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Sensor-augmented pump therapy – on the way to artificial pancreas
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"apellidos" => "Ricart" ] 4 => array:1 [ "colaborador" => "por el Grupo Español de Diabetes" ] 5 => array:1 [ "apellidos" => "Embarazo" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1134323010630013?idApp=UINPBA00004N" "url" => "/11343230/0000002600000003/v1_201305021326/S1134323010630013/v1_201305021326/es/main.assets" ] "es" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Revisión</span>" "titulo" => "Sensor-augmented pump therapy – on the way to artificial pancreas" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "143" "paginaFinal" => "146" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Schönauer, A. Thomas" "autores" => array:2 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Schönauer" "email" => array:1 [ 0 => "mschoenauer@email.de" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">†</span>" "identificador" => "cr0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "af0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Thomas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "af0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Akademische Lehrpraxis der Universität Leipzig, Leipzig (Germany)." "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "af0005" ] 1 => array:3 [ "entidad" => "Medtronic. Diabetes Division. Germany" "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "af0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "†" "correspondencia" => "M. Schonauer. Akademische Lehrpraxis der Universitat Leipzig. Diabetes-Zentrum DDG. August-Bebel-Str. 71. D-04275 Leipzig (Germany)." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 686 "Ancho" => 1017 "Tamanyo" => 98422 ] ] "descripcion" => array:1 [ "es" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">HbA<span class="elsevierStyleInf">1c</span> trend in patients, wearing the sensor ≥<span class="elsevierStyleHsp" style=""></span>70% of the time (Real-Trend study: randomization of patients with MDI in CSII or SaP)<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a></p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">The development of insulin pump therapy</span><p id="p0035" class="elsevierStylePara elsevierViewall">The development of an artificial pancreas was first proposed by A.H. Kadish<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> more than four decades ago. This so-called closedloop system appeared and still appears to be the best possible solution for insulin treatment, especially for patients with type 1 diabetes. This kind of system was realised as early as the 1970s with the Biostator. This was a device as large as a table, to which the patient was connected. Blood sugar was measured in blood obtained from a vein and insulin was infused directly via a venous access, just like glucose in the case of falling blood sugar levels. At that time it was optimistically thought that the equipment only needed to be sufficiently reduced in size for patients to be offered a portable system suitable for everyday use. It was expected that the substantial obstacles, namely the fact that sensors for continuous glucose measuring were not yet available and the problem of the unfavourable risk-benefit ratio associated with infusion of insulin and glucose via a venous port, would soon be overcome.<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a></p><p id="p0040" class="elsevierStylePara elsevierViewall">Pursuit of the goal of physiological insulin administration led to the development of small insulin pumps and hence to insulin pump therapy (CSII-continuous subcutaneous insulin infusion). After a hesitant start in the eighties, an established form of insulin therapy was developed.<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> At present between 10% and 20% of patients with type 1 diabetes are treated with CSII in a number of western countries, such as Germany, Netherlands, France, Switzerland and Austria.<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> In 2009 this rate was actually more than 35% in the USA.<a class="elsevierStyleCrossRefs" href="#bb0020"><span class="elsevierStyleSup">4,5</span></a> One of the essential preconditions for the widespread use of CSII was the wide availability of self-monitoring of blood glucose levels. This made it possible to adjust the insulin to the patient's current need and to control functioning of the infusion system (pump, reservoir and infusion set). However, this was an open system (open-loop), which means insulin delivery is not controlled by a glucose sensor and relevant algorithms. In a sense, it is therefore a compromise on the vision of an artificial pancreas.</p><p id="p0045" class="elsevierStylePara elsevierViewall">The most important advantage of CSII is that, using solely short-acting insulin, it adjusts the basal insulin dosage to the diabetic's individual physiological insulin requirement, which can only be depicted with variable basal rate programming in patients with type 1 diabetes.<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> This results in a number of advantages over multiple dose injection therapy (MDI):<ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="u0005"><span class="elsevierStyleLabel">•</span><p id="p0050" class="elsevierStylePara elsevierViewall">In most pump patients, insulin delivery based on demand leads to close-to-normal glycaemia with HbA1c around 7%, without increasing the risk of hypoglycaemia.<a class="elsevierStyleCrossRefs" href="#bb0035"><span class="elsevierStyleSup">7-9</span></a> The lower HbA<span class="elsevierStyleInf">1c</span> compared with MDI lessens the progression of diabetic complications and may even cause their regression to some extent.<a class="elsevierStyleCrossRefs" href="#bb0050"><span class="elsevierStyleSup">10,11</span></a> Markedly smaller blood sugar fluctuations can also be seen, which in turn is likely to be associated with a reduction of vascular risk.<a class="elsevierStyleCrossRefs" href="#bb0060"><span class="elsevierStyleSup">12-14</span></a></p></li><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">•</span><p id="p0055" class="elsevierStylePara elsevierViewall">Even diabetic patients who achieve their target blood sugar levels with difficulty or not at all on MDI usually achieve comparably better control with the aid of an insulin pump.</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">•</span><p id="p0060" class="elsevierStylePara elsevierViewall">Various options for bolus delivery allow optimal insulin adjustment to meals with a variable glycaemic index.<a class="elsevierStyleCrossRefs" href="#bb0075"><span class="elsevierStyleSup">15-17</span></a> High postprandial blood sugar peaks, which are a risk factor for the development of macrovascular diseases (proven at least for type 2 diabetes),<a class="elsevierStyleCrossRefs" href="#bb0090"><span class="elsevierStyleSup">18,19</span></a> are more likely to be avoided.</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">•</span><p id="p0065" class="elsevierStylePara elsevierViewall">The pump allows patients to achieve a more flexible daily profile that is influenced far less by the insulin therapy. This leads to an increase in the diabetic's exercise tolerance and functional capacity. Consequently everyday work activities (e.g. business travellers, doctors, etc.) can be managed better.</p></li><li class="elsevierStyleListItem" id="u0025"><span class="elsevierStyleLabel">•</span><p id="p0070" class="elsevierStylePara elsevierViewall">An increased insulin requirement (e.g. during infection) or reduced requirement (e.g. during sport) can be simply responded to by temporary adjustment of the basal insulin dose.</p></li></ul></p><p id="p0075" class="elsevierStylePara elsevierViewall">The conceptual and clinical advantages as an improvement in HbA1c and/or a decrease in hypoglycaemic events are all the more impressive the worse the initial situation was on the previous MDI.<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> The advantages of CSII have been demonstrated by a large number of experimental and clinical trials but particularly by meta-analyses of randomised, controlled clinical trials (RCTs).<a class="elsevierStyleCrossRefs" href="#bb0105"><span class="elsevierStyleSup">21,22</span></a> In the meta-analysis by Pickup et al. <a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> on 22 studies with a high evidence level, it was shown that in patients with frequent hypoglycaemic episodes their rate decreased by a factor of 4.19, hence to 23.9%. At the same time HbA<span class="elsevierStyleInf">1c</span> improved by an average of 0.61%. This improvement was also confirmed by the meta-analysis of Jeitler et al. <a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> (mean HbA<span class="elsevierStyleInf">1c</span> improvement of 0.55%). Hence CSII versus MDI is not only demonstrably more physiological but also more successful, even if not every patient can realise these advantages.</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Use of continuous glucose monitoring (CGM) in CSII for sensor-augmented pump therapy (SaP)</span><p id="p0080" class="elsevierStylePara elsevierViewall">Patients usually measure their blood sugar after getting up/before breakfast, again before meals and finally before going to bed. They will take additional measurements sporadically, if their blood sugar is not within the desired range or they feel they are having or about to have a hypoglycaemic episode. A total of 5-6 blood sugar measurements a day form the diagnostic basis for CSII. However, CSII has various possible ways of controlling insulin delivery by means of different bolus options or temporary change to the basal rate. If these are utilised, a more extensive database of glucose levels than that provided by self-measurement of glucose at specific time points is valuable. The use of a glucose sensor with continuous, automatic glucose measurement at intervals of a few minutes (CGM) has been demonstrated to be very advantageous for this purpose, more than with all other treatment options (<a class="elsevierStyleCrossRef" href="#f0005">figure 1</a>). The use of a sensor means not only that the open-loop is gaining the essential component for further development into a closed-loop system, but it also turns CSII into a new form of therapy, namely sensor-augmented pump (SaP) therapy.</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0085" class="elsevierStylePara elsevierViewall">A glucose sensor used for CGM is minimally invasive, which means a small needle electrode is pushed under the skin and measures glucose in the interstitial space with the aid of chemical principles similar to self-monitoring of blood glucose, i.e. conversion of glucose into gluconic acid and hydrogen peroxide with the aid of the enzyme glucose oxidase, dissociation of the hydroxide peroxide at an electrode and measurement of the resulting flow of current dependent on the glucose concentration.<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> A measurement is taken every 10 seconds. These individual measurements are combined to form a mean measurement over 5<span class="elsevierStyleHsp" style=""></span>min and indicated on a display. A sensor is used for 6 days.</p><p id="p0090" class="elsevierStylePara elsevierViewall">This gives the patient an opportunity to influence his glucose profile directly, which mainly includes active avoidance of hypoglycaemic events. Adjustable alert thresholds for hypoglycaemic and hyperglycaemic levels help patients to do this. The advantages of CGM with current glucose levels have been demonstrated in several RCTs. Among these, the JDRF (Juvenile Diabetes Research Foundation) studies are hitherto the largest and methodologically best RCTs involving CGM.<a class="elsevierStyleCrossRefs" href="#bb0120"><span class="elsevierStyleSup">24,25</span></a> As a result of the application and dependent on the level of use of CGM, the HbA1c levels in JDRF I study (baseline HbA1c ><span class="elsevierStyleHsp" style=""></span>7-10%, 322 patients with type 1 diabetes) improved over 6 months as a result of adequate use of CGM in adults aged over 25 years, being the effect only significant in this age group with a 0.5% HbA<span class="elsevierStyleInf">1c</span> improvement.<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> In well-controlled patients with type 1 diabetes (JDRF <<span class="elsevierStyleHsp" style=""></span>7 study, 129 patients with type 1 diabetes), this value did remain constant at 6.4% although the time spent in the range of hypoglycaemic glucose levels (≤ 70<span class="elsevierStyleHsp" style=""></span>mg/dl) was reduced by 41% from a daily average of 91<span class="elsevierStyleHsp" style=""></span>min to 54<span class="elsevierStyleHsp" style=""></span>min. In this trial, all three age groups showed good compliance in terms of adequate use of the CGM system, which is why the positive effect was relevant irrespective of the age group.<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a></p><p id="p0095" class="elsevierStylePara elsevierViewall">These improvements become visible particularly on CSII because of the potential fine control of therapy. The Paradigm® VEO system comprises the insulin pump, with the option of transferring the current glucose levels recorded by a glucose sensor via a wireless interface to the system display (<a class="elsevierStyleCrossRef" href="#f0010">figure 2</a>). These data can also be incorporated into the bolus delivery calculation (Bolus Wizard) and, after suitable confirmation by a conventional blood sugar measurement, entered into the insulin bolus calculation. As with the previous model (Paradigm® REAL-Time), under normal conditions the glucose sensor does not yet intervene automatically in glycaemic regulation but offers the patient a complete overview of his glucose profile. The system hence works as an “open system”, either in CSII mode (i.e. without the CGM component) or in SaP mode (if a glucose sensor is being used).</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0100" class="elsevierStylePara elsevierViewall">The superiority of SaP over classic CSII has been demonstrated in RCTs, for example in the multicentre REAL Trend study (<a class="elsevierStyleCrossRef" href="#f0015">figure 3</a>)<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> In this study, the patients had previously been treated with ICT, on which they displayed inadequate glycaemic control. On SAP, their HbA<span class="elsevierStyleInf">1c</span> improved by 1.23% over the course of the 6 months of the study for the group of 91 patients who wore the sensor ≥<span class="elsevierStyleHsp" style=""></span>70% of the time or by 1.14% for all patients (n<span class="elsevierStyleHsp" style=""></span>= 115). By comparison, the percentage improvement on CSII was only 0.55%.</p><elsevierMultimedia ident="f0015"></elsevierMultimedia></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Sensor-augmented pump therapy (SaP) with automated hypoglycaemia management</span><p id="p0105" class="elsevierStylePara elsevierViewall">The Paradigm® VEO system is the first to offer the possibility of treatment control by means of a glucose sensor. The system initially sounds an alert if there is a risk of or an actual hypoglycaemic event depending on the threshold setting. If the patient does not respond to these alerts because he is deeply asleep, for example, the insulin pump automatically suspends insulin delivery for 120<span class="elsevierStyleHsp" style=""></span>min, a function known as LGS low glucose suspend. After this period of time, it automatically switches back on if the patient has not already done so manually. By this mechanism, hypoglycaemia can largely be avoided.<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a> Hyperglycaemia or even diabetic ketoacidosis are unlikely to arise because of the relatively short suspension of 120<span class="elsevierStyleHsp" style=""></span>min maximum. It is therefore the first time that a glucose sensor intervenes directly in therapy, making it a major advance towards an automated insulin pump system and hence towards an artificial pancreas.</p><p id="p0110" class="elsevierStylePara elsevierViewall">There is currently intensive research work on further steps towards a closed-loop system. In the creation of an “artificial pancreas”, the key challenge is to develop algorithms for controlled insulin delivery based on measured glucose levels, while subcutaneous measurement and subcutaneous insulin delivery are favoured in view of the cost-benefit-risk relationship and the available hardware. The measurement of glucose in the interstitial fluid and the resulting physiological time lag to the blood glucose concentration as well as the non-physiological infusion of insulin into subcutaneous tissue pose a special challenge to this algorithm.</p><p id="p0115" class="elsevierStylePara elsevierViewall">It should further be noted that insulin must be delivered in such a way that the glucose concentration can be predicted as lying in the normoglycaemic range. Previous studies show that normoglycaemic glucose regulation is achieved solely in the basal phase without food intake and without physical activity but unphysiologically high glucose levels occur after meals. The problem is essentially due to subcutaneous exogenous insulin, which unlike endocrine insulin is peripherally active first and only then hepatically active so that gluconeogenesis is not immediately halted. Thus, its pharmacodynamics is independent of the glucose stimulus. For this purpose, the short-acting insulin analogues currently available on the market are still too slow. In any event, however, the activities and the number of studies and publications on this subject have markedly increased.</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Summary</span><p id="p0120" class="elsevierStylePara elsevierViewall">Sensor-augmented pump therapy is a major advance towards a closed-loop system. In the process, the glucose sensor, which is an essential component of the artificial pancreas, is being introduced directly into insulin pump therapy (<a class="elsevierStyleCrossRef" href="#f0020">figure 4</a>). Assuming continuous use of the CGM component, the positive effects of CSII are markedly enhanced. Automated intervention when hypoglycaemia is ignored or not noticed means that the lowest level of a closed-loop has already been realised in a marketable product (LGS low glucose suspend). After decades of waiting, the diabetology vision of an artificial pancreas now seems within reach. ¿</p><elsevierMultimedia ident="f0020"></elsevierMultimedia></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Declaration of potential conflicts of interest</span><p id="p0125" class="elsevierStylePara elsevierViewall">Dr. Martin Schonauer is a diabetologist, with no commercial interests in respect of the technology and therapy presented. Dr. Andreas Thomas is Scientific Manager of Medtronic, Diabetes Division, Germany.<elsevierMultimedia ident="b0005"></elsevierMultimedia></p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xres108758" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec96179" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "The development of insulin pump therapy" ] 3 => array:2 [ "identificador" => "s0010" "titulo" => "Use of continuous glucose monitoring (CGM) in CSII for sensor-augmented pump therapy (SaP)" ] 4 => array:2 [ "identificador" => "s0015" "titulo" => "Sensor-augmented pump therapy (SaP) with automated hypoglycaemia management" ] 5 => array:2 [ "identificador" => "s0020" "titulo" => "Summary" ] 6 => array:2 [ "identificador" => "s0025" "titulo" => "Declaration of potential conflicts of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2010-03-19" "fechaAceptado" => "2010-05-11" "PalabrasClave" => array:1 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec96179" "palabras" => array:4 [ 0 => "continuous glucose monitoring" 1 => "sensor-augmented pump therapy" 2 => "low glucose suspend" 3 => "closed loop" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "es" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">The continuous subcutaneous insulin infusion (CSII) is an established form of insulin therapy for patients with type 1 diabetes mellitus. The vision, the development of an artificial pancreas (closed-loop) is not yet realized. One important precondition for this to achieve, the availability of continuous glucose monitoring (CGM), is given. The combination of CSII and CGM turns CSII into a new form of therapy, the sensor-augmented pump therapy (SaP). The superiority of SaP over classic CSII has been proven in randomised, controlled clinical trials. In this article, we review this new possibility of insulin therapy.</p>" ] ] "nomenclatura" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleSectionTitle" id="st0015">List of acronyms quoted in the text:</span>" "listaDefinicion" => array:1 [ 0 => array:1 [ "definicion" => array:6 [ 0 => array:2 [ "termino" => "CGM" "descripcion" => "<p id="p0005" class="elsevierStylePara elsevierViewall">continuous glucose monitoring</p>" ] 1 => array:2 [ "termino" => "CSII" "descripcion" => "<p id="p0010" class="elsevierStylePara elsevierViewall">continuous subcutaneous insulin infusión</p>" ] 2 => array:2 [ "termino" => "LGS" "descripcion" => "<p id="p0015" class="elsevierStylePara elsevierViewall">low glucose suspend</p>" ] 3 => array:2 [ "termino" => "MDI" "descripcion" => "<p id="p0020" class="elsevierStylePara elsevierViewall">multiple dose injection</p>" ] 4 => array:2 [ "termino" => "RTCs" "descripcion" => "<p id="p0025" class="elsevierStylePara elsevierViewall">randomised, controlled clinical trials</p>" ] 5 => array:2 [ "termino" => "SaP" "descripcion" => "<p id="p0030" class="elsevierStylePara elsevierViewall">sensor-augmented pump therapy.</p>" ] ] ] ] ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 714 "Ancho" => 1016 "Tamanyo" => 130306 ] ] "descripcion" => array:1 [ "es" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Treatment options for patients with diabetes mellitus and the helpful/necessary diagnostic options</p>" ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 976 "Ancho" => 2092 "Tamanyo" => 219004 ] ] "descripcion" => array:1 [ "es" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Innovations and components of the Paradigm® VEO insulin pump system with the option of sensor-augmented pump (SaP) therapy resulting from connection to the glucose sensor</p>" ] ] 2 => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 686 "Ancho" => 1017 "Tamanyo" => 98422 ] ] "descripcion" => array:1 [ "es" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">HbA<span class="elsevierStyleInf">1c</span> trend in patients, wearing the sensor ≥<span class="elsevierStyleHsp" style=""></span>70% of the time (Real-Trend study: randomization of patients with MDI in CSII or SaP)<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a></p>" ] ] 3 => array:7 [ "identificador" => "f0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 686 "Ancho" => 2091 "Tamanyo" => 109659 ] ] "descripcion" => array:1 [ "es" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Development of CSII from its initial basic functions via extended functions and the use of CGM through to the closed-loop system.</p> <p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">The years and decisive influences in terms of measuring technology are shown on the right</p>" ] ] 4 => array:5 [ "identificador" => "b0005" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:2 [ "titulo" => "Key messages" "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0135" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0030"><span class="elsevierStyleLabel">•</span><p id="p0140" class="elsevierStylePara elsevierViewall">Sensor-augmented pump therapy, currently the most physiological form of insulin treatment, results from combination of continuous glucose monitoring with CSII.</p></li><li class="elsevierStyleListItem" id="u0035"><span class="elsevierStyleLabel">•</span><p id="p0145" class="elsevierStylePara elsevierViewall">The latest type of insulin pump can interrupt automatically the insulin delivery for two hours in situations of ignored or unnoticed hypoglycaemia.</p></li><li class="elsevierStyleListItem" id="u0040"><span class="elsevierStyleLabel">•</span><p id="p0150" class="elsevierStylePara elsevierViewall">For patients with hypoglycaemia unawareness, the low glucose suspend function is an additional safety feature of insulin pumps, which may help them to achieve close-to-normal glycemic controls.</p></li></ul></p></span>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" 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"referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous glucose monitoring and intensive treatment of type 1 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "JDRF Continuous Glucose Monitoring Study Group" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0805017" "Revista" => array:6 [ "tituloSerie" => "NEJM" "fecha" => "2008" "volumen" => "359" "paginaInicial" => "1464" "paginaFinal" => "1476" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18779236" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bb0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of continuous glucose monitoring in well-controlled type 1 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.W. Beck" 1 => "for JDRF CGM Study Group" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc09-0108" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2009" "volumen" => "32" "paginaInicial" => "1378" "paginaFinal" => "1383" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19429875" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bb0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incremental Value of Continuous Glucose Monitoring When Starting Pump Therapy in Patients With Poorly Controlled Type 1 Diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Raccah" 1 => "V. Sulmont" 2 => "Y. Reznik" 3 => "B. Guerci" 4 => "H. Hanaire" 5 => "N. Jeandidier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc09-0750" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care." "fecha" => "2009" "volumen" => "32" "paginaInicial" => "2245" "paginaFinal" => "2250" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19767384" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bb0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Preventing Hypoglycemia Using Predictive Alarm Algorithms and Insulin Pump Suspension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.A. Buckingham" 1 => "E. Cobry" 2 => "P. Clinton" 3 => "V. Gage" 4 => "K. Caswell" 5 => "E. Kunselman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/dia.2008.0032" "Revista" => array:6 [ "tituloSerie" => "Diabetes Technol Ther." "fecha" => "2009" "volumen" => "11" "paginaInicial" => "93" "paginaFinal" => "97" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19848575" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "es" "url" => "/11343230/0000002600000003/v1_201305021326/S1134323010630025/v1_201305021326/es/main.assets" "Apartado" => array:4 [ "identificador" => "7305" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Revisión" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/11343230/0000002600000003/v1_201305021326/S1134323010630025/v1_201305021326/es/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1134323010630025?idApp=UINPBA00004N" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Octubre | 107 | 10 | 117 |
| 2024 Septiembre | 137 | 17 | 154 |
| 2024 Agosto | 138 | 22 | 160 |
| 2024 Julio | 132 | 8 | 140 |
| 2024 Junio | 102 | 15 | 117 |
| 2024 Mayo | 116 | 6 | 122 |
| 2024 Abril | 142 | 11 | 153 |
| 2024 Marzo | 173 | 15 | 188 |
| 2024 Febrero | 183 | 16 | 199 |
| 2024 Enero | 218 | 10 | 228 |
| 2023 Diciembre | 172 | 12 | 184 |
| 2023 Noviembre | 206 | 8 | 214 |
| 2023 Octubre | 211 | 28 | 239 |
| 2023 Septiembre | 136 | 9 | 145 |
| 2023 Agosto | 150 | 10 | 160 |
| 2023 Julio | 170 | 14 | 184 |
| 2023 Junio | 182 | 12 | 194 |
| 2023 Mayo | 232 | 21 | 253 |
| 2023 Abril | 185 | 15 | 200 |
| 2023 Marzo | 186 | 24 | 210 |
| 2023 Febrero | 171 | 19 | 190 |
| 2023 Enero | 160 | 23 | 183 |
| 2022 Diciembre | 185 | 13 | 198 |
| 2022 Noviembre | 233 | 30 | 263 |
| 2022 Octubre | 216 | 20 | 236 |
| 2022 Septiembre | 219 | 39 | 258 |
| 2022 Agosto | 155 | 15 | 170 |
| 2022 Julio | 143 | 17 | 160 |
| 2022 Junio | 158 | 21 | 179 |
| 2022 Mayo | 205 | 27 | 232 |
| 2022 Abril | 230 | 12 | 242 |
| 2022 Marzo | 246 | 22 | 268 |
| 2022 Febrero | 233 | 22 | 255 |
| 2022 Enero | 180 | 25 | 205 |
| 2021 Diciembre | 122 | 31 | 153 |
| 2021 Noviembre | 170 | 26 | 196 |
| 2021 Octubre | 135 | 39 | 174 |
| 2021 Septiembre | 119 | 27 | 146 |
| 2021 Agosto | 150 | 28 | 178 |
| 2021 Julio | 116 | 23 | 139 |
| 2021 Junio | 112 | 11 | 123 |
| 2021 Mayo | 151 | 14 | 165 |
| 2021 Abril | 333 | 75 | 408 |
| 2021 Marzo | 190 | 34 | 224 |
| 2021 Febrero | 178 | 32 | 210 |
| 2021 Enero | 155 | 32 | 187 |
| 2020 Diciembre | 146 | 13 | 159 |
| 2020 Noviembre | 151 | 35 | 186 |
| 2020 Octubre | 115 | 19 | 134 |
| 2020 Septiembre | 184 | 34 | 218 |
| 2020 Agosto | 120 | 23 | 143 |
| 2020 Julio | 101 | 11 | 112 |
| 2020 Junio | 80 | 10 | 90 |
| 2020 Mayo | 113 | 19 | 132 |
| 2020 Abril | 110 | 13 | 123 |
| 2020 Marzo | 124 | 28 | 152 |
| 2020 Febrero | 132 | 22 | 154 |
| 2020 Enero | 111 | 11 | 122 |
| 2019 Diciembre | 134 | 25 | 159 |
| 2019 Noviembre | 192 | 13 | 205 |
| 2019 Octubre | 176 | 16 | 192 |
| 2019 Septiembre | 120 | 7 | 127 |
| 2019 Agosto | 76 | 2 | 78 |
| 2019 Julio | 63 | 18 | 81 |
| 2019 Junio | 100 | 21 | 121 |
| 2019 Mayo | 148 | 38 | 186 |
| 2019 Abril | 87 | 40 | 127 |
| 2019 Marzo | 22 | 3 | 25 |
| 2019 Febrero | 28 | 7 | 35 |
| 2019 Enero | 25 | 5 | 30 |
| 2018 Diciembre | 20 | 4 | 24 |
| 2018 Noviembre | 42 | 4 | 46 |
| 2018 Octubre | 79 | 22 | 101 |
| 2018 Septiembre | 114 | 12 | 126 |
| 2018 Agosto | 44 | 1 | 45 |
| 2018 Julio | 36 | 3 | 39 |
| 2018 Junio | 29 | 1 | 30 |
| 2018 Mayo | 26 | 3 | 29 |
| 2018 Abril | 36 | 2 | 38 |
| 2018 Marzo | 87 | 0 | 87 |
| 2018 Febrero | 25 | 0 | 25 |
| 2018 Enero | 63 | 0 | 63 |
| 2017 Diciembre | 41 | 1 | 42 |
| 2017 Noviembre | 13 | 0 | 13 |
| 2017 Octubre | 22 | 3 | 25 |
| 2017 Septiembre | 21 | 1 | 22 |
| 2017 Agosto | 16 | 2 | 18 |
| 2017 Julio | 12 | 0 | 12 |
| 2017 Junio | 21 | 3 | 24 |
| 2017 Mayo | 25 | 4 | 29 |
| 2017 Abril | 15 | 1 | 16 |
| 2017 Marzo | 29 | 2 | 31 |
| 2017 Febrero | 85 | 0 | 85 |
| 2017 Enero | 14 | 5 | 19 |
| 2016 Diciembre | 11 | 2 | 13 |
| 2016 Noviembre | 11 | 0 | 11 |
| 2016 Octubre | 11 | 0 | 11 |
| 2016 Septiembre | 10 | 0 | 10 |
| 2016 Agosto | 8 | 1 | 9 |
| 2016 Julio | 4 | 4 | 8 |
| 2016 Junio | 11 | 2 | 13 |
| 2016 Mayo | 5 | 7 | 12 |
| 2016 Abril | 13 | 4 | 17 |
| 2016 Marzo | 7 | 11 | 18 |
| 2016 Febrero | 7 | 12 | 19 |
| 2016 Enero | 5 | 13 | 18 |
| 2015 Diciembre | 5 | 12 | 17 |
| 2015 Noviembre | 8 | 12 | 20 |
| 2015 Octubre | 11 | 12 | 23 |
| 2015 Septiembre | 8 | 5 | 13 |
| 2015 Agosto | 6 | 3 | 9 |
| 2015 Julio | 6 | 2 | 8 |
| 2015 Junio | 1 | 1 | 2 |
| 2015 Mayo | 6 | 2 | 8 |
| 2015 Abril | 14 | 9 | 23 |
| 2015 Marzo | 8 | 3 | 11 |
| 2015 Febrero | 2 | 2 | 4 |
| 2015 Enero | 19 | 0 | 19 |
| 2014 Diciembre | 16 | 5 | 21 |
| 2014 Noviembre | 4 | 2 | 6 |
| 2014 Octubre | 23 | 6 | 29 |
| 2014 Septiembre | 21 | 4 | 25 |
| 2014 Agosto | 8 | 3 | 11 |
| 2014 Julio | 17 | 1 | 18 |
| 2014 Junio | 14 | 1 | 15 |
| 2014 Mayo | 13 | 3 | 16 |
| 2014 Abril | 8 | 3 | 11 |
| 2014 Marzo | 13 | 2 | 15 |
| 2014 Febrero | 13 | 8 | 21 |
| 2014 Enero | 11 | 3 | 14 |
| 2013 Diciembre | 10 | 1 | 11 |
| 2013 Noviembre | 10 | 1 | 11 |
| 2013 Octubre | 8 | 6 | 14 |
| 2013 Septiembre | 9 | 3 | 12 |
| 2013 Agosto | 6 | 1 | 7 |
| 2013 Julio | 2 | 1 | 3 |
| 2013 Junio | 0 | 1 | 1 |
| 2010 Abril | 98 | 0 | 98 |
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