Running Head: STROKE DX OF NON-DIABETIC PATIENTS AND HEMOGLOBIN A1C 1

Stroke Diagnosis of Non-Diabetic Patients and Hemoglobin A1C Lab Values

Deanna Elizabeth Cheathem

Dietetic Intern

NFS 780 – Fall 2019

University of Southern Mississippi

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Abstract

Current research suggests that individuals who present to the hospital with stroke like symptoms

are likely to have associated altered hemoglobin A1C (HbA1C) lab values. Due to the increased

risk of occurrence of stroke in patients with diabetes mellitus, connotations of high HbA1C and

stroke activity has been used as a predicting factor. The objective of the current research is to

observe the correlation of altered HbA1C lab values of ≥ 6.5 and diagnoses of stroke or stroke

like symptoms among non-diabetic patients. This observational retrospective study aims to

examine the occurrence of stroke diagnosis outcomes and the association with altered HbA1C

lab values. Additional influential factors such as comorbidities and tobacco use will also be

recorded and analyzed by frequency and percentage values. The sample size will be gathered

from the Singing River Health Systems in the Gulf Coast region of Mississippi. These facilities

currently have a pre-screening process in place for altered HbA1C lab values and this will be

utilized to further select non-diabetic patients who are 18 years of age or older and do not use

oral medication to help manage adequate glucose metabolism. The results of the study have not

yet been gathered, but the implications of this research are needed as past contradictory data

creates an increased need for clarification and definitive correlations between HbA1C lab values

and the prediction of stroke occurrence in patients. If the predicted supposition is exhibited, the

collected research can be beneficial for emergency response facilities across the nation to help

cut costs, time, and improve efficiency of the treatment and diagnosis of strokes based on the

initial lab assessment of HbA1C.

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TABLE OF CONTENTS

Literature Review ………………………………………………………………………………4-6

Study Question and Objectives …………………………………………………………………...7

Methods…………………………………………………………………………………………....7

Study Design ……………………………………………………………………………...8

Subject Selection ………………………………………………………………………….8

Variables and Data Collection…………………………………………………………….9

Statistical Analysis ………………………………………………………………………..9

Discussion ……………………………………………………………………………………….10

Dissemination Plan ……………………………………………………………………...10

References ……………………………………………………………………………………….12

Appendix A ……………………………………………………………………………………...13

Appendix B ……………………………………………………………………………………...14
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Literature Review

Individuals who are diagnosed with diabetes mellitus are at a higher risk of suffering

from a stroke or stroke like episodes. This reoccurring association leads to a general conjecture

that if an individual’s HbA1C is elevated, then there is an increase in risk of a stroke or for stroke

like symptoms. Past research has found an adverse association with functional outcomes and

stroke incidences, while others have been able to identify a positive relationship of higher

HbA1C levels measured on admission as an independent predictor for stroke patients.

Contradictory results continue to be presented, leading to the need of further data collection and

analyzation in order to help clearly define the relationship of altered HbA1C lab values as the

predictor criteria for patients who have had a stroke or stroke like episode.

Atypical glucose results related to inappropriate glucose metabolism has been utilized as

an independent risk factor for acute ischemic stroke activity for patients upon admittance to a

hospital facility. Diabetes mellitus and individuals who are considered to be pre-diabetic have a

known positive correlation of poor glucose metabolism and higher HbA1C lab values (Glao et

al., 2016 & Lei, Wu, Liu, Chen, 2015). Many studies have identified that individuals who have a

history or are currently diagnosed with a form of diabetes mellitus, are more likely to have other

related poor health outcomes, such as a stroke or stroke like episodes. When a stroke is onset

due to a continuous state of hyperglycemia, long-term glycemic measures, such as HbA1C, is a

suitable and more robust tool to use to represent or predict the patient’s associated risks with

inappropriate glucose metabolism. Glao et al. (2016) collected and analyzed data from the stroke

registry at a hospital in Hawaii and classified patients into three groups in accordance to their

glucose metabolism or HbA1C: <5.9, 5.9 to 6.7, and ≤6.7. The collected and analyzed data

exhibited that patients with higher HbA1C or lower glucose metabolism function, had
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significantly higher risks of negative outcomes as compared to patients with more normal

HbA1C lab values. The comparison of the three divided tertiles in this study shows that

admitted patients with a HbA1C value ≥ 6.7 had a modified Rankin scale (mRS) score of ≥ 3.

A mRS score of 3-5 defines a poor outcome or loss of functional independence related to stroke

occurrence (Gao et al., 2016).

The observation of HbA1C lab values and associated poor outcomes can be used to

assume that HbA1C levels may be a determinant or have the potential to predict outcomes for

patients who have had a stroke or a stroke like episode. Congruently, Lei et al. (2015) & Robson

et al. (2016), observed similar results as the categorized third tercile displayed a significant trend

towards greater mortality rates for those with increased HbA1C lab values that were collected

upon admission to the hospital. Robson et al. (2016), observed that patients who experienced a

stroke had a HbA1C lab value that was 0.4% higher than compared to the control group in the

observation of admission blood glucose and functional outcome. Contraindicating results were

evaluated as Wang et al. (2019) found no connotation of altered HbA1C lab values related to the

admitted patients’ stroke activity or diagnosis.

A clear definition of the influence of altered HbA1C lab values and poor outcomes

related to stroke occurrence has yet to be determined. Even so, many credible rationalizations

can be argued to help gain a better understanding as to why individuals with increased HbA1C

lab values experience higher rates of poor outcomes and stroke activity. A constant state of

hyperglycemia may lead to microvascular damage, which indirectly leads to a cascade effect of

lactate accumulation, intracellular acidosis, and an altered chemical imbalance within the brain

that is a delicate microenvironment. This prolonged disruption can develop oxidative stress and
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contribute to elevated coagulation factors, hence, increasing the risk of a blood clot or occlusion

to develop (Galo et al., 2016, Lee et al., 2018, & Wang et al., 2019).

Current acute stroke protocols vary from facility to facility as the lack of evidence

supporting definitive predicting factors have prevented specific qualifications to be used as

standardized forecasting tool. Stroke units are prevalent within the acute care health system, but

a specific lab value has yet to be identified to be used to diagnose stroke activity conclusively.

As seen in Appendix A, Figure A1 exhibits the current stroke evaluation protocol that is utilized

within the Singing River Health Systems in Ocean Springs and Pascagoula, Mississippi.

Therefore, the purpose of the current research is to observe the correlation of altered HbA1C lab

values of ≥ 6.5 and diagnoses of stroke or stroke like symptoms among non-diabetic patients.
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Study Questions and Objectives

Research Question: Are elevated hemoglobin A1C lab values of 6.5 or greater associated with

non-diabetic patients admitted with the diagnosis of a stroke or stroke like symptoms?

Objective 1: To explore the correlation between altered hemoglobin A1C lab values of ≥ 6.5

and diagnoses of stroke or stroke like symptoms among non-diabetic patients.

Objective 2: When controlling for comorbidities, determine the type and frequency of co-

morbidities among non-diabetic patients admitted with stroke or stroke like symptoms with a

hemoglobin A1C of ≥ 6.5.

Objective 3: Assess the association between hemoglobin A1C of ≥ 6.5 and stroke or stroke-

like symptoms among non-diabetic patients when controlling for co-morbidities.

Methods

Study Design

An observational retrospective design will be utilized for this study as this type of design

helps to examine past exposures to suspected factors and the relationship to the outcome being

measured. This study design will assist with yielding true incident rates and provide a

foundation to observe specific associations. Consequently, predictable factors can be

established for the outcome measurement of stroke occurrence and altered HbA1C. For this

study, the patients’ charts and lab values will be observed as well as recording any additional

comorbidities such as cardiovascular conditions and social factors like tobacco use. Collectively,

any additional comorbidities need to be observed so that further connections or possible skewed

results will have an explanation. The data will be gathered and analyzed to evaluate the

correlation of HbA1C lab values and the occurrence of strokes or stroke like symptoms.
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Subject Selection

The subjects will be identified and recruited through the Singing River Health System at

Ocean Springs Hospital in Ocean Springs, Mississippi and Singing River Hospital in Pascagoula,

Mississippi. Any patient that is admitted to these facilities will be screened and the inclusion and

exclusion criteria will be applied for further subject selection. As seen in Appendix B, Figure 1B

exhibits the inclusion and exclusion criteria that will be utilized for selecting eligible patients for

this study. Any patient that is admitted with the suspicion of a stroke or if they had stroke like

symptoms will have their HbA1C lab value assessed per the Singing River Health System Stroke

Protocol. Patients that are ≥ 18 years of age and have a HbA1C of 6.5 or greater will be selected

for observation. Patients that are under 18 years of age, utilize glucose control medications, or if

they have had a previous or current diagnosis of diabetes mellitus will be excluded. Diabetic

patients are to be excluded to help improve the validity and have greater clarification of the

relationship of HbA1C and the relationship to the outcome of stroke activity. Sequentially, all

non-diabetic patients admitted to the Singing River Health System from January 1, 2018 to

December 31, 2018 will be collected. The desired sample size will be approximately 80 patients

in reference to a 95% confidence interval at a 0.05 degree of margin of error.

Variables and Data Collection

The data collection instrument will be observation of variables that be collected by

utilizing the reporting and consult request system that is already in place via EPIC at the Singing

River Health System. Currently, when a patient is admitted to one of the Singing River facilities

a consult for a registered dietitian is requested when a patient is diagnosed with a stroke or stroke

like symptoms with an altered HbA1C. Any patients that have a consult requested, indicating

altered HbA1C, will be screened to assess the qualification of that patient for this data collection.
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Through observation of the medical record, a nominal level of measurement will be

implemented for the variables of diagnosis of stroke or stroke like symptoms, categorization of

HbA1C ≥ 6.5, gender, race, and associated comorbidities. Interval measurements will be used

for the age of the patient through the observation of the medical chart as well. Privacy will be a

fundamental part of the structure of this future research as all medical chart observations will

have the patients’ names and medical identity numbers redacted.

Statistical Analysis

Data that is collected will be analyzed through various forms of descriptive and

inferential statistics to assess the correlations of the evaluated variables to the outcome of stroke

incidences being measured. Categorization of diagnosis of stroke or stroke like symptoms and

HbA1C will be assessed by frequency and percentage. Associated comorbidities will be

observed and the frequency of the most reoccurring ailments will be analyzed through

percentages in relation to the occurrence of stroke diagnoses. Gender and race will also be

measured through frequency, while the age of the observed patients will be assessed through

mean and standard deviation.

Inferential statistics will be analyzed through the contingency coefficient method for the

association of stroke diagnoses and altered HbA1C lab values as this is a coefficient that helps to

determine whether two variables are independent or dependent of each other. Coexisting

comorbidities that are observed through frequency of occurrence will be further analyzed

through correlation and linear regression to help identify any patterns of disease states and

occurrences of strokes or stroke like symptoms. Collectively, the analyzation of the observed

and collected data will help portray a more clear and definitive cause and effect relationship of

altered glucose metabolism as a predicting factor of a stroke diagnosis.

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Discussion

Dissemination Plan

Typical acute stroke care protocol begins with identifying signs and symptoms of stroke

like activity and to activate an emergency response via emergency medical service (EMS) action.

The EMS assessments and actions include basic emergency medical care and a pre-hospital

stroke assessment to help establish the timeframe of the onset of symptoms. The time that the

EMS takes to transport the patient to the hospital often varies, but the national average, however,

is about 7-10 minutes. Upon arrival to the emergency department (ED) an immediate neurologic

assessment is conducted by reviewing the patient’s medical history, assessing the timing of the

onset of symptoms, and utilizing a NIH Stroke Scale measurement tool. This assessment

typically takes about 25 minutes to complete. At this point, the patient is taken for a CT scan to

look for any signs of hemorrhaging and this stage of stroke protocol takes about 45 minutes. The

CT scan is analyzed and if the results indicate stroke activity, the patient is admitted to the stroke

unit and treated with the stroke pathway established by that facility.

Having a better understanding of the predicting capabilities of HbA1C and the outcome

of stroke activity can help to reduce the time spent testing and assessing the patient to determine

the proper treatment protocol. The results of this research may help to support a more definitive

stance of using altered HbA1C lab values for stroke diagnosis and help begin initial stroke

treatment actions more quickly in the ED of hospital facilities. Reducing this time will not only

help save lives, but it may also help to prevent additional complications while trying to care for

the patient. The data collected and analyzed may be beneficial for emergency departments to

understand so that they can implement a better predicting lab test during their immediate

neurologic assessment by the stroke team when the patient is admitted to the ED. The results can
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be rushed and come back quicker than the CT scan and result readings. This cut back on time

will help costs, efficiency, and overall health outcomes for patients admitted for a stroke or

stroke like episode.

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References

Gao, Y., Jiang, L., Wang, H., Yu, C., Wang, W., Liu, S., … Wu, J. (2016). Association between

Elevated Hemoglobin A1c Levels and the Outcomes of Patients with Small-Artery

Occlusion: A Hospital-Based Study. PLOS ONE, 11(8), e0160223.

https://doi.org/10.1371/journal.pone.0160223

Lee, K.-J., Lee, J. S., & Jung, K.-H. (2018). Interactive effect of acute and chronic glycemic

indexes for severity in acute ischemic stroke patients. BMC Neurology, 18(1), 105.

https://doi.org/10.1186/s12883-018-1109-1

Lei, C., Wu, B., Liu, M., & Chen, Y. (2015). Association between hemoglobin A1C levels and

clinical outcome in ischemic stroke patients with or without diabetes. Journal of Clinical

Neuroscience, 22(3), 498–503. https://doi.org/10.1016/j.jocn.2014.08.030

Robson, R., Lacey, A. S., Luzio, S. D., Van Woerden, H., Heaven, M. L., Wani, M., … Hewitt,

J. (2016). HbA 1c measurement and relationship to incident stroke. Diabetic Medicine,

33(4), 459–462. https://doi.org/10.1111/dme.13057

Wang, H., Cheng, Y., Chen, S.,Wang, Li, X., Zhu, Z., & Zhang, W. (2019). Impact of Elevated

Hemoglobin A1c Levels on Functional Outcome in Patients with Acute Ischemic Stroke.

Journal of Stroke and Cerebrovascular Diseases, 28(2), 470–476.

https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.10.026
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Appendix A

Figure A1. Decision Flow Chart of Admitted Patients and Dietary Consult for Altered HbA1C
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Appendix B

Figure B1. Inclusion & Exclusion Criteria