Comparison between a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) using continuous glucose monitoring in metabolically optimized type 1 diabetes patients: A randomized open-labelled parallel study

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=> "aff0020" ] ] ] 8 => array:3 [ "nombre" => "Federico" "apellidos" => "Soriguer" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 9 => array:3 [ "nombre" => "María Teresa" "apellidos" => "Anarte" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 10 => array:3 [ "nombre" => "Gemma" "apellidos" => "Rojo-Martínez" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Diabetes Centre, Department of Endocrinology and Nutrition, General University Hospital of Malaga, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "CIBERDEM (Carlos III Health Institute), Malaga, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Personality, Assessment and Psychological Treatment, Faculty of Psychology, University of Malaga, Malaga, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Instituto de Investigación Biomédica de Málaga (IBIMA), Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Department of Endocrinology, Clinical Universitary of Navarra, Pamplona, Navarra, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⽽" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Comparación entre múltiples dosis de insulina (insulina glargina una vez al día y lispro en las comidas) e infusión subcutánea continua de insulina con monitorización continua de glucosa en pacientes con diabetes tipo 1 metabólicamente optimizados. Estudio randomizado" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1395 "Ancho" => 1584 "Tamanyo" => 80715 ] ] "descripcion" => array:1 [ "en" => "DQOL at baseline, and after 6 and 12 months with MDI and CSII. *p<0.05 basal⬜6 month in 2 groups; **p<0.05 6 month⬜12 month in CSII group." ] ] ] "textoCompleto" => "IntroductionContinuous subcutaneous insulin infusion (CSII) as therapy for patients with type 1 diabetes became available more than 30 years ago.<a class="elsevierStyleCrossRef" href="#bib0215">1</a> Since then several meta-analyses have reviewed multiple daily injections (MDI) therapy, most with MDI/NPH vs. CSII, discovering greater efficacy in glycaemic control with CSII therapy, in addition to a decrease in the incidence of hypoglycaemic events.<a class="elsevierStyleCrossRefs" href="#bib0220">2⬜7</a> These meta-analyses established CSII therapy as the gold standard for insulin therapy in patients with type 1 diabetes. In addition, the relative benefit of CSII therapy over MDI/NPH is greater at higher baseline HbA1c values.<a class="elsevierStyleCrossRef" href="#bib0250">8</a> The limitations of MDI/NPH have been alleviated with the introduction of glargine, a long-acting insulin analogue with a flatter and more prolonged time-action profile.<a class="elsevierStyleCrossRef" href="#bib0255">9</a> Combined with rapid-acting insulin analogues, glargine provides better glycaemic control than intermediate-acting insulin NPH, with no increased risk of hypoglycaemia.<a class="elsevierStyleCrossRefs" href="#bib0260">10,11</a> The question of whether CSII therapy with ultra-rapid insulin continues to be the gold standard in intensive insulin treatment for type 1 diabetes, however, is still not resolved.Whereas several authors have found no difference between CSII and MDI with glargine in a variety of end-points, others have found CSII to be superior. Several randomized studies have performed a comparative evaluation of CSII vs. MDI with insulin glargine (MDI/G).<a class="elsevierStyleCrossRefs" href="#bib0270">12⬜17</a> In adults, HbA1C results are similar with both treatments. However, in the study by Hirsch et al.<a class="elsevierStyleCrossRef" href="#bib0280">14</a> the results obtained from the measurement of serum levels of fructosamine and the reduced exposure to hyperglycaemia assessed through continuous glucose monitoring (CGMS) showed better metabolic control with CSII.Severe hypoglycaemia remains one of the most feared complications.<a class="elsevierStyleCrossRef" href="#bib0300">18</a> The scientific evidence that CSII therapy reduces the frequency of severe hypoglycaemia compared to MDI/NPH is very strong.<a class="elsevierStyleCrossRef" href="#bib0305">19</a> Pickup and Keen,<a class="elsevierStyleCrossRef" href="#bib0220">2</a> in their review, found that the rate of severe hypoglycaemia was four times lower with CSII than with MDI, and the greatest improvements occurred in those patients with higher rates of severe hypoglycaemia when treated with MDI. The frequency of mild hypoglycaemia is also lower with CSII, with a reduction of 75% after switching from MDI.<a class="elsevierStyleCrossRef" href="#bib0310">20</a> Several studies comparing MDI based on glargine or detemir have found a lower incidence of nocturnal hypoglycaemia than with NPH.<a class="elsevierStyleCrossRef" href="#bib0315">21</a> On the other hand, studies comparing the incidence of severe hypoglycaemia during CSII and MDI with long-acting analogues have given contrasting results, with some finding no difference<a class="elsevierStyleCrossRefs" href="#bib0280">14,15,17</a> while others found that patients prone to hypoglycaemia had fewer hypoglycaemic episodes during CSII.<a class="elsevierStyleCrossRef" href="#bib0310">20</a>Currently there is strong interest in glycaemic variability, due to the possible relationship with microvascular and macrovascular disease.<a class="elsevierStyleCrossRefs" href="#bib0320">22,23</a> Indeed, glycaemic variability in combination with HbA1c could be a more realistic indicator of glycaemic control and long-term risk of complications than HbA1c alone.<a class="elsevierStyleCrossRefs" href="#bib0330">24,25</a> Several authors found that glucose variability during CSII was smaller than during MDI/NPH.<a class="elsevierStyleCrossRefs" href="#bib0340">26,27</a> Other studies have compared the effects on glucose variability of CSII and MDI based on long-acting analogues and have found either no differences, or higher or lower glucose variability<a class="elsevierStyleCrossRefs" href="#bib0270">12,14,16,28⬜30</a> during CSII.There are conflicting results concerning the effects of CSII therapy on quality of life. A meta-analysis in 2007 concluded that the effects of CSII on quality of life remain unclear.<a class="elsevierStyleCrossRef" href="#bib0365">31</a> More recent studies have obtained different results, some finding a better quality of life<a class="elsevierStyleCrossRefs" href="#bib0375">15,27,32</a> but others seeing a similar quality of life with CSII.<a class="elsevierStyleCrossRef" href="#bib0295">17</a>The objectives of this study were to determine: (1) whether CSII is more effective than MDI therapy using insulin analogues (rapid and long) in metabolic control and QOL, and (2) whether CSII therapy has supplemental benefits in patients with type 1 diabetes who are optimized with MDI therapy using insulin analogues.Materials and methodsThis was a randomized, parallel group, open-label study performed in the Diabetes Centre of the Endocrinology and Nutrition Department of Carlos Haya University Hospital in Malaga, Spain.SubjectsInclusion criteria: patients aged 18⬜65 years with type 1 diabetes for more than 5 years.Exclusion criteria: acute coronary syndrome or stroke in the last 6 months, active proliferative retinopathy, uncontrolled hypertension, severe vegetative neuropathy, impaired hepatic/renal function, prior use of CSII or insulin glargine, patients unable to use CSII or MDI or patients planning pregnancy.A total of 45 patients met the inclusion criteria.The sample size calculation was performed to detect a difference of 1.5% in HbA1c using a standard deviation of 1.2, a α=0.05 (two-tailed), and a power of 90%. The resulting minimum size was 15 patients per group, including 15% of lost patients. To obtain 30 patients (15 CSII and 15 MDI/G) 45 is selected in case had lost over 15% calculated on the protocol development. The key is the intergroup comparison (CSII vs. MDI/G) and is carried out at 12 months.During the first 6 months seven patients were lost, leaving 38 patients; then, without meeting criteria for CSII therapy, these 38 patients were randomized, 15 to CSII and 23 to MDI/G during six months, with no patients lost in this phase. The 7 patients withdrawing of the study at the first phase owed to the inability to follow protocol and monthly visits.All the subjects provided written informed consent. The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines and with the approval of the Ethics Committee of Carlos Haya University Hospital.DesignRandomized clinical trial (2 MDI/G: 1 CSII) with a prior homogenization phase with MDI/G.<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">⬢Phase 1: educational homogenization and adherence.Forty-five patients with type 1 diabetes, under treatment with MDI/NPH and rapid analogues, were switched to MDI with glargine as basal insulin and followed-up monthly for 6 months. The patients used insulin lispro (Eli Lilly Inc., Indianapolis, IN) before each meal and a single dose of glargine. Seven patients dropped out of the study in Phase 1.</li><li class="elsevierStyleListItem" id="lsti0010">⬢Phase 2: randomization. After the first 6 months, from this metabolically optimized group, 15 patients were randomly assigned to CSII therapy. These CSII patients received insulin lispro via a multi-programmable insulin infusion system (Paradigm 712, Medtronic, USA). 23 patients continued with MDI/G once daily in the evening plus mealtime insulin lispro; both groups completed 6 further months (23 patients MDI/G vs. 15 patients CSII), with monthly follow-up.</li></ul>All the patients developed skills necessary for intensive functional therapy including self-monitoring of blood glucose (SMBG) using a plasma-calibrated memory glucose metre (OneTouch Ultra; Lifescan, Milpitas, CA), carbohydrate counting, insulin adjustment and technical aspects of the pumps. The glycaemic targets were identical for both treatment groups: glycaemia of 80⬜120mg/dl (4.4⬜6.6mmol/L) before and <150mg/dl (8.3mmol/L) 2h after meals. Three days of glycaemia monitoring via CGSM (Medtronic, USA) was done at the end of each treatment period and the time spent with blood glucose<70mg/dl/3.9mmol/L, >180mg/dl/10mmol/L, and 70⬜180mg/dl/3.9⬜9.9mmol/L was recorded.<a class="elsevierStyleCrossRef" href="#bib0380">33</a>Variables and instruments<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">⬢Sociodemographics: sex and age.</li><li class="elsevierStyleListItem" id="lsti0020">⬢Anthropometric: weight, BMI.</li><li class="elsevierStyleListItem" id="lsti0025">⬢Insulin therapy: daily insulin dose (DID) (insulin/kg), basal insulin dose (%), bolus insulin dose (%)</li><li class="elsevierStyleListItem" id="lsti0030">⬢Complications: mild hypoglycaemia (episodes per week), severe hypoglycaemia (episodes per 6 months) and ketoacidosis episodes. Hypoglycaemia was defined according to the ADA criteria.<a class="elsevierStyleCrossRef" href="#bib0385">34</a></li><li class="elsevierStyleListItem" id="lsti0035">⬢Metabolic control parameters: HbA1c (HPLC; Diabetes Control and Complications Trial [DCCT] Research Group aligned).</li><li class="elsevierStyleListItem" id="lsti0040">⬢Glycaemic variability parameters: obtained by standard deviation (SD), low blood glucose index (LBGI) and high blood glucose index (HBGI),<a class="elsevierStyleCrossRef" href="#bib0390">35</a> obtained from CGSM.</li><li class="elsevierStyleListItem" id="lsti0045">⬢Quality of life parameters: the quality of life during each treatment phase was measured using a version of the Diabetes Quality of Life (EsDQOL) questionnaire of the DCCT Research Group, adapted to the Spanish population.<a class="elsevierStyleCrossRef" href="#bib0395">36</a> The scale consists of 43 items that are 4 dimensions: satisfaction with treatment (15 items), impact of treatment (17 items), social/vocational concerns (7 items) and concern regarding the future effects of diabetes (4 items). Each item has 5 possible answers on Likert scoring from 1 to 5. Satisfaction subscale responses to each item ranged from ⬓very satisfied⬽ (1 point) to ⬓not satisfied⬽ (5 points). In the other three subscales, responses ranged from ⬓never⬽ (1 point) to ⬓always⬽ (5 points). A total score and subscales score can be obtained. A lower score means better quality of life. It is designed to be self-administered.</li><li class="elsevierStyleListItem" id="lsti0050">⬢The primary objectives were the HbA1c value at the end of each treatment phase, with a goal of HbA1c <7.5% and the QOL during each phase.</li></ul>Data analysis and statisticsThe data are presented as mean±SD or proportions. At baseline, homogeneity between the randomized sequence groups (CSII and MDI/G) was tested using two-sample unpaired Student's t-test for normally distributed data, or the Wilcoxon rank sum test for non-normally distributed data. To compare the scores before and after treatment two types of analysis were used. For the variables with scores that adjusted to a normal distribution a repeated measures ANOVA was used. For the variables with scores that did not follow a normal distribution a non-parametric contrast test was used (Wilcoxon test). For comparison of means the Student t test was used for related or independent samples and the chi-square test was used to determine the association between qualitative variables. Analyses per protocol were done and carried out with SPSS software (18.0 version). The confidence intervals were set at 95%.ResultsBaseline data (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1</a>)The mean age of patients was 29.8±8.5 years, 46% were men, the duration of diabetes was 13.7±7 years, the mean HbA1c was 8.4±1.2% (68±9.7mmol/mol), 33% with <7.5% (58.5mmol/mol). The baseline characteristics were similar for both treatment groups.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Phase 1: homogenization (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>)Metabolic control: in the first 6 months (MDI/NPH to MDI/glargine) (n=38), there was an improvement in HbA1c, with a mean decrease of 0.5% (8.4±1.2% vs. 7.9±0.7%; p<0.032) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), a HbA1c <7.5% was reached by 36.8% of the patients (vs. 33% at baseline; p<0.7) and the frequency of severe hypoglycaemia declined (0.44±0.9 vs. 0.050±0.2; p<0.014) with no changes in mild hypoglycaemia. There was an increase in the number of self-analyses per day (3±1.2 vs. 4.33±1.5; p<0.0001) and an increase in BMI (25.4±3 vs. 25.9±3.5; p<0.014). The total daily insulin decreased 8% (0.87±0.29 vs. 0.80±0.25IU/kg; p<0.049) and basal insulin decreased 12% (41.8±16.4 vs. 36.8±15.7IU/day; p<0.001). There were no episodes of ketoacidosis in the group. With respect to the CGMS data, there was an increase in periods of normoglycaemia (15.8±11% vs. 23±18.4%; p<0.03) and a significant improvement in glycaemic variability measured by the SD of CGMS (66.9±14 vs. 59.4±16; p<0.05).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Quality of life: significant changes were perceived in the overall EsDQOL (99.72±18.38 vs. 92.07±17.65; p<0.007) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) and an improvement in the subscale ⬓satisfaction with treatment⬽ (39.15±8.54 vs. 35.45±7.46; p<0.01).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Phase 2: after randomization (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>)Metabolic control: In the CSII group, after 6 months HbA1c values decreased significantly (7.9±0.7% [63±5.5mmol/mol] to 7±0.6% [53±4.5]; p<0.00) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), with 67% of patients achieving the objective of 7.5% (vs. 6m: 36.8%) (p=0.5). There was an improvement in time in normoglycaemia (23±18.4 vs. 50±1.6%; p<0.002), time in hyperglycaemia (69.4±21.5 vs. 42.3±12%; p<0.02) and HBGI (CGMS) (8.1±4.5 vs. 5.4±0.3; p<0.045).In the MDI/G group, no significant change was seen in HbA1c (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In CGMS, decreases were seen in mean glycaemia (162±30mg/dl vs. 146.78±36; p<0.04), and time in hyperglycaemia (69.38±43.16 vs. 43±16.2%; p<0.01) and an increase in time in normoglycaemia (23±18.4 vs. 50.7±18%; p<0.01).Although a tendency towards better control parameters was seen in the metabolic variables evaluated in the two groups, significantly lower levels of HbA1c were only seen in the CSII group compared with the MDI/G group (MDI/G 7.6±0.9 vs. CSII 7±0.6%; p<0.03), with a higher number of self-tests per day in the CSII group compared to the MDI/G group: 4.7±1.6 vs. 3.2±1.5 (p<0.008). There is a positive correlation in the set of the 38 patients at 12 months between the number of SMBG and reached HbA1c (r=↙0.45, p=0.005.) which does not occur in each group independently (MDI/G r=0.3; p=0.13; CSII r=0.4; p=0.14).No changes were seen in BMI, insulin dose, mild or severe hypoglycaemia or episodes of ketosis or ketoacidosis in the two groups.Quality of life: the total DQOL score decreased significantly in the CSII group (91.66±22 to 84.53±1.63; p<0.045) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The differences between groups (CSII vs. MDI/G) in absolute scores for total DQOL and the subscales were not significant.There were no serious adverse events during the study.DiscussionFor many years, the advantages of CSII therapy made it a superior treatment compared with MDI/NPH. The incorporation of the long-acting analogues glargine and detemir, soluble insulins with a more predictable absorption, more stable blood levels and with the possibility of improving glycaemic control, have now raised the question of whether these new insulins can replace the need for CSII in people with type 1 diabetes.The factors that have an impact on metabolic improvements associated with CSII therapy are still poorly known. Dependency upon pre-CSII results after switching could help to explain the discrepancies regarding the efficacy of the prior studies comparing MDI and CSII. In our study the sample was metabolically optimized during the first 6 months with MDI/G, with the aim of later comparing both therapeutic options randomly.Sufficient scientific evidence exists to assert that CSII therapy is superior to MDI/NPH in addressing three problems: (1) elevated HbA1c; (2) repetitive severe hypoglycaemia and (3) glycaemic fluctuations.<a class="elsevierStyleCrossRef" href="#bib0400">37</a> However, what is the situation with MDI/G?Metabolic controlCombined with rapid-acting insulin analogues, glargine provides better glycaemic control than NPH, without increasing the risk of hypoglycaemia.<a class="elsevierStyleCrossRefs" href="#bib0260">10,11</a> Our findings are in agreement with these previous publications. In the first 6 months we detected a significant change in HbA1c upon switching from MDI/NPH to MDI/G, with a significant increase in periods of normoglycaemia and SD, and a significant decrease in episodes of severe hypoglycemia. We also found a significant increase in the number of self-tests per day due to the intensification of the insulin treatment with structured re-education and monthly visits. There was a decrease in daily total and basal insulin and an increase in BMI, probably in relation to the overall metabolic improvement.A systematic review published in 2012 of randomized studies<a class="elsevierStyleCrossRef" href="#bib0405">38</a> concluded that CSII provides better HbA1c than MDI, with a low level of evidence. Some of these studies performed a comparative evaluation of CSII vs. MDI with insulin glargine (MDI/G).<a class="elsevierStyleCrossRefs" href="#bib0270">12⬜17</a> However, only two randomized studies, one in adolescents<a class="elsevierStyleCrossRef" href="#bib0270">12</a> and the other in adults,<a class="elsevierStyleCrossRef" href="#bib0280">14</a> although of short duration, were able to confirm that CSII therapy may improve glycaemic control when compared to MDI with analogues. Doyle et al.<a class="elsevierStyleCrossRef" href="#bib0270">12</a> randomized 32 adolescents with type 1 diabetes to MDI/G or CSII for 16 weeks and reported a decrease in HbA1c in the CSII group. Hirsch et al.<a class="elsevierStyleCrossRef" href="#bib0280">14</a> randomized 100 patients with type 1 diabetes to MDI/G or CSII for 5 weeks and demonstrated both a decrease in fructosamine as well as a decrease in the area under the glucose curve using CGMS. In our study, the CSII group achieved better HbA1c than the MDI/G group after 6 months, but no differences were found in the other variables.To the best of our knowledge, this is the first randomized study in adult patients to report better HbA1c with CSII therapy vs. MDI/G in a maximally optimized adult group and with a prolonged follow-up of 6 months.In a recent paper derived of the large database of the T1D Exchange clinic registry, Miller et al.<a class="elsevierStyleCrossRef" href="#bib0410">39</a> communicate that a higher number of SMBG measurements per day were associated with non-Hispanic white race, insurance coverage, higher household income, and use of an insulin pump for insulin delivery (p<0.001 for each factor). After adjusting for these factors, a higher number of SMBG measurements per day was strongly associated with a lower HbA1c level (adjusted p<0.001), with the association being present in all age-groups and in both insulin pump and injection users.Was there an association between the frequency of SMBG and changes in HbA1c in our study? In this study the frequency and timing of SMBG measurements for study purposes with a structured SMBG regimen was used. Patients in the intensive MDI/G treatment made an average 3.2±1.4/day while the demands of CSII therapy are always greater and patients CSII group made an average of 4.7±1.7, thus we cannot rule out that the differences in the two groups of intensive insulin treatment relates to the number of different daily self-analysis performed and better treatment settings. This may be part of the advantages of this intensive treatment.HypoglycaemiaAs very strong evidence exists that CSII therapy reduces the frequency of severe hypoglycaemia compared with MDI/NPH therapy, this clinical problem is the main indication in many countries.<a class="elsevierStyleCrossRef" href="#bib0305">19</a> Pickup and Keen<a class="elsevierStyleCrossRef" href="#bib0220">2</a>, in their meta-analysis, found that the rate of severe hypoglycaemia was four times lower with CSII than with MDI, and the greatest improvements occurred in those patients with higher rates of severe hypoglycaemia when treated with MDI. Long-acting analogues, however, with their improved predictability and flatter absorption profile can lower the frequency of hypoglycaemia.<a class="elsevierStyleCrossRef" href="#bib0315">21</a> In fact, these functional strategies must be used and explored in patients with poor metabolic control before initiating CSII treatment. Our study confirms this because we reported a significant decrease in severe hypoglycaemia after switching from MDI/NPH to MDI/G. Studies comparing the incidence of severe hypoglycaemia during CSII and MDI based on short- and long-acting analogues have given contrasting results, some finding no difference<a class="elsevierStyleCrossRefs" href="#bib0280">14,15,17</a> while others found that patients prone to hypoglycaemia had fewer hypoglycaemic episodes during CSII.<a class="elsevierStyleCrossRef" href="#bib0310">20</a> In our study, no significant differences in episodes of severe hypoglycaemia were found between the MDI/G group and the CSII group, and no significant changes were seen in mild hypoglycaemia in either treatment phase.Glycaemic variabilityGlycaemic variability is included as an indication for treatment with CSII in some references<a class="elsevierStyleCrossRef" href="#bib0415">40</a> but not in others.<a class="elsevierStyleCrossRef" href="#bib0305">19</a> CSII should control glucose variability better than any MDI regimen, because during CSII the basal rate of insulin administration can be adjusted continuously and because the constant delivery of small amounts of insulin should minimize glucose oscillations.Several authors have found that glucose variability during CSII was smaller than during MDI with NPH.<a class="elsevierStyleCrossRefs" href="#bib0340">26,27</a> On the other hand, other studies have compared the effects on glucose variability of CSII and MDI based on long-acting analogues and have found either no difference, or higher or lower glucose variability during CSII.<a class="elsevierStyleCrossRefs" href="#bib0270">12,14,16,29,30</a> It should be noted, however, that the studies differed for patient selection, degree of metabolic control at study entry and the methods used to measure variability. A few studies have investigated this aspect using continuous glucose monitoring systems, but with differing results.<a class="elsevierStyleCrossRefs" href="#bib0290">16,29,30</a> Some found more variability with CSII<a class="elsevierStyleCrossRef" href="#bib0355">29</a> but others concluded that glucose variability was lower in CSII when glucose control was good (HbA1C<7.5%).<a class="elsevierStyleCrossRefs" href="#bib0290">16,30</a> Clearly, more work is needed on this important subject.In the present study, the variables of glucose variability (SD, LBGI and HBGI of CGSM data) were evaluated every 6 months. In the switch from MDI/NPH to MDI/G we reported less glycaemic variability according to the SD of CGSM, which was not repeated after randomization when comparing MDI/G vs. CSII. Given the limited value that this measurement has for the overall evaluation of glycaemic variability and the low number of patients we cannot provide a conclusive result.Quality of lifeQuality of life is an important criterion in decision making, but difficult to quantify.In a recent revision, Barnard et al.<a class="elsevierStyleCrossRef" href="#bib0365">31</a> systematically evaluated 18 articles that met adequate inclusion criteria and concluded that the effects of CSII on quality of life remain unclear.In our study, during the first phase of treatment (NPH to MDI/G) an improvement was noted in the DQOL, at the expense of the subscale ⬓satisfaction with treatment.⬽ After randomization, as occurred with HbA1c, the capacity of MDI/G to improve QOL appeared to have reached its limit during the first 6 months and in the following months no changes were reported in the MDI/G group. However, CSII therapy, as with HbA1c, goes further in improving QOL. These results differ from another Spanish study by Lozano-Serrano et al.,<a class="elsevierStyleCrossRef" href="#bib0420">41</a> who found no differences between CSII and MDI using the same test as in our study (the Spanish version of the Diabetes Quality of Life specific for diabetes related ESQOL), though our results are nevertheless in agreement with other publications. The systematic review of randomized studies published in 2012<a class="elsevierStyleCrossRef" href="#bib0400">37</a> concluded that CSII achieves a better QOL than MDI, but with a low level of evidence.The most robust study to date is by Hoogma et al.<a class="elsevierStyleCrossRef" href="#bib0345">27</a>, with 272 randomized patients in 5 countries treated either with MDI/NPH or CSII and assessed via DQOL, SF-12 and an additional questionnaire evaluating lifestyle, manageability of the disease and acceptability of the types of treatment, which were better for the group of patients using pumps.In adults, only 5 randomized studies have measured quality of life using different questionnaires for CSII vs. MDI,<a class="elsevierStyleCrossRefs" href="#bib0375">15,17,27</a> though only 2 with MDI/G,<a class="elsevierStyleCrossRefs" href="#bib0375">15,17</a> and have obtained different results. Bolli et al.<a class="elsevierStyleCrossRef" href="#bib0375">15</a>, using the diabetes treatment satisfaction questionnaire (DTSQ), found a better quality of life in the CSII group, but Thomas et al.<a class="elsevierStyleCrossRef" href="#bib0295">17</a>, using the DQOL, found no differences after 6 months of follow up. Nicolucci et al.<a class="elsevierStyleCrossRef" href="#bib0425">42</a>, in a large (1341 patients), multicentre, case⬜control study, reported comparative data on QOL for MDI (90% glargine) and CSII. They used the DQOL, DTSQ and the SF-36 Health Survey. Their results suggest that gains in QOL in the CSII group came from greater flexibility, less fear of hypoglycaemia and higher satisfaction with treatment.Strengths and limitationsThe principal limitation of this study is the small sample size, due mainly to the lack of finance for more CGMS and CSII, which might then have revealed more differences. Concerning the study design, contacts between participants and healthcare providers were more frequent than in normal daily life. This may diminish the external validity of the study, but reinforces the conclusion that CSII could be better than MDI/G even under strict conditions of patient follow-up.The strengths of this study are the incorporation of CGMS to evaluate both treatments and the initial homogenization phase, with a group of motivated and metabolically optimized patients in whom it was difficult to show improvements and who were not usual candidates for CSII. The subsequent randomization enabled us to eliminate any personal bias in the differences found between the two alternative therapies. And finally, a prolonged follow-up of 6 months for each phase of the trial controlled the ⬓dragging⬽ phenomenon of some of the variables studied.ConclusionsTo the best of our knowledge, this is the first randomized study in adult patients to find better HbA1c with CSII therapy vs. MDI/G in a maximally optimized adult group and with a prolonged follow-up of 6 months, with no worsening in the other metabolic variables (weight, mild, severe hypoglycaemia) and QOL.Further studies are needed to define the impact on glycaemic variability and QOL and to establish groups of patients who would benefit from this therapy, as well as determine the most cost-effective indications for this therapeutic alternative.Conflict of interestsThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres828429" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec824630" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres828430" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec824631" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Subjects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Variables and instruments" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Data analysis and statistics" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Baseline data (Table 1)" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Phase 1: homogenization (Table 2)" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Phase 2: after randomization (Table 2)" ] ] ] 7 => array:3 [ "identificador" => "sec0055" "titulo" => "Discussion" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Metabolic control" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Hypoglycaemia" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Glycaemic variability" ] 3 => array:2 [ "identificador" => "sec0075" "titulo" => "Quality of life" ] ] ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Strengths and limitations" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Conclusions" ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict of interests" ] 11 => array:2 [ "identificador" => "xack278014" "titulo" => "Acknowledgements" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-05-26" "fechaAceptado" => "2015-09-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec824630" "palabras" => array:3 [ 0 => "CSII" 1 => "MDI" 2 => "Type 1 diabetes" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec824631" "palabras" => array:3 [ 0 => "ISCI" 1 => "MDI" 2 => "Diabetes tipo 1" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Background and objectiveAdvantages of continuous subcutaneous insulin infusion (CSII) over multiple daily injections with glargine (MDI/G) are still uncertain. We compared CSII vs. MDI/G therapy in unselected patients with type 1 diabetes using continuous glucose monitoring (CGSM). The primary end-points were glycaemic control and quality of life (QOL). MethodsA total of 45 patients with long-term diabetes and mean HbA1c values of 8.6±1.8% (70.5±15.4mmol/mol), previously treated with MDI/NPH, were switched to MDI/G for 6 months and then, unfulfilling therapy CSII indication, were randomly assigned to CSII or MDI/G for another six months. We evaluated QOL (EsDqol) and glycaemic control by measuring HbA1c levels, rate of hypoglycaemia, ketoacidosis and CGSM data. ResultsAfter the first phase (MDI/NPH to MDI/G) there was a significant improvement in total EsDQOL (99.72±18.38 vs. 92.07±17.65; p<0.028), a 0.5% decrease in HbA1c values (8.4±1.2 vs. 7.9±0.7% [68±9.7 vs. 63±5.5mmol/mol]; p<0.032), an improvement in glycaemic variability (standard deviation 66.9±14 vs. 59.4±16mg/dl; p<0.05), a decrease in insulin requirements (0.87±0.29 vs. 0.80±0.25U/kg; p<0.049), a decrease in number of severe hypoglycaemia episodes (0.44±0.9 vs. 0.05±0.2; p<0.014), and an increase in periods of normoglycaemia measured with CGSM (15.8±10.9% vs. 23±18.4%; p<0.003). Six months after randomization, significant improvements were seen in the HbA1c (7.9±0.7 vs. 7±0.6% [63±5.5 vs. 53±4.5mmol/mol]; p<0.001) and EsQOL (91.66±22 vs. 84.53±1.63; p<0.045) only in the CSII group. The HbA1c value was significantly lower when compared with the MDI/G group (CSII 7±0.6% [53±4.5mmol/mol] vs. MDI/G 7.6±0.9% [59.6±7.7mmol/mol]; p<0.03). ConclusionsIntensive insulin therapy with CSII vs. MDI/G was associated with better levels of HbA1c in patients with long-term type 1 diabetes." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Introducción y objetivoLas ventajas de la infusión subcutánea continua de insulina (ISCI) sobre múltiples inyecciones diarias de insulina con glargina (MDI/G) son todavía inciertas. Comparamos ISCI frente a MDI/G en pacientes con diabetes tipo 1 sin indicación de terapia ISCI utilizando la monitorización continua de glucosa (CGSM). Los objetivos primarios fueron el control glucémico y la calidad de vida (QOL). MétodosUn total de 45 pacientes con diabetes 1 de largo tiempo de evolución y valores medios de HbA1c de 8,6±1,8% (70,5±15,4mmol/mol), previamente tratados con MDI/NPH, fueron cambiados a MDI/G durante 6 meses y luego sin cumplir criterios clínicos para terapia ISCI asignados aleatoriamente a ISCI o MDI/G durante seis meses. Se evaluó la calidad de vida (EsDqol) y el control de la glucemia mediante la medición de los niveles de HbA1c, la tasa de hipoglucemias, cetoacidosis y datos de CGSM. ResultadosDespués de la primera fase (MDI/NPH a MDI/G) hubo una mejora significativa en EsDQOL total (99,72±18,38 vs. 92,07±17,65; p<0.028), una disminución de 0,5% en los valores de HbA1c (8,4±1,2 vs. 7,9±0,7% [68±9,7 vs. 63±5,5mmol/mol]; p<0,032), una mejora en la variabilidad de la glucemia (desviación estándar 66,9±14 vs. 59,4±16mg/dl; p <0,05), una disminución en las necesidades de insulina (0,87±0,29 vs. 0,80±0,25U/kg; p <0,049), una disminución en el número de episodios de hipoglucemia grave (0,44±0,9 vs. 0,05±0,2; p <0,014), y un aumento en los periodos de normoglucemia medidos con CGSM (15,8±10,9% vs. 23±18,4%; p <0,003). Seis meses después de la aleatorización, se observaron mejoras significativas en la HbA1c (7,9±0,7 vs. 7±0,6%; [63±5,5 vs. 53±4.5mmol/mol]; p <0,001) y la calidad de vida (91,66±22 vs. 84,53±1,63; p <0,045) sólo en el grupo ISCI. El valour de HbA1c fue significativamente menor en ISCI en comparación con el grupo MDI/G (CSII 7±0,6% [53±4,5mmol/mol] vs. MDI/G 7,6±0,9% [59,6±7,7mmol/mol]; p<0,03). ConclusionesLa terapia insulínica intensiva con ISCI vs. MDI/G se asoció con mejores niveles de HbA1c en pacientes con diabetes tipo 1 de larga evolución." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1355 "Ancho" => 1593 "Tamanyo" => 82723 ] ] "descripcion" => array:1 [ "en" => "HbA1c at baseline, and after 6 and 12 months with MDI and CSII. *p<0.05 basal⬜6 month in 2 groups; **p<0.05 6 month⬜12 month in CSII group; $p<0.05 MDI/G vs. CSII 12 month." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1395 "Ancho" => 1584 "Tamanyo" => 80715 ] ] "descripcion" => array:1 [ "en" => "DQOL at baseline, and after 6 and 12 months with MDI and CSII. *p<0.05 basal⬜6 month in 2 groups; **p<0.05 6 month⬜12 month in CSII group." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "ns, not significant." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total N=38 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MDI/G N=23 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CSII N=15 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29.8±8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28±7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender (men/women) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21/24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15/15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Years with diabetes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13±7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.3±6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index (kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25±3.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24.9±3.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26±3.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Daily insulin dose/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.87±0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.87±0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.87±0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mild hypoglycaemia/week \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.04±3.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.03±3.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.07±3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe hypoglycaemia/6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.44±0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.43±1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.46±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SMBG/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3±1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.8±1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.2±1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HbA1c % (mmol/mol) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.4±1.2 (68±9.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.3±1.2 (67.2±9.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.5±1.2 (69.4±9.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ketoacidosis (previous 6 months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hospitalization (previous year) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preproliferative retinopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proliferative retinopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Incipient nephropathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Established nephropathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Unawareness hypoglycaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1393869.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics at start of treatment." ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Homogenization phase</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Randomized study</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Basal MDI/NPH \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 months MDI/glargine \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months MDI/glargine \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months CSII \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.4±3.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.9±3.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.8±3.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.8±3.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.42 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Basal insulin dose (IU/day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.8±16.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36.8±15.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.7±12.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.34±18.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total insulin dose (IU/kg/day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.87±0.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.80±0.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.049 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.77±0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.78±0.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HbA1c % (mmol/mol) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.4±1.2 (68±9.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.9±0.7 (63±5.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.032 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.6±0.9 (59.6±7.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7±0.6 (53±4.5)<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HbA1c <7.5% (58.5mmol/mol) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36.8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SMBG/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3±1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.3±1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.2±1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.7±1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.008 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe hypoglycaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.44±0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.050±0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05±0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.29±1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">CGMS</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean glycaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">172.2±42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">162±30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.104 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">146.78±36<a class="elsevierStyleCrossRef" href="#tblfn0005">#</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">145±20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Standard deviation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.9±14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59.4±16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58±13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65±24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">% normoglycaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.8±10.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23±18.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50.7±18<a class="elsevierStyleCrossRef" href="#tblfn0005">#</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50±13.6<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.84 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">% hypoglycaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.3±9.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.3±7.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.4±8.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.6±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">% hyperglycaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73.7±21.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69.38±21.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43±16.2<a class="elsevierStyleCrossRef" href="#tblfn0005">#</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42±12<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.88 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LBGI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.1± 2.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.8±1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.74± 2.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.89±2.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBGI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.7±5.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.1±4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.8±4.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.4± 3<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DQOL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99.72±18.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92.07±17.65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92.78+20.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84.5±18<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Satisfaction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39.15±8.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.45±7.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.08+6.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.53+9.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Impact \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.94±6.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33.48±7.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.219 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33.39+10.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.80+6.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.613 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Social concerns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.8±5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.21±5.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.317 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.34+5.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.26+4.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.514 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Worry about future \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.35±2.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.1±2.69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.582 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.95+3.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.93+2.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.335 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1393870.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "#" "nota" => "p<0.05 MDI/G 6 M vs. MDI/G12 M." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "*" "nota" => "p<0.05 MDI/G 6 M vs. CSII 12 M." ] ] ] "descripcion" => array:1 [ "en" => "Comparative analysis between the homogenization and randomization phases." ] ] 4 => array:5 [ "identificador" => "tbl0005" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => false "mostrarDisplay" => true "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alberto Machadoc, Victor Martina, Isabel Cardonad, Magdalena de-la-Higuerae, Stella Gonzalez-Romeroa,b,d, Elehazara Rubiob,d, Sonsoles Morcillob,d, María-José Tapiaa,d, Natalia Colomoa,b,d, Mónica Carreirac,d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">a Diabetes Centre, Department of Endocrinology and Nutrition, General University Hospital of Malaga \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">b CIBERDEM (Carlos III Health Institute), Malaga, Spain. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">c Department of Personality, Assessment and Psychological Treatment. Faculty of Psychology. University of Malaga, Malaga, Spain. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">d Instituto de Investigación Biomédica de Málaga (IBIMA), Spain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">e Servicio de Endocrinología y Nutrición. Clinica Universitaria de Navarra \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1393868.png" ] ] ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:42 [ 0 => array:3 [ "identificador" => "bib0215" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.C. Pickup" 1 => "H. Keen" 2 => "J.A. Parsons" 3 => "K.G. 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AM designed the study and analysis and conducted data collection. VM conducted data collection and data interpretation. IC conducted data collection. MH conducted data collection and data interpretation. SG conducted data collection and data interpretation. SM designed the study and analysis. MC conducted data collection and data interpretation. MTA was involved in the design of the psychological assessment protocol of this study, and the coordination the data collection process, and in the interpretation of the data and in reviewing. GR and FS designed the study and analysis and helped write the manuscript." 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Original article

Comparison between a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) using continuous glucose monitoring in metabolically optimized type 1 diabetes patients: A randomized open-labelled parallel study

Comparación entre múltiples dosis de insulina (insulina glargina una vez al día y lispro en las comidas) e infusión subcutánea continua de insulina con monitorización continua de glucosa en pacientes con diabetes tipo 1 metabólicamente optimizados. Estudio randomizado

María Soledad Ruiz-de-Adanaa,b,d, Marta-Elena Dominguez-Lopeza,b,d, Inmaculada Gonzalez-Moleroa,b,d,⽽

Corresponding author

inmagonzalezmolero@hotmail.com

Corresponding author.

, Alberto Machadoc, Victor Martina, Isabel Cardonad, Magdalena de-la-Higuerae, María-José Tapiaa,d, Federico Soriguera,b,d, María Teresa Anartec,d, Gemma Rojo-Martíneza,b,d

a Diabetes Centre, Department of Endocrinology and Nutrition, General University Hospital of Malaga, Spain

b CIBERDEM (Carlos III Health Institute), Malaga, Spain

c Department of Personality, Assessment and Psychological Treatment, Faculty of Psychology, University of Malaga, Malaga, Spain

d Instituto de Investigación Biomédica de Málaga (IBIMA), Spain

e Department of Endocrinology, Clinical Universitary of Navarra, Pamplona, Navarra, Spain

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        "titulo" => "Comparaci&#243;n entre m&#250;ltiples dosis de insulina &#40;insulina glargina una vez al d&#237;a y lispro en las comidas&#41; e infusi&#243;n subcut&#225;nea continua de insulina con monitorizaci&#243;n continua de glucosa en pacientes con diabetes tipo 1 metab&#243;licamente optimizados&#46; Estudio randomizado"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">DQOL at baseline&#44; and after 6 and 12 months with MDI and CSII&#46; &#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 basal&#11036;6 month in 2 groups&#59; &#42;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 6 month&#11036;12 month in CSII group&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Continuous subcutaneous insulin infusion &#40;CSII&#41; as therapy for patients with type 1 diabetes became available more than 30 years ago&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a> Since then several meta-analyses have reviewed multiple daily injections &#40;MDI&#41; therapy&#44; most with MDI&#47;NPH vs&#46; CSII&#44; discovering greater efficacy in glycaemic control with CSII therapy&#44; in addition to a decrease in the incidence of hypoglycaemic events&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">2&#11036;7</span></a> These meta-analyses established CSII therapy as the gold standard for insulin therapy in patients with type 1 diabetes&#46; In addition&#44; the relative benefit of CSII therapy over MDI&#47;NPH is greater at higher baseline HbA1c values&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">8</span></a> The limitations of MDI&#47;NPH have been alleviated with the introduction of glargine&#44; a long-acting insulin analogue with a flatter and more prolonged time-action profile&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">9</span></a> Combined with rapid-acting insulin analogues&#44; glargine provides better glycaemic control than intermediate-acting insulin NPH&#44; with no increased risk of hypoglycaemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">10&#44;11</span></a> The question of whether CSII therapy with ultra-rapid insulin continues to be the gold standard in intensive insulin treatment for type 1 diabetes&#44; however&#44; is still not resolved&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Whereas several authors have found no difference between CSII and MDI with glargine in a variety of end-points&#44; others have found CSII to be superior&#46; Several randomized studies have performed a comparative evaluation of CSII vs&#46; MDI with insulin glargine &#40;MDI&#47;G&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#11036;17</span></a> In adults&#44; HbA1C results are similar with both treatments&#46; However&#44; in the study by Hirsch et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> the results obtained from the measurement of serum levels of fructosamine and the reduced exposure to hyperglycaemia assessed through continuous glucose monitoring &#40;CGMS&#41; showed better metabolic control with CSII&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Severe hypoglycaemia remains one of the most feared complications&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> The scientific evidence that CSII therapy reduces the frequency of severe hypoglycaemia compared to MDI&#47;NPH is very strong&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> Pickup and Keen&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">2</span></a> in their review&#44; found that the rate of severe hypoglycaemia was four times lower with CSII than with MDI&#44; and the greatest improvements occurred in those patients with higher rates of severe hypoglycaemia when treated with MDI&#46; The frequency of mild hypoglycaemia is also lower with CSII&#44; with a reduction of 75&#37; after switching from MDI&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a> Several studies comparing MDI based on glargine or detemir have found a lower incidence of nocturnal hypoglycaemia than with NPH&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> On the other hand&#44; studies comparing the incidence of severe hypoglycaemia during CSII and MDI with long-acting analogues have given contrasting results&#44; with some finding no difference<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">14&#44;15&#44;17</span></a> while others found that patients prone to hypoglycaemia had fewer hypoglycaemic episodes during CSII&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Currently there is strong interest in glycaemic variability&#44; due to the possible relationship with microvascular and macrovascular disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">22&#44;23</span></a> Indeed&#44; glycaemic variability in combination with HbA1c could be a more realistic indicator of glycaemic control and long-term risk of complications than HbA1c alone&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">24&#44;25</span></a> Several authors found that glucose variability during CSII was smaller than during MDI&#47;NPH&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">26&#44;27</span></a> Other studies have compared the effects on glucose variability of CSII and MDI based on long-acting analogues and have found either no differences&#44; or higher or lower glucose variability<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;14&#44;16&#44;28&#11036;30</span></a> during CSII&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">There are conflicting results concerning the effects of CSII therapy on quality of life&#46; A meta-analysis in 2007 concluded that the effects of CSII on quality of life remain unclear&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">31</span></a> More recent studies have obtained different results&#44; some finding a better quality of life<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">15&#44;27&#44;32</span></a> but others seeing a similar quality of life with CSII&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The objectives of this study were to determine&#58; &#40;1&#41; whether CSII is more effective than MDI therapy using insulin analogues &#40;rapid and long&#41; in metabolic control and QOL&#44; and &#40;2&#41; whether CSII therapy has supplemental benefits in patients with type 1 diabetes who are optimized with MDI therapy using insulin analogues&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">This was a randomized&#44; parallel group&#44; open-label study performed in the Diabetes Centre of the Endocrinology and Nutrition Department of Carlos Haya University Hospital in Malaga&#44; Spain&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Subjects</span><p id="par0040" class="elsevierStylePara elsevierViewall">Inclusion criteria&#58; patients aged 18&#11036;65 years with type 1 diabetes for more than 5 years&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Exclusion criteria&#58; acute coronary syndrome or stroke in the last 6 months&#44; active proliferative retinopathy&#44; uncontrolled hypertension&#44; severe vegetative neuropathy&#44; impaired hepatic&#47;renal function&#44; prior use of CSII or insulin glargine&#44; patients unable to use CSII or MDI or patients planning pregnancy&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">A total of 45 patients met the inclusion criteria&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The sample size calculation was performed to detect a difference of 1&#46;5&#37; in HbA1c using a standard deviation of 1&#46;2&#44; a <span class="elsevierStyleItalic">&#945;</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05 &#40;two-tailed&#41;&#44; and a power of 90&#37;&#46; The resulting minimum size was 15 patients per group&#44; including 15&#37; of lost patients&#46; To obtain 30 patients &#40;15 CSII and 15 MDI&#47;G&#41; 45 is selected in case had lost over 15&#37; calculated on the protocol development&#46; The key is the intergroup comparison &#40;CSII vs&#46; MDI&#47;G&#41; and is carried out at 12 months&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">During the first 6 months seven patients were lost&#44; leaving 38 patients&#59; then&#44; without meeting criteria for CSII therapy&#44; these 38 patients were randomized&#44; 15 to CSII and 23 to MDI&#47;G during six months&#44; with no patients lost in this phase&#46; The 7 patients withdrawing of the study at the first phase owed to the inability to follow protocol and monthly visits&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">All the subjects provided written informed consent&#46; The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines and with the approval of the Ethics Committee of Carlos Haya University Hospital&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Design</span><p id="par0070" class="elsevierStylePara elsevierViewall">Randomized clinical trial &#40;2 MDI&#47;G&#58; 1 CSII&#41; with a prior homogenization phase with MDI&#47;G&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#11042;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Phase 1&#58; educational homogenization and adherence&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Forty-five patients with type 1 diabetes&#44; under treatment with MDI&#47;NPH and rapid analogues&#44; were switched to MDI with glargine as basal insulin and followed-up monthly for 6 months&#46; The patients used insulin lispro &#40;Eli Lilly Inc&#46;&#44; Indianapolis&#44; IN&#41; before each meal and a single dose of glargine&#46; Seven patients dropped out of the study in Phase 1&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#11042;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Phase 2&#58; randomization&#46; After the first 6 months&#44; from this metabolically optimized group&#44; 15 patients were randomly assigned to CSII therapy&#46; These CSII patients received insulin lispro via a multi-programmable insulin infusion system &#40;Paradigm 712&#44; Medtronic&#44; USA&#41;&#46; 23 patients continued with MDI&#47;G once daily in the evening plus mealtime insulin lispro&#59; both groups completed 6 further months &#40;23 patients MDI&#47;G vs&#46; 15 patients CSII&#41;&#44; with monthly follow-up&#46;</p></li></ul></p><p id="par0090" class="elsevierStylePara elsevierViewall">All the patients developed skills necessary for intensive functional therapy including self-monitoring of blood glucose &#40;SMBG&#41; using a plasma-calibrated memory glucose metre &#40;OneTouch Ultra&#59; Lifescan&#44; Milpitas&#44; CA&#41;&#44; carbohydrate counting&#44; insulin adjustment and technical aspects of the pumps&#46; The glycaemic targets were identical for both treatment groups&#58; glycaemia of 80&#11036;120<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;4&#46;4&#11036;6&#46;6<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; before and &#60;150<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;8&#46;3<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; 2<span class="elsevierStyleHsp" style=""></span>h after meals&#46; Three days of glycaemia monitoring via CGSM &#40;Medtronic&#44; USA&#41; was done at the end of each treatment period and the time spent with blood glucose<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>70<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#47;3&#46;9<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#44; &#62;180<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#47;10<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#44; and 70&#11036;180<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#47;3&#46;9&#11036;9&#46;9<span class="elsevierStyleHsp" style=""></span>mmol&#47;L was recorded&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Variables and instruments</span><p id="par0095" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#11042;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Sociodemographics&#58; sex and age&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#11042;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Anthropometric&#58; weight&#44; BMI&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#11042;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Insulin therapy&#58; daily insulin dose &#40;DID&#41; &#40;insulin&#47;kg&#41;&#44; basal insulin dose &#40;&#37;&#41;&#44; bolus insulin dose &#40;&#37;&#41;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#11042;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Complications&#58; mild hypoglycaemia &#40;episodes per week&#41;&#44; severe hypoglycaemia &#40;episodes per 6 months&#41; and ketoacidosis episodes&#46; Hypoglycaemia was defined according to the ADA criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">34</span></a></p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#11042;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Metabolic control parameters&#58; HbA1c &#40;HPLC&#59; Diabetes Control and Complications Trial &#91;DCCT&#93; Research Group aligned&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#11042;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Glycaemic variability parameters&#58; obtained by standard deviation &#40;SD&#41;&#44; low blood glucose index &#40;LBGI&#41; and high blood glucose index &#40;HBGI&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">35</span></a> obtained from CGSM&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#11042;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Quality of life parameters&#58; the quality of life during each treatment phase was measured using a version of the Diabetes Quality of Life &#40;EsDQOL&#41; questionnaire of the DCCT Research Group&#44; adapted to the Spanish population&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">36</span></a> The scale consists of 43 items that are 4 dimensions&#58; satisfaction with treatment &#40;15 items&#41;&#44; impact of treatment &#40;17 items&#41;&#44; social&#47;vocational concerns &#40;7 items&#41; and concern regarding the future effects of diabetes &#40;4 items&#41;&#46; Each item has 5 possible answers on Likert scoring from 1 to 5&#46; Satisfaction subscale responses to each item ranged from &#11027;very satisfied&#11069; &#40;1 point&#41; to &#11027;not satisfied&#11069; &#40;5 points&#41;&#46; In the other three subscales&#44; responses ranged from &#11027;never&#11069; &#40;1 point&#41; to &#11027;always&#11069; &#40;5 points&#41;&#46; A total score and subscales score can be obtained&#46; A lower score means better quality of life&#46; It is designed to be self-administered&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#11042;</span><p id="par0135" class="elsevierStylePara elsevierViewall">The primary objectives were the HbA1c value at the end of each treatment phase&#44; with a goal of HbA1c &#60;7&#46;5&#37; and the QOL during each phase&#46;</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Data analysis and statistics</span><p id="par0140" class="elsevierStylePara elsevierViewall">The data are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD or proportions&#46; At baseline&#44; homogeneity between the randomized sequence groups &#40;CSII and MDI&#47;G&#41; was tested using two-sample unpaired Student&#39;s <span class="elsevierStyleItalic">t</span>-test for normally distributed data&#44; or the Wilcoxon rank sum test for non-normally distributed data&#46; To compare the scores before and after treatment two types of analysis were used&#46; For the variables with scores that adjusted to a normal distribution a repeated measures ANOVA was used&#46; For the variables with scores that did not follow a normal distribution a non-parametric contrast test was used &#40;Wilcoxon test&#41;&#46; For comparison of means the Student <span class="elsevierStyleItalic">t</span> test was used for related or independent samples and the chi-square test was used to determine the association between qualitative variables&#46; Analyses per protocol were done and carried out with SPSS software &#40;18&#46;0 version&#41;&#46; The confidence intervals were set at 95&#37;&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Baseline data &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1</a>&#41;</span><p id="par0145" class="elsevierStylePara elsevierViewall">The mean age of patients was 29&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;5 years&#44; 46&#37; were men&#44; the duration of diabetes was 13&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7 years&#44; the mean HbA1c was 8&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2&#37; &#40;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;7<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#41;&#44; 33&#37; with &#60;7&#46;5&#37; &#40;58&#46;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#41;&#46; The baseline characteristics were similar for both treatment groups&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Phase 1&#58; homogenization &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#41;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Metabolic control&#58; in the first 6 months &#40;MDI&#47;NPH to MDI&#47;glargine&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#41;&#44; there was an improvement in HbA1c&#44; with a mean decrease of 0&#46;5&#37; &#40;8&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2&#37; vs&#46; 7&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;032&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; a HbA1c &#60;7&#46;5&#37; was reached by 36&#46;8&#37; of the patients &#40;vs&#46; 33&#37; at baseline&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;7&#41; and the frequency of severe hypoglycaemia declined &#40;0&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9 vs&#46; 0&#46;050<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;014&#41; with no changes in mild hypoglycaemia&#46; There was an increase in the number of self-analyses per day &#40;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 vs&#46; 4&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; and an increase in BMI &#40;25&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3 vs&#46; 25&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;014&#41;&#46; The total daily insulin decreased 8&#37; &#40;0&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;29 vs&#46; 0&#46;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;25<span class="elsevierStyleHsp" style=""></span>IU&#47;kg&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;049&#41; and basal insulin decreased 12&#37; &#40;41&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;4 vs&#46; 36&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;7<span class="elsevierStyleHsp" style=""></span>IU&#47;day&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; There were no episodes of ketoacidosis in the group&#46; With respect to the CGMS data&#44; there was an increase in periods of normoglycaemia &#40;15&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#37; vs&#46; 23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41; and a significant improvement in glycaemic variability measured by the SD of CGMS &#40;66&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14 vs&#46; 59&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">Quality of life&#58; significant changes were perceived in the overall EsDQOL &#40;99&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;38 vs&#46; 92&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;65&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; and an improvement in the subscale &#11027;satisfaction with treatment&#11069; &#40;39&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;54 vs&#46; 35&#46;45<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;46&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Phase 2&#58; after randomization &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#41;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Metabolic control&#58; In the CSII group&#44; after 6 months HbA1c values decreased significantly &#40;7&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7&#37; &#91;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93; to 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6&#37; &#91;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; with 67&#37; of patients achieving the objective of 7&#46;5&#37; &#40;vs&#46; 6<span class="elsevierStyleHsp" style=""></span>m&#58; 36&#46;8&#37;&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#41;&#46; There was an improvement in time in normoglycaemia &#40;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;4 vs&#46; 50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; time in hyperglycaemia &#40;69&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;5 vs&#46; 42&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; and HBGI &#40;CGMS&#41; &#40;8&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5 vs&#46; 5&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;3&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;045&#41;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">In the MDI&#47;G group&#44; no significant change was seen in HbA1c &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In CGMS&#44; decreases were seen in mean glycaemia &#40;162<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mg&#47;dl vs&#46; 146&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#44; and time in hyperglycaemia &#40;69&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>43&#46;16 vs&#46; 43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;2&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and an increase in time in normoglycaemia &#40;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;4 vs&#46; 50&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Although a tendency towards better control parameters was seen in the metabolic variables evaluated in the two groups&#44; significantly lower levels of HbA1c were only seen in the CSII group compared with the MDI&#47;G group &#40;MDI&#47;G 7&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9 vs&#46; CSII 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#44; with a higher number of self-tests per day in the CSII group compared to the MDI&#47;G group&#58; 4&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6 vs&#46; 3&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41;&#46; There is a positive correlation in the set of the 38 patients at 12 months between the number of SMBG and reached HbA1c &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8601;0&#46;45&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#46;&#41; which does not occur in each group independently &#40;MDI&#47;G <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;13&#59; CSII <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;4&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;14&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">No changes were seen in BMI&#44; insulin dose&#44; mild or severe hypoglycaemia or episodes of ketosis or ketoacidosis in the two groups&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Quality of life&#58; the total DQOL score decreased significantly in the CSII group &#40;91&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22 to 84&#46;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;63&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;045&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The differences between groups &#40;CSII vs&#46; MDI&#47;G&#41; in absolute scores for total DQOL and the subscales were not significant&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">There were no serious adverse events during the study&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0190" class="elsevierStylePara elsevierViewall">For many years&#44; the advantages of CSII therapy made it a superior treatment compared with MDI&#47;NPH&#46; The incorporation of the long-acting analogues glargine and detemir&#44; soluble insulins with a more predictable absorption&#44; more stable blood levels and with the possibility of improving glycaemic control&#44; have now raised the question of whether these new insulins can replace the need for CSII in people with type 1 diabetes&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The factors that have an impact on metabolic improvements associated with CSII therapy are still poorly known&#46; Dependency upon pre-CSII results after switching could help to explain the discrepancies regarding the efficacy of the prior studies comparing MDI and CSII&#46; In our study the sample was metabolically optimized during the first 6 months with MDI&#47;G&#44; with the aim of later comparing both therapeutic options randomly&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Sufficient scientific evidence exists to assert that CSII therapy is superior to MDI&#47;NPH in addressing three problems&#58; &#40;1&#41; elevated HbA1c&#59; &#40;2&#41; repetitive severe hypoglycaemia and &#40;3&#41; glycaemic fluctuations&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">37</span></a> However&#44; what is the situation with MDI&#47;G&#63;</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Metabolic control</span><p id="par0205" class="elsevierStylePara elsevierViewall">Combined with rapid-acting insulin analogues&#44; glargine provides better glycaemic control than NPH&#44; without increasing the risk of hypoglycaemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">10&#44;11</span></a> Our findings are in agreement with these previous publications&#46; In the first 6 months we detected a significant change in HbA1c upon switching from MDI&#47;NPH to MDI&#47;G&#44; with a significant increase in periods of normoglycaemia and SD&#44; and a significant decrease in episodes of severe hypoglycemia&#46; We also found a significant increase in the number of self-tests per day due to the intensification of the insulin treatment with structured re-education and monthly visits&#46; There was a decrease in daily total and basal insulin and an increase in BMI&#44; probably in relation to the overall metabolic improvement&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">A systematic review published in 2012 of randomized studies<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">38</span></a> concluded that CSII provides better HbA1c than MDI&#44; with a low level of evidence&#46; Some of these studies performed a comparative evaluation of CSII vs&#46; MDI with insulin glargine &#40;MDI&#47;G&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#11036;17</span></a> However&#44; only two randomized studies&#44; one in adolescents<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">12</span></a> and the other in adults&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> although of short duration&#44; were able to confirm that CSII therapy may improve glycaemic control when compared to MDI with analogues&#46; Doyle et al&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">12</span></a> randomized 32 adolescents with type 1 diabetes to MDI&#47;G or CSII for 16 weeks and reported a decrease in HbA1c in the CSII group&#46; Hirsch et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> randomized 100 patients with type 1 diabetes to MDI&#47;G or CSII for 5 weeks and demonstrated both a decrease in fructosamine as well as a decrease in the area under the glucose curve using CGMS&#46; In our study&#44; the CSII group achieved better HbA1c than the MDI&#47;G group after 6 months&#44; but no differences were found in the other variables&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; this is the first randomized study in adult patients to report better HbA1c with CSII therapy vs&#46; MDI&#47;G in a maximally optimized adult group and with a prolonged follow-up of 6 months&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">In a recent paper derived of the large database of the T1D Exchange clinic registry&#44; Miller et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">39</span></a> communicate that a higher number of SMBG measurements per day were associated with non-Hispanic white race&#44; insurance coverage&#44; higher household income&#44; and use of an insulin pump for insulin delivery &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001 for each factor&#41;&#46; After adjusting for these factors&#44; a higher number of SMBG measurements per day was strongly associated with a lower HbA<span class="elsevierStyleInf">1c</span>&#160;level &#40;adjusted&#160;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; with the association being present in all age-groups and in both insulin pump and injection users&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Was there an association between the frequency of SMBG and changes in HbA1c in our study&#63; In this study the frequency and timing of SMBG measurements for study purposes with a structured SMBG regimen was used&#46; Patients in the intensive MDI&#47;G treatment made an average 3&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&#47;day while the demands of CSII therapy are always greater and patients CSII group made an average of 4&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7&#44; thus we cannot rule out that the differences in the two groups of intensive insulin treatment relates to the number of different daily self-analysis performed and better treatment settings&#46; This may be part of the advantages of this intensive treatment&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Hypoglycaemia</span><p id="par0230" class="elsevierStylePara elsevierViewall">As very strong evidence exists that CSII therapy reduces the frequency of severe hypoglycaemia compared with MDI&#47;NPH therapy&#44; this clinical problem is the main indication in many countries&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> Pickup and Keen<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">2</span></a>&#44; in their meta-analysis&#44; found that the rate of severe hypoglycaemia was four times lower with CSII than with MDI&#44; and the greatest improvements occurred in those patients with higher rates of severe hypoglycaemia when treated with MDI&#46; Long-acting analogues&#44; however&#44; with their improved predictability and flatter absorption profile can lower the frequency of hypoglycaemia&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> In fact&#44; these functional strategies must be used and explored in patients with poor metabolic control before initiating CSII treatment&#46; Our study confirms this because we reported a significant decrease in severe hypoglycaemia after switching from MDI&#47;NPH to MDI&#47;G&#46; Studies comparing the incidence of severe hypoglycaemia during CSII and MDI based on short- and long-acting analogues have given contrasting results&#44; some finding no difference<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">14&#44;15&#44;17</span></a> while others found that patients prone to hypoglycaemia had fewer hypoglycaemic episodes during CSII&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a> In our study&#44; no significant differences in episodes of severe hypoglycaemia were found between the MDI&#47;G group and the CSII group&#44; and no significant changes were seen in mild hypoglycaemia in either treatment phase&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Glycaemic variability</span><p id="par0235" class="elsevierStylePara elsevierViewall">Glycaemic variability is included as an indication for treatment with CSII in some references<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">40</span></a> but not in others&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> CSII should control glucose variability better than any MDI regimen&#44; because during CSII the basal rate of insulin administration can be adjusted continuously and because the constant delivery of small amounts of insulin should minimize glucose oscillations&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Several authors have found that glucose variability during CSII was smaller than during MDI with NPH&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">26&#44;27</span></a> On the other hand&#44; other studies have compared the effects on glucose variability of CSII and MDI based on long-acting analogues and have found either no difference&#44; or higher or lower glucose variability during CSII&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;14&#44;16&#44;29&#44;30</span></a> It should be noted&#44; however&#44; that the studies differed for patient selection&#44; degree of metabolic control at study entry and the methods used to measure variability&#46; A few studies have investigated this aspect using continuous glucose monitoring systems&#44; but with differing results&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">16&#44;29&#44;30</span></a> Some found more variability with CSII<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">29</span></a> but others concluded that glucose variability was lower in CSII when glucose control was good &#40;HbA1C<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>7&#46;5&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">16&#44;30</span></a> Clearly&#44; more work is needed on this important subject&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">In the present study&#44; the variables of glucose variability &#40;SD&#44; LBGI and HBGI of CGSM data&#41; were evaluated every 6 months&#46; In the switch from MDI&#47;NPH to MDI&#47;G we reported less glycaemic variability according to the SD of CGSM&#44; which was not repeated after randomization when comparing MDI&#47;G vs&#46; CSII&#46; Given the limited value that this measurement has for the overall evaluation of glycaemic variability and the low number of patients we cannot provide a conclusive result&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Quality of life</span><p id="par0250" class="elsevierStylePara elsevierViewall">Quality of life is an important criterion in decision making&#44; but difficult to quantify&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">In a recent revision&#44; Barnard et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">31</span></a> systematically evaluated 18 articles that met adequate inclusion criteria and concluded that the effects of CSII on quality of life remain unclear&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">In our study&#44; during the first phase of treatment &#40;NPH to MDI&#47;G&#41; an improvement was noted in the DQOL&#44; at the expense of the subscale &#11027;satisfaction with treatment&#46;&#11069; After randomization&#44; as occurred with HbA1c&#44; the capacity of MDI&#47;G to improve QOL appeared to have reached its limit during the first 6 months and in the following months no changes were reported in the MDI&#47;G group&#46; However&#44; CSII therapy&#44; as with HbA1c&#44; goes further in improving QOL&#46; These results differ from another Spanish study by Lozano-Serrano et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">41</span></a> who found no differences between CSII and MDI using the same test as in our study &#40;the Spanish version of the Diabetes Quality of Life specific for diabetes related ESQOL&#41;&#44; though our results are nevertheless in agreement with other publications&#46; The systematic review of randomized studies published in 2012<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">37</span></a> concluded that CSII achieves a better QOL than MDI&#44; but with a low level of evidence&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The most robust study to date is by Hoogma et al&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a>&#44; with 272 randomized patients in 5 countries treated either with MDI&#47;NPH or CSII and assessed via DQOL&#44; SF-12 and an additional questionnaire evaluating lifestyle&#44; manageability of the disease and acceptability of the types of treatment&#44; which were better for the group of patients using pumps&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">In adults&#44; only 5 randomized studies have measured quality of life using different questionnaires for CSII vs&#46; MDI&#44;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">15&#44;17&#44;27</span></a> though only 2 with MDI&#47;G&#44;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">15&#44;17</span></a> and have obtained different results&#46; Bolli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">15</span></a>&#44; using the diabetes treatment satisfaction questionnaire &#40;DTSQ&#41;&#44; found a better quality of life in the CSII group&#44; but Thomas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a>&#44; using the DQOL&#44; found no differences after 6 months of follow up&#46; Nicolucci et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">42</span></a>&#44; in a large &#40;1341 patients&#41;&#44; multicentre&#44; case&#11036;control study&#44; reported comparative data on QOL for MDI &#40;90&#37; glargine&#41; and CSII&#46; They used the DQOL&#44; DTSQ and the SF-36 Health Survey&#46; Their results suggest that gains in QOL in the CSII group came from greater flexibility&#44; less fear of hypoglycaemia and higher satisfaction with treatment&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Strengths and limitations</span><p id="par0275" class="elsevierStylePara elsevierViewall">The principal limitation of this study is the small sample size&#44; due mainly to the lack of finance for more CGMS and CSII&#44; which might then have revealed more differences&#46; Concerning the study design&#44; contacts between participants and healthcare providers were more frequent than in normal daily life&#46; This may diminish the external validity of the study&#44; but reinforces the conclusion that CSII could be better than MDI&#47;G even under strict conditions of patient follow-up&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">The strengths of this study are the incorporation of CGMS to evaluate both treatments and the initial homogenization phase&#44; with a group of motivated and metabolically optimized patients in whom it was difficult to show improvements and who were not usual candidates for CSII&#46; The subsequent randomization enabled us to eliminate any personal bias in the differences found between the two alternative therapies&#46; And finally&#44; a prolonged follow-up of 6 months for each phase of the trial controlled the &#11027;dragging&#11069; phenomenon of some of the variables studied&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusions</span><p id="par0285" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; this is the first randomized study in adult patients to find better HbA1c with CSII therapy vs&#46; MDI&#47;G in a maximally optimized adult group and with a prolonged follow-up of 6 months&#44; with no worsening in the other metabolic variables &#40;weight&#44; mild&#44; severe hypoglycaemia&#41; and QOL&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">Further studies are needed to define the impact on glycaemic variability and QOL and to establish groups of patients who would benefit from this therapy&#44; as well as determine the most cost-effective indications for this therapeutic alternative&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflict of interests</span><p id="par0295" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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              "titulo" => "Baseline data &#40;Table 1&#41;"
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              "titulo" => "Phase 1&#58; homogenization &#40;Table 2&#41;"
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              "titulo" => "Metabolic control"
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              "titulo" => "Hypoglycaemia"
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              "titulo" => "Glycaemic variability"
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              "titulo" => "Quality of life"
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    "fechaRecibido" => "2015-05-26"
    "fechaAceptado" => "2015-09-03"
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            2 => "Type 1 diabetes"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Advantages of continuous subcutaneous insulin infusion &#40;CSII&#41; over multiple daily injections with glargine &#40;MDI&#47;G&#41; are still uncertain&#46; We compared CSII vs&#46; MDI&#47;G therapy in unselected patients with type 1 diabetes using continuous glucose monitoring &#40;CGSM&#41;&#46; The primary end-points were glycaemic control and quality of life &#40;QOL&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A total of 45 patients with long-term diabetes and mean HbA1c values of 8&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8&#37; &#40;70&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;4<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#41;&#44; previously treated with MDI&#47;NPH&#44; were switched to MDI&#47;G for 6 months and then&#44; unfulfilling therapy CSII indication&#44; were randomly assigned to CSII or MDI&#47;G for another six months&#46; We evaluated QOL &#40;EsDqol&#41; and glycaemic control by measuring HbA1c levels&#44; rate of hypoglycaemia&#44; ketoacidosis and CGSM data&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">After the first phase &#40;MDI&#47;NPH to MDI&#47;G&#41; there was a significant improvement in total EsDQOL &#40;99&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;38 vs&#46; 92&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;65&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;028&#41;&#44; a 0&#46;5&#37; decrease in HbA1c values &#40;8&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 vs&#46; 7&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7&#37; &#91;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;7 vs&#46; 63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;032&#41;&#44; an improvement in glycaemic variability &#40;standard deviation 66&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14 vs&#46; 59&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; a decrease in insulin requirements &#40;0&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;29 vs&#46; 0&#46;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;25<span class="elsevierStyleHsp" style=""></span>U&#47;kg&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;049&#41;&#44; a decrease in number of severe hypoglycaemia episodes &#40;0&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9 vs&#46; 0&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;014&#41;&#44; and an increase in periods of normoglycaemia measured with CGSM &#40;15&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;9&#37; vs&#46; 23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#46; Six months after randomization&#44; significant improvements were seen in the HbA1c &#40;7&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7 vs&#46; 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6&#37; &#91;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5 vs&#46; 53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and EsQOL &#40;91&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22 vs&#46; 84&#46;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;63&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;045&#41; only in the CSII group&#46; The HbA1c value was significantly lower when compared with the MDI&#47;G group &#40;CSII 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6&#37; &#91;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93; vs&#46; MDI&#47;G 7&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9&#37; &#91;59&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;7<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Intensive insulin therapy with CSII vs&#46; MDI&#47;G was associated with better levels of HbA1c in patients with long-term type 1 diabetes&#46;</p></span>"
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            "titulo" => "Background and objective"
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            "titulo" => "Methods"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Las ventajas de la infusi&#243;n subcut&#225;nea continua de insulina &#40;ISCI&#41; sobre m&#250;ltiples inyecciones diarias de insulina con glargina &#40;MDI&#47;G&#41; son todav&#237;a inciertas&#46; Comparamos ISCI frente a MDI&#47;G en pacientes con diabetes tipo 1 sin indicaci&#243;n de terapia ISCI utilizando la monitorizaci&#243;n continua de glucosa &#40;CGSM&#41;&#46; Los objetivos primarios fueron el control gluc&#233;mico y la calidad de vida &#40;QOL&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Un total de 45 pacientes con diabetes 1 de largo tiempo de evoluci&#243;n y valores medios de HbA1c de 8&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;8&#37; &#40;70&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;4<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#41;&#44; previamente tratados con MDI&#47;NPH&#44; fueron cambiados a MDI&#47;G durante 6 meses y luego sin cumplir criterios cl&#237;nicos para terapia ISCI asignados aleatoriamente a ISCI o MDI&#47;G durante seis meses&#46; Se evalu&#243; la calidad de vida &#40;EsDqol&#41; y el control de la glucemia mediante la medici&#243;n de los niveles de HbA1c&#44; la tasa de hipoglucemias&#44; cetoacidosis y datos de CGSM&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Despu&#233;s de la primera fase &#40;MDI&#47;NPH a MDI&#47;G&#41; hubo una mejora significativa en EsDQOL total &#40;99&#44;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#44;38 vs&#46; 92&#44;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#44;65&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;028&#41;&#44; una disminuci&#243;n de 0&#44;5&#37; en los valores de HbA1c &#40;8&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2 vs&#46; 7&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;7&#37; &#91;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;7 vs&#46; 63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;032&#41;&#44; una mejora en la variabilidad de la glucemia &#40;desviaci&#243;n est&#225;ndar 66&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14 vs&#46; 59&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#59; p &#60;0&#44;05&#41;&#44; una disminuci&#243;n en las necesidades de insulina &#40;0&#44;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;29 vs&#46; 0&#44;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;25<span class="elsevierStyleHsp" style=""></span>U&#47;kg&#59; p &#60;0&#44;049&#41;&#44; una disminuci&#243;n en el n&#250;mero de episodios de hipoglucemia grave &#40;0&#44;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;9 vs&#46; 0&#44;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;2&#59; p &#60;0&#44;014&#41;&#44; y un aumento en los periodos de normoglucemia medidos con CGSM &#40;15&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#44;9&#37; vs&#46; 23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#44;4&#37;&#59; p &#60;0&#44;003&#41;&#46; Seis meses despu&#233;s de la aleatorizaci&#243;n&#44; se observaron mejoras significativas en la HbA1c &#40;7&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;7 vs&#46; 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;6&#37;&#59; &#91;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;5 vs&#46; 53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93;&#59; p &#60;0&#44;001&#41; y la calidad de vida &#40;91&#44;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22 vs&#46; 84&#44;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;63&#59; p &#60;0&#44;045&#41; s&#243;lo en el grupo ISCI&#46; El valour de HbA1c fue significativamente menor en ISCI en comparaci&#243;n con el grupo MDI&#47;G &#40;CSII 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;6&#37; &#91;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93; vs&#46; MDI&#47;G 7&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;9&#37; &#91;59&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;7<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La terapia insul&#237;nica intensiva con ISCI vs&#46; MDI&#47;G se asoci&#243; con mejores niveles de HbA1c en pacientes con diabetes tipo 1 de larga evoluci&#243;n&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
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          1 => array:2 [
            "identificador" => "abst0030"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">HbA1c at baseline&#44; and after 6 and 12 months with MDI and CSII&#46; &#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 basal&#11036;6 month in 2 groups&#59; &#42;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 6 month&#11036;12 month in CSII group&#59; &#36;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 MDI&#47;G vs&#46; CSII 12 month&#46;</p>"
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      1 => array:7 [
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        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">DQOL at baseline&#44; and after 6 and 12 months with MDI and CSII&#46; &#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 basal&#11036;6 month in 2 groups&#59; &#42;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 6 month&#11036;12 month in CSII group&#46;</p>"
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        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ns&#44; not significant&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MDI&#47;G<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CSII<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender &#40;men&#47;women&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#47;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#47;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Years with diabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Daily insulin dose&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mild hypoglycaemia&#47;week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe hypoglycaemia&#47;6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SMBG&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HbA1c &#37; &#40;mmol&#47;mol&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 &#40;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 &#40;67&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 &#40;69&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ketoacidosis &#40;previous 6 months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hospitalization &#40;previous year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preproliferative retinopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proliferative retinopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Incipient nephropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Established nephropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Unawareness hypoglycaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Homogenization phase</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Randomized study</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Basal<br>MDI&#47;NPH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 months<br>MDI&#47;glargine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months<br>MDI&#47;glargine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months<br>CSII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Basal insulin dose &#40;IU&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total insulin dose &#40;IU&#47;kg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;049&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;77<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HbA1c &#37; &#40;mmol&#47;mol&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 &#40;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7 &#40;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;032&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9 &#40;59&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6 &#40;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HbA1c &#60;7&#46;5&#37; &#40;58&#46;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SMBG&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe hypoglycaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;050<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleBold">CGMS</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean glycaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">172&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">162<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;104&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">146&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#35;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">145<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Standard deviation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#37; hyperglycaemia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;2<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#35;</span></a>&nbsp;\t\t\t\t\t\t\n
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                      "titulo" => "Continuous subcutaneous insulin infusion&#58; an approach to achieving normoglycaemia"
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                      "titulo" => "Continuous subcutaneous insulin infusion at 25 years&#58; evidence base for the expanding use of insulin pump therapy in type 1 diabetes"
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        "texto" => "<p id="par0300" class="elsevierStylePara elsevierViewall">This study was undertaken with finance from the <span class="elsevierStyleGrantSponsor" id="gs1">Fondo de Investigaci&#243;n Sanitaria</span> &#40;ISCIII&#41; &#40;PI07&#47;90330&#41;&#44; <span class="elsevierStyleGrantSponsor" id="gs2">Junta de Andaluc&#237;a</span> &#40;0240&#47;2006&#41;&#46;</p> <p id="par0305" class="elsevierStylePara elsevierViewall">We acknowledge other collaborations&#58;<elsevierMultimedia ident="tbl0005"></elsevierMultimedia></p> <p id="par0310" class="elsevierStylePara elsevierViewall">MSRA designed the study and analysis&#44; conducted data collection&#44; data interpretation and writing of the manuscript&#46; MDL conducted data collection&#44; data interpretation and writing of the manuscript&#46; IGM conducted data collection&#44; data interpretation and writing of the manuscript&#46; AM designed the study and analysis and conducted data collection&#46; VM conducted data collection and data interpretation&#46; IC conducted data collection&#46; MH conducted data collection and data interpretation&#46; SG conducted data collection and data interpretation&#46; SM designed the study and analysis&#46; MC conducted data collection and data interpretation&#46; MTA was involved in the design of the psychological assessment protocol of this study&#44; and the coordination the data collection process&#44; and in the interpretation of the data and in reviewing&#46; GR and FS designed the study and analysis and helped write the manuscript&#46;</p>"
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Article information

ISSN: 23870206
Original language: English

DOI:10.1016/j.medcle.2015.09.006

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