Impaired glucose metabolism and the risk of vascular events and mortality after ischemic stroke: A systematic review and meta-analysis

BackgroundDiabetes mellitus (DM), prediabetes, and insulin resistance are highly prevalent in patients with ischemic stroke (IS). DM is associated with higher risk for poor outcomes after IS.ObjectiveInvestigate the risk of recurrent vascular events and mortality associated with impaired glucose metabolism compared to normoglycemia in patients with IS and transient ischemic attack (TIA).MethodsSystematic literature search was performed in PubMed, Embase, Cochrane Library on 21st March 2024 and via citation searching. Studies that comprised IS or TIA patients and exposures of impaired glucose metabolism were eligible. Study Quality Assessment Tool was used for risk of bias assessment. Covariate adjusted outcomes were pooled using random-effects meta-analysis.Main outcomesRecurrent stroke, cardiac events, cardiovascular and all-cause mortality and composite of vascular outcomes.ResultsOf 10,974 identified studies 159 were eligible. 67% had low risk of bias. DM was associated with an increased risk for composite events (pooled HR (pHR) including 445,808 patients: 1.58, 95% CI 1.34-1.85, I2 = 88%), recurrent stroke (pHR including 1.161.527 patients: 1.42 (1.29-1.56, I2 = 92%), cardiac events (pHR including 443,863 patients: 1.55, 1.50-1.61, I2 = 0%), and all-cause mortality (pHR including 1.031.472 patients: 1.56, 1.34-1.82, I2 = 99%). Prediabetes was associated with an increased risk for composite events (pHR including 8,262 patients: 1.50, 1.15-1.96, I2 = 0%) and recurrent stroke (pHR including 10,429 patients: 1.50, 1.18-1.91, I2 = 0), however, not with mortality (pHR including 9,378 patients, 1.82, 0.73-4.57, I2 = 78%). Insulin resistance was associated with recurrent stroke (pHR including 21,363 patients: 1.56, 1.19-2.05, I2 = 55%), but not with mortality (pHR including 21,363 patients: 1.31, 0.66-2.59, I2 = 85%).DiscussionDM is associated with a 56% increased relative risk of death after IS and TIA. Risk estimates regarding recurrent events are similarly high between prediabetes and DM, indicating high cardiovascular risk burden already in precursor stages of DM. There was a high heterogeneity across most outcomes.