Association between insulin resistance and post-ischaemic stroke outcome in patients without diabetes: protocol for a systematic review and meta-analysis.
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ABSTRACT: Introduction
Insulin resistance is an independent risk factor for atherosclerosis, coronary artery disease and ischaemic stroke. Currently, insulin resistance is not usually included in post-stroke risk stratification. This systematic review and meta-analysis intends to determine if available scientific knowledge supports an association between insulin resistance and post-stroke outcomes in patients without diabetes.Methods and analysis
The authors will conduct a literature search in Medline, Embase, Web of Science and Cochrane Central. The review will include studies that assess the association between elevated insulin homeostasis model of insulin resistance (HOMA-IR) and post-stroke outcome (functional outcome and recurrent stroke). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will be used. The primary outcome will be post-stroke functional outcome (Modified Rankin Scale), and the secondary outcome will be recurrent ischaemic stroke. Comparison of outcome will be made between highest and lowest HOMA-IR range (as defined in each article included in this systematic review). Risk of bias will be assessed qualitatively. Meta-analysis will be performed if sufficient homogeneity exists between studies. Heterogeneity of outcomes will be assessed by I².Ethics and dissemination
No human or animal subjects or samples were/will be used. The results will be published in a peer-reviewed journal, and will be disseminated at local and international neurology conferences.Prospero registration number
CRD42020173608.
SUBMITTER: Hadwen J
PROVIDER: S-EPMC8006852 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPeople with hyperglycaemia concomitant with an acute stroke have greater mortality, stroke severity, and functional impairment when compared with those with normoglycaemia at stroke presentation. This is an update of a Cochrane Review first published in 2011.ObjectivesTo determine whether intensively monitoring insulin therapy aimed at maintaining serum glucose within a specific normal range (4 to 7.5 mmol/L) in the first 24 hours of acute ischaemic stroke influences outcome.Search methodsWe searched the Cochrane Stroke Group Trials Register (September 2013), CENTRAL (The Cochrane Library 2013, Issue 8), MEDLINE (1950 to September 2013), EMBASE (1980 to September 2013), CINAHL (1982 to September 2013), Science Citation Index (1900 to September 2013), and Web of Science (ISI Web of Knowledge) (1993 to September 2013). We also searched ongoing trials registers and SCOPUS.Selection criteriaRandomised controlled trials (RCTs) comparing intensively monitored insulin therapy versus usual care in adults with acute ischaemic stroke.Data collection and analysisWe obtained a total of 1565 titles through the literature search. Two review authors independently selected the included articles and extracted the study characteristics, study quality, and data to estimate the odds ratio (OR) and 95% confidence interval (CI), mean difference (MD) and standardised mean difference (SMD) of outcome measures. We resolved disagreements by discussion.Main resultsWe included 11 RCTs involving 1583 participants (791 participants in the intervention group and 792 in the control group). We found that there was no difference between the treatment and control groups in the outcomes of death or dependency (OR 0.99, 95% CI 0.79 to 1.23) or final neurological deficit (SMD -0.09, 95% CI -0.19 to 0.01). The rate of symptomatic hypoglycaemia was higher in the intervention group (OR 14.6, 95% CI 6.6 to 32.2). In the subgroup analyses of diabetes mellitus (DM) versus non-DM, we found no difference for the outcomes of death and disability or neurological deficit. The number needed to treat was not significant for the outcomes of death and final neurological deficit. The number needed to harm was nine for symptomatic hypoglycaemia.Authors' conclusionsAfter updating the results of our previous review, we found that the administration of intravenous insulin with the objective of maintaining serum glucose within a specific range in the first hours of acute ischaemic stroke does not provide benefit in terms of functional outcome, death, or improvement in final neurological deficit and significantly increased the number of hypoglycaemic episodes. Specifically, those people whose glucose levels were maintained within a tighter range with intravenous insulin experienced a greater risk of symptomatic and asymptomatic hypoglycaemia than those people in the control group.
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Project description:Microglia, the major endogenous immune cells of the central nervous system, mediate critical degenerative and regenerative responses in ischaemic stroke. Microglia become "activated", proliferating, and undergoing changes in morphology, gene and protein expression over days and weeks post-ischaemia, with deleterious and beneficial effects. Pro-inflammatory microglia (commonly referred to as M1) exacerbate secondary neuronal injury through the release of reactive oxygen species, cytokines and proteases. In contrast, microglia may facilitate neuronal recovery via tissue and vascular remodelling, through the secretion of anti-inflammatory cytokines and growth factors (a profile often termed M2). This M1/M2 nomenclature does not fully account for the microglial heterogeneity in the ischaemic brain, with some simultaneous expression of both M1 and M2 markers at the single-cell level. Understanding and regulating microglial activation status, reducing detrimental and promoting repair behaviours, present the potential for therapeutic intervention, and open a longer window of opportunity than offered by acute neuroprotective strategies. Pharmacological modulation of microglial activation status to promote anti-inflammatory gene expression can increase neurogenesis and improve functional recovery post-stroke, based on promising preclinical data. Cell-based therapies, using preconditioned microglia, are of interest as a method of therapeutic modulation of the post-ischaemic inflammatory response. Currently, there are no clinically-approved pharmacological options targeting post-ischaemic inflammation. A major developmental challenge for clinical translation will be the selective suppression of the deleterious effects of microglial activity after stroke whilst retaining (or enhancing) the neurovascular repair and remodelling responses of microglia.
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Project description:BACKGROUND:Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. METHODS:We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. RESULTS:The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P=0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P=0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P=0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P=0.02), but not smaller MIs. CONCLUSIONS:Among patients with insulin resistance without diabetes mellitus, pioglitazone reduced the risk for acute coronary syndromes after a recent cerebrovascular event. Pioglitazone appeared to have its most prominent effect in preventing spontaneous type 1 MIs. CLINICAL TRIAL REGISTRATION:URL: http://clinicaltrials.gov. Unique identifier: NCT00091949.
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Project description:Erythropoietin (EPO), which is inversely associated with blood haemoglobin (Hb), exerts neuroprotective effects in experimental ischaemic stroke (IS). However, clinical treatment trials have so far been negative. Here, in patients with IS, we analysed whether serum EPO is associated with (1) initial stroke severity, (2) recovery and (3) functional outcome.Prospective. Controls available at baseline.A Swedish hospital-initiated study with outpatient follow-up after 3 months.Patients (n=600; 64% males, mean age 56 years, controls n=600) were included from the Sahlgrenska Academy Study on IS (SAHLSIS).In addition to EPO and Hb, initial stroke severity was assessed by the Scandinavian Stroke Scale (SSS) and compared with SSS after 3 months (follow-up) as a measure of recovery. Functional outcome was evaluated using the modified Rankin Scale (mRS) at follow-up. Serum EPO and SSS were divided into quintiles in the multivariate regression analyses.Serum EPO was 21% and 31% higher than in controls at the acute phase of IS and follow-up, respectively. In patients, acute serum EPO was 19.5% higher in severe versus mild IS. The highest acute EPO quintile adjusted for sex, age and Hb was associated with worse stroke severity quintile (OR 1.70, 95% CI 1.00 to 2.87), better stroke recovery quintile (OR 1.93, CI 1.09 to 3.41) and unfavourable mRS 3-6 (OR 2.59, CI 1.15 to 5.80). However, the fourth quintile of EPO increase (from acute to follow-up) was associated with favourable mRS 0-2 (OR 3.42, CI 1.46 to 8.03). Only the last association withstood full adjustment.The crude associations between EPO and worse stroke severity and outcome lost significance after multivariate modelling. However, in patients in whom EPO increased, the association with favourable outcome remained after adjustment for multiple covariates.
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Project description:ObjectiveContrast extravasation (CE) after endovascular therapy (EVT) is commonly present in acute ischaemic stroke (AIS) patients. Substantial uncertainties remain about the relationship between CE and the outcomes of EVT in patients with AIS. Therefore, we aimed to evaluate this association.DesignA systematic review and meta-analysis of published studies were performed.Data sourceWe systematically searched the Medline and Embase databases for relevant clinical studies. The last literature search in databases was performed in June 2020.Eligibility criteria for study selectionWe included studies exploring the associations between CE and the outcomes of EVT in patients with AIS undergoing EVT.Data extraction and synthesisTwo reviewers extracted relevant information and data from each article independently. We pooled ORs with CIs using a random-effects meta-analysis to calculate the associations between CE and outcomes of EVT. The magnitude of heterogeneity between estimates was quantified with the I2 statistic with 95% CIs.ResultsFifteen observational studies that enrolled 1897 patients were included. Patients with CE had higher risks of poor functional outcome at discharge (2.38, 95% CI 1.45 to 3.89 p=0.001; n=545) and poor functional outcome at 90 days (OR 2.16, 95% CI 1.20 to 3.90; n=1194). We found no association between CE and in-hospital mortality (OR 0.95, 95% CI 0.27 to 3.30; n=376) or 90-day mortality (OR 1.38, 95% CI 0.81 to 2.36; n=697) after EVT. Moreover, CE was associated with higher risks of post-EVT intracranial haemorrhage (ICH) (OR 6.68, 95% CI 3.51 to 12.70; n=1721) and symptomatic ICH (OR 3.26, 95% CI 1.97 to 5.40; n=1092).ConclusionsThis systematic review and meta-analysis indicates that in patients with AIS undergoing EVT, CE is associated with higher risks of unfavourable functional outcomes and ICH. Thus, we should pay more attention to CE in patients with AIS undergoing EVT.
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Project description:IntroductionLimited data exist on the outcome of pregnancies and deliveries in women with ischaemic stroke. We investigated the incidence of pregnancy- and delivery-related complications in women with ischaemic stroke before and after pregnancy compared with stroke-free matched controls.Patients and methodsOf our 1008 consecutive patients aged 15-49 years with first-ever ischaemic stroke, 1994-2007, we included women with pregnancy data before or after stroke recorded in the Medical Birth Register (MBR) (n = 152), and for them searched stroke-free controls matched by age, parity, year of birth, residential area and multiplicity (n = 608). Data on hospital admissions and deaths (1987-2014) came from national health registries. Poisson regression mixed models allowed comparison of the incidence of complications.ResultsA total of 124 stroke mothers had 207 singleton pregnancies before and 45 mothers 68 pregnancies after stroke. The incidence rate ratio (IRR) for the composite outcome of pregnancy and delivery complications adjusted for socioeconomic status and maternal smoking was 1.43 (95% confidence interval [CI] 1.00-2.03, p = 0.05) for pre-stroke mothers, and 1.09 (95% CI 0.66-1.78) for post-stroke mothers, compared with matched controls. Similarly, the adjusted IRR for post-stroke hospital admission during pregnancy was 1.85 (95% CI 1.03-3.31). The IRR for perinatal death of the child was 3.43 (95% CI 0.57-20.53) before and 8.88 (95% CI 0.81-97.95) after stroke.Discussion and conclusionsCompared with stroke-free mothers, we found a higher incidence of pregnancy- and delivery-related complications in mothers with ischaemic stroke. Larger studies are needed to verify our results.
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Project description:BackgroundReducing stroke occurrence requires the effective management of cardiovascular and other stroke risk factors.PurposeTo describe pre- and post-stroke medication use, focusing on antithrombotic therapy and mortality risk, in individuals hospitalised for ischaemic stroke (IS) in the United Kingdom.MethodUsing primary care electronic health records from the United Kingdom, we identified patients hospitalised for IS (July 2016-September 2019) and classed them into three groups: atrial fibrillation (AF) diagnosed pre-stroke, AF diagnosed post-stroke, and non-AF stroke (no AF diagnosed pre-/post-stroke). We determined use of cardiovascular medications in the 90 days pre- and post-stroke and calculated mortality rates.ResultsThere were 3201 hospitalised IS cases: 76.2% non-AF stroke, 15.7% AF pre-stroke, and 8.1% AF post-stroke. Oral anticoagulant (OAC) use increased between the pre- and post-stroke periods as follows: 54.3%-78.7% (AF pre-stroke group), 2.3%-84.8% (AF post-stroke group), and 3.4%-7.3% (non-AF stroke group). Corresponding increases in antiplatelet use were 30.8%-35.4% (AF pre-stroke group) 38.5%-47.5% (AF post-stroke group), and 37.5%-87.3% (non-AF stroke group). Among all IS cases, antihypertensive use increased from 66.8% pre-stroke to 78.8% post-stroke; statin use increased from 49.6%-85.2%. Mortality rates per 100 person-years (95% CI) were 17.30 (14.70-20.35) in the AF pre-stroke group and 9.65 (8.81-10.56) among all other stroke cases.ConclusionOur findings identify areas for improvement in clinical practice, including optimising the level of OAC prescribing to patients with known AF, which could potentially help reduce the future burden of stroke.
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