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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Machine Learning⋆</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Matteo Ruggiero</string-name>
          <email>matteoruggiero7@gmail.com</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Luigi Di Biasi</string-name>
          <email>ldibiasi@unisa.it</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Fabiola De Marco</string-name>
          <email>fdemarco@unisa.it</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Alessia Auriemma Citarella</string-name>
          <email>aauriemmacitarella@unisa.it</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Machine Learning</institution>
          ,
          <addr-line>Heart rate, Diabetes, T1DM</addr-line>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>University of Salerno</institution>
          ,
          <addr-line>Fisciano</addr-line>
          ,
          <country country="IT">Italy</country>
        </aff>
      </contrib-group>
      <pub-date>
        <year>2026</year>
      </pub-date>
      <abstract>
        <p>Efective diabetes management is critical for reducing the risk of complications such as cardiovascular disease, nephropathy, and neuropathy while enhancing patient quality of life. Contemporary technologies like continuous glucose monitoring (CGM) and flash glucose monitoring (FGM) have improved clinical outcomes through realtime data and personalized care. However, these devices' high cost and invasive nature limit their accessibility and acceptance, particularly among uninsured or underinsured populations. This study proposes a non-invasive, cost-efective alternative by examining the relationship between heart rate and blood glucose levels in individuals with type 1 diabetes (T1DM). Machine learning techniques were employed to analyze patient data, including regression analysis, k-nearest neighbors (KNN), neural networks, ensemble bagged trees, and statistical methods such as ANOVA and Tukey's test. Results indicated that 96.3% of the cohort exhibited a statistically significant correlation between heart rate and blood glucose levels, with pronounced variations observed at extreme glycemic values. However, the heart rate was less responsive to moderate glucose fluctuations. These findings suggest that heart rate monitoring may serve as a viable non-invasive proxy for detecting significant glycemic events, ofering a promising alternative to traditional blood glucose monitoring systems and potentially mitigating the economic and physical burdens associated with current technologies.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1. Introduction</title>
      <p>https://caislab.di.unisa.it/about/ (M. Ruggiero); https://docenti.unisa.it/029717/home (L. D. Biasi);
CEUR
Workshop</p>
      <p>
        ISSN1613-0073
although less frequent, can provoke dizziness, seizures, cardiac arrhythmias, and even death [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ].
Maintaining glucose control (GC) is crucial to prevent complications like retinopathy, nephropathy, and
neuropathy [
        <xref ref-type="bibr" rid="ref12">12</xref>
        ].
      </p>
      <p>
        Several glycemic control methods are available. Hemoglobin A1C Testing (H1T) measures average
glucose over 90 days but lacks real-time feedback [
        <xref ref-type="bibr" rid="ref14">14</xref>
        ]. Urine testing ofers semiquantitative glucose
estimates from single voidings or 24-hour collections [
        <xref ref-type="bibr" rid="ref15">15</xref>
        ]. Self-monitoring of blood glucose (SMBG)
and Continuous Glucose Monitoring Systems (CGMs) enable real-time tracking and data sharing
[
        <xref ref-type="bibr" rid="ref16">16</xref>
        ]. SMBG, involving frequent finger pricks, correlates with improved HbA1c levels [
        <xref ref-type="bibr" rid="ref17 ref18">17, 18</xref>
        ]. CGMs,
using electromagnetic or ISF-based sensing, provide continuous glucose data, ofering superior daily
monitoring compared to SMBG [
        <xref ref-type="bibr" rid="ref19 ref20">19, 20</xref>
        ]. However, BGC can feel invasive [21]. Frequent testing disrupts
routines and may cause anxiety [22]. SMBG may cause pain, while CGMs can lead to skin irritation
and privacy concerns [23, 24].
      </p>
      <p>This work investigates noninvasive alternatives, relying on the hypothesis (WH1): “Changes in
ECG (Electrocardiogram) patterns are a proxy for glucose level or danger.” Preliminary results [25, 26]
support WH1. Higher glucose levels correlate with reduced heart rate variability (HRV) [26], and
distinct HR distributions appear before hypoglycemia episodes [25]. Together, these findings suggest
that heartbeat patterns reflect blood glucose trends.</p>
      <p>Given the noninvasive nature of ECG wearables, heartbeat-based blood glucose monitoring (BCM)
could improve patient comfort over traditional BGC. This study aims to answer two questions: “Is it
possible to detect and discriminate between hypoglycemia or hyperglycemia events using ECG time
series? – RQ1”; “Is it possible to detect modification in a heartbeat and estimate HR trends using glucose
monitoring data time-series? – RQ2”.</p>
    </sec>
    <sec id="sec-2">
      <title>2. Related works</title>
      <p>This section discusses studies on the relationship between glycemic values and heart rate patterns. In
[29], the authors examined the relationship between glycemic states (hypoglycemia, hyperglycemia, and
normoglycemia) and ECG-derived features. They found a significant increase in heart rate when blood
glucose drops below 60 mg/dL (hypoglycemia), with a p-value &lt; 0.0001, but no significant correlation
with hyperglycemia. In [30], a study of 148 type 1 diabetes patients revealed that higher HbA1c levels
(reflecting higher blood glucose) were associated with increased heart rate, supported by a p-value &lt;
0.004. The study in [31] used data from 31 patients to predict hypoglycemia with machine learning
models using smartwatch and CGM data. The model correlated increased heart rate, reduced heart rate
variability, and heightened electrodermal activity with hypoglycemia, achieving an ROC AUC of 0.76 ±
0.07. In [32], data from 128 type 2 diabetes patients showed that higher age and blood glucose were
positively correlated. Increased parasympathetic activity also correlated with higher blood glucose
levels, suggesting that changes in blood glucose may proportionally afect heart rate.</p>
    </sec>
    <sec id="sec-3">
      <title>3. Background</title>
      <p>For experimentation, we used various pre-processing and statistical techniques.</p>
      <p>A sliding window approach processed sequential data, with a moving mean calculated in each window
to smooth fluctuations, reveal trends, and improve stability. ANOVA assessed diferences between
group means by partitioning variance. A high F-statistic and p-value&lt;0.05 indicate significant group
diferences. In order to identify specific groups, Tukey’s HSD test was applied post-ANOVA, comparing
all possible group pairs and controlling error rates. A p-value&lt;0.05 denotes statistical significance. For
predictive modeling, using distance metrics like Euclidean or Manhattan, K-Nearest Neighbors (KNN)
estimated new instances based on the majority label or mean of K closest neighbors. Weighted K-Nearest
Neighbors (WKNN) improved accuracy by giving closer neighbors greater weight via inverse distance.
Finally, Ensemble-Bagging Trees (EBT) reduced variance by aggregating decision tree outputs trained
on bootstrapped data subsets. While increasing computational cost, EBT yielded more generalized
models. Hyperparameter tuning for EBT followed the same process as KNN.</p>
    </sec>
    <sec id="sec-4">
      <title>4. Methods</title>
      <p>This section outlines the methodologies employed to address the research questions of this study. We
utilized a combination of statistical tests and experimental procedures (machine learning) to investigate
the relationship between heart rate and glycemia in patients with T1DM. We are aware that we
empirically estimated the parameters for sliding window size, time intervals for moving averages,
and thresholds for min/max. While these selections yielded strong initial results, future work will
focus on systematically optimizing these parameters to enhance performance further. In addition,
a comprehensive sensitivity analysis will be undertaken to evaluate the robustness of the proposed
approach against variations in parameter values and to ensure stability and generalizability across
diferent operating conditions.</p>
      <sec id="sec-4-1">
        <title>4.1. Dataset and Preprocessing</title>
        <p>This contribution uses a pre-processed version of the HUPA-UCM Diabetes Dataset [27] extended by
computing new features from glucose levels and heart rates. The original dataset comprises blood
glucose levels, steps, calories, heart rate, and sleep data of 24 T1DM patients, sampled every five minutes,
collected by the authors through CGM and Fitbit Ionic smartwatch, and contains up to 144085 rows.
HUPA-UCM Diabetes Dataset contains only patients with type 1 diabetes mellitus, and no additional
diseases are directly specified. It is important to consider patients 23 and 24, who have more glycemic
readings than the remaining patients.</p>
        <p>We extended HUPA-UCM by computing moving metrics, statistical features, and labels, as described
below. We categorized blood glucose levels (BGL) to compare heart rate (HR) across glycemic groups.
Each patient’s data was labeled based on BGL: very low (&lt;60 mg/dL), low (60–89 mg/dL), good (90–179
mg/dL), high (180–249 mg/dL), and very high (&gt;250 mg/dL). Moving averages of HR and BGL were
computed using sliding windows to smooth fluctuations and capture trends. Maximum and minimum
BGL values were calculated within each 10-observation window. Additional features included moving
averages (11-observation centered and 5-observation shifted) and frequency counts for values above or
below 1.15% and 1.25% of the max and min values in each window.</p>
        <p>We calculated the heart mean (HM) as the average HR over six consecutive observations. The Heart
Trend (HT) was then computed as the deviation of the HR sum from the previous HM, with negative HT
indicating an increasing HR trend (labeled ”U”) and non-negative HT indicating a stable or decreasing
trend (labeled ”D”).</p>
      </sec>
      <sec id="sec-4-2">
        <title>4.2. Heart rate trend prediction</title>
        <p>We split the entire EDATA by Patient to predict Patient-specific heart rate trends, generating 24
subdataset (PSD).</p>
        <p>Also, for each PSD, we generated two subsets of PSD, holding out 10% of the entire dataset for
the test set, to evaluate the model’s performance on unseen data. During model training, a 20-fold
cross-validation was also requested. We completed the training process individually for each patient to
identify the most accurate models.</p>
        <p>For each PSD, we used the features reported in Table 1 as prediction features and heart rate trend as
the prediction class.</p>
      </sec>
      <sec id="sec-4-3">
        <title>4.3. Statistical Analysis</title>
        <p>The ANOVA was used to test whether there was a statistically significant diference in heart rate as a
function of diferent glycaemic levels in patients with DM: it was used to test for significant diferences
Glucose Rate Moving Average (column_glucose_rate_moving)</p>
        <p>A moving average centered on 11 observations for blood glucose levels (BGL).</p>
        <p>Heart Rate Moving Average (heart_rate_moving_avg)</p>
        <p>A moving average centered on 11 observations for heart rate (HR).
(glucose_rate_left_avg)</p>
        <p>A left-shifted moving average calculated over five observations for blood glucose levels (BGL).
(heart_rate_left_avg)</p>
        <p>A left-shifted moving average calculated over five observations for heart rate (HR).</p>
        <p>Description
Blood glucose levels of the patient.</p>
        <p>The caloric intake associated with the patient.</p>
        <p>The maximum blood glucose level within a sliding window.</p>
        <p>The frequency of glucose values above 1.15% of the maximum value within a sliding window.</p>
        <p>The frequency of glucose values above 1.25% of the maximum value within a sliding window.</p>
        <p>The minimum blood glucose level within a sliding window.</p>
        <p>The frequency of glucose values below 1.15% of the minimum value within a sliding window.</p>
        <p>The frequency of glucose values below 1.25% of the minimum value within a sliding window.</p>
        <p>Glucose Rate Left Shifted Average
Heart Rate Left Shifted Average
Max in Window (max_in_window)
Frequency Above Threshold 1.15 (count_above_max_1.15)
Frequency Above Threshold 1.25 (count_above_max_1.25)
Min in Window (min_in_window)
Frequency Below Threshold 1.15 (count_below_min_1.15)</p>
        <p>Frequency Below Threshold 1.25 (count_below_min_1.25)
Calories</p>
        <p>Performance metrics of the model during testing
between the heart rate averages in the various blood glucose groups defined above. In our case, p-value
&lt; 0.05 is considered the threshold for determining significance, suggesting that the variability in heart
rate between glycemic groups is not due to chance.</p>
        <p>In this T1DM scenario, if the p-value is less than 0.05, there is a significant diference in heart rate
between at least two of the glycemic groups. Therefore, the blood glucose level could significantly
impact heart rate, warranting further analysis. Also, a high F value indicates that the group variation is
much greater than the internal variation, suggesting significant diferences.</p>
        <p>The ANOVA Test does not allow for a precise understanding of the efect of blood glucose categories
(glucose_label) on heart rate, so Tukey’s posthoc test was applied. Tukey’s test was applied to all
patients who showed a p-value &lt; 0.05 after the ANOVA Test to identify which blood glucose groups
show significant diferences in heart rate.</p>
      </sec>
    </sec>
    <sec id="sec-5">
      <title>5. Results and Discussion</title>
      <p>Tables 2 and 3 summarize each patient’s validation and testing accuracies. Ensemble Bagged Trees
emerged as the top performer in 20 out of 24 patients, while Weighted K-Nearest Neighbors led in the
remaining four. Across patients, validation accuracy ranged from 60.4 % to 81.3 %, with a similar spread
in test performance. This variability underscores that, although ECG-based predictors can capture
glycemic trends, their reliability is patient-dependent.</p>
      <p>ANOVA outcomes (Table 4) reveal that 23 of 24 patients (95.8 %) exhibited significant diferences
between heart rate distributions across glycemic categories ( &lt; 0.05 ). Patient 22 was the lone exception
( ≥ 0.05 ;  = 1.74 ), indicating no clear heart rate stratification by glycemic state and suggesting that,
in some individuals, ECG features may lack sensitivity to glucose shifts. The high  -values observed in
the other patients confirm pronounced efect sizes, particularly when contrasting extreme glycemic
bands.</p>
      <p>Post hoc Tukey comparisons (Table 4) further clarify these efects. The largest mean diferences
occurred between “Very Low” and “Very High” glycemic states (MaD), with confidence intervals
excluding zero—evidence of robust heart rate modulation at glycemic extremes. In contrast, adjacent
labels such as “Good” versus “High” rarely reached statistical significance, implying that mid-range
glucose changes induce subtler cardiovascular responses that may fall below the detection threshold of
consumer-grade wearables.</p>
      <p>Our findings align with prior work showing that ECG-derived metrics can flag hypo- and
hyperglycemia, but add nuance by quantifying patient-level variability. Narasimhan et al. (2023) reported
population-average heart rate increases of 5–7 bpm during hypoglycemic episodes, yet noted
intersubject standard deviations exceeding 3 bpm—which mirrors our observed 20 % spread in model accuracy.
Likewise, González et al. (2021) highlighted the need for personalized calibration to reach clinical-grade
sensitivity, a recommendation reinforced by our patient-specific performance gaps.</p>
      <p>Clinically, these results suggest two pathways forward. First, the consistent accuracy of Ensemble
Bagged Trees in most patients indicates that tree-based ensembles can robustly capture non-linear
ECG–glycemia relationships, making them strong candidates for embedded algorithms in wearable
platforms. Second, the pronounced failure in certain individuals (e.g., Patient 22) and the modest
performance on mid-range glucose shifts underscore the necessity of integrating complementary
signals—such as photoplethysmography, activity level, or stress markers—to boost sensitivity and
reduce false negatives in critical glycemic ranges.</p>
      <p>However, consumer wearables—used here for heart rate capture—can sufer from motion artifacts
and variable signal fidelity, particularly during exercise or when there is poor sensor contact. Our
moving-average smoothing mitigated some noise, but real-world deployment will demand adaptive
ifltering and on-device quality checks. Furthermore, the five-minute sampling interval may miss rapid
glycemic excursions; integrating continuous or higher-frequency monitoring could unveil transient
ECG patterns predictive of imminent hypo- or hyperglycemia.</p>
      <p>Lastly, beyond model optimization, patient engagement and data privacy are pivotal. Personalized
model training requires substantial amounts of labeled data, which can be burdensome for users.
Federated learning approaches could reconcile the need for individualized calibration with privacy
preservation, as has been trialed successfully in diabetes glucose prediction (Li et al., 2024). Future
studies should therefore not only refine algorithmic approaches but also develop scalable pipelines for
secure data collection, model updating, and clinical validation in diverse T1DM cohorts.</p>
    </sec>
    <sec id="sec-6">
      <title>6. Conclusion</title>
      <p>With the advent of modern FGM and CGM sensors, glycemic control in T1DM patients has become
faster and more accurate. However, these technologies can be perceived as invasive and sufer from
limited user acceptance. This study investigated whether non-invasive ECG tracking via consumer
smart devices could serve as a viable alternative by exploring the relationship between blood glucose
levels (BGL) and heart rate (HR). Two research questions were formulated (Section 1: Introduction) to
examine both the existence of a statistical link and the feasibility of predictive modeling.</p>
      <p>To address RQ1, we applied ANOVA and Tukey’s post-hoc tests to data from 24 T1DM patients.
ANOVA revealed that 23 of 24 patients exhibited significant HR diferences across glycemic categories
(p&lt;0.05), with the most pronounced efects observed when comparing extreme glycemic states. Tukey’s
tests localized these diferences, confirming that HR variability tracks BGL fluctuations in a statistically
robust manner. Collectively, these findings provide strong evidence of a positive correlation between
BGL and HR in T1DM.</p>
      <p>RQ2 was explored through supervised machine learning models (KNN, WKNN, and Ensemble Bagged
Trees), which exploit features such as glycemic rate of change, threshold counts, and caloric intake.
The Heart Trend (HT) parameter successfully classified HR shifts as rising (’U’) or stable/decreasing
(’D’), demonstrating that HR dynamics inferred from BGL trends can be predicted with moderate to
high accuracy. Ensemble Bagged Trees achieved the best performance in most patients, highlighting
the utility of non-linear ensemble methods for capturing complex ECG–glycemia relationships.</p>
      <p>Our results underscore the potential of integrating ECG-based monitoring into routine diabetes
management. Together, statistical analysis, machine learning and wearable devices could provide
continuous, non-invasive alerts for impending hypo- or hyperglycemic events, reducing finger-prick
frequency and improving patient comfort.</p>
    </sec>
    <sec id="sec-7">
      <title>7. Limitations and Future Work</title>
      <p>Although the examination of the relationship between heart rate patterns and glycemic states yields
promising results for non-invasive glucose monitoring in patients with T1DM, several limitations should
be considered when interpreting the findings and applying the methodology in clinical practice.</p>
      <p>First, our cohort consisted of only 24 T1DM patients, without non-diabetic controls, which limited
external validity. Also, this study focuses exclusively on patients with T1DM and cannot be generalized
T2DM, which accounts for approximately 90–95% of all diabetes cases and involves diferent
pathophysiological mechanisms that may afect the heart rate–glucose relationship. Moreover, the lack of control
subjects without diabetes limits the ability to isolate diabetes-specific efects on cardiac dynamics.</p>
      <p>Second, the five‐minute sampling interval and reliance on consumer‐grade wearables introduce
temporal gaps and measurement noise that may obscure rapid glycemic excursions or subtle heart
rate variability. Third, model parameters—such as sliding window size, moving‐average intervals, and
classification thresholds—were tuned empirically; the absence of a formal sensitivity analysis raises
concerns about robustness across diferent populations and operating conditions. Fourth, potential
confounders (sleep quality, BMI, physical activity, emotional stress, medication) were recorded but not
integrated into the predictive framework, limiting insight into multifactorial influences on HR–BGL
dynamics.</p>
      <p>To address these issues, future studies should:
• Use bigger cohorts (including healthy controls) and balance glycemic reading distributions.
• Increase sampling frequency or fuse multi‐sensor data (e.g., continuous ECG, PPG, accelerometry)
to capture transient events.
• Perform systematic parameter optimization (e.g., grid search, genetic algorithms[33], wavelet
transforms) and comprehensive sensitivity analyses.
• Develop personalized and privacy‐preserving modeling strategies—such as patient‐specific
models, transfer learning (Digital Twins), or federated learning—to accommodate inter‐individual
variability.
• Incorporate additional physiological and behavioral variables (sleep metrics, BMI[34], stress
markers, medication timing) and apply explainability methods (LIME, SHAP) to ensure clinical
interpretability.</p>
      <p>• Develop a multimodal system that can analyze extra data, like electrodermal activity (EDA).
These eforts will be crucial in translating ECG-based approaches into reliable, non-invasive tools for
diabetes management.</p>
      <p>Despite these limitations, this research aims to establish a preliminary foundation for non-invasive
ECG-based glucose monitoring approaches.</p>
    </sec>
    <sec id="sec-8">
      <title>8. Acknowledgments</title>
      <p>D3 4 Health – Digital Driven Diagnostics, Prognostics and Therapeutics for Sustainable Health Care
(Project PNC0000001 – CUP: B53C22006090001), funded by the European Union – NextGenerationEU
under the National Plan for Complementary Investments to the NRRP.</p>
    </sec>
    <sec id="sec-9">
      <title>Declaration on Generative AI</title>
      <p>During the preparation of this work, the author(s) used Grammarly to check grammar and spelling.
After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full
responsibility for the publication’s content.
[21] J. Wu, Y. Liu, H. Yin, M. Guo, A new generation of sensors for non-invasive blood glucose
monitoring, American journal of translational research 15 (2023) 3825.
[22] L. Messer, R. Johnson, K. Driscoll, J. Jones, Best friend or spy: a qualitative meta-synthesis on the
impact of continuous glucose monitoring on life with type 1 diabetes, Diabetic Medicine 35 (2018)
409–418.
[23] J.-P. Le Floch, B. Bauduceau, M. Lévy, H. Mosnier-Pudar, C. Sachon, B. Kakou, Self-Monitoring of
Blood Glucose, Cutaneous Finger Injury, and Sensory Loss in Diabetic Patients, Diabetes Care 31
(2008) e73–e73. URL: https://doi.org/10.2337/dc08-1174. doi:10.2337/dc08-1174.
arXiv:https://diabetesjournals.org/care/article-pdf/31/10/e73/598535/zdc01008000e73.
[24] A. Berg, C. Zachariae, K. Nørgaard, J. Svensson, Skin problems due to treatment with diabetes
technology: A narrative review, Medical Research Archives 11 (2023). URL: https://esmed.org/
MRA/mra/article/view/4747. doi:10.18103/mra.v11i11.4747.
[25] V. Calcaterra, P. Bosoni, L. Sacchi, G. V. Zuccotti, S. Mannarino, R. Bellazzi, C. Larizza, Continuous
glucose and heart rate monitoring in young people with type 1 diabetes: an exploratory study
about perspectives in nocturnal hypoglycemia detection, Metabolites 11 (2020) 5.
[26] J. P. Singh, M. G. Larson, C. J. O’Donnell, P. F. Wilson, H. Tsuji, D. M. Lloyd-Jones, D. Levy,
Association of hyperglycemia with reduced heart rate variability (the framingham heart study), The
American Journal of Cardiology 86 (2000) 309–312. URL: https://www.sciencedirect.com/science/
article/pii/S0002914900009206. doi:https://doi.org/10.1016/S0002-9149(00)00920-6.
[27] Hidalgo, J. Ignacio; Alvarado, Jorge; Botella, Marta; Aramendi, Aranzazu; Velasco, J. Manuel;
Garnica, Oscar (2024), “HUPA-UCM Diabetes Dataset”, Mendeley Data, V1, doi: 10.17632/3hbcscwz44.1
[28] G. B. Drummond, S. L. Vowler, Analysis of variance: variably complex, Advances in Physiology</p>
      <p>Education 36 (2012) 85–88.
[29] Nguyen, Linh Lan and Su, Steven and Nguyen, Hung T., Identification of Hypoglycemia
and Hyperglycemia in Type 1 Diabetic patients using ECG parameters, 2012 Annual
International Conference of the IEEE Engineering in Medicine and Biology Society, 2012, 2716-2719,
doi=10.1109/EMBC.2012.6346525
[30] Michael Y Torchinsky and Ricardo Gomez and Jay Rao and Alfonso Vargas and Donald E Mercante
and Stuart A Chalew, Poor glycemic control is associated with increased diastolic blood pressure
and heart rate in children with Type 1 diabetes, Journal of Diabetes and its Complications, 2004,
220-223, https://doi.org/10.1016/S1056-8727(03)00031-X
[31] Lehmann, Vera and Föll, Simon and Maritsch, Martin and van Weenen, Eva and Kraus, Mathias and
Lagger, Sophie and Odermatt, Katja and Albrecht, Caroline and Fleisch, Elgar and Zueger, Thomas
and Wortmann, Felix and Stettler, Christoph, Noninvasive Hypoglycemia Detection in People With
Diabetes Using Smartwatch Data, Diabetes Care, 2023, 993-997, https://doi.org/10.2337/dc22-2290
[32] Novikov, Roman and Zhukova, Liudmila and Novopashin, Maxim, ossibility to Detect Glycemia
with Heart Rate Variability in Patients with Type 2 Diabetes Mellitus in a Non-Invasive Glycemic
Monitoring System, 2019 Actual Problems of Systems and Software Engineering (APSSE), 2019,
177-181, 10.1109/APSSE47353.2019.00030
[33] Di Biasi, Luigi and De Marco, Fabiola and Auriemma Citarella, Alessia and Barra, Paola and
Piotto Piotto, Stefano and Tortora, Genovefa, Hybrid approach for the design of cnns using genetic
algorithms for melanoma classification, International Conference on Pattern Recognition, 2022,
514-528, 10.1007/978-3-031-37660-3_36
[34] Islam, U., Mehmood, G., Al-Atawi, A., Khan, F., Alwageed, H. &amp; Cascone, L. NeuroHealth guardian:
A novel hybrid approach for precision brain stroke prediction and healthcare analytics. Journal
Of Neuroscience Methods. 409 pp. 110210 (2024),
https://www.sciencedirect.com/science/article/pii/S0165027024001559</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <ref id="ref1">
        <mixed-citation>
          [1]
          <string-name>
            <surname>Katsarou</surname>
            <given-names>A</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Gudbjörnsdottir</surname>
            <given-names>S</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Rawshani</surname>
            <given-names>A</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Dabelea</surname>
            <given-names>D</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bonifacio</surname>
            <given-names>E</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Anderson</surname>
            <given-names>BJ</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Jacobsen</surname>
            <given-names>LM</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Schatz</surname>
            <given-names>DA</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Lernmark</surname>
            <given-names>Å</given-names>
          </string-name>
          .
          <article-title>Type 1 diabetes mellitus</article-title>
          .
          <source>Nat Rev Dis Primers</source>
          .
          <source>2017 Mar</source>
          <volume>30</volume>
          ;3:
          <fpage>17016</fpage>
          . doi:
          <volume>10</volume>
          .1038/nrdp.
          <year>2017</year>
          .16. PMID:
          <volume>28358037</volume>
          .
        </mixed-citation>
      </ref>
      <ref id="ref2">
        <mixed-citation>
          [2]
          <string-name>
            <surname>Roglic</surname>
          </string-name>
          , Gojka.
          <source>WHO Global report on diabetes: A summary</source>
          .
          <source>International Journal of Noncommunicable Diseases</source>
          <volume>1</volume>
          (
          <issue>1</issue>
          ):p
          <fpage>3</fpage>
          -
          <lpage>8</lpage>
          ,
          <string-name>
            <surname>Apr-Jun</surname>
          </string-name>
          <year>2016</year>
          . | DOI: 10.4103/
          <fpage>2468</fpage>
          -
          <lpage>8827</lpage>
          .
          <fpage>184853</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref3">
        <mixed-citation>
          [3]
          <string-name>
            <surname>Ramírez-Guerrero</surname>
            <given-names>G</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Müller-Ortiz</surname>
            <given-names>H</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Pedreros-Rosales</surname>
            <given-names>C</given-names>
          </string-name>
          .
          <article-title>Polyuria in adults. A diagnostic approach based on pathophysiology</article-title>
          .
          <source>Rev Clin Esp (Barc)</source>
          . 2022 May;
          <volume>222</volume>
          (
          <issue>5</issue>
          ):
          <fpage>301</fpage>
          -
          <lpage>308</lpage>
          . doi:
          <volume>10</volume>
          .1016/j.rceng.
          <year>2021</year>
          .
          <volume>03</volume>
          .003.
          <article-title>Epub 2021 Sep 9</article-title>
          . PMID:
          <volume>34509418</volume>
          .
        </mixed-citation>
      </ref>
      <ref id="ref4">
        <mixed-citation>
          [4]
          <string-name>
            <surname>Ramírez-Guerrero</surname>
            <given-names>G</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Müller-Ortiz</surname>
            <given-names>H</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Pedreros-Rosales</surname>
            <given-names>C</given-names>
          </string-name>
          .
          <article-title>Polyuria in adults. A diagnostic approach based on pathophysiology</article-title>
          .
          <source>Rev Clin Esp (Barc)</source>
          . 2022 May;
          <volume>222</volume>
          (
          <issue>5</issue>
          ):
          <fpage>301</fpage>
          -
          <lpage>308</lpage>
          . doi:
          <volume>10</volume>
          .1016/j.rceng.
          <year>2021</year>
          .
          <volume>03</volume>
          .003.
          <article-title>Epub 2021 Sep 9</article-title>
          . PMID:
          <volume>34509418</volume>
          .
        </mixed-citation>
      </ref>
      <ref id="ref5">
        <mixed-citation>
          [5]
          <string-name>
            <surname>Sailer</surname>
            <given-names>C</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Winzeler</surname>
            <given-names>B</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Christ-Crain</surname>
            <given-names>M</given-names>
          </string-name>
          .
          <article-title>Primary polydipsia in the medical and psychiatric patient: characteristics, complications and therapy</article-title>
          .
          <source>Swiss Med Wkly. 2017 Nov</source>
          <volume>1</volume>
          ;
          <fpage>147</fpage>
          :w14514. doi:
          <volume>10</volume>
          .4414/smw.
          <year>2017</year>
          .14514. PMID:
          <volume>29120013</volume>
          .
        </mixed-citation>
      </ref>
      <ref id="ref6">
        <mixed-citation>
          [6]
          <string-name>
            <surname>Dhatariya</surname>
            ,
            <given-names>K.K.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Glaser</surname>
            ,
            <given-names>N.S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Codner</surname>
            ,
            <given-names>E.</given-names>
          </string-name>
          et al.
          <article-title>Diabetic ketoacidosis</article-title>
          .
          <source>Nat Rev Dis Primers</source>
          <volume>6</volume>
          ,
          <issue>40</issue>
          (
          <year>2020</year>
          ). https://doi.org/10.1038/s41572-020-0165-1
        </mixed-citation>
      </ref>
      <ref id="ref7">
        <mixed-citation>
          [7]
          <string-name>
            <surname>Roche</surname>
            <given-names>EF</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Menon</surname>
            <given-names>A</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Gill</surname>
            <given-names>D</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Hoey</surname>
            <given-names>H.</given-names>
          </string-name>
          <article-title>Clinical presentation of type 1 diabetes</article-title>
          .
          <source>Pediatr Diabetes</source>
          .
          <source>2005 Jun;6</source>
          (
          <issue>2</issue>
          ):
          <fpage>75</fpage>
          -
          <lpage>8</lpage>
          . doi:
          <volume>10</volume>
          .1111/j.
          <fpage>1399</fpage>
          -
          <lpage>543X</lpage>
          .
          <year>2005</year>
          .
          <volume>00110</volume>
          .x.
          <source>PMID: 15963033.</source>
        </mixed-citation>
      </ref>
      <ref id="ref8">
        <mixed-citation>
          [8]
          <string-name>
            <given-names>V. M.</given-names>
            <surname>Montori</surname>
          </string-name>
          ,
          <string-name>
            <given-names>B. R.</given-names>
            <surname>Bistrian</surname>
          </string-name>
          ,
          <string-name>
            <surname>M. M. McMahon</surname>
          </string-name>
          , Hyperglycemia in Acutely Ill Patients, JAMA
          <volume>288</volume>
          (
          <year>2002</year>
          )
          <fpage>2167</fpage>
          -
          <lpage>2169</lpage>
          . URL: https: //doi.org/10.1001/jama.288.17.2167. doi:
          <volume>10</volume>
          .1001/jama.288.17.2167. arXiv:https://jamanetwork.com/journals/jama/articlepdf/195453/jct20008.pdf.
        </mixed-citation>
      </ref>
      <ref id="ref9">
        <mixed-citation>
          [9]
          <string-name>
            <given-names>P. E.</given-names>
            <surname>Cryer</surname>
          </string-name>
          ,
          <string-name>
            <given-names>A. M.</given-names>
            <surname>Arbeláez</surname>
          </string-name>
          , Hypoglycemia in diabetes,
          <source>Textbook of diabetes</source>
          (
          <year>2017</year>
          )
          <fpage>513</fpage>
          -
          <lpage>533</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref10">
        <mixed-citation>
          [10]
          <string-name>
            <surname>M. J. Fowler</surname>
          </string-name>
          ,
          <article-title>Microvascular and macrovascular complications of diabetes</article-title>
          ,
          <source>Clinical diabetes 29</source>
          (
          <year>2011</year>
          )
          <fpage>116</fpage>
          -
          <lpage>122</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref11">
        <mixed-citation>
          [11]
          <string-name>
            <surname>Michael</surname>
            <given-names>Brownlee;</given-names>
          </string-name>
          <article-title>The Pathobiology of Diabetic Complications: A Unifying Mechanism</article-title>
          .
          <source>Diabetes 1 June</source>
          <year>2005</year>
          ;
          <volume>54</volume>
          (
          <issue>6</issue>
          ):
          <fpage>1615</fpage>
          -
          <lpage>1625</lpage>
          . https://doi.org/10.2337/diabetes.
          <source>54.6.1615</source>
        </mixed-citation>
      </ref>
      <ref id="ref12">
        <mixed-citation>
          [12]
          <string-name>
            <given-names>M. F.</given-names>
            <surname>Moen</surname>
          </string-name>
          ,
          <string-name>
            <given-names>M.</given-names>
            <surname>Zhan</surname>
          </string-name>
          ,
          <string-name>
            <given-names>L. D.</given-names>
            <surname>Walker</surname>
          </string-name>
          ,
          <string-name>
            <given-names>L. M.</given-names>
            <surname>Einhorn</surname>
          </string-name>
          ,
          <string-name>
            <given-names>S. L.</given-names>
            <surname>Seliger</surname>
          </string-name>
          ,
          <string-name>
            <given-names>J. C.</given-names>
            <surname>Fink</surname>
          </string-name>
          , et al.,
          <article-title>Frequency of hypoglycemia and its significance in chronic kidney disease</article-title>
          ,
          <source>Clinical Journal of the American Society of Nephrology</source>
          <volume>4</volume>
          (
          <year>2009</year>
          )
          <fpage>1121</fpage>
          -
          <lpage>1127</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref13">
        <mixed-citation>
          [13]
          <string-name>
            <given-names>C. A.</given-names>
            <surname>Phillips</surname>
          </string-name>
          ,
          <string-name>
            <surname>M. E. Molitch,</surname>
          </string-name>
          <article-title>The relationship between glucose control and the development and progression of diabetic nephropathy</article-title>
          ,
          <source>Current diabetes reports 2</source>
          (
          <year>2002</year>
          )
          <fpage>523</fpage>
          -
          <lpage>529</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref14">
        <mixed-citation>
          [14]
          <string-name>
            <given-names>E.</given-names>
            <surname>Eyth</surname>
          </string-name>
          ,
          <string-name>
            <given-names>R.</given-names>
            <surname>Naik</surname>
          </string-name>
          , Hemoglobin A1C, StatPearls Publishing,
          <source>Treasure Island (FL)</source>
          ,
          <year>2023</year>
          . URL: http: //europepmc.org/books/NBK549816.
        </mixed-citation>
      </ref>
      <ref id="ref15">
        <mixed-citation>
          [15]
          <string-name>
            <given-names>D. E.</given-names>
            <surname>Goldstein</surname>
          </string-name>
          ,
          <string-name>
            <given-names>R. R.</given-names>
            <surname>Little</surname>
          </string-name>
          ,
          <string-name>
            <given-names>R. A.</given-names>
            <surname>Lorenz</surname>
          </string-name>
          ,
          <string-name>
            <given-names>J. I.</given-names>
            <surname>Malone</surname>
          </string-name>
          ,
          <string-name>
            <given-names>D.</given-names>
            <surname>Nathan</surname>
          </string-name>
          ,
          <string-name>
            <given-names>C. M.</given-names>
            <surname>Peterson</surname>
          </string-name>
          ,
          <string-name>
            <given-names>D. B.</given-names>
            <surname>Sacks</surname>
          </string-name>
          , Tests of glycemia in diabetes,
          <source>Diabetes care 27</source>
          (
          <year>2004</year>
          )
          <fpage>1761</fpage>
          -
          <lpage>1773</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref16">
        <mixed-citation>
          [16]
          <string-name>
            <given-names>S.</given-names>
            <surname>Lembo</surname>
          </string-name>
          ,
          <string-name>
            <given-names>P.</given-names>
            <surname>Barra</surname>
          </string-name>
          ,
          <string-name>
            <given-names>S. R.</given-names>
            <surname>Dash</surname>
          </string-name>
          and
          <string-name>
            <given-names>L.</given-names>
            <surname>Di</surname>
          </string-name>
          <string-name>
            <surname>Biasi</surname>
          </string-name>
          , ”
          <article-title>Challenges and Opportunities of Symbiotic AI in Rare Disease Diagnosis</article-title>
          ,”
          <source>2024 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)</source>
          , Lisbon, Portugal,
          <year>2024</year>
          , pp.
          <fpage>6820</fpage>
          -
          <lpage>6825</lpage>
          , doi: 10.1109/BIBM62325.
          <year>2024</year>
          .
          <volume>10822548</volume>
          . keywords: Training;
          <article-title>Symbiosis;Knowledge engineering;Economics;Ethics;Data security;Collaboration;Psychology;Medical diagnosis;Diseases;Symbiotic AI;rare diseases;diagnosis;predictive analytics;healthcare,</article-title>
        </mixed-citation>
      </ref>
      <ref id="ref17">
        <mixed-citation>
          [17]
          <string-name>
            <given-names>R.</given-names>
            <surname>Ziegler</surname>
          </string-name>
          ,
          <string-name>
            <given-names>B.</given-names>
            <surname>Heidtmann</surname>
          </string-name>
          ,
          <string-name>
            <given-names>D.</given-names>
            <surname>Hilgard</surname>
          </string-name>
          ,
          <string-name>
            <given-names>S.</given-names>
            <surname>Hofer</surname>
          </string-name>
          ,
          <string-name>
            <given-names>J.</given-names>
            <surname>Rosenbauer</surname>
          </string-name>
          ,
          <string-name>
            <given-names>R.</given-names>
            <surname>Holl</surname>
          </string-name>
          ,
          <string-name>
            <surname>DPV-Wiss-Initiative</surname>
          </string-name>
          ,
          <article-title>Frequency of smbg correlates with hba1c and acute complications in children and adolescents with type 1 diabetes</article-title>
          ,
          <source>Pediatric diabetes 12</source>
          (
          <year>2011</year>
          )
          <fpage>11</fpage>
          -
          <lpage>17</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref18">
        <mixed-citation>
          [18]
          <string-name>
            <given-names>S. V.</given-names>
            <surname>Edelman</surname>
          </string-name>
          , Importance of glucose control,
          <source>Medical Clinics of North America</source>
          <volume>82</volume>
          (
          <year>1998</year>
          )
          <fpage>665</fpage>
          -
          <lpage>687</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref19">
        <mixed-citation>
          [19]
          <string-name>
            <given-names>D.</given-names>
            <surname>Olczuk</surname>
          </string-name>
          ,
          <string-name>
            <given-names>R.</given-names>
            <surname>Priefer</surname>
          </string-name>
          ,
          <article-title>A history of continuous glucose monitors (cgms) in self-monitoring of diabetes mellitus</article-title>
          ,
          <source>Diabetes &amp; Metabolic Syndrome: Clinical Research &amp; Reviews</source>
          <volume>12</volume>
          (
          <year>2018</year>
          )
          <fpage>181</fpage>
          -
          <lpage>187</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref20">
        <mixed-citation>
          [20]
          <string-name>
            <given-names>C.</given-names>
            <surname>Choleau</surname>
          </string-name>
          ,
          <string-name>
            <given-names>J.-C.</given-names>
            <surname>Klein</surname>
          </string-name>
          ,
          <string-name>
            <given-names>G.</given-names>
            <surname>Reach</surname>
          </string-name>
          ,
          <string-name>
            <given-names>B.</given-names>
            <surname>Aussedat</surname>
          </string-name>
          ,
          <string-name>
            <given-names>V.</given-names>
            <surname>Demaria-Pesce</surname>
          </string-name>
          , G. Wilson,
          <string-name>
            <given-names>R.</given-names>
            <surname>Giford</surname>
          </string-name>
          , W. Ward,
          <article-title>Calibration of a subcutaneous amperometric glucose sensor: Part 1. efect of measurement uncertainties on the determination of sensor sensitivity and background current</article-title>
          ,
          <source>Biosensors and Bioelectronics</source>
          <volume>17</volume>
          (
          <year>2002</year>
          )
          <fpage>641</fpage>
          -
          <lpage>646</lpage>
          .
        </mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>