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

Short- (3-4 week) and long-term (1-4 yrs) results of the use of intensive insulin therapy schemes were used in 37 patients with severe forms of type I diabetes mellitus. Its beneficial effect on metabolism, remaining secretory beta-cell function, the frequency and expression of hypoglycemic reactions, manifestations of peripheral and visceral neuropathy, diabetic encephalopathy was proved.
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PMID:[Short- and long-term results of intensive insulin therapy in patients with severe forms of diabetes mellitus type I]. 306 38

Type 1 diabetes can lead to several well-described complications such as retinopathy, nephropathy and peripheral neuropathy. Evidence is accumulating that it is also associated with gradually developing end-organ damage in the central nervous system. This relatively unknown complication can be referred to as "diabetic encephalopathy" and is characterised by electrophysiological and neuroradiological changes, such as delayed latencies of evoked potentials, modest cerebral atrophy and (periventricular) white matter lesions. Furthermore, individuals with type 1 diabetes may show performance deficits in a wide range of cognitive domains. The exact mechanisms underlying this diabetic encephalopathy are only partially known. Chronic metabolic and vascular changes appear to play an important role. Interestingly, the differences in the "cognitive profile" between type 1 and type 2 diabetes also suggest a critical role for disturbances of insulin action in the central nervous system.
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PMID:Cerebral dysfunction in type 1 diabetes: effects of insulin, vascular risk factors and blood-glucose levels. 1509 82

Substantial evidence collected from clinical data and experimental studies has indicated that CNS is not spared from diabetes complications. Impairments in CNS function are well documented in both type 1 and type 2 diabetic patients as well as in various animal models of diabetes, in terms of alterations in cognition, neuropsychology, neurobehavior, electrophysiology, structure, neurochemistry and apoptotic activities. These data suggest that primary diabetic encephalopathy exists as a definable diabetic complication. The mechanisms underlying this CNS complication are not clear. Experimental studies have suggested that neuronal apoptosis may play an important role in neuronal loss and impaired cognitive function. In diabetes multiple factors are responsible for neuronal apoptosis, such as a perturbed IGF system, hyperglycemia and the aging process itself. Recent data suggest that insulin/C-peptide deficiency may exert an eminent role. Administration of C-peptide partially corrects the perturbed IGF system in the brain and prevents neuronal apoptosis in hippocampus of type 1 diabetes. In neuroblastoma SH-SY5Y cells C-peptide provides a dose-dependent stimulation on cell proliferation and an anti-apoptotic effect as well. These studies provide a basis for administration of C-peptide as a potentially effective therapy for type 1 diabetes.
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PMID:C-peptide and central nervous system complications in diabetes. 1519 73

Type 1 diabetes mellitus correlates with several brain disturbances, including hypersensitivity to stress, cognitive impairment, increased risk of stroke and dementia. Within the central nervous system, the hippocampus is considered a special target for alterations associated with diabetes. Neurogenesis is a plastic event restricted to few adult brain areas: the subgranular zone of the dentate gyrus and the subventricular zone (SVZ). First, we studied the ability for neurogenesis in the dentate gyrus and SVZ of chronic diabetic mice induced by streptozotocin (STZ). Using bromodeoxyuridine (BrdU) labelling of cells in the S-phase, we observed a strong reduction in cell proliferation rate in both brain regions of diabetic mice killed 20 days after STZ administration. Second, because oestrogens are active neuroprotective agents, we investigated whether 17beta-oestradiol (200 micro g pellet implant in cholesterol during 10 days) restored brain cell proliferation in the diabetic mouse brain. Our results demonstrated a complete reversibility of dentate gyrus cell proliferation in oestrogen-treated diabetic mice. This plasticity change was not exclusive to the hippocampus because oestrogen treatment restored BrdU incorporation into newborn cells of the SVZ region of diabetic animals. Oestrogen treatment did not alter the hyperglycemic status of STZ-diabetic mice. Moreover, oestrogen did not modify BrdU incorporation in control animals. These data show that oestrogen treatment strongly stimulates brain neurogenesis of diabetic mice and open up new venues for understanding the potential neuroprotective role of steroid hormones in diabetic encephalopathy.
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PMID:Oestradiol restores cell proliferation in dentate gyrus and subventricular zone of streptozotocin-diabetic mice. 1527 Oct 63

Microangiopathic end-organ injury is common in type 1 diabetes. However, the pathophysiology of diabetic encephalopathy is poorly understood. The authors studied 10 normotensive patients with type 1 diabetes with retinopathy, autonomic neuropathy, but without nephropathy, and 10 healthy subjects. Proton magnetic resonance spectroscopy was performed at 1.5 T in the frontal cortex, thalamus, and posterior frontal white matter. There was no change in N-acetyl-containing compounds (NA), but choline-containing compounds (Cho) were increased in the white matter and in the thalamus; myo-inositol was increased in the white matter, glucose excess was found in all brain, and water intensity was increased in the cortical voxel in the patients. Calculated lifetime glycemic exposure correlated inversely with Cho and NA in white matter and with Cho in thalamus. Concentrations of soluble intercellular adhesion molecules and vascular cell adhesion molecules were increased in the patients. In conclusion, in patients with type 1 diabetes, the increase in adhesion molecules and an association between altered brain metabolites and glycemic exposure suggest the presence of a vascularly mediated, progressive metabolic disturbance in the brain.
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PMID:Brain metabolic alterations in patients with type 1 diabetes-hyperglycemia-induced injury. 1562 13

We have previously shown that hippocampal neuronal apoptosis accompanied by impaired cognitive functions occurs in type 1 diabetic BB/Wor rats. To differentiate the contribution by insulin deficiency vs. that by hyperglycemia on neuronal apoptosis, we examined the activities of various apoptotic pathways in hippocampi from type 1 diabetic BB/Wor rats (hyperglycemic and insulinopenic) and type 2 diabetic BBZDR/Wor rats (hyperglycemic and hyperinsulinemic). DNA fragmentation was demonstrated by LM-PCR in type 1 diabetic BB/Wor rats, but was not detectable in duration- and hyperglycemia-matched type 2 BBZDR/Wor rats. Of various apoptotic pathways, Fas activations, 8-OHdG expression, and caspase-12 were demonstrated in type 1 diabetic BB/Wor rats only. In contrast, perturbations of the IGF and NGF systems and PARP activation were demonstrated in type 1 and to a lesser extent in type 2 diabetes. Expressions of Bax and active caspase-3 were significantly increased in type 1, but not in type 2, diabetic rats. These data suggest a lesser apoptogenic stress in type 2 vs. type 1 diabetes. These differences translated into a more profound neuronal loss in the hippocampus of type 1 rats. The results demonstrate that caspase-dependent apoptotic activities dominate in type 1 diabetes, whereas PARP-mediated caspase-independent apoptotic stress is present in both type 1 and type 2 diabetes. The findings suggest that insulin deficiency plays a compounding role to that of hyperglycemia in neuronal apoptosis underpinning primary diabetic encephalopathy.
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PMID:The role of impaired insulin/IGF action in primary diabetic encephalopathy. 1577 48

Primary diabetic encephalopathy is a recently recognized late complication of diabetes resulting in a progressive decline in cognitive faculties. In the spontaneously type 1 diabetic BB/Wor rat, we recently demonstrated that cognitive impairment was associated with hippocampal apoptotic neuronal loss. Here, we demonstrate that replacement of proinsulin C-peptide in this insulinopenic model significantly prevented spatial learning and memory deficits and hippocampal neuronal loss. C-peptide replacement prevented oxidative stress-, endoplasmic reticulum-, nerve growth factor receptor p75-, and poly(ADP-ribose) polymerase-related apoptotic activities. It partially ameliorated apoptotic stresses mediated via impaired insulin and IGF activities. These findings were associated with the prevention of increased expression of Bax and active caspase 3 and the frequency of caspase 3-positive neurons. The results show that several partially interrelated apoptotic mechanisms are involved in primary encephalopathy and suggest that impaired insulinomimetic action by C-peptide plays a prominent role in cognitive dysfunction and hippocampal apoptosis in type 1 diabetes. Although these abnormalities were not fully prevented by C-peptide replacement, the findings suggest that this regime will substantially prevent cognitive decline in the type 1 diabetic population.
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PMID:The effect of C-peptide on cognitive dysfunction and hippocampal apoptosis in type 1 diabetic rats. 1585 38

Examination of 91 patients with diabetic retinopathy in the presence of type I diabetes mellitus (DM-1) showed that 56% of the patients had a great variety of organ-specific and organ-nonspecific autoantibodies (AABs), including those to the microsomal and cytoplasmic fractions of endocrine glands, such as pancreas, thyroid, and pituitary. AABs were most common to the pituitary (23.2%), total myelin protein (18.7%), and denatured DNA (17.6%). There were correlations between AAB and the duration of DM-1 more than 20 years (78.3%; p < 0.05), between the total myelin protein AAB and encephalopathy (31.3%; p < 0.05), between the denatured DNA AAB and the increased retinal vascular permeability (29.3%; p < 0.05), which suggests their implication in vascular wall disintegration. No correlations could be found between AAB to the pituitary, pancreas, and thyroid and obvious pathology of the glands. Combined therapy with the immunomodulators thymactid and lycopide yielded a total beneficial effect (AAB disappearance, decreased titers, and no changes) in 88.3% of case while beneficial effect of insulin therapy was obtained in 53.9% of cases, which suggests that it is expedient to include of currently available immunomodulators into traditional insulin therapy.
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PMID:[Systemic autoantibodies and their correction in patients with diabetic retinopathy in type 1 diabetes mellitus]. 1721 99

Presence of IgG autoantibodies to broad spectrum of tissues' antigens in patients with diabetic retinopathy under type I diabetes mellitus was studied. Increased levels of antibodies to different antigens were observed in 56% of patients. Increased levels of antibodies to hypophysis, denaturated DNA, and myelin basic protein were detected most frequently. Correlation in presence of autoantibodies of different specificity with diabetes length as well as with frequency of respiratory infections was established. There was relation between level of antibodies to DNA and increased permeability of microvascular network of retina as well as between presence of autoantibodies to myelin basic protein and encephalopathy in patients with type I diabetes mellitus.
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PMID:[Immunologic autoagression in patients with diabetic retinopathy under type I diabetes mellitus]. 1729 82

In this review we will describe the interaction between insulin and C-peptide which enhances and attenuates insulin-signaling functions. We will describe how replenishment of C-peptide prevents and reverses the early metabolic abnormalities in type 1 diabetic polyneuropathy, such as Na(+)/K(+)-ATPase activity and endoneurial vascular NO release, resulting in prevention and reversal of early nerve dysfunction. The effects on expression of neurotrophic factors and their receptors, mediated by corrections of early gene responses and transcription factors, have downstream beneficial effects on cytoskeletal protein mRNAs and protein expression. Similar effects probably underlie corrections of cell adhesive molecules. The end-effects are prevention and reversal of myelinated and unmyelinated axonal degeneration, atrophy, and loss. Similarly, progressive degeneration of the node and paranode is prevented and repaired by C-peptide replacement with normalization of the molecular constituents of these functionally important structures. Cognitive dysfunction is now recognized as a complication of type 1 diabetes. Experimentally it is linked to impaired synaptic plasticity and eventually apoptotic neuronal loss caused by impaired insulin action and neurotrophic support. C-peptide replacement partially prevents hippocampal neuronal apoptosis and cognitive deficits. It is therefore becoming increasingly clear that C-peptide has major functions in supporting insulin action with a multitude of beneficial effects on diabetic polyneuropathy and primary diabetic encephalopathy in type 1 diabetes.
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PMID:Is C-peptide replacement the missing link for successful treatment of neurological complications in type 1 diabetes? 1822 Jul 11


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