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Glycemic changes during menstrual cycles in women with type 1 diabetes
Cambios glucémicos durante el ciclo menstrual en mujeres con diabetes mellitus tipo 1
Lucrecia Herranz
Corresponding author
, Lourdes Saez-de-Ibarra, Natalia Hillman, Ruth Gaspar, Luis Felipe Pallardo
Unidad de Diabetes, Departamento de Endocrinología, Hospital Universitario La Paz, Madrid, 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">It is not unusual for diabetes practitioners to come across the comment from women with type 1 diabetes that their fluctuations in blood glucose control are the effect of the menstrual cycle&#46; It is generally agreed that perimenstrual changes in blood glucose occur in some&#44; but not all women with type 1 diabetes&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> with the percentage of women experiencing a menstrual cycle phenomenon varying from 44&#37; to 61&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">2&#8211;5</span></a> However&#44; studies addressing this issue are of limited value&#44; since the number of women included in the studies is low<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">2&#44;4&#44;5</span></a> or the results are based on self-reported changes&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The most common pattern in the menstrual cycle phenomenon is an increase in blood glucose during the luteal phase&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">2&#8211;6</span></a> which has been attributed to changes in insulin sensitivity along the menstrual cycle&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">2&#44;4&#44;7</span></a> though some studies have not found variations in insulin sensitivity related to the menstrual cycle&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">8&#44;9</span></a> The presence of premenstrual syndrome<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">10&#44;11</span></a> or changes in appetite&#44; energy intake or gastric emptying<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">10&#44;12</span></a> may account for the premenstrual hyperglycemia&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The general recommendation given to adjust insulin requirements during the premenstrual period is to increase overnight insulin dose<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> or overall basal insulin rate&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">To ensure more accuracy when giving instructions for diabetes management to women in their reproductive years this study aimed to determine the percentage of women with type 1 diabetes who experience cyclic changes in glycemia&#44; to analyze which clinical characteristics relate to the menstrual cycle phenomenon&#44; and to evaluate the changes in glycemic parameters along the menstrual cycle&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Subjects&#44; materials and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">This study was performed at the Hospital Universitario La Paz&#44; Madrid&#44; Spain&#46; Ethical approval for this research was provided by the hospital&#39;s ethical committee&#44; and all women gave their informed consent&#46; We retrospectively analyzed 168 menstrual cycles from 26 women with type 1 diabetes who were on preconceptional care &#40;mean number of menstrual cycles per women&#58; 6&#46;5 &#40;2&#46;2&#41;&#41; during two consecutive years&#46; Only women with complete glucose data were included&#46; The participants had a mean age of 35 &#40;5&#46;4&#41; years&#44; a mean diabetes duration of 15&#46;3 &#40;6&#46;3&#41; years and a mean BMI of 22&#46;7 &#40;2&#46;3&#41;<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46; Four women had diabetic retinopathy and one woman had diabetic nephropathy&#46; None of the women used hormonal contraception during the study&#46; Eleven women had already had a child and 17 had a child after the study period&#44; and none required treatment for infertility&#46; Mean age at menarche was 12&#46;5 &#40;6&#46;3&#41; and in 23 subjects menarche had occurred before the diagnosis of diabetes&#46; Only regular menstrual cycles were included in the study &#40;cycle length 21&#8211;35 days&#41;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">15</span></a> and&#44; if pregnancy ensued&#44; the last menstrual cycle before conception was not included in the study&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">All women were on insulin pump therapy and were instructed on insulin dose adjustment&#44; correcting doses and carbohydrate counting&#46; Total daily insulin dose was downloaded to a computer from insulin pumps&#46; Women performed home blood glucose monitoring &#40;6&#46;6 &#40;0&#46;9&#41; glucose readings&#47;day&#41; using the One Touch UltraSmart &#40;LifeScan&#44; Milipitas&#44; CA&#41;&#46; The glucose readings stored in the meter were downloaded to a computer&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A1c was measured in each subject at the end of the study period using high performance liquid chromatography DCCT &#40;Diabetes Control and Complications Trial&#41;-aligned method &#40;Variant II HPLC analyzer&#59; BioRad&#44; Richmond&#44; VA&#41;&#46; The A1C reference intervals are 20&#8211;42<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol &#40;4&#8211;6&#37;&#41;&#44; and the interassay precision coefficient of variation for control materials with a DCCT-assigned A1C content of 5&#46;3 and 9&#46;6&#37; is 2&#46;1 and 2&#37;&#44; respectively&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">For each menstrual cycle we evaluated mean glucose&#44; mean glucose standard deviation&#44; mean fasting glucose&#44; percentage of glucose readings above 140<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;7&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41;&#44; percentage of glucose readings below 55<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;3&#46;1<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; and mean insulin dose in four consecutive periods&#58; early follicular phase &#40;mean length 7&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4 days&#41;&#44; late follicular phase &#40;mean length 7&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6 days&#41;&#44; early luteal phase &#40;7 days&#41; and late luteal phase &#40;7 days&#41;&#46; To determine the day of ovulation we subtracted 14 days from the length of a complete menstrual cycle&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> To calculate early follicular and late follicular phase the total days of the follicular phase were divided by two&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">A woman was identified as having cyclic changes in glycemia when mean glucose rose &#40;at least 15<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41; from early follicular phase to late luteal phase in two thirds of her menstrual cycles&#46; At the end of the study period all&#44; but one woman&#44; were interviewed for symptoms of premenstrual syndrome and self-perception of premenstrual changes in glycemic control&#46; The telephone inquiry included three items&#58; &#40;1&#41; &#191;Do you have premenstrual symptoms&#63; &#40;2&#41; &#191;Do you experience perimenstrual changes in glucose levels&#63; And if yes&#58; &#40;3&#41; &#191;what type of glycemic changes do you observe&#63;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Statistical analyses were conducted using SPSS version 11&#46;0 statistical software &#40;SPSS&#44; Chicago&#44; IL&#41;&#46; To compare mean values among quantitative variables&#44; the independent-samples Student&#39;s <span class="elsevierStyleItalic">t</span>-test or&#44; when appropriate&#44; the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test were used&#46; For multiple comparisons the one way analysis of variance&#44; with the Bonferroni procedure for post hoc contrasts&#44; was used&#46; To compare categorical variables&#44; the chi-square test and the Fisher exact test were used&#46; Data are reported as means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD or as percentage&#46; A <span class="elsevierStyleItalic">p</span> value &#40;bilateral&#41; &#60;0&#46;05 was considered significant&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">Of the 26 women&#44; 17 &#40;65&#46;4&#37;&#41; had cyclic changes in glycemia related to the menstrual cycle&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> is an example of the pattern of glucose in a woman with cyclic changes and in a woman without cyclic changes&#46; Characteristics of women with cyclic changes in glycemia and those without cyclic changes in glycemia were similar&#44; with the exception of age at the diagnosis of diabetes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">A1c at the end of the study period was not significantly different in women with and without cyclic changes in glycemia&#58; 50 &#40;7&#41; vs&#46; 48 &#40;10&#41;<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#59; &#40;6&#46;7 &#40;0&#46;6&#41; vs&#46; 6&#46;5 &#40;0&#46;9&#41; &#37;&#41;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;075&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Mean glucose during the early follicular phase was similar in women with and with out cyclic changes in glycemia &#40;7&#46;6 &#40;1&#46;6&#41; vs&#46; 7&#46;3 &#40;1&#46;5&#41;<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;290&#41;&#46; In women with cyclic changes in glycemia mean glucose rose significantly from early follicular to luteal phase &#40;early luteal&#58; 8&#46;2 &#40;1&#46;5&#41;<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;041 and late luteal&#58; 8&#46;4 &#40;1&#46;7&#41;<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#46; In women without cyclic changes in glycemia mean glucose did not change along the menstrual cycle &#40;early luteal&#58; 7&#46;5 &#40;1&#46;4&#41;<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#44; late luteal&#58; 7&#46;4 &#40;1&#46;5&#41;<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;848&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Mean &#37; of glucose readings &#62;140<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;7&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; during early follicular phase was similar in women with and without cyclic changes in glycemia &#40;52&#46;2 &#40;16&#46;3&#41; vs&#46; 54&#46;4 &#40;16&#46;0&#41; &#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;237&#41;&#46; In women with cyclic changes in glycemia mean &#37; of glucose readings &#62;140<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;7&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; rose significantly from early follicular to luteal phase &#40;early luteal&#58; 58&#46;4 &#40;16&#46;0&#41; &#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;026 and late luteal&#58; 61&#46;0 &#40;16&#46;9&#41; &#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#46; In women without cyclic changes in glycemia mean &#37; of glucose readings &#62;140<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;7&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; did not change along the menstrual cycle &#40;early luteal&#58; 51&#46;8 &#40;17&#46;9&#41; &#37;&#44; late luteal&#58; 49&#46;3 &#40;18&#46;1&#41; &#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;759&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Mean fasting glucose&#44; which was similar in women with and without glycemic cyclic changes during the early follicular phase&#44; did not increase along the menstrual cycle in women with cyclic changes in glycemia &#40;7&#46;4 &#40;2&#46;4&#41; vs&#46; 7&#46;8 &#40;2&#46;0&#41; vs&#46; 7&#46;9 &#40;2&#46;2&#41; vs&#46; 8&#46;1 &#40;2&#46;5&#41;<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;177&#41; nor in women without cyclic changes in glycemia &#40;7&#46;9 &#40;2&#46;1&#41; vs&#46; 7&#46;9 &#40;2&#46;5&#41; vs&#46; 8&#46;1 &#40;2&#46;1&#41; vs&#46; 7&#46;9 &#40;2&#46;2&#41;<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;940&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Mean &#37; of glucose readings below 55<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;3&#46;1<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41;&#44; which was similar in women with and without glycemic cyclic changes during the early follicular phase&#44; did not change along the menstrual cycle in women with cyclic changes in glycemia &#40;5&#46;7 &#40;5&#46;5&#41; vs&#46; 5&#46;1 &#40;5&#46;0&#41; vs&#46; 4&#46;6 &#40;5&#46;0&#41; vs&#46; 4&#46;3 &#40;4&#46;8&#41; &#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;191&#41; nor in women without cyclic changes in glycemia &#40;5&#46;9 &#40;5&#46;9&#41; vs&#46; 7&#46;6 &#40;6&#46;1&#41; vs&#46; 5&#46;0 &#40;5&#46;0&#41; vs&#46; 6&#46;2 &#40;5&#46;1&#41; &#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;154&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Mean glucose standard deviation&#44; which was similar in women with and without glycemic cyclic changes during the early follicular phase&#44; did not change along the menstrual cycle in women with cyclic changes in glycemia &#40;3&#46;4 &#40;0&#46;8&#41; vs&#46; 3&#46;4 &#40;0&#46;6&#41; vs&#46; 3&#46;4 &#40;0&#46;6&#41; vs&#46; 3&#46;5 &#40;0&#46;6&#41;<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;237&#41; nor in women without cyclic changes in glycemia &#40;3&#46;4 &#40;0&#46;8&#41; vs&#46; 3&#46;5 &#40;0&#46;8&#41; vs&#46; 3&#46;4 &#40;0&#46;9&#41; vs&#46; 3&#46;3 &#40;0&#46;6&#41; mmol&#47;L&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;288&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Mean insulin dose&#44; which was similar in women with and without cyclic changes during the early follicular phase&#44; did not change significantly along the four phases in women with cyclic changes &#40;32&#46;1 &#40;5&#46;6&#41; vs&#46; 32&#46;0 &#40;5&#46;7&#41; vs&#46; 32&#46;9 &#40;5&#46;7&#41; vs&#46; 33&#46;7 &#40;5&#46;5&#41;<span class="elsevierStyleHsp" style=""></span>U&#47;day&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;090&#41; nor in women without cyclic changes &#40;31&#46;4 &#40;7&#46;0&#41; vs&#46; 31&#46;1 &#40;7&#46;1&#41; vs&#46; 31&#46;6 &#40;7&#46;0&#41; vs&#46; 31&#46;9 &#40;7&#46;0&#41;<span class="elsevierStyleHsp" style=""></span>U&#47;kg&#47;day&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;950&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows mean glucose&#44; mean &#37; of glucose readings &#62;140<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;7&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; and mean insulin dose along the menstrual cycle for women with and without cyclic changes&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">In this study 65&#46;4&#37; of the women with type 1 diabetes experienced cyclic changes in glycemia with a reproducible pattern along a mean of six menstrual cycles per women&#44; with an increase in mean glucose from early follicular phase to late luteal phase&#46; The observed frequency of menstrual cycle glycemic changes is slightly higher than that reported before&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">2&#8211;5</span></a> Interestingly&#44; since our data provide information on insulin dose for each menstrual phase&#44; we found that women with no cyclic changes in glycemia had no change in their insulin dose along the menstrual cycle&#44; implying that lack of cyclic glycemic changes in these women is not due to the ability to adjust insulin&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">When comparing clinical characteristics of women with and without cyclic changes in glycemia the only difference we found was that women with cyclic changes had a much latter age of diabetes onset&#58; 22 years vs&#46; 14 years&#46; Though earlier onset of diabetes might have induced some dysfunction in the hypothalamus-pituitary-ovary axis&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a> we found no difference in age at menarche&#44; frequency of menarche occurring after the diagnosis of diabetes&#44; fertility or A1c levels between both groups&#46; Additionally&#44; all women included in this study had regular menstrual cycles&#46; Premenstrual syndrome&#44; which has been related to the menstrual cycle phenomenon in women with type 1 diabetes&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">10&#44;11</span></a> was experienced with similar frequency by women with cyclic changes in glycemia and by women without cyclic changes in glycemia&#46; Our results do not support that the presence of premenstrual syndrome may contribute to increase blood glucose&#46; It is interesting to note that self perception of changes in glycemia related to the menstrual cycle was as frequent in women with cyclic changes as in women without cyclic changes&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In the women with cyclic changes in glycemia&#44; the rise in mean glucose during luteal phase was accompanied by an increase in the mean percentage of glucose readings &#62;140<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; implying that hyperglycemic excursions are more frequent in the luteal phase&#44; as has been reported with the use of continuous glucose monitors in women with type 1 diabetes&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">4&#44;6</span></a> However&#44; mean fasting glucose did not increase along the menstrual cycle in contrast with previous reports&#44;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">6&#44;13</span></a> therefore a general recommendation for increasing overnight insulin dose cannot be given&#46; We did not find an increase in the frequency glucose readings below 55<span class="elsevierStyleHsp" style=""></span>mg&#47;dl in the follicular phase&#44; though hypoglycemia associated to menstruation has also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a> Although the women with cyclic glycemic changes tended to increase insulin dose&#44; this increase was not statistically significant&#46; The women in this study had no specific instructions for premenstrual adjustment of insulin dose&#44; however all had good metabolic control and were in an intensive therapy education program&#44; consequently additional instructions are needed when cyclic glycemic changes are confirmed&#46; To minimize hyperglycemic excursions adjustment of insulin sensitivity factor&#44; used for correction dose&#44; may be useful to mitigate the decrease in insulin sensitivity&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">2&#44;4&#44;7</span></a> Alternately&#44; modifying the type of bolus insulin may be useful if variations in food choice<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a> are detected&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">This study is a clinical study&#44; based on the day to day tools that women with type 1 diabetes can use to increase their skills on managing glycaemic changes related to menstrual cycles&#46; It is therefore limited&#44; in as much as other methods of evaluation such as continuous glucose monitoring&#44; ovulation tests or parameters of insulin resistance have not been used&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion&#44; almost two thirds of women with type 1 diabetes experience a menstrual cycle phenomenon&#44; attributable to an increase in hyperglycemic excursions during the luteal phase&#46; Self perception of cyclic glycemic changes does not correlate with blood glucose monitoring results&#44; therefore it is necessary to instruct women on evaluating their weekly mean glucose from their glucose meter before establishing cyclic changes in their insulin management&#46; Our data do not support specific changes in overnight insulin dose&#46; Beyond adjustments in basal insulin&#44; exploration of the causes of hyperglycemic excursions during the luteal phase should help to ensure more accuracy when giving instructions for diabetes management in women with cyclic glycemic changes&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflicts of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "identificador" => "xres690110"
          "titulo" => "Abstract"
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              "identificador" => "abst0005"
              "titulo" => "Background and objective"
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              "titulo" => "Patients and methods"
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          "titulo" => "Resumen"
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              "titulo" => "Fundamento y objetivo"
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              "titulo" => "Pacientes y m&#233;todos"
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          "titulo" => "Introduction"
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          "titulo" => "Subjects&#44; materials and methods"
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        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Results"
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          "titulo" => "Discussion"
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    "fechaRecibido" => "2015-07-31"
    "fechaAceptado" => "2015-11-26"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec696157"
          "palabras" => array:3 [
            0 => "Menstrual cycle"
            1 => "Glycemic change"
            2 => "Type 1 diabetes"
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec696156"
          "palabras" => array:3 [
            0 => "Ciclo menstrual"
            1 => "Cambios gluc&#233;micos"
            2 => "Diabetes tipo 1"
          ]
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To determine frequency of women with type 1 diabetes showing menstrual cyclic changes in glycemia&#44; analyze their clinical characteristics&#44; and assess the pattern of glycemic changes&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We analyzed glucose meter readings along 168 menstrual cycles of 26 women with type 1 diabetes&#46; We evaluated mean glucose&#44; mean glucose standard deviation&#44; mean fasting glucose&#44; percentage of glucose readings &#62;7&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;L and &#60;3&#46;1<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#44; and mean insulin dose in 4 periods for each cycle&#46; A woman was identified as having cyclic changes when mean glucose rose from early follicular to late luteal in two-thirds of her menstrual cycles&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A percentage of 65&#46;4 of the women had cyclic changes&#46; Characteristics of women with and without cyclic changes&#44; including self-perception of glycemic changes&#44; were similar with exception of age at diabetes diagnosis &#40;22&#46;5 &#91;7&#46;5&#93; vs&#46; 14&#46;4 &#91;9&#46;5&#93; years&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;039&#41;&#46; In women with cyclic changes mean percentage of glucose readings &#62;7&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;L rose from early follicular &#40;52&#46;2 &#91;16&#46;3&#93; &#37;&#41; to early and late luteal &#40;58&#46;4 &#91;16&#46;0&#93; &#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0269&#59; 61&#46;0 &#91;16&#46;9&#93; &#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Almost two-thirds of women with type 1 diabetes experience a menstrual cycle phenomenon&#44; attributable to an increase in hyperglycemic excursions during the luteal phase&#46; Enabling women to evaluate their weekly mean glucose from their meter and exploring the causes of hyperglycemic excursions during luteal phase should ensure more accuracy when giving instructions for diabetes management in women with premenstrual hyperglycemia&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Patients and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Fundamento y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Determinar la frecuencia de mujeres con diabetes tipo 1 que experimentan cambios gluc&#233;micos durante el ciclo menstrual&#44; analizar sus caracter&#237;sticas cl&#237;nicas&#44; y evaluar el patr&#243;n de los cambios gluc&#233;micos&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Analizamos las lecturas de los gluc&#243;metros a lo largo de 168 ciclos menstruales en 26 mujeres con diabetes tipo 1&#46; Evaluamos la glucemia media&#44; la desviaci&#243;n est&#225;ndar media&#44; la glucemia media basal&#44; el porcentaje de lecturas &#62;<span class="elsevierStyleHsp" style=""></span>7&#44;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;l y &#60;<span class="elsevierStyleHsp" style=""></span>3&#44;1<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#44; y la dosis de insulina media en 4 per&#237;odos de cada ciclo&#46; Se consider&#243; que una mujer ten&#237;a cambios c&#237;clicos cuando la glucemia media se elev&#243; entre la fase folicular temprana y la fase l&#250;tea tard&#237;a en dos tercios de sus ciclos menstruales&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El 65&#44;4&#37; de las mujeres experimentaron cambios c&#237;clicos&#46; Las caracter&#237;sticas de las mujeres con y sin cambios c&#237;clicos&#44; incluyendo la autopercepci&#243;n de cambios gluc&#233;micos&#44; fueron similares&#44; exceptuando la edad de diagn&#243;stico de la diabetes &#40;22&#44;5 &#91;7&#44;5&#93; frente a 14&#44;4 &#91;9&#44;5&#93; a&#241;os&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;039&#41;&#46; En mujeres con cambios c&#237;clicos el porcentaje medio de los valores de glucosa &#62;<span class="elsevierStyleHsp" style=""></span>7&#44;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;l se elev&#243; entre la fase folicular temprana &#40;52&#44;2 &#91;16&#44;3&#93; &#37;&#41; y la fase l&#250;tea temprana y tard&#237;a &#40;58&#44;4 &#91;16&#44;0&#93; &#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0269&#59; 61&#44;0 &#91;16&#44;9&#93; &#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;000&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Casi dos tercios de las mujeres con diabetes tipo 1 experimentan fen&#243;menos del ciclo menstrual atribuibles a un incremento de las excursiones hipergluc&#233;micas durante la fase l&#250;tea&#46; Posibilitar que las mujeres eval&#250;en su glucemia media semanal a partir de las lecturas de los gluc&#243;metros&#44; y explorar las causas de las excursiones hipergluc&#233;micas durante la fase l&#250;tea podr&#237;a garantizar una mayor precisi&#243;n al impartir instrucciones para la gesti&#243;n de la diabetes en mujeres con hiperglucemia premenstrual&#46;</p></span>"
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            "titulo" => "Pacientes y m&#233;todos"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Herranz L&#44; Saez-de-Ibarra L&#44; Hillman N&#44; Gaspar R&#44; Pallardo LF&#46; Cambios gluc&#233;micos durante el ciclo menstrual en mujeres con diabetes mellitus tipo 1&#46; Med Clin &#40;Barc&#41;&#46; 2016&#59;146&#58;287&#8211;291&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Glucose pattern &#40;mg&#47;dl&#41; along two menstrual cycles in a woman with cyclic changes &#40;A&#41; and in a woman without cyclic changes &#40;B&#41;&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Mean glucose mg&#47;dl &#40;A&#41;&#44; mean &#37; of glucose readings &#62;140<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;7&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; &#40;B&#41; and mean insulin dose U&#47;day &#40;C&#41; along the menstrual cycle for women with&#40;&#9652;&#41; and without &#40;&#9675;&#41; cyclic changes&#46; &#42;Comparison between early follicular and early luteal and late luteal in women with cyclic changes in glycemia&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&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">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;2 &#40;5&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&#46;7 &#40;5&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;107&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">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#46;1 &#40;1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;426&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">Diabetes duration &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;7 &#40;6&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&#46;2 &#40;5&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;066&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">Age at diabetes diagnosis &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#46;5 &#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#46;4 &#40;9&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;039&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">Diabetic microangiopathy &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;000&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">Age at menarche &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;758&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">Menstrual cycle duration &#40;days&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;4 &#40;2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;9 &#40;2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;293&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">Menarche before diabetes &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">94&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;268&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">Premenstrual syndrome &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;688&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">Pregnancy after the study period &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;418&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">Pregnancy before the study period &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;683&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">Self perception of cyclic changes &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Characteristics of women with and with out cyclic changes in glycemic during the menstrual cycle&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:18 [
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                  "host" => array:1 [
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                            0 => "D&#46;S&#46; Barata"
                            1 => "L&#46;F&#46; Adan"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Changes in insulin sensitivity&#44; secretion and glucose effectiveness during the menstrual cycle"
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                          "etal" => false
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                0 => array:2 [
                  "contribucion" => array:1 [
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                0 => array:2 [
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                    0 => array:2 [
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                        0 => array:2 [
                          "etal" => false
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