<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "http://dtd.nlm.nih.gov/publishing/2.0/journalpublishing.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" article-type="review-article" dtd-version="2.0">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JD</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Diabetes</journal-id>
      <journal-title>JMIR Diabetes</journal-title>
      <issn pub-type="epub">2371-4379</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v6i1e20270</article-id>
      <article-id pub-id-type="pmid">33724201</article-id>
      <article-id pub-id-type="doi">10.2196/20270</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Review</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Telemetric Interventions Offer New Opportunities for Managing Type 1 Diabetes Mellitus: Systematic Meta-review</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Richardson</surname>
            <given-names>Caroline</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>van der Velde</surname>
            <given-names>Enno</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Burner</surname>
            <given-names>Elizabeth</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Eberle</surname>
            <given-names>Claudia</given-names>
          </name>
          <degrees>MD, Prof Dr</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <address>
            <institution>Medicine with Specialization in Internal Medicine and General Medicine</institution>
            <institution>Hochschule Fulda - University of Applied Sciences</institution>
            <addr-line>Leipziger Strasse 123</addr-line>
            <addr-line>Fulda, 36037</addr-line>
            <country>Germany</country>
            <phone>49 661 9640 ext 6328</phone>
            <email>claudia.eberle@hs-fulda.de</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-7878-2020</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Stichling</surname>
            <given-names>Stefanie</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-1017-1976</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Medicine with Specialization in Internal Medicine and General Medicine</institution>
        <institution>Hochschule Fulda - University of Applied Sciences</institution>
        <addr-line>Fulda</addr-line>
        <country>Germany</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Claudia Eberle <email>claudia.eberle@hs-fulda.de</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <season>Jan-Mar</season>
        <year>2021</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>16</day>
        <month>3</month>
        <year>2021</year>
      </pub-date>
      <volume>6</volume>
      <issue>1</issue>
      <elocation-id>e20270</elocation-id>
      <history>
        <date date-type="received">
          <day>19</day>
          <month>5</month>
          <year>2020</year>
        </date>
        <date date-type="rev-request">
          <day>29</day>
          <month>6</month>
          <year>2020</year>
        </date>
        <date date-type="rev-recd">
          <day>20</day>
          <month>7</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>16</day>
          <month>2</month>
          <year>2021</year>
        </date>
      </history>
      <copyright-statement>©Claudia Eberle, Stefanie Stichling. Originally published in JMIR Diabetes (http://diabetes.jmir.org), 16.03.2021.</copyright-statement>
      <copyright-year>2021</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Diabetes, is properly cited. The complete bibliographic information, a link to the original publication on http://diabetes.jmir.org/, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://diabetes.jmir.org/2021/1/e20270" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>The prevalence of diabetes mellitus (DM) is increasing rapidly worldwide. Simultaneously, technological advances are offering new opportunities for better management of type 1 diabetes mellitus (T1DM). Telemetry, the remote acquisition of patient data via a telecommunication system, is a promising field of application in eHealth and is rapidly gaining importance.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>The aim of this study was to summarize the current evidences available on the effectiveness of telemetric approaches in T1DM management. This systematic meta-review examined different types of interventions of the technologies used in communication between health care professionals and patients as well as the key outcomes.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>We performed a systematic search in Web of Science Core Collection, EMBASE, Cochrane Library, MEDLINE via PubMed, and CINAHL databases in April 2020 with regard to the effectiveness of telemetric interventions for T1DM. We classified the interventions into 4 categories according to the technology used: (1) real-time video communication, (2) real-time audio communication, (3) asynchronous communication, and (4) combined forms of communication (real-time and asynchronous). We considered various study designs such as systematic reviews, clinical trials, meta-analyses, and randomized controlled trials and focused on the key outcomes. Additionally, a funnel plot based on hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) values and different quality assessments were performed.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>We identified 17 (6 high quality and 9 moderate quality) eligible publications: randomized controlled trials (n=9), systematic reviews and meta-analyses (n=5), cohort studies (n=2), and qualitative publications (n=1). Of 12 studies, 8 (67%) indicated a (significant or nonsignificant) reduction in HbA<sub>1c</sub> levels; 65% (11/17) of the studies reported overall (mildly) positive effects of telemetric interventions by addressing all the measured outcomes. Asynchronous interventions were the most successful for patients diagnosed with T1DM, but no technology was clearly superior. However, there were many nonsignificant results and not sustained effects, and in some studies, the control group benefited from telemetric support or increased frequency of contacts.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>Based on the currently available literature, this systematic meta-review shows that telemetric interventions cause significant reduction in HbA<sub>1c</sub> levels and result in overall positive effects in T1DM management. However, more specified effects of telemetric approaches in T1DM management should be analyzed in detail in larger cohorts.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>type 1 diabetes</kwd>
        <kwd>telemetry</kwd>
        <kwd>telemedicine</kwd>
        <kwd>telemonitoring</kwd>
        <kwd>digital health</kwd>
        <kwd>eHealth</kwd>
        <kwd>diabetes management</kwd>
        <kwd>systematic meta-review</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <p>The historical origins of digital health date back to the 1970s, when telematics, the science of telecommunications and informatics, emerged [<xref ref-type="bibr" rid="ref1">1</xref>]. Telemedicine developed as a technology-supported physician-patient relationship in the 1970s/80s as a subarea of telematics. In the 1990s, the emergence of the internet resulted in new communication channels and the development of eHealth [<xref ref-type="bibr" rid="ref1">1</xref>]. Mobile health, which was developed as a subarea of eHealth in 2010, is referred by the World Health Organization as “medical and public health practice supported by mobile devices such as mobile phones, patient monitoring devices, personal digital assistants, and other wireless devices” [<xref ref-type="bibr" rid="ref2">2</xref>]. Nowadays, digital health defines the intersection of digital transformations with health, life, and communities [<xref ref-type="bibr" rid="ref3">3</xref>].</p>
      <p>Telemedicine is a digital field of application and part of eHealth and digitalization in the health care sector [<xref ref-type="bibr" rid="ref4">4</xref>]. The exchange between different user groups (eg, physician, patient, service provider) takes place in these apps [<xref ref-type="bibr" rid="ref5">5</xref>]. When integrating users in the area of eHealth, and thus in telemedicine, a distinction is made between different forms of communication structures. This review focuses on the communication structure of “physician to patient,” which defines the communication between physicians (or health care professionals) and patients [<xref ref-type="bibr" rid="ref5">5</xref>]. Telemetry has the advantage that no physical presence is necessary [<xref ref-type="bibr" rid="ref6">6</xref>]. Telemetry is characterized by the American Telemedicine Association as “remote acquisition, recording, and transmission of patient data via a telecommunications system to a health care professional for analysis and decision making” [<xref ref-type="bibr" rid="ref6">6</xref>]. In telemetric interventions, patients upload data (eg, dietary habits and glucose levels) and health care professionals review these data and offer feedback (eg, regarding medication and lifestyle) [<xref ref-type="bibr" rid="ref6">6</xref>,<xref ref-type="bibr" rid="ref7">7</xref>]. In this regard, telementoring describes the use of telecommunications (eg, audio or video) and electronic information processing technologies to provide those customized instructions [<xref ref-type="bibr" rid="ref6">6</xref>].</p>
      <p>This systematic meta-review focuses on telemetry by using the example of patients diagnosed with type 1 diabetes mellitus (T1DM). DM is one of the most prevalent chronic diseases worldwide [<xref ref-type="bibr" rid="ref8">8</xref>]. Globally, approximately 463 million adults (age range 20-79 years) are diagnosed with DM [<xref ref-type="bibr" rid="ref8">8</xref>]. T1DM accounts for 5%-10% of all DM forms and can arise at any age; however, it is frequently reported in kids and young adults [<xref ref-type="bibr" rid="ref8">8</xref>]. The prevalence of T1DM has been increasing in the past decades. Globally, about 1.1 million children and adolescents (age range 0-19 years) are diagnosed with T1DM [<xref ref-type="bibr" rid="ref8">8</xref>]. From a pathophysiological and a clinical view, T1DM is a very complex disease, which is dependent on beta-cell demolition by the T cells of the immune system, resulting in the total lack of insulin [<xref ref-type="bibr" rid="ref9">9</xref>]. Comorbidities such as microvascular (eg, nephropathy, retinopathy, and neuropathy) and macrovascular (eg, cardiovascular disease, stroke) complications are closely and frequently related to DM [<xref ref-type="bibr" rid="ref9">9</xref>]. Optimal glycemic control is <italic>the</italic> therapy goal to reduce and prevent such diabetic complications and comorbidities. Intensive therapeutic measures address the delay of onset of diabetic complications as well as comorbidities in T1DM [<xref ref-type="bibr" rid="ref10">10</xref>]. Therefore, technological advances in diabetes therapy may provide powerful novel solutions for a better and more closed-meshed disease management [<xref ref-type="bibr" rid="ref11">11</xref>]. Several studies have examined the capability of telemetry in the treatment of DM [<xref ref-type="bibr" rid="ref12">12</xref>-<xref ref-type="bibr" rid="ref14">14</xref>]. The use of technological apps may be an attractive option for T1DM management. Previous studies have shown feasibility and satisfaction by using telemedicine [<xref ref-type="bibr" rid="ref13">13</xref>,<xref ref-type="bibr" rid="ref14">14</xref>]. However, the evidence for the impact of telemetric interventions in the context of diabetes therapy and the potential of these interventions should be examined further. Therefore, this systematic meta-review intended to assess the current evidence for the effectiveness of telemetric interventions in the management of T1DM. Not only randomized controlled trials (RCTs), as it is often the case in the literature, but also various study designs, including clinical trials, systematic reviews, and meta-analyses, were considered.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Search Strategy</title>
        <p>We performed a systematic search in Web of Science Core Collection, EMBASE, Cochrane Library, MEDLINE via PubMed, and CINAHL databases in April 2020. The systematic meta-review was carried out based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [<xref ref-type="bibr" rid="ref15">15</xref>]. Peer-reviewed full-text publications assessing the effectiveness of telemetric interventions in patients with T1DM, published from 2008 to April 2020, were included. We selected keywords from the medical subject headings and EMBASE subject headings databases and used title/abstract terms. The following Boolean logic was applied: (Diabetes Mellitus) AND (Telemetry OR Telemonitoring OR Telemedicine). No restrictions for geographical locations were placed. Initially, we carried out an extensive literature search with a strategy that covered different types of DM (T1DM, type 2 DM [T2DM], and gestational DM). During the process, T1DM studies were selected for this systematic meta-review. We additionally carried out manual researches of the references of the included examinations to recognize other reasonable publications. All search terms for the individual databases are provided in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>.</p>
      </sec>
      <sec>
        <title>Inclusion Criteria</title>
        <p>We included publications written in English and German with the target group patients diagnosed with T1DM. These publications addressed interventions in the field of telemetry, telemedicine, and telemonitoring for their diabetes therapy. The intervention involved direct interaction between the patients and health care professionals, that is, feedback from health care professionals based on the transmitted patient data. We included the following study designs: systematic reviews, meta-analyses, clinical trials, and RCTs.</p>
      </sec>
      <sec>
        <title>Exclusion Criteria</title>
        <p>Since this systematic meta-review focused on T1DM, we excluded participants diagnosed with other forms of DM (such as T2DM, gestational DM, and other types of diabetes) as well as mixed collectives, meaning that studies included not only patients with T1DM but also people diagnosed with other types of DM. Moreover, we excluded individual studies that were already included in the identified systematic reviews and meta-analyses; therefore, no data from systematic reviews/meta-analyses and individual studies are pooled, leading to a possible bias. Abstracts, posters, comments, letters, study protocols, notes, and proceedings papers were excluded. In addition, publications that focused on the description of the technology were rejected. Telemetry is a wide term and may cover different technologies. Since the way of communication between patients and health care professionals is different compared to that in telemetric interventions, we analyzed interventions with mobile apps in other studies separately. We also eliminated studies providing only pooled data (ie, with patients of other diseases and with digital apps other than telemetry). Furthermore, duplicates and studies that addressed prevention or diagnosis of DM were rejected. The literature search is documented in the PRISMA flowchart (<xref rid="figure1" ref-type="fig">Figure 1</xref>). As <xref rid="figure1" ref-type="fig">Figure 1</xref> shows, we selected T1DM studies from our extensive literature search.</p>
        <fig id="figure1" position="float">
          <label>Figure 1</label>
          <caption>
            <p>PRISMA flowchart of the procedure for the search and selection of suitable publications (adapted from Moher et al [<xref ref-type="bibr" rid="ref15">15</xref>]). GDM: gestational diabetes mellitus; T1DM: type 1 diabetes mellitus, T2DM: type 2 diabetes mellitus.</p>
          </caption>
          <graphic xlink:href="diabetes_v6i1e20270_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Data Extraction</title>
        <p>We extracted the year of publication, study designs, durations, intervention and control groups, outcome measures, sample sizes, country, statistical significances, and conclusions. Intervention and control group data included the technologies used, feedback methods, the frequency of contact, and data transmission. The significance involved the comparison of the intervention group with the control group (intergroup) and the comparison within the intervention group, that is, from the baseline to the end of the study (intragroup), depending on what was reported. In relation to the systematic reviews and meta-analyses, the <italic>overall</italic> effects were extracted (overall positive effect, no effect, or inconclusive results). The quality of life (QoL) was divided into diabetes-related quality of life (DRQoL) as well as health-related quality of life (HRQoL).</p>
      </sec>
      <sec>
        <title>Data Synthesis and Analysis</title>
        <p>A qualitative analysis was conducted. The selected studies differed regarding sample, design, and measures. A proper meta-analysis was therefore not possible. For analysis, the studies were classified into different categories based on a scheme that we developed. First, the publications were systematized into 4 categories according to the technologies used to communicate between the health care professionals and the patients (<xref ref-type="boxed-text" rid="box1">Textbox 1</xref>).</p>
        <boxed-text id="box1" position="float">
          <title>Categories for the classification of the different intervention types.</title>
          <p>
            <bold>Different intervention types</bold>
          </p>
          <list list-type="bullet">
            <list-item>
              <p>Real-time communication video: Synchronous face-to-face communication by videoconferencing and videoconsulting.</p>
            </list-item>
            <list-item>
              <p>Real-time communication audio: Synchronous communication by telephone calls (telephone coaching and counselling).</p>
            </list-item>
            <list-item>
              <p>Asynchronous communication: Asynchronous communication by email, SMS text messaging, internet/web-based platforms, server, home gateway, or post.</p>
            </list-item>
            <list-item>
              <p>Combined forms of communication: The intervention involves real-time and asynchronous communication.</p>
            </list-item>
          </list>
        </boxed-text>
        <p>Due to the heterogeneity, systematic reviews and meta-analyses were not assigned to these categories. Second, the studies were differentiated according to their designs. Third, these were structured based on key outcomes: hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>), body weight, blood pressure, QoL, cost-effectiveness, and time saved (<xref rid="figure2" ref-type="fig">Figure 2</xref>).</p>
        <fig id="figure2" position="float">
          <label>Figure 2</label>
          <caption>
            <p>Scheme for structuring the included studies. BP: blood pressure; HbA<sub>1c</sub>: hemoglobin A<sub>1c</sub>; DRQoL: diabetes-related quality of life; HRQoL: health-related quality of life; MA: meta-analysis; SR: systematic review; RCT: randomized controlled trial.</p>
          </caption>
          <graphic xlink:href="diabetes_v6i1e20270_fig2.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Assessment of Risk of Bias</title>
        <p>A quality assessment of the studies was conducted to determine the risk of bias. Since we included different study designs, we applied 3 different quality appraisal tools. First, we applied A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2), a validated and widely used tool for the evaluation of systematic reviews and meta-analyses. AMSTAR 2 rates the study quality as high, moderate, low, or critically low. Second, we used Effective Public Health Practice Project (EPHPP), a validated instrument that addresses studies on health-related topics. Since this tool is suitable for quantitative intervention studies, we used it for RCTs and cohort studies. EPHPP consists of the following components: selection bias, study design, confounders, blinding, data collection methods, and withdrawals and drop-outs. The instrument rates the study quality as strong, moderate, or weak. Third, we applied the validated National Institute for Health and Care Excellence (NICE) quality appraisal checklist for qualitative studies. The NICE checklist includes the following components: theoretical approach, study design, data collection, trustworthiness, analysis, and ethics. This tool rates the study quality as ++ (high), + (moderate), or – (low). In addition, the publication bias was assessed visually as a funnel plot by using HbA<sub>1c</sub> values. The studies were extremely heterogeneous. Without systematic reviews, meta-analyses, and cohort studies (ie, without control group) and excluding a study that compared 2 telemetric applications, we generated a funnel plot based on 6 RCTs. Intervention effect was expressed as the mean difference using HbA<sub>1c</sub> values at the end of the study.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Study Characteristics</title>
        <p>The database search resulted in 1647 records. After removing duplicates, 1116 publications were screened for eligibility. We excluded 875 of these records based on titles/abstracts for the reasons given in <xref rid="figure1" ref-type="fig">Figure 1</xref>. After reviewing 241 full-text publications and an additional research of reference lists, a total of 189 studies were identified (T1DM, n=23; T2DM, n=99; gestational DM, n=11; and both T1DM/T2DM, n=51). We excluded 6 individual studies [<xref ref-type="bibr" rid="ref16">16</xref>-<xref ref-type="bibr" rid="ref21">21</xref>] that were already involved in the systematic reviews/meta-analyses. Finally, 17 publications were included in this synthesis. <xref ref-type="supplementary-material" rid="app2">Multimedia Appendix 2</xref> provides a detailed summary of each publication selected for inclusion in this systematic meta-review, including all measured outcomes. <xref ref-type="table" rid="table1">Table 1</xref> shows the features of the included studies. Most studies (with exception of systematic reviews and meta-analyses due to their heterogeneity) were performed in Europe (n=6), followed by in the United States (n=3), Asia (n=1), and Russia (n=1), along with not specified (n=1). We categorized the studies by the type of intervention: real-time communication via video (n=3), asynchronous communication (n=4), and combined forms of communication (n=4). One qualitative study did not explain the intervention in detail. No real-time audio interventions were identified. Most studies were RCTs (n=9), systematic reviews and meta-analyses (n=5), as well as cohort studies (n=2), and qualitative publications (n=1). A presentation of all the intervention effects (significant and nonsignificant) on the key outcomes is provided in <xref ref-type="supplementary-material" rid="app3">Multimedia Appendix 3</xref>. Two systematic reviews and meta-analyses were assessed as high-quality studies, whereas 2 were rated as moderate and 1 as critically low quality. Of the real-time video interventions, 3 were high-quality studies. Furthermore, 4 asynchronous interventions were rated as moderate quality. Of the combined interventions, 1 was rated as high, 2 as moderate, and 1 as weak-quality study. In addition, the qualitative publication was of moderate quality. The detailed quality appraisals are presented in <xref ref-type="supplementary-material" rid="app4">Multimedia Appendix 4</xref>.</p>
        <table-wrap position="float" id="table1">
          <label>Table 1</label>
          <caption>
            <p>Baseline characteristics of all the included publications.</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="30"/>
            <col width="30"/>
            <col width="740"/>
            <col width="0"/>
            <col width="200"/>
            <thead>
              <tr valign="top">
                <td colspan="4">Characteristics of the publications</td>
                <td>Values, n (%)</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td colspan="5">
                  <bold>Study design (n=17)</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="3">Systematic reviews and meta-analyses (total)</td>
                <td>5 (29)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="3">Randomized controlled trial (total)<sup>a</sup></td>
                <td>9 (53)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="3">Cohort (total)<sup>b</sup></td>
                <td>2 (12)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="3">Qualitative (total)</td>
                <td>1 (6)</td>
              </tr>
              <tr valign="top">
                <td colspan="5">
                  <bold>Year of publication (n=17)</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="3">2008-2011</td>
                <td>2 (12)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="3">2012-2014</td>
                <td>4 (24)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="3">2015-2017</td>
                <td>5 (29)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="3">2018-2020</td>
                <td>6 (35)</td>
              </tr>
              <tr valign="top">
                <td colspan="5">
                  <bold>Excluding systematic reviews and meta-analyses (n=12)</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="4">
                  <bold>Location</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>
                  <break/>
                </td>
                <td>United States</td>
                <td colspan="2">3 (25)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>
                  <break/>
                </td>
                <td>Europe</td>
                <td colspan="2">6 (50)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>
                  <break/>
                </td>
                <td>Asia</td>
                <td colspan="2">1 (8)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>
                  <break/>
                </td>
                <td>Russia</td>
                <td colspan="2">1 (8)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>
                  <break/>
                </td>
                <td>Not specified</td>
                <td colspan="2">1 (8)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td colspan="4">
                  <bold>Intervention type</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>
                  <break/>
                </td>
                <td>Real-time video</td>
                <td colspan="2">3 (25)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>
                  <break/>
                </td>
                <td>Asynchronous</td>
                <td colspan="2">4 (33)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>
                  <break/>
                </td>
                <td>Combined forms</td>
                <td colspan="2">4 (33)</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>
                  <break/>
                </td>
                <td>Not specified</td>
                <td colspan="2">1 (8)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table1fn1">
              <p><sup>a</sup>This included 1 pilot randomized controlled trial.</p>
            </fn>
            <fn id="table1fn2">
              <p><sup>b</sup>This included 1 pilot cohort study.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>HRQoL and DRQoL were evaluated using very different methods. Validated instruments were used to measure these outcomes, for example, 36-item Short Form Health Survey, Diabetes Quality of Life questionnaire, PedsQLTM 3.0 Diabetes Module questionnaire, 12-item Short Form Health Survey, and European Quality of Life survey. There were also specially designed questionnaires.</p>
      </sec>
      <sec>
        <title>Effectiveness of Telemetry: Key Outcomes</title>
        <p>Of 17 studies, 11 (65%) reported overall (mildly) positive effects of the telemetric interventions in relation to all measured outcomes (<xref ref-type="supplementary-material" rid="app2">Multimedia Appendix 2</xref>). <xref ref-type="table" rid="table2">Table 2</xref> presents the significant effects (intragroup and intergroup) on the key outcomes. Of 12 studies, 8 (67%) indicated a (significant or nonsignificant) reduction (intragroup or intergroup) in HbA<sub>1c</sub> levels in the intervention group. Descriptive examination of the funnel plot by using HbA<sub>1c</sub> values based on 6 RCTs indicated a mild form of asymmetry (<xref ref-type="supplementary-material" rid="app5">Multimedia Appendix 5</xref>).</p>
        <table-wrap position="float" id="table2">
          <label>Table 2</label>
          <caption>
            <p>Impact of the interventions on selected outcomes (intragroup and intergroup) (n=17).<sup>a</sup></p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="180"/>
            <col width="150"/>
            <col width="100"/>
            <col width="90"/>
            <col width="120"/>
            <col width="90"/>
            <col width="70"/>
            <col width="70"/>
            <col width="130"/>
            <thead>
              <tr valign="top">
                <td>Outcomes/  <break/>  
            interventions</td>
                <td>Hemoglobin A<sub>1c</sub></td>
                <td>Blood  <break/>  
            pressure</td>
                <td>Body  <break/>  
            weight</td>
                <td>Diabetes-related quality of life</td>
                <td>Health-related quality of life </td>
                <td>Costs</td>
                <td>Time saved</td>
                <td>Others or not significant</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td>Systematic  <break/>  
            review and meta-analysis</td>
                <td>3</td>
                <td>—<sup>b</sup></td>
                <td>—</td>
                <td>1</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
              </tr>
              <tr valign="top">
                <td>Real-time video<sup>c</sup></td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>✓</td>
              </tr>
              <tr valign="top">
                <td>Asynchronous</td>
                <td>1</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
              </tr>
              <tr valign="top">
                <td>Combined</td>
                <td>1</td>
                <td>—</td>
                <td>—</td>
                <td>1</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
              </tr>
              <tr valign="top">
                <td>Not specified<sup>c</sup></td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>—</td>
                <td>✓</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table2fn1">
              <p><sup>a</sup>All studies that reported significant intervention effects are mentioned in this table, including those effects that were not sustainable. This table does not include studies reporting nonsignificant intervention effects. The values in the tables indicate the number of studies that examined the outcome and these studies showed improvement in that particular outcome.</p>
            </fn>
            <fn id="table2fn2">
              <p><sup>b</sup>Not available.</p>
            </fn>
            <fn id="table2fn3">
              <p><sup>c</sup>Studies in this category did not examine any of the listed outcomes nor report any significant effects.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Systematic Reviews and Meta-Analyses</title>
        <sec>
          <title>HbA<sub>1c</sub> Levels (n=5)</title>
          <p>All 5 systematic reviews and meta-analyses analyzed HbA<sub>1c</sub> levels as the targeted outcome. Three studies (60%) reported overall positive effects in terms of reducing HbA<sub>1c</sub> levels significantly. Lee et al [<xref ref-type="bibr" rid="ref12">12</xref>] (high-quality study) described a mean reduction of 0.18% (95% CI 0.04-0.33, <italic>P</italic>=.01). Peterson [<xref ref-type="bibr" rid="ref22">22</xref>] (critically low-quality study) outlined that 12 studies showed a decline in HbA<sub>1c</sub> levels in their intervention groups. However, Viana et al [<xref ref-type="bibr" rid="ref23">23</xref>] (moderate-quality study) and Shulman et al [<xref ref-type="bibr" rid="ref24">24</xref>] (high-quality study) found no significant decrease in HbA<sub>1c</sub> levels following telemedical interventions (mean deviation –0.124%, 95% CI, –0.268 to 0.020; <italic>P</italic>=.09 [<xref ref-type="bibr" rid="ref25">25</xref>] and mean deviation –0.12, 95% CI, –0.35 to 0.11; <italic>P</italic>&#62;.05 [<xref ref-type="bibr" rid="ref24">24</xref>], respectively).</p>
        </sec>
        <sec>
          <title>Blood Pressure and Body Weight (n=1)</title>
          <p>Lee et al [<xref ref-type="bibr" rid="ref12">12</xref>] (high-quality study) observed no benefits through telemedicine on either blood pressure or body weight.</p>
        </sec>
        <sec>
          <title>DRQoL (n=3) and HRQoL (n=1)</title>
          <p>Three studies examined the DRQoL. Two high-quality studies (67%) found no effects [<xref ref-type="bibr" rid="ref12">12</xref>,<xref ref-type="bibr" rid="ref24">24</xref>] and a moderate-quality review [<xref ref-type="bibr" rid="ref26">26</xref>] that only included 1 suitable study found a significant improvement in DRQoL. In addition, 1 review observed no benefits on generic HRQoL [<xref ref-type="bibr" rid="ref12">12</xref>].</p>
        </sec>
        <sec>
          <title>Cost-Effectiveness (n=1)</title>
          <p>One high-quality study described that the limited data available on the costs of telemedicine suggested no differences between the groups [<xref ref-type="bibr" rid="ref24">24</xref>]. One of the included studies of this review reported that the intervention group omitted the 3-month visit, which saved US $142 [<xref ref-type="bibr" rid="ref24">24</xref>].</p>
        </sec>
      </sec>
      <sec>
        <title>Asynchronous Interventions</title>
        <sec>
          <title>HbA<sub>1c</sub> Levels (n=3)</title>
          <p>A cohort study (moderate quality) reported significantly reduced mean HbA<sub>1c</sub> levels at the end of the assessment phase (<italic>P</italic>=.01) [<xref ref-type="bibr" rid="ref27">27</xref>]. However, another 2 moderate-quality RCTs found no significant differences HbA<sub>1c</sub> values between groups (<italic>P</italic>=.84 [<xref ref-type="bibr" rid="ref28">28</xref>] and <italic>P</italic>=.49 [<xref ref-type="bibr" rid="ref29">29</xref>]). One of these studies [<xref ref-type="bibr" rid="ref28">28</xref>] examined telemedicine in addition to conventional care in the intervention group.</p>
        </sec>
        <sec>
          <title>HRQoL (n=1)</title>
          <p>One moderate-quality RCT observed that changes in HRQoL between the first visit and the final visit did not differ between the groups [<xref ref-type="bibr" rid="ref30">30</xref>].</p>
        </sec>
      </sec>
      <sec>
        <title>Combined Interventions</title>
        <sec>
          <title>HbA<sub>1c</sub> Levels (n=4)</title>
          <p>All 4 RCTs considered the outcome HbA<sub>1c</sub>. Only 1 study (moderate quality) showed significant improvements in the HbA<sub>1c</sub> levels in the patients undergoing interventions (8.7% to 7.7%) compared to the controls (8.7% to 8.4%, <italic>P</italic>&#60;.05) [<xref ref-type="bibr" rid="ref31">31</xref>]. Gandrud et al (weak-quality study) [<xref ref-type="bibr" rid="ref32">32</xref>] and Yaron et al [<xref ref-type="bibr" rid="ref25">25</xref>] (high-quality study) reported positive but no significant differences in the effects on HbA<sub>1c</sub> levels between the telemedicine and usual care groups. In addition, 1 moderate-quality publication mentioned no improvement in HbA<sub>1c</sub> levels, with no statistically significant difference (<italic>P</italic>=.56 for control group, <italic>P</italic>=.45 for telemetry group, and <italic>P</italic>=.60 between groups) [<xref ref-type="bibr" rid="ref33">33</xref>].</p>
        </sec>
        <sec>
          <title>DRQoL (n=2)</title>
          <p>According to an RCT (weak-quality study), a number of QoL indicators increased significantly due to telemetry compared to that in the control group (<italic>P</italic>&#60;.05) [<xref ref-type="bibr" rid="ref31">31</xref>]. However, another moderate-quality RCT showed no significant increase in QoL by 6.5 points and 1.3 points for intervention group and control group (<italic>P</italic>=.06), respectively [<xref ref-type="bibr" rid="ref32">32</xref>].</p>
        </sec>
        <sec>
          <title>Cost-Effectiveness (n=2) and Time Saved (n=1)</title>
          <p>Yaron et al (high-quality study) [<xref ref-type="bibr" rid="ref25">25</xref>] and Bertuzzi et al (moderate-quality study) [<xref ref-type="bibr" rid="ref33">33</xref>] reported a cost reduction through telemedicine (no significance reported). Direct expenses were 24% lesser in the intervention group, while indirect costs diminished by 22% [<xref ref-type="bibr" rid="ref25">25</xref>]. One of these studies also mentioned that patients saved time for each visit (mean 115 [SD 86] min) [<xref ref-type="bibr" rid="ref33">33</xref>].</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <sec>
        <title>Principal Results</title>
        <p>This systematic meta-review highlighted the variety of telemetric interventions and technologies used in diabetes care by focusing on T1DM management. Considering all the study designs, asynchronous interventions were found to be the most successful for people with T1DM in improving the key diabetic outcomes, but no technology was clearly superior. However, the results might be inconsistent in terms of the different key outcomes, but fortunately, an improvement in terms of HbA<sub>1c</sub> values was found. HbA<sub>1c</sub> was by far the most investigated outcome in these studies. Overall, most systematic reviews and meta-analyses (high and moderate quality) showed a significant reduction in HbA<sub>1c</sub> values. The other systematic reviews and meta-analyses also indicated positive effects, but they were not statistically significant. The study of Lee et al [<xref ref-type="bibr" rid="ref12">12</xref>], a high-quality study, achieved a significant and clear reduction of –0.18% (95% CI 0.04-0.33, <italic>P</italic>=.01). Moreover, HbA<sub>1c</sub> levels were improved significantly in most asynchronous interventions. HbA<sub>1c</sub> values clearly decreased when combined interventions (asynchronous and real-time communication) were applied, but 1 moderate-quality study showed significant improvements and 3 more (high, moderate, and weak quality) reported positive but not significant effects. Our findings indicated a trend toward better glycemic control for patients with T1DM by means of telemedicine. This result has potential practical implications. The fact that HbA<sub>1c</sub> levels could be significantly improved in many studies is a promising result in view of the fact that an optimized glycemic control reduces the risk of comorbidities and complications as well as progression of microvascular and macrovascular consequences among patients with T1DM [<xref ref-type="bibr" rid="ref10">10</xref>]. However, there are only few results for the other outcomes to be able to reach firm inferences. Blood pressure and body weights were examined by 1 meta-analysis. Lee et al (high-quality study) noticed that there are only few studies available revealing no obvious benefits [<xref ref-type="bibr" rid="ref12">12</xref>]. Aside from that, 2 systematic reviews and meta-analyses (high and moderate quality) outlined no effects in terms of QoL, but a moderate-quality study demonstrated positive tendencies in improving the QoL. Overall, the studies reported that data availability is limited and further investigations are needed. Besides, DRQoL improved significantly in the “real-time video intervention” with weak quality. The moderate-quality asynchronous intervention showed no differences in HRQoL. However, DRQoL also improved obviously in combined interventions, that is, significantly in a weak-quality study and not significantly in a moderate-quality study. In general, there were only few studies on the cost-effectiveness of telemetric interventions. Costs were significantly reduced through “asynchronous interventions,” which was shown by a high-quality study. This high-quality study also demonstrated significant time saving through the asynchronous intervention. With combined interventions, 2 moderate-quality studies also showed clear cost reductions.</p>
        <p>In our view, telemetry enables close diabetes management and offers the advantage of overcoming the physical presence. Telemetric technologies allow a higher frequency of contacts between patients and health care professionals. Telemetric interventions also increase, in our view, patient compliance, reliance, and empowerment. The patients implement recommendations for action more successfully in everyday life. They are supervised and managed effectively and more closely and may feel more secure in terms of diabetes therapy. Another systematic review and meta-analysis [<xref ref-type="bibr" rid="ref12">12</xref>] that recently examined telemetry for the management of clinical outcomes of T1DM also showed that the evidence regarding body weight and blood pressure is clearly limited. In practice, considering the restricted availability of resources, it is important whether the telemetric interventions are cost-effective and time-saving. Therefore, these outcomes are of major importance and should be considered more often in studies in future. Interestingly and surprisingly, fasting blood glucose values seem to be a neglected outcome in these T1DM studies. Since accurate blood sugar measurements are required to reach euglycemic conditions with appropriate insulin doses [<xref ref-type="bibr" rid="ref9">9</xref>], this outcome is very important.</p>
        <p>The systematic reviews and meta-analyses were heterogeneous since telemetry can cover various interventions and technologies and the authors used different definitions of telemedical approaches. Additionally, the variability of the methods used in the studies made it difficult to reach firm conclusions. Studies often suffered from small sample sizes, poor study designs, lack of controls, or no long-term intervention effects. Some studies had samples of patients with poorly controlled diabetes that led to greater intervention effects. Overall, there were not many significant results both for intergroup and intragroup comparisons.</p>
        <p>Interestingly, the control group was often not a real or pure control group with usual care. The control group often had an increased frequency of contacts with health care professionals (more than 4 times a year), which led to improved outcomes. In some studies, the control group benefited from telemetric support. Moreover, several studies did not adequately define usual care. The intervention effects might be greater if the telemetric group was compared to a pure control group. Besides, the high number of nonsignificant results is particularly noticeable. This could be related to an often low statistical power. It is also concerning that some studies did not publish <italic>P</italic> values. Furthermore, based on the findings, the long-term effects can be questioned. Some studies found significant positive postintervention effects, but they did not last for a long term. Long follow-up periods are therefore important.</p>
        <p>Our review is, as far as we know, the first systematic meta-review on telemedicine in T1DM management. Compared to other papers, this systematic meta-review included different study designs, looked at a variety of outcomes, and carried out a differentiated analysis based on a developed scheme. We also analyzed the findings in detail and differentiated them based on the intergroup or intragroup comparison, significant or not significant effects, and effect sizes. In this way, we were able to contribute to a multifaceted view of the topic.</p>
      </sec>
      <sec>
        <title>Limitations</title>
        <p>Some limitations have to be considered when interpreting and using the results. To the best of our knowledge and the elected inclusion and exclusion criteria, we included all suitable studies. Some of the systematic reviews and meta-analyses reported that the poor quality of the included studies was a weakness. Furthermore, numerous definitions of telemetry and telemedicine include different technologies. For the reasons mentioned above, we decided to exclude smartphone app–based interventions, which may be a limitation. Besides, the definition of usual care was insufficient and heterogeneous across the publications. Some studies did not use a control group in the sense of usual care. It is notable that in some studies, the control group had a similar frequency of contacts as the intervention group. In some studies, the control group received telemetric support. These circumstances influence the results achieved and must be considered. Overall, the studies displayed different characteristics and methods, which lead to heterogeneity and can influence the reliability of the results.</p>
      </sec>
      <sec>
        <title>Comparison With Prior Work</title>
        <p>In a nutshell, other reviews showed similar inconsistent findings. Lee et al [<xref ref-type="bibr" rid="ref12">12</xref>] observed no benefits in the interventions with telemedicine focused on blood pressure, body weight, and QoL in 38 RCTs. The overall value of the included interventions was insufficient for glycemic control and other clinical outcomes among patients with T1DM. Viana et al [<xref ref-type="bibr" rid="ref23">23</xref>] examined telecare interventions to improve patients’ compliance and HbA<sub>1c</sub> values and found no decrease in HbA<sub>1c</sub> levels after telecare (<italic>P</italic>=.09). Another systematic review [<xref ref-type="bibr" rid="ref34">34</xref>] mentioned that 7 of the 14 included publications indicated statistically significant decreases in the observed outcomes, while 79% mentioned success with their telemetric interventions. Baron et al [<xref ref-type="bibr" rid="ref35">35</xref>] investigated the effectiveness of mobile monitoring technologies for HbA<sub>1c</sub> levels in 24 studies and found inconsistent evidence for T1DM.</p>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>This systematic meta-review offered a comprehensive summary of the effectiveness of telemetric interventions in T1DM management and provided insights into the application of telemetric interventions. The evidence for the effectiveness of telemetric approaches in the management of T1DM might be inconsistent. Further studies with a clear and homogeneous methodology are necessary for research and for patients. In addition, we need further research to understand how, why, and when technology can improve the outcomes. Studies should not only focus on HbA<sub>1c</sub> but also address other outcomes, in particular, fasting blood glucose, blood pressure, QoL, cost-effectiveness, and time saved. Additionally, future studies should provide sufficient statistical power. Further research regarding T1DM is required to examine the special needs of this subgroup in more detail and to develop and adapt suitable interventions. The alarming number of findings with nonsignificant <italic>P</italic> values reveals a need for better study planning as well as RCTs with large sample sizes. In conclusion, telemetry might be a promising approach for people diagnosed with T1DM, especially asynchronous interventions, but its potential should be explored further.</p>
      </sec>
    </sec>
  </body>
  <back>
    <app-group>
      <supplementary-material id="app1">
        <label>Multimedia Appendix 1</label>
        <p>Search terms for the databases.</p>
        <media xlink:href="diabetes_v6i1e20270_app1.pdf" xlink:title="PDF File  (Adobe PDF File), 91 KB"/>
      </supplementary-material>
      <supplementary-material id="app2">
        <label>Multimedia Appendix 2</label>
        <p>Detailed summary of each publication selected for inclusion in the systematic meta-review, including all measured outcomes (n=17).</p>
        <media xlink:href="diabetes_v6i1e20270_app2.pdf" xlink:title="PDF File  (Adobe PDF File), 606 KB"/>
      </supplementary-material>
      <supplementary-material id="app3">
        <label>Multimedia Appendix 3</label>
        <p>Detailed presentation of all intervention effects (significant and nonsignificant) on the key outcomes.</p>
        <media xlink:href="diabetes_v6i1e20270_app3.pdf" xlink:title="PDF File  (Adobe PDF File), 446 KB"/>
      </supplementary-material>
      <supplementary-material id="app4">
        <label>Multimedia Appendix 4</label>
        <p>Quality assessment using A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) (n=5 studies).</p>
        <media xlink:href="diabetes_v6i1e20270_app4.pdf" xlink:title="PDF File  (Adobe PDF File), 481 KB"/>
      </supplementary-material>
      <supplementary-material id="app5">
        <label>Multimedia Appendix 5</label>
        <p>Funnel plot assessing publication bias using HbA1c levels (%) at the end of the study.</p>
        <media xlink:href="diabetes_v6i1e20270_app5.pdf" xlink:title="PDF File  (Adobe PDF File), 621 KB"/>
      </supplementary-material>
    </app-group>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">AMSTAR 2</term>
          <def>
            <p>A MeaSurement Tool to Assess systematic Reviews</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">DM</term>
          <def>
            <p>diabetes mellitus</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">DRQoL</term>
          <def>
            <p>diabetes-related quality of life</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">EPHPP</term>
          <def>
            <p>Effective Public Health Practice Project</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">HbA<sub>1c</sub></term>
          <def>
            <p>hemoglobin A<sub>1c</sub></p>
          </def>
        </def-item>
        <def-item>
          <term id="abb6">HRQoL</term>
          <def>
            <p>health-related quality of life</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb7">NICE</term>
          <def>
            <p>National Institute for Health and Care Excellence</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb8">PRISMA</term>
          <def>
            <p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb9">QoL</term>
          <def>
            <p>quality of life</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb10">RCT</term>
          <def>
            <p>randomized controlled trial</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb11">T1DM</term>
          <def>
            <p>type 1 diabetes mellitus</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb12">T2DM</term>
          <def>
            <p>type 2 diabetes mellitus</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <ack>
      <p>This manuscript was created in the context of the project with the number EB 440/4-1 by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). Therefore, we would like to thank the DFG for strongly supporting this research work.</p>
    </ack>
    <fn-group>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
    <ref-list>
      <ref id="ref1">
        <label>1</label>
        <nlm-citation citation-type="book">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Meister</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Becker</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Leppert</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Drop</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <person-group person-group-type="editor">
            <name name-style="western">
              <surname>Pfannstiel</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Da-Cruz</surname>
              <given-names>P</given-names>
            </name>
            <name name-style="western">
              <surname>Mehlich</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
          <article-title>Digital Health, Mobile Health und Co. – Wertschöpfung durch Digitalisierung und Datenverarbeitung</article-title>
          <source>Digitale Transformation von Dienstleistungen im Gesundheitswesen I</source>
          <year>2017</year>
          <publisher-loc>Wiesbaden</publisher-loc>
          <publisher-name>Springer Fachmedien Wiesbaden</publisher-name>
          <fpage>185</fpage>
          <lpage>212</lpage>
        </nlm-citation>
      </ref>
      <ref id="ref2">
        <label>2</label>
        <nlm-citation citation-type="book">
          <person-group person-group-type="author">
            <collab>World Health Organization</collab>
          </person-group>
          <article-title>mHealth: New horizons for health through mobile technologies: Second global survey on eHealth</article-title>
          <source>Global Observatory for eHealth series - Volume 3</source>
          <year>2011</year>
          <publisher-loc>Geneva</publisher-loc>
          <publisher-name>World Health Organization</publisher-name>
        </nlm-citation>
      </ref>
      <ref id="ref3">
        <label>3</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Sonnier</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
          <source>The story of digital health</source>
          <access-date>2021-03-03</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://storyofdigitalhealth.com/">https://storyofdigitalhealth.com/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref4">
        <label>4</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <collab>Bundesministeriums für Wirtschaft und Energie</collab>
          </person-group>
          <article-title>Ökonomische Bestandsaufnahme und Potenzialanalyse der digitalen Gesundheitswirtschaft</article-title>
          <source>Studie im Auftrag des Bundesministeriums für Wirtschaft und Energie (IC4 – 80 14 36/01)</source>
          <year>2016</year>
          <access-date>2021-03-03</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.bmwi.de/Redaktion/DE/Publikationen/Studien/oekonomische-bestandsaufnahme-und-potenzialanalyse-der-digitalen-gesundheitswirtschaft.html">https://www.bmwi.de/Redaktion/DE/Publikationen/Studien/oekonomische-bestandsaufnahme-und-potenzialanalyse-der-digitalen-gesundheitswirtschaft.html</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref5">
        <label>5</label>
        <nlm-citation citation-type="book">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Fischer</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Krämer</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <source>eHealth in Deutschland - Anforderungen und Potenziale innovativer Versorgungsstrukturen</source>
          <year>2016</year>
          <publisher-loc>Berlin Heidelberg</publisher-loc>
          <publisher-name>Springer Vieweg</publisher-name>
        </nlm-citation>
      </ref>
      <ref id="ref6">
        <label>6</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <collab>American Telemedicine Association</collab>
          </person-group>
          <source>Telehealth basics</source>
          <year>2018</year>
          <access-date>2020-05-19</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.americantelemed.org/resource/why-telemedicine/">https://www.americantelemed.org/resource/why-telemedicine/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref7">
        <label>7</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <collab>American Telemedicine Association</collab>
          </person-group>
          <source>What we learned about telemedicine and healthcare AI this year</source>
          <year>2018</year>
          <access-date>2020-05-19</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.americantelemed.org/industry-news/what-we-learned-about-telemedicine-and-healthcare-ai-this-year/">https://www.americantelemed.org/industry-news/what-we-learned-about-telemedicine-and-healthcare-ai-this-year/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref8">
        <label>8</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <collab>International Diabetes Federation</collab>
          </person-group>
          <source>IDF Diabetes Atlas 9th edition</source>
          <year>2019</year>
          <access-date>2021-03-03</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.diabetesatlas.org/en/resources/">https://www.diabetesatlas.org/en/resources/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref9">
        <label>9</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <collab>American Diabetes Association</collab>
          </person-group>
          <article-title>2. Classification and Diagnosis of Diabetes:</article-title>
          <source>Diabetes Care</source>
          <year>2020</year>
          <month>01</month>
          <volume>43</volume>
          <issue>Suppl 1</issue>
          <fpage>S14</fpage>
          <lpage>S31</lpage>
          <pub-id pub-id-type="doi">10.2337/dc20-S002</pub-id>
          <pub-id pub-id-type="medline">31862745</pub-id>
          <pub-id pub-id-type="pii">43/Supplement_1/S14</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref10">
        <label>10</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <collab>Diabetes ControlComplications Trial Research Group</collab>
            <name name-style="western">
              <surname>Nathan</surname>
              <given-names>D M</given-names>
            </name>
            <name name-style="western">
              <surname>Genuth</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Lachin</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Cleary</surname>
              <given-names>P</given-names>
            </name>
            <name name-style="western">
              <surname>Crofford</surname>
              <given-names>O</given-names>
            </name>
            <name name-style="western">
              <surname>Davis</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Rand</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Siebert</surname>
              <given-names>C</given-names>
            </name>
          </person-group>
          <article-title>The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus</article-title>
          <source>N Engl J Med</source>
          <year>1993</year>
          <month>09</month>
          <day>30</day>
          <volume>329</volume>
          <issue>14</issue>
          <fpage>977</fpage>
          <lpage>86</lpage>
          <pub-id pub-id-type="doi">10.1056/NEJM199309303291401</pub-id>
          <pub-id pub-id-type="medline">8366922</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref11">
        <label>11</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Tchero</surname>
              <given-names>H</given-names>
            </name>
            <name name-style="western">
              <surname>Kangambega</surname>
              <given-names>P</given-names>
            </name>
            <name name-style="western">
              <surname>Briatte</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Brunet-Houdard</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Retali</surname>
              <given-names>G</given-names>
            </name>
            <name name-style="western">
              <surname>Rusch</surname>
              <given-names>E</given-names>
            </name>
          </person-group>
          <article-title>Clinical Effectiveness of Telemedicine in Diabetes Mellitus: A Meta-Analysis of 42 Randomized Controlled Trials</article-title>
          <source>Telemed J E Health</source>
          <year>2019</year>
          <month>07</month>
          <volume>25</volume>
          <issue>7</issue>
          <fpage>569</fpage>
          <lpage>583</lpage>
          <pub-id pub-id-type="doi">10.1089/tmj.2018.0128</pub-id>
          <pub-id pub-id-type="medline">30124394</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref12">
        <label>12</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Lee</surname>
              <given-names>SWH</given-names>
            </name>
            <name name-style="western">
              <surname>Ooi</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Lai</surname>
              <given-names>YK</given-names>
            </name>
          </person-group>
          <article-title>Telemedicine for the Management of Glycemic Control and Clinical Outcomes of Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Studies</article-title>
          <source>Front Pharmacol</source>
          <year>2017</year>
          <volume>8</volume>
          <fpage>330</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://doi.org/10.3389/fphar.2017.00330"/>
          </comment>
          <pub-id pub-id-type="doi">10.3389/fphar.2017.00330</pub-id>
          <pub-id pub-id-type="medline">28611672</pub-id>
          <pub-id pub-id-type="pmcid">PMC5447671</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref13">
        <label>13</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Mignerat</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Lapointe</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Vedel</surname>
              <given-names>I</given-names>
            </name>
          </person-group>
          <article-title>Using telecare for diabetic patients: A mixed systematic review</article-title>
          <source>Health Policy and Technology</source>
          <year>2014</year>
          <month>06</month>
          <volume>3</volume>
          <issue>2</issue>
          <fpage>90</fpage>
          <lpage>112</lpage>
          <pub-id pub-id-type="doi">10.1016/j.hlpt.2014.01.004</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref14">
        <label>14</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Verhoeven</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Tanja-Dijkstra</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Nijland</surname>
              <given-names>N</given-names>
            </name>
            <name name-style="western">
              <surname>Eysenbach</surname>
              <given-names>G</given-names>
            </name>
            <name name-style="western">
              <surname>van Gemert-Pijnen</surname>
              <given-names>Lisette</given-names>
            </name>
          </person-group>
          <article-title>Asynchronous and synchronous teleconsultation for diabetes care: a systematic literature review</article-title>
          <source>J Diabetes Sci Technol</source>
          <year>2010</year>
          <month>05</month>
          <day>01</day>
          <volume>4</volume>
          <issue>3</issue>
          <fpage>666</fpage>
          <lpage>84</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/20513335"/>
          </comment>
          <pub-id pub-id-type="doi">10.1177/193229681000400323</pub-id>
          <pub-id pub-id-type="medline">20513335</pub-id>
          <pub-id pub-id-type="pmcid">PMC2901046</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref15">
        <label>15</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Moher</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Liberati</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Tetzlaff</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Altman</surname>
              <given-names>DG</given-names>
            </name>
            <collab>PRISMA Group</collab>
          </person-group>
          <article-title>Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement</article-title>
          <source>PLoS Med</source>
          <year>2009</year>
          <month>07</month>
          <day>21</day>
          <volume>6</volume>
          <issue>7</issue>
          <fpage>e1000097</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://dx.plos.org/10.1371/journal.pmed.1000097"/>
          </comment>
          <pub-id pub-id-type="doi">10.1371/journal.pmed.1000097</pub-id>
          <pub-id pub-id-type="medline">19621072</pub-id>
          <pub-id pub-id-type="pmcid">PMC2707599</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref16">
        <label>16</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Landau</surname>
              <given-names>Z</given-names>
            </name>
            <name name-style="western">
              <surname>Mazor-Aronovitch</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Boaz</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Blaychfeld-Magnazi</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Graph-Barel</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Levek-Motola</surname>
              <given-names>N</given-names>
            </name>
            <name name-style="western">
              <surname>Pinhas-Hamiel</surname>
              <given-names>O</given-names>
            </name>
          </person-group>
          <article-title>The effectiveness of Internet-based blood glucose monitoring system on improving diabetes control in adolescents with type 1 diabetes</article-title>
          <source>Pediatr Diabetes</source>
          <year>2012</year>
          <month>03</month>
          <volume>13</volume>
          <issue>2</issue>
          <fpage>203</fpage>
          <lpage>7</lpage>
          <pub-id pub-id-type="doi">10.1111/j.1399-5448.2011.00800.x</pub-id>
          <pub-id pub-id-type="medline">21848925</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref17">
        <label>17</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Schiaffini</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Tagliente</surname>
              <given-names>I</given-names>
            </name>
            <name name-style="western">
              <surname>Carducci</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Ullmann</surname>
              <given-names>N</given-names>
            </name>
            <name name-style="western">
              <surname>Ciampalini</surname>
              <given-names>P</given-names>
            </name>
            <name name-style="western">
              <surname>Lorubbio</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Cappa</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Impact of long-term use of eHealth systems in adolescents with type 1 diabetes treated with sensor-augmented pump therapy</article-title>
          <source>J Telemed Telecare</source>
          <year>2016</year>
          <month>07</month>
          <volume>22</volume>
          <issue>5</issue>
          <fpage>277</fpage>
          <lpage>81</lpage>
          <pub-id pub-id-type="doi">10.1177/1357633X15598425</pub-id>
          <pub-id pub-id-type="medline">26289613</pub-id>
          <pub-id pub-id-type="pii">1357633X15598425</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref18">
        <label>18</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Rigla</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Hernando</surname>
              <given-names>ME</given-names>
            </name>
            <name name-style="western">
              <surname>Gómez</surname>
              <given-names>Enrique J</given-names>
            </name>
            <name name-style="western">
              <surname>Brugués</surname>
              <given-names>Eulalia</given-names>
            </name>
            <name name-style="western">
              <surname>García-Sáez</surname>
              <given-names>Gema</given-names>
            </name>
            <name name-style="western">
              <surname>Capel</surname>
              <given-names>I</given-names>
            </name>
            <name name-style="western">
              <surname>Pons</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>de Leiva</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Real-time continuous glucose monitoring together with telemedical assistance improves glycemic control and glucose stability in pump-treated patients</article-title>
          <source>Diabetes Technol Ther</source>
          <year>2008</year>
          <month>06</month>
          <volume>10</volume>
          <issue>3</issue>
          <fpage>194</fpage>
          <lpage>9</lpage>
          <pub-id pub-id-type="doi">10.1089/dia.2007.0273</pub-id>
          <pub-id pub-id-type="medline">18473693</pub-id>
          <pub-id pub-id-type="pii">10.1089/dia.2007.0273</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref19">
        <label>19</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Lehmkuhl</surname>
              <given-names>HD</given-names>
            </name>
            <name name-style="western">
              <surname>Storch</surname>
              <given-names>EA</given-names>
            </name>
            <name name-style="western">
              <surname>Cammarata</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Meyer</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Rahman</surname>
              <given-names>O</given-names>
            </name>
            <name name-style="western">
              <surname>Silverstein</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Malasanos</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Geffken</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <article-title>Telehealth behavior therapy for the management of type 1 diabetes in adolescents</article-title>
          <source>J Diabetes Sci Technol</source>
          <year>2010</year>
          <month>01</month>
          <day>01</day>
          <volume>4</volume>
          <issue>1</issue>
          <fpage>199</fpage>
          <lpage>208</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/20167185"/>
          </comment>
          <pub-id pub-id-type="doi">10.1177/193229681000400125</pub-id>
          <pub-id pub-id-type="medline">20167185</pub-id>
          <pub-id pub-id-type="pmcid">PMC2825642</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref20">
        <label>20</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Izquierdo</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Morin</surname>
              <given-names>PC</given-names>
            </name>
            <name name-style="western">
              <surname>Bratt</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Moreau</surname>
              <given-names>Z</given-names>
            </name>
            <name name-style="western">
              <surname>Meyer</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Ploutz-Snyder</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Wade</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Weinstock</surname>
              <given-names>RS</given-names>
            </name>
          </person-group>
          <article-title>School-centered telemedicine for children with type 1 diabetes mellitus</article-title>
          <source>J Pediatr</source>
          <year>2009</year>
          <month>09</month>
          <volume>155</volume>
          <issue>3</issue>
          <fpage>374</fpage>
          <lpage>9</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jpeds.2009.03.014</pub-id>
          <pub-id pub-id-type="medline">19464030</pub-id>
          <pub-id pub-id-type="pii">S0022-3476(09)00234-0</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref21">
        <label>21</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Esmatjes</surname>
              <given-names>E</given-names>
            </name>
            <name name-style="western">
              <surname>Jansà</surname>
              <given-names>Margarida</given-names>
            </name>
            <name name-style="western">
              <surname>Roca</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Pérez-Ferre</surname>
              <given-names>Natalia</given-names>
            </name>
            <name name-style="western">
              <surname>del Valle</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Martínez-Hervás</surname>
              <given-names>Sergio</given-names>
            </name>
            <name name-style="western">
              <surname>Ruiz de Adana</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Linares</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Batanero</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Vázquez</surname>
              <given-names>Federico</given-names>
            </name>
            <name name-style="western">
              <surname>Gomis</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>de Solà-Morales</surname>
              <given-names>Oriol</given-names>
            </name>
            <collab>Telemed-Diabetes Group</collab>
          </person-group>
          <article-title>The efficiency of telemedicine to optimize metabolic control in patients with type 1 diabetes mellitus: Telemed study</article-title>
          <source>Diabetes Technol Ther</source>
          <year>2014</year>
          <month>07</month>
          <volume>16</volume>
          <issue>7</issue>
          <fpage>435</fpage>
          <lpage>41</lpage>
          <pub-id pub-id-type="doi">10.1089/dia.2013.0313</pub-id>
          <pub-id pub-id-type="medline">24528195</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref22">
        <label>22</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Peterson</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Improving type 1 diabetes management with mobile tools: a systematic review</article-title>
          <source>J Diabetes Sci Technol</source>
          <year>2014</year>
          <month>07</month>
          <volume>8</volume>
          <issue>4</issue>
          <fpage>859</fpage>
          <lpage>64</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/24876414"/>
          </comment>
          <pub-id pub-id-type="doi">10.1177/1932296814529885</pub-id>
          <pub-id pub-id-type="medline">24876414</pub-id>
          <pub-id pub-id-type="pii">1932296814529885</pub-id>
          <pub-id pub-id-type="pmcid">PMC4764226</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref23">
        <label>23</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Viana</surname>
              <given-names>LV</given-names>
            </name>
            <name name-style="western">
              <surname>Gomes</surname>
              <given-names>MB</given-names>
            </name>
            <name name-style="western">
              <surname>Zajdenverg</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Pavin</surname>
              <given-names>EJ</given-names>
            </name>
            <name name-style="western">
              <surname>Azevedo</surname>
              <given-names>MJ</given-names>
            </name>
            <collab>Brazilian Type 1 Diabetes Study Group</collab>
          </person-group>
          <article-title>Interventions to improve patients' compliance with therapies aimed at lowering glycated hemoglobin (HbA<sub>1c</sub>) in type 1 diabetes: systematic review and meta-analyses of randomized controlled clinical trials of psychological, telecare, and educational interventions</article-title>
          <source>Trials</source>
          <year>2016</year>
          <month>02</month>
          <day>17</day>
          <volume>17</volume>
          <fpage>94</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-016-1207-6"/>
          </comment>
          <pub-id pub-id-type="doi">10.1186/s13063-016-1207-6</pub-id>
          <pub-id pub-id-type="medline">26888087</pub-id>
          <pub-id pub-id-type="pii">10.1186/s13063-016-1207-6</pub-id>
          <pub-id pub-id-type="pmcid">PMC4758163</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref24">
        <label>24</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Shulman</surname>
              <given-names>RM</given-names>
            </name>
            <name name-style="western">
              <surname>O'Gorman</surname>
              <given-names>CS</given-names>
            </name>
            <name name-style="western">
              <surname>Palmert</surname>
              <given-names>MR</given-names>
            </name>
          </person-group>
          <article-title>The impact of telemedicine interventions involving routine transmission of blood glucose data with clinician feedback on metabolic control in youth with type 1 diabetes: a systematic review and meta-analysis</article-title>
          <source>Int J Pediatr Endocrinol</source>
          <year>2010</year>
          <volume>2010</volume>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://ijpeonline.biomedcentral.com/articles/10.1155/2010/536957"/>
          </comment>
          <pub-id pub-id-type="doi">10.1155/2010/536957</pub-id>
          <pub-id pub-id-type="medline">20886054</pub-id>
          <pub-id pub-id-type="pmcid">PMC2945636</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref25">
        <label>25</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Yaron</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Sher</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>Sorek</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Shomer</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Levek</surname>
              <given-names>N</given-names>
            </name>
            <name name-style="western">
              <surname>Schiller</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Gaspar</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Frumkin Ben-David</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Mazor-Aronovitch</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Tish</surname>
              <given-names>E</given-names>
            </name>
            <name name-style="western">
              <surname>Shapira</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Pinhas-Hamiel</surname>
              <given-names>O</given-names>
            </name>
          </person-group>
          <article-title>A randomized controlled trial comparing a telemedicine therapeutic intervention with routine care in adults with type 1 diabetes mellitus treated by insulin pumps</article-title>
          <source>Acta Diabetol</source>
          <year>2019</year>
          <month>06</month>
          <volume>56</volume>
          <issue>6</issue>
          <fpage>667</fpage>
          <lpage>673</lpage>
          <pub-id pub-id-type="doi">10.1007/s00592-019-01300-1</pub-id>
          <pub-id pub-id-type="medline">30783823</pub-id>
          <pub-id pub-id-type="pii">10.1007/s00592-019-01300-1</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref26">
        <label>26</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Edwards</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Noyes</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Lowes</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Haf Spencer</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Gregory</surname>
              <given-names>JW</given-names>
            </name>
          </person-group>
          <article-title>An ongoing struggle: a mixed-method systematic review of interventions, barriers and facilitators to achieving optimal self-care by children and young people with type 1 diabetes in educational settings</article-title>
          <source>BMC Pediatr</source>
          <year>2014</year>
          <month>09</month>
          <day>12</day>
          <volume>14</volume>
          <fpage>228</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://bmcpediatr.biomedcentral.com/articles/10.1186/1471-2431-14-228"/>
          </comment>
          <pub-id pub-id-type="doi">10.1186/1471-2431-14-228</pub-id>
          <pub-id pub-id-type="medline">25213220</pub-id>
          <pub-id pub-id-type="pii">1471-2431-14-228</pub-id>
          <pub-id pub-id-type="pmcid">PMC4263204</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref27">
        <label>27</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Peña</surname>
              <given-names>Nancy Villarreal</given-names>
            </name>
            <name name-style="western">
              <surname>Torres</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Cardona</surname>
              <given-names>JAC</given-names>
            </name>
            <name name-style="western">
              <surname>Iniesta</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>Impact of telemedicine assessment on glycemic variability in children with type 1 diabetes mellitus</article-title>
          <source>Diabetes Technol Ther</source>
          <year>2013</year>
          <month>02</month>
          <volume>15</volume>
          <issue>2</issue>
          <fpage>136</fpage>
          <lpage>42</lpage>
          <pub-id pub-id-type="doi">10.1089/dia.2012.0243</pub-id>
          <pub-id pub-id-type="medline">23289433</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref28">
        <label>28</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Boogerd</surname>
              <given-names>E</given-names>
            </name>
            <name name-style="western">
              <surname>Maas-Van Schaaijk</surname>
              <given-names>NM</given-names>
            </name>
            <name name-style="western">
              <surname>Sas</surname>
              <given-names>TC</given-names>
            </name>
            <name name-style="western">
              <surname>Clement-de Boers</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Smallenbroek</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Nuboer</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Noordam</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Verhaak</surname>
              <given-names>CM</given-names>
            </name>
          </person-group>
          <article-title>Sugarsquare, a Web-Based Patient Portal for Parents of a Child With Type 1 Diabetes: Multicenter Randomized Controlled Feasibility Trial</article-title>
          <source>J Med Internet Res</source>
          <year>2017</year>
          <month>08</month>
          <day>22</day>
          <volume>19</volume>
          <issue>8</issue>
          <fpage>e287</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.jmir.org/2017/8/e287/"/>
          </comment>
          <pub-id pub-id-type="doi">10.2196/jmir.6639</pub-id>
          <pub-id pub-id-type="medline">28830853</pub-id>
          <pub-id pub-id-type="pii">v19i8e287</pub-id>
          <pub-id pub-id-type="pmcid">PMC5585595</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref29">
        <label>29</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Bromuri</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Puricel</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Schumann</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Krampf</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Ruiz</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Schumacher</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>An expert Personal Health System to monitor patients affected by Gestational Diabetes Mellitus: A feasibility study</article-title>
          <source>AIS</source>
          <year>2016</year>
          <month>03</month>
          <day>15</day>
          <volume>8</volume>
          <issue>2</issue>
          <fpage>219</fpage>
          <lpage>237</lpage>
          <pub-id pub-id-type="doi">10.3233/AIS-160365</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref30">
        <label>30</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Ruiz de Adana</surname>
              <given-names>MS</given-names>
            </name>
            <name name-style="western">
              <surname>Alhambra-Expósito</surname>
              <given-names>Maria Rosa</given-names>
            </name>
            <name name-style="western">
              <surname>Muñoz-Garach</surname>
              <given-names>Araceli</given-names>
            </name>
            <name name-style="western">
              <surname>Gonzalez-Molero</surname>
              <given-names>I</given-names>
            </name>
            <name name-style="western">
              <surname>Colomo</surname>
              <given-names>N</given-names>
            </name>
            <name name-style="western">
              <surname>Torres-Barea</surname>
              <given-names>I</given-names>
            </name>
            <name name-style="western">
              <surname>Aguilar-Diosdado</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Carral</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Serrano</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Martínez-Brocca</surname>
              <given-names>Maria A</given-names>
            </name>
            <name name-style="western">
              <surname>Duran</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Palomares</surname>
              <given-names>R</given-names>
            </name>
            <collab>Diabetes Group of SAEDYN (Andalusian Society of Endocrinology‚ Diabetes‚Nutrition)</collab>
          </person-group>
          <article-title>Randomized Study to Evaluate the Impact of Telemedicine Care in Patients With Type 1 Diabetes With Multiple Doses of Insulin and Suboptimal HbA in Andalusia (Spain): PLATEDIAN Study</article-title>
          <source>Diabetes Care</source>
          <year>2020</year>
          <month>02</month>
          <volume>43</volume>
          <issue>2</issue>
          <fpage>337</fpage>
          <lpage>342</lpage>
          <pub-id pub-id-type="doi">10.2337/dc19-0739</pub-id>
          <pub-id pub-id-type="medline">31831473</pub-id>
          <pub-id pub-id-type="pii">dc19-0739</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref31">
        <label>31</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Laptev</surname>
              <given-names>DN</given-names>
            </name>
            <name name-style="western">
              <surname>Peterkova</surname>
              <given-names>VA</given-names>
            </name>
          </person-group>
          <article-title>Use of telemedicine improves glycemic control and quality of life in type 1 diabetes children on insulin pump therapy</article-title>
          <source>Diabetes mellitus</source>
          <year>2018</year>
          <month>02</month>
          <day>17</day>
          <volume>20</volume>
          <issue>6</issue>
          <fpage>420</fpage>
          <lpage>426</lpage>
          <pub-id pub-id-type="doi">10.14341/dm8677</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref32">
        <label>32</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Gandrud</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Altan</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Buzinec</surname>
              <given-names>P</given-names>
            </name>
            <name name-style="western">
              <surname>Hemphill</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Chatterton</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Kelley</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Vojta</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Intensive remote monitoring versus conventional care in type 1 diabetes: A randomized controlled trial</article-title>
          <source>Pediatr Diabetes</source>
          <year>2018</year>
          <month>02</month>
          <day>21</day>
          <pub-id pub-id-type="doi">10.1111/pedi.12654</pub-id>
          <pub-id pub-id-type="medline">29464831</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref33">
        <label>33</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Bertuzzi</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Stefani</surname>
              <given-names>I</given-names>
            </name>
            <name name-style="western">
              <surname>Rivolta</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>Pintaudi</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>Meneghini</surname>
              <given-names>E</given-names>
            </name>
            <name name-style="western">
              <surname>Luzi</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Mazzone</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Teleconsultation in type 1 diabetes mellitus (TELEDIABE)</article-title>
          <source>Acta Diabetol</source>
          <year>2018</year>
          <month>02</month>
          <volume>55</volume>
          <issue>2</issue>
          <fpage>185</fpage>
          <lpage>192</lpage>
          <pub-id pub-id-type="doi">10.1007/s00592-017-1084-9</pub-id>
          <pub-id pub-id-type="medline">29209814</pub-id>
          <pub-id pub-id-type="pii">10.1007/s00592-017-1084-9</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref34">
        <label>34</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Peterson</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Improving type 1 diabetes management with mobile tools: a systematic review</article-title>
          <source>J Diabetes Sci Technol</source>
          <year>2014</year>
          <month>07</month>
          <volume>8</volume>
          <issue>4</issue>
          <fpage>859</fpage>
          <lpage>64</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/24876414"/>
          </comment>
          <pub-id pub-id-type="doi">10.1177/1932296814529885</pub-id>
          <pub-id pub-id-type="medline">24876414</pub-id>
          <pub-id pub-id-type="pii">1932296814529885</pub-id>
          <pub-id pub-id-type="pmcid">PMC4764226</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref35">
        <label>35</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Baron</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>McBain</surname>
              <given-names>H</given-names>
            </name>
            <name name-style="western">
              <surname>Newman</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>The impact of mobile monitoring technologies on glycosylated hemoglobin in diabetes: a systematic review</article-title>
          <source>J Diabetes Sci Technol</source>
          <year>2012</year>
          <month>09</month>
          <day>01</day>
          <volume>6</volume>
          <issue>5</issue>
          <fpage>1185</fpage>
          <lpage>96</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/23063046"/>
          </comment>
          <pub-id pub-id-type="doi">10.1177/193229681200600524</pub-id>
          <pub-id pub-id-type="medline">23063046</pub-id>
          <pub-id pub-id-type="pmcid">PMC3570854</pub-id>
        </nlm-citation>
      </ref>
    </ref-list>
  </back>
</article>
