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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JMIR</journal-id>
      <journal-id journal-id-type="nlm-ta">J Med Internet Res</journal-id>
      <journal-title>Journal of Medical Internet Research</journal-title>
      <issn pub-type="epub">1438-8871</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">v23i3e23475</article-id>
      <article-id pub-id-type="pmid">33759789</article-id>
      <article-id pub-id-type="doi">10.2196/23475</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>Diabetology 4.0: Scoping Review of Novel Insights and Possibilities Offered by Digitalization</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Eysenbach</surname>
            <given-names>Gunther</given-names>
          </name>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Kukafka</surname>
            <given-names>Rita</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Akturk</surname>
            <given-names>Halis</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Joakimsen</surname>
            <given-names>Ragnar</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>Prof Dr, MD</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>
            <fax>49 661 9640 648</fax>
            <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 id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Löhnert</surname>
            <given-names>Maxine</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-0688-2687</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">
        <month>3</month>
        <year>2021</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>24</day>
        <month>3</month>
        <year>2021</year>
      </pub-date>
      <volume>23</volume>
      <issue>3</issue>
      <elocation-id>e23475</elocation-id>
      <history>
        <date date-type="received">
          <day>13</day>
          <month>8</month>
          <year>2020</year>
        </date>
        <date date-type="rev-request">
          <day>3</day>
          <month>9</month>
          <year>2020</year>
        </date>
        <date date-type="rev-recd">
          <day>13</day>
          <month>10</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>18</day>
          <month>1</month>
          <year>2021</year>
        </date>
      </history>
      <copyright-statement>©Claudia Eberle, Stefanie Stichling, Maxine Löhnert. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.03.2021.</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 the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on http://www.jmir.org/, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://www.jmir.org/2021/3/e23475" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>The increasing prevalence of diabetes mellitus and associated morbidity worldwide justifies the need to create new approaches and strategies for diabetes therapy. Therefore, the ongoing digitalization offers novel opportunities in this field.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>The aim of this study is to provide an updated overview of available technologies, possibilities, and novel insights into diabetes therapy 4.0.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>A scoping review was carried out, and a literature search was performed using electronic databases (MEDLINE [PubMed], Cochrane Library, Embase, CINAHL, and Web of Science). The results were categorized according to the type of technology presented.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>Different types of technology (eg, glucose monitoring systems, insulin pens, insulin pumps, closed-loop systems, mobile health apps, telemedicine, and electronic medical records) may help to improve diabetes treatment. These improvements primarily affect glycemic control. However, they may also help in increasing the autonomy and quality of life of people who are diagnosed with diabetes mellitus.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>Diabetes technologies have developed rapidly over the last few years and offer novel insights into diabetes therapy and a chance to improve and individualize diabetes treatment. Challenges that need to be addressed in the following years relate to data security, interoperability, and the development of standards.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>diabetes mellitus</kwd>
        <kwd>telemedicine</kwd>
        <kwd>mobile apps</kwd>
        <kwd>electronic health records</kwd>
        <kwd>digital technology</kwd>
        <kwd>eHealth</kwd>
        <kwd>mobile phone</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <sec>
        <title>Background</title>
        <p>The ongoing digitalization changed the way of practicing medicine in general. Currently, it is possible to store and retrieve vast amounts of data and use different technologies to assist in diagnosis and therapy [<xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref2">2</xref>]. This technological development offers the opportunity to improve the treatment of diabetes mellitus (DM) in particular and in different ways [<xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref3">3</xref>].</p>
        <p>In 2014, the global prevalence of DM among adults aged more than 18 years was estimated at approximately 8.5% and is believed to have increased since then, not taking into account the number of unreported cases [<xref ref-type="bibr" rid="ref4">4</xref>]. As the high and rising prevalence and morbidity of DM, new strategies are needed.</p>
        <p>In diabetes management, the measurement of blood glucose levels plays a key role. Therefore, different types of systems are available, which differ in when and how often the measurement takes place [<xref ref-type="bibr" rid="ref5">5</xref>]. Furthermore, more than 200 million people with DM require insulin treatment [<xref ref-type="bibr" rid="ref6">6</xref>]. Currently, there are mainly 2 possibilities to deliver insulin: multiple daily injections or continuous subcutaneous insulin infusions [<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref6">6</xref>]. For both, different technological solutions are available in the market. Another important aspect of diabetes management depends on patient self-management. This means that people with DM must make several decisions, for example, when and what to eat, when to exercise, and, if required, the insulin dose and timing [<xref ref-type="bibr" rid="ref7">7</xref>]. Technological innovations such as mobile health (mHealth) apps or advances in telemedicine may be used in different ways to overcome challenges such as the ones mentioned above [<xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref8">8</xref>-<xref ref-type="bibr" rid="ref17">17</xref>]. The purpose of diabetes technologies is to avoid complications of insulin therapy and to give people with DM more autonomy so that their quality of life (QoL) can be improved [<xref ref-type="bibr" rid="ref18">18</xref>]. Furthermore, it must be noted that we have considered all types of diabetes and that they have different therapeutic needs. Type 1 and type 2 diabetes have different pathogeneses, leading to various therapy recommendations and needs. In addition to some similarities, type 1 diabetes therapy focuses more on insulin therapy, whereas type 2 diabetes management focuses more on nutrition and exercise. In a closer analysis of the technologies, it is important to differentiate between the types of diabetes and their needs.</p>
      </sec>
      <sec>
        <title>Objective</title>
        <p>The aim of this study is to provide an overview of the updated diabetes technologies available and the possibilities offered by digitalization of the treatment of DM.</p>
      </sec>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Data Sources and Search Terms</title>
        <p>We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews to assess the scope of the literature on the topic [<xref ref-type="bibr" rid="ref19">19</xref>]. The electronic databases MEDLINE (PubMed), Cochrane Library, Embase, CINAHL, and Web of Science were searched. For example, in PubMed, the following search strategy was used for a title and abstract search: if available in MeSH terms: “Diabetes Mellitus” OR “diabetes” OR “blood glucose assessment” AND “Telemedicine” OR “Mobile Applications” OR “digitization” OR “digital treatment,” an additional search in the reference lists and Google Scholar was conducted.</p>
      </sec>
      <sec>
        <title>Study Selection and Eligibility Criteria</title>
        <p>The results of the literature search were transferred to the literature management program, Citavi, which was used to remove duplicates. Via a search of titles and abstracts, potentially relevant studies were extracted. Studies published in English or German between January 2008 and January 2020 that focused on technologies in DM therapy were included. Furthermore, to be included, the studies had to make remarks or comments on the clinical effectiveness, for example, effect on glycemic control, of the type of technology that was presented. There were no limitations to the study design. Studies that focused only on the comorbidities of DM were excluded. As this paper is a scoping review, we selected those studies from our presorted studies that seemed to give great overviews and explanations but still reported on clinical effectiveness.</p>
      </sec>
      <sec>
        <title>Data Extraction and Data Synthesis</title>
        <p>The included studies were thematically categorized according to the type of technology presented. We then extracted the following data from each study: author, year, study design, objective, and main findings.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Overview</title>
        <p>Our search yielded a total of 4935 results, of which we included 67 studies (including systematic and narrative reviews). The search results can be categorized into the following types of technology: glucose monitoring systems, insulin pens, insulin pumps, closed-loop systems, mHealth apps, telemedicine, and electronic medical records (EMRs).</p>
      </sec>
      <sec>
        <title>Glucose Monitoring Systems</title>
        <p>Most people with DM rely on self-monitoring of blood glucose (SMBG). Although there is a correlation between increased frequency of SMBG and a reduction in glycated hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>), SMBG only gives a short impression of blood glucose levels without any information about the change in glucose levels and glucose variability [<xref ref-type="bibr" rid="ref5">5</xref>]. To gain this information, continuous glucose monitoring (CGM) systems can be used.</p>
        <p>CGM systems measure the glucose level at regular intervals, 24 hours a day, and translate the measurements into data about glucose direction and rate of change [<xref ref-type="bibr" rid="ref18">18</xref>]. On the basis of this information, CGM use without additional SMBG is as safe and effective as CGM use with SMBG support [<xref ref-type="bibr" rid="ref20">20</xref>]. In addition, several experimental studies have shown that the use of CGM systems improves glycemic control through a significant reduction in HbA<sub>1c</sub> [<xref ref-type="bibr" rid="ref21">21</xref>-<xref ref-type="bibr" rid="ref25">25</xref>], and this has been shown in combination with insulin pump therapy [<xref ref-type="bibr" rid="ref22">22</xref>] and with multiple daily insulin injections [<xref ref-type="bibr" rid="ref24">24</xref>]. Another positive effect was demonstrated by Jones et al [<xref ref-type="bibr" rid="ref26">26</xref>] in their systematic review targeting pregnant women with pre-existing diabetes, showing that a reduction in hypertensive disorders is possible when CGM is used. However, they assumed only low-quality evidence because only 2 studies included the outcome [<xref ref-type="bibr" rid="ref26">26</xref>]. Further aspects of CGM can improve diabetes self-management, flexibility, and QoL. In particular, the option for alarms and the possibility of device connection with smartphones or smartwatches give the participants a feeling of greater safety and freedom [<xref ref-type="bibr" rid="ref27">27</xref>]. Furthermore, CMG measures subcutaneous glucose as a substitute for blood sugar. Old systems had to be calibrated regularly, whereas newer systems did not require calibration, which benefits the patients.</p>
        <p>The Juvenile Diabetes Research Foundation recognized an association between greater CGM use and a greater decrease in HbA<sub>1c</sub> levels. However, they also noticed a decrease in CGM usage over the study duration, especially in children and adolescents [<xref ref-type="bibr" rid="ref21">21</xref>]. Reasons for discontinuation include discomfort when wearing the CGM system, problems with inserting the sensor, or with the adhesive holding the sensor on the skin [<xref ref-type="bibr" rid="ref28">28</xref>]. An alternative to minimize skin reactions is to use implantable CGM systems, which can be as safe and accurate as transcutaneous CGM systems [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref>].</p>
        <p>Most of the studies relate to the so-called real-time CGM. Another type of CGM system is the intermittently scanned CGM system, also called flash glucose monitoring. These terms refer to CGM systems that can only be used on demand. This means that patients must use a reader device to scan the sensor to determine the glucose level [<xref ref-type="bibr" rid="ref5">5</xref>]. This can be an alternative suitable for the masses because of lower costs relative to real-time CGM while also providing more information than with SMBG. However, it depends on the patients’ willingness to scan the device several times a day [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref32">32</xref>].</p>
      </sec>
      <sec>
        <title>Insulin Pens</title>
        <p>Insulin pens are a technological invention for multiple daily insulin injections and are used as an alternative to insulin dosing via syringe. There are 2 types of insulin pens. Reusable pens have a delivery chamber in which insulin cartridges can be inserted. This makes it easy to change the type of insulin and is more economical than alternative prefilled pens. These contain a built-in single-use insulin cartridge. As a result, they are very convenient and easy to use, which is helpful for patients who have difficulties inserting the cartridges in reusable pens [<xref ref-type="bibr" rid="ref33">33</xref>]. Overall, insulin pens have several advantages in terms of user friendliness, comfort of injections, and accuracy in delivering small doses of insulin. This leads to greater patient satisfaction and less reported pain [<xref ref-type="bibr" rid="ref33">33</xref>,<xref ref-type="bibr" rid="ref34">34</xref>].</p>
        <p>However, there seems to be no improvement in glycemic control in insulin pens compared with the use of vials and syringes [<xref ref-type="bibr" rid="ref35">35</xref>]. The advance in their development to so-called smart pens has changed this [<xref ref-type="bibr" rid="ref36">36</xref>]. Smart pens include a memory function to track insulin doses and often have Bluetooth connectivity to transfer data to a smartphone app [<xref ref-type="bibr" rid="ref18">18</xref>]. These functions seem to help patients improve their glycemic control [<xref ref-type="bibr" rid="ref36">36</xref>].</p>
        <p>The first FDA-approved smart pen, InPen, was launched in the United States in December 2017. In addition to digital diaries, it provides a dose calculator based on information on previous insulin doses, insulin on board, and current blood glucose levels. In addition, the app can be connected to some CGM systems [<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref37">37</xref>,<xref ref-type="bibr" rid="ref38">38</xref>]. This allows better diabetes management [<xref ref-type="bibr" rid="ref39">39</xref>].</p>
      </sec>
      <sec>
        <title>Insulin Pumps</title>
        <p>Insulin pumps are small programmable computerized devices that allow continuous subcutaneous insulin infusions, so a more physiological insulin release can be mimicked. This is realized by an individual basal insulin rate, which is released hourly and set by the medical staff. In addition, bolus insulin can be released after meals or as a correction to reduce the target glucose levels [<xref ref-type="bibr" rid="ref40">40</xref>,<xref ref-type="bibr" rid="ref41">41</xref>]. The use of insulin pumps is associated with a reduction in HbA<sub>1c</sub> levels without an increased risk of hypoglycemia and seems to be more effective than multiple daily insulin injections [<xref ref-type="bibr" rid="ref42">42</xref>-<xref ref-type="bibr" rid="ref44">44</xref>].</p>
        <p>There are different types of insulin pumps [<xref ref-type="bibr" rid="ref40">40</xref>], and in a patch insulin pump, the insulin needle is a part of the pump and is inserted when the pump is attached directly to the surface of the skin. Controls of these pumps are on the device itself, or a remote can be used, so that there is no tubing. Examples are the V-Go and Omnipod insulin pumps [<xref ref-type="bibr" rid="ref45">45</xref>,<xref ref-type="bibr" rid="ref46">46</xref>]. Tethered insulin pumps have tubing between the pump itself and the cannula, so the pump can be worn under or outside clothing or carried around in a pocket. Examples are the Medtronic MiniMed 670G and Tandem t:slim X2 insulin pumps [<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref48">48</xref>]. Although they are rarely used, other types are implantable insulin pumps. These are implanted into the peritoneal cavity and remain there; therefore, the users have to travel to get the pump refilled with insulin [<xref ref-type="bibr" rid="ref40">40</xref>].</p>
        <p>The current development in insulin pump technology is a direct and wireless communication between insulin pumps and CGM systems, for example, via infrared technology. Such systems are called sensor-augmented insulin pumps (SAPs) [<xref ref-type="bibr" rid="ref41">41</xref>]. In contrast to closed-loop systems, SAPs still require manual adjustment and input from the wearer [<xref ref-type="bibr" rid="ref49">49</xref>,<xref ref-type="bibr" rid="ref50">50</xref>]. However, the use of SAP can further reduce the risk of hypoglycemic episodes and improve glycemic control [<xref ref-type="bibr" rid="ref51">51</xref>-<xref ref-type="bibr" rid="ref53">53</xref>]. SAPs can have different features; however, they often include a bolus calculator, an automated insulin suspension, and custom reminders. The bolus calculator calculates insulin doses for meals after the number of carbohydrates the wearer intents to eat are put in [<xref ref-type="bibr" rid="ref49">49</xref>]. An automated insulin suspension allows the SAP to suspend insulin delivery when the CGM detects an unexpectedly low glucose level or risk of hypoglycemia [<xref ref-type="bibr" rid="ref51">51</xref>]. Custom reminders can be set to remind the individual to check their glucose levels or to set a bolus amount. In addition, safety alerts for missed bolus doses or blockage in the tubing or cannula can be set [<xref ref-type="bibr" rid="ref49">49</xref>,<xref ref-type="bibr" rid="ref54">54</xref>].</p>
      </sec>
      <sec>
        <title>Closed-Loop Systems</title>
        <p>Closed-loop systems, also referred to as artificial pancreas, are a combination of a CGM system and an insulin pump that can release insulin automatically [<xref ref-type="bibr" rid="ref50">50</xref>]. These systems can be understood as fully automatic pumps that replace an endocrine pancreas; however, there are currently no such pumps in the market. Closed-loop pumps need to be calibrated, and patients need to assess their carbohydrate intake and tell the pump the time and amount of carbohydrates they will eat.</p>
        <p>A step between SAPs and closed-loop systems are hybrid closed-loop systems such as MiniMed 670 G. This means that next to the manual mode where a basal insulin rate is set, they have the ability to use an automatic mode where insulin delivery is adjusted based on the CGM results. However, meal-related boluses remain user-dependent based on their carbohydrate intake [<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref56">56</xref>]. Nevertheless, hybrid closed-loop systems have shown improved HbA<sub>1c</sub> levels and time in range and decreased time spent in hypo- and hyperglycemias [<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref57">57</xref>,<xref ref-type="bibr" rid="ref58">58</xref>]. In addition, a closed-loop system consisting of the t:slim X2 insulin pump, Control-IQ Technology, and Dexcom G6 as a CGM system has been shown to improve glycemic control and time in range [<xref ref-type="bibr" rid="ref59">59</xref>,<xref ref-type="bibr" rid="ref60">60</xref>].</p>
        <p>In addition, the #WeAreNotWaiting movement has developed systems for a do-it-yourself artificial pancreas (DIY AP). They used CGM systems, insulin pumps, and smartphone technology to run algorithms to calculate the insulin dose. These algorithms are openly shared by the community and have introduced various systems consisting of different components and using different interfaces. It must be noted that DIY AP are unregulated and therefore have potential safety concerns [<xref ref-type="bibr" rid="ref61">61</xref>]. Although there are mainly observational studies about the effectiveness of DIY AP, they seem to improve the HbA<sub>1c</sub> levels [<xref ref-type="bibr" rid="ref62">62</xref>,<xref ref-type="bibr" rid="ref63">63</xref>].</p>
      </sec>
      <sec>
        <title>Telemedicine</title>
        <p>Despite the advances in glucose monitoring systems and improvements in insulin delivery, the proportion of people with DM achieving their glycemic control targets has not improved [<xref ref-type="bibr" rid="ref64">64</xref>]. As a key contributor to poor glycemic control, <italic>therapeutic inertia</italic> is considered. <italic>Therapeutic inertia</italic> is defined as failure of initiation or intensification of therapy in a timely manner according to evidence-based clinical guidelines. It is a multifactorial problem, in which different stakeholders such as patients, health care providers, or the industry are involved [<xref ref-type="bibr" rid="ref65">65</xref>,<xref ref-type="bibr" rid="ref66">66</xref>]. Moreover, it underlines the need for care between visits to health care providers in diabetes treatment [<xref ref-type="bibr" rid="ref67">67</xref>]. Telemedicine is becoming increasingly important as a solution to this problem [<xref ref-type="bibr" rid="ref66">66</xref>]. Telemedicine describes the use of telecommunication systems to deliver health care at a distance, for example, through remote monitoring or real-time video conferencing [<xref ref-type="bibr" rid="ref68">68</xref>]. This means that patients can communicate with their providers in an efficient way. However, health care providers can quickly provide feedback [<xref ref-type="bibr" rid="ref67">67</xref>].</p>
        <p>The open definition of telemedicine provides scope for various interventions, such as phone coaching interventions [<xref ref-type="bibr" rid="ref69">69</xref>], tele-education [<xref ref-type="bibr" rid="ref70">70</xref>,<xref ref-type="bibr" rid="ref71">71</xref>], teleconsultations [<xref ref-type="bibr" rid="ref72">72</xref>], real-time transmission of blood glucose levels [<xref ref-type="bibr" rid="ref73">73</xref>], and web-based case management programs [<xref ref-type="bibr" rid="ref74">74</xref>]. In addition, a combination of different components is possible [<xref ref-type="bibr" rid="ref68">68</xref>,<xref ref-type="bibr" rid="ref75">75</xref>]. Although there is a lack of evidence on long-term health outcomes, it is estimated that telemedical interventions lower HbA<sub>1c</sub> levels with high certainty [<xref ref-type="bibr" rid="ref68">68</xref>,<xref ref-type="bibr" rid="ref76">76</xref>-<xref ref-type="bibr" rid="ref79">79</xref>]. In addition, improvement in blood glucose and cholesterol, QoL, and the number of SMBG checks is possible [<xref ref-type="bibr" rid="ref77">77</xref>,<xref ref-type="bibr" rid="ref78">78</xref>]. This can be especially important in rural and medically underserved areas [<xref ref-type="bibr" rid="ref71">71</xref>].</p>
      </sec>
      <sec>
        <title>mHealth Apps</title>
        <p>Apps for mobile devices such as smartphones focusing on health-related topics are called mHealth apps, and as the app market is very dynamic, they exist in a large variety. Diabetes apps vary in their range of considered topics and features [<xref ref-type="bibr" rid="ref9">9</xref>,<xref ref-type="bibr" rid="ref10">10</xref>,<xref ref-type="bibr" rid="ref12">12</xref>,<xref ref-type="bibr" rid="ref13">13</xref>,<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref80">80</xref>-<xref ref-type="bibr" rid="ref82">82</xref>]. Common features include tracking of blood glucose levels or insulin usage, calculating an insulin dose, monitoring of diet, weight or physical activity, providing education, or allowing communication and exchange of data with health care professionals or social networks [<xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref8">8</xref>-<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref80">80</xref>-<xref ref-type="bibr" rid="ref84">84</xref>].</p>
        <p>Even with these features, there is great variability and development [<xref ref-type="bibr" rid="ref16">16</xref>]. For example, attempts have been made to create bolus calculators that provide personalized and adaptive insulin recommendations [<xref ref-type="bibr" rid="ref85">85</xref>] or to create apps that use augmented reality to improve estimations regarding carbohydrate intake [<xref ref-type="bibr" rid="ref86">86</xref>]. With such features, apps support diabetes self-management, especially for people using SMBG [<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref84">84</xref>,<xref ref-type="bibr" rid="ref87">87</xref>-<xref ref-type="bibr" rid="ref89">89</xref>]. In addition, some apps are able to connect with other devices such as CGM systems, smart pens, or insulin pumps. Some devices come with their own app, for example, apps belonging to CGM systems allow wireless synchronization between the glucometer itself and an individual’s smartphone [<xref ref-type="bibr" rid="ref81">81</xref>]. However, even with these features, not all needs expressed by people with DM are met. Adults with type 2 DM additionally wish for features that help in reducing the cognitive and emotional burden of diabetes self-management [<xref ref-type="bibr" rid="ref90">90</xref>]. This is in line with recent findings showing that apps fail to provide relevant features to empower patients, even though there were complaints about a lack of personalized feedback, lack of education provided, and usability issues in the past [<xref ref-type="bibr" rid="ref83">83</xref>,<xref ref-type="bibr" rid="ref87">87</xref>,<xref ref-type="bibr" rid="ref91">91</xref>].</p>
        <p>Features such as writing a digital diary instead of a standard paper diary are not considered to affect QoL [<xref ref-type="bibr" rid="ref92">92</xref>]. However, because of the combination of different features in most apps, it is difficult to determine the impact of specific app features on clinical outcomes [<xref ref-type="bibr" rid="ref8">8</xref>]. Diabetes apps are supposed to improve glycemic control through significant reduction of HbA<sub>1c</sub>, although evidence on safety and effectiveness is limited, especially regarding long-term outcomes [<xref ref-type="bibr" rid="ref93">93</xref>-<xref ref-type="bibr" rid="ref95">95</xref>].</p>
        <p>Nevertheless, mHealth apps have several advantages. Nearly all patients and health care professionals have smartphones, and in contrast to diabetes devices, which are often left behind, smartphones are almost always in a patient’s reach [<xref ref-type="bibr" rid="ref81">81</xref>,<xref ref-type="bibr" rid="ref96">96</xref>]. Moreover, apps have the ability to display data in colored charts and tables, which can be updated live and transferred via email or in cloud-based web portals [<xref ref-type="bibr" rid="ref81">81</xref>]. In addition, an improvement in the reliability of patients’ diabetes data is possible because errors such as illegible handwriting or incomplete data entries can be minimized [<xref ref-type="bibr" rid="ref81">81</xref>,<xref ref-type="bibr" rid="ref97">97</xref>]. However, some disadvantages should be considered before using or recommending apps. First, there is a risk that during constant updates, bugs emerge and features are removed without warning or new pricing models are introduced [<xref ref-type="bibr" rid="ref81">81</xref>]. Furthermore, especially, older patients can have special needs, such as a large font size because of bad eyesight, so not all apps suit them [<xref ref-type="bibr" rid="ref98">98</xref>]. Moreover, apps are mostly not regulated by a governing body unless they meet the definition of medical devices. This holds a potential safety risk, especially regarding possible misinformation and data security [<xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref81">81</xref>,<xref ref-type="bibr" rid="ref94">94</xref>]. Finally, it must be considered that some apps are only available on one operating system, Android or iOS [<xref ref-type="bibr" rid="ref81">81</xref>]. This means that individualized recommendations should be provided to people with DM.</p>
      </sec>
      <sec>
        <title>EMR</title>
        <p>The use of EMR offers the opportunity to transfer data of diabetes technology, such as glucose monitoring systems, insulin pumps, or insulin pens, directly to the patients’ medical records. This makes everyday life in primary health care easier and is a step toward an automated institution. This can be realized by setting up stations where patients can transfer their data to their EMRs. To achieve this service for devices of different providers, collaboration with engineers and technicians is needed [<xref ref-type="bibr" rid="ref99">99</xref>]. Another possibility is the use of apps to transfer data into the EMR. The prerequisite for this is that the systems used are compatible with one another, for example, the platform <italic>HealthKit</italic> of the mobile device company Apple can be used with compatible CGM systems and compatible EMR vendor patient apps [<xref ref-type="bibr" rid="ref100">100</xref>].</p>
        <p>In addition to their use in primary health care, the collected data of EMRs can be used in public health surveillance to better understand the disease [<xref ref-type="bibr" rid="ref101">101</xref>]. However, at present, there is a lack of quality in the collected data and more structured variables are needed to exploit the full potential of this use [<xref ref-type="bibr" rid="ref102">102</xref>].</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <sec>
        <title>Principal Findings</title>
        <p>In total, digital diabetology has a huge potential to improve the health and QoL of patients with DM, especially glycemic control and diabetes therapy, using glucose monitoring systems, insulin pens, insulin pumps, closed-loop systems, mHealth apps, telemedicine, and EMR.</p>
        <p>The variability of diabetes technologies shows that in the past decades, there has been a rapid development of care-supporting technologies. Advances in reducing the size and improving the accuracy of devices are not yet mentioned. It is believed that in the next 5 years, there will be many more advances, especially in CGM systems and automated insulin delivery through closed-loop systems. This includes the expectation that more systems will be available in the market [<xref ref-type="bibr" rid="ref103">103</xref>]. Nevertheless, there are some points about the technologies that need to be discussed.</p>
        <p>The advances in all the aforementioned technologies seem to improve glycemic control and, consequently, QoL. Therefore, they fulfill the purpose of diabetes technologies [<xref ref-type="bibr" rid="ref18">18</xref>]. However, more data, especially on long-term outcomes, are needed [<xref ref-type="bibr" rid="ref8">8</xref>,<xref ref-type="bibr" rid="ref25">25</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref76">76</xref>,<xref ref-type="bibr" rid="ref95">95</xref>]. Moreover, the technologies differ in the kind of improvement they make and their effectiveness. For example, insulin pens are an improvement compared with syringes in terms of pain and user friendliness; however, improvement in glycemic control seems to be possible with smart pens [<xref ref-type="bibr" rid="ref33">33</xref>-<xref ref-type="bibr" rid="ref36">36</xref>]. In contrast, insulin pumps are more likely to improve glycemic control than insulin pens [<xref ref-type="bibr" rid="ref42">42</xref>-<xref ref-type="bibr" rid="ref44">44</xref>]. However, insulin pump therapy does not suit everybody; for example, people doing athletics could experience problems with their pump because of failure or disconnection [<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref104">104</xref>]. Therefore, an individualized solution that considers the patients’ needs and expectations is needed. This applies, in particular, to the recommendation of a diabetes mHealth app. It is possible that younger patients are more likely to benefit from an mHealth app intervention or that older patients have special needs that must be considered [<xref ref-type="bibr" rid="ref93">93</xref>,<xref ref-type="bibr" rid="ref98">98</xref>]. In addition, factors such as patients’ digital literacy should be considered. This is important because, despite the widespread use of smartphones, digital literacy barriers are common in vulnerable populations, which could reduce the effectiveness of diabetes technologies [<xref ref-type="bibr" rid="ref105">105</xref>].</p>
        <p>For such considerations, well-trained and educated health care personnel are needed [<xref ref-type="bibr" rid="ref106">106</xref>]. Diabetes technologies can save time for patients who would spend less time at health care institutions and for health care personnel, because many processes can be automated [<xref ref-type="bibr" rid="ref72">72</xref>,<xref ref-type="bibr" rid="ref106">106</xref>]. However, this is still a type of future vision, because often enough missing interoperability between devices, especially of different providers, prohibits the automation of processes [<xref ref-type="bibr" rid="ref107">107</xref>]. This goes hand in hand with missing standards and regulation of, for example, mHealth apps, which lead to potential health risks, for example, through misinformation [<xref ref-type="bibr" rid="ref81">81</xref>,<xref ref-type="bibr" rid="ref94">94</xref>,<xref ref-type="bibr" rid="ref106">106</xref>]. In addition, the question of data safety is a major issue. Because these technologies deal with sensible patient data, protection must be of the highest priority. However, the missing regulation, specifically in mHealth apps, can lead to providers who store user data on remote servers that are more vulnerable to security breaches [<xref ref-type="bibr" rid="ref81">81</xref>,<xref ref-type="bibr" rid="ref94">94</xref>,<xref ref-type="bibr" rid="ref106">106</xref>,<xref ref-type="bibr" rid="ref107">107</xref>]. Therefore, there are still some aspects to address in the future.</p>
      </sec>
      <sec>
        <title>Limitations</title>
        <p>It should be noted that this study is a scoping review. This means that the presented data are not complete and provide an updated overview of the area of digital diabetology. Systematic reviews and meta-analyses should be taken into account to investigate the effects of technology type on diabetes therapy in more detail.</p>
        <p>The technologies themselves also have limitations that must be considered. There is a time lag in tissue-glucose results and insulin effects, which affects digital therapy approaches. In addition, there must be a certain willingness on the part of the patient to use the technologies and the patient requires skills to use the tools.</p>
        <p>Furthermore, some studies showed rather small intervention effects with regard to HbA<sub>1c</sub> levels. The effect sizes must be examined in more detail.</p>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>In general, the different types of diabetes technologies offer a chance to individualize diabetology and improve the health and QoL of people with DM. With a look at the great advances that have been made in the last few years, rapid further development of diabetes technologies can be expected. In particular, the opportunity to connect different devices to create an automated insulin delivery will become more important. However, to use the full potential of digitalization, regulations and laws must be created to set standards and ensure data security.</p>
      </sec>
    </sec>
  </body>
  <back>
    <app-group/>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">CGM</term>
          <def>
            <p>continuous glucose monitoring</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">DIY AP</term>
          <def>
            <p>do-it-yourself artificial pancreas</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">DM</term>
          <def>
            <p>diabetes mellitus</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">EMR</term>
          <def>
            <p>electronic medical record</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">HbA<sub>1c</sub></term>
          <def>
            <p>glycated hemoglobin A<sub>1c</sub></p>
          </def>
        </def-item>
        <def-item>
          <term id="abb6">mHealth</term>
          <def>
            <p>mobile health</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb7">QoL</term>
          <def>
            <p>quality of life</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb8">SAP</term>
          <def>
            <p>sensor-augmented insulin pump</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb9">SMBG</term>
          <def>
            <p>self-monitoring of blood glucose</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). The authors would like to thank DFG for the support of this research.</p>
    </ack>
    <fn-group>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
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