Background: Demographic and clinical characteristics are known to influence the outcome in acute ischemic stroke (AIS) patients. Purpose: This study is aimed at evaluating short- and long-term outcomes in diabetic AIS patients. In addition, the study also evaluates the impact of diabetes on the performance of indigenously reported biomarker, inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and known biomarkers, neuron-specific enolase (NSE) and glial-derived S-100 beta beta protein (S-100ββ). Methods: This study was performed on 29 diabetes and 75 non-diabetes AIS patients. Outcome of AIS patients was analyzed by using modified Rankin scale at discharge, then at 12 and 18 months after discharge. Based on the obtained scores, patients were classified as improved group (scales 1-3) and dependent/expired group (scales 3-6). Blood samples were collected during admission and at discharge/expired time. Levels of NSE, S100ββ, and ITIH4 were analyzed in all samples. Results: On discharge, frequencies of dependent/expired outcome were 4/29 (14%) and 19/75 (17%) in diabetic and non-diabetic AIS patients. However, follow-up outcome at 12 and 18 months showed higher dependent/expired cases of 43 and 41% among diabetic AIS patients compared to 27 and 21% in non-diabetic patients. Multivariate analysis revealed that diabetes is an independent risk factor for dependent/expired outcome in AIS patients (OR 0.484 (at discharge); 1.307 (at 12 months) and 1.675 (at 18 months)). NSE, S100ββ, and ITIH4 showed a differential expression in both the outcome groups of AIS patients, irrespective of diabetes. Conclusion: Diabetes increases the risk of dependent/expired outcome in AIS patients. Also, serum NSE, S100ββ, and ITIH4 are independent biomarkers for prognosis of outcome in AIS patients, irrespective of diabetes.

1.
Mathers CD, Lopez A, Stein C, Murray CJL: Deaths and Disease Burden by Cause: Global Burden of Disease Estimates for 2001 by World Bank Country Groups. Bethesda, Disease Control Priorities Project Working Paper 18.
2.
Karatepe AG, Gunaydin R, Kaya T, Turkmen G: Comorbidity in patients after stroke: impact on functional outcome. J Rehabil Med 2008;40:831-835.
3.
Stead LG, Gilmore RM, Bellolio MF, Mishra S, Bhagra A, Vaidyanathan L, Decker WW, Brown RD Jr: Hyperglycemia as an independent predictor of worse outcome in non-diabetic patients presenting with acute ischemic stroke. Neurocrit Care 2009;10:181-186.
4.
Reeves MJ, Vaidya RS, Fonarow GC, Liang L, Smith EE, Matulonis R, Olson DM, Schwamm LH; Get with the Guidelines Steering Committee and Hospitals: Quality of care and outcomes in patients with diabetes hospitalized with ischemic stroke: findings from get with the guidelines - stroke. Stroke 2010;41:e409-e417.
5.
Jia Q, Zhao X, Wang C, Wang Y, Yan Y, Li H, Zhong L, Liu L, Zheng H, Zhou Y, Wang Y: Diabetes and poor outcomes within 6 months after acute ischemic stroke: the China national stroke registry. Stroke 2011;42:2758-2762.
6.
Policardo L, Seghieri G, Francesconi P, Anichini R, Franconi F, Seghieri C, Del Prato S: Gender difference in diabetes-associated risk of first-ever and recurrent ischemic stroke. J Diabetes Complications 2015;29:713-717.
8.
Umemura T, Kawamura T: Effect of diabetes on stroke symptoms and mortality: lessons from a recent large population-based cohort study. J Diabetes Investig 2014;5:14-16.
9.
Barr TL, Matarin MD, Warch JS, Singleton AB, Conley YP: Biomarkers for Acute Ischemic Stroke, 2013, Application No. 13/580571, United States Patent Application 20130189243, Kind Code: A1.
10.
Els T, Bruckmann J, Röhn G, Daffertshofer M, Mönting JS, Ernestus RI, Hennerici M: Spermidine: a predictor for neurological outcome and infarct size in focal cerebral ischemia? Stroke 2001;32:43-46.
11.
Purrucker JC, Herrmann O, Lutsch JK, Zorn M, Schwaninger M, Bruckner T, Auffarth GU, Veltkamp R: Serum protein S100β is a diagnostic biomarker for distinguishing posterior circulation stroke from vertigo of nonvascular causes. Eur Neurol 2014;72:278-284.
12.
Kashyap RS, Nayak AR, Deshpande PS, Kabra D, Purohit HJ, Taori GM, Daginawala HF: Inter-alpha-trypsin inhibitor heavy chain 4 is a novel marker of acute ischemic stroke. Clin Chim Acta 2009;402:160-163.
13.
Nayak AR, Kashyap RS, Kabra D, Purohit HJ, Taori GM, Daginawala HF: Time course of inflammatory cytokines in acute ischemic stroke patients and their relation to inter-alfa trypsin inhibitor heavy chain 4 and outcome. Ann Indian Acad Neurol 2012;15:181-185.
14.
Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T: Cerebrovascular disease in the community: results of a WHO collaborative study. Bull World Health Organ 1980;58:113-130.
15.
Harrison JK, McArthur KS, Quinn TJ: Assessment scales in stroke: clinimetric and clinical considerations. Clin Interv Aging 2013;8:201-211.
16.
Barrett-Connor E, Khaw KT: Diabetes mellitus: an independent risk factor for stroke? Am J Epidemiol 1988;128:116-123.
17.
Air EL, Kissela BM: Diabetes, the metabolic syndrome, and ischemic stroke: epidemiology and possible mechanisms. Diabetes Care 2007;30:3131-3140.
18.
Tuomilehto J, Rastenyte D, Jousilahti P: Diabetes mellitus as a risk factor for death from stroke. Prospective study of the middle-aged Finnish population. Stroke 1996;27:210-215.
19.
Kissela BM, Khoury J, Kleindorfer D, Woo D, Schneider A, Alwell K, Miller R, Ewing I, Moomaw CJ, Szaflarski JP, Gebel J, Shukla R, Broderick JP: Epidemiology of ischemic stroke in patients with diabetes: the greater cincinnati/northern Kentucky stroke study. Diabetes Care 2005;28:355-359.
20.
Peters SA, Huxley RR, Woodward M: Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775,385 individuals and 12,539 strokes. Lancet 2014;383:1973-1980.
21.
Qiao Q, Hu G, Tuomilehto J, Nakagami T, Balkau B, Borch-Johnsen K, et al; DECODA Study Group: Age- and sex-specific prevalence of diabetes and impaired glucose regulation in 11 Asian cohorts. Diabetes Care 2003;26:1770-1780.
22.
Klein R, Klein BE, Lee KE, Cruickshanks KJ, Moss SE: The incidence of hypertension in insulin-dependent diabetes. Arch Intern Med 1996;156:622-627.
23.
Codreanu I, Sali V, Gaibu S, Suveica L, Popa S, Perico N, Ene-Iordache B, Carminati S, Feehally J, Remuzzi G: Prevalence of hypertension and diabetes and coexistence of chronic kidney disease and cardiovascular risk in the population of the republic of moldova. Int J Hypertens 2012;2012:951734.
24.
Antikainen R, Jousilahti P, Tuomilehto J: Systolic blood pressure, isolated systolic hypertension and risk of coronary heart disease, strokes, cardiovascular disease and all-cause mortality in the middle-aged population. J Hypertens 1998;16:577-583.
25.
Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, Wright AD, Turner RC, Holman RR: Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000;321:412-419.
26.
Arauz-Pacheco C, Parrott MA, Raskin P; American Diabetes Association: Treatment of hypertension in adults with diabetes. Diabetes Care 2003;26(suppl 1):S80-S82.
27.
Cooper ME, Johnston CI: Optimizing treatment of hypertension in patients with diabetes. JAMA 2000;283:3177-3179.
28.
Ahmad O, Wardlaw J, Whiteley WN: Correlation of levels of neuronal and glial markers with radiological measures of infarct volume in ischaemic stroke: a systematic review. Cerebrovasc Dis 2012;33:47-54.
29.
Pandey A, Saxena K, Verma M, Bharosay A: Correlative study between neuron-specific enolase and blood sugar level in ischemic stroke patients. J Neurosci Rural Pract 2011;2:50-54.
30.
Marenholz I, Heizmann CW, Fritz G: S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun 2004;322:1111-1122.
31.
Stevens H, Jakobs C, de Jager AE, Cunningham RT, Korf J: Neurone-specific enolase and N-acetyl-aspartate as potential peripheral markers of ischaemic stroke. Eur J Clin Invest 1999;29:6-11.
32.
Cunningham RT, Watt M, Winder J, McKinstry S, Lawson JT, Johnston CF, Hawkins SA, Buchanan KD: Serum neurone-specific enolase as an indicator of stroke volume. Eur J Clin Invest 1996;26:298-303.
33.
Fassbender K, Schmidt R, Schreiner A, Fatar M, Mühlhauser F, Daffertshofer M, Hennerici M: Leakage of brain-originated proteins in peripheral blood: temporal profile and diagnostic value in early ischemic stroke. J Neurol Sci 1997;148:101-105.
34.
Foerch C, Otto B, Singer OC, Neumann-Haefelin T, Yan B, Berkefeld J, Steinmetz H, Sitzer M: Serum S100B predicts a malignant course of infarction in patients with acute middle cerebral artery occlusion. Stroke 2004;35:2160-2164.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.