Among all the neurological diseases of adult life, cerebrovascular accidents rank first in frequency of importance. At least 50% of neurological diseases in general hospitals are due to stroke [1]. Cerebrovascular accident includes ischemic stroke, hemorrhagic stroke, and cerebrovascular anomalies such as intracranial aneurysm, AV malformation, and cortical venous thrombosis [2]. Stroke, after heart disease and cancer, is the third most common cause of death. With the introduction of effective treatment for hypertension, there has been a marked reduction in the frequency of stroke [3]. Diabetes mellitus, by its association with microvascular and macrovascular disease, is an important risk factor in the genesis of stroke. Most diabetic patients with stroke have raised glycosylated hemoglobin, indicating that most of them have uncontrolled diabetes [4]. Diabetics and patients with stress hyperglycemia have severe strokes resulting in poor outcomes. Stroke is twice more common in diabetics than in non-diabetics [5]. Hypertension is common in diabetes and accelerates atherosclerosis, which promotes intracranial small-vessel disease and heart disease, leading to lacunar and embolic infarction, respectively [6]. Ischemic stroke, which includes TIA, is the most common type of stroke and is caused by a blockage that cuts off the blood supply to affected parts of the brain. Ischemic strokes are often referred to as cerebrovascular accidents and could be thrombotic or embolic events [7]. The effects of the blockage are related to its location in the brain rather than the source. However, the source becomes vitally important in identifying the cause for individual management and secondary stroke prevention [8]. Intracerebral hemorrhagic stroke differs from an ischemic stroke in that it is caused by a ruptured blood vessel as opposed to a blood clot. The ruptured vessel interrupts blood flow and delivery of essential nutrients and oxygen to the affected area of the brain. A ruptured blood vessel may release blood very rapidly, which may lead to a sudden build-up in cerebral pressure resulting in unconsciousness or death [9]. Approximately 10-15% of all strokes are hemorrhagic and have an estimated mortality rate of 40%-50%. Several risk factors determine the outcome of stroke. Hyperglycemia, fever, and neuroprotective agents are those which are widely studied [10].

A total of 109 patients with acute stroke admitted to the Department of Medicine, Government Kallakurichi Medical College, Kallakurichi, in May 2021 were enrolled. Inclusion criteria: Patients aged >40 years who were admitted within 24 hours of symptom onset with a first-ever cerebrovascular accident were included. Admission blood glucose was measured within 24 hours of stroke onset. Exclusion criteria: Patients admitted more than 24 hours after stroke onset; patients who received intravenous glucose before or during the study period; patients in whom reliable information regarding diabetes status could not be obtained; patients who died before diabetes status could be established; and patients with illnesses presenting with stroke-like symptoms were excluded. Of the 109 enrolled patients, nine were lost to follow-up; therefore, 100 patients were included in the final analysis. A complete history was obtained and a clinical examination was performed. Blood pressure, blood glucose, urea, creatinine, electrolytes, hemoglobin, total and differential leukocyte counts, urine sugar, albumin and deposits, electrocardiogram, and chest X-ray were assessed. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Once a clinical diagnosis of acute stroke was made, a venous blood sample was obtained within 24 hours of symptom onset for glucose estimation. In patients without a previous history of diabetes whose admission blood glucose was >110 mg/dL (6.1 mmol/L), HbA1c was measured. HbA1c reflects average glycemic exposure over the preceding several weeks and was used to help distinguish previously unrecognized diabetes from stress hyperglycemia. In this study, an HbA1c value >6.4% was used to classify newly diagnosed diabetes, whereas an HbA1c value <6.4% was used in the classification of stress hyperglycemia. Patients were classified into four glycemic groups: (1) euglycemia: admission blood glucose <110 mg/dL (6.1 mmol/L) without known diabetes; (2) known diabetes: previous history of diabetes; (3) newly diagnosed diabetes: admission blood glucose >110 mg/dL (6.1 mmol/L), no previous history of diabetes, and HbA1c >6.4%; and (4) stress hyperglycemia: admission blood glucose >110 mg/dL (6.1 mmol/L), no previous history of diabetes, and HbA1c <6.4%. The patients were followed up for thirty days, and the outcome in the form of death, poor, moderate, and good improvement was recorded. Patients who were unable to return to any form of work, had persistent disability requiring residential placement, were dependent in activities of daily living, or had a stable deficit with no recovery were classified as having poor outcomes. Patients whose symptoms improved, who were independent in day-to-day activities, showed improvement in motor function and aphasia, and had no persistent disability were grouped as having a good outcome. Patients who fell between these two groups were classified as having a moderate outcome. Statistical Analysis Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS), version 24.0. Quantitative variables were summarized using appropriate descriptive statistics, and categorical variables were summarized as frequencies and percentages. Categorical variables were compared using the chi-square test where appropriate, and continuous variables were compared using suitable parametric or non-parametric tests. A p-value <0.05 was considered statistically significant.

Among the 100 patients, 66 had hypertension, 28 had diabetes, 14 had hypercholesterolemia, 6 had a previous history of myocardial infarction, and one woman had atrial fibrillation. More than half of the male patients were smokers and one-third had a history of alcohol intake. Table 3 summarizes the neurological presentations, including right hemiplegia in 55 patients and left hemiplegia in 39 patients. Among the 100 patients, 56 patients had elevated admission-day blood glucose levels and 44 patients had normal blood glucose values. Diabetes was present in 28 patients and stress hyperglycemia in another 28 patients. In the ischemic stroke group, stress hyperglycemia amounted to one-third of the patients and one-fifth in the hemorrhagic group (Tables 1-4). Severity of stroke was assessed with the NIH Stroke Scale. Admission day hyperglycemic patients had a higher score when compared with euglycemic patients (17.27 vs. 9.5, respectively), which was statistically significant (p = 0.001). Among the admission-day hyperglycemic patients, those with newly detected diabetes had the highest mean NIHSS. Hence, an elevated blood sugar at the time of stroke resulted in severe stroke (Table 5). Table 1. Age-wise distribution Age (years) Male Female Total % 41-50 16 4 20 20 51-60 28 10 38 38 61-70 9 11 20 20 71-80 10 9 19 19 >80 3 0 3 3 Total 66 34 100 100 Table 2. Risk factors Risk factors Male % of risk-factor cases Female % of risk-factor cases Total Hypertension 42 63.64 24 36.36 66 Diabetes 17 60.71 11 39.29 28 Hypercholesterolemia 10 71.43 4 28.56 14 Atrial fibrillation 0 0 1 100 1 Coronary artery disease 4 66.66 2 33.33 6 Smoking 40 100 0 0 40 Alcohol 25 96.15 1 3.85 26 Table 3. Clinical presentation Clinical presentation Male % Female % Total Right hemiplegia 38 69.1 17 30.9 55 Left hemiplegia 25 64.1 14 35.9 39 Faciobrachial monoplegia 2 40 3 60 5 Cerebellar symptoms 1 100 0 0 1 Loss of consciousness 31 60.8 20 39.2 51 Hemianopia 2 66.6 1 33.3 3 Aphasia 22 57.9 16 42.1 38 Bladder and bowel involvement 16 59.3 11 40.7 27 Table 4. Glycemic status Glycemic status Total Euglycemia 44 Stress hyperglycemia 28 Known diabetes 16 Newly diagnosed diabetes 12 The size of the lesion was analyzed with the help of a CT scan of the brain. Most of the euglycemic patients had small-sized infarcts and hemorrhages, whereas the majority of admission day hyperglycemic patients had large-sized lesions with edema and midline shift. These data were statistically significant (p = 0.001). Hyperglycemia, through increased anaerobic metabolism, increased brain lactate, impaired mitochondrial function, vascular disease, increased free-radical production, and increased expression of c-fos and cox-2, causes severe brain injury and large-sized infarcts. Hyperglycemia can disrupt the blood-brain barrier, resulting in large hemorrhage and hemorrhagic transformation of infarcts (Tables 6 and 7). Table 5. Stroke severity Glycemic status NIHSS Euglycemia 9.5 Stress hyperglycemia 16.33 Known diabetes 17.3 Newly diagnosed diabetes 19.4 Table 6. Glycemic status among ischemic and hemorrhagic stroke Glycemic status Ischemic stroke Hemorrhagic stroke Total No. % No. % Euglycemia 34 77.27 10 22.73 44 Stress hyperglycemia 23 82.14 5 17.86 28 Known diabetes 10 62.5 6 37.5 16 Newly diagnosed diabetes 6 50 6 50 12 Table 7. Size of the lesion Glycemic status Total Small Medium Large Euglycemia 44 29 8 7 Stress hyperglycemia 28 1 14 13 Known diabetes 16 2 6 8 Newly diagnosed diabetes 12 0 6 6 Table 8. Clinical outcomes Glycemic status Total Death Poor Moderate Good No. % No. % No. % No. % Euglycemia 44 7 15.91 2 4.54 6 13.64 29 65.91 Stress hyperglycemia 28 10 35.71 8 28.57 9 32.14 1 3.54 Known diabetes 16 7 43.75 3 18.75 5 31.25 1 6.25 Newly diagnosed diabetes 12 6 50 4 33.33 2 16.67 0 0 In this study of 100 acute stroke patients, euglycemic patients had better outcomes than patients with admission-day hyperglycemia. Among euglycemic patients, 29 of 44 (65.9%) had a good functional outcome. In contrast, only 2 of 56 (3.6%) patients with admission-day hyperglycemia had a good functional outcome at 30-day follow-up. Early mortality was higher among patients with admission-day hyperglycemia. Twenty-three of 56 hyperglycemic patients (41.1%) died within 30 days, compared with 7 of 44 euglycemic patients (15.9%). Poor outcome was recorded in 15 of 56 hyperglycemic patients (26.8%) and 2 of 44 euglycemic patients (4.5%). Table 9. Outcome in stroke subtypes Stroke subtype Group Glycemic status Good Moderate Poor Death / Total Hemorrhage Group Euglycemia 3 3 0 4 / 10 Stress hyperglycemia 0 1 1 3 / 5 Known diabetes 0 3 2 1 / 6 Newly diagnosed diabetes 0 2 3 1 / 6 Total 3 9 6 9 / 27 Infarct Group Euglycemia 26 3 2 3 / 34 Stress hyperglycemia 1 8 7 7 / 23 Known diabetes 1 2 1 6 / 10 Newly diagnosed diabetes 0 0 1 5 / 6 Total 28 13 11 21 / 73 Hemorrhage: χ² = 12.75, p = 0.17 (not significant). Infarct: χ² = 50.6, p = 0.001 (significant). Table 10. Outcome of stroke in non-diabetic patients Parameter Ischemic stroke Hemorrhagic stroke Euglycemia Stress hyperglycemia Euglycemia Stress hyperglycemia Total 34 23 10 5 NIHSS 7.62 15.56 14.4 19.8 Death, No. 3 7 4 3 Death, % 8.82 30.43 40 60 Poor, No. 2 7 0 1 Poor, % 5.88 30.43 0 20 Moderate, No. 3 8 3 1 Moderate, % 8.82 34.78 30 20 Good, No. 26 1 3 0 Good, % 76.47 4.35 30 0 Average blood glucose level (mg/dL) 91.68 144.43 102.12 240.6

In the ischemic stroke group, early mortality was 8.82% in euglycemic patients and 46.15% in patients with admission-day hyperglycemia. Poor outcome was observed in 5.88% of euglycemic patients and 23.3% of hyperglycemic patients. Among non-diabetic patients with ischemic stroke, mortality was 30.43% in those with stress hyperglycemia compared with 8.82% in those with euglycemia. This corresponds to approximately a 3.5-fold higher mortality in the stress-hyperglycemia group. A similar statistically significant association was not demonstrated in the hemorrhagic-stroke subgroup. Our study showed a positive association between admission-day glucose and adverse stroke outcome (r = 0.71, p = 0.01). Previous studies have similarly reported that admission or persistent hyperglycemia is associated with worse neurological and functional outcomes after ischemic stroke [4,6,7,11]. In the present study, hyperglycemia was present in 56% of all patients and in 53.4% of patients with ischemic stroke (39 of 73). The adverse prognostic association of acute hyperglycemia has been demonstrated in both diabetic and non-diabetic patients. A systematic review by Capes et al. found that stress hyperglycemia in patients without known diabetes was associated with increased mortality and poorer functional recovery after stroke [7]. Studies by Bruno et al., Baird et al., and Parsons et al. also support an association between hyperglycemia and worse ischemic-stroke outcome [4,6,11]. Capes et al. performed a systematic review of observational studies examining stress hyperglycemia and prognosis after stroke [7]. In patients without known diabetes, stress hyperglycemia after ischemic stroke was associated with substantially higher short-term mortality and poorer functional recovery. The evidence for hemorrhagic stroke was less consistent [7]. In our study, ischemic-stroke patients with admission-day hyperglycemia also had higher early mortality than euglycemic patients. Similar findings were observed among non-diabetic patients. Patients with ischemic stroke and stress hyperglycemia had approximately 3.5-fold higher early mortality than euglycemic patients. Previous imaging-based work has also demonstrated an association between acute hyperglycemia and worse ischemic-stroke outcome [11]. In patients with established diabetes, the contribution of an acute stress response could not be separately quantified because pre-stroke glucose values were unavailable. Although observational studies consistently associate hyperglycemia with poor stroke outcome, this association does not establish that intensive glucose lowering improves neurological recovery. The Glucose Insulin in Stroke Trial (GIST) evaluated glucose-potassium-insulin infusion in acute stroke patients with mild to moderate hyperglycemia and established the feasibility of this approach, but did not provide conclusive evidence of improved clinical outcome [12]. Therefore, treatment claims should remain cautious and consistent with evidence-based acute stroke care. More recent evidence continues to support the prognostic relevance of acute hyperglycemia. Williams et al. reported that admission hyperglycemia was independently associated with increased short- and long-term mortality after acute ischemic stroke [20]. In a large Get With The Guidelines-Stroke cohort of thrombolysed patients, both admission hyperglycemia and elevated HbA1c were associated with increased mortality and adverse clinical outcomes [21]. Stress-induced hyperglycemia is also common in acute ischemic stroke. A 2023 systematic review and meta-analysis of 13 studies involving 4,552 patients estimated a pooled incidence of 24% [22]. Contemporary studies increasingly assess stress hyperglycemia relative to chronic glycemic status; a 2024 systematic review and meta-analysis found that a higher stress hyperglycemia ratio was associated with poorer prognosis after acute ischemic stroke [23]. In intracerebral hemorrhage, admission hyperglycemia has likewise been associated with adverse outcome. Béjot et al. found that higher admission blood glucose was independently associated with functional disability and one-month mortality after first-ever intracerebral hemorrhage [24]. Importantly, the association between hyperglycemia and poor prognosis does not prove that intensive glucose lowering improves recovery. In the SHINE randomized clinical trial, intensive glucose control did not improve 90-day functional outcome compared with standard treatment in hyperglycemic acute ischemic stroke and was associated with severe hypoglycemia [25]. This supports careful glucose management while avoiding unsupported claims that intensive normalization itself improves neurological outcome

Admission-day hyperglycemia was associated with greater stroke severity, larger lesion size, increased mortality, and poorer 30-day functional outcome. The association was particularly evident in ischemic stroke. Admission glucose may therefore serve as a useful prognostic marker in patients with acute stroke. As this was an observational study, causal benefit from glucose-lowering therapy cannot be inferred from these data

1. Adams HP Jr, Brott TG, Furlan AJ, Gomez CR, Grotta J, Helgason CM, et al. Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the management of patients with acute ischemic stroke. Circulation. 1996;94(5):1167-1174. doi:10.1161/01.CIR.94.5.1167. 2. Anderson RE, Tan WK, Martin HS, Meyer FB. Effects of glucose and PaO2 modulation on cortical intracellular acidosis, NADH redox state, and infarction in the ischemic penumbra. Stroke. 1999;30(1):160-170. doi:10.1161/01.STR.30.1.160. 3. Demchuk AM, Buchan AM. Predictors of stroke outcome. Neurol Clin. 2000;18(2):455-473. doi:10.1016/S0733-8619(05)70202-4. 4. Baird TA, Parsons MW, Phan TG, Butcher KS, Desmond P, Tress BM. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke. 2003;34:2208-2214. doi:10.1161/01.STR.0000085087.41330.FF. 5. Broderick JP, Brott T, Tomsick T, Miller R, Huster G. Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage. J Neurosurg. 1993;78(2):188-191. doi:10.3171/jns.1993.78.2.0188. 6. Bruno A, Levine SR, Frankel MR, Brott TG, Lin Y, Tilley BC, et al. Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial. Neurology. 2002;59(5):669-674. doi:10.1212/WNL.59.5.669. 7. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke. 2001;32(10):2426-2432. doi:10.1161/hs1001.096194. 8. Hamilton MG, Tranmer BI, Auer RN. Insulin reduction of cerebral infarction due to transient focal ischemia. J Neurosurg. 1995;82(2):262-268. doi:10.3171/jns.1995.82.2.0262. 9. Kawai N, Keep RF, Betz AL. Hyperglycemia and the vascular effects of cerebral ischemia. Acta Neurochir Suppl. 1997;70:27-29. doi:10.1007/978-3-7091-6837-0_8. 10. Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI. Insulin resistance and risk for stroke. Neurology. 2002;59(6):809-815. doi:10.1212/WNL.59.6.809. 11. Parsons MW, Barber PA, Desmond PM, Baird TA, Darby DG, Byrnes G, Tress BM, Davis SM. Acute hyperglycemia adversely affects stroke outcome: a magnetic resonance imaging and spectroscopy study. Ann Neurol. 2002;52(1):20-28. doi:10.1002/ana.10241. 12. Scott JF, Robinson GM, French JM, O'Connell JE, Alberti KG, Gray CS. Glucose potassium insulin infusions in the treatment of acute stroke patients with mild to moderate hyperglycemia: the Glucose Insulin in Stroke Trial (GIST). Stroke. 1999;30(4):793-799. doi:10.1161/01.STR.30.4.793. 13. Williams LS, Rotich J, Qi R, Fineberg N, Espay A, Bruno A, et al. Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke. Neurology. 2002;59(1):67-71. doi:10.1212/WNL.59.1.67. 14. Masrur S, Cox M, Bhatt DL, Smith EE, Ellrodt G, Fonarow GC, Schwamm L. Association of acute and chronic hyperglycemia with acute ischemic stroke outcomes post-thrombolysis: findings from Get With The Guidelines-Stroke. J Am Heart Assoc. 2015;4(10):e002193. doi:10.1161/JAHA.115.002193. 15. Zhang H, Yue K, Jiang Z, Wu X, Li X, Luo P, Jiang X. Incidence of stress-induced hyperglycemia in acute ischemic stroke: a systematic review and meta-analysis. Brain Sci. 2023;13(4):556. doi:10.3390/brainsci13040556. 16. Jiang Z, Wang K, Duan H, Du H, Gao S, Chen J, Fang S. Association between stress hyperglycemia ratio and prognosis in acute ischemic stroke: a systematic review and meta-analysis. BMC Neurol. 2024;24(1):13. doi:10.1186/s12883-023-03519-6. 17. Béjot Y, Aboa-Eboulé C, Hervieu M, Jacquin A, Osseby GV, Rouaud O, Giroud M. The deleterious effect of admission hyperglycemia on survival and functional outcome in patients with intracerebral hemorrhage. Stroke. 2012;43(1):243-245. doi:10.1161/STROKEAHA.111.632950. 18. Johnston KC, Bruno A, Pauls Q, Hall CE, Barrett KM, Barsan W, et al. Intensive vs standard treatment of hyperglycemia and functional outcome in patients with acute ischemic stroke: the SHINE randomized clinical trial. JAMA. 2019;322(4):326-335. doi:10.1001/jama.2019.9346.