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Original article
Impaired awareness of hypoglycaemia in subjects with type 1 diabetes. Results of an online survey in a diabetes web site
Hipoglucemia desapercibida en personas con diabetes tipo 1. Resultados de una encuesta “on line” en una Web de diabetes
Ignacio Congeta,
Corresponding author
iconget@clinic.ub.es

Corresponding author.
, Dalia Ávilab, Marga Giméneza, Carmen Quirosa, Vanesa Salaverriac, Belen Dueñasc
a Diabetes Unit. Endocrinology and Nutrition, IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), Hospital Clínic i Universitari, Barcelona, Spain
b Endocrinology and Nutrition Department, Health Services Center, University of León, León, Spain
c Fundación para la Diabetes, Madrid, Diabetes Unit, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hypoglycaemia is the most relevant adverse event related to insulin treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">1&#44;2</span></a> Repeated episodes of hypoglycaemia in subjects with type 1 diabetes &#40;T1D&#41; may result in failure to recognize hypoglycaemia symptoms and signs at a physiologically normal threshold&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> Impaired awareness of hypoglycaemia &#40;IAH&#41; may occur in up to 20&#8211;25&#37; of individuals with T1D and the lack of warning symptoms places them at high risk for severe hypoglycaemia &#40;SH&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">4&#44;5</span></a> In addition&#44; both IAH and SH represent the main limiting factor to achieve optimal beneficial glycaemic control precluding its beneficial effects&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In order to identify IAH&#44; different questionnaires and self-report measures are being used in clinical practice&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">7&#44;8</span></a> Among these&#44; despite some limitations&#44; the Clarke test is one of the most frequently used&#44; providing detailed assessment of IAH&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">7</span></a> This test encompasses eight questions regarding exposure to hypoglycaemia and a subjective estimation of the glycaemic threshold for the generation of symptoms and signs&#46; The use of the Clarke questionnaire which was conceived in English requires its validation in a different language before its use in clinical practice and research purposes in non-English speaking populations&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">We recently conducted and published the psychometric validation of the Clarke questionnaire in two different languages&#44; Spanish and Catalan&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> In our study&#44; we sought to evaluate the frequency of IAH using the Spanish version of the Clarke test in a free access diabetes-related web portal&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">We collected &#40;March 2014&#8211;January 2015 inclusive&#41; anonymous data from a free access Spanish version of the Clarke test previously uploaded in the website of the <span class="elsevierStyleItalic">Fundaci&#243;n para la Diabetes</span> &#40;<a href="http://www.fundaciondiabetes.org/encuestas/box_encuesta_clarke.htm">http&#58;&#47;&#47;www&#46;fundaciondiabetes&#46;org&#47;encuestas&#47;box&#95;encuesta&#95;clarke&#46;htm</a>&#41;&#46; This is a free access web portal for patients and health care professionals&#46; In addition to the eight questions included in the questionnaire&#44; on a previous page we asked for information regarding the type of diabetes &#40;T1D&#44; T2D&#44; other types of diabetes&#44; I do not know&#41;&#44; age &#40;four categories&#58; 18&#8211;35&#59; 36&#8211;55&#59; 56&#8211;65 and &#62;65 years old&#41;&#44; and duration of the disease &#40;five categories&#58; &#60;2&#59; 2&#8211;5&#59; 5&#8211;10&#59; 10&#8211;15 and &#62;15 years&#41;&#46; In the Clarke Test a score &#60;3 designates normal awareness&#59; 3 indicates uncertain awareness and &#62;4 designates IAH &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; According to the Clarke test&#44; severe hypoglycaemia is defined as episodes where the patient is unconscious or had a seizure and needed glucagon or intravenous glucose&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Results are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD or &#37;&#46; Comparisons were performed using the Student&#39;s <span class="elsevierStyleItalic">t</span>-test or an ANOVA for repeated measurements&#46; Comparisons between proportions were made with a Chi-square test&#46; A <span class="elsevierStyleItalic">p</span> value &#60;0&#46;05 was considered statistically significant&#46; All statistical calculations were performed using the Statistical Package for Social Science &#40;SPSS&#44; v 19&#46;0&#41; for personal computers&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0030" class="elsevierStylePara elsevierViewall">Only those with T1D diabetes &#40;418&#41; were included in the analysis&#44; with 51&#46;2&#37; being in the 36&#8211;55 years of age range&#46; Regarding disease duration&#44; 34&#46;7&#37; had had T1D for more than 15 years&#59; 20&#46;6&#37; between 11 and 15 years&#59; 17&#46;2&#37; between 2 and 5 years&#59; 16&#46;5&#37; between 6 and 10 years and in only 11&#37; subjects&#44; T1D had been diagnosed less than 2 years before&#46; We found the presence of IAH in 23&#46;4&#37; of questionnaires&#46; Uncertain awareness was found in 15&#46;3&#37; and normal awareness of hypoglycaemia was found in 61&#46;3&#37; of the participants&#46; There was a significant positive relationship between the duration of T1D and the Clarke test score &#40;&#60;2 years 1&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;30&#59; 2&#8211;5 years 1&#46;83<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;62&#59; 6&#8211;10 years 2&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;73&#59; 11&#8211;15 years 2&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;79&#59; &#62;15 years 2&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;13&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#46; The longer the duration of T1D&#44; the higher the score in the Clarke test &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; According to the Clarke test 14&#46;1&#37; of the participants had had at least one episode of severe hypoglycaemia in the previous year and half had done so &#40;7&#46;4&#37;&#41; on 2 or more occasions&#46; All but one of the participants with 2 or more episodes of severe hypoglycaemia had IAH&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">According to an online survey using the Spanish version of the Clarke questionnaire we found that up to &#8764;25&#37; of adult participants with T1D have IAH and that the prevalence of this condition increases with the duration of the disease&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Data regarding the prevalence of IAH in Spain are still very scarce in comparison with other countries&#46; This is probably due&#44; at least in part&#44; to the infrequent use of specific questionnaires dedicated to the detection of IAH mainly because of the lack of translated versions to Spanish&#46; In 2014 we performed a psychometric analysis of the Spanish version of the Clarke questionnaire<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> and described that the Spanish version of Clarke Test displays good psychometric properties and could be considered a useful tool for evaluating IAH in patients with T1D using Spanish as the native language&#46; With the use of this test in our routine clinical practice we detected IAH in 16&#37; of an adult population with T1D &#40;average of 20 years of T1D duration&#44; unpublished data&#41; and in 9&#37; of young adults transferred from paediatric to adult Diabetes Units &#40;average of 8 years of TD1 duration&#44; data published only in abstract form&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We report here information regarding the prevalence of IAH in a large group of individuals with T1D based on a survey performed using a anonymous free access online questionnaire with the Spanish version of the Clarke Test&#46; Our results are similar to those of other authors and surveys and confirm the relationship between the presence of IAH and disease duration&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">10&#44;11</span></a> In addition to this&#44; 7&#37; of the participants in the present study fulfilled the very recent definition of problematic hypoglycaemia and were designated as IAH by the test&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> Thus&#44; despite modern patient education and improvements in the insulin therapy&#44; severe hypoglycaemia and IAH are still far from being solved in T1D&#46; Repeated non-severe and severe episodes of hypoglycaemia&#44; and the presence of IAH are major barriers to achieving normoglycaemia over a lifetime of using intensive insulin therapy and thereby preclude the long-term benefits of euglycemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">6&#44;12&#44;13</span></a> In addition&#44; hypoglycaemia and its consequences have a very negative impact on the perceived quality of life of individuals with T1D&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">14&#8211;16</span></a> Considering our results&#44; evaluation and review of the presence of risk factors for severe hypoglycaemia should mandatorily include screening for the presence of IAH using adequate versions of specific questionnaires&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Our study has limitations&#46; The most important limitation is inherent to the study design&#46; We relied on data from an anonymous&#44; free access on-line survey&#44; and therefore cannot totally guarantee the truthfulness and accuracy of the results&#46; In addition to this&#44; it is possible that mostly those patients with T1D affected by recurrent episodes of hypoglycaemia or specially interested in that subject answered the questionnaire&#46; However&#44; the large number of participants&#44; as well as&#44; the fact that our findings can be extrapolated to previous reports on the same subject&#44; could be considered a significant strength of our work&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In summary&#44; at least 25&#37; of T1D participants in an online survey using a Spanish version of a currently used questionnaire showed impaired awareness of hypoglycaemia&#46; The presence of this condition increases with the duration of the disease and allows the identification of subjects prone to severe episodes of hypoglycaemia&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest regarding the manuscript&#46;</p></span></span>"
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    "fechaRecibido" => "2015-10-28"
    "fechaAceptado" => "2015-11-10"
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        0 => array:4 [
          "clase" => "keyword"
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            0 => "Hypoglycaemia"
            1 => "Hypoglycaemia unawareness"
            2 => "Type 1 diabetes mellitus"
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          "clase" => "keyword"
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          "palabras" => array:3 [
            0 => "Hipoglucemia"
            1 => "Hipoglucemia desapercibida"
            2 => "Diabetes mellitus tipo 1"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess the frequency of impaired awareness of hypoglycaemia &#40;IAH&#41; using a specific questionnaire &#40;Spanish version&#41; in a free access diabetes-related web site&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Data from a free access Spanish version of the Clarke test previously uploaded to the website of the <span class="elsevierStyleItalic">Fundaci&#243;n para la Diabetes</span> &#40;March 2014&#8211;January 2015&#41; were assessed&#46; In addition to the eight questions in Clarke&#39;s questionnaire&#44; information on type of diabetes&#44; age&#44; and disease duration was obtained&#46; The Clarke test divided participants into three categories&#58; normal awareness&#44; uncertain and IAH&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Of the 418 participants with type 1 diabetes&#44; 51&#46;2&#37; were aged 36&#8211;55 years&#46; In 34&#46;7&#37;&#44; diabetes had been diagnosed &#62;15 years before&#44; while disease duration was &#60;2 years in 11&#37;&#46; According to Clarke categories&#44; 23&#46;4&#37; had IAH&#44; 15&#46;3&#37; uncertain awareness&#44; and 61&#46;3&#37; normal awareness&#46; The longer the duration of diabetes&#44; the higher the Clarke test score&#46; According to the Clarke test&#44; 14&#46;1&#37; of participants had experienced at least one episode of severe hypoglycaemia in the previous year&#44; and half of these &#40;7&#46;4&#37;&#41; had suffered severe hypoglycaemia two or more times&#46; All but one of the participants with two or more episodes of severe hypoglycaemia had IAH&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our study shows that the rate of IAH using an online survey is similar &#40;25&#37;&#41; to that previously reported in other geographical areas&#44; increases with diabetes duration&#44; and identifies subjects prone to severe hypoglycaemia&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Determinar la frecuencia de hipoglucemia desapercibida &#40;HD&#41; en una amplia cohorte de pacientes adultos con diabetes tipo 1 &#40;DT1&#41; a trav&#233;s de un cuestionario espec&#237;fico disponible para ser rellenado en la Web de manera voluntaria&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Metodolog&#237;a</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Desde marzo de 2014 a enero de 2015 se recogieron los resultados del cuestionario en lengua espa&#241;ola de percepci&#243;n de la hipoglucemia para adultos con DT1 &#40;Test de Clarke versi&#243;n en castellano&#41; disponible <span class="elsevierStyleItalic">on-line</span> en la p&#225;gina Web de la Fundaci&#243;n para la Diabetes&#46; Adem&#225;s&#44; la encuesta <span class="elsevierStyleItalic">on-line</span> inclu&#237;a datos sobre el tipo de diabetes&#44; la edad y el tiempo de evoluci&#243;n de la enfermedad&#46; La puntuaci&#243;n final del cuestionario cataloga a los pacientes en 3 categor&#237;as&#58; percepci&#243;n normal&#44; indeterminada y anormal-HD ante una situaci&#243;n de hipoglucemia&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De los 418 participantes con DT1 el 51&#44;2&#37; ten&#237;a una edad entre 36-55 a&#241;os&#46; En el 34&#44;7&#37; la DT1 la diabetes ten&#237;a una duraci&#243;n<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>15 a&#241;os y en el 11&#37; menos de 2 a&#241;os&#46; De acuerdo con el resultado del cuestionario de Clarke&#44; un 23&#44;4&#37; de los pacientes presentaba una HD&#44; un 15&#44;3&#37; una percepci&#243;n indeterminada y en el 61&#44;3&#37; el resultado fue normal&#46; A mayor duraci&#243;n de la DT1&#44; mayor puntuaci&#243;n del cuestionario&#46; El 14&#44;1&#37; de los participantes hab&#237;a tenido una hipoglucemia grave durante el a&#241;o anterior y la mitad de ellos &#40;7&#44;4&#37;&#41; hab&#237;a presentado<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2 episodios&#46; De estos &#250;ltimos todos&#44; excepto uno&#44; presentaban HD&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Como en estudios precedentes realizados en otras &#225;reas geogr&#225;ficas&#44; nuestro estudio demuestra que casi una cuarta parte de los pacientes con DT1 tiene alterada la capacidad para percibir los s&#237;ntomas de hipoglucemia&#46; Esta anomal&#237;a es m&#225;s frecuente conforme aumenta la duraci&#243;n de la enfermedad&#44; e identifica las personas en riesgo de presentar hipoglucemia grave&#46;</p></span>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Clarke test results by duration of T1D&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="7" align="left" valign="top">Escoja la categor&#237;a que mejor le describe &#40;s&#243;lo una&#41;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;a&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="6" align="left" valign="top">Siempre tengo s&#237;ntomas cuando mi az&#250;car en sangre est&#225; bajo&#46;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;b&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="6" align="left" valign="top">Algunas veces tengo s&#237;ntomas cuando mi az&#250;car en sangre est&#225; bajo&#46;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;c&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="6" align="left" valign="top">Ya no tengo s&#237;ntomas cuando mi az&#250;car en sangre est&#225; bajo&#46;</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="7" align="left" valign="top">&#191;Ha perdido alguno de los s&#237;ntomas que sol&#237;a presentar ante una bajada de<br>az&#250;car&#63; &#40;hipoglucemia&#41;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;a&#41; S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;b&#41; No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="7" align="left" valign="top">En los &#250;ltimos <span class="elsevierStyleUnderline">seis meses</span>&#44; &#191;Con qu&#233; frecuencia ha tenido episodios de<br>HIPOGLUCEMIA GRAVE SIN PERDIDA DE CONOCIMIENTO&#63; &#40;episodios en los que se ha sentido confundido&#44; desorientado&#44; cansado <span class="elsevierStyleUnderline">y sin posibilidad de tratar usted mismo</span> la situaci&#243;n de hipoglucemia&#41;&#46;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;a&#41; Nunca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;b&#41; Una&#47;dos veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;c&#41; 1 vez cada 2 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;d&#41; Una vez al mes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;e&#41; M&#225;s de una vez al mes&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="7" align="left" valign="top">En <span class="elsevierStyleUnderline">el &#250;ltimo a&#241;o</span>&#44; &#191;Con qu&#233; frecuencia ha tenido episodios de<br><span class="elsevierStyleUnderline">HIPOGLUCEMIA GRAVE CON P&#201;RDIDA DE CONOCIMIENTO</span>&#63; &#40;episodios acompa&#241;ados de p&#233;rdida de conciencia o convulsiones que <span class="elsevierStyleUnderline">hayan requerido la administraci&#243;n</span> de glucag&#243;n o glucosa intravenosa&#41;&#46;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;a&#41; Nunca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;b&#41; 1 vez&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;c&#41; 2 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;d&#41; 3 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;e&#41; 5 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;f&#41; 6 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;g&#41; 7 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;h&#41; 8 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;i&#41; 9 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;j&#41; 10 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;k&#41; 11 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;l&#41; 12 veces o m&#225;s&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleUnderline">En el &#250;ltimo mes</span>&#44; &#191;<span class="elsevierStyleUnderline">Con</span> qu&#233; frecuencia ha tenido lecturas inferiores a 70<span class="elsevierStyleHsp" style=""></span>mg&#47;dl con s&#237;ntomas&#63;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;a&#41; Nunca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;b&#41; de 1 a 3 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;c&#41; 2 &#243; 3 veces&#47;semana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;d&#41; 4 &#243; 5 veces&#47;semana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;e&#41; Casi cada d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="7" align="left" valign="top">En el &#250;ltimo mes&#44; &#191;con qu&#233; frecuencia ha tenido lecturas inferiores a 70<span class="elsevierStyleHsp" style=""></span>mg&#47;dl <span class="elsevierStyleUnderline">sin</span> s&#237;ntomas&#63;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;a&#41; Nunca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;b&#41; De 1 a 3 veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;c&#41; 2 &#243; 3 veces&#47;semana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;d&#41; 4 &#243; 5 veces&#47;semana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;e&#41; Casi cada d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="7" align="left" valign="top">&#191;Hasta cu&#225;nto ha de bajar su az&#250;car en sangre para notar s&#237;ntomas&#63;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;a&#41; 60&#8211;69<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;b&#41; 50&#8211;59<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;c&#41; 40&#8211;49<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;d&#41; inferior a 40<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="7" align="left" valign="top">&#191;Hasta qu&#233; punto puede decir por sus s&#237;ntomas que su az&#250;car en sangre es bajo&#63;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;a&#41; Nunca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;b&#41; Casi nunca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;c&#41; Algunas veces&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;d&#41; Casi siempre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;e&#41; Siempre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleBold">C&#225;lculo de la puntuaci&#243;n</span>&#58;</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">Preguntas 1&#58; b &#243; c<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>R</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">Pregunta 2&#58; a<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>R</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">Pregunta 3&#58; b&#44; c&#44; d&#44; e &#40;cualquiera de ellas&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>R</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">Pregunta 4&#58; b&#44; c&#44; d&#44; e&#44; f&#44; g&#44; h&#44; i&#44; j&#44; k&#44; l &#40;cualquiera de ellas&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>R</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">Pregunta 5 y 6&#58; respuesta pregunta 5<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>respuesta pregunta 6<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>R</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">Pregunta 7&#58; c &#243; d<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>R</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">Pregunta 8&#58; a&#44; b &#243; c<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>R</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">La suma total de R determina el grado de percepci&#243;n del paciente frente a la hipoglucemia&#58;</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">1-2 R<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>percepci&#243;n normal&#59;</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">3 R<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>percepci&#243;n de categor&#237;a indeterminada&#59;</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top">&#62;3R percepci&#243;n anormal ante una situaci&#243;n de hipoglucemia &#40;hipoglucemia desapercibida&#41;</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Spanish version of the Clarke test&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a></p>"
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                          "etal" => false
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                            2 => "J&#46;V&#46; Freeman"
                            3 => "C&#46;J&#46; Emery"
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                  "host" => array:1 [
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                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;E&#46; Cryer"
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        "texto" => "<p id="par0065" class="elsevierStylePara elsevierViewall">We are indebted to all of those who participated in the survey and to the personnel from the &#8220;Fundaci&#243;n para la Diabetes&#8221; for their help&#46;</p>"
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