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Higher Insulin Resistance Level is Associated with Worse Clinical Response in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis

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Abstract

Insulin resistance is linked to atherosclerotic cardiovascular diseases and stroke. We investigated whether there is a relationship between insulin resistance and clinical findings and outcomes of acute ischemic stroke patients treated with intravenous thrombolysis. In our study, 180 acute ischemic stroke non-diabetic patients treated with intravenous recombinant tissue-type plasminogen activator (iv rt-PA) were evaluated for insulin resistance assessed by homeostasis model assessment insulin resistance (HOMA-IR). The threshold for HOMA-IR was determined as 2.7. Patients were grouped as HOMA-IR > 2.7 and HOMA-IR ≤ 2.7. Clinical features at baseline, 24th hour, and 3rd month were examined. Computed tomography (CT) findings for hemorrhagic transformation were also assessed. Patients with HOMA-IR > 2.7 had significantly higher National Institutes of Health Stroke Scale (NIHSS) scores at 24th hour (p = 0.005) and higher modified Rankin Scale (mRS) scores at 3rd month (p = 0.011). Logistic regression analysis displayed that the presence of HOMA-IR > 2.7 increases the likelihood of poor outcome 2.93 times (confidence interval [CI] 1.001–1.079) (p = 0.003). There was no statistically significant difference between baseline clinical features, hemorrhagic transformation (p = 1.000), and mortality (p = 0.350) rates. Insulin resistance at higher levels seems to be associated with poor clinical courses and outcomes in patients who received iv rt-PA.

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References

  1. Haratz S, Tanne D. Diabetes, hyperglycemia and the management of cerebrovascular disease. Curr Opin Neurol. 2011;24(1):81–8. doi:10.1097/WCO.0b013e3283418fed.

    Article  PubMed  Google Scholar 

  2. Martini SR, Kent TA. Hyperglycemia in acute ischemic stroke: a vascular perspective. J Cereb Blood Flow Metab. 2007;27(3):435–51. doi:10.1038/sj.jcbfm.9600355.

    Article  CAS  PubMed  Google Scholar 

  3. Demchuk AM, Morgenstern LB, Krieger DW, Linda Chi T, Hu W, Wein TH, et al. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke. 1999;30(1):34–9.

    Article  CAS  PubMed  Google Scholar 

  4. Putaala J, Sairanen T, Meretoja A, Lindsberg PJ, Tiainen M, Liebkind R, et al. Post-thrombolytic hyperglycemia and 3-month outcome in acute ischemic stroke. Cerebrovasc Dis. 2011;31(1):83–92. doi:10.1159/000321332.

    Article  CAS  PubMed  Google Scholar 

  5. Hafez S, Coucha M, Bruno A, Fagan SC, Ergul A. Hyperglycemia, acute ischemic stroke, and thrombolytic therapy. Transl Stroke Res. 2014;5(4):442–53. doi:10.1007/s12975-014-0336-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Luitse MJ, Biessels GJ, Rutten GE, Kappelle LJ. Diabetes, hyperglycaemia, and acute ischaemic stroke. Lancet Neurol. 2012;11(3):261–71. doi:10.1016/S1474-4422(12)70005-4.

    Article  PubMed  Google Scholar 

  7. Gonzalez-Moreno EI, Camara-Lemarroy CR, Gonzalez-Gonzalez JG, Gongora-Rivera F. Glycemic variability and acute ischemic stroke: the missing link? Transl Stroke Res. 2014;5(6):638–46. doi:10.1007/s12975-014-0365-7.

    Article  PubMed  Google Scholar 

  8. Luitse MJ, van Seeters T, Horsch AD, Kool HA, Velthuis BK, Kappelle LJ, et al. Admission hyperglycaemia and cerebral perfusion deficits in acute ischaemic stroke. Cerebrovasc Dis. 2013;35(2):163–7. doi:10.1159/000346588.

    Article  CAS  PubMed  Google Scholar 

  9. Meigs JB, Mittleman MA, Nathan DM, Tofler GH, Singer DE, Murphy-Sheehy PM, et al. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. Jama. 2000;283(2):221–8.

    Article  CAS  PubMed  Google Scholar 

  10. Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Shulman GI, et al. Impaired insulin sensitivity among nondiabetic patients with a recent TIA or ischemic stroke. Neurology. 2003;60(9):1447–51.

    Article  CAS  PubMed  Google Scholar 

  11. Reddy KJ, Singh M, Bangit JR, Batsell RR. The role of insulin resistance in the pathogenesis of atherosclerotic cardiovascular disease: an updated review. J Cardiovasc Med (Hagerstown). 2010;11(9):633–47. doi:10.2459/JCM.0b013e328333645a.

    Article  Google Scholar 

  12. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008;294(1):E15–26. doi:10.1152/ajpendo.00645.2007.

    Article  CAS  PubMed  Google Scholar 

  13. Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI. Insulin resistance and risk for stroke. Neurology. 2002;59(6):809–15.

    Article  CAS  PubMed  Google Scholar 

  14. Viscoli CM, Brass LM, Carolei A, Conwit R, Ford GA, Furie KL, et al. Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial. Am Heart J. 2014;168(6):823–9. doi:10.1016/j.ahj.2014.07.016. e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Arslan M, Atmaca A, Ayvaz G, Başkal NN, Beyhan Z, Bolu E, et al. Metabolik Sendrom Kilavuzu. 2009.

    Google Scholar 

  16. Geloneze B, Repetto EM, Geloneze SR, Tambascia MA, Ermetice MN. The threshold value for insulin resistance (HOMA-IR) in an admixtured population IR in the Brazilian Metabolic Syndrome Study. Diabetes Res Clin Pract. 2006;72(2):219–20. doi:10.1016/j.diabres.2005.10.017.

    Article  CAS  PubMed  Google Scholar 

  17. Adams Jr HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41.

    Article  PubMed  Google Scholar 

  18. Larrue V, von Kummer RR, Muller A, Bluhmki E. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke. 2001;32(2):438–41.

    Article  CAS  PubMed  Google Scholar 

  19. Wahlgren N, Ahmed N, Davalos A, Hacke W, Millan M, Muir K, et al. Thrombolysis with alteplase 3–4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008;372(9646):1303–9. doi:10.1016/S0140-6736(08)61339-2.

    Article  CAS  PubMed  Google Scholar 

  20. Desilles JP, Meseguer E, Labreuche J, Lapergue B, Sirimarco G, Gonzalez-Valcarcel J, et al. Diabetes mellitus, admission glucose, and outcomes after stroke thrombolysis: a registry and systematic review. Stroke. 2013;44(7):1915–23. doi:10.1161/STROKEAHA.111.000813.

    Article  CAS  PubMed  Google Scholar 

  21. Parsons MW, Barber PA, Desmond PM, Baird TA, Darby DG, Byrnes G, et al. Acute hyperglycemia adversely affects stroke outcome: a magnetic resonance imaging and spectroscopy study. Ann Neurol. 2002;52(1):20–8. doi:10.1002/ana.10241.

    Article  PubMed  Google Scholar 

  22. Ribo M, Molina C, Montaner J, Rubiera M, Delgado-Mederos R, Arenillas JF, et al. Acute hyperglycemia state is associated with lower tPA-induced recanalization rates in stroke patients. Stroke. 2005;36(8):1705–9. doi:10.1161/01.STR.0000173161.05453.90.9f.

    Article  CAS  PubMed  Google Scholar 

  23. Gray SM, Meijer RI, Barrett EJ. Insulin regulates brain function, but how does it get there? Diabetes. 2014;63(12):3992–7. doi:10.2337/db14-0340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kleinridders A, Ferris HA, Cai W, Kahn CR. Insulin action in brain regulates systemic metabolism and brain function. Diabetes. 2014;63(7):2232–43. doi:10.2337/db14-0568.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tennant KA, Brown CE. Diabetes augments in vivo microvascular blood flow dynamics after stroke. J Neurosci. 2013;33(49):19194–204. doi:10.1523/JNEUROSCI.3513-13.2013.

    Article  CAS  PubMed  Google Scholar 

  26. Calleja AI, Garcia-Bermejo P, Cortijo E, Bustamante R, Rojo Martinez E, Gonzalez Sarmiento E, et al. Insulin resistance is associated with a poor response to intravenous thrombolysis in acute ischemic stroke. Diabetes Care. 2011;34(11):2413–7. doi:10.2337/dc11-1242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Demet Funda Bas.

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We declare that this study has been approved by the local ethics committee (Eskisehir Osmangazi University) and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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The authors declare that they have no competing interests.

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Bas, D.F., Ozdemir, A.O., Colak, E. et al. Higher Insulin Resistance Level is Associated with Worse Clinical Response in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis. Transl. Stroke Res. 7, 167–171 (2016). https://doi.org/10.1007/s12975-016-0453-y

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