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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 10  |  Issue : 1  |  Page : 29-33

Correlation of serum albumin with ischemia modified albumin in acute stroke patients with or without diabetes mellitus


1 Department of Biochemistry, J.N. Medical College, KLE University, Belagavi, Karnataka, India
2 Department of Neurology, J.N. Medical College, KLE University, Belagavi, Karnataka, India

Date of Web Publication18-Jan-2017

Correspondence Address:
Dr. Jayaraj G Gudi
Room No. 53, Charaka Hostel, J.N. Medical College Campus, Nehru Nagar, Belagavi - 590 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5006.198579

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  Abstract 

Introduction: Stroke is the leading cause of mortality and morbidity worldwide. Diabetes mellitus (DM) is most commonly associated with the acute stroke. Abnormalities in serum albumin are known to occur in acute stroke patients. Ischemia-modified albumin (IMA) is a novel marker of acute stroke and hence, it is important to know the factors affecting IMA estimation. The objective of this study was to find out the correlation between serum albumin and IMA in acute stroke with or without DM.
Subjects and Methods: This cross-sectional study comprised sixty acute stroke patients (thirty with DM, thirty without DM) and thirty healthy controls. The blood sample was collected from the patients soon after the clinical diagnosis of stroke. IMA and albumin were measured. IMA concentration was expressed in absorbance units. Pearson's correlation coefficient was estimated.
Results: In stroke with DM (r = 0.103, P = 0.58) and control (r = 0.007, P = 0.96) groups, there was a negative correlation between IMA and serum albumin which was statistically not significant. In stroke without DM group, there was a positive correlation between IMA and serum albumin which was again statistically insignificant (r = 0.111, P = 0.56).
Discussion and Conclusion: There was no statistically significant correlation between IMA and serum albumin levels in all the three groups. Hence, it can be concluded that IMA concentration is independent of serum albumin concentration and probably, it depends on the severity and duration of ischemia or oxidative stress in acute stroke patients.

Keywords: Acute stroke, diabetes mellitus, ischemia modified albumin, serum albumin


How to cite this article:
Gudi JG, Malleshappa A, Naik KR. Correlation of serum albumin with ischemia modified albumin in acute stroke patients with or without diabetes mellitus. Indian J Health Sci Biomed Res 2017;10:29-33

How to cite this URL:
Gudi JG, Malleshappa A, Naik KR. Correlation of serum albumin with ischemia modified albumin in acute stroke patients with or without diabetes mellitus. Indian J Health Sci Biomed Res [serial online] 2017 [cited 2019 Jul 17];10:29-33. Available from: http://www.ijournalhs.org/text.asp?2017/10/1/29/198579


  Introduction Top


An acute ischemic stroke results from prolonged cerebral ischemia leading to cerebral neuronal death. Stroke is a major contributor to the burden of morbidity and mortality. According to the WHO, stroke is the second leading cause of death after ischemic heart disease in high and middle-income countries, whereas sixth leading cause in low-income countries.[1] Diagnosis of acute stroke at the earliest is very crucial since it can significantly reduce the mortality and improve the outcome. Currently, the diagnosis is based on neuroimaging techniques.[2] However, these facilities are time-consuming, costly and not widely available. Alternate approach would be the use of biomarkers.

Several studies have been published correlating several biochemical markers to stroke, but none are approved for clinical use. Ischemia-modified albumin (IMA) is the only marker which has been approved by Food and Drug Administration (FDA) of the United States for early diagnosis of myocardial ischemia. IMA is a novel marker developed by quantifying the decrease in metal binding capacity. Several attempts have been made to understand the significance of IMA in context with acute ischemic condition other than myocardial infarctions such as acute stroke, and pulmonary embolism, but the data show variable results, and the available data are insufficient and inconclusive.[3],[4] Diabetes mellitus (DM) is frequently associated with stroke. Diabetes is known to accelerate the atherosclerosis process and hence increases the risk of stroke. DM is also known to influence the IMA concentration.[5]

There are many factors which can affect the IMA levels in stroke patients. Few studies suggest that the serum albumin levels could influence the IMA estimation and hence suggested few modifications to the IMA estimation.[6] There are many studies in the literature which have reported decreased albumin levels in acute stroke patients. Hence, this study was undertaken to assess the correlation of serum albumin levels with the IMA levels in acute stroke patients with or without DM.


  Subjects and Methods Top


Study population

This study comprised the patients of acute stroke (diagnosed clinically and radiologically) with and without DM, attending casualty and intensive care unit of KLES' Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi. Apparently, healthy volunteers who attended the blood bank of Dr. Prabhakar Kore Hospital and Medical Research Centre were taken as controls. This study included ninety subjects of either sex, aged more than 18 years, of which thirty cases of acute stroke with diabetes, thirty cases of acute stroke without diabetes and thirty normal healthy controls. Informed and written consent was obtained from all the subjects involved in the study. Institutional ethical committee clearance was obtained before start of the study.

Patients presenting with the symptoms of acute stroke within 12 h of onset of symptoms were included in the study. Clinical data with other relevant information were obtained as per the proforma. Initially, blood sample was drawn from all the patients immediately after the clinical diagnosis. Patients with confirmed diagnosis of acute stroke by brain computerized tomography and/or magnetic resonance imaging were included in the case group. Detailed history including diabetes history was taken and included them in different groups accordingly. The patients with diabetes history who are on treatment for hyperglycemia (either oral hypoglycemic drugs or insulin) were only included in diabetes group. Serum was separated from the blood and used for further analyses.

Analytical methods

IMA was measured by albumin cobalt binding test as described by Bar-Or et al.[7] To 200 μl of serum 50 μl of cobalt chloride was added and kept for 10 min incubation. Dithiothreitol 50 μl was added and incubated for 2 min. Later, 1 ml of sodium chloride was added. The absorbance of assay mixture was read at 470 nm using a spectrophotometer and values recorded in absorbance units.

Serum albumin was measured by SIEMENS Dimension® RxL Max clinical chemistry system based on the bromocresol purple (BCP) dye-binding method. In this assay, serum albumin quantitatively binds to BCP to form an albumin-BCP complex that is measured as an endpoint reaction at 596/694 nm.

Statistical analysis

SPSS software version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp.) was used for the statistical analyses. The measured parameters were expressed as mean ± standard deviation. The data generated were compared using ANOVA at 5% level of significance. Correlations between the parameters were done using Pearson's correlation coefficient test at 5% level of significance.


  Results Top


There was a statistically significant difference between the three groups with respect to mean serum albumin values when compared with ANOVA (P < 0.01). Mean serum albumin value of "control" group (4.0 ± 0.4 g/dL) was higher than the "stroke with DM" (3.6 ± 0.6 g/dL) or "stroke without DM" (3.8 ± 0.4 g/dL) groups. Comparison of serum albumin values of three groups with each other by post hoc Bonferroni test showed significant difference (P < 0.01) between "control" and "stroke with DM" groups [[Table 1] and Graph 1].
Table 1: Mean±standard deviation values of human serum albumin in the three groups and results of ANOVA


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Mean IMA values were high in "stroke with DM" (0.23 ± 0.03) or "stroke without DM" (0.21 ± 0.03) groups when compared with the "controls" (0.16 ± 0.03). There was a statistically significant difference (P < 0.001) between the three groups when compared by ANOVA [Table 2].
Table 2: Mean and standard deviation values of ischemia-modified albumin in the three groups and results of ANOVA


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There was no statistically significant correlation between IMA and serum albumin levels in all the three groups. In "stroke with DM" group, there was a statistically insignificant negative correlation between IMA values and serum albumin values (r = –0.103, P = 0.58). In "stroke without DM" group, there was a statistically insignificant positive correlation between IMA values and serum albumin values (r = 0.111, P = 0.56). In "control" group, there was a statistically insignificant negative correlation (r = –0.007, P = 0.96) between IMA values and serum albumin values [Graphs 2-4].




  Discussion Top


IMA, the only FDA approved biomarker for ischemia has been shown to increase in various ischemic conditions including coronary artery disease, acute stroke, and mesenteric ischemia. Originally, IMA was studied in acute coronary syndrome patients.

In this study, IMA level was significantly higher in stroke patients than controls. This is in accordance with many previous studies.[8],[9] The exact mechanism of formation of IMA in any ischemia including stroke is not known. The proposed mechanisms for conversion of serum albumin to IMA include hypoxia, acidosis, superoxide radical injury, exposure to free iron and copper, etc. Reactive oxygen species are well-known as factors responsible for chemical and molecular damage of many biological molecules. Most of the recent studies reported that IMA levels increased in many diseases where oxidative stress is proposed as the main mechanism supporting the hypothesis that IMA generation depends strongly on the high oxidative stress state.

In our study, we also estimated and compared serum albumin levels in all the three study groups. We also tried to assess the correlation of serum albumin with IMA levels in the three groups separately. Serum albumin values were higher in "control" group than "stroke with DM" or "stroke without DM" groups. This is in line with results of many studies which analyzed the role of albumin in acute stroke. The First National Health and Nutrition Examination Survey I epidemiologic follow-up study showed lower serum albumin level is associated with higher stroke incidence and death risk due to stroke.[10] Xu et al. also observed in their Northern Manhattan study, lower albumin levels in stroke patients with various etiologies.[11] Folsom et al. reported lower serum albumin levels in diabetics than nondiabetics which was also observed in our study.[12]

Gaze et al. studied the correlation between serum albumin and IMA in healthy nonischemic patients and observed that there was a significant (r = –0.888, P < 0.0001) negative correlation between IMA and albumin both over the entire range of albumin concentrations and in the low albumin concentration subgroup (r = –0.85, P < 0.0001), but there was a less significant negative correlation between the two in the group with albumin levels within the reference interval.[13] A study done by Kumar et al. revealed a significant negative correlation (r = –0.473, P < 0.001) between serum albumin levels and IMA levels in acute myocardial infarction patients.[6] No study has reported the correlation of IMA with serum albumin in acute stroke patients.


  Conclusion Top


In our study, there was a negative correlation in "stroke with DM" or "control" groups; although, it was statistically not significant. In "stroke without DM" group, there was a statistically insignificant positive correlation. Hence, it can be concluded that IMA concentration is independent of serum albumin concentration in acute stroke patients and probably the IMA concentration depends on the severity and duration of ischemia or oxidative stress.

Some of the limitations of the present study include small sample size for the results to be generalized for acute stroke diagnosis. The effect of DM on the IMA levels and serum albumin levels was not considered in the present study. Further large-scale studies devoid of the above limitations are required to confirm the findings of this study.


  Acknowledgment Top


We thank immensely to Indian Council of Medical Research for funding this research project.

Financial support and sponsorship

We are very grateful to Indian Council of Medical Research for providing the financial support.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
World Health Organisation. Available from: http://www.who.int/chp/steps/stroke/en/. [Last accessed on 2012 Oct 16].  Back to cited text no. 1
    
2.
Kasper DL, Hauser S, Jameson JL, Fauci AS, Longo DL, Loscalzo J. Harrison′s Principles of Internal Medicine. 19 th ed. New York: McGraw-Hill, Medical Publishing Division; 2015.  Back to cited text no. 2
    
3.
Ertekin B, Kocak S, Defne Dundar Z, Girisgin S, Cander B, Gul M, et al. Diagnostic value of ischemia-modified albumin in acute coronary syndrome and acute ischemic stroke. Pak J Med Sci 2013;29:1003-7.  Back to cited text no. 3
    
4.
Gad MS, Zakaria NH, Elgayar NH. Evaluation of the role of ischemia modified albumin as a new biochemical marker for differentiation between ischemic and hemorrhagic stroke. Alexandria J Med 2015;51:213-7.  Back to cited text no. 4
    
5.
Dahiya K, Aggarwal K, Seth S, Singh V, Sharma TK. Type 2 diabetes mellitus without vascular complications and ischemia modified albumin. Clin Lab 2010;56:187-90.  Back to cited text no. 5
    
6.
Kumar A, Uthappa S, Surendran S, Michael M, Sushitha E. Correlation of albumin concentration and ischemia modified albumin in the diagnosis of acute myocardial infarction. Int J Biomed Adv Res 2015;6:310-5.  Back to cited text no. 6
    
7.
Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report. J Emerg Med 2000;19:311-5.  Back to cited text no. 7
    
8.
Abboud H, Labreuche J, Meseguer E, Lavallee PC, Simon O, Olivot JM, et al. Ischemia-modified albumin in acute stroke. Cerebrovasc Dis 2007;23:216-20.  Back to cited text no. 8
    
9.
Gunduz A, Turedi S, Mentese A, Altunayoglu V, Turan I, Karahan SC, et al. Ischemia-modified albumin levels in cerebrovascular accidents. Am J Emerg Med 2008;26:874-8.  Back to cited text no. 9
    
10.
Gillum RF, Ingram DD, Makuc DM. Relation between serum albumin concentration and stroke incidence and death: The NHANES I Epidemiologic Follow-up Study. Am J Epidemiol 1994;140:876-88.  Back to cited text no. 10
    
11.
Xu WH, Dong C, Rundek T, Elkind MS, Sacco RL. Serum albumin levels are associated with cardioembolic and cryptogenic ischemic strokes: Northern Manhattan Study. Stroke 2014;45:973-8.  Back to cited text no. 11
    
12.
Folsom AR, Ma J, Eckfeldt JH, Nieto FJ, Metcalf PA, Barnes RW. Low serum albumin. Association with diabetes mellitus and other cardiovascular risk factors but not with prevalent cardiovascular disease or carotid artery intima-media thickness. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Ann Epidemiol 1995;5:186-91.  Back to cited text no. 12
    
13.
Gaze DC, Crompton L, Collinson P. Ischemia-modified albumin concentrations should be interpreted with caution in patients with low serum albumin concentrations. Med Princ Pract 2006;15:322-4.  Back to cited text no. 13
    



 
 
    Tables

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