Diabetes, hyperglycaemia, and acute ischaemic stroke

Department of Neurology, University Medical Centre Utrecht Stroke Centre and Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Utrecht, Netherlands.
The Lancet Neurology (Impact Factor: 21.9). 03/2012; 11(3):261-71. DOI: 10.1016/S1474-4422(12)70005-4
Source: PubMed


Diabetes and ischaemic stroke often arise together. People with diabetes have more than double the risk of ischaemic stroke after correction for other risk factors, relative to individuals without diabetes. Multifactorial treatment of risk factors for stroke-in particular, lifestyle factors, hypertension, and dyslipidaemia-will prevent a substantial number of these disabling strokes. Hyperglycaemia occurs in 30-40% of patients with acute ischaemic stroke, also in individuals without a known history of diabetes. Admission hyperglycaemia is associated with poor functional outcome, possibly through aggravation of ischaemic damage by disturbing recanalisation and increasing reperfusion injury. Uncertainty surrounds the question of whether glucose-lowering treatment for early stroke can improve clinical outcome. Achievement of normoglycaemia in the early stage of stroke can be difficult, and the possibility of hypoglycaemia remains a concern. Phase 3 studies of glucose-lowering therapy in acute ischaemic stroke are underway.

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    • "). Due to the prolonged period of hyperglycemia, diabetes leads to irreversible tissue damage such as retinopathy, nephropathy, arteriosclerosis and vascular damage (Luitse et al., 2012). Streptozotocin (STZ) is a cytotoxic substance obtained from the soil microbes, Streptomyces achromogenes that induces DM in experimental animals (Shrilatha and Muralidhara, 2007). "

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    • "Our data are in accordance with epidemiological studies showing that risk factors for vascular disease, including T2D (Luchsinger et al., 2007), are also risk factors for dementia. People with diabetes have more than double risk of ischemic stroke and prolonged hyperglycaemia is associated with microvascular complications (Luitse et al., 2012). Moreover, cerebrovascular disease increases the severity of the clinical symptoms of AD (Launer et al., 2008; Helzner et al., 2009). "
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    ABSTRACT: Aging remains the main risk factor to suffer Alzheimer's disease (AD), though epidemiological studies also support that type 2 diabetes (T2D) is a major contributor. In order to explore the close relationship between both pathologies we have developed an animal model presenting both AD and T2D, by crossing APP/PS1 mice (AD model) with db/db mice (T2D model). We traced metabolic and cognitive evolution before T2D or AD pathology is present (4 weeks of age), when T2D has debuted but no senile plaques are present (14 weeks of age) and when both pathologies are well established (26 weeks of age). APP/PS1xdb/db mice showed an age-dependent synergistic effect between T2D and AD. Significant brain atrophy and tau pathology were detected in the cortex by 14 weeks, that spread to the hippocampus by 26 weeks of age. Severe cognitive impairment was also detected as soon as at 14 weeks of age. Interestingly, in APP/PS1xdb/db mice we observed a shift in Aβ soluble/insoluble levels, and whereas more toxic soluble species were favoured, senile plaques (SP) were reduced. An overall increase of microglia activation was observed in APP/PS1xdb/db mice. We also found exacerbated hemorrhagic burden in APP/PS1xdbd/db mice, suggesting that blood brain barrier alterations may be responsible for the early pathological features observed. Moreover, metabolic parameters can predict many of these alterations, supporting a role for T2D in AD pathology. This new model provides a relevant tool to further explore the relationship between T2D, AD and vascular implications, offering the possibility to assess therapeutic approaches, that by improving T2D metabolic control could delay or prevent AD pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Psychoneuroendocrinology 07/2015; 62:69-79. DOI:10.1016/j.psyneuen.2015.07.606 · 4.94 Impact Factor
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    • "T2DM is an established risk factor for microvascular and macrovascular complications throughout the body, including brain stroke and small vessel disease.75 Therefore, vascular damage is likely to be one of the main reasons for the cognitive impairment in T2DM subjects, including VD subjects. "
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction and dementia in the elderly. T2DM has been thought to be associated with vascular diseases, eventually leading to vascular dementia, but recent studies have established that T2DM is also associated with Alzheimer's disease (AD). With the increase in the number of elderly individuals with T2DM, the number of diabetic patients with cognitive dysfunction has been increasing. T2DM may accelerate AD-associated pathologies through insulin resistance. Vascular pathologies may also be associated with cognitive dysfunction and dementia in T2DM subjects. Several other mechanisms also seem to be involved in T2DM-related cognitive dysfunction. More investigations to clarify the association of T2DM with cognitive impairment are warranted. These investigations may help to increase our understanding of AD and open a new door to the development of therapeutics. Recent pharmaceutical advancement in T2DM treatment has resulted in the availability of a wide range of antidiabetics. Some evidence has suggested that antidiabetic therapies help to prevent cognitive dysfunction. At present, however, the optimal level of blood glucose control and the best combination of medications to achieve it in terms of cognitive preservation have not been established. More investigation is warranted. Cognitive dysfunction is an emerging new complication of T2DM that requires further study.
    Clinical Interventions in Aging 06/2014; 9:1011-1019. DOI:10.2147/CIA.S48926 · 2.08 Impact Factor
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