Impact of diabetes on clinical and safety outcomes in acute ischemic stroke patients receiving reperfusion therapy: A meta-analysis

Bradley, Sian; Smokovski, Ivica; Bhaskar, Sonu

doi:10.17219/acem/146273

Cited by 5 publications

(4 citation statements)

References 53 publications

(65 reference statements)

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“…32 Our male infarct size data support the above finding and are consistent with repeated clinical studies which indicate diabetes history and hyperglycemia are associated with increased infarct size and poorer functional outcome after pharmacological thrombolysis, mechanical or expectant therapy. 2,3,33,34 DM2 is a systemic disease which affects the brain parenchyma as well as its vasculature in ways that…”

Section: Discussionmentioning

confidence: 99%

“…2 Clinical trials indicate that DM2 increases the risk of poor functional outcome at discharge and 90 days after stroke in the patients receiving intravenous tPA (tissue-type plasminogen activator) or endovascular treatment. 3 DM2 and acute hyperglycemia are also associated with lower intravenous tPA–induced recanalization rate. 4,5 The exact mechanism by which DM2 and hyperglycemia exacerbate postreperfusion ischemic injury, while multifactorial and still being elucidated, appears to involve at least in part the compromised cerebral microvascular structure and function including endothelial dysfunction, thickened capillary basement membrane, and increased angiogenesis, increased blood-brain barrier permeability, and reduced cerebral vasoreactivity.…”

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confidence: 96%

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Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice

Zhu

Davis

Allen

et al. 2023

Stroke

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Background: Type 2 diabetes (DM2) exacerbates stroke injury, reduces efficacy of endovascular therapy, and worsens long-term functional outcome. Sex differences exist in stroke incidence, response to therapy, poststroke microvascular dysfunction, and functional recovery. In this study, we tested the hypotheses that poor outcome after stroke in the setting of DM2 is linked to impaired microvascular tissue reperfusion and that male and female DM2 mice exhibit different microvascular reperfusion response after transient middle cerebral artery occlusion (MCAO). Methods: Transient MCAO was induced for 60 minutes using an intraluminal filament in young adult DM2 and nondiabetic control male and female mice. Capillary flux in deep cortical layers was assessed using optical coherence tomography–based optical microangiography (OMAG), and associated regional brain infarct size was evaluated by hematoxylin and eosin staining. Results: Compared to baseline, MCAO reduced absolute capillary red blood cell flux by 84% at 24 hours post-MCAO in male DM2 ( P <0.001) but not male control mice. When normalized to pre-MCAO baseline, red blood cell flux 24 hours after stroke was 64% lower in male DM2 mice than male nondiabetic controls ( P <0.01). In females, MCAO decreased capillary flux by 48% at 24 hours post-MCAO compared with baseline in DM2 ( P <0.05) but not in control mice. Red blood cell flux of female DM2 mice did not differ from that of nondiabetic controls either before or 24 hours after MCAO. Furthermore, normalized capillary flux 24 hours after MCAO failed to differ between female DM2 mice and nondiabetic controls. Concomitantly, male but not female DM2 mice experienced 25% larger infarct in caudate-putamen versus respective nondiabetic controls ( P <0.05). Conclusions: DM2 impairs capillary perfusion and exacerbates ischemic deep brain injury in male but not female young adult mice. Premenopausal females appear to be protected against DM2-related capillary dysfunction and brain injury.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice

Zhu

Davis

Allen

et al. 2023

Stroke

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“…Our study revealed that diabetes mellitus is another factor that is associated with futile recanalization. A meta-analysis has demonstrated that diabetes mellitus is linked to unfavorable functional outcomes, increased mortality, and poor postprocedural safety outcomes, including symptomatic intracranial hemorrhage (sICH) and hypertension (HT) ( 14 ). Genceviciute also discovered that diabetes mellitus, especially admission hyperglycemia, was associated with less frequently successful reperfusion, worse 3-month functional outcomes, and in-hospital symptomatic intracranial hemorrhage in acute anterior circulation stroke patients who underwent EVT ( 15 , 16 ).…”

Section: Discussionmentioning

confidence: 99%

Predictors of futile recanalization in basilar artery occlusion patients undergoing endovascular treatment: a post hoc analysis of the ATTENTION trial

Yi,

Li,

Lin

et al. 2023

Front. Neurol.

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BackgroundFew studies have focused on factors associated with futile recanalization in patients with an acute basilar artery occlusion (BAO) that was treated with modern endovascular therapy (EVT). The aim of this study was to explore the factors associated with futile recanalization in patients with an acute BAO presented within 12 h.MethodsThis is a post-hoc analysis of the ATTENTION trial (The Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion, ClinicalTrials.gov, number NCT 04751708). Demographics, clinical characteristics, acute stroke workflow interval times, and imaging characteristics were compared between the futile recanalization and favorable recanalization groups. The favorable outcome was defined as a modified Rankin scale (mRS) score of 0–3 at 90 days, successful reperfusion was defined as thrombolysis in cerebral infarction (TICI) 2b and 3 on the final angiogram, and futile recanalization was defined as failure to achieve a favorable outcome despite successful reperfusion. A multivariate analysis was performed to identify the predictors of futile recanalization.ResultsIn total, 185 patients were included in the final analysis: 89 (48.1%) patients had futile recanalization and 96 (51.9%) patients had favorable recanalization. In the multivariable logistic regression analysis, older age (OR 1.04, 95% CI 1.01 to 1.08, p = 0.01) and diabetes mellitus (OR 3.35, 95% CI 1.40 to 8.01, p = 0.007) were independent predictors of futile recanalization.ConclusionFutile recanalization occurred in nearly half of patients with acute BAO following endovascular treatment. Old age and diabetes mellitus were identified as independent predictors of futile recanalization after endovascular therapy for acute BAO.

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“…Diabetes mellitus type 2 (DMT2) patients are several times more susceptible to a stroke event due to various cerebrovascular complications [ 92 ]. Micro- and macro-vascular changes characteristic for DM lead to particularly poor IS outcomes, increased mortality, and poor post-procedural quality of life [ 93 , 94 ]. Moreover, glucose-lowering therapies are insufficient protection against IS risks in DM [ 95 , 96 ].…”

Section: Ongoing 3pm Research Towards Vulnerable Groups In the Popula...mentioning

confidence: 99%

The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation

Golubnitschaja,

Polivka,

Potuznik

et al. 2024

EPMA Journal

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Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990–2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep–wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population—all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.

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Impact of diabetes on clinical and safety outcomes in acute ischemic stroke patients receiving reperfusion therapy: A meta-analysis

Abstract: Bradley SA, Smokovski I, Bhaskar SMM. Impact of diabetes on clinical and safety outcomes in acute ischemic stroke patients receiving reperfusion therapy: A meta-analysis [published online as ahead of print on February 25, 2022].

Cited by 5 publications

References 53 publications

Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice

Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice

Predictors of futile recanalization in basilar artery occlusion patients undergoing endovascular treatment: a post hoc analysis of the ATTENTION trial

The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation

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