Hyperglycemia and Diabetes mellitus (DM) is a common comorbidity of ischemic stroke, and it is associated with adverse events such as early neurological deterioration (END), infarct growth, hemorrhagic transformation, and increased mortality. In PART I, we evaluated the association between fibrinogen, a prothrombotic protein, and END of diabetic patients with ischemic stroke. In PART II, we evaluated potential effects of admission hyperglycemia on outcomes, infarct growth, and hemorrhagic transformation after endovascular treatment (EVT). In part III, in diabetic rats, we evaluated the ant-ischemic effects of pretreatment with evogliptin, a dipeptidyl peptidase (DPP-4) inhibitor, and metformin, respectively, and combined. PART I: Early Neurological deterioration and fibrinogen We included 3814 ischemic stroke patients within 72 hours of onset. To evaluate the association between fibrinogen and END (National Institutes of Health Stroke Scale [NIHSS] ≥ 2 increase within 1 week of admission), analysis based on propensity score matching between END and non-END population in DM (END, n=261; non-END, n=522) and non-DM populations (END, n=399; non-END, n=798) was performed. Fibrinogen levels were overall higher in the END subgroup compared to non-END subgroup. Only in the DM population were fibrinogen levels an independent predictor for END (fibrinogen levels 300–599 mg/dL, odds ratio: 1.618, 95% confidence interval: 1.037 – 2.525, p=0.034, fibrinogen levels ≥600 mg/dL, 2.575, 1.018 – 6.514, p=0.046; non-DM population, p=0.393). In diabetic patients with acute ischemic stroke, elevated fibrinogen is associated with END dose-dependently. PART II: Adverse effects of hyperglycemia after reperfusion therapy Between January 2011 and May 2016, patients that underwent EVT with pre-procedural and post-procedural diffusion-weighted imaging were identified from a multicenter registry. Normoglycemia was defined as a glucose level ≤110 mg/dL, moderate hyperglycemia as >110 and ≤170 mg/dL, and overt hyperglycemia as >170 mg/dL. Its effects on poor outcomes (3-month modified Rankin Scale score 3–6), infarct growth, and parenchymal hematoma type 2 were analyzed. Of 720 patients encountered, 341 patients were eligible. Glycated hemoglobin levels were higher in overt hyperglycemia group compared to normoglycemia/moderate hyperglycemia group (p<0.001). Moderate hyperglycemia (odds ratio 2.37 [95% confidence interval 1.26–4.45], p=0.007) and overt hyperglycemia (2.84 [1.19–6.81], p=0.019) were associated with poor outcomes. Post-procedural infarct volumes were significantly greater in hyperglycemic patients (padjusted = 0.003). Both findings were confirmed in the total population, and the non-reperfusion subgroup. Only overt hyperglycemia (9.28 [1.66–51.88], p = 0.011) was associated with parenchymal hematoma type 2. This association was confirmed in the total population, and reperfusion subgroup. PART III: Potential neuroprotection of antidiabetic drugs Type 1 diabetes was induced by intraperitoneal injection of streptozotocin in rats aged… Advisors/Committee Members: 대학원 의학과, 201625063, 이, 성준.