Introduction: In various acute conditions, including acute ischemic stroke (AIS), a stress response occurs, often leading to elevated blood glucose (BG) levels, the so-called stress hyperglycemia (SH). Its adequate assessment would be particularly useful in clinical practice, both for identifying high-risk patients and for therapeutic behavior.
Aim: The aim of this article is to analyze cortisol levels and glycated hemoglobin (HbA1c)-based glycemic variables as markers for assessment of stress response in AIS and to look for an association with adverse clinical outcome.
Materials and Methods: A cross-sectional study including 114 patients with AIS, stratified according to BG at admission (admBG) and the presence of diabetes mellitus (DM)—with normoglycemia, SH, previously and newly diagnosed type 2 DM was conducted. Serum cortisol levels, as well as HbA1c-based glycemic variables were evaluated according to the severity of stroke (assessed by National Institutes of Health Stroke Scale, NIHSS score) and the prevalence of fatal outcome.
Results: The SH group demonstrated the greatest AIS severity at admission, accompanied by the highest serum cortisol levels, with a significant difference in both indicators compared to the NG group (NIHSS 15.33 ± 8.39 vs.10.63 ± 6.12, p = 0.016; serum cortisol 1039 ± 668 vs. 701.7 ± 380.8 p = 0.046). Furthermore, in patients with a fatal outcome compared to survivors, we observed significantly more severe AIS (NIHSS 15.93 ± 5.31 vs. 9.72 ± 6.31, p < 0.0001), as well as higher serum cortisol levels (1060 ± 572.1 vs. 610.5 ± 284.8, p < 0.0001). In contrast to admBG, HbA1c-based glycemic variables demonstrated the highest values in the SH group. Both cortisol and glycemic variables, but not admBG, showed positive correlation with AIS severity at admission.
Conclusion: Serum cortisol levels could be useful in assessing the severity of AIS and identifying high-risk patients. HbA1c-based glycemic variables are better determinants of stress response than absolute BG values.
Marik PE, Bellomo R. Stress hyperglycemia: an essential survival response! Crit Care Med. 2013;41(6):e93-4. doi: 10.1097/CCM.0b013e318283d124.
Farrokhi F, Smiley D, Umpierrez GE. Glycemic control in non-diabetic critically ill patients. Best Pract Res Clin Endocrinol Metab. 2011;25(5):813-24. doi: 10.1016/j.beem.2011.05.004.
Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet. 2009 May 23;373(9677):1798-807. doi: 10.1016/S0140-6736(09)60553-5.
Boyadzhieva M. Glycemic control in critically ill patients. Varna Medical University Press; 2017. (in Bulgarian).
Mifsud S, Schembri EL, Gruppetta M. Stress-induced hyperglycaemia. Br J Hosp Med. 2018;79(11):634-9. doi: 10.12968/hmed.2018.79.11.634.
Liao WI, Sheu WH, Chang WC, Hsu CW, Chen YL, Tsai SH. An elevated gap between admission and A1C-derived average glucose levels is associated with adverse outcomes in diabetic patients with pyogenic liver abscess. PLoS One. 2013;8(5):e64476. doi: 10.1371/journal.pone.0064476.
Roberts GW, Quinn SJ, Valentine N, Alhawassi T, O'Dea H, Stranks SN, et al. Relative hyperglycemia, a marker of critical illness: introducing the stress hyperglycemia ratio. J Clin Endocrinol Metab. 2015;100(12):4490-7. doi: 10.1210/jc.2015-2660.
Chen PC, Liao WI, Wang YC, Chang WC, Hsu CW, Chen YH, et al. An elevated glycemic gap is associated with adverse outcomes in diabetic patients with community-acquired pneumonia. Medicine (Baltimore). 2015;94(34):e1456. doi: 10.1097/MD.0000000000001456.
Fawzy F, Saad MSS, ElShabrawy AM, Eltohamy MM. Effect of glycemic gap on short term outcome in critically ill patient: In zagazig university hospitals. Diabetes Metab Syndr. 2019;13(2):1325-8. doi: 10.1016/j.dsx.2019.01.042.
Liao WI, Wang JC, Chang WC, Hsu CW, Chu CM, Tsai SH. Usefulness of glycemic gap to predict icu mortality in critically ill patients with diabetes. Medicine (Baltimore). 2015;94(36):e1525. doi: 10.1097/MD.0000000000001525.
Liao WI, Lin CS, Lee CH, Wu YC, Chang WC, Hsu CW, et al. An elevated glycemic gap is associated with adverse outcomes in diabetic patients with acute myocardial infarction. Sci Rep. 2016;6:27770. doi: 10.1038/srep27770.
Christensen H, Boysen G, Johannesen HH. Serum-cortisol reflects severity and mortality in acute stroke. J Neurol Sci. 2004;217(2):175-80. doi: 10.1016/j.jns.2003.09.013.
Cheung NW, Wong KYC, Kovoor P, McLean M. Stress hyperglycemia: A prospective study examining the relationship between glucose, cortisol and diabetes in myocardial infarction. J Diabetes Complications. 2019;33(4):329-334. doi: 10.1016/j.jdiacomp.2018.12.015.
Sobczak J, Burzyńska M, Sikora A, Wysocka A, Karawani J, Sikora JP. Post-traumatic stress response and appendicitis in children-clinical usefulness of selected biomarkers. Biomedicines. 2023;11(7):1880. doi: 10.3390/biomedicines11071880.
Tziomalos K, Dimitriou P, Bouziana SD, Spanou M, Kostaki S, Angelopoulou SM, et al. Stress hyperglycemia and acute ischemic stroke in-hospital outcome. Metabolism. 2017;67:99-105. doi: 10.1016/j.metabol.2016.11.011.
Mi D, Wang P, Yang B, Pu Y, Yang Z, Liu L. Correlation of hyperglycemia with mortality after acute ischemic stroke. Ther Adv Neurol Disord. 2018;11:175628561773168. doi: 10.1177/1756285617731686.
Barugh AJ, Gray P, Shenkin SD, MacLullich AMJ, Mead GE. Cortisol levels and the severity and outcomes of acute stroke: a systematic review. J Neurol. 2014;261(3):533-45. doi: 10.1007/s00415-013-7231-5.
Anne M, Juha K, Timo M, Mikko T, Olli V, Kyösti S, et al. Neurohormonal activation in ischemic stroke: effects of acute phase disturbances on long-term mortality. Curr Neurovasc Res. 2007;4(3):170-5. doi: 10.2174/156720207781387169.
Neidert S, Katan M, Schuetz P, Fluri F, Ernst A, Bingisser R, et al. Anterior pituitary axis hormones and outcome in acute ischaemic stroke. J Intern Med. 2011;269(4):420-32. doi: 10.1111/j.1365-2796.2010.02327.x.
Zierath D, Tanzi P, Cain K, Shibata D, Becker K. Plasma α-melanocyte stimulating hormone predicts outcome in ischemic stroke. Stroke. 2011;42(12):3415-20. doi: 10.1161/STROKEAHA.111.627331.
Saini G, Kaur K, Bhatia L, Kaur R, Singh J, Singh G. Single serum cortisol value as a prognostic marker in acute ischemic stroke. Cureus. 2023;15(6):e40887. doi: 10.7759/cureus.40887.