Neurological Sciences

, Volume 39, Issue 9, pp 1571–1577 | Cite as

The initial glycemic variability is associated with early neurological deterioration in diabetic patients with acute ischemic stroke

  • Jiaojie Hui
  • Jianping Zhang
  • Xuqiang Mao
  • Zaiwang Li
  • Xinxin Li
  • Fengyun Wang
  • Tao Wang
  • Qingfang Yuan
  • Sunwei Wang
  • Mengjia Pu
  • Guangjun XiEmail author
Original Article


The association between glycemic variability and early neurological deterioration (END) in acute ischemic stroke remains unclear. This study attempted to explore whether initial glycemic variability increases END in diabetic patients with acute ischemic stroke. We enrolled type 2 diabetic patients undergoing acute ischemic stroke from November 2015 to November 2016. A total of 336 patients within 72 h from stroke onset were included. The serum glucose levels were checked four times per day during the initial 3 hospital days. The standard deviation of blood glucose (SDBG) values and the mean amplitude of glycemic excursions (MAGE) were calculated for glycemic variability. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) ≥ 2 points between hospital days 0 and 5. The frequencies of END and HbA1c were significantly different in subjects grouped according to tertiles of MAGE (9.09, 12.07 and 50.00%, p < 0.001 for END; 7.36 ± 1.91, 7.83 ± 1.93 and 8.56 ± 1.79, p < 0.001 for HbA1c). Compared to patients without END, patients with END had significantly higher HbA1c levels (8.30 ± 1.92 vs 7.80 ± 1.93, p = 0.043), increased SDBG (3.42 ± 1.14 vs 2.60 ± 0.96, p < 0.001), and increased MAGE (6.46 ± 2.09 vs 4.59 ± 1.91, p < 0.001). In a multivariable logistic regression, stroke etiology (OR 0.675; 95% CI 0.485–0.940, p = 0.020), baseline NIHSS (OR 1.086; 95% CI 1.004–1.175, p = 0.040), and MAGE (OR 1.479; 95% CI 1.162–1.882, p = 0.001) were significantly associated with END. Initial glycemic variability is associated with END in diabetic patients with acute ischemic stroke.


Acute ischemic stroke Glycemic variability Early neurological deterioration 


Funding information

This research was supported by National Natural Science Foundation of China (No.81201051, Guangjun Xi; No.81401619, Jiaojie Hui; No.81671219, Zaiwang Li), Natural Science Foundation of Jiangsu Province (No.BK2012097, Guangjun Xi; No.BK20151109, Zaiwang Li) and Medical Young Talents Program of Jiangsu Province (No.QNRC2016191, Guangjun Xi; No.QNRC2016178, Jiaojie Hui).

Compliance with ethical standards

All study documents and procedures were approved by the Ethics Committees at all participating hospitals. All patients or their designated relatives gave their written informed consent prior to participation in this study. There was no delay in patients’ receiving treatment due to participation of the study.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, Creager MA, Culebras A, Eckel RH, Hart RG, Hinchey JA, Howard VJ, Jauch EC, Levine SR, Meschia JF, Moore WS, Nixon JV, Pearson TA (2011) Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:517–584CrossRefPubMedGoogle Scholar
  2. 2.
    Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Selvin E, Coresh J, Shahar E, Zhang L, Steffes M, Sharrett AR (2005) Glycaemia (haemoglobin A1c) and incident ischaemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study. Lancet Neurol 4:821–826CrossRefPubMedGoogle Scholar
  4. 4.
    McCormick M, Hadley D, McLean JR, Macfarlane JA, Condon B, Muir KW (2010) Randomized, controlled trial of insulin for acute poststroke hyperglycemia. Ann Neurol 67:570–578PubMedGoogle Scholar
  5. 5.
    Gray CS, Hildreth AJ, Sandercock PA, O’Connell JE, Johnston DE, Cartlidge NE, Bamford JM, James OF, Alberti KG (2007) Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol 6:397–406CrossRefPubMedGoogle Scholar
  6. 6.
    Monnier L, Colette C, Owens DR (2008) Glycemic variability: the third component of the dysglycemia in diabetes. Is it important? How to measure it? J Diabetes Sci Technol 2:1094–1100CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Gonzalez-Moreno EI, Camara-Lemarroy CR, Gonzalez-Gonzalez JG, Gongora-Rivera F (2014) Glycemic variability and acute ischemic stroke: the missing link? Transl Stroke Res 5:638–646CrossRefPubMedGoogle Scholar
  8. 8.
    Ceriello A, Ihnat MA (2010) Glycaemic variability’: a new therapeutic challenge in diabetes and the critical care setting. Diabet Med 27:862–867CrossRefPubMedGoogle Scholar
  9. 9.
    Al-Dorzi HM, Tamim HM, Arabi YM (2010) Glycaemic fluctuation predicts mortality in critically ill patients. Anaesth Intensive Care 38:695–702PubMedGoogle Scholar
  10. 10.
    Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295:1681–1687CrossRefPubMedGoogle Scholar
  11. 11.
    Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D (2008) Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 57:1349–1354CrossRefPubMedGoogle Scholar
  12. 12.
    Seners P, Baron JC (2017) Revisiting ‘progressive stroke’: incidence, predictors, pathophysiology, and management of unexplained early neurological deterioration following acute ischemic stroke. J Neurol 265:216–225Google Scholar
  13. 13.
    Toni D, Fiorelli M, Gentile M, Bastianello S, Sacchetti ML, Argentino C, Pozzilli C, Fieschi C (1995) Progressing neurological deficit secondary to acute ischemic stroke. A study on predictability, pathogenesis, and prognosis. Arch Neurol 52:670–675CrossRefPubMedGoogle Scholar
  14. 14.
    Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS (1994) Effect of blood pressure and diabetes on stroke in progression. Lancet 344:156–159CrossRefPubMedGoogle Scholar
  15. 15.
    Serena J, Rodriguez-Yanez M, Castellanos M (2006) Deterioration in acute ischemic stroke as the target for neuroprotection. Cerebrovasc Dis 21(Suppl 2):80–88CrossRefPubMedGoogle Scholar
  16. 16.
    Alvarez FJ, Segura T, Castellanos M, Leira R, Blanco M, Castillo J, Davalos A, Serena J (2004) Cerebral hemodynamic reserve and early neurologic deterioration in acute ischemic stroke. J Cereb Blood Flow Metab 24:1267–1271CrossRefPubMedGoogle Scholar
  17. 17.
    Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553CrossRefPubMedGoogle Scholar
  18. 18.
    Adams HJ, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh ER (1993) 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 24:35–41CrossRefPubMedGoogle Scholar
  19. 19.
    Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF (1970) Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 19:644–655CrossRefPubMedGoogle Scholar
  20. 20.
    Kim JT, Park MS, Chang J, Lee JS, Choi KH, Cho KH (2013) Proximal arterial occlusion in acute ischemic stroke with low NIHSS scores should not be considered as mild stroke. PLoS One 8:e70996CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kruyt ND, Biessels GJ, Devries JH, Roos YB (2010) Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management. Nat Rev Neurol 6:145–155CrossRefPubMedGoogle Scholar
  22. 22.
    Fuentes B, Castillo J, San JB, Leira R, Serena J, Vivancos J, Davalos A, Nunez AG, Egido J, Diez-Tejedor E (2009) The prognostic value of capillary glucose levels in acute stroke: the GLycemia in Acute Stroke (GLIAS) study. Stroke 40:562–568CrossRefPubMedGoogle Scholar
  23. 23.
    Roquer J, Rodriguez-Campello A, Cuadrado-Godia E, Giralt-Steinhauer E, Jimenez-Conde J, Degano IR, Ois A (2014) Ischemic stroke in prediabetic patients. J Neurol 261:1866–1870CrossRefPubMedGoogle Scholar
  24. 24.
    Brownlee M, Hirsch IB (2006) Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA 295:1707–1708CrossRefPubMedGoogle Scholar
  25. 25.
    Yoon JE, Sunwoo JS, Kim JS, Roh H, Ahn MY, Woo HY, Lee KB (2017) Poststroke glycemic variability increased recurrent cardiovascular events in diabetic patients. J Diabetes Complicat 31:390–394CrossRefPubMedGoogle Scholar
  26. 26.
    Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625CrossRefPubMedGoogle Scholar
  27. 27.
    Ohara M, Fukui T, Ouchi M, Watanabe K, Suzuki T, Yamamoto S, Yamamoto T, Hayashi T, Oba K, Hirano T (2016) Relationship between daily and day-to-day glycemic variability and increased oxidative stress in type 2 diabetes. Diabetes Res Clin Pract 122:62–70CrossRefPubMedGoogle Scholar
  28. 28.
    Costantino S, Paneni F, Battista R, Castello L, Capretti G, Chiandotto S, Tanese L, Russo G, Pitocco D, Lanza GA, Volpe M, Luscher TF, Cosentino F (2017) Impact of glycemic variability on chromatin remodeling, oxidative stress and endothelial dysfunction in type 2 diabetic patients with target HbA1c levels. Diabetes 66:2472–2482Google Scholar
  29. 29.
    Carbonell T, Rama R (2007) Iron, oxidative stress and early neurological deterioration in ischemic stroke. Curr Med Chem 14:857–874CrossRefPubMedGoogle Scholar
  30. 30.
    Llombart V, Dominguez C, Bustamante A, Rodriguez-Sureda V, Martin-Gallan P, Vilches A, Garcia-Berrocoso T, Penalba A, Hernandez-Guillamon M, Rubiera M, Ribo M, Eschenfelder C, Giralt D, Molina CA, Alvarez-Sabin J, Rosell A, Montaner J (2014) Fluorescent molecular peroxidation products: a prognostic biomarker of early neurologic deterioration after thrombolysis. Stroke 45:432–437CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Critical Care MedicineThe Affiliated Wuxi People’s Hospital of Nanjing Medical UniversityWuxiChina
  2. 2.Department of NeurologyThe Affiliated Wuxi People’s Hospital of Nanjing Medical UniversityWuxiPeople’s Republic of China

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