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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 4  |  Page : 228-231

Effect of glycemic control on the severity and outcome of stroke in Saudi Arabia


1 Department of Neurology, Ain Shams University, Cairo, Egypt; Department of Neurology, King Abdulaziz Hospital, Mecca, Kingdom of Saudi Arabia
2 Department of Clinical Pathology, Ain Shams University, Cairo, Egypt

Date of Submission30-Apr-2015
Date of Acceptance26-Jun-2015
Date of Web Publication27-Nov-2015

Correspondence Address:
Magdy A Mostafa
Department of Neurology, King Abdulaziz Hospital, Mecca, Kingdom of Saudi Arabia

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-1083.170652

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  Abstract 

Background
Diabetes mellitus (DM) is a well-known risk factor of ischemic stroke. However, the effect of glycemic control regardless of the presence of DM on the clinical picture of stroke and its impact on the severity and outcome of stroke is not fully investigated.
Objective
The aim of this study was to assess the impact of prestroke glycemic control regardless of the presence of past history of DM on the size of infarction, stroke severity, and functional outcome in patients with acute ischemic stroke.
Patients and methods
We measured glycosylated hemoglobin (HbA1c) level as an indicator for glycemic control in the last 3 months before stroke in 56 patients with the diagnosis of the first attack of acute ischemic stroke. There were 26 female and 30 male patients between 45 and 94 years of age. After history taking and full clinical examination, the size of infarction was measured using computed tomography scan of the brain. Stroke severity within 72 h from onset of symptoms was assessed using the National Institute of Health Stroke Scale and outcome of stroke after 2 months was assessed using the modified Barthel Index, both of which were assessed for each stroke patient.
Results
There was a significant positive correlation between the value of HbA1c and both the size of infarction and National Institute of Health Stroke Scale score assessed within 72 h from symptom onset (P < 0.01). In contrast, increased HbA1c value was significantly associated with a decrease in the modified Barthel Index score assessed after 2 months (P < 0.001).
Conclusion
Glycemic control has a significant effect on ischemic stroke severity and outcome.

Keywords: glycemic control, outcome of stroke, glycosylated hemoglobin


How to cite this article:
Mostafa MA, Mohamed NA. Effect of glycemic control on the severity and outcome of stroke in Saudi Arabia. Egypt J Neurol Psychiatry Neurosurg 2015;52:228-31

How to cite this URL:
Mostafa MA, Mohamed NA. Effect of glycemic control on the severity and outcome of stroke in Saudi Arabia. Egypt J Neurol Psychiatry Neurosurg [serial online] 2015 [cited 2017 Dec 12];52:228-31. Available from: http://www.ejnpn.eg.net/text.asp?2015/52/4/228/170652


  Introduction Top


Diabetes mellitus (DM) is a well-established independent risk factor for stroke, and this increased risk has been linked to the pathophysiological changes seen in the cerebral vessels of patients with diabetes. Several studies showed that patients with diabetes who develop stroke have a less-favorable outcome compared with those without [1] .

Glycosylated hemoglobin A1c (HbA1c) reflects mean ambient fasting and postprandial glycemia over a 2-3-month period. Although HbA1c testing is mainly used for monitoring blood sugar control in patients with diabetes, the WHO now recommends that HbA1c can be used as a diagnostic test for diabetes. A value of HbA1c of 6.5% is recommended as the cutoff point for diagnosing diabetes. For patients with DM, the goal of therapy is less than 7.0%. One advantage of using HbA1c for diagnosis is that the test does not require a fasting blood sample [2] . Some studies suggested that the individuals, both with and without DM, with an elevated HbA1c have a higher rate of microvascular complications [3] .

However, it is still unclear whether stroke features, severity, and prognosis differ according to glycemic control. Although several studies compared the patients on the basis of the clinical prestroke diagnosis of DM, no evaluation of HbA1c in the whole study cohort was available. As a result, there could have been interference from patients with subclinical DM who were included in the group without a diagnosis of DM [4] .


  Aim of work Top


The aim of this study was to study the effect of prestrike glycemic control (HbA1c) regardless of past history of DM on the size of infarction, severity of clinical picture, and outcome in ischemic stroke patients.


  Patients and methods Top


This study was conducted on 56 patients with the diagnosis of ischemic stroke. The patients were recruited from King Abdulaziz Hospital in Mecca. The only inclusion criterion was the confirmed diagnosis of first ischemic stroke with onset of symptoms in the last 72 h before admission. The following exclusion criteria were applied:

  1. Age below 40 years;
  2. Negative computed tomographic (CT) scan of the brain both on admission and on follow-up;
  3. Presence of hepatic or renal failure; and
  4. Presence of medical conditions that may affect the level of HbA1c, such as anemia, hemoglobinopathies, pregnancy, and alcoholism.


All patients were subjected to full clinical assessment including history taking and full general and neurological examination. CT scan of the brain was performed for each patient to exclude intracranial hemorrhage and to diagnose cerebral infarction. If CT scan was negative, it was repeated after 72 h. The size of the lesion was calculated according to the formula 0.5 × A × B × C [where A and B are the largest perpendicular diameters measured on CT and C is the slice thickness (10 mm)]. All scans were performed on Siemens Somaton Balance scanner (Siemens Company, Germany). Full laboratory investigation was carried out, including complete blood count, renal function tests, liver function tests, coagulation profile, and lipid profile including serum cholesterol, HDL, LDL and triglycerides. HbA1c was evaluated for each patient using high performance liquid chromatography with a cation exchanger. In addition, ECG, transthoracic echocardiography, and carotid duplex were performed as part of stroke workup. Stroke severity within 72 h from onset of symptoms was assessed for each patient using the National Institute of Health Stroke Scale (NIHSS). In addition, stroke outcome after 2 months from admission was assessed for each patient using the modified Barthel Index.

Statistical analysis

IBM SPSS statistics (version 22.0, 2013; USA) was used for data analysis. Data were expressed as median and percentiles for quantitative nonparametric measures. The ranked Spearman correlation test was used to study the possible association between two variables for nonparametric data. The probability of error at 0.05 was considered significant, whereas at 0.01 and 0.001 it was considered highly significant.


  Results Top


Fifty-six patients diagnosed with acute ischemic stroke were studied [26 female (46%) and 30 male (54%) patients]. Their ages ranged from 45 to 94 years with a median value of 63.5 years. The presence of past history of DM in each patient was assessed. Positive past history of DM was found in 32 stroke patients (57%), whereas 24 patients (43%) were free of diabetic history. CT scan of the brain was used to measure the size of infarction. HbA1c was measured as indicator for the state of glycemic control in the last 3 months before onset of stroke. NIHSS score was calculated for each patient within the first 72 h from onset of symptoms, and functional outcome after 2 months was assessed using the modified Barthel Index. The range, median value, and the 25th and the 75th percentiles for each parameter are presented in [Table 1].
Table 1 Descriptive data of the whole sample


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On studying the possible association between the value of HbA1c and the infarction size, there was a significant positive correlation between HbA1c value and size of infarction among all cases (r = 0.489, P < 0.001); the same relation was present between HbA1c value and NIHSS score (r = 0.385, P < 0.003). In contrast, there was a significant negative association between HbA1c value and modified Barthel Index score (r = −0.350, P < 0.001) ([Figure 1], [Figure 2], [Figure 3]).
Figure 1 Correlation between HbA1c and size of infarction (P < 0.05). HbA1c, glycosylated hemoglobin

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Figure 2 Correlation between HbA1c and National Institute of Health score (NIHSS) (P < 0.05). HbA1c, glycosylated hemoglobin

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Figure 3 Correlation between HbA1c and Barthel Index score (P < 0.05). HbA1c, glycosylated hemoglobin

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As regards age, serum cholesterol, HDL, LDL, and serum triglycerides, there was no significant correlation between any of them and the infarction size. In addition, no significant correlation was found with either NIHSS or modified Barthel Index scores.


  Discussion Top


Hyperglycemia in relation to acute ischemic stroke is common both in patients with and in patients without a diagnosis of DM. It has been suggested to worsen survival. However, recent results from several clinical studies indicate that, in particular, patients with stroke and stress hyperglycemia, but not diabetes, have increased mortality [4],[5],[6] . In contrast, earlier studies found that patients with acute ischemic stroke and similar glucose concentrations had similar outcome regardless of whether or not they had diabetes [7] .

In this study, the role of HbA1c was systematically evaluated with respect to severity and outcome after ischemic stroke regardless of whether or not patients had DM. Thus, the effect of stress hyperglycemia is eliminated. In this work, we found a strong relationship between prestroke glycemic control and neurological outcome. HbA1c was a good independent predictor of stroke severity in the whole study group, not only in patients with DM. Our results demonstrate that poor prestroke glycemic control is an independent determinant of stroke severity; moreover, it is a robust marker of neurological functional outcome. These results are supported by the effect of HbA1c value on the infarction size.

Results from three newly published studies [1],[8],[9] also show that high HbA1c is independently associated with poor outcome 1 year after stroke, supporting our findings. Nevertheless, one of the studies, based on data from the Fukuoka Stroke Registry [9] , only included patients with known DM; moreover, only one of these studies investigated the effect of HbA1c on acute stroke severity [1] .

In the previous study, stress hyperglycemia was related to increased mortality, but it lost its predictive value when the analysis was adjusted for prestroke glycemic control. Moreover, stress hyperglycemia was not correlated with stroke severity in an independent manner. In addition, it did not influence the functional outcome 1 year after stroke [1] . These findings support the importance of the use of HbA1c indicating the state of prestroke glycemic control over glucose tolerance curve as prognostic marker of stroke severity and outcome.

The exact mechanism by which poor prestroke glycemic control affects survival of stroke patients is less clear. General complications related to poorly controlled DM could be one explanation. An increased HbA1c level reflects poor long-term glycemic control and has specific implications for the structure and function of the vascular bed, including small and large cerebral vessels. Increased HbA1c level might also be a marker of poor compliance, indicating an unhealthy lifestyle.

In contrast, Murros and colleagues found that prestroke blood glucose level, unlike poststroke blood glucose level, did not have any predictive value concerning stroke outcome. In this study, the case fatality rate, severity of hemiparesis, functional outcome, and infarct size did not differ according to the state of prestroke glycemic control, but fasting blood glucose level of the nondiabetic patients was correlated strongly with the severity of hemiparesis and predicted stroke outcome. Therefore, it was concluded that high fasting blood glucose values after stroke reflect a stress response to a more severe ischemic brain lesion [10] .

This is in agreement with some relatively recent randomized controlled trials [11],[12],[13] , which have found that intensive glycemic control could not reduce cerebrovascular risk in diabetic patients, but it is important to highlight that all these studies used a cutoff HbA1c higher than 6.4%. Therefore, additional studies are needed to elucidate whether intensified prestroke glycemic control may improve clinical course and outcome in patients with acute ischemic stroke.

One of the limitations of this study is that it did not distinguish between different types of ischemic stroke and so the results of this study cannot be specified. It is well-known that certain types of ischemic stroke are more related to the diabetic history. Another limitation is related to the lack of data on the duration of diabetes and serial measurements of the HbA1c during the follow-up period.


  Conclusion Top


Measurement of HbA1c in every ischemic stroke patient is very important even if the patient is not known to be diabetic because the prestroke glycemic control is a predictor of stroke severity and outcome.

Acknowledgements

The author gratefully acknowledges several colleagues and technicians in the laboratory of King Abdulaziz Hospital, Mecca, Saudi Arabia, for their help and technical support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Hjalmarsson C, Manhem K, Bokemark L, Andersson B. The role of prestroke glycemic control on severity and outcome of acute ischemic stroke. Stroke Res Treat 2014; 2014 :694569.  Back to cited text no. 1
    
2.
John WG. Use of HbA1c in the diagnosis of diabetes. Diabetic Med 2012; 29 :1350-1357.  Back to cited text no. 2
    
3.
Wu D, Xu H, Wang Y. Association of subclinical diabetic peripheral neuropathy with glycosylated hemoglobin and the course of disease. J Bengbu Med Col 2012; 8 :53-55.  Back to cited text no. 3
    
4.
Shimoyama T, Kimura K, Uemura J, Saji N, Shibazaki K. Elevated glucose level adversely affects infarct volume growth and neurological deterioration in non-diabetic stroke patients, but not diabetic stroke patients. Eur J Neurol 2014; 21 :402-410.  Back to cited text no. 4
    
5.
Nardi K, Milia P, Eusebi P, Paciaroni M, Caso V, Agnelli G. Predictive value of admission blood glucose level on short-term mortality in acute cerebral ischemia. J Diabetes Complications 2012; 26 :70-76.  Back to cited text no. 5
    
6.
Hu GC, Hsieh SF, Chen YM, Hsu H, Hu Y, Chien K. Relationship of initial glucose level and all-cause death in patients with ischemic stroke: the roles of diabetes mellitus and glycosylated hemoglobin level. Eur J Neurol 2012; 19 :884-891.  Back to cited text no. 6
    
7.
Woo J, Lam CW, Kay R, Wong AH, Teoh R, Nicholls MG. The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke. Arch Neurol 1990; 47 :1174-1177.  Back to cited text no. 7
    
8.
Wu S, Wang C, Jia Q, Liu G, Hoff K, Wang X, et al. HbA1c is associated with increased all-cause mortality in the first year after acute ischemic stroke. Neurol Res 2014; 36 :444-452.  Back to cited text no. 8
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9.
Kuwashiro T, Sugimori H, Ago T, Kuroda J, Kamouchi M, Kitazono T. The impact of predisposing factors on long-term outcome after stroke in diabetic patients: the Fukuoka Stroke Registry. Eur J Neurol 2013; 20 :921-927.  Back to cited text no. 9
    
10.
Murros K, Fogelholm R, Kettunen S, Vuorela AL, Valve J. Blood glucose, glycosylated haemoglobin, and outcome of ischemic brain infarction. J Neurol Sci 1992; 111 :59-64.  Back to cited text no. 10
    
11.
Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009; 360 :129-139.  Back to cited text no. 11
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12.
Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, et al. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358 :2545-2559.  Back to cited text no. 12
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13.
Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358 :2560-2572.  Back to cited text no. 13
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