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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a consequence of global aging of the human population, the occurrence of cognitive impairment and dementia is rapidly becoming a significant burden for medical care and public health systems. By the year 2020, the WHO predicts there will be nearly 29 million demented people in both developed and developing countries. Primary and secondary prevention of dementia through individual and population-level interventions could reduce this imminent risk. Vascular risk factors such as type 2 diabetes, hypertension, dietary fat intake, high cholesterol, and obesity have emerged as important influences on the risk of both vascular and Alzheimer's dementia. Understanding the reasons for differences between populations in genetic vulnerability and environmental exposures may help to identify modifiable risk factors that may lead to effective prevention of vascular and Alzheimer's dementia.
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PMID:Can dementia be prevented? Brain aging in a population-based context. 1501 10

Insulin is best known for its action on peripheral insulin target tissues such as the adipocyte, muscle and liver to regulate glucose homeostasis. In the central nervous system (CNS), insulin and the insulin receptor are found in specific brain regions where they show evidence of participation in a variety of region-specific functions through mechanisms that are different from its direct glucose regulation in the periphery. While the insulin/insulin receptor associated with the hypothalamus plays important roles in regulation of the body energy homeostasis, the hippocampus- and cerebral cortex-distributed insulin/insulin receptor has been shown to be involved in brain cognitive functions. Emerging evidence has suggested that insulin signaling plays a role in synaptic plasticity by modulating activities of excitatory and inhibitory receptors such as glutamate and GABA receptors, and by triggering signal transduction cascades leading to alteration of gene expression that is required for long-term memory consolidation. Furthermore, deterioration of insulin receptor signaling appears to be associated with aging-related brain degeneration such as the Alzheimer's dementia and cognitive impairment in aged subjects suffering type 2 diabetes mellitus.
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PMID:Insulin and the insulin receptor in experimental models of learning and memory. 1509 74

Type 2 diabetes and dementia in the elderly are major public health problems. Cross-sectional studies have suggested that these two conditions may be inter-related, but the nature of this association is uncertain. Causation can only be established through studies with a longitudinal design, taking into account the many potential confounding factors in any study of cognition. A literature search has identified 10 studies (nine population-based and one of case-controlled design) that included a definable diabetic population and assessments of cognitive function at baseline and at follow-up. These 10 studies utilised a combination of domain-specific cognitive assessments and a clinical diagnosis of dementia in the assessment of cognitive function. Diabetes was associated with either an accelerated cognitive decline or an increased incidence of dementia in eight of nine of the population-based studies. One study demonstrated a relationship between diabetes and vascular cognitive impairment, but not with other types of dementia. No association between type 2 diabetes and cognitive decline was demonstrated in the case-controlled study. These studies provide compelling evidence to support the view that people with type 2 diabetes are at increased risk of developing cognitive impairment in comparison with the general population.
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PMID:The relationship between type 2 diabetes and cognitive dysfunction: longitudinal studies and their methodological limitations. 1509 83

Insulin therapy is an effective measure of improving glucose control even in elderly patients with type 2 diabetes. However, it is controversial whether insulin therapy does disturb the quality of life (QOL) as well as cognitive function in the elderly. In our previous study of 455 diabetic patients, the well-being as assessed by the morale scale was similar in three treatment groups. In contrast, the symptom-burden, social burden, and worry about diabetes as assessed by the Elderly Diabetes Burden Scales was more increased in insulin-treated group as compared to the diet-treated group after adjustment for age, gender, HbAlc, frequency of hypoglycemia, microangiopathy, macroangiopathy, and social support. In another study of 213 patients, MMSE scores were similar among treatment groups, while attention and learning were most impaired in insulin-treated groups after adjustment for age, gender, HbAlc, and duration of diabetes. Although the mechanism for the association between insulin treatment and cognitive impairment is unknown, hyperglycemia, hypoglycemia, and cerebral complications in insulin-treated patients may be possible explanations. Whatever mechanism may be involved, hypoglycemia should be considered especially if unexpectedly low HbAlc (< 6.5%) is observed or atypical neuropsychological symptoms appear. It is unknown how insulin withdrawal is successful in elderly diabetic patients. Using rapid or ultrarapid insulin injections three times daily, good glucose control achieved the goal of plasma glucose level of < 140 mg/dl before meals and at bedtime. Then, insulin therapy was converted to oral treatment of glimepiride (2 to 6 mg/day) and/or voglibose (0.6 mg/day) in 30 patients with poorly controlled Type 2 diabetes. About 83% of the patients were successful in the insulin withdrawal according to the criteria of HbAlc levels after two months < 8.0%. After removal of glucose toxicity, insulin withdrawal should be attempted to improve QOL in elderly patients with diabetes mellitus.
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PMID:[Insulin therapy in elderly patients with diabetes mellitus]. 1514 44

Interest in characterizing the role of impaired insulin actions in Alzheimer's disease (AD) and vascular dementia is growing exponentially. This review details what is currently known about insulin, insulin-like growth factor type I (IGF-I) and IGF-II proteins and their corresponding receptors in the brain, and delineates the major controversies pertaining to alterations in the expression and function of these molecules in AD. The various experimental animal models generated by over-expression, mutation, or depletion of genes that are critical to the insulin or IGF signaling cascades are summarized, noting the degrees to which they reproduce the histopathological, biochemical, molecular, or behavioral abnormalities associated with AD. Although no single model was determined to be truly representative of AD, depletion of the neuronal insulin receptor and intracerebroventricular injection of Streptozotocin reproduce a number of important aspects of AD-type neurodegeneration, and therefore provide supportive evidence that AD may be caused in part by neuronal insulin resistance, i.e. brain diabetes. The extant literature did not resolve whether the CNS insulin resistance in AD represents a local disease process, or complication/extension of peripheral insulin resistance, i.e. chronic hyperglycemia, hyperinsulinemia, and Type 2 diabetes mellitus. The available epidemiological data are largely inconclusive with regard to the contribution of Type 2 diabetes mellitus to cognitive impairment and AD-type neurodegeneration. A major conclusion drawn from this review is that there is a genuine need for thorough and comprehensive study of the neuropathological changes associated with diabetes mellitus, in the presence or absence of superimposed AD or vascular dementia. Strategies for intervention may depend entirely upon whether the CNS disease processes are mediated by peripheral, central, or both types of insulin resistance.
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PMID:Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer's disease. 1575 Feb 14

Type II diabetes mellitus (DM2) is associated with an increased risk of cognitive dysfunction and dementia. The increased risk of dementia concerns both Alzheimer's disease and vascular dementia. Although some uncertainty remains into the exact pathogenesis, several mechanisms through which DM2 may affect the brain have now been identified. First, factors related to the 'metabolic syndrome', a cluster of metabolic and vascular risk factors (e.g. dyslipidaemia and hypertension) that is closely linked to DM2, may be involved. A number of these risk factors are predictors of cerebrovascular disease, accelerated cognitive decline and dementia. Secondly, hyperglycaemia may be involved, through adverse effects of potentially 'toxic' glucose metabolites on the brain and its vasculature. Thirdly, insulin itself may be involved. Insulin can directly modulate synaptic plasticity and learning and memory, and disturbances in insulin signalling pathways in the periphery and in the brain have recently been implicated in Alzheimer's disease and brain aging. Insulin also regulates the metabolism of beta-amyloid and tau, the building blocks of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease. In this paper, the evidence for the association between DM2 and dementia and for each of these underlying mechanisms will be reviewed, with emphasis on the role of insulin itself.
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PMID:Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology? 1624 41

Epidemiological and experimental data suggest that type 2 diabetes (DM2) and sporadic late-onset Alzheimer's disease (AD) share a common mechanism, that is able to produce accumulation of insulin and amyloid beta 42 (Abeta42), the major pathogenic events respectively of the two conditions. In 71 non diabetic patients with amnestic mild cognitive impairment we found a significant linear correlation between fasting plasma levels of insulin and Abeta42 (R = +0.25, P < 0.05). The levels of both peptides were elevated in comparison to 48 age-matched cognitively normal controls. The correlation of insulin and Abeta42 plasma levels suggests a pathogenic link between DM2 and sporadic AD.
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PMID:Plasma levels of insulin and amyloid beta 42 are correlated in patients with amnestic Mild Cognitive Impairment. 1634 82

Posttraumatic hyperactivity is a neurobehavioral symptom commonly seen in patients after traumatic brain injury (TBI). No useful animal model has yet been established for evaluation of this important symptom. We induced either mild (MILD, 0.7-0.9 atm) or moderate (MOD, 1.3-1.6 atm) lateral fluid percussion injury (LFPI) in Mongolian gerbils. Open-field and T-maze tests were used during a 7-day period after the trauma. All animals were perfusion fixed for histopathological examinations. Transient locomotor hyperactivity was found with a peak at 6 hr after injury in the MILD animals, whereas MOD animals showed prolonged and severe hyperlocomotion throughout the 7-day posttrauma period (P < 0.0001). Interestingly, the temporal profile of the posttraumatic hyperactivity was similar to that of the working memory deficit in both injury groups. Histological examination revealed significant neural tissue damages, including cortical necrosis, white matter rarefaction, and neuronal loss in the hippocampus in the ipsilateral hemisphere of the MOD animals, vs. only negligible changes in the MILD animals. Correlation analysis revealed that the volume of white matter lesions was significantly correlated with both posttraumatic hyperactivity (r = 0.591, P < 0.01) and working memory deficit (r = -0.859, P < 0.0001). Taken together, our findings confirm the successful reproduction of posttraumatic hyperactivity following experimental TBI. The posttraumatic hyperlocomotion probably shared pathomechanisms common to those of cognitive dysfunction caused by LFPI, supporting the speculation from previous studies that some neurobehavioral abnormities intimately correlate with TBI-induced cognitive dysfunction. Histopathologically, significant involvement of white matter damage in the posttraumatic functional deficits was indicated.
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PMID:Transient versus prolonged hyperlocomotion following lateral fluid percussion injury in mongolian gerbils. 1639 4

This article reviews the clinical and experimental researches on cognitive impairment related to diabetes in the recent decade. Most clinical studies indicate that the cognitive impairment in patients with type 1 diabetes mellitus is related to recurrent hypoglycemia closely. There is little research about whether or not hyperglycemia is related to cognitive impairment in patients with type 1 diabetes mellitus. Most studies indicate that the cognitive impairment in type 2 diabetes involves multiple factors through multiple mechanisms, including blood glucose, blood lipid, blood pressure, level of insulin, medication, chronic complication, etc. But, there has been no large-scale, multi-center, randomized controlled clinical trial in China recently. And what is more, some problems exist in this field of research, such as the lack of golden criterion of cognitive function measurement, different population of studied objects, and incomprehensive handling of confounding factors. Experimental studies found that hippocampal long-term potentiation (LTP) was impaired, which were manifested by impairment of spatial memory and decreased expression of LTP, but it's relation to hyperglycemia, the duration of diabetes, learning and memory has always been differently reported by different researches. Thus, there are a lot of unknown things to be explored and studied in order to clarify its mechanism. TCM has abundant clinical experience in treating cerebral disease with medicine that enforces the kidney and promotes wit. However, there has been no research on treating diabetic cognitive impairment, which requires work to be done actively and TCM to be put into full play, in order to improve the treatment of diabetes and enhance living quality of patients.
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PMID:Current status of clinical and experimental researches on cognitive impairment in diabetes. 1657 Dec 91

Insulin resistance (reduced ability of insulin to stimulate glucose utilization) is common in North American and Europe, where as many as one third of all older adults suffer from prodromal or clinical type 2 diabetes mellitus. It has long been known that insulin-resistant conditions adversely affect general health status. A growing body of findings suggests that insulin contributes to normal brain functioning and that peripheral insulin abnormalities increase the risk for memory loss and neurodegenerative disorders such as Alzheimer's disease. Potential mechanisms for these effects include insulin's role in cerebral glucose metabolism, peptide regulation, modulation of neurotransmitter levels, and modulation of many aspects of the inflammatory network. An intriguing question is whether insulin abnormalities also influence the pathophysiology of multiple sclerosis (MS), an autoimmune disorder characterized by elevated inflammatory biomarkers, central nervous system white matter lesions, axonal degeneration, and cognitive impairment. MS increases the risk for type 1 diabetes mellitus. Furthermore, the lack of association between MS and type 2 diabetes may suggest that insulin resistance affects patients with MS and the general population at the same alarming rate. Therefore, insulin resistance may exacerbate phenomena that are common to MS and insulin-resistant conditions, such as cognitive impairments and elevated inflammatory responses. Interestingly, the thiazolidinediones, which are used to treat patients with type 2 diabetes, have been proposed as potential therapeutic agents for both Alzheimer's disease and MS. The agents improve insulin sensitivity, reduce hyperinsulinemia, and exert anti-inflammatory actions. Ongoing studies will determine whether thiazolidinediones improve cognitive functioning for patients with type 2 diabetes or Alzheimer's disease. Future studies are needed to examine the effects of thiazolidinediones on patients with MS.
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PMID:Insulin resistance, inflammation, and cognition in Alzheimer's Disease: lessons for multiple sclerosis. 1663 Dec 7


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