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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 decline in cognitive function has been reported in type 1 diabetes, but its relation to different disease factors such as hypoglycemic events and peripheral neuropathy is controversial. The objective of the present study was to identify factors that are important for cognitive impairment in type 1 diabetes. A cross-sectional study was performed in adult patients (N=150) with type 1 diabetes (duration 26.6+/-11.4 years). Function in different cognitive domains was evaluated by the same trained examiner, in order to eliminate inter-rater variability. Peripheral nerve function was tested quantitatively. Predictors of cognitive impairment were identified using multiple regression analysis. The major finding was that long diabetes duration and young age of diabetes onset were the strongest predictors of low scores in psychomotor speed, memory, processing speed, attention, working memory, verbal ability, general intelligence, executive functions and a low global score. The number of previous hypoglycemic events had no defined effect upon cognitive functioning. Other significant predictors were low compound muscle action potential (CMAP) (for visual perception-organization), old age (for visual-spatial ability), short stature, high BMI and hypertension. Presence of retinopathy and long-term metabolic control correlated with nerve conduction defects, but not with cognitive impairment. Although a history of hypoglycemic events was not a predictor of cognitive impairment, we cannot exclude the possibility that the influence of young age of diabetes onset depends on the effect of hypoglycemic events early in life. The clinical relationships of cognitive impairment differ from those of peripheral neuropathy, indicating a different pathogenesis. The influence of diabetes duration, BMI, height, age and CMAP may suggest that loss of the neuroprotective effects of insulin or insulin-like growth factors plays a role.
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PMID:Predictors of cognitive impairment in type 1 diabetes. 1788

Hypoglycaemia is the commonest side-effect of insulin treatment for diabetes, and is the single greatest barrier to achieving and maintaining good glycaemic control. Severe hypoglycaemia (requiring assistance for recovery) is associated with significant morbidity and is feared by most people with type 1 diabetes and their families. It causes stress and anxiety and may influence self-management and glycaemic control. The annual prevalence of severe hypoglycaemia is around 30% in people with type 1 diabetes, and is higher in those with risk factors such as strict glycaemic control, impaired awareness of hypoglycaemia and increasing duration of diabetes. It is also common during sleep (nocturnal hypoglycaemia). Neurological manifestations include coma, convulsions, transient hemiparesis and stroke, while reduced consciousness and cognitive dysfunction may cause accidents and injuries. Cardiac events may be precipitated such as arrhythmias, myocardial ischaemia and cardiac failure. Hypoglycaemia can affect all aspects of life, including employment, driving, recreational activities involving exercise, and travel, and measures should be taken in all of these situations to avoid this potentially dangerous side-effect of insulin therapy.
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PMID:How hypoglycaemia can affect the life of a person with diabetes. 1808 77

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

Individuals with type 1 diabetes show mild performance deficits in a range of neuropsychological tests compared to healthy controls, but the mechanisms underlying this cognitive deterioration are still poorly understood. Basically, two diabetes-related mechanisms can be postulated: recurrent severe hypoglycaemia and/or chronic hyperglycaemia. Intensive insulin therapy in type 1 diabetes, resulting in a durable improvement of glycaemic control, has been shown to lower the risk of long-term microvascular and macrovascular complications. The down side of striving for strict glycaemic control is the considerably elevated risk of severe hypoglycaemia, sometimes leading to seizure or coma. While retrospective studies in adult patients with type 1 diabetes have suggested an association between a history of recurrent severe hypoglycaemia and a modest or even severe degree of cognitive impairment, large prospective studies have failed to confirm this association. Only fairly recently, better appreciation of the possible deleterious effects of chronic hyperglycaemia on brain function and structure is emerging. In addition, it can be hypothesized that hyperglycaemia associated microvascular changes in the brain are responsible for the cognitive decline in patients with type 1 diabetes. This review presents various pathophysiological considerations concerning the cognitive decline in patients with type 1 diabetes.
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PMID:Hyperglycaemia as a determinant of cognitive decline in patients with type 1 diabetes. 1839 73

Diabetic polyneuropathy (DPN) occurs more frequently in type 1 diabetes resulting in a more severe DPN. The differences in DPN between the two types of diabetes are due to differences in the availability of insulin and C-peptide. Insulin and C-peptide provide gene regulatory effects on neurotrophic factors with effects on axonal cytoskeletal proteins and nerve fiber integrity. A significant abnormality in type 1 DPN is nodal degeneration. In the type 1 BB/Wor-rat, C-peptide replacement corrects metabolic abnormalities ameliorating the acute nerve conduction defect. It corrects abnormalities of neurotrophic factors and the expression of neuroskeletal proteins with improvements of axonal size and function. C-peptide corrects the expression of nodal adhesive molecules with prevention and repair of the functionally significant nodal degeneration. Cognitive dysfunction is a recognized complication of type 1 diabetes, and is associated with impaired neurotrophic support and apoptotic neuronal loss. C-peptide prevents hippocampal apoptosis and cognitive deficits. It is therefore clear that substitution of C-peptide in type 1 diabetes has a multitude of effects on DPN and cognitive dysfunction. Here the effects of C-peptide replenishment will be extensively described as they pertain to DPN and diabetic encephalopathy, underpinning its beneficial effects on neurological complications in type 1 diabetes.
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PMID:The effects of C-peptide on type 1 diabetic polyneuropathies and encephalopathy in the BB/Wor-rat. 1843 23

Type 1 diabetes is a common metabolic disorder accompanied by an increased secretion of glucocorticoids and cognitive deficits. Chronic excess of glucocorticoids per se can evoke similar neuropathological signals linked to its major target in the brain, the hippocampus. This deleterious action exerted by excess adrenal stress hormone is mediated by glucocorticoid receptors (GRs). The aim of the present study was to assess whether excessive stimulation of GR is causal to compromised neuronal viability and cognitive performance associated with the hippocampal function of the diabetic mice. For this purpose, mice had type 1 diabetes induced by streptozotocin (STZ) administration (170 mg/kg, i.p.). After 11 days, these STZ-diabetic mice showed increased glucocorticoid secretion and hippocampal alterations characterized by: (1) increased glial fibrillary acidic protein-positive astrocytes as a marker reacting to neurodegeneration, (2) increased c-Jun expression marking neuronal activation, (3) reduced Ki-67 immunostaining indicating decreased cell proliferation. At the same time, mild cognitive deficits became obvious in the novel object-placement recognition task. After 6 days of diabetes the GR antagonist mifepristone (RU486) was administered twice daily for 4 days (200 mg/kg, p.o.). Blockade of GR during early type 1 diabetes attenuated the morphological signs of hippocampal aberrations and rescued the diabetic mice from the cognitive deficits. We conclude that hippocampal disruption and cognitive impairment at the early stage of diabetes are caused by excessive GR activation due to hypercorticism. These signs of neurodegeneration can be prevented and/or reversed by GR blockade with mifepristone.
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PMID:Glucocorticoid receptor blockade normalizes hippocampal alterations and cognitive impairment in streptozotocin-induced type 1 diabetes mice. 1878 48

The occurrence of diabetes and dementia is very high in older patients. The fact that both conditions are concurrent raises the question of a possible link between the two. Cognitive functions of non-demented patients with diabetes have been extensively studied. In type 1 diabetes, only a mild decrease of the speed of information processing and of the psychomotor efficiency has been shown. Cognitive decline seems to be related to poor metabolic control and not to hypoglycaemia. In older patients with type 2 diabetes, memory and executive functions have been found impaired. Longitudinal studies of the literature have shown that diabetic patients have a higher chance of developing dementia than non-diabetic patient, with a relative risk (RR) between 1.26 and 2.83. The risk of vascular dementia was increased in 3 out of 5 studies, with a RR ranging between 2 and 2.6. With regard to Alzheimer's disease, the results are conflicting. Half of the studies found an increased risk in diabetic patients (RR: 1.3-2). The possible causal mechanisms of dementia in diabetic patients remain hypothetical. MRI studies showed varying degrees of cortical atrophy, cerebral infarcts and deep white matter lesions. In neuropathological studies, senile plaques and neurofibrillary tangle were not found with higher severity in the brain of diabetic patients than in the brain of age-matched controls. Several hypotheses have been raised to explain the relationship between diabetes and cognitive decline. Micro and macrovascular changes in the brain could induce cerebral hypoxia and ischemic conditions resulting in cellular death or white matter lesions. The occurrence of vascular lesions might reduce the threshold at which dementia will occur in Alzheimer disease. The deposition of advanced glycation end products doesn't spare the brain and they have been found in senile plaques, where they can reduce the solubility of proteins such as the beta amyloid and Tau proteins. Some authors favour the hypothesis of a brain insulin resistance because, in a few small studies, insulin was found to improve memory.
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PMID:[Diabetes mellitus and cognition: is there a link?]. 1878 78

Alzheimer's disease (AD) has characteristic histopathological, molecular, and biochemical abnormalities, including cell loss; abundant neurofibrillary tangles; dystrophic neurites; amyloid precursor protein, amyloid-beta (APP-Abeta) deposits; increased activation of prodeath genes and signaling pathways; impaired energy metabolism; mitochondrial dysfunction; chronic oxidative stress; and DNA damage. Gaining a better understanding of AD pathogenesis will require a framework that mechanistically interlinks all these phenomena. Currently, there is a rapid growth in the literature pointing toward insulin deficiency and insulin resistance as mediators of AD-type neurodegeneration, but this surge of new information is riddled with conflicting and unresolved concepts regarding the potential contributions of type 2 diabetes mellitus (T2DM), metabolic syndrome, and obesity to AD pathogenesis. Herein, we review the evidence that (1) T2DM causes brain insulin resistance, oxidative stress, and cognitive impairment, but its aggregate effects fall far short of mimicking AD; (2) extensive disturbances in brain insulin and insulin-like growth factor (IGF) signaling mechanisms represent early and progressive abnormalities and could account for the majority of molecular, biochemical, and histopathological lesions in AD; (3) experimental brain diabetes produced by intracerebral administration of streptozotocin shares many features with AD, including cognitive impairment and disturbances in acetylcholine homeostasis; and (4) experimental brain diabetes is treatable with insulin sensitizer agents, i.e., drugs currently used to treat T2DM. We conclude that the term "type 3 diabetes" accurately reflects the fact that AD represents a form of diabetes that selectively involves the brain and has molecular and biochemical features that overlap with both type 1 diabetes mellitus and T2DM.
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PMID:Alzheimer's disease is type 3 diabetes-evidence reviewed. 1988 99

Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment and the need for assistance from other persons in order to manage the situation. Such episodes represent the most feared side effect to insulin treatment and are regarded as the major limiting factor for achievement of recommended glycaemic targets in type 1 diabetes. The series of studies that constitute this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire to novel preventive measures of, severe hypoglycaemia. Our studies confirm that severe hypoglycaemia is still a major clinical problem in type 1 diabetes. The individual susceptibility to severe hypoglycaemia is highly varying and conventional risk factors - with major contribution from hypoglycaemia unawareness - only account for a limited part of this variation. Results from a case-series suggest that the use of psychoactive substances may be as significant as alcohol for promotion of risk of severe hypoglycaemia - a finding which needs to be confirmed by case-control studies. We identified elevated renin-angiotensin system activity as a novel predictor of risk of severe hypoglycaemia in type 1 diabetes with potential clinical significance. Thus, three sequential renin-angiotensin system-related risk factors were associated with severe hypoglycaemia, and by including these factors in a common model both subjects at low and at high risk within a one-year period were identified. Preliminary data suggest that this is explained by impaired capability of subjects with high renin-angiotensin system activity to maintain cognitive function during hypoglycaemia. The clinical implications of this finding which, however, must await additional independent confirmation, include prediction and possibly some prevention of severe hypoglycaemia. An evaluation of renin-angiotensin system activity may - together with assessment of other risk factors - contribute to rational individualized setting of glycaemic targets and thereby open for prevention of severe hypoglycaemia. Furthermore, subjects with elevated renin-angiotensin system activity and a high rate of severe hypoglycaemia might benefit from pharmacological blockade of the renin-angiotensin system by ACE inhibitors or angiotensin II receptor blockers or even renin blockers. This should be addressed in controlled trials.
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PMID:Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors. 1993 37

Acute hyperglycaemia impairs cognitive function. It is however not known, whether different brain regions are equally exposed to glucose during acute hyperglycemia or whether the brain is able to adjust its glucose uptake or metabolism in response to blood glucose fluctuation. We studied the effect of acute hyperglycaemia on the brain glucose concentration in seven men with type 1 diabetes with daily glucose fluctuations of 11 +/- 3 mmol/l, and in eleven age-matched non-diabetic men. Glucose was quantified with proton magnetic resonance spectroscopy in three different brain regions at baseline (fasting glycaemia) and twice during a 2 h hyperglycaemic clamp with plasma glucose increase of 12 mmol/l. The increase in brain glucose during acute hyperglycaemia in the non-diabetic group was: cortex (2.7 +/- 0.9 mmol/l) > thalamus (2.3 +/- 0.7 mmol/l) > white matter (1.7 +/- 0.7 mmol/l, P = 0.021 vs. cortex) and in the diabetic group: cortex (2.0 +/- 0.7 mmol/l) > white matter (1.3 +/- 0.7 mmol/l) > thalamus (1.1 +/- 0.4 mmol/l, P = 0.010 vs. cortex). In the diabetic group, the glucose increase in the thalamus was attenuated compared to the non-diabetic participants (P = 0.011). In conclusion, the increase of glucose during acute hyperglycaemia seems to be dependent on the brain tissue type. The high exposure of cortex to excess glucose and the altered glucose uptake or metabolism in the thalamus may thus contribute to hyperglycaemia related cognitive dysfunction.
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PMID:Evidence for abnormal glucose uptake or metabolism in thalamus during acute hyperglycaemia in type 1 diabetes--a 1H MRS study. 2042 2


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