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      <p>

        <strong>When using this resource, please cite: </strong>

        <br><span>Novak, V., &amp; Mendez, L. (2020). Cerebral Vasoregulation in Diabetes (version 1.0.0). <i>PhysioNet</i>. <a href="https://doi.org/10.13026/m40k-4758">https://doi.org/10.13026/m40k-4758</a>.</span>

      </p>

<h2 id="abstract">Abstract</h2>

<p><span><span><span>This observational study evaluated the effects of type 2 diabetes on cerebral vasoregulation and functional outcomes, measured by blood flow responses to hypocapnia and hypercapnia, Valsalva maneuver, head-up tilt, and sit-to-stand test. This dataset contains 37 diabetic participants and 49 controls (aged &nbsp;55 to 75 years) with continuous measurements of cerebral blood flow using transcranial Doppler and MRI, heart rate, blood pressure, and respiratory parameters, balance, walking, laboratory and retinopathy measures. </span></span></span></p>

<hr>

<h2 id="background">Background</h2>

<p><span><span><span><span>DM is known to be associated with the development of autonomic neuropathy with orthostatic hypotension (OH). Clinical symptoms of OH (dizziness and cognitive decline) suggest cerebral hypoperfusion.</span></span></span></span></p>

<p><span><span><span><span>Our long-term goal was to assess whether diabetes affects the cerebrovascular response to orthostatic hypotension (OH) in older adults. Specifically, this proposal evaluated the effects of diabetic autonomic neuropathy with OH on cerebral vasoregulation using transcranial Doppler ultrasound and magnetic resonance imaging (MRI) at 3 Tesla.</span></span></span></span></p>

<hr>

<h2 id="methods">Methods</h2>

<p><span><span><span>The&nbsp;<strong>GE-71_Protocol.pdf&nbsp;</strong>file contains a write-up of the full experimental protocol.</span></span></span></p>

<p><span><span><span><strong>Day 1-Screening:</strong> Subjects were asked to sign informed consent. Medical history, MRI questionnaire and pre-tests (vital signs, anthropometric measurements, transcranial Doppler (TCD) window, autonomic test and blood draw) were performed. Ophthalmologic examination (level of diabetic retinopathy) was done at Beetham Eye Institute. Eye exam evaluating the level of retinopathy were processed (see Summary table).</span></span></span></p>

<p><u>Links to the PhysioNet directory:</u></p>

<ul>

    <li><span><span><span><span>Data/Labview/Converted/Head-up-tilt-day1</span></span></span></span></li>

    <li><span><span><span><span>Data_description/GE-71_Data_Summary_table.csv</span></span></span></span></li>

</ul>

<p><span><span><span><strong>Day 2</strong></span></span></span></p>

<ul>

    <li><span><span><span><span><strong>Head-up Tilt Test with TCD</strong>: Subjects checked into the SAFE laboratory at BIDMC CRC.&nbsp;<u>Instrumentation for head-up tilt:</u> ECG, blood pressure (BP), TCD of the middle cerebral artery (MCA) and brachial artery (BRA), CO<sub>2</sub>, O<sub>2,</sub> and respiration monitoring. After resting for 10 minutes, a Valsalva maneuver test was performed twice. &nbsp;Then the subject hyperventilated or 3 minutes and breathed a mixture of air with 5% CO<sub>2</sub> (rebreathing test) in a supine position to assess cerebral vasoreactivity and vasomotor range. Then subject was allowed to rest and subsequently, the table was moved to upright positon at 70 degrees for a 5-minute head-up tilt baseline test. After 5 minute rest, the tilt was repeated and the&nbsp;subject repeated 3-minute hyperventilation and followed CO<sub>2</sub> rebreathing test in upright position. </span></span></span></span>&nbsp;</li>

    <li><span><span><span><span><strong>Sit-to-Stand Test:</strong> Instrumentation for sit to stand test: ECG, BP, TCD middle cerebral artery (MCA), brachial artery (BRA) ultrasound, CO<sub>2</sub>, O<sub>2</sub> and respiration monitoring. Sway measurements using a force plate: sway trajectory in mediolateral, anteroposterior, and vertical direction, center of pressure. The patients were then instructed to sit with their leg elevated for 5 minutes and then stood up for 3 minutes with their eyes open. They then sit down again for 5 minutes and stood up for 3 minutes with their eyes closed. &nbsp;Subjects were standing on a force plate that measured postural sway.</span></span></span></span></li>

    <li><span><span><span><span><strong>Walk test:&nbsp; </strong>Subjects were asked to walk at their normal walking speed for 5 minutes.</span></span></span></span></li>

</ul>

<p><span><span><span><u>Links to the Physionet directory:</u></span></span></span></p>

<ul>

    <li><span><span><span><span>Data/Labview/Converted/Head-up-tilt-day2</span></span></span></span></li>

    <li><span><span><span><span>Data/Labview/Converted/Sit-to-stand</span></span></span></span></li>

    <li><span><span><span><span>Data/Pedar</span></span></span></span></li>

    <li><span><span><span><span>Portapress not uploaded</span></span></span></span></li>

</ul>

<p>&nbsp;</p>

<p><span><span><span><strong>Day 3-MRI:</strong> Subjects checked in at the MRI Center and were asked to fill out an MRI safety questionnaire. &nbsp;Vital signs, CO<sub>2</sub> and glucose were measured. The MRI study (T1- and T2-weighted imaging) was done at 3T MRI. A noninvasive MR angiography sequence (CO<sub>2</sub> rebreathing and hyperventilation) was also performed. <span>Processed data in the summary table.</span></span></span></span></p>

<p><span><span><span><u>Links to the PhysioNet directory:</u></span></span></span></p>

<ul>

    <li><span><span><span><span>MRI not uploaded.</span></span></span></span></li>

    <li><span><span><span><span>Data_description/GE-71_Data_Summary_table.csv</span></span></span></span></li>

</ul>

<hr>

<h2 id="description">Data Description</h2>

<p><span><span><span><strong>IRB approval information</strong></span></span></span></p>

<ul>

    <li><span><span><span><span>IRB Protocol #: 2003P000013</span></span></span></span></li>

    <li><span><span><span><span>Principal Investigator: Vera Novak</span></span></span></span></li>

    <li><span><span><span><span>Protocol Title: Cerebral vasoregulation in diabetes</span></span></span></span></li>

    <li><span><span><span><span>Funding: External - American Diabetes Association</span></span></span></span></li>

    <li><span><span><span><span>Review Type: Expedited #8</span></span></span></span></li>

    <li><span><span><span><span>Study Completion Date: 09/13/2019</span></span></span></span></li>

    <li><span><span><span><span>IRB Approval Date: 09/24/2019</span></span></span></span></li>

    <li><span><span><span><span>Notification Date: 09/24/2019</span></span></span></span></li>

</ul>

<p><span><span><span>The following folders are located in the “<strong>Data</strong>” folder. These folders contain open-format files:</span></span></span></p>

<ul>

    <li><span><span><span><span><strong>Labview</strong> – Recordings during baseline head-up tilt test (59 subjects), head-up tilt test with CO2 rebreathing (57 subjects) and sit-to-stand test (31 subjects) were obtained.</span></span></span></span>

    <ul>

        <li><span><span><span><span>Head-up tilt test was performed at 80<sup>O</sup> angle. </span></span></span></span>

        <ul>

            <li><span><span><span><span>The files in the folder&nbsp;<strong>Head-up-tilt_Day1&nbsp;</strong>correspond to the autonomic tests that we did in the screening visit. &nbsp;The protocol consists of a short baseline and a 5-minute head-up tilt. In channel number 1, named as a Marker, we put some markers to identify all the procedures recorded in the test. In the file, <strong>Head-up-tilt_Day1_Marker </strong>will find which specific markers per subject. </span></span></span></span></li>

            <li><span><span><span><span>The files in the folder&nbsp;<strong>Head-up-tilt_Day2&nbsp;</strong>corresponds to the autonomic tests that we did in the visit 2, which took about 25minutes. In channel number 1, named as a Marker, we put some markers to identify all the procedures recorded in the test. In the file, <strong>Head-up-tilt_Day2_Marker will find which specific markers per subject.</strong></span></span></span></span></li>

            <li><span><span><span><span><u>Head-up&nbsp;tilt Day2&nbsp;with CO<sub>2&nbsp;</sub>Rebreathing:</u> The&nbsp;subject was tilted upright to an angle of&nbsp;80<sup>O</sup>&nbsp;angle for&nbsp; 5 minutes, followed by a 5-minute supine rest. CO<sub>2</sub> rebreathing began for 1 minute and then the subject was tilted upright for 5 minutes and CO<sub>2</sub> rebreathing continued in upright position. CO<sub>2</sub> rebreathing may improve orthostatic blood tolerance, cerebral blood flow, and blood pressure. The head-up tilt test was interrupted&nbsp;if symptoms&nbsp;of&nbsp;pre-syncope&nbsp;occur&nbsp;and&nbsp;the patient would be returned to the supine position.</span></span></span></span></li>

        </ul>

        </li>

        <li><span><span><span><span>Sit-To-Stand test was performed for 5 minutes with legs elevated on the chair in front of the subject and asked to stand-up from a sitting position and stand for 3 minutes with eyes open. That procedure was repeated with eyes closed.</span></span></span></span>

        <ul>

            <li><span><span><span><span>The files in the folder <strong>Sit-to-stand </strong>corresponds to the autonomic tests that we did in the visit 2. These files last for 17 minutes. In channel number 1, named as a Marker, we put four (4) markers to identify the procedures recorded in the test as it is described below:</span></span></span></span>

            <ol>

                <li><span><span><span><span>5 minutes of rest</span></span></span></span></li>

                <li><span><span><span><span>3 minutes standing-up with eyes open</span></span></span></span></li>

                <li><span><span><span><span>5 minutes of rest</span></span></span></span></li>

                <li><span><span><span><span>3 minutes standing-up with eyes closed</span></span></span></span></li>

            </ol>

            </li>

        </ul>

        </li>

    </ul>

    </li>

    <li><span><span><span><span><strong>Portapress</strong> – Blood pressure measurements of head-up tilt test (24 subjects).&nbsp;Data were not included in this dataset. </span></span></span></span></li>

    <li><span><span><span><span><strong>Pedar&nbsp;</strong>–&nbsp;Measurements of foot pressure distribution placing 99 sensors on the foot insole (maximum pressure, maximum force, mean pressure, mean force, relative load) calculated and then averaged over the 5 minutes walking at usual speed (26 subjects).</span></span></span></span></li>

    <li><span><span><span><span><strong>Papers</strong>: <span>12 articles published using this dataset.</span></span></span></span></span></li>

</ul>

<p>&nbsp;</p>

<p><span><span><span>The following .csv files are located in the Data Description directory:</span></span></span></p>

<ul>

    <li><span><span><span><span>The <strong>GE-71_Files_and_channels.csv</strong> contains a deep description of the used channels and localization of the data in the Physionet platform.</span></span></span></span></li>

    <li><span><span><span><span>The <strong>GE-71_Data_Dictionary.csv</strong> file enlists all the variables of the study (variable description and units) and provides real values from two participants as examples.</span></span></span></span></li>

    <li><span><span><span><span>The <strong>GE-71_Data_Summary_Table.csv</strong> file contains the complete data summary table, which includes the study variables and values for every subject (demographics, MRI, past medical history, medications, laboratory, eye examination, cognitive and walking test). </span></span></span></span></li>

    <li><span><span><span><span>The&nbsp;<strong>GE-71_Files_per_subject.csv</strong>&nbsp;file enlists open-format data files from the “Data” folder available for each subject.</span></span></span></span></li>

    <li><span><span><span><span>The&nbsp;<strong>GE-71_Head-up-tilt-Day1_Markers_per_subject.csv</strong>&nbsp;file enlists open-format data the markers from the “Head-up-tilt-Day1” folder available for each subject.</span></span></span></span></li>

    <li><span><span><span><span>The&nbsp;<strong>GE-71_Head-up-tilt-Day2_Markers_per_subject.csv</strong>&nbsp;file enlists open-format data the markers from the “Head-up-tilt-Day2” folder available for each subject.</span></span></span></span></li>

</ul>

<hr>

<h2 id="usage-notes">Usage Notes</h2>

<p><span><span><span><span><span>Formats in which the files are provided:</span></span></span></span></span></p>

<ul>

    <li><span><span><span><span><span>Labview files in DAT, and HEA formats</span></span></span></span></span></li>

    <li><span><span><span><span><span>Pedar files in DAT, and HEA formats</span></span></span></span></span></li>

</ul>

<hr>

  <h2 id="acknowledgements">Acknowledgements</h2>

  <p><span><span><span><span>Vera Novak was funded by American Diabetes Association Grant (1-03-CR-23), National Institutes of Health (NIH) Older American Independence Center Grant (2P60 AG08812), NIH Program project AG004390, and General Clinical Research Center (GCRC) Grant (M01-RR01032)&nbsp;supported this study.&nbsp;</span></span></span></span></p>

  <hr>

<h2 id="conflicts-of-interest">Conflicts of Interest</h2>

<p><span><span><span><span>The authors do not have any actual or potential conflicts of interest. Appropriate approval and procedures were used concerning human subjects.&nbsp;</span></span></span></span></p>

<hr>

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    <li>Low PA. Autonomic neuropathy. Semin Neurol 1987;7:49-57</li>

    <li>Low PA, McLeod JG. The autonomic neuropathies. In: Low PA, ed. Clinical Autonomic Disorders: Evaluation and Management. Boston, MA: Little, Brown and Company, 1993:395-421</li>

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    <li>Lepicovska V, Novak P, Hatala R, Kus T, Nadeau R. Time frequency mapping during tilt and syncope. The Canadian Journal of Cardiology 1991;8:82B.Abstract</li>

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