Liraglutide in a real-world setting: Joint modeling of metabolic response, prediction of efficacy, and cardiovascular risk | Endocrinología, Diabetes y Nutrición (English ed.)

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true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "376" "paginaFinal" => "384" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Isabel Alonso-Troncoso, Carmen Carollo-Limeres, Mónica Rios-Prego, Ipek Guler, Carmen Cadarso-Suárez, Alexis F-Mariño" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Isabel" "apellidos" => "Alonso-Troncoso" "email" => array:1 [ 0 => "ialonsot61@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carmen" "apellidos" => "Carollo-Limeres" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Mónica" "apellidos" => "Rios-Prego" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Ipek" "apellidos" => "Guler" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Carmen" "apellidos" => "Cadarso-Suárez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Alexis" "apellidos" => "F-Mariño" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio Endocrinología, Complejo Hospitalario Universitario de Pontevedra, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Bioestadística, Facultad de Medicina, Universidad Santiago de Compostela, Santiago de Compostela, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio Medicina Interna, Complejo Hospitalario Universitario de Pontevedra, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio Endocrinología, Complejo Hospitalario Universitario de Vigo, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Liraglutida en vida real: modelización conjunta de la respuesta metabólica, predicción de eficacia y riesgo cardiovascular" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 973 "Ancho" => 2124 "Tamanyo" => 96140 ] ] "descripcion" => array:1 [ "en" => "Effect of LRG treatment on HbA1c (A) and body weight (B) over time (mean) for patients in treatment for 12 months (n 171) and 24 months (n 85)." ] ] ] "textoCompleto" => "IntroductionType 2 diabetes mellitus (T2DM) affects people throughout the world. Its prevalence has been increasing dramatically as a result of aging populations and the rising prevalence of obesity.<a class="elsevierStyleCrossRefs" href="#bib0155">1,2</a>Insulin resistance is an underlying cause of T2DM and is associated with obesity. Consequently, weight reduction is a key goal of treatment. Whenever possible, medications should be chosen to promote weight loss.Weight gain can offset the beneficial effects of good glycemic control and discourage patients from adhering to treatment. Even moderate weight loss has been shown to improve glycemic control.<a class="elsevierStyleCrossRefs" href="#bib0165">3,4</a> Guidelines<a class="elsevierStyleCrossRefs" href="#bib0165">3,5,6</a> recommend a patient-centered approach.The safety and efficacy profile of the GLP1-RA liraglutide (LRG) has been evaluated in clinical trials,<a class="elsevierStyleCrossRefs" href="#bib0185">7,8</a> which have shown that, in addition to controlling glycemia, LRG can reduce body weight. A meta-analysis<a class="elsevierStyleCrossRef" href="#bib0195">9</a> evaluating the results of head-to-head trials showed LRG to be one of the most effective drugs for control of glycemia and obesity.Conditions affecting people with T2DM (hypertension, dyslipidemia, obesity, physical inactivity) increase the risk of heart disease. LRG<a class="elsevierStyleCrossRef" href="#bib0200">10</a> and empagliﬂozin<a class="elsevierStyleCrossRef" href="#bib0205">11</a> reduce cardiovascular and all-cause mortality when added to standard care in clinical trials. Ongoing studies are investigating the cardiovascular beneﬁts of other agents in these drug classes. Real-world and post-marketing studies are being promoted to provide data that will help clinicians to choose appropriate options and corroborate safety.The primary objective of the present study was to evaluate the metabolic effectiveness and safety of LRG in T2DM patients in real-world clinical practice over a longer period than during clinical trials. The secondary objectives were to evaluate potential clinical predictors of response, effectiveness of LRG in various patient subgroups, and changes in cardiovascular risk. A special analysis of patients receiving insulin treatment was performed.MethodsStudy designWe performed a 1-year observational, retrospective cohort study (October 2015 to October 2016). We identified patients treated with LRG according to the indications of usual clinical practice.<a class="elsevierStyleCrossRef" href="#bib0210">12</a>The study was approved by the Ethics Committee of the Galician Health Service (SERGAS) and conducted according to the requirements of the Declaration of Helsinki and the principles of Good Clinical Practice.PatientsThe study population comprised outpatients followed under conditions of routine clinical practice. The inclusion criteria were T2DM, age ≥18 years, and body mass index (BMI) ≥30kg/m2.Study variablesThe variables we recorded at baseline were sex, age, diabetes duration, cardiovascular risk factors (hypertension, dyslipidemia, smoking, general vascular disease, sleep apnea syndrome), and previous treatment (metformin, combined oral antidiabetic drugs, insulin).The parameters evaluated during follow-up (at 3, 6, 12, 18, 24, 30, and 36 months) were body weight, BMI, percentage of excess BMI lost (% EBMIL), HbA1c, fasting blood glucose, systolic and diastolic blood pressure, and lipid profile.We also evaluated the proportion of patients achieving an HbA1C target of <7% and a composite endpoint (CEP), which was defined as follows:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•CEP I: HbA1c reduction ≥1 and weight loss ≥5%</li><li class="elsevierStyleListItem" id="lsti0010">•CEP II: HbA1c reduction ≥1 and weight loss ≥3%</li><li class="elsevierStyleListItem" id="lsti0015">•CEP III: HbA1c reduction ≥0.4 and weight loss ≥5%</li><li class="elsevierStyleListItem" id="lsti0020">•CEP IV: HbA1c reduction ≥0.4 and weight loss ≥3%</li><li class="elsevierStyleListItem" id="lsti0025">•CEP V: HbA1c reduction ≥0.4 and no weight increase or weight loss >3% with no increase in HbA1c</li></ul>We evaluated baseline characteristics that could be predictive of response to LRG. We analyzed response (HbA1C, weight) by subgroups: age, sex, diabetes duration, treatment at baseline. Patients who were receiving insulin were evaluated to study the effect of adding LRG.We evaluated the risk of cardiovascular disease using Regicor Calculator, which is adapted to the Spanish population.<a class="elsevierStyleCrossRef" href="#bib0215">13</a>Statistical analysisA linear mixed-effects model<a class="elsevierStyleCrossRef" href="#bib0220">14</a> was used to study the overall reduction in weight and HbA1c during treatment. The model enables us to study the effect of time and duration of diabetes flexibly using a quadratic function to determine whether the responses are linear or not over time.The linear mixed effects model is constructed with a bivariate structure to investigate the time-dependent relationship between weight and HbA1c values. We used the bivariate longitudinal analysis introduced by Thiébaut et al.,<a class="elsevierStyleCrossRef" href="#bib0225">15</a> which enables testing of the difference between the longitudinal outcomes and joint testing of a treatment effect on a set of outcomes.The statistical analysis was performed using R, Version 2.12.0 (R Development Core Team, Vienna, Austria) and SAS, Version 9.2 (SAS Institute Inc., Cary, North Carolina, USA). Statistical significance was set at p<0.05.ResultsBaseline sampleThe study population comprised 209 patients. Twenty-two were withdrawn. Metabolic response was evaluated in the remaining 187 cases. Of these, 171 patients completed 12 months on treatment (Group A), 85 completed 24 months (Group B), and 20 completed 36 months (Group C).The reasons for withdrawal were LRG-related adverse events (13 cases), death (5 cases), acute complications (2 cases), and lost cases (2 cases).LRG was discontinued in 34 cases (18%) owing to lack of efficacy, which the physician considered as inadequate glycemic and/or weight response according to his individualized objectives. Most of them discontinued treatment between 3 and 6 months from the start. These patients were considered for the effectiveness evaluation.We evaluated the descriptive baseline characteristics of the basal 187 patients (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Metabolic responseOverall, the mean reduction in weight was 8.6kg at 12 months, 8.5kg at 24 months, and 9kg at 36 months. The mean reduction in HbA1c was 1.7% at 12 months, 24 months, and 36 months. A significant reduction in HbA1c (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A) and weight (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B) was observed as early as week 12, and this was maintained at 12 and 24 months.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the progress of metabolic variables for patients who had received treatment for 12 months, 24 months, and 36 months. We found a marked and stable improvement over time in most of the metabolic parameters analyzed.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>HbA1c <7% was achieved by 42% of patients at 12 months and by 40% at 24 months. The results at 12–24 months for each of the CEP defined (see Material and Methods, Study variables) were as follows: CEP I, 34%–36%; CEP II, 39%–44%; CEP III, 49%–48%; CEP IV, 59%–57%; and CEP V, 74%–79%. There were no differences between sexes. The results for HbA1c compared with changes in body weight from baseline to 12 and 24 months are shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> (scatterplot). Most patients achieved a reduction in both parameters.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Correlation between metabolic response and study variablesWe evaluated HbA1c over time (at 12/24 months) according to age, diabetes duration, baseline antidiabetic medication and sex. With respect to age, the variation was as follows: <50 years, −2.3%/−1.68%; 51–65 years, −1.3%/−1.2%; >65 years, −1.3%/−1.5%. According to duration of diabetes: <5 years, −1.7%/−1.5%; 5–10 years, −1.5%/−1.2%; >10 years, −1.2%/−1.1% and baseline antidiabetic medication: metformin, −1.7%/−1.5%; oral agents, −1.6%/−1.2%; insulin, −1.4%/−1.5%. According to sex: female, −1.5%/−1.4%; male −1.56%/−1.3%.The decrease in HbA1c was significant in all the subgroups, although there were no significant differences between the subgroups.Statistical correlation studies results are shown at <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. The results of the bivariate linear mixed effects model (weight and HbA1c) are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3A</a>. No correlations were found between reduction in weight and HbA1c with respect to age or sex. According to the baseline BMI value, the reduction in HbA1c was inversely correlated with BMI, although weight reduction was not. Therefore, LRG reduced BMI equally well at all baseline BMI values. However, the decrease in HbA1c was lower with a higher baseline BMI.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The HbA1c reduction was inversely correlated with duration of diabetes, although weight reduction was not. The relationship was linear, that is, the lower the duration of diabetes, the greater the reduction in HbA1c.The correlation of the random intercept and slopes for the reduction in weight and HbA1c was obtained based on a longitudinal multivariate model (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 3B</a>). The intercept represents the correlation between the baseline measurements; the slope represents the time-dependent correlation between weight and HbA1c. The model therefore indicated that the greater the initial BMI, the lower the decrease in the HbA1c slope, and the higher the initial HbA1c, the greater the decrease in the slope of HbA1c.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>The duration of therapy with LRG was directly correlated with the decrease in weight and HbA1c as a result of the initial and early response that was maintained over time. In this case, the relationship was quadratic, not linear (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and B).Effect of adding LRG to previous insulin treatmentOf the 68 patients (36%) receiving insulin at baseline (0.55±0.4IU/kg), 59 patients were evaluated at 12 months and 23 (39%) had stopped insulin. Of the 30 patients evaluated at 24 months, 8 (26%) had stopped insulin. The patients who continued to take insulin reduced their dose to 0.41±0.2IU/kg at 12 months and to 0.43±0.2IU/kg at 24 months.In patients receiving insulin, baseline HbA1c fell from 9.5±1.8 to 9.3±1.7% at 12 months (n=36) and to 8.9±1.3% at 24 months. In the subgroup of patients who stopped insulin, baseline HbA1c fell to 7.2±1.4% (n=23) at 12 months and to 7.7±1.5% (n=8) at 24 months. A significant reduction in weight was observed: from 98.1±15.6kg to 89.5±15.5kg at 12 months and 88.2±13.9kg at 24 months.Evaluation of %EBMIL with LRG treatmentEBMIL is the criterion used to evaluate metabolic surgery, which was considered successful (EBMIL >50%) in 15 patients (9%) at 12 months and in 7 patients (8%) at 24 months. EBMIL was >10% in 125 patients (73%) at 12 months and in 65 patients (77%) at 24 months.Adverse eventsNo serious adverse events were observed. Thirteen patients stopped treatment because of digestive intolerance (nausea and vomiting 7 cases, diarrhea 4 cases, and increased amylase 2 cases). No patients had pancreatitis or pancreatic cancer. Five patients died (cancer of the liver, lung, colon, bladder, and genitals). Acute complications (major intercurrent process or adverse event not related to LRG) were observed in 2 cases (ACVA and appendicitis).Cardiovascular risk during treatment with LRGCardiovascular risk evolution was evaluated using REGICOR.<a class="elsevierStyleCrossRef" href="#bib0215">13</a> Patients on LRG treatment for 12 months: at baseline at very high risk was 14 (10%) it decreased to 5 (3%) at 12months; 38 (26%) patients at high risk decreased to 17 (12%) at 12months; 58 (40%) patients at moderate risk increased to 71 (49%) and 34 (24%) patients at low risk increased to 51 (35%) at 12months.Patients on LRG treatment for 24months: at baseline at very high risk was 7 (8%) it decreased to 3 (4%) at 24months; 24 (30%) patients at high risk decreased to 15 (19%) at 24months; 30 (38%) patients at moderate risk increased to 33 (41%) and 19 (24%) patients at low risk increased to 29 (36%) at 24months. Treatment with LRG for 12–24 months, combined with other treatments used in real-world practice, reduced cardiovascular risk from high to moderate-low.DiscussionWe performed a retrospective observational cohort study to evaluate the metabolic effectiveness and safety of LRG in patients with T2DM in real-world clinical practice over a longer period than that usually assessed in clinical trials. We found that therapy with LRG reduced weight at 12, 24, and 36 months. Hb1Ac also decreased to target in almost half of the study population at 12 and 24 months. Most patients achieved the composite endpoint. Adding LRG to basal insulin treatment enabled nearly one-third of patients to stop insulin; the remainder were able to reduce their dose by one-third and weight reduction was significant.In a recent review of 124 publications,<a class="elsevierStyleCrossRef" href="#bib0230">16</a> HbA1c was significantly reduced after 6 months of treatment with LRG (mean change from baseline 0.9%–2.2%; HbA1c <7.0%, 29.5–65.0%). The NICE composite endpoint (HbA1c reduction ≥1% and weight loss ≥3%) was met in 16.9–47.0% of cases, and the absolute weight change was −1.3 to −8.65kg. Our results were consistent with the best of these, even though the time on treatment with LRG was longer than most of them.When our results were compared with those of EVIDENCE,<a class="elsevierStyleCrossRef" href="#bib0235">17</a> the most longer (24months) and big population sample (n 2019) in this review, the greater mean HbA1c and weight reduction in our series can be explained by the shorter duration of diabetes and higher initial weight.This review includes three Spanish studies; Gomez Peralta et al.<a class="elsevierStyleCrossRef" href="#bib0240">18</a> reported a 4.4kg reduction at 3months (n 158); Diaz-Soto G et al.,<a class="elsevierStyleCrossRef" href="#bib0245">19</a> a 0.9% HbA1c reduction at 4months (n 59) and Mezquita-Raya et al.,<a class="elsevierStyleCrossRef" href="#bib0250">20</a> a 1.1% HbA1c and 4.6kg reduction at 6 months of LRG treatment.Later Lecube et al.<a class="elsevierStyleCrossRef" href="#bib0255">21</a> reported a HbA1c decrease near 1.2% and weight loss 7.3kg during 6 months treatment.A recent multicentric publication in Spain<a class="elsevierStyleCrossRef" href="#bib0260">22</a> (24months treatment) reports a HbA1c reduction ranging from 1.0% to 1.5% and body weight from 5kg to 10kg.We found that the metabolic response was early (3–6 months) and maintained over time. This finding could be explained by the appropriate selection of responders in our real-world setting.Evaluation of the reduction in HbA1c using the random intercept and slope model revealed a correlation with the baseline value (the higher the baseline value, the greater the reduction). In contrast, the reduction and intercept for the HbA1c slope were lower at higher BMI levels, probably because LRG was indicated for patients with relatively low baseline HbA1c and very high baseline BMI, with correction of high BMI being the main objective of therapy with LRG in this subgroup. Given the findings for baseline BMI and the subsequent reduction therefore, treatment with LRG reduced BMI equally well across all baseline BMI values. Consequently, the effect of LRG on weight could be independent of the effect on HbA1c. This result supports the indication of LRG for weight reduction.The reduction in HbA1c was inversely correlated with duration of diabetes. The relationship was linear, that is, the lower the duration of diabetes, the greater the reduction in HbA1c. In contrast, no correlation was observed for the reduction in weight; the effect of therapy on weight was independent of duration of diabetes. These findings also support an independent effect of LRG on glycemia and on weight.Treatment of diabetes and obesity should be intensified once the diagnosis has been confirmed, and every opportunity should be taken to create a legacy effect.<a class="elsevierStyleCrossRefs" href="#bib0265">23–25</a> The efficacy and maintained effect of LRG over time make it a promising option when attempting to create a legacy effect in obese patients with diabetes.The decrease in weight and HbA1c was more pronounced as the time on LRG increased. However, this finding can be explained by the initial and early response, which was maintained over time. The statistical analysis showed that the initial glycemia and weight responses were based on a quadratic model and not on a linear model, thus confirming these early responses as major predictive markers of response to LRG.Given that the effects of therapy with LRG were clear after 12 weeks, a 3-month trial period may be sufficient to demonstrate the potential of the drug to reduce both weight and HbA1c. Treatment could be discontinued in patients who do not respond within this period.Addition of LRG to insulin has proven to be effective in reversing weight gain, decreasing the insulin dose, and improving glycemic control in obese patients.<a class="elsevierStyleCrossRef" href="#bib0280">26</a> The results of the subgroup of patients who were taking insulin at baseline are particularly interesting. Some were able to stop or reduce insulin dose, and both weight and Hb1Ac improved considerably. Consequently, in obese patients with T2DM, treatment with GLP1-RA should be considered before starting with insulin<a class="elsevierStyleCrossRefs" href="#bib0165">3,5,6</a> or uptitrating its dose. We may be able to “rescue” patients who received intensive therapy with insulin before LRG was marketed. Our results of combined LRG and insulin therapy may help to understand the results of previous studies.<a class="elsevierStyleCrossRef" href="#bib0260">22</a>Evaluation of the EBMIL enabled us to compare our results with those obtained with bariatric surgery.<a class="elsevierStyleCrossRefs" href="#bib0285">27,28</a> Our results suggest that LRG treatment in T2DM obese patients could facilitate or even eliminate the need for surgery in patients who could reach the target %EBMIL with LRG alone.Most adverse effects involved the gastrointestinal tract and were mild. These were less frequent than in clinical trials.<a class="elsevierStyleCrossRef" href="#bib0185">7</a> The favorable safety profile of LRG could facilitate adherence to dietary modifications and ensure continued health benefits over time.Recent trials evaluating LRG,<a class="elsevierStyleCrossRef" href="#bib0200">10</a> empagliflozin,<a class="elsevierStyleCrossRef" href="#bib0205">11</a> semaglutide,<a class="elsevierStyleCrossRef" href="#bib0295">29</a> canagliflozin<a class="elsevierStyleCrossRef" href="#bib0300">30</a> showed improved cardiovascular outcomes in patients with T2DM. The mechanism underlying these results and the question of whether outcome was a class effect or not remain open to debate. Our results for cardiovascular risk are consistent with those of the LEADER trial.<a class="elsevierStyleCrossRef" href="#bib0200">10</a> In our study, we cannot attribute the improvement in cardiovascular risk exclusively to LRG. The treatment schedule was multifactorial, as recommended in guidelines. The addition of LRG could enable high-risk patients to be reclassified as moderate-low risk.This study has limitations mainly related to its observational retrospective design. The criterion to define lack of efficacy and discontinue LRG treatment was not predefined, it was individualized decided by the physician. We must consider the influence of confounding factors. The combined antidiabetic therapy prescribed did not include SGLT2i. Future results of metabolic effectiveness studies in real-world clinical practice including combined SGLT2i and GLP1-RA may be compared with our results just using GLP-RA.Real-world data have the potential to improve the quality and delivery of medical care, reduce overall costs, and improve outcomes by accelerating our understanding of how best to incorporate new therapies into everyday clinical practice. Such data help to fill the knowledge gap between clinical trials and actual clinical practice.ConclusionsIn conclusion, we found that therapy with LRG under conditions of routine clinical practice produced a better metabolic response (weight loss and reduction in Hb1Ac) than that observed in clinical trials. The early effect observed in responders at 3 months was maintained at 12 and 24 months and was the best predictor of response to LRG. The weight response was independent of baseline BMI, baseline HbA1c, and duration of diabetes. The HbA1c response was greater when baseline HbA1c was higher and duration of diabetes was shorter. LRG could delay or reduce the insulin dose in a significant subgroup of obese patients by improving weight simultaneously with glycemic control. We also observed an improvement in cardiovascular risk factors enabling patients to be transferred from the high-risk category to medium-low risk. Consequently, LRG would be a suitable candidate for inclusion in multifactorial interventions aimed at reducing the risk of cardiovascular events.Founding sourcesMedical writing, editorial assistance (Cociente, S.L.), and the statistical analysis were funded by a grant from Novo Nordisk. The authors take full responsibility for the content and conclusions stated in this manuscript. Novo Nordisk neither influenced the content of this publication nor was involved in the study design or in the collection, analysis, or interpretation of the data reported.Conflict of interestsThe authors declare no conflict of interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1226550" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 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" => "xpalclavsec1140151" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec1140153" "titulo" => "Abbreviations" ] 3 => array:2 [ "identificador" => "xpalclavsec1140152" "titulo" => "Abreviaturas" ] 4 => array:3 [ "identificador" => "xres1226551" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 5 => array:2 [ "identificador" => "xpalclavsec1140150" "titulo" => "Palabras clave" ] 6 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 7 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Patients" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Study variables" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 8 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Baseline sample" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Metabolic response" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Correlation between metabolic response and study variables" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Effect of adding LRG to previous insulin treatment" ] 4 => array:2 [ "identificador" => "sec0060" "titulo" => "Evaluation of %EBMIL with LRG treatment" ] 5 => array:2 [ "identificador" => "sec0065" "titulo" => "Adverse events" ] 6 => array:2 [ "identificador" => "sec0070" "titulo" => "Cardiovascular risk during treatment with LRG" ] ] ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0085" "titulo" => "Founding sources" ] 12 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict of interests" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-06-28" "fechaAceptado" => "2018-09-07" "PalabrasClave" => array:2 [ "en" => array:3 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1140151" "palabras" => array:5 [ 0 => "Type 2 diabetes mellitus" 1 => "Liraglutide" 2 => "Efficacy" 3 => "Real-world studies" 4 => "Cardiovascular risk" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abreviaturas" "identificador" => "xpalclavsec1140152" "palabras" => array:4 [ 0 => "T2DM" 1 => "LRG" 2 => "GLP1-RA" 3 => "% EBMIL" ] ] 2 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1140153" "palabras" => array:4 [ 0 => "T2DM" 1 => "LRG" 2 => "GLP1-RA" 3 => "% EBMIL" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1140150" "palabras" => array:5 [ 0 => "Diabetes mellitus tipo 2" 1 => "Liraglutida" 2 => "Eficacia" 3 => "Estudios en vida real" 4 => "Riesgo cardiovascular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Introduction and objectivesThe worldwide prevalence of type 2 diabetes mellitus increases in parallel to that of obesity. Liraglutide (LRG), a glucagon-like peptide-1 receptor agonist, can reduce body weight. This study assessed the metabolic efficacy of LRG in real-world clinical practice. MethodsAn observational, retrospective cohort study including patients treated with LRG for at least one year (187 patients). Anthropometric and metabolic variables, a composite endpoint, factors predicting response to LRG, and cardiovascular risk over time were assessed. A linear mixed-effects model with a bivariate structure was constructed to investigate the time-dependent relationship between weight and HbA1c values. ResultsHbA1c levels and weight significantly decreased in the first 12 weeks, and the decrease persisted at 12 and 24 months in all subgroups studied. Mean weight and HbA1c decreases after 24 months were 8.5kg and 1.7% respectively. HbA1c values <7% were achieved by 42% of patients at 12 months and by 40% at 24 months. Treatment with LRG allowed for reduction in insulin dose. No serious adverse events were noted. Cardiovascular risk decreased from high to moderate-low. ConclusionsUnder standard clinical practice conditions, LRG achieved a better metabolic response than seen in clinical trials. Efficacy at 12 weeks of treatment is a good predictor of response. LRG allows for delaying or reducing insulin dose by improving both weight and glucose control. Cardiovascular risk improved." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 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 objetivosLa prevalencia mundial de diabetes mellitus tipo 2 aumenta junto a la de la obesidad. Liraglutida (LRG), un agonista del receptor del péptido similar al GLP1, es un fármaco antidiabético capaz de reducir peso. Evaluamos en práctica clínica de vida real su eficacia metabólica. MétodoEstudio de cohorte observacional retrospectivo. Se incluyeron los pacientes tratados al menos durante un año con LRG (187 pacientes). Evaluamos variables antropométricas, metabólicas, objetivos combinados, factores predictivos de respuesta y evolución del riesgo cardiovascular. Se construyó un modelo de efectos mixtos lineales de estructura bivariante para investigar la relación tiempo-dependiente entre el peso y los valores de HbA1c. ResultadosDescenso significativo de los valores de HbA1c y peso en las primeras 12 semanas de tratamiento, mantenido a los 12 y 24 meses, en todos los subgrupos estudiados. Reducción media de peso y HbA1c tras 24 meses de tratamiento de 8,5 kg y 1,7%. El valor de HbA1c fue <7% en 42% de pacientes a los 12 meses, 40% a los 24 meses. El tratamiento con LRG permitió reducir la dosis de insulina. No registramos eventos adversos graves. El riesgo cardiovascular mejoró. ConclusionesBajo condiciones de práctica clínica habitual la respuesta metabólica a LRG resultó mejor que la observada en ensayos clínicos. La eficacia a las 12 semanas de tratamiento es un buen predictor de respuesta. LRG permite retrasar o reducir la insulinoterapia. Los pacientes mejoraron su riesgo cardiovascular." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 973 "Ancho" => 2124 "Tamanyo" => 96140 ] ] "descripcion" => array:1 [ "en" => "Effect of LRG treatment on HbA1c (A) and body weight (B) over time (mean) for patients in treatment for 12 months (n 171) and 24 months (n 85)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1483 "Ancho" => 1511 "Tamanyo" => 116572 ] ] "descripcion" => array:1 [ "en" => "Scatter plot of changes in body weight and HbA1c from baseline to 12 and 24 months after LRG introduction." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "CVD: cardiovascular disease; HbA1c: glycated hemoglobin A1c; ND: no data; SAS: sleep apnea syndrome; SD: standard deviation." "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">104 (56%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83 (44%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.4±10.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤50 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 (21%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51–65 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 (53%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>65 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 (26%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diabetes duration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.1±6.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83 (44%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–10 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (28%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>10 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 (27%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous treatment</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Metformin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (17%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Combined OAD<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">92 (49%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Insulin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 (32%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fasting plasma glucose, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">208.7±72.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HbA1c % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.6±1.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI kg/m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39.2±6.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weight kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">103.2±17.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abdominal circumference cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">121.8±11.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SAS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (15%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smokers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (17%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CVD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (20%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2095797.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Combined oral antidiabetic drugs: metformin, sulfonylureas, pioglitazone. Patients on sodium-glucose cotransporter 2 inhibitors (SGLT2i) were not included." ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics (n=187)." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "BMI: body mass index; DBP: diastolic blood pressure; HbA1c: glycated hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; SBP: systolic blood pressure." "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-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Metabolic variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Time in LRG treatment</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">24 months \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">36 months \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean±SD (change with respect to basal value)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weight, kg</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">102.8±17.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95.4±17.4 (−7.4±6.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">102.6±19.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94.7±18.4 (−7.9±6.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95.1±18 (−7.5±6.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">108.2±17.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">97.8±17 (−10.4±9.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98.8±17.8 (−9.4±8.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99.2±19.3 (−9±9.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HbA1c, %</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.7±1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.3±1.8 (−1.4±1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.9±1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.3±1.8 (−1.6±2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.5±1.7 (−1.4±1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.9±1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.8±1.4 (−2.1±2.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7±1.2 (−1.9±2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.2±1.4 (−1.7±1.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI, kg/m2</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39.2±6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.3±5.6 (−2.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38.9±5.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.8±5.2 (−3.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36±5.6 (−2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40.4±6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.6±5 (−3.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.9±5.2 (−3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.1±5.7 (−3.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SBP, mmHg</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">154.2±23.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">140.3±18.8 (−13.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">154.4±25.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">139.7±18.1 (−14.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">138.1±17.7 (−16.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">160±19.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">140.5±17.7 (−19.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">144.5±21.4 (−15.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">135.5±12 (−25) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DBP, mmHg</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85.4±14.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79.6±11.9 (−5.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85.9±15.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77.8±10.9 (−8.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78.7±12.7 (−7.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">91±12.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78.3±13.4 (−12.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79.8±14.3 (−11.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79±10.7 (−12) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Basal glucose,mg/dL</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">214.3±72.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">157.6±60.1 (−56.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">224.5±69.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">154.7±56.5 (−69.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">164.4±62.2 (−60.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">235±69.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">146.2±54.4 (−89) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">150.9±43.8 (−84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">176.1±70.4 (−59) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cholesterol, mg/dL</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">200.3±42.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">184.6±43.3 (−15.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">202.9±39.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">187.2±49.6 (−15.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">183.6±35.9 (−19.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">224.7±42.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">192.5±41.7 (−32.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">177.8±35.9 (−46.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">196.6±47 (−28.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HDL-C, mg/dL</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49±12.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50.7±11.9 (+1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.7±12.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.3±12.4 (+2.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.4±10.2 (−0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46.1±10.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.1±14.5 (+7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47.6±10.4 (+1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46.9±10.3 (+0.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LDL-C, mg/dL</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">108.5±38.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99.9±40.3 (−8.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">107.3±37.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">102.6±45.7 (−4.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99.7±32.8 (−7.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">134.0±44.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">106.7±35.9 (−27.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">97.4±36.2 (−36.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46.7±10.5 (−87.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triglycerides, mg/dL</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">229.6±144.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">180.2±89.4 (−49.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">245.7±136.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">171.7±70.8 (−74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">186.1±97.1 (−59.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">252.7±121.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">173.7±64.6 (−79) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">182.9±11.7 (−69.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">187.4±86.6 (−65.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2095798.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Evolution of metabolic variables according to the group studied: Group A (n 171) patients treated for 12 months, Group B (n 85) patients treated for 24 months and Group C (n 20) patients treated for 36 months." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3A" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table 3" "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SD: standard deviation. Treatment time2 and duration of diabetes2 are a quadratic effect of treatment time and duration of diabetes, respectively. These variables capture the non-linear effect of the corresponding outcomes." "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Weight reduction model</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HbA1c reduction model</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Coeff (SD) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Coeff (SD) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intercept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.31 (2.71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.09 (0.97) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.04 (0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.84 (0.58) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.22 (0.20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.08 (0.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.04 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment time \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.21 (0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.03 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment time2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.005 (0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.0009 (0.0003) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Duration of diabetes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.16 (0.11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.08 (0.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Duration of diabetes2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.007 (0.004) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 (0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2095795.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results of the bivariate linear mixed effects model." ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 3B" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table 3" "rol" => "short" ] ] "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=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intercept weight reduction \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intercept HbA1c reduction \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Slope weight reduction \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Slope HbA1c reduction \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intercept weight \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intercept HbA1c \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Slope weight \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.12 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2095796.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Intercept and slopes for reduction in weight and HbA1c." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Maps of trends in diagnosed diabetes and obesity, April 2017; CDC's Division of Diabetes Translation. 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Liraglutide in a real-world setting: Joint modeling of metabolic response, prediction of efficacy, and cardiovascular risk

Liraglutida en vida real: modelización conjunta de la respuesta metabólica, predicción de eficacia y riesgo cardiovascular

Isabel Alonso-Troncosoa,

Corresponding author

ialonsot61@gmail.com

Corresponding author.

, Carmen Carollo-Limeresb, Mónica Rios-Pregoc, Ipek Gulerb, Carmen Cadarso-Suárezb, Alexis F-Mariñod

a Servicio Endocrinología, Complejo Hospitalario Universitario de Pontevedra, Spain

b Unidad de Bioestadística, Facultad de Medicina, Universidad Santiago de Compostela, Santiago de Compostela, Spain

c Servicio Medicina Interna, Complejo Hospitalario Universitario de Pontevedra, Spain

d Servicio Endocrinología, Complejo Hospitalario Universitario de Vigo, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Type 2 diabetes mellitus &#40;T2DM&#41; affects people throughout the world&#46; Its prevalence has been increasing dramatically as a result of aging populations and the rising prevalence of obesity&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Insulin resistance is an underlying cause of T2DM and is associated with obesity&#46; Consequently&#44; weight reduction is a key goal of treatment&#46; Whenever possible&#44; medications should be chosen to promote weight loss&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Weight gain can offset the beneficial effects of good glycemic control and discourage patients from adhering to treatment&#46; Even moderate weight loss has been shown to improve glycemic control&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4</span></a> Guidelines<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;5&#44;6</span></a> recommend a patient-centered approach&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The safety and efficacy profile of the GLP1-RA liraglutide &#40;LRG&#41; has been evaluated in clinical trials&#44;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#44;8</span></a> which have shown that&#44; in addition to controlling glycemia&#44; LRG can reduce body weight&#46; A meta-analysis<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> evaluating the results of head-to-head trials showed LRG to be one of the most effective drugs for control of glycemia and obesity&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Conditions affecting people with T2DM &#40;hypertension&#44; dyslipidemia&#44; obesity&#44; physical inactivity&#41; increase the risk of heart disease&#46; LRG<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> and empagli&#64258;ozin<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> reduce cardiovascular and all-cause mortality when added to standard care in clinical trials&#46; Ongoing studies are investigating the cardiovascular bene&#64257;ts of other agents in these drug classes&#46; Real-world and post-marketing studies are being promoted to provide data that will help clinicians to choose appropriate options and corroborate safety&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The primary objective of the present study was to evaluate the metabolic effectiveness and safety of LRG in T2DM patients in real-world clinical practice over a longer period than during clinical trials&#46; The secondary objectives were to evaluate potential clinical predictors of response&#44; effectiveness of LRG in various patient subgroups&#44; and changes in cardiovascular risk&#46; A special analysis of patients receiving insulin treatment was performed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study design</span><p id="par0035" class="elsevierStylePara elsevierViewall">We performed a 1-year observational&#44; retrospective cohort study &#40;October 2015 to October 2016&#41;&#46; We identified patients treated with LRG according to the indications of usual clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The study was approved by the Ethics Committee of the Galician Health Service &#40;SERGAS&#41; and conducted according to the requirements of the Declaration of Helsinki and the principles of Good Clinical Practice&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patients</span><p id="par0045" class="elsevierStylePara elsevierViewall">The study population comprised outpatients followed under conditions of routine clinical practice&#46; The inclusion criteria were T2DM&#44; age &#8805;18 years&#44; and body mass index &#40;BMI&#41; &#8805;30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Study variables</span><p id="par0050" class="elsevierStylePara elsevierViewall">The variables we recorded at baseline were sex&#44; age&#44; diabetes duration&#44; cardiovascular risk factors &#40;hypertension&#44; dyslipidemia&#44; smoking&#44; general vascular disease&#44; sleep apnea syndrome&#41;&#44; and previous treatment &#40;metformin&#44; combined oral antidiabetic drugs&#44; insulin&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The parameters evaluated during follow-up &#40;at 3&#44; 6&#44; 12&#44; 18&#44; 24&#44; 30&#44; and 36 months&#41; were body weight&#44; BMI&#44; percentage of excess BMI lost &#40;&#37; EBMIL&#41;&#44; HbA1c&#44; fasting blood glucose&#44; systolic and diastolic blood pressure&#44; and lipid profile&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">We also evaluated the proportion of patients achieving an HbA1C target of &#60;7&#37; and a composite endpoint &#40;CEP&#41;&#44; which was defined as follows&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel"><span class="elsevierStyleBold">&#8226;</span></span><p id="par0065" class="elsevierStylePara elsevierViewall">CEP I&#58; HbA1c reduction &#8805;1 and weight loss &#8805;5&#37;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel"><span class="elsevierStyleBold">&#8226;</span></span><p id="par0070" class="elsevierStylePara elsevierViewall">CEP II&#58; HbA1c reduction &#8805;1 and weight loss &#8805;3&#37;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel"><span class="elsevierStyleBold">&#8226;</span></span><p id="par0075" class="elsevierStylePara elsevierViewall">CEP III&#58; HbA1c reduction &#8805;0&#46;4 and weight loss &#8805;5&#37;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel"><span class="elsevierStyleBold">&#8226;</span></span><p id="par0080" class="elsevierStylePara elsevierViewall">CEP IV&#58; HbA1c reduction &#8805;0&#46;4 and weight loss &#8805;3&#37;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel"><span class="elsevierStyleBold">&#8226;</span></span><p id="par0085" class="elsevierStylePara elsevierViewall">CEP V&#58; HbA1c reduction &#8805;0&#46;4 and no weight increase or weight loss &#62;3&#37; with no increase in HbA1c</p></li></ul></p><p id="par0090" class="elsevierStylePara elsevierViewall">We evaluated baseline characteristics that could be predictive of response to LRG&#46; We analyzed response &#40;HbA1C&#44; weight&#41; by subgroups&#58; age&#44; sex&#44; diabetes duration&#44; treatment at baseline&#46; Patients who were receiving insulin were evaluated to study the effect of adding LRG&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">We evaluated the risk of cardiovascular disease using Regicor Calculator&#44; which is adapted to the Spanish population&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0100" class="elsevierStylePara elsevierViewall">A linear mixed-effects model<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> was used to study the overall reduction in weight and HbA1c during treatment&#46; The model enables us to study the effect of time and duration of diabetes flexibly using a quadratic function to determine whether the responses are linear or not over time&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The linear mixed effects model is constructed with a bivariate structure to investigate the time-dependent relationship between weight and HbA1c values&#46; We used the bivariate longitudinal analysis introduced by Thi&#233;baut et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> which enables testing of the difference between the longitudinal outcomes and joint testing of a treatment effect on a set of outcomes&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The statistical analysis was performed using R&#44; Version 2&#46;12&#46;0 &#40;R Development Core Team&#44; Vienna&#44; Austria&#41; and SAS&#44; Version 9&#46;2 &#40;SAS Institute Inc&#46;&#44; Cary&#44; North Carolina&#44; USA&#41;&#46; Statistical significance was set at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Baseline sample</span><p id="par0115" class="elsevierStylePara elsevierViewall">The study population comprised 209 patients&#46; Twenty-two were withdrawn&#46; Metabolic response was evaluated in the remaining 187 cases&#46; Of these&#44; 171 patients completed 12 months on treatment &#40;Group A&#41;&#44; 85 completed 24 months &#40;Group B&#41;&#44; and 20 completed 36 months &#40;Group C&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The reasons for withdrawal were LRG-related adverse events &#40;13 cases&#41;&#44; death &#40;5 cases&#41;&#44; acute complications &#40;2 cases&#41;&#44; and lost cases &#40;2 cases&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">LRG was discontinued in 34 cases &#40;18&#37;&#41; owing to lack of efficacy&#44; which the physician considered as inadequate glycemic and&#47;or weight response according to his individualized objectives&#46; Most of them discontinued treatment between 3 and 6 months from the start&#46; These patients were considered for the effectiveness evaluation&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">We evaluated the descriptive baseline characteristics of the basal 187 patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Metabolic response</span><p id="par0135" class="elsevierStylePara elsevierViewall">Overall&#44; the mean reduction in weight was 8&#46;6<span class="elsevierStyleHsp" style=""></span>kg at 12 months&#44; 8&#46;5<span class="elsevierStyleHsp" style=""></span>kg at 24 months&#44; and 9<span class="elsevierStyleHsp" style=""></span>kg at 36 months&#46; The mean reduction in HbA1c was 1&#46;7&#37; at 12 months&#44; 24 months&#44; and 36 months&#46; A significant reduction in HbA1c &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41; and weight &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41; was observed as early as week 12&#44; and this was maintained at 12 and 24 months&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the progress of metabolic variables for patients who had received treatment for 12 months&#44; 24 months&#44; and 36 months&#46; We found a marked and stable improvement over time in most of the metabolic parameters analyzed&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">HbA1c &#60;7&#37; was achieved by 42&#37; of patients at 12 months and by 40&#37; at 24 months&#46; The results at 12&#8211;24 months for each of the CEP defined &#40;see Material and Methods&#44; Study variables&#41; were as follows&#58; CEP I&#44; 34&#37;&#8211;36&#37;&#59; CEP II&#44; 39&#37;&#8211;44&#37;&#59; CEP III&#44; 49&#37;&#8211;48&#37;&#59; CEP IV&#44; 59&#37;&#8211;57&#37;&#59; and CEP V&#44; 74&#37;&#8211;79&#37;&#46; There were no differences between sexes&#46; The results for HbA1c compared with changes in body weight from baseline to 12 and 24 months are shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> &#40;scatterplot&#41;&#46; Most patients achieved a reduction in both parameters&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Correlation between metabolic response and study variables</span><p id="par0150" class="elsevierStylePara elsevierViewall">We evaluated HbA1c over time &#40;at 12&#47;24 months&#41; according to age&#44; diabetes duration&#44; baseline antidiabetic medication and sex&#46; With respect to age&#44; the variation was as follows&#58; &#60;50 years&#44; &#8722;2&#46;3&#37;&#47;&#8722;1&#46;68&#37;&#59; 51&#8211;65 years&#44; &#8722;1&#46;3&#37;&#47;&#8722;1&#46;2&#37;&#59; &#62;65 years&#44; &#8722;1&#46;3&#37;&#47;&#8722;1&#46;5&#37;&#46; According to duration of diabetes&#58; &#60;5 years&#44; &#8722;1&#46;7&#37;&#47;&#8722;1&#46;5&#37;&#59; 5&#8211;10 years&#44; &#8722;1&#46;5&#37;&#47;&#8722;1&#46;2&#37;&#59; &#62;10 years&#44; &#8722;1&#46;2&#37;&#47;&#8722;1&#46;1&#37; and baseline antidiabetic medication&#58; metformin&#44; &#8722;1&#46;7&#37;&#47;&#8722;1&#46;5&#37;&#59; oral agents&#44; &#8722;1&#46;6&#37;&#47;&#8722;1&#46;2&#37;&#59; insulin&#44; &#8722;1&#46;4&#37;&#47;&#8722;1&#46;5&#37;&#46; According to sex&#58; female&#44; &#8722;1&#46;5&#37;&#47;&#8722;1&#46;4&#37;&#59; male &#8722;1&#46;56&#37;&#47;&#8722;1&#46;3&#37;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The decrease in HbA1c was significant in all the subgroups&#44; although there were no significant differences between the subgroups&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Statistical correlation studies results are shown at <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; The results of the bivariate linear mixed effects model &#40;weight and HbA1c&#41; are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3A</a>&#46; No correlations were found between reduction in weight and HbA1c with respect to age or sex&#46; According to the baseline BMI value&#44; the reduction in HbA1c was inversely correlated with BMI&#44; although weight reduction was not&#46; Therefore&#44; LRG reduced BMI equally well at all baseline BMI values&#46; However&#44; the decrease in HbA1c was lower with a higher baseline BMI&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">The HbA1c reduction was inversely correlated with duration of diabetes&#44; although weight reduction was not&#46; The relationship was linear&#44; that is&#44; the lower the duration of diabetes&#44; the greater the reduction in HbA1c&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The correlation of the random intercept and slopes for the reduction in weight and HbA1c was obtained based on a longitudinal multivariate model &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 3B</a>&#41;&#46; The intercept represents the correlation between the baseline measurements&#59; the slope represents the time-dependent correlation between weight and HbA1c&#46; The model therefore indicated that the greater the initial BMI&#44; the lower the decrease in the HbA1c slope&#44; and the higher the initial HbA1c&#44; the greater the decrease in the slope of HbA1c&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">The duration of therapy with LRG was directly correlated with the decrease in weight and HbA1c as a result of the initial and early response that was maintained over time&#46; In this case&#44; the relationship was quadratic&#44; not linear &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and B&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Effect of adding LRG to previous insulin treatment</span><p id="par0180" class="elsevierStylePara elsevierViewall">Of the 68 patients &#40;36&#37;&#41; receiving insulin at baseline &#40;0&#46;55<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4<span class="elsevierStyleHsp" style=""></span>IU&#47;kg&#41;&#44; 59 patients were evaluated at 12 months and 23 &#40;39&#37;&#41; had stopped insulin&#46; Of the 30 patients evaluated at 24 months&#44; 8 &#40;26&#37;&#41; had stopped insulin&#46; The patients who continued to take insulin reduced their dose to 0&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2<span class="elsevierStyleHsp" style=""></span>IU&#47;kg at 12 months and to 0&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2<span class="elsevierStyleHsp" style=""></span>IU&#47;kg at 24 months&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">In patients receiving insulin&#44; baseline HbA1c fell from 9&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8 to 9&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7&#37; at 12 months &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>36&#41; and to 8&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3&#37; at 24 months&#46; In the subgroup of patients who stopped insulin&#44; baseline HbA1c fell to 7&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#41; at 12 months and to 7&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41; at 24 months&#46; A significant reduction in weight was observed&#58; from 98&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;6<span class="elsevierStyleHsp" style=""></span>kg to 89&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;5<span class="elsevierStyleHsp" style=""></span>kg at 12 months and 88&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;9<span class="elsevierStyleHsp" style=""></span>kg at 24 months&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Evaluation of &#37;EBMIL with LRG treatment</span><p id="par0190" class="elsevierStylePara elsevierViewall">EBMIL is the criterion used to evaluate metabolic surgery&#44; which was considered successful &#40;EBMIL &#62;50&#37;&#41; in 15 patients &#40;9&#37;&#41; at 12 months and in 7 patients &#40;8&#37;&#41; at 24 months&#46; EBMIL was &#62;10&#37; in 125 patients &#40;73&#37;&#41; at 12 months and in 65 patients &#40;77&#37;&#41; at 24 months&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Adverse events</span><p id="par0195" class="elsevierStylePara elsevierViewall">No serious adverse events were observed&#46; Thirteen patients stopped treatment because of digestive intolerance &#40;nausea and vomiting 7 cases&#44; diarrhea 4 cases&#44; and increased amylase 2 cases&#41;&#46; No patients had pancreatitis or pancreatic cancer&#46; Five patients died &#40;cancer of the liver&#44; lung&#44; colon&#44; bladder&#44; and genitals&#41;&#46; Acute complications &#40;major intercurrent process or adverse event not related to LRG&#41; were observed in 2 cases &#40;ACVA and appendicitis&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Cardiovascular risk during treatment with LRG</span><p id="par0200" class="elsevierStylePara elsevierViewall">Cardiovascular risk evolution was evaluated using REGICOR&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> Patients on LRG treatment for 12 months&#58; at baseline at very high risk was 14 &#40;10&#37;&#41; it decreased to 5 &#40;3&#37;&#41; at 12<span class="elsevierStyleHsp" style=""></span>months&#59; 38 &#40;26&#37;&#41; patients at high risk decreased to 17 &#40;12&#37;&#41; at 12<span class="elsevierStyleHsp" style=""></span>months&#59; 58 &#40;40&#37;&#41; patients at moderate risk increased to 71 &#40;49&#37;&#41; and 34 &#40;24&#37;&#41; patients at low risk increased to 51 &#40;35&#37;&#41; at 12<span class="elsevierStyleHsp" style=""></span>months&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Patients on LRG treatment for 24<span class="elsevierStyleHsp" style=""></span>months&#58; at baseline at very high risk was 7 &#40;8&#37;&#41; it decreased to 3 &#40;4&#37;&#41; at 24<span class="elsevierStyleHsp" style=""></span>months&#59; 24 &#40;30&#37;&#41; patients at high risk decreased to 15 &#40;19&#37;&#41; at 24<span class="elsevierStyleHsp" style=""></span>months&#59; 30 &#40;38&#37;&#41; patients at moderate risk increased to 33 &#40;41&#37;&#41; and 19 &#40;24&#37;&#41; patients at low risk increased to 29 &#40;36&#37;&#41; at 24<span class="elsevierStyleHsp" style=""></span>months&#46; Treatment with LRG for 12&#8211;24 months&#44; combined with other treatments used in real-world practice&#44; reduced cardiovascular risk from high to moderate-low&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discussion</span><p id="par0210" class="elsevierStylePara elsevierViewall">We performed a retrospective observational cohort study to evaluate the metabolic effectiveness and safety of LRG in patients with T2DM in real-world clinical practice over a longer period than that usually assessed in clinical trials&#46; We found that therapy with LRG reduced weight at 12&#44; 24&#44; and 36 months&#46; Hb1Ac also decreased to target in almost half of the study population at 12 and 24 months&#46; Most patients achieved the composite endpoint&#46; Adding LRG to basal insulin treatment enabled nearly one-third of patients to stop insulin&#59; the remainder were able to reduce their dose by one-third and weight reduction was significant&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In a recent review of 124 publications&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> HbA1c was significantly reduced after 6 months of treatment with LRG &#40;mean change from baseline 0&#46;9&#37;&#8211;2&#46;2&#37;&#59; HbA1c &#60;7&#46;0&#37;&#44; 29&#46;5&#8211;65&#46;0&#37;&#41;&#46; The NICE composite endpoint &#40;HbA1c reduction &#8805;1&#37; and weight loss &#8805;3&#37;&#41; was met in 16&#46;9&#8211;47&#46;0&#37; of cases&#44; and the absolute weight change was &#8722;1&#46;3 to &#8722;8&#46;65<span class="elsevierStyleHsp" style=""></span>kg&#46; Our results were consistent with the best of these&#44; even though the time on treatment with LRG was longer than most of them&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">When our results were compared with those of EVIDENCE&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> the most longer &#40;24<span class="elsevierStyleHsp" style=""></span>months&#41; and big population sample &#40;<span class="elsevierStyleItalic">n</span> 2019&#41; in this review&#44; the greater mean HbA1c and weight reduction in our series can be explained by the shorter duration of diabetes and higher initial weight&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">This review includes three Spanish studies&#59; Gomez Peralta et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> reported a 4&#46;4<span class="elsevierStyleHsp" style=""></span>kg reduction at 3<span class="elsevierStyleHsp" style=""></span>months &#40;<span class="elsevierStyleItalic">n</span> 158&#41;&#59; Diaz-Soto G et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> a 0&#46;9&#37; HbA1c reduction at 4<span class="elsevierStyleHsp" style=""></span>months &#40;<span class="elsevierStyleItalic">n</span> 59&#41; and Mezquita-Raya et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> a 1&#46;1&#37; HbA1c and 4&#46;6<span class="elsevierStyleHsp" style=""></span>kg reduction at 6 months of LRG treatment&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Later Lecube et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> reported a HbA1c decrease near 1&#46;2&#37; and weight loss 7&#46;3<span class="elsevierStyleHsp" style=""></span>kg during 6 months treatment&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">A recent multicentric publication in Spain<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> &#40;24<span class="elsevierStyleHsp" style=""></span>months treatment&#41; reports a HbA1c reduction ranging from 1&#46;0&#37; to 1&#46;5&#37; and body weight from 5<span class="elsevierStyleHsp" style=""></span>kg to 10<span class="elsevierStyleHsp" style=""></span>kg&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">We found that the metabolic response was early &#40;3&#8211;6 months&#41; and maintained over time&#46; This finding could be explained by the appropriate selection of responders in our real-world setting&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Evaluation of the reduction in HbA1c using the random intercept and slope model revealed a correlation with the baseline value &#40;the higher the baseline value&#44; the greater the reduction&#41;&#46; In contrast&#44; the reduction and intercept for the HbA1c slope were lower at higher BMI levels&#44; probably because LRG was indicated for patients with relatively low baseline HbA1c and very high baseline BMI&#44; with correction of high BMI being the main objective of therapy with LRG in this subgroup&#46; Given the findings for baseline BMI and the subsequent reduction therefore&#44; treatment with LRG reduced BMI equally well across all baseline BMI values&#46; Consequently&#44; the effect of LRG on weight could be independent of the effect on HbA1c&#46; This result supports the indication of LRG for weight reduction&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">The reduction in HbA1c was inversely correlated with duration of diabetes&#46; The relationship was linear&#44; that is&#44; the lower the duration of diabetes&#44; the greater the reduction in HbA1c&#46; In contrast&#44; no correlation was observed for the reduction in weight&#59; the effect of therapy on weight was independent of duration of diabetes&#46; These findings also support an independent effect of LRG on glycemia and on weight&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Treatment of diabetes and obesity should be intensified once the diagnosis has been confirmed&#44; and every opportunity should be taken to create a legacy effect&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">23&#8211;25</span></a> The efficacy and maintained effect of LRG over time make it a promising option when attempting to create a legacy effect in obese patients with diabetes&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">The decrease in weight and HbA1c was more pronounced as the time on LRG increased&#46; However&#44; this finding can be explained by the initial and early response&#44; which was maintained over time&#46; The statistical analysis showed that the initial glycemia and weight responses were based on a quadratic model and not on a linear model&#44; thus confirming these early responses as major predictive markers of response to LRG&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Given that the effects of therapy with LRG were clear after 12 weeks&#44; a 3-month trial period may be sufficient to demonstrate the potential of the drug to reduce both weight and HbA1c&#46; Treatment could be discontinued in patients who do not respond within this period&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Addition of LRG to insulin has proven to be effective in reversing weight gain&#44; decreasing the insulin dose&#44; and improving glycemic control in obese patients&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> The results of the subgroup of patients who were taking insulin at baseline are particularly interesting&#46; Some were able to stop or reduce insulin dose&#44; and both weight and Hb1Ac improved considerably&#46; Consequently&#44; in obese patients with T2DM&#44; treatment with GLP1-RA should be considered before starting with insulin<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;5&#44;6</span></a> or uptitrating its dose&#46; We may be able to &#8220;rescue&#8221; patients who received intensive therapy with insulin before LRG was marketed&#46; Our results of combined LRG and insulin therapy may help to understand the results of previous studies&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Evaluation of the EBMIL enabled us to compare our results with those obtained with bariatric surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">27&#44;28</span></a> Our results suggest that LRG treatment in T2DM obese patients could facilitate or even eliminate the need for surgery in patients who could reach the target &#37;EBMIL with LRG alone&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Most adverse effects involved the gastrointestinal tract and were mild&#46; These were less frequent than in clinical trials&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> The favorable safety profile of LRG could facilitate adherence to dietary modifications and ensure continued health benefits over time&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Recent trials evaluating LRG&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> empagliflozin&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> semaglutide&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> canagliflozin<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> showed improved cardiovascular outcomes in patients with T2DM&#46; The mechanism underlying these results and the question of whether outcome was a class effect or not remain open to debate&#46; Our results for cardiovascular risk are consistent with those of the LEADER trial&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> In our study&#44; we cannot attribute the improvement in cardiovascular risk exclusively to LRG&#46; The treatment schedule was multifactorial&#44; as recommended in guidelines&#46; The addition of LRG could enable high-risk patients to be reclassified as moderate-low risk&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">This study has limitations mainly related to its observational retrospective design&#46; The criterion to define lack of efficacy and discontinue LRG treatment was not predefined&#44; it was individualized decided by the physician&#46; We must consider the influence of confounding factors&#46; The combined antidiabetic therapy prescribed did not include SGLT2i&#46; Future results of metabolic effectiveness studies in real-world clinical practice including combined SGLT2i and GLP1-RA may be compared with our results just using GLP-RA&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Real-world data have the potential to improve the quality and delivery of medical care&#44; reduce overall costs&#44; and improve outcomes by accelerating our understanding of how best to incorporate new therapies into everyday clinical practice&#46; Such data help to fill the knowledge gap between clinical trials and actual clinical practice&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conclusions</span><p id="par0300" class="elsevierStylePara elsevierViewall">In conclusion&#44; we found that therapy with LRG under conditions of routine clinical practice produced a better metabolic response &#40;weight loss and reduction in Hb1Ac&#41; than that observed in clinical trials&#46; The early effect observed in responders at 3 months was maintained at 12 and 24 months and was the best predictor of response to LRG&#46; The weight response was independent of baseline BMI&#44; baseline HbA1c&#44; and duration of diabetes&#46; The HbA1c response was greater when baseline HbA1c was higher and duration of diabetes was shorter&#46; LRG could delay or reduce the insulin dose in a significant subgroup of obese patients by improving weight simultaneously with glycemic control&#46; We also observed an improvement in cardiovascular risk factors enabling patients to be transferred from the high-risk category to medium-low risk&#46; Consequently&#44; LRG would be a suitable candidate for inclusion in multifactorial interventions aimed at reducing the risk of cardiovascular events&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Founding sources</span><p id="par0305" class="elsevierStylePara elsevierViewall">Medical writing&#44; editorial assistance &#40;Cociente&#44; S&#46;L&#46;&#41;&#44; and the statistical analysis were funded by a grant from <span class="elsevierStyleGrantSponsor" id="gs1">Novo Nordisk</span>&#46; The authors take full responsibility for the content and conclusions stated in this manuscript&#46; Novo Nordisk neither influenced the content of this publication nor was involved in the study design or in the collection&#44; analysis&#44; or interpretation of the data reported&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflict of interests</span><p id="par0310" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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              "titulo" => "Patients"
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              "titulo" => "Study variables"
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          "titulo" => "Results"
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              "titulo" => "Baseline sample"
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              "titulo" => "Metabolic response"
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              "titulo" => "Correlation between metabolic response and study variables"
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              "identificador" => "sec0055"
              "titulo" => "Effect of adding LRG to previous insulin treatment"
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              "identificador" => "sec0060"
              "titulo" => "Evaluation of &#37;EBMIL with LRG treatment"
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              "identificador" => "sec0065"
              "titulo" => "Adverse events"
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              "identificador" => "sec0070"
              "titulo" => "Cardiovascular risk during treatment with LRG"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2018-06-28"
    "fechaAceptado" => "2018-09-07"
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        0 => array:4 [
          "clase" => "keyword"
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          "identificador" => "xpalclavsec1140151"
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            0 => "Type 2 diabetes mellitus"
            1 => "Liraglutide"
            2 => "Efficacy"
            3 => "Real-world studies"
            4 => "Cardiovascular risk"
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        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abreviaturas"
          "identificador" => "xpalclavsec1140152"
          "palabras" => array:4 [
            0 => "T2DM"
            1 => "LRG"
            2 => "GLP1-RA"
            3 => "&#37; EBMIL"
          ]
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        2 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1140153"
          "palabras" => array:4 [
            0 => "T2DM"
            1 => "LRG"
            2 => "GLP1-RA"
            3 => "&#37; EBMIL"
          ]
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          "palabras" => array:5 [
            0 => "Diabetes mellitus tipo 2"
            1 => "Liraglutida"
            2 => "Eficacia"
            3 => "Estudios en vida real"
            4 => "Riesgo cardiovascular"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The worldwide prevalence of type 2 diabetes mellitus increases in parallel to that of obesity&#46; Liraglutide &#40;LRG&#41;&#44; a glucagon-like peptide-1 receptor agonist&#44; can reduce body weight&#46; This study assessed the metabolic efficacy of LRG in real-world clinical practice&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">An observational&#44; retrospective cohort study including patients treated with LRG for at least one year &#40;187 patients&#41;&#46; Anthropometric and metabolic variables&#44; a composite endpoint&#44; factors predicting response to LRG&#44; and cardiovascular risk over time were assessed&#46; A linear mixed-effects model with a bivariate structure was constructed to investigate the time-dependent relationship between weight and HbA1c values&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">HbA1c levels and weight significantly decreased in the first 12 weeks&#44; and the decrease persisted at 12 and 24 months in all subgroups studied&#46; Mean weight and HbA1c decreases after 24 months were 8&#46;5<span class="elsevierStyleHsp" style=""></span>kg and 1&#46;7&#37; respectively&#46; HbA1c values &#60;7&#37; were achieved by 42&#37; of patients at 12 months and by 40&#37; at 24 months&#46; Treatment with LRG allowed for reduction in insulin dose&#46; No serious adverse events were noted&#46; Cardiovascular risk decreased from high to moderate-low&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Under standard clinical practice conditions&#44; LRG achieved a better metabolic response than seen in clinical trials&#46; Efficacy at 12 weeks of treatment is a good predictor of response&#46; LRG allows for delaying or reducing insulin dose by improving both weight and glucose control&#46; Cardiovascular risk improved&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and objectives"
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          1 => array:2 [
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            "titulo" => "Methods"
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          2 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La prevalencia mundial de diabetes mellitus tipo 2 aumenta junto a la de la obesidad&#46; Liraglutida &#40;LRG&#41;&#44; un agonista del receptor del p&#233;ptido similar al GLP1&#44; es un f&#225;rmaco antidiab&#233;tico capaz de reducir peso&#46; Evaluamos en pr&#225;ctica cl&#237;nica de vida real su eficacia metab&#243;lica&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohorte observacional retrospectivo&#46; Se incluyeron los pacientes tratados al menos durante un a&#241;o con LRG &#40;187 pacientes&#41;&#46; Evaluamos variables antropom&#233;tricas&#44; metab&#243;licas&#44; objetivos combinados&#44; factores predictivos de respuesta y evoluci&#243;n del riesgo cardiovascular&#46; Se construy&#243; un modelo de efectos mixtos lineales de estructura bivariante para investigar la relaci&#243;n tiempo-dependiente entre el peso y los valores de HbA1c&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Descenso significativo de los valores de HbA1c y peso en las primeras 12 semanas de tratamiento&#44; mantenido a los 12 y 24 meses&#44; en todos los subgrupos estudiados&#46; Reducci&#243;n media de peso y HbA1c tras 24 meses de tratamiento de 8&#44;5 kg y 1&#44;7&#37;&#46; El valor de HbA1c fue &#60;7&#37; en 42&#37; de pacientes a los 12 meses&#44; 40&#37; a los 24 meses&#46; El tratamiento con LRG permiti&#243; reducir la dosis de insulina&#46; No registramos eventos adversos graves&#46; El riesgo cardiovascular mejor&#243;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Bajo condiciones de pr&#225;ctica cl&#237;nica habitual la respuesta metab&#243;lica a LRG result&#243; mejor que la observada en ensayos cl&#237;nicos&#46; La eficacia a las 12 semanas de tratamiento es un buen predictor de respuesta&#46; LRG permite retrasar o reducir la insulinoterapia&#46; Los pacientes mejoraron su riesgo cardiovascular&#46;</p></span>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Effect of LRG treatment on HbA1c &#40;A&#41; and body weight &#40;B&#41; over time &#40;mean&#41; for patients in treatment for 12 months &#40;<span class="elsevierStyleItalic">n</span> 171&#41; and 24 months &#40;<span class="elsevierStyleItalic">n</span> 85&#41;&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39 &#40;21&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>51&#8211;65 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 &#40;53&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;65 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48 &#40;26&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83 &#40;44&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>5&#8211;10 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;10 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Metformin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Combined OAD<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">208&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>72&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">8&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">39&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">103&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">121&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">102&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">95&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;4 &#40;&#8722;7&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group B&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">102&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">94&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;4 &#40;&#8722;7&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18 &#40;&#8722;7&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">108&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17 &#40;&#8722;10&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;8 &#40;&#8722;9&#46;4&#177;8&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;3 &#40;&#8722;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">HbA1c&#44; &#37;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8 &#40;&#8722;1&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8 &#40;&#8722;1&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7 &#40;&#8722;1&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4 &#40;&#8722;2&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 &#40;&#8722;1&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4 &#40;&#8722;1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">BMI&#44; kg</span>&#47;<span class="elsevierStyleItalic">m</span><span class="elsevierStyleSup">2</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#46;2<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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;6 &#40;&#8722;2&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;2 &#40;&#8722;3&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;6 &#40;&#8722;2&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;4<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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5 &#40;&#8722;3&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;2 &#40;&#8722;3&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;7 &#40;&#8722;3&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">SBP&#44; mmHg</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">140&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;8 &#40;&#8722;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">139&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;1 &#40;&#8722;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">138&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;7 &#40;&#8722;16&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">160<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">140&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;7 &#40;&#8722;19&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">144&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;4 &#40;&#8722;15&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">135&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12 &#40;&#8722;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">DBP&#44; mmHg</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;9 &#40;&#8722;5&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;9 &#40;&#8722;8&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;7 &#40;&#8722;7&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;4 &#40;&#8722;12&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;3 &#40;&#8722;11&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;7 &#40;&#8722;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Basal glucose&#44;mg&#47;dL</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">214&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>72&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">157&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>60&#46;1 &#40;&#8722;56&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">224&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>69&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>56&#46;5 &#40;&#8722;69&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">164&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>62&#46;2 &#40;&#8722;60&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">235<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>69&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">146&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>54&#46;4 &#40;&#8722;89&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>43&#46;8 &#40;&#8722;84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">176&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>70&#46;4 &#40;&#8722;59&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Cholesterol&#44; mg&#47;dL</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">200&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">184&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>43&#46;3 &#40;&#8722;15&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">202&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">187&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>49&#46;6 &#40;&#8722;15&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">183&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#46;9 &#40;&#8722;19&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">224&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">192&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>41&#46;7 &#40;&#8722;32&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">177&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#46;9 &#40;&#8722;46&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">196&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>47 &#40;&#8722;28&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">HDL-C&#44; mg&#47;dL</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;9 &#40;&#43;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group B&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;4 &#40;&#43;2&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;2 &#40;&#8722;0&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;5 &#40;&#43;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;4 &#40;&#43;1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;3 &#40;&#43;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">LDL-C&#44; mg&#47;dL</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">108&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>38&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>40&#46;3 &#40;&#8722;8&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group B&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">107&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>37&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>45&#46;7 &#40;&#8722;4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#46;8 &#40;&#8722;7&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">134&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>44&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">106&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#46;9 &#40;&#8722;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;2 &#40;&#8722;36&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;5 &#40;&#8722;87&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">229&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>144&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">180&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>89&#46;4 &#40;&#8722;49&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">245&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>136&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">186&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>97&#46;1 &#40;&#8722;59&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Group C&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">252&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>121&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">173&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>64&#46;6 &#40;&#8722;79&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">182&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;7 &#40;&#8722;69&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">187&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>86&#46;6 &#40;&#8722;65&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Evolution of metabolic variables according to the group studied&#58; Group A &#40;<span class="elsevierStyleItalic">n</span> 171&#41; patients treated for 12 months&#44; Group B &#40;<span class="elsevierStyleItalic">n</span> 85&#41; patients treated for 24 months and Group C &#40;<span class="elsevierStyleItalic">n</span> 20&#41; patients treated for 36 months&#46;</p>"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#46; Treatment time<span class="elsevierStyleSup">2</span> and duration of diabetes<span class="elsevierStyleSup">2</span> are a quadratic effect of treatment time and duration of diabetes&#44; respectively&#46; These variables capture the non-linear effect of the corresponding outcomes&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Coeff &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Coeff &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Intercept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">5&#46;31 &#40;2&#46;71&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;05&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Male sex&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Treatment time&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Treatment time<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Duration of diabetes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Slope weight&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Intercept and slopes for reduction in weight and HbA1c&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Maps of trends in diagnosed diabetes and obesity&#44; April 2017&#59; CDC&#39;s Division of Diabetes Translation&#46; United States Diabetes Surveillance System&#46; <a target="_blank" href="https://www.cdc.gov/diabetes/statistics/slides/maps_diabetesobesity94.pdf">https&#58;&#47;&#47;www&#46;cdc&#46;gov&#47;diabetes&#47;statistics&#47;slides&#47;maps&#95;diabetesobesity94&#46;pdf</a> &#40;accessed 20&#46;06&#46;18&#41;&#46;"
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            ]
            1 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Worldwide trends in body-mass index&#44; underweight&#44; overweight&#44; and obesity from 1975 to 2016&#58; a pooled analysis of 2416 population-based measurement studies in 128&#46;9 million children&#44; adolescents&#44; and adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Abarca-G&#243;mez"
                            1 => "Z&#46;A&#46; Abdeen"
                            2 => "Z&#46;A&#46; Hamid"
                            3 => "N&#46;M&#46; Abu-Rmeileh"
                            4 => "B&#46; Acosta-Cazares"
                            5 => "C&#46; Acuin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(17)32129-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2017"
                        "volumen" => "390"
                        "paginaInicial" => "2627"
                        "paginaFinal" => "2642"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29029897"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
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              "identificador" => "bib0165"
              "etiqueta" => "3"
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Article information

ISSN: 25300180
Original language: English

DOI:10.1016/j.endien.2019.06.001

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Year/Month	Html	Pdf	Total

2024 November	1	0	1
2024 October	21	1	22
2024 September	19	2	21
2024 August	21	4	25
2024 July	18	4	22
2024 June	20	2	22
2024 May	29	6	35
2024 April	16	4	20
2024 March	23	3	26
2024 February	7	3	10
2024 January	19	0	19
2023 December	18	2	20
2023 November	22	2	24
2023 October	27	3	30
2023 September	11	0	11
2023 August	14	2	16
2023 July	14	1	15
2023 June	30	1	31
2023 May	70	1	71
2023 April	69	0	69
2023 March	40	1	41
2023 February	15	1	16
2023 January	17	3	20
2022 December	14	3	17
2022 November	13	3	16
2022 October	12	7	19
2022 September	11	6	17
2022 August	14	9	23
2022 July	10	8	18
2022 June	16	7	23
2022 May	6	4	10
2022 April	13	10	23
2022 March	20	5	25
2022 February	17	5	22
2022 January	22	6	28
2021 December	21	7	28
2021 November	13	9	22
2021 October	34	8	42
2021 September	41	13	54
2021 August	59	8	67
2021 July	40	6	46
2021 June	33	8	41
2021 May	24	9	33
2021 April	31	14	45
2021 March	19	12	31
2021 February	33	5	38
2021 January	25	10	35
2020 December	28	6	34
2020 November	28	7	35
2020 October	18	8	26
2020 September	17	7	24
2020 August	20	10	30
2020 July	20	8	28
2020 June	16	7	23
2020 May	16	5	21
2020 April	6	2	8
2020 March	16	3	19
2020 February	17	1	18
2020 January	13	3	16
2019 December	14	18	32
2019 November	1	0	1

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