Associations of glycated hemoglobin with etiology, lesions, and outcome of ischemic stroke: Japan Stroke Data Bank

Background Despite abundant evidence linking hyperglycemia to stroke, its heterogeneous effects across stroke etiologies and lesions remain unclear. We examined the associations between admission glycated hemoglobin (HbA1c) levels and stroke subtypes, lesions, and functional outcomes. Methods Adults with acute ischemic stroke admitted between 2016 and 2020 were analyzed using a Japanese nationwide registry. Patients were grouped by admission HbA1c (<6.0%, 6.0–6.9%, 7.0–7.9%, and ≥ 8.0%). Stroke subtypes were determined using the Trial of Org 10,172 in Acute Stroke Treatment criteria. Lesion was categorized as cerebral cortex, basal ganglia/corona radiata, thalamus, brainstem, or cerebellum. Unfavorable outcome was defined as discharge modified Rankin Scale (mRS) >2 for patients with premorbid mRS ≤2, or higher discharge mRS than premorbid mRS for others. Associations were assessed using multivariable mixed-effects logistic regression analysis. Results Among 13,569 patients, HbA1c was <6.0% in 7001 (51.6%), 6.0–6.9% in 4201 (31.0%), 7.0–7.9% in 1264 (9.3%), and ≥ 8.0% in 1103 (8.1%). Higher HbA1c levels were associated with a greater proportion of large artery atherosclerosis (adjusted OR for HbA1c ≥8.0% vs <6.0%, 1.40; 95% CI, 1.19–1.65) and lower proportion of cardioembolism (0.63; 0.50–0.79). Elevated HbA1c levels were associated with higher prevalence of brainstem lesions (2.35; 1.82–3.02) and lower prevalence of cerebral cortex and basal ganglia/corona radiata lesions, even after adjusting for stroke subtype. Unfavorable outcomes were more common in patients with higher HbA1c levels (overall, 1.56; 1.31–1.85), particularly in those with large artery atherosclerosis and cardioembolism. Conclusions Higher admission HbA1c levels were associated with a higher proportion of large artery atherosclerosis and a lower proportion of cardioembolism, with a higher proportion of brainstem lesions and a lower proportion of cortical and basal ganglia/corona radiata lesions, and with worse functional outcomes.