Acute ischemic stroke remains a significant cause of death and long-term disability and represents a significant burden on global health [1]. The degree of functional recovery in ischemic stroke depends on various factors, including age, pre-stroke neurological severity, stroke characteristics, vascular risk factors, reperfusion therapy, and metabolic disturbances on admission [2]. One of these, blood glucose, is of special importance, as it is cheap, readily available, and is routinely measured when patients present to the ED.  Hyperglycemia is frequently seen during acute phase of ischemic stroke and can even happen in patients with a known history of diabetes as well as in those without diabetes [3]. High blood glucose on admission may be related to chronic dysglycemia or to an acute stress response, which can be driven by the release of increased amounts of catecholamines and cortisol [4].

Hyperglycemia can exacerbate cerebral ischemic damage via increased oxidative stress, anaerobic glycolysis, lactic acidosis, endothelial dysfunction, inflammatory activity and disruption of the blood brain barrier [5]. These alterations can contribute to cerebral oedema, neuronal damage and the development of haemorrhagic transformation, which can have negative effects on neurological recovery [6].

There are several clinical studies that showed that elevated glucose at admission with acute ischemic stroke (AIS) is associated with poor outcomes. In the large thrombectomy registry, about 30% of the patients had hyperglycemia, and those with hyperglycemia had worse 90-day modified Rankin Scale score, higher mortality, and higher incidence of symptomatic intracranial hemorrhage [7]. The same effect was observed in another large vessel occlusion patient cohort where elevated blood glucose levels on admission predicted poor functional outcome and mortality [8]. There is also evidence that suggesting that a very high glucose level at admission is independently linked to impaired functional independence and higher mortality after an endovascular procedure in registry data [9]. The same correlation between high admission glucose and poor 90-day outcomes has been observed in patients who receive intravenous thrombolysis [10][11].  In recent years, it has been understood that stress hyperglycemia is important, not just the level of glucose itself. The stress hyperglycemia ratio (SHR), defined as the ratio of the glucose level increase to the patient's chronic glucose level, has been shown to be independently associated with reduced functional outcome after ischemic stroke [12].

Increased SHR has been linked to increased disability at 3 months [13], neurological deterioration within the initial 48 hours after reperfusion therapy [14] and poor functional outcome after AIS [15]. The results indicate that rapid glucose level modulation can provide further prognostic information besides the absolute glucose level.  The modified Rankin Scale is a common measure of post-stroke disability, especially at 90 days. Because BG is a routine measure on admission, its association with future functional status could aid in reaching a diagnosis of the patient's functional level as early as possible and identify patients at higher risk of disability.

Objective

To determine the association between admission blood glucose levels and functional outcomes in patients with acute ischemic stroke.

This prospective observational cohort study was conducted at Nishtar Hospital, Multan from June 2024 to June 2025. The sample size was calculated using the WHO/OpenEpi sample size calculator. Taking an expected prevalence of admission hyperglycemia of approximately 29%, a 95% confidence level, and 7% absolute precision, the calculated sample size was approximately 162 patients. After allowing for approximately 10% loss to follow-up or incomplete data, the final sample size was 180 patients. Patients were enrolled using a non-probability consecutive sampling technique. Patients aged 18 years or older of either gender, presenting within 24 hours of symptom onset with acute ischemic stroke confirmed by clinical examination and neuroimaging, were included. Only patients with documented admission blood glucose levels and available functional outcome assessment at 90 days were included. Patients with hemorrhagic stroke, transient ischemic attack, previous stroke with significant residual disability, severe hypoglycemia at presentation, conditions markedly affecting blood glucose such as diabetic ketoacidosis or hyperosmolar hyperglycemic state, severe systemic infection, terminal illness, or incomplete follow-up data were excluded. Data Collection Demographic and clinical information including age, gender, diabetes mellitus, hypertension, smoking status, dyslipidemia, previous cardiovascular disease, time from symptom onset to hospital presentation, and treatment received was recorded. Stroke severity at admission was assessed using the National Institutes of Health Stroke Scale (NIHSS). A venous blood sample was obtained at admission, and random blood glucose was measured before initiation of glucose-lowering therapy. Admission hyperglycemia was defined as blood glucose ≥140 mg/dL (7.8 mmol/L). Glycated hemoglobin (HbA1c), where available, was also documented to differentiate chronic glycemic abnormalities from acute hyperglycemia. We assessed functional outcome at 90 days using the modified Rankin Scale (mRS). Patients with an mRS score of 0–2 were classified as having a favorable functional outcome, whereas those with an mRS score of 3–6 were classified as having a poor functional outcome. Mortality within 90 days was included within mRS score 6. The association between admission blood glucose and functional outcome was assessed using glucose both as a continuous variable and according to hyperglycemia status. Statistical Analysis Data were analyzed using SPSS version 26. Quantitative variables were presented as mean±SD or median with interquartile range, as appropriate, while categorical variables were expressed as frequency and percentage. Admission blood glucose levels were compared between patients with favorable and poor functional outcomes using the independent-samples t-test or Mann–Whitney U test. Categorical variables were compared using the Chi-square or Fisher’s exact test. Adjusted odds ratios with 95% confidence intervals were reported, and a p-value ≤0.05 was considered statistically significant.

The mean age of the 180 patients was 64.2±12.7 years. There were 104 (57.8%) males and 76 (42.2%) females. Hypertension was present in 108 (60.0%) patients, diabetes mellitus in 61 (33.9%), dyslipidemia in 65 (36.1%), current smoking in 44 (24.4%), and atrial fibrillation in 29 (16.1%). The mean admission NIHSS score was 10.0±6.0, while mean admission blood glucose was 156.1±55.4 mg/dL. Admission hyperglycemia was present in 58 (32.2%) patients, and mean HbA1c was 6.4±1.3%. Intravenous thrombolysis was given to 64 (35.6%) patients and mechanical thrombectomy to 22 (12.2%).

Table 1. Baseline Clinical Characteristics of Study Participants

Patients with poor functional outcome were older than those with favorable outcome, with mean ages of 68.1±11.9 versus 61.0±12.5 years (p<0.001). Mean admission glucose was also higher in the poor-outcome group (177.0±61.0 vs. 139.0±42.0 mg/dL, p<0.001), along with a higher NIHSS score (13.9±5.7 vs. 6.8±4.1, p<0.001) and HbA1c (6.8±1.5% vs. 6.1±1.0%, p<0.001). Diabetes was present in 39 (48.1%) versus 22 (22.2%) patients (p<0.001), and hypertension in 56 (69.1%) versus 52 (52.5%) (p=0.024).

Table 2. Comparison of Patients According to 90-Day Functional Outcome

Among normoglycemic patients, mRS scores of 0, 1, and 2 were seen in 17 (13.9%), 28 (23.0%), and 34 (27.9%) patients, compared with 3 (5.2%), 8 (13.8%), and 9 (15.5%) in the hyperglycemia group. Scores of 3, 4, and 5 occurred in 22 (18.0%), 10 (8.2%), and 2 (1.6%) normoglycemic patients versus 13 (22.4%), 12 (20.7%), and 2 (3.4%) hyperglycemic patients. Mortality was 7.4% versus 19.0% (p=0.021), and the overall mRS distribution differed significantly between the groups (p=0.007).

Table 3. Functional Outcomes According to Admission Hyperglycemia

Multivariable analysis showed that admission hyperglycemia was independently associated with poor functional outcome (adjusted OR 2.63, 95% CI 1.28–5.39, p=0.008). Higher admission NIHSS score was also a significant predictor (OR 1.18 per point, 95% CI 1.10–1.27, p<0.001), as was increasing age (OR 1.04 per year, 95% CI 1.01–1.07, p=0.011). Diabetes mellitus (OR 1.74, p=0.142), hypertension (OR 1.41, p=0.337), and intravenous thrombolysis (OR 0.54, p=0.078) were not independently significant predictors.

Table 4. Multivariable Logistic Regression for Predictors of Poor Functional Outcome at 90 Days

This study aimed to assess the relationship between blood glucose level on admission and functional outcome after 90 days in 180 acute ischemic stroke patients. The mean age was 64.2 ± 12.7 years, and 57.8% of the patients were male, while 60.0% and 33.9% had hypertension and diabetes mellitus, respectively. 58 (32.2%) patients had admission hyperglycemia. This is similar to previous studies in which 30% of patients with acute ischemic stroke had hyperglycemia upon admission. A previous study showed 35.6% prevalence [15] and a recent prospective cohort study revealed hyperglycemia in 38.9% of patients. There was a very high correlation between the admission blood glucose and functional recovery. The mean BG level of patients with poor 90-day outcome was significantly higher than that of patients with favorable outcome (177.0±61.0 vs. 139.0±42.0 mg/dL, p<0.001). Likewise, the patients with admission hyperglycemia had a poor functional outcome at discharge (65.5%) versus the normoglycemic (35.2%) patients (p<0.001). Admission hyperglycemia was also previously found to be a significant predictor of a shift towards more severe 90-day mRS scores in a study of 2,908 patients that showed an adjusted common OR of 1.69. A previous study published in 2015 found that hyperglycemia on admission was correlated with a worse 90 day mRS distribution, with an adjusted OR of 0.46 for favorable functional outcome [16]. The present study also revealed that mortality rate was higher with admission hyperglycemia, 11 (19.0%) patients had died while 9 (7.4%) patients were normoglycemic at admission (p=0.021). This is similar to the results of earlier studies that found that 90-day mortality rates for hyperglycemic patients were 40% while they were 23% for those without hyperglycemia. Another previous research reported mortality rates of 12.8% and 6.8% in hyperglycemic and normoglycemic patients, respectively. The results indicate that patients with high glucose levels at presentation might constitute a subgroup with higher risk to develop disability and mortality after acute ischemic stroke [17]. Another significant factor was the severity of the stroke. At admission the NIHSS score was significantly higher in patients with poor outcome compared to those with favourable outcome (13.9 ± 5.7 vs 6.8 ± 4.1, p < 0.001). Each additional NIHSS score was independently associated with a 18% increase in the odds of poor functional outcome (adjusted OR 1.18, 95% CI 1.10–1.27, p<0.001) in the multivariable analysis. Baseline neurological severity, along with admission glucose, was also determined as an independent predictor of poor 90-day functional outcome in previous studies. This is logical since a greater neurological deficit, and thus more severe cerebral injury is associated with a higher NIHSS score [18]. Functional outcome was also significantly related with age. The mean age of patients with poor outcomes was 68.1±11.9 years vs 61.0±12.5 years for patients with favorable outcomes (p<0.001). Poor outcome was independently related to increasing age (adjusted OR 1.04 per year, 95% CI 1.01–1.07, p=0.011). A similar association has been reported previously with increasing age independently predicting adverse 3 month functional outcome in addition to stroke severity and admission glucose level. Older patients may have less neurological reserve, higher vascular comorbidities, and less ability to recover function after an acute cerebral ischemia [19]. Univariate analysis also showed that diabetes mellitus and long-term glycemic status were associated with outcome. Patients who had poor outcomes had a higher prevalence of diabetes (48.1 % vs. 22.2 %), higher mean HbA1c (6.8±1.5 % vs. 6.1±1.0 %), and were less likely to be treated with ACE inhibitors or statins compared to the favorable-outcome group (p<0.001 for all). In earlier studies that included patients receiving reperfusion therapy, there was an increased risk of an unfavorable 90-day functional outcome (OR 1.81) and death (OR 1.75) with elevated admission glucose and HbA1c. In the present multivariable analysis, diabetes was not independently significant (adjusted OR 1.74, p=0.142), however, indicating that the glucose level at the time of presentation may have additional prognostic value beyond the previous diagnosis of diabetes. Previous studies also have revealed that glucose levels at admission could be a more important predictor than diabetes alone [20]. Patients with poor outcomes had a higher prevalence of hypertension compared to those with favourable outcomes (69.1% vs. 52.5%, p=0.024), but this difference was not statistically significant, after adjustment (adjusted OR 1.41, p=0.337). Patients who had favorable outcomes had a higher prevalence rate of intravenous thrombolysis (42.4% vs. 27.2%, p=0.033); however, this was not an independent predictor in the final model (adjusted OR 0.54, p=0.078). Importantly, some studies in patients who were treated with endovascular reperfusion have persisted in demonstrating that hyperglycemia at admission is also associated with poor outcome, regardless of treatment, and other established prognostic variables [21]. There were some limitations in this study. It was carried out at one centre and on a small number of patients (180) and may not be representative. Blood glucose was determined at one time point (admission) and could be affected by acute stress, prior food consumption, or diabetes. Complete long term glycemic (blood glucose) information may not have been available for all patients and therefore was not considered. Assessment of functional outcome was performed at 90 days with focus on the modified Rankin Scale (which can be influenced by rehabilitation, treatment differences, recurrent vascular events, and other factors after the patient leaves the hospital). Other clinical factors, such as infarct size, stroke subtype, and reperfusion time after stroke, were also possible sources of residual confounding for the observed association.

It is concluded that elevated admission blood glucose was significantly associated with poor functional outcome in patients with acute ischemic stroke. Patients with hyperglycemia had a higher frequency of poor 90-day functional outcome and mortality compared with normoglycemic patients. Admission hyperglycemia remained an independent predictor of poor outcome after adjustment for age, stroke severity, diabetes mellitus, hypertension, and thrombolytic treatment. Higher NIHSS score and increasing age were also significant predictors of unfavorable outcome. Admission blood glucose may therefore serve as a simple and readily available marker for early risk stratification in patients with acute ischemic stroke.