted therapies.
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PMID:Neuropathology of diabetic neuropathy and its correlations with neurophysiology. 935 80

Cytoarchitectonics and neuronal organization of sexual dimorphism zones (ZSD) of amygdala, one of the brain higher neuroendocrine centres were studied and reactive changes of this zone neurons were analysed in rats with chronic alloxan diabetes that modulate type I diabetes mellitus in man. Structural organization of main ZSD of amygdala--dorsomedial, anterior and basolateral nuclei displays its characteristic topographical and cytoarchitectonic peculiarities. Neuronal organisation of main amygdala zones is characterized by different ratio of intensely and sparsely dendritic long-axonal neurons. Neurons of all ZSD respond to insulin deficiency--induced disturbances of carbohydrate metabolism in the same type. Reactive changes of neurons defined consist in chromatophilia development and neuron shrinkage and also in significant decline in cell nuclear volume.
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PMID:[Structural and functional organization of sexual dimorphism zones of the amygdala in the normal state and in alloxan diabetes]. 960 67

Insulin-dependent diabetes mellitus is a chronic metabolic disease that causes long-term secondary complications such as neuropathy. The occurrence of diabetic neuropathy has generally been thought of as being associated with hyperglycaemia. However, in a previous light microscopic examination of plantar nerves in diabetic BB/Wor rats treated with insulin implants we found that eu-/hyperglycaemic rats present a normal picture, whereas eu-/hypoglycaemic rats show severe changes. The aim of the present work is to supplement our previous light microscopic report with electron microsocpic data from the lateral plantar nerve of normal, eu-/hyperglycaemic and eu-/hypoglycaemic BB/Wor rats. Under the electron microscope lateral plantar nerves collected from eu-/hyperglycaemic rats presented a qualitatively normal picture. In addition, the fibre numbers and the size distribution of the myelinated fibres were normal. In contrast, specimens from eu-/hypoglycaemic BB/Wor rats showed severe qualitative changes, interpreted as signs of axonal de- and regeneration. The total number of axons was somewhat subnormal and the sizes of the myelinated fibres were strongly shifted towards smaller diameters. These data confirm our previous light microscopic observations. We conclude that eu-/hypoglycaemic BB/Wor rats treated with insulin implants, but not similarly treated eu-/hyperglycaemic animals, develop a neuropathy in their plantar nerves.
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PMID:Hypoglycaemic neuropathy in BB/Wor rats treated with insulin implants: electron microscopic observations. 970 30

Theiler's murine encephalomyelitis virus (TMEV) disease is induced following intracerebral inoculation of TMEV, a member of picornavirus family, in susceptible animals. The pathogenesis of paralytic syndrome is associated with a chronic progressive demyelinating disease characterized by perivascular of immune inflammatory cells. Although TMEV induced demyelinating disease (TMEV IDD) is initiated by virus specific CD4+ T cells targeting CNS persistent virus, CD4+ T cell responses against self myelin epitopes activated via epitope spreading contribute to chronic disease pathogenesis. In the present report we delineated possible pathogenic mechanisms related with inflammatory process, leading to demyelination and axonal loss. The importance of proinflammatory cytokines in sustaining the inflammatory process and cause direct oligodendrotoxicity is emphasized. Different approaches in therapeutic strategies affecting cytokines are also presented.
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PMID:[Theiler's virus encephalomyelitis infection as a model for multiple sclerosis: cytokines and pathogenic mechanisms]. 1243 2

Diabetic polyneuropathy (DPN) shows more severe functional and structural changes in type 1 than in type 2 human and experimental diabetes. We have previously suggested that these differences may be due to insulin and/or C-peptide deficiencies in type 1 diabetes. To further explore these differences between type I and type 2 DPN, we examined factors underlying nerve fiber regeneration in the hyperinsulinemic type 2 BB/Z-rat and compared these with previous data obtained from the iso-hyperglycemic, insulin and C-peptide-deficient type 1 diabetic BB/Wor-rat. The expression of neurotrophic factors and cytoskeletal proteins were studied in L4 and L5 dorsal root ganglia (DRG) at various time points after sciatic nerve crush. The data were compared to those of nondiabetes-prone BB-rats. Insulin-like growth factor 1 (IGF-1) and TrkA levels were lower in DRG from type 1 than from those of type 2 and control BB-rats. On the other hand, IGF-1 receptor expression was increased at baseline in type 1 BB/Wor-rats and decreased after crush injury, whereas its expression increased after crush injury in both control and type 2 BB/Z-rats. Following crush injury, betaII- and betaIII-tubulins were upregulated in type 2 BB/Z and control rats, which did not occur in type 1 BB/Wor-rats. Furthermore, type 2 BB/Z-rats showed the normal downregulation of low and medium molecular neurofilament (NF-L and NF-M, respectively), which did not occur in type 1 BB/Wor-rats. These findings were associated with significantly milder abnormalities in axonal elongation and caliber growth of regenerating fibers in type 2 compared to type 1 diabetic rats. These data suggest that impaired insulin signaling in type 1 diabetic nerve may be of greater significance in the regulation of neurotrophic and neurocytoskeletal protein synthesis than hyperglycemia in explaining the differences in nerve fiber regeneration between type 2 and type 1 diabetes.
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PMID:Insulin deficiency rather than hyperglycemia accounts for impaired neurotrophic responses and nerve fiber regeneration in type 1 diabetic neuropathy. 1263 30

The IGF system plays vital roles in neuronal development, metabolism, regeneration and survival. It consists of IGF-I, IGF-II, insulin, IGF-I-receptor, and those of IGF-II and insulin as well as IGF-binding proteins. In the last decades it has become clear that perturbations of the IGF system play important roles in the pathogenesis of diabetic neurological complications. In the peripheral nervous system IGF-I, insulin, and C-peptide particularly in type 1 diabetes participate in the development of axonal degenerative changes and contributes to impaired regenerative capacities. These abnormalities of the IGF system appear to be less pronounced in type 2 diabetes, which may in part account for the relatively milder neurological complications in this type of diabetes. The members of the IGF system also provide anti-apoptotic effects on both peripheral and central nervous system neurons. Furthermore, both insulin and C-peptide and probably IGF-I possess gene regulatory capacities on myelin constituents and axonal cytoskeletal proteins. Therefore, replenishment of various members of the IGF system provides a reasonable rational for prevention and treatment of diabetic neurological complications.
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PMID:The insulin-like growth factor system and neurological complications in diabetes. 1466 47


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