Original Article
Glycaemic variability and oxidative stress in children, with type 1 diabetes attending a summer camp
Variabilidad glucémica y estrés oxidativo en niños con diabetes tipo 1 asistentes a un campamento
N. Colomoa,b,
, M.J. Tapiaa, M.R. Vallejoa, F. García-Torresa, E. Rubio-Martína,b, F.F. Caballeroc, J.M. Jiménezd, M.J. Pelaeze, A.M. Gómeze, I. Sáncheze, J.P. López-Siguerod, F. Soriguera,b, M.S. Ruiz de Adanaa,b
Corresponding author
a UGC de Endocrinología y Nutrición, Hospital Universitario Carlos Haya, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain
b CIBER de diabetes y enfermedades metabólicas asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
c Servicio de Psiquiatría, Universidad Autónoma de Madrid, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
d UGC de Pediatría, Hospital Universitario Carlos Haya, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain
e Asociación de Diabéticos de Málaga (ADIMA), Málaga, Spain
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"apellidos" => "Soriguer" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 12 => array:3 [ "nombre" => "M.S." "apellidos" => "Ruiz de Adana" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "UGC de Endocrinología y Nutrición, Hospital Universitario Carlos Haya, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "CIBER de diabetes y enfermedades metabólicas asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Psiquiatría, Universidad Autónoma de Madrid, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "UGC de Pediatría, Hospital Universitario Carlos Haya, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Asociación de Diabéticos de Málaga (ADIMA), Málaga, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Variabilidad glucémica y estrés oxidativo en niños con diabetes tipo 1 asistentes a un campamento" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Since the publication of the Diabetes Control and Complications Trial, HbA1c has been considered the main parameter for assessment of metabolic control in both children and adults with type 1 diabetes (T1DM).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However, recent studies with continuous glucose monitoring (CGM) systems have revealed wide fluctuations in glucose values in children with T1DM, even in those with excellent HbA1c levels.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Interest in studying the impact of these glucose fluctuations has therefore increased.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a> The concept of glycaemic variability encompasses both diurnal variability (fluctuations in glucose within a single day) and day-to-day variability (fluctuations in glucose between one day and the next). Diurnal variability can be estimated using the standard deviation (SD) around the mean of glucose values for one day, and through the mean amplitude of glycaemic excursions (MAGE).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The mean of daily differences (MODD)<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> is a day-to-day variability marker. Other parameters for evaluating the risk of reaching extreme glycaemic values are the low blood glucose index (LBGI), which is a measure of the risk of hypoglycaemia,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and the high blood glucose index (HBGI), which is a measure of the risk of hyperglycaemia.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Glycaemic variability has recently been associated with an increase in the production of free radicals and oxidative stress.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Isoprostanes are considered good markers of oxidative stress, as they are stable products derived from the process of oxidation of arachidonic acid by oxygen free radicals and have been shown to increase with oxidative damage.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> Isoprostanes can be estimated by measuring the 24-h urinary excretion rate of 8-iso-prostaglandin F2 alpha (8-iso-PGF2α).</p><p id="par0015" class="elsevierStylePara elsevierViewall">The objectives of this study are to assess glycaemic variability and oxidative stress by the urinary excretion rate of 8-iso-PGF2α in a group of children and adolescents with T1DM attending a summer camp, and to analyse the relationship between both.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients and study design</span><p id="par0020" class="elsevierStylePara elsevierViewall">We did a cross-sectional study that included 54 children and adolescents with T1DM aged between 7 and 16, attending a 7-day summer camp in Málaga in July 2009. The summer camp was organised by a local diabetes association.</p><p id="par0025" class="elsevierStylePara elsevierViewall">All the children gave verbal consent to participate in the study and their parents signed an informed consent.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Measurements</span><p id="par0030" class="elsevierStylePara elsevierViewall">We collected sociodemographic and clinical data, including information on the duration of diabetes, the diabetes treatment and the presence of chronic diabetes-related complications. Diabetic retinopathy was considered to be present if there was a history of having received laser coagulation; diabetic nephropathy was considered to be present in patients with positive albuminuria requiring treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, and diabetic neuropathy was considered to be present if the sensitivity of the hands and/or feet was altered or reduced.</p><p id="par0035" class="elsevierStylePara elsevierViewall">During the camp, 7 blood glucose measurements were taken per day (one measurement before each meal [breakfast, lunch and dinner], one measurement 2<span class="elsevierStyleHsp" style=""></span>h after each meal [breakfast, lunch and dinner] and one measurement at 3:00<span class="elsevierStyleHsp" style=""></span>a.m.) from all participants, using the Roche Diagnostics Accu-Chek Aviva Nano<span class="elsevierStyleSup">®</span> glucose metre. The glycaemia data stored in the glucose metres were transferred to a computer using the Roche Diagnostics Accu-Chek Smart Pix<span class="elsevierStyleSup">®</span> device. For each participant, the Roche Diagnostics Accu-Chek Smart Pix<span class="elsevierStyleSup">®</span> Data Management System software automatically calculated the percentage of blood glucose values in hypoglycaemia (glycaemia <70<span class="elsevierStyleHsp" style=""></span>mg/dl [3.9<span class="elsevierStyleHsp" style=""></span>mmol/l]), normoglycaemia (glycaemia 70–180<span class="elsevierStyleHsp" style=""></span>mg/dl [3.9–10.0<span class="elsevierStyleHsp" style=""></span>mmol/l]) and hyperglycaemia (glycaemia ≥180<span class="elsevierStyleHsp" style=""></span>mg/dl [10.0<span class="elsevierStyleHsp" style=""></span>mmol/l]), mean glycaemia, SD, LBGI and HBGI.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We collected data on the daily dose of insulin, the number of episodes of hypoglycaemia (glycaemia <70<span class="elsevierStyleHsp" style=""></span>mg/dl [3.9<span class="elsevierStyleHsp" style=""></span>mmol/l] with or without symptoms of hypoglycaemia<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>), number of episodes of severe hypoglycaemia (hypoglycaemia requiring the assistance of other persons<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>), number of episodes of ketosis (ketonuria measured using Bayer Ketostix<span class="elsevierStyleSup">®</span> urine strips in children being treated with multiple daily insulin injections [MDII] and ketonaemia determined by an Abbott MediSense Optium Xceed Meter<span class="elsevierStyleSup">®</span> in children with continuous subcutaneous insulin infusion [CSII] systems) and number of episodes of ketoacidosis that occurred during the camp.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The weight and height of participants were measured on the first day of the camp using standardised methods. Body mass index (BMI) was calculated as weight (in kilograms) divided by height squared (in metres). <span class="elsevierStyleItalic">Z</span>-scores were calculated for weight and BMI using recently published Spanish growth charts.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">At the start of the camp HbA1c was measured in a capillary blood sample using a DCA 2000 Analyzer<span class="elsevierStyleSup">®</span> (Bayer Corporation, Elkhart, USA).</p><p id="par0055" class="elsevierStylePara elsevierViewall">The 24-h urine sample was taken at home by each participant after the end of the camp. Although all the participants were requested to take a urine sample, only 14 children submitted it. The participants were asked to keep the urine samples refrigerated at 4<span class="elsevierStyleHsp" style=""></span>°C during the collection process and to take them to the hospital within 24<span class="elsevierStyleHsp" style=""></span>h of finishing collecting them. At the hospital the samples were immediately stored at −80<span class="elsevierStyleHsp" style=""></span>°C after adding 0.005% BHT, since storage at −20<span class="elsevierStyleHsp" style=""></span>°C is insufficient to prevent the formation of 8-isoprostanes. Measurement of 8-iso-PGF2α was carried out using an enzyme immunoassay method (Cayman Chemical Company, Ann Arbor, USA). The intraassay and interassay coefficients of variation were 15.2 and 18.5 respectively. The urinary creatinine level was determined using the enzyme spectrophotometric method based on alkaline picrate.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Assessment of glycaemic variability</span><p id="par0060" class="elsevierStylePara elsevierViewall">SD, LBGI and HBGI were calculated automatically for each participant by the Accu-Chek Smart Pix Data Management System<span class="elsevierStyleSup">®</span> program using the blood glucose values recorded during the camp with the Accu-Chek Aviva Nano<span class="elsevierStyleSup">®</span> glucose metre. The formulas for calculating LBGI and HBGI are published.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> The risk categories are LBGI: minimal (LBGI<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>1.1), low (1.1<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>LBGI<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>2–5), moderate (2.5<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>LBGI<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>5.0) and high (LBGI<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>5.0), and HBGI: low (HBGI<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>4.5), moderate (4.5<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>HBGI<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>9.0) and high (HBGI<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>9.0).</p><p id="par0065" class="elsevierStylePara elsevierViewall">MAGE is the mean of the absolute differences between the peak and the nadir of the glucose values over 24<span class="elsevierStyleHsp" style=""></span>h, where peaks are defined as glucose values that precede an increase and are then followed by a decrease that exceeds mean glycaemia by more than 1 SD.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> A MAGE value of over 100<span class="elsevierStyleHsp" style=""></span>mg/dl was regarded as high variability.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The MODD index was estimated as the absolute mean of daily differences in glycaemia using paired blood glucose values on successive days.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD of the MODD was calculated for each patient using the blood glucose values on 5 consecutive days. A MODD value of over 36<span class="elsevierStyleHsp" style=""></span>mg/dl was considered as high day-to-day variability.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">Continuous variables are expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation or median and interquartile range, and categorical variables as percentages. The normal distribution of continuous variables was determined using the Shapiro–Wilk test. The two-group comparisons for continuous variables were determined using Student's <span class="elsevierStyleItalic">t</span>-test, or the Mann–Whitney non-parametric test where necessary. We calculated Spearman correlation coefficients to assess the correlations between study variables. We set a 95% confidence level for the two-tailed hypothesis tests.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the sociodemographic and clinical characteristics of the participants. As regards treatment, 3 of the children had CSII pumps with a rapid-acting insulin analogue, and the remaining children used MDII. Of the latter, 45 received a combination of long-acting insulin analogues (insulin glargine or detemir) and rapid-acting insulin analogues (insulin lispro, aspart or glulisine), and 6 received a combination of neutral protamine Hagedorn (NPH) insulin and rapid-acting insulin analogues (insulin lispro, aspart or glulisine). None of the participants exhibited microvascular complications.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">A significant reduction in insulin requirement was observed during the camp (0.85<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.26<span class="elsevierStyleHsp" style=""></span>IU/kg at the start of the camp vs 0.69<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.24<span class="elsevierStyleHsp" style=""></span>IU/kg at the end, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001). Glycaemic control parameters, markers of glycaemic variability and episodes of acute diabetes-related complications are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. The mean number of episodes of mild hypoglycaemia per subject during the whole camp was 5.1 (range 0–17). One child had an episode of severe hypoglycaemia requiring intramuscular administration of glucagon to resolve it. Five episodes of ketosis were identified; these were treated at the camp and none of the cases developed into ketoacidosis. Of all children, 54% exhibited an HbA1c value ≤7.5% (58<span class="elsevierStyleHsp" style=""></span>mmol/mol). The median SD, MAGE and MODD indexes were in the high range, mean LBGI was within the moderate risk category and mean HBGI was within the low risk category. 74% of the children had a MODD value of over 36<span class="elsevierStyleHsp" style=""></span>mg/dl. LBGI values indicated a high risk of hypoglycaemia in 26% of the participants and a moderate risk in 39%. The median urinary excretion rate of 8-iso-PGF2α measured in 14 children at the end of the camp was 864.39<span class="elsevierStyleHsp" style=""></span>pg/mg creatinine.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">We found no statistically significant differences in markers of glycaemic variability (SD, MAGE, MODD and HBGI), HbA1c, duration of diabetes (4.79<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.28 years vs 4.75<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.18 years; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.98), age (11.86<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.91 years vs 11.25<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.46 years; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.33) and sex (50% male vs 42.5% male, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.63) between the children who submitted the 24-hour urine sample and those who did not (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). LBGI and time in hypoglycaemia were significantly lower in the group of children who did not submit the urine sample (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><p id="par0095" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the positive and statistically significant correlations that were observed between duration of diabetes, HbA1c, mean glycaemia, SD and the HBGI, and MAGE and MODD indices. LBGI correlated positively with MAGE and negatively with mean glycaemia. However, neither age nor urinary excretion rate of 8-iso-PGF2α correlated with markers of glycaemic variability (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">This study shows considerable glycaemic variability in children and adolescents with T1DM attending a summer camp. However, no correlations were found between high glycaemic variability and oxidative stress measured through the urinary excretion rate of 8-iso-PGF2α.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The objectives of the study included, on the one hand, assessment of glycaemic variability in children with T1DM, specifically in the context of summer camp. It is known that children and adolescents with T1DM are very prone to exhibit extreme glycaemic values, mainly due to variations in insulin sensitivity, level of physical activity and food intake.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> Specialised camps for children and adolescents with T1DM offer us an opportunity to study glycaemic excursions outside the hospital setting.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> For example, Choleau et al.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> assessed day-to-day glycaemic variability, estimated using the MODD index, which was calculated from blood glucose readings, in a group of 100 children with T1DM treated with MDII at a summer camp, reporting that the median MODD index was 77<span class="elsevierStyleHsp" style=""></span>mg/dl and that in 99% of the participants the MODD value was over 36<span class="elsevierStyleHsp" style=""></span>mg/dl. Another recent study<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> of 48 children and adolescents with T1DM who underwent an ambulatory 3-day CGM showed high day-to-day glycaemic variability (MODD 63<span class="elsevierStyleHsp" style=""></span>mg/dl in the group of children on MDII and MODD 61<span class="elsevierStyleHsp" style=""></span>mg/dl in the group on CSII), and a high diurnal variability, especially in the group of children treated with MDII (MAGE 117<span class="elsevierStyleHsp" style=""></span>mg/dl in the group of children on MDII and MAGE 88<span class="elsevierStyleHsp" style=""></span>mg/dl in the group on CSII). Our results for glycaemic variability are consistent with data presented previously, and are even higher than those found in studies assessing children in their everyday lives, highlighting the fact that summer camps, even under the supervision of a specialist medical team, constitute an unusual situation.</p><p id="par0110" class="elsevierStylePara elsevierViewall">On the other hand, we wanted to study oxidative stress and its relationship with glycaemic variability. Cerriello and Ihnat demonstrated that glycaemic variability can contribute to accelerated formation of free radicals,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and furthermore Giacco et al.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> showed that oxidative stress can play an essential role in the development of diabetes-related microvascular and macrovascular complications, so this evidence indicates that glycaemic variability could have a greater deleterious effect on the development of complications than sustained hyperglycaemia.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Nevertheless, the debate on the significance of glycaemic variability as a clinical finding in diabetes continues. Indeed, a recent study carried out on children with T1DM found no relationship between glycaemic variability assessed with CGM and vascular dysfunction.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Monnier et al.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> demonstrated a close relationship between glycaemic variability and oxidative stress measured through urinary excretion rate of 8-iso-PGF2α in 21 subjects with type 2 diabetes (T2DM). However, it is difficult to replicate these results. DeVries's group, was not able to demonstrate this association in a group of adult patients with T1DM,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> nor in another group of patients with T2DM treated with oral antidiabetics (OAD).<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> One possible explanation for the inconsistency of these results is that the methodology used to measure the urinary excretion rate of 8-iso-PGF2α differed between the two groups, as DeVries<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,27</span></a> used tandem mass spectrometry, which is less prone to interference than the enzyme immunoassay technique used by Monnier.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Another factor that could exert an influence is the potential effect of insulin on oxidative stress. In a recent study<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> assessing subjects with T1DM and T2DM receiving various hypoglycaemic treatment regimens (OAD only, OAD with insulin and insulin only), it was found that patients being treated with insulin, alone or in combination with OAD, had a lower urinary excretion rate of 8-iso-PGF2α than patients treated with OAD only.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our 8-iso-PGF2α urinary excretion results differ from those published by other authors, on which we have commented above, as they describe lower urinary 8-iso-PGF2α values in adult populations with T1DM or T2DM.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25–28</span></a> However, there are fewer studies assessing oxidative stress and its relationship with T1DM in child populations. Gleisner et al.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> described an 8-iso-PGF2α urinary excretion rate of 1672<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1706<span class="elsevierStyleHsp" style=""></span>pg/mg creatinine, measured by enzyme immunoassay, in a group of children with T1DM of less than five years’ duration. However, they did not find statistically significant differences between the urinary excretion rate of 8-iso-PGF2α in these children with T1DM and 13 healthy controls paired for age and sex. In their study on 48 children and adolescents with T1DM, Schreiver et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> found a creatinine-normalized 8-iso-PGF2α urinary excretion rate of 2530<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>240<span class="elsevierStyleHsp" style=""></span>pg/mg creatinine, measured by tandem mass spectrometry, and were unable to establish a correlation between glycaemic variability parameters and urinary excretion rate of 8-iso-PGF2α. The urinary 8-iso-PGF2α data we describe in our study are also lower than those found in these two studies on paediatric populations. In this case, although all the study subjects have T1DM and are being treated exclusively with insulin, the methodology used to measure urinary 8-iso-PGF2α is also different (enzyme immunoassay in our study and that of Gleisner vs tandem mass spectrometry in Schreiver's study), and other factors, such as the duration of the diabetes and the type of treatment (MDII vs CSII), are also different in this study and those referenced above, which could affect the results. In any case, further studies are needed, on the one hand to assess urinary 8-iso-PGF2α values in a healthy paediatric population in order to obtain reference values, and on the other, in homogeneous groups containing a larger number of children with T1DM.</p><p id="par0120" class="elsevierStylePara elsevierViewall">The limitations of our study include its cross-sectional design and the high percentage of participants who did not take the urine sample, which means that the relationship between glycaemic variability and oxidative stress could not be properly assessed. The glycaemic variability parameters were estimated from the data for determinations of blood glucose and not from a CGM system; however, a recent study showed that the MODD index calculated from four blood glucose measurements in a group of children with T1DM correlated well (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.87) with the MODD index calculated from information collected by a CGM system, and concluded that blood glucose determinations could also be used to calculate the MODD index.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion, high intraday and day-to-day glycaemic variability and moderately high urinary 8-iso-PGF2α excretion were observed in children and adolescents with T1DM attending a summer camp. However, we did not find correlations between markers of glycaemic variability and oxidative stress measured by the rate of urinary excretion of 8-iso-PGF2α. Further studies are needed to evaluate oxidative stress and its relationship with glycaemic variability in children with T1DM.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres369688" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objective" 2 => "Patients and methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec348848" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres369687" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivos" 2 => "Pacientes y método" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec348847" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients and study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Measurements" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Assessment of glycaemic variability" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-05-18" "fechaAceptado" => "2013-09-10" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec348848" "palabras" => array:5 [ 0 => "Glycaemic variability" 1 => "Oxidative stress" 2 => "Type 1 diabetes" 3 => "8-Iso-prostaglandin F2 alpha" 4 => "Children" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec348847" "palabras" => array:5 [ 0 => "Variabilidad glucémica" 1 => "Estrés oxidativo" 2 => "Diabetes mellitus tipo 1" 3 => "8-Iso-prostaglandina F2 alfa" 4 => "Niños" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess glycaemic variability, oxidative stress and their relationship in children and adolescents with type 1 diabetes (T1DM) attending a summer camp.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cross-sectional study that included 54 children and adolescents with T1DM aged 7–16, attending a 7-day summer camp. Sociodemographic information, clinical data, and blood glucose values measured using an Accu-Chek Nano<span class="elsevierStyleSup">®</span> glucose metre were recorded. Glucose variability markers (standard deviation [SD], low blood glucose index [LBGI], high blood glucose index [HBGI], mean amplitude of glyacemic excursions [MAGE] and mean of daily differences [MODD]) were calculated. Oxidative stress was assessed by the measurement of 8-iso-prostaglandin F2 alpha (PGF2α) in a 24-h urine sample collected at the end of the camp in 14 children.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The Median SD, MAGE and MODD indexes were in the high range (61, 131 and 58<span class="elsevierStyleHsp" style=""></span>mg/dl, respectively), LBGI in the moderate range (3.3), and HBGI in the low range (4.5). The mean HbA1c was 7.6% and the median urinary excretion rate of 8-iso-PGF2α was 864.39<span class="elsevierStyleHsp" style=""></span>pg/mg creatinine. The Spearman correlation coefficients between markers of glycaemic variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations were found between markers of glycaemic variability and urinary 8-iso-PGF2α.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">High glycaemic variability was observed in children and adolescents attending a summer camp. However, no correlations were found between markers of glycaemic variability and oxidative stress measured by urinary 8-iso-PGF2α. Further studies are needed to address the relationship between oxidative stress and glycaemic variability in children with T1DM.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Analizar variabilidad glucémica, el estrés oxidativo y la relación entre ambos en un grupo de en niños y adolescentes con diabetes tipo 1 (DM1) que asistieron a un campamento.</p> <span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y método</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio transversal que incluyó a 54 niños con DM1 entre 7 y 16 años de edad que asistieron a un campamento de verano de 7 días. Se recogieron datos sociodemográficos, clínicos y valores de glucemia capilar medidos con un glucómetro Accu-Chek Nano<span class="elsevierStyleSup">®</span>. Se calcularon los marcadores de variabilidad glucémica: desviación estándar (DE), índice de glucemia baja (LBGI), índice de glucemia elevada (HBGI), amplitud media de las excursiones glucémicas (MAGE) y media de las diferencias diarias (MOOD). El estrés oxidativo fue evaluado mediante la medición de 8-iso-prostaglandina F2 alfa (PGF2α) en una muestra de orina de 24<span class="elsevierStyleHsp" style=""></span>h recogida en 14 niños al final del campamento.</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La mediana de DE, MAGE y MOOD se encontraron en un rango elevado (61, 131 y 59<span class="elsevierStyleHsp" style=""></span>mg/dl, respectivamente), LBGI en la categoría de riesgo moderado (3,3) y HBGI en la categoría de riesgo bajo (4,5). La media de HbA1c fue del 7,6%. La media de la tasa de excreción urinaria de 8-iso-PGF2α fue 864,39<span class="elsevierStyleHsp" style=""></span>pg/mg creatinina. No se encontraron correlaciones estadísticamente significativas entre marcadores de variabilidad glucémica y 8-iso PGF2α urinario.</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se ha objetivado una alta variabilidad glucémica en niños y adolescentes con DM1 asistentes a un campamento de verano. Sin embargo, no se han encontrado correlaciones entre marcadores de variabilidad glucémica y de estrés oxidativo medido por 8-iso-PGF2α urinario.</p>" ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as: Colomo N, Tapia MJ, Vallejo MR, García-Torres F, Rubio-Martín E, Caballero FF, et al. Variabilidad glucémica y estrés oxidativo en niños con diabetes tipo 1 asistentes a un campamento. An Pediatr (Barc). 2014;81:174–180.</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Previous conference presentations: XXI Congreso de la Sociedad Española de Diabetes (Barcelona, 15–17 April 2010): Elevada variabilidad glucémica en niños con diabetes tipo 1 asistentes a un campamento de verano. 3rd International Conference on Advanced Technologies and Treatment for Diabetes (Basel, Switzerland, 10–13 February 2010). Standardised analysis of glycaemia and glycaemic variability in children with type 1 diabetes attending a summer camp. 34.° Congreso de la Sociedad Andaluza de Endocrinología y Nutrición (Granada, 5–7 November 2009). Análisis estandarizado de las glucemias y de la variabilidad glucémica en niños con diabetes tipo 1 asistentes a un campamento de verano.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation, unless otherwise specified.</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">BMI: body mass index; CSII: continuous subcutaneous insulin infusion; MDII: multiple daily insulin injections; NPH: neutral protamine Hagedorn.</p>" "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"><td 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" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Participants (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>54) \t\t\t\t\t\t\n \t\t\t\t</td></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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Age (years)</span> \t\t\t\t\t\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">11.41<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.33 \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" 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="elsevierStyleItalic">Sex</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Male (<span class="elsevierStyleItalic">n</span> [%]) \t\t\t\t\t\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">25 (35.2) \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female (<span class="elsevierStyleItalic">n</span> [%]) \t\t\t\t\t\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">29 (64.8) \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="char" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Duration of diabetes (years)</span> \t\t\t\t\t\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">4.76<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.7 \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" 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="elsevierStyleItalic">Diabetes treatment</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>MDII with NPH insulin (<span class="elsevierStyleItalic">n</span> [%]) \t\t\t\t\t\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">6 (11.1) \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MDII with long-acting insulin analogues (<span class="elsevierStyleItalic">n</span> [%]) \t\t\t\t\t\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">45 (83.3) \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CSII (<span class="elsevierStyleItalic">n</span> [%]) \t\t\t\t\t\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 (5.6) \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" 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"><span class="elsevierStyleItalic">Weight (kg) (Z-score)</span> \t\t\t\t\t\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">44.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.8 (0.18<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.71) \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="char" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">BMI (kg/m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">) (Z-score)</span> \t\t\t\t\t\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">19.23<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.66 (−0.69<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.66) \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="char" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Daily insulin dose (IU/kg/day)</span> \t\t\t\t\t\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">0.85<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.26 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab556674.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Sociodemographic and clinical characteristics of the study population.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as median and interquartile range, unless otherwise specified.</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">SD: standard deviation; HbA1c: haemoglobin A1c; HBGI: high blood glucose index; LBGI: low blood glucose index, time in hypoglycaemia (glycaemia <70<span class="elsevierStyleHsp" style=""></span>mg/dl), normoglycaemia (glycaemia between 70 and 180<span class="elsevierStyleHsp" style=""></span>mg/dl) and hyperglycaemia (glycaemia ≥180<span class="elsevierStyleHsp" style=""></span>mg/dl); MAGE: mean amplitude of glycaemic excursions; MODD: mean of daily differences; 8-iso-PGF2α: 8-iso-prostaglandin F2 alpha.</p>" "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"><td 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" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">All participants (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>54) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Participants with urine sample (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>14) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Participants without urine sample (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>40) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">HbA1c (%) (mean</span><span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD)</span> \t\t\t\t\t\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">7.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.2 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.59 \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"><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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Mean glycaemia (mg/dl)</span> \t\t\t\t\t\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">131 (110–146) \t\t\t\t\t\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">121 (106–146) \t\t\t\t\t\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">133 (113–146) \t\t\t\t\t\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">0.38 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Glycaemia SD (mg/dl)</span> \t\t\t\t\t\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">61 (50–72) \t\t\t\t\t\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">59 (40–74) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61 (52–70) \t\t\t\t\t\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">0.97 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">HBGI</span> \t\t\t\t\t\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">4.5 (2.2–6.9) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.7 (1.2–7.4) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.8 (2.9–6.4) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.75 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">LBGI</span> \t\t\t\t\t\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">3.3 (2.3–5.1) \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">3.9 (3.3–6.0) \t\t\t\t\t\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">2.7 (1.9–4.7) \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="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" 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">Percentage of blood glucose values in</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hyperglycaemia (%) (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.49 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Normoglycaemia (%) (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.2 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>16.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.98 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hypoglycaemia (%) (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.5 \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="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" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Episodes of hypoglycaemia per participant</span> \t\t\t\t\t\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">5.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.1 \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">0.13 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Episodes of severe hypoglycaemia</span> \t\t\t\t\t\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 \t\t\t\t\t\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">0.55 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Episodes of ketosis</span> \t\t\t\t\t\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 \t\t\t\t\t\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">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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.78 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Episodes of ketoacidosis</span> \t\t\t\t\t\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 \t\t\t\t\t\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 \t\t\t\t\t\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 \t\t\t\t\t\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">- \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MAGE (mg/dl)</span> \t\t\t\t\t\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">131 (85–159) \t\t\t\t\t\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">122 (68 –196) \t\t\t\t\t\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">131 (94–153) \t\t\t\t\t\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">0.92 \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="char" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MODD (mg/dl)</span> \t\t\t\t\t\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">56 (41–67) \t\t\t\t\t\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">63 (40–72) \t\t\t\t\t\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">56 (41–67) \t\t\t\t\t\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">0.64 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">8-iso-PGF2α (pg/mg creatinine)</span> \t\t\t\t\t\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">– \t\t\t\t\t\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">864.39 (723.39–1292.59) \t\t\t\t\t\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">– \t\t\t\t\t\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">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab556672.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Mann–Whitney test to compare the groups of children with and without the 24-h urine sample.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Markers of glycaemic control, glycaemic variability, episodes of acute complications and urinary excretion rate of 8-iso-prostaglandin F2 alpha in the whole study population and in groups, according to whether or not the 24-hour urine sample was submitted.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">SD: standard deviation; MG: mean glycaemia; HbA1c: haemoglobin A1c; HBGI: high blood glucose index; LBGI: low blood glucose index; MAGE: mean amplitude of glycaemic excursions; MODD: mean of daily differences; 8-iso-PGF2α: 8-iso-prostaglandin F2 alpha.</p>" "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"><td 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" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Time with diabetes (years) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">HbA1c (%) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">MG (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">SD (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">HBGI \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">LBGI \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">MAGE (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">MODD (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">18-Iso-PGF2α (pg/mg creatinine) \t\t\t\t\t\t\n \t\t\t\t</td></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 " 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">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><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><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><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><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" 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">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">0.26 \t\t\t\t\t\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="" 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><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><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><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" 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">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">0.21 \t\t\t\t\t\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">0.48<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">***</span></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">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><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><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><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" 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">MG \t\t\t\t\t\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">0.47<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">***</span></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">0.53<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">***</span></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">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><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><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><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" 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">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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.19 \t\t\t\t\t\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">0.54<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">***</span></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">0.52<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">***</span></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">0.83<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">***</span></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">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><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><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" 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">HGBI \t\t\t\t\t\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">0.55<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">***</span></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">0.57<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">***</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" 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continuous glucose sensing in pediatric patients with type 1 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E. Boland" 1 => "T. Monsod" 2 => "M. Delucia" 3 => "C.A. Brandt" 4 => "S. Fernando" 5 => "W.V. Tamborlane" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2001" "volumen" => "24" "paginaInicial" => "1858" "paginaFinal" => "1862" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11679447" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The glucose area under the profiles obtained with continuous glucose monitoring system relationships with HbA(lc) in pediatric type 1 diabetic patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Salardi" 1 => "S. Zucchini" 2 => "R. Santoni" 3 => "L. Ragni" 4 => "S. Gualandi" 5 => "A. Cicognani" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2002" "volumen" => "25" "paginaInicial" => "1840" "paginaFinal" => "1844" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12351488" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The median is not the only message: a clinician's perspective on mathematical analysis of glycemic variability and modeling in diabetes mellitus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.L. McCall" 1 => "B.P. 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| 2021 September | 24 | 41 | 65 |
| 2021 August | 27 | 32 | 59 |
| 2021 July | 18 | 36 | 54 |
| 2021 June | 26 | 34 | 60 |
| 2021 May | 32 | 35 | 67 |
| 2021 April | 45 | 33 | 78 |
| 2021 March | 40 | 24 | 64 |
| 2021 February | 29 | 16 | 45 |
| 2021 January | 34 | 23 | 57 |
| 2020 December | 35 | 13 | 48 |
| 2020 November | 24 | 14 | 38 |
| 2020 October | 26 | 7 | 33 |
| 2020 September | 29 | 12 | 41 |
| 2020 August | 22 | 17 | 39 |
| 2020 July | 27 | 10 | 37 |
| 2020 June | 25 | 10 | 35 |
| 2020 May | 19 | 18 | 37 |
| 2020 April | 35 | 15 | 50 |
| 2020 March | 32 | 16 | 48 |
| 2020 February | 35 | 20 | 55 |
| 2020 January | 28 | 12 | 40 |
| 2019 December | 69 | 14 | 83 |
| 2019 November | 30 | 13 | 43 |
| 2019 October | 25 | 20 | 45 |
| 2019 September | 25 | 10 | 35 |
| 2019 August | 83 | 22 | 105 |
| 2019 July | 32 | 23 | 55 |
| 2019 June | 34 | 15 | 49 |
| 2019 May | 54 | 37 | 91 |
| 2019 April | 73 | 26 | 99 |
| 2019 March | 26 | 15 | 41 |
| 2019 February | 30 | 19 | 49 |
| 2019 January | 41 | 16 | 57 |
| 2018 December | 43 | 23 | 66 |
| 2018 November | 118 | 28 | 146 |
| 2018 October | 109 | 20 | 129 |
| 2018 September | 57 | 15 | 72 |
| 2018 August | 6 | 0 | 6 |
| 2018 July | 7 | 0 | 7 |
| 2018 June | 12 | 0 | 12 |
| 2018 May | 45 | 0 | 45 |
| 2018 April | 18 | 0 | 18 |
| 2018 March | 16 | 0 | 16 |
| 2018 February | 25 | 0 | 25 |
| 2018 January | 19 | 0 | 19 |
| 2017 December | 21 | 0 | 21 |
| 2017 November | 14 | 0 | 14 |
| 2017 October | 17 | 0 | 17 |
| 2017 September | 20 | 0 | 20 |
| 2017 August | 15 | 0 | 15 |
| 2017 July | 18 | 0 | 18 |
| 2017 June | 36 | 5 | 41 |
| 2017 May | 24 | 6 | 30 |
| 2017 April | 29 | 10 | 39 |
| 2017 March | 15 | 2 | 17 |
| 2017 February | 16 | 6 | 22 |
| 2017 January | 18 | 10 | 28 |
| 2016 December | 38 | 12 | 50 |
| 2016 November | 42 | 5 | 47 |
| 2016 October | 58 | 8 | 66 |
| 2016 September | 43 | 3 | 46 |
| 2016 August | 26 | 3 | 29 |
| 2016 July | 21 | 7 | 28 |
Show all
