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

Non-insulin dependent diabetes mellitus (NIDDM) has been associated with a number of physiological consequences including neuropathy, retinopathy and incidence of vascular disease. Recently, several authors reviewed studies that suggested that NIDDM is associated with cognitive impairments leading to a higher incidence of dementia and Alzheimer's disease. The current diagnostic practices that typically exclude from an AD diagnostic any patients with suspected vascular dementia, makes it very hard to resolve this issue and likely result in an underestimation of the number of people with Alzheimer's disease and diabetes. When people with cerebrovascular disease are included, diabetes is associated with an increased risk for Alzheimer's disease. Studies that have examined peripheral glucoregulation in Alzheimer's disease are not consistent but some show small to moderate impairments in insulin sensitivity. One recent study suggest that in people that have both diabetes and an ApoE4 allele, the risk of developing Alzheimer's disease is more than double the risk of people with an ApoE4 allele without diabetes. Although diabetes does not produce any of the usual brain pathology associated with Alzheimer's disease, one study has shown that diabetes dramatically increases the amyloid deposition and neurofibrillary tangles in people with the ApoE4 genotype. Taken together, the data available suggest that diabetes is probably a risk factor for Alzheimer's disease mainly through the cerebrovascular disease diabetes causes. In people with other risk factors such as ApoE4 allele, diabetes appears to lead to a more dramatic increase in Alzheimer's disease pathology.
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PMID:Diabetes, Alzheimer's disease and apolipoprotein genotype. 1295 80

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

Hypertension is one of the most important modifiable risk factors for cardiovascular pathology, such as atherosclerosis and cardiac left ventricular hypertrophy, including acute events such as stroke and myocardial infarction (MI). In particular, the risk of ischaemic and haemorrhagic stroke is directly and continuously related to high blood pressure levels. The renin-angiotensin system (RAS) plays an important role in volume homeostasis and blood pressure regulation. It also helps to prevent cell and organ damage from ischaemia during acute volume loss. However, angiotensin-II (A-II)--the main effector peptide of the RAS--also exerts a number of pathological effects, which are mediated by the AT 1 receptor. The Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) programme consists of two parallel trials where ONTARGET as a large, long-term study compares the efficacy of the angiotensin-receptor antagonist, telmisartan, the renin-angiotensin-converting enzyme (ACE) inhibitor, ramipril and combination therapy with telmisartan plus ramipril for reducing cardiovascular and cerebral risk. Telmisartan, due to its long duration of action, compares favourably with other angiotensin-receptor antagonists. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril was shown to reduce the risk for MI and other cardiovascular events in patients at high risk for pathological cardiac events, but without heart failure or a low ejection fraction. The cardiovascular outcomes of high-risk patients using the same criteria as those of the HOPE study will be assessed in both trials. TRANSCEND differs from ONTARGET in that this trial will enrol patients who do not tolerate ACE inhibitors. This parallel study will therefore be able to compare telmisartan and placebo treatment. Both ONTARGET and TRANSCEND trials feature the same primary composite end point: death caused by cardiovascular disease, acute MI, stroke and hospitalisation because of congestive heart failure. The secondary end points will focus on reductions in the development of Type 2 diabetes mellitus, nephropathy, cognitive decrease and dementia as well as atrial fibrillation.
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PMID:Challenges in improving prognosis and therapy: the Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial programme. 1515 18

The prolyl oligopeptidase (POP) family of serine proteases includes prolyl oligopeptidase, dipeptidyl peptidase IV, acylaminoacyl peptidase and oligopeptidase B. The enzymes of this family specifically hydrolyze oligopeptides with less than 30 amino acids. Many of the POP family enzymes have evoked pharmaceutical interest as they have roles in the regulation of peptide hormones and are involved in a variety of diseases such as dementia, trypanosomiasis and type 2 diabetes. In this study we have clarified the evolutionary relationships of these four POP family enzymes and analyzed POP sequences from different sources. The phylogenetic trees indicate that the four enzymes were present in the last common ancestor of all life forms and that the beta-propeller domain has been part of the family for billions of years. There are striking differences in the mutation rates between the enzymes and POP was found to be the most conserved enzyme of this family. However, the localization of this enzyme has changed throughout evolution, as three archaeal POPs seem to be membrane bound and one third of the bacterial as well as two eukaryotic POPs were found to be secreted out of the cell. There are also considerable distinctions between the mutation rates of the different substrate binding subsites of POP. This information may help in the development of species-specific POP inhibitors.
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PMID:Evolutionary relationships of the prolyl oligopeptidase family enzymes. 1520 35

Type 2 diabetes in the elderly is associated with increased incidence of vascular disease, particularly, atherosclerosis of large blood vessels. Together with other risk factors such as dyslipidemia, atherosclerosis increases the risk for coronary heart disease and stroke. Most studies that have examined the impact of type 2 diabetes and other heart disease risk factors on cognitive functions do not provide evidence that heart disease risk factors (with the possible exception of triglycerides) further increase the likelihood of observing cognitive deficits in diabetic patients. However, none of these studies used imaging techniques to evaluate atherosclerosis or evidence of cerebrovascular disease, such as infarctions. The few studies that have included brain imaging suggest that evidence of cerebrovascular disease further increases the risk for dementia in diabetic patients. The results of longitudinal studies suggest that diabetes is an independent risk factor for cognitive decline and dementia. The pattern of neuropsychological performance observed in type 2 diabetic patients appears to be the result of multiple interacting processes developing over time. In addition to the detrimental effects of protracted impaired glucose regulation on the central nervous system, type 2 diabetes pathology also encompasses the detrimental effects of associated complications such as cerebrovascular disease, which is likely the main cause of the observed processing speed/reaction time decrements.
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PMID:The relationships between atherosclerosis, heart disease, type 2 diabetes and dementia. 1526 76

We examined change in neuropsychological test performance related to type 2 diabetes mellitus across a 6-year interval. A population-based sample of 274 elderly participants (36 with diabetes and 238 without diabetes) was examined at four occasions at a 2-year interval. The participants were 80-93 years of age (M = 82.8 years) and without dementia at baseline. The test battery included tests of speed, visuospatial ability, short-term memory, semantic memory, episodic memory, and the Mini Mental Status Examination. Several models, taking into account diabetes and demographic data, were analyzed using SAS Proc Mixed multilevel modeling. At baseline, there were no significant differences in the neuropsychological tests related to diabetes. The longitudinal analyses, however, showed that diabetes was a significant predictor of decline for many of the tests. These findings points to the conclusion that type 2 diabetes is associated with accelerated cognitive decline in old age that may result in dementia.
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PMID:Type 2 diabetes mellitus contributes to cognitive decline in old age: a longitudinal population-based study. 1532 38

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

A progressive chain of pathophysiological events links cardiovascular risk factors to clinical manifestations of disease and life-threatening cardiovascular events. This chain--the cardiovascular continuum--underlies cardiovascular disease and holds the key to its prevention and treatment. Progressive tissue damage can result in morbidity from congestive heart failure, end-stage heart disease, nephrotic proteinuria and dementia and, eventually, death from cardio- or cerebrovascular causes. The renin-angiotensin-aldosterone system (RAAS) is involved at all stages of the cardiovascular continuum, because the effector molecules of the RAAS, angiotensin II in particular, have direct pathobiological effects on a variety of tissues, including the endothelium, vascular smooth muscle and the renal mesangium. Clinical trials of angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors have demonstrated the essential validity of this hypothesis. Interruption of the RAAS has been shown to reduce cardiovascular morbidity and mortality in patients with left ventricular hypertrophy, heart failure and post-myocardial infarction, as well as renal disease in patients with type 2 diabetes. Key questions remain, however. What are the clinical effects of combination ARB and ACE inhibitor treatment? How will combinations of RAAS blockade with other agents, such as statins, affect the cardiovascular continuum? Answers to these questions will require well-planned, adequately powered clinical trials, such as the Programme of Research tO evaluate Telmisartan End-organ proteCTION (PROTECTION) and the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programmes. However, it is already clear that RAAS blockade is an essential part of blocking progression along the cardiovascular continuum.
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PMID:The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. 1582 52


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