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Brief report
Effect of dapagliflozin on arterial stiffness in patients with type 2 diabetes mellitus
Efecto de dapagliflozina sobre la rigidez arterial en pacientes con diabetes mellitus tipo 2
Juan Carlos Hidalgo Santiagoa, Juan Maraver Delgadob, Manuel Cayón Blancoc, Juan Bosco López Saezd, Pablo Gómez-Fernándezb,
Corresponding author
pgomezf@senefro.org

Corresponding author.
a Centro de Salud San Telmo, Jerez de la Frontera, Cádiz, Spain
b Unidad de Factores de Riesgo Vascular, Hospital Universitario del SAS, Jerez de la Frontera, Cádiz, Spain
c Endocrinología, Hospital Universitario del SAS, Jerez de la Frontera, Cádiz, Spain
d Facultad de Medicina, Universidad de Cádiz, Cádiz, 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">Type 2 diabetes mellitus &#40;DM2&#41; has a high incidence of cardiovascular &#40;CV&#41; morbidity and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The increase in arterial stiffness &#40;AS&#41; observed in DM2 may contribute to this fact&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The new anti-diabetic sodium glucose cotransporter type 2 &#40;SGLT2i&#41; inhibitor drugs reduce total mortality and CV morbidity and mortality in subjects with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The CV benefits of the SGLT2i derive from the reduction of blood glucose&#44; weight and blood pressure &#40;BP&#41;&#44; the increase in natriuresis&#44; the preservation of renal function and possible direct CV effects&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> A decrease in AS promoted by the SGLT2i has also been suggested as an additional mechanism&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> However&#44; there are no studies that analyse the long-term effect of SGLT2i on AS in patients with DM2&#46; The purpose of this research was to study&#44; prospectively&#44; the long-term effect of an SGLT2i&#44; dapagliflozin&#44; on the carotid-femoral pulse wave velocity &#40;c-fPWV&#41;&#44; a standard measurement of AS in subjects with DM2&#46;</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">Study design and population</span><p id="par0010" class="elsevierStylePara elsevierViewall">Observational&#44; prospective&#44; longitudinal study&#46; 32 subjects diagnosed with DM2 in whom treatment with dapagliflozin 10<span class="elsevierStyleHsp" style=""></span>mg&#47;day was indicated according to routine clinical practice were included&#46; All patients gave informed consent to participate&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Variables</span><p id="par0015" class="elsevierStylePara elsevierViewall">Blood samples were obtained before the start&#44; at 6 months and at 12 months of treatment with dapagliflozin for routine biochemical and haematological determinations&#44; and 24<span class="elsevierStyleHsp" style=""></span>h urine and first morning urine for creatinine&#44; glucose&#44; sodium&#44; uric acid and albumin determination&#46; Glomerular filtration rate &#40;GFR&#41; was estimated using the Chronic Kidney Disease Epidemiology Collaboration &#40;CKD-EPI&#41; formula&#46; Diabetic nephropathy was diagnosed due to a decreased GFR &#40;&#60;60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and&#47;or albuminuria &#40;albumin&#47;creatinine in urine<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#41; and exclusion of other causes of nephropathy&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">BP measurement was carried out on each of the visits with an Omron M1 &#40;Omron Healthcare Co&#46; Ltd&#44; Kyoto&#44; Japan&#41;&#44; following the recommendations of the European hypertension society&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Prior to dapagliflozin therapy and 12 months after treatment&#44; c-fPWV was determined using the SphygmoCor Xcel &#40;AtCor Medical Ply Ltd Suite 11&#44; 1059-1063 Victoria Road West Ryde&#44; NSW 2114 Australia&#41;&#46; The carotid pulse wave was measured by applanation tonometry &#40;high fidelity micromanometer &#91;Millar Instrument&#93;&#41; and&#44; simultaneously&#44; the femoral pulse wave was measured with an inflated cuff over the femoral artery&#46; The c-fPWV was calculated as the ratio between the corrected distance between the pulse wave measurement sites and the delay time between the carotid and femoral pulse waves&#46; The average of 2 high quality measurements was considered as a valid result&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">The results are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation or as median and interquartile range&#44; depending on the distribution assessed by the Shapiro&#8211;Wilk test&#46; Categorical variables are expressed as frequencies&#46; The analysis of the differences between the baseline values and those at 6 and 12 months was performed using the repeated measures ANOVA&#46; The comparison between baseline c-fPWV values and at 12 months was performed with the Wilcoxon test&#46; The study of the participation of variables potentially affecting the c-fPWV was carried out through multiple regression&#46; The statistical analysis was performed with SPSS 22 &#40;IBM Corp&#46; Released 2013&#46; IBM SPSS Statistics for Windows&#44; Version 22&#46;0&#46; Armonk&#44; NY&#58; IBM Corp&#41;&#46; Values of p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 were considered significant&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">Of the 32 patients who started the study&#44; 4 &#40;2 men and 2 women&#41; discontinued the study before 6 months &#40;2 for genital mycosis&#44; one for dyspepsia and one lost to follow-up&#41;&#46; Compared to the rest of the patients who completed the follow-up&#44; those 4 patients were older &#40;66&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10 vs&#46; 53&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;7 years&#41;&#44; their DM was longer &#40;17&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6 vs&#46; 13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;5 years&#41;&#44; lower GFR &#40;81&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21 vs&#46; 95&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&#44; higher c-fPWV &#40;11&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;3 vs&#46; 9&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4<span class="elsevierStyleHsp" style=""></span>m&#47;s&#41; and similar HbA1c &#40;8&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 vs&#46; 8&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3&#37;&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The age was 53&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;7 years&#44; 61&#37; male&#46; DM duration was 13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;5 years&#46; 14&#37; had a history of CV disease&#44; 18&#37; of retinopathy and 32&#37; of diabetic nephropathy&#46; 96&#37; took oral hypoglycaemic agents &#40;metformin 89&#37;&#59; sulfonylureas &#91;SU&#93; 14&#37;&#59; dipeptidyldipeptidase inhibitors &#91;DPP4i&#93;&#41; 50&#37;&#59; glinides 10&#37;&#59; thiazolidinediones 3&#46;6&#37;&#41;&#46; 14&#37; received GLP-1 &#40;glucagon-like peptide-1&#41; receptor agonists treatment and 64&#37; were treated with insulin glargine&#46; During follow-up&#44; the treatment with SU was suspended in 3 patients&#44; treatment with GLP-1 agonists in one and the insulin was reduced&#47;suspended in 2 cases&#46; The initial weight was 93&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;6<span class="elsevierStyleHsp" style=""></span>kg&#44; observing a significant decrease at 6 and 12 months of dapagliflozin treatment &#40;91&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>kg&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000 and 92&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;4<span class="elsevierStyleHsp" style=""></span>kg&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#44; respectively&#41;&#46; Systolic blood pressure &#40;SBP&#41; at 6 months &#40;136&#46;5 &#91;19&#93; mmHg&#41; &#40;median &#91;interquartile range&#93;&#41; and at 12 months &#40;136&#46;5 &#91;22&#93; mmHg&#41; was lower than SBP prior to the start of dapagliflozin &#40;144&#46;5 &#91;29&#93;&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#46; A significant decrease in diastolic BP &#40;DBP&#41; was also observed at 6 and 12 months &#40;78 &#91;10&#93; and 77 &#91;12&#93; mmHg vs&#46; 83&#46;5 &#91;11&#93; mmHg&#44; respectively&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; No significant changes in heart rate were observed&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Changes of haematological and biochemical parameters in blood and urine are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">42&#46;8&#37; of the patients had high c-fPWV baseline values &#40;&#8805;10<span class="elsevierStyleHsp" style=""></span>m&#47;s&#41;&#46; Among the 9 patients with diabetic nephropathy&#44; 44&#37; had high c-fPWV values&#46; This percentage was reduced to 37&#37; among those without nephropathy&#46; The c-fPWV decreased significantly at 12 months of treatment &#40;9&#46;1 &#91;8&#46;4&#8211;10&#46;1&#93; vs&#46; 9&#46;65 &#91;8&#46;75&#8211;11&#46;2&#93; m&#47;s&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The percentage variation was quantitatively but not significantly higher in patients with high baseline c-fPWV values &#40;&#8211;7&#46;8&#37; &#91;&#8211;3- &#8211;19&#37;&#93; vs&#46; &#8211;2&#46;8&#37; &#91;2- &#8211;9&#37;&#93;&#41;&#46; Neither weight loss&#44; BP&#44; HbA1c&#44; changes in GFR nor uricemia showed a significant participation in the changes of the c-fPWV in the multiple regression analysis&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">As in other studies&#44; our data confirm that dapagliflozin produces a sustained decrease in blood glucose&#44; weight&#44; BP and uricemia&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Our main finding is that&#44; for the first time&#44; dapagliflozin demonstrates a medium-long term AS decrease in subjects with DM2 that may have CV and renal benefits by decreasing central BP&#44; attenuating the damage induced by pulsatility&#46; Structural echocardiography changes or cardiac function were not evaluated&#46; We do observe a decrease in albuminuria in which a decrease in c-fPWV could participate together with renal hemodynamic changes&#44; and the decrease in weight and BP induced by dapagliflozin&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The underlying mechanisms of the decrease in c-fPWV are not clear&#46; AS is influenced by neurohumoral and structural factors&#46; In subjects with DM2 the administration of dapagliflozin&#44; acutely&#44; reduces the c-fPWV&#44; regardless of changes in BP&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The persistent decrease in c-fPWV after 12 months suggests that there may be a structural component in the reduction of AS&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Chronic kidney disease with reduced GFR is associated with an increase in AS&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In our study&#44; subjects in whom DM coexisted with kidney disease had a higher baseline c-fPWV&#59; however&#44; after treatment with dapagliflozin&#44; we only observed a slight non-significant decrease in GFR&#44; so this variable does not seem to contribute to the observed changes in AS&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Hyperglycaemia induces changes in collagen that increase AS&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> A better glycaemic control is associated with an attenuation&#47;prevention of increased AS in DM2&#46; A significant decrease in HbA1c is observed in our study&#44; but we did not objectify a significant relationship between glycaemic and c-fPWV changes&#46; On the other hand&#44; the decrease in BP&#44; weight&#44; insulin dose and administration of some antihypertensive drugs are associated with the decrease in c-fPWV&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In our study&#44; insulin was reduced&#47;suspended in only 2 cases&#44; changes in other hypoglycaemic agents with possible vascular effects were minimal&#44; antihypertensive treatment was not modified and&#44; in the regression study&#44; neither weight nor BP changes were shown as significant explanatory variables for a decreased c-fPWV&#44; probably due to the limited number of cases&#46; Neither the significant decrease in uricemia&#44; attributable to an increase in urinary uric acid excretion&#44; showed a significant relationship with the decrease in c-fPWV&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">An increase in the total Na&#43; content is found in DM2&#46; There is a link between the increase in Na&#43; content and structural and functional changes of large arteries&#44; independent of BP&#44; with increased AS&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> SGLT2i&#44; by inhibiting the sodium-glucose cotransporter and the Na&#43;&#47;H&#43; exchanger in the proximal tubule&#44; induces natriuresis&#46; The few studies that have quantified the natriuretic effect of SGLT2i have observed a transient increase in urinary sodium excretion&#46; We observed a slight decrease in serum Na&#43;&#44; which we attribute to a decrease in blood glucose and a persistent increase in natriuresis&#44; which&#44; however&#44; did not reach statistical significance when it was related to urinary creatinine excretion&#46; In the absence of a strict sodium intake control&#44; the evaluation of natriuresis is difficult&#46; We believe&#44; however&#44; that our data suggest a probable persistent increase in dapagliflozin-induced natriuresis which&#44; on the other hand&#44; has been shown to reduce the tissue content of Na&#43; in subjects with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The increase in natriuresis&#44; together with the reduction of the Na&#43; content of the smooth muscle fibre of the myocardium and the vascular wall by inhibition of the Na&#43;&#47;H&#43; exchanger can contribute to the reduction of AS&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0085" class="elsevierStylePara elsevierViewall">The administration of dapagliflozin produces in subjects with DM2 a medium-long term decrease in AS&#44; in which multiple mechanisms can be involved&#58; decrease of blood glucose&#44; BP&#44; weight&#44; uric acid and Na&#43; body content&#44; among others&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The longitudinal nature of the study with medium-long term data&#44; without relevant changes in concomitant treatment&#44; reinforces our results&#46; However&#44; our study has limitations&#58; its observational nature&#44; the lack of control of sodium intake and the reduced number of patients&#46; Since the 4 patients who did not complete the follow-up had higher c-fPWV values and the fact that in our study the decrease in c-fPWV seems to be of greater magnitude in cases in which it is abnormally high&#44; the inclusion of these patients could have reinforced our findings&#46; Long-term randomized studies in DM2 with CV event analysis are necessary to confirm the beneficial effect of SGLT2i on AS and its participation in CV benefits&#44; and its comparison with new hypoglycaemic agents with possible vascular effects&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interests</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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    "fechaRecibido" => "2019-02-14"
    "fechaAceptado" => "2019-05-23"
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            0 => "Diabetes mellitus"
            1 => "Arterial stiffness"
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            0 => "Diabetes mellitus"
            1 => "Rigidez arterial"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Oral antidiabetic inhibitors of the sodium-glucose cotransporter &#40;SGLT2i&#41; reduce cardiovascular morbidity and mortality in DM2&#46; The increase in arterial stiffness can participate in this morbidity and mortality&#46; The aim of this study was to analyse the effect of the administration of dapagliflozin on arterial stiffness&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Prospective observational study that included 32 patients with DM2&#46; Before starting dapagliflozin&#44; and at 6 and 12 months&#44; biochemical parameters in blood and urine were analysed&#46; Before starting dapagliflozin and at 12 months the velocity of the carotid-femoral pulse &#40;VPc-f&#41; was determined by tonometry&#46; Changes in the variables and their interrelation was analysed by repeated data ANOVA&#44; Wilcoxon&#39;s test and multiple regression&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A significant decrease in the VPc-f was observed&#46; There was no association between decreased VPc-f and changes in blood glucose&#44; uric acid&#44; blood pressure or weight&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Dapagliflozin&#44; in subjects with DM2&#44; produces a medium to long-term decrease in arterial stiffness&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Patients and methods"
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          2 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los antidiab&#233;ticos orales inhibidores del cotransportador sodio-glucosa &#40;iSGLT2&#41; reducen la morbimortalidad cardiovascular en la DM2&#46; El aumento de la rigidez arterial puede participar en esta morbimortalidad&#46; El objetivo de este trabajo fue analizar el efecto de la administraci&#243;n de dapagliflozina en la rigidez arterial&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional&#44; prospectivo que incluy&#243; 32 pacientes con DM2&#46; Antes del inicio de dapagliflozina y a los 6 y 12 meses se analizaron par&#225;metros bioqu&#237;micos en sangre y orina&#46; Basalmente y a los 12 meses se determin&#243; la velocidad de pulso car&#243;tida-femoral &#40;VPc-f&#41; mediante tonometr&#237;a&#46; El an&#225;lisis de los cambios en las variables y su interrelaci&#243;n se hizo mediante ANOVA de datos repetidos&#44; test de Wilconson y regresi&#243;n m&#250;ltiple&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Se objetivo un descenso significativo de la VPc-f&#46; No se evidenci&#243; asociaci&#243;n entre descenso de VPc-f y cambios de la glucemia&#44; uricemia&#44; presi&#243;n arterial ni del peso&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Dapagliflozina&#44; en sujetos con DM2&#44; produce a medio-largo plazo&#44; una disminuci&#243;n de la rigidez arterial&#46;</p></span>"
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Urine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diuresis &#40;median &#91;interquartile range&#93;&#41; &#40;l&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;9 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;8 &#40;1&#46;3&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;9 &#40;1&#46;5&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glucose &#40;median &#91;interquartile range&#93;&#41; &#40;g&#47;24<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63 &#40;53&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79 &#40;62&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glucose &#40;median &#91;interquartile range&#93;&#41; &#40;g&#47;g creat&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;33 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;35&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;59&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Albumin&#47;creat&#46; &#40;median &#91;interquartile range&#93;&#41; &#40;mg&#47;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;116&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;94&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;056&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;053&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Log&#46; albumin&#47;creat&#46; &#40;&#215; &#177; SD&#41; &#40;mg&#47;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Na&#43; &#40;&#215; &#177; SD&#41; &#40;mEq&#47;24<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">212<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">256<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>92<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">258<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>83<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Na&#43;&#47;creat&#46; &#40;median &#91;interquartile range&#93;&#41; &#40;mEq&#47;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">132 &#40;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154 &#40;96&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos