GUIA 4

Vista previa del material en texto

Propósitos de Lectura: 
• Reconocer las partes del Artículo de Investigación. ~ 
~íl!J.!)®@, • 
• 
ldentíficar las características particulares de la sección Metodología. 
Buscar información especmca . 
• 
©'mm~JJ.!M§) 
Analizar las características y los segmentos textuales de la sección 
Metodología. 
• Reconocer vocabulario de la especialidad . 
En esta guía se trabajará con el mismo texto de la Guía 3: "Patients' perceptions of 
nutrítion e are provided by general practitioners: focus on Type 2 diabetes". 
1. Lea nuevamente el abstract de la Guía 3, para realizar las siguientes 
actividades, según lo trabajado en la guia anterior. 
a. Responda en forma oral: 
n ¿Cuál es el objetivo del estudio? 
n ¿Cuál es el fundamento del estudio?' 
n ¿Dónde se realízó? 
= ¿Qué especialidad médica tienen los investigadores involucrados? 
= ¿Cuál es la conclusión? 
b. Relea la sección Metodología del abstract y anote la información que espera 
encontrar ampliada en el artículo de investigación. 
Methods 
Nine hundrcd and thitty-nine individuals wiith Type 2 diabetes completed a 54-item online 
smvey. Individual survey iten1s related to demographic information, health-related 
attributes, perspectivas on ideal care and retlections 011 previous care . 
.. ' ............. ' ........ , .... ' .............. , ........ , ............................... '' .................................................................. , ,. ,. ' .... . 
2. Lea las funciones que tienen las distimtas partes del artículo de investigación 
científica (AIC), para tildar las que cree corresponden a la sección Metodología. 
Función del discurso ✓ 
ll Presentar antecedentes 
ll Revisión de investigaciones relacionadas 
ll Presentación de la nueva información 
ll Descripción del procedimiento de recolección de datos 
5,9 
u Descripción del procedimiento experimental 
u Descripción del procedimiento de análisis de datos 
u Indicar resultados consistentes 
u Indicar o presentar observaciones no consistentes 
u Resaltar los resultados generales de la investigación 
u Explicar los resultados específicos 
u Establecer las conclusiones 
3. Lea la siguiente explicación, para corroborar o corregir las respuestas 
anteriores: 
[!] INFORMAClóN QUE SE INCLUYE EN U\ SECCIÓN METODOLOGIA DE UN AIC 
u Descripción general del experimento 
a Población / Muestra 
a Lugar 
1:1 Restricciones / condiciones limitantes 
u Técnicas de muestreo 
1:1 Procedimiento * 
u Materiales * 
u Variables 
u Tratamiento estadístico 
(En general, el procedimiento y los materiales constituyen información obligatoria, la 
descripción del experimento, la población, el lugar, las condiciones limitantes, las técnicas 
de muestreo, las variables y el tratamiento estadístico son optativas.) 
Extraído de Weissberg, R. y S. Buker. (1990). Writfng up research. Experimental research report writ/ng for 
students of Englísh. New Jersey: Prentice Hall Regents. 
S EGÚN NWOGU (1997) LA SECCIÓN M ETODOLOGIA DE UN AIC DE M EDICINA CONSTA DE LOS 
SIGUIENTES SEGMENTOS TEXTUALES: 
Segmento Textual 4: Describir los procedimientos de recolección de datos 
a. Especificar la fuente de los datos 
b. Especificar el tamaño de la muestra 
c. Especificar el criterio de recolección de datos 
Segmento Textual 5: Describir los procedimientos experimentales 
a. Identificar los principales instrumentos usados en el experimento 
b. Reconstruir el proceso experimental 
c. Especificar los criterios de éxito 
60 
l 
Segmento Textual 6: Describir los procedimientos de análisis de datos 
a. Definir terminología 
b. Especificar el proceso de clasificación de datos 
c. Identificar los Instrumentos de análisis o procedimientos 
d. Especif icar modificaciones a los instrumentos/ procedimientos 
Extraído de Nwogu, K. (1997). The medica! research paper. structure and functlons. Eng/ish for 
Specífic Purposes, 16 (2), 135. [Traducción Propia) 
4. Lea el texto a continuación, para ubicar los títulos y subtítulos en el lugar 
correcto. 
Participant sampling 
Methods 
Data cmalysis 
Suruey instru.ment 
Patients' perceptions of nutrition care p1·ovided by general 
practitioners: focus on Type 2 diabetes 
T.auren R.ill*, Roger Hughes, Ren Oeshrow tillld Michael Leveritt 
A cross-sectional online survey was developed using LitueSurvey version 1.82. 
The besl practice guidelines for n1anagement of Type 2 diabetes in Auslralian 
5 general practice were used to inform the survey content, as this document describes 
the expected practices of GPs in this context. Aftcr a rcview of rclevant literature 
and discussions with patients with Type 2 diabetes that were known to the research 
team, sorne additional topics were identified as requiring investigation and were 
included in the survey. such as diabetes related characteristics and prívate health 
10 insurance coverage. Fifty-four survey items were clustered iato four sections, each 
with a distinct rationale for investigation anda variety of l'esponse modes (Table 1). 
Sections 1 and 2, respectively, related to general demographics and health-related 
attributes of respondents. Questions within these sections were included to enable 
the identification of relationships between participant characteristics and patient 
15 perceptions. \-\l'here possible, question response formats wcre composcd in a 
comparable fom1at to the Diabetes Australia, Queensland (DAQ) information 
database to enable comparisons belween the survey sample and the potential 
participant pool. Additional demographíc questions were included wbich were 
relevant to the Australian general practice context due to the potential to intlucnce 
20 health services received by respondents, such as possession of a Medicare carel, 
chronic disease management plan and prívate health insurance. A number of 
health-related attributes were also included due to the potential intluence on the 
nature of health care received by respondents, such as frequency and continuity of 
GP coasultalions and consultations with additional health care providers. 
25 Toe third survey section related to the perspectives of respondents regarding 
61 
'ideal nutrition care'. This infon11ation enabled a comparison between the 
perspectives of patient regarding preferred nutrition care and the documented best 
practice gtúdelines for care in this context. Questions were modelled from the 
recommended practices listed in the best practice guidelines for Type 2 diabetes 
30 management in general practice. 
General uue practices were included in addition to uutrition-specific practices 
for use as references to other aspects of care wh.icb are usually expected to be 
provided by GPs. Toe fou1th survey section focused on respoudents' reflections of 
nutrition care previously received from ·their GP. This information enabled 
35 respondents to identify practices that nave been provided by their GP as well as 
report on their satisfaction witb ·this received care. Questions reflected the content 
of Section three, as derived from tbe best practice guidelines for the management of 
Type 2 diabetes in general practice. 
lnitial survey piloting comprised of a review of the online survey by five GPs. 
40 These GPs provided feedback on face validity and reasonableness of question 
wording. Recommendations for changes to survey wording included minor word 
editing, which was completed prior to further piloting. Secondary survey piloting 
comprised of tbe online completion of the smvey by 10 individuals witb Type 2 
diabetes, for feedback on tbe interpretation and understanding of survey items. Toe 
45 primary purpose of tbis pilot phase was to minimize question ambiguity. After 
completion of the survey, these individuals were asked to comment on their 
intcrpretation of each survey item as wcH as the clarity of item wording and survey 
layout. The r<.x:ommendations to SLLrvey wording for the purposes of maximizing 
question interpretation and understanding included minor word editing, and this 
50was completed prior to data collection. The finalized survey was intended to take 15 
minutes to complete and was only available in Englisb. 
The potential partic:ipant pool were individuals with Type 2 diabetes who were 
registered with DAQ in Febn1ary 2011 (n = 9518). DAQ is Queensland's primary 
55 organization for support, advocacy and researcb for people 'A~th Type 2 diabetes. 
An introductoty e-mail was sent by DAQ to the potential participant pool including 
a b1ief description of the study, assurance of confidentiality, a link to complete tbe 
survey and contact details of the research team. Confidentiality of survey responses 
was ensured through the certified. anonymous LimeSurvey program. Two reminder 
60 e-mails were sent to tbe potential participant pool, 2 and 4 weeks after tbe initial e-
mail. 
All analyses were conducted using the SPSS statistical software package version 19. 
Descriptive statistics were calculated for each survey item including frequency 
65 distribution, mean and mode responses. Gender and age were compared between 
survey respondents and the total potential participant pool using chi-square 
goodness-of-fit analyses to test for representation of the survey sample. Level of 
education was compared between survey respondents and the 2008 AusDiab 
survey using chi-square goodness-of-fit analysis. Part:ic:ipants' expectation for 
70 nutrition care, rate of receiving nutiition care and satisfaction with nutrition care 
were compared ,.,,ith demographic characteristics including gender, level of 
educat:ion and income using Pearson's chi-squared tests. In order to comply with 
the assumptions underpinning chisqL1are analyses, categories were collapsed to 
62 
75 
ensure that <20% of cells remained below minimum counts. Statistical s ignificance 
level was set at P < 0.05. 
Sc.uJun R..llon.aae t,• lnvcolgadun 
,\lhlWll íl'lilhcall,-..1 o, 
ttl~llb\ctu:• o( lhl-
tria mpki by • comp.,.un 
h> 1h.r. OAO ti.ul pwuaual 
purtlaf""U pool. 
LllAhlo IJcnlllkMklln uf 
rt.blMlni.hips betwcm 
f'l&t1lttJW11 c:hJr&1.effibO llflJ 
p!lOCftt rcrcqi110m. 
[1t1h"8 rocn-p1.-l,lon 
ltc1""<m 1uLla11 ptr,,«;ti,a 
ur tt1c ldelll lc\1tl ul OV uutn1,oo 
urc •td 1bc Wl.u.inmtcd bCII 
pr.klk.c MIUl.kll•• ro, W'C' 1i1 
thiuanlut. 
[n.at,b rdlc-i.-riun uf p11fffl1 
'itldÍ..,M"1 fl nu l nliOl1 cwc 
rc«hed In tbe¡eirw:ral pr..tc:~ 
• •Ont: •nd ""ulLbtJl'Ct,.'C:¡ftJ 
crt.lNcmcnl uf hc!Jlh)' nirtJllitM 
pr.,_i..,c., 
MC'(). mullipie fflOiK'r q1.M11UI(~ J", piltnl 
A,m,,_,.,, 
A~• 
O<todo .. 
LJ1.,r.:•lonkwl 
l lolbc:hulJ jncomc 
Mewc.,< dl,,i,iloty mJ pri,•"' 
btahh hNm.ntt 
'(Cm .SU'ICC' dt.tfDO!iL\ 
O.:n.1amahc.-u.:io 
h~,~ncyut Ju1bdt'k<blf!d 
GP conwllatAJtt• 
hcfcttnn: of QlftlmUllt º' CP 
(lt "'"· Cl1ochronclU11kin) 
(',,..uJl•lun •11lii ald.bóml ~Hllh 
an~,Jcn 
l ,p1u..,.11tto/ "diabdo•. tt1c,,.,,1 
phr(ok'«\" -odacd '""- f«:1..-. 
.w1 f.':;ªb.a wmr4icatKJftlttl ~bda• 
" """""" ""Jll' ..i -dn,.,unlrn_w:,,:• 
bpialWn'J d klnfMt1 ol CUlrlblJn 
UD Jaabc.ts ffilNJFmtnl., 
1, ..... ,_ ni ·-"""' di cun-gldl(UIOII rm,mmc_ncbt._..• 
IMcUlllkxJ of 6.,nhrr i,dnmullkon 
iwlit..bk ID ('UIIMC~ 
C'>rcn:rrc~ fil p«eKCI micJ lr.l 
~ ... , 
S.1tdtt1ion11fklcriti ..... pratf\llll 
~f'Ccl~cd .Jc,q~ iJI nutril5un.f'dAcd ... ,,,... 
l\,R:cl'to'CJ n:h11...irullip l,e111Cat 
Wf'P-1111 anJ hcalth U'lt~ 
n:rctn~J dhc1h~ne.. ol 11wunon C11tr 
r.:cl\c.J 
AtUJt>f r.kc.'ll~t a~ pM"ltto.l 
Att.- of a.re 1't\(ü1t1a, ~crncnl 
•0t-m1.~ que••• d.:nwd 1n c-..u,-..hblc ,trffl.lf to OAO 11Mftw. 
"('.,.,t roctl~ 4.WJ'l,wd h,a l:11t4il pr.11dke ¡uldtbtlel tur n\Ul.af!Cl'IC!nl ul Tyf,e l ~bdn: in A.lw1ilk.Jn ,encn.l pnk,in • 
'()ue;lttll" nt.1.e 10 u.re pt .a.tll.:.C'I r,U\i dcJ rrum .. unldcnl1Ard bcal1b pmlDllll\.l'IAI 
Re-• 
MC'O 
MC'O 
MC'O 
MC'O 
y~.inu 
M('Q 
M(''() 
MC'() 
v ..... 
M(-0 
S.rt Uhrt 
S.rt Ul.,11 
S.rt Ul.,n 
'L¡,l Ulcn 
S.¡,lU1'<rt 
M('() 
'-rt Ul..crt 
MCO 
MCO 
l-rt Li\.c n 
O,,.• 
Or<• 
5. Normalmente las tablas y gráficos se Incluyen en la sección Resultados, ¿por 
qué cree que se ha incluido la tabla 1 en esta sección? 
6. Teniendo en cuenta las respuestas dadas en los ejercicios 2 y 3, 
a. tilde los verbos que pueden aparecer en esta sección; 
b. relea el texto y resalte los verbos que efectivamente ahí se 
encuentran; 
c. justifique las respuestas correctas; 
d. complete la columna de características (presente/ pasado, voz 
activa/voz pasiva, estado/ acción) sólo de los verbos que tildó al 
completar el punto a; 
63 
V ERBOS V ERBOS QUE CREE JUSTIFICACIÓN DE LAS C ARACTERISTICAS 
PUEDEN A PARECER EN R ESPUESTAS (PRESENTE/P ASADO -
LA S ECCIÓN C ORRECTAS Voz A CTIVPJV oz P ASIVA 
M ETODOLOGIA - EsTAOOiAcc16N) 
were conducted 
failed 
were included 
were used 
reported 
examines 
has been 
selected 
was observed 
may encourage 
improves 
indicate 
were found 
were comparad 
was perceived 
reflects 
are influenced 
suggests 
were sent 
provided 
was developed 
dominates 
were identified 
e. Entre los renglones 31 y 51 predominan los verbos en voz activa, 
¿puede explicar por qué? 
........................................................ ...... ... ................ ' .. .. ... ..... . .. . . 
f. ¿Qué conclusión puede extraer acerca de los verbos en la sección 
" metodología" ? 
64 
[±] Los VERBOS EN LA SECCIÓN M ETODOLOGÍA DEL AIC DE MEDICINA Con frecuencia, en la sección metodolog ía se utiliza la voz pasiva para 
describir lo que se hizo y los materiales y herramientas usadas. 
En estos casos no se explicita el agente: es decir, no se agrega quien realizó la acción a 
través de "by". 
Ejemplo: The samples were collected (&y 1:Jo). 
Aunque en ciertos casos, se puede usar la voz. activa (especialmente cuando el autor 
forma parte de un equipo de investigación); la voz. pasiva es lo más frecuente. 
Hay una distinción importante para tener en cuenta: 
• Voz pasiva en presente: se refiere a lo que se hace normalmente, describir los 
equipos, herramientas o métodos que se usan normalmente. 
• Voz pasiva en pasado: se utiliza para describir lo que el investigador hizo. 
Otra manera de aclarar qué es lo que hizo el investigador es incluyendo frases como: "In 
this study" o "In our experiment". 
Adaptado de: Glasman-Deal, H. (201 O). Scienoe researoh wrilíng for non-nativa speakers of English. London: 
Wortd Scientific Publishing Co. 
7. Lea el texto más detenidamente, para responder: 
a. En las secciones 1 y 2, ¿para qué se incluyeron las preguntas? 
b. En las secciones 1 y 2, ¿para qué se diseñaron con el formato de la 
base de datos de Queensland? 
c. ¿Qué palabra le ayudó las encontrar las respuestas en a y b? 
d. ¿Cuáles son las razones por las cuales se incluyeron preguntas 
relacionadas a preguntas demográficas y relacionadas con la salud? 
.............. ' ........ ...... ........................... ' ..... ' ... ' ...... ...... .. ' ................ . 
. . . . . . . . . . . . . . ' ... ' .................. ...................................... .... ..... ... ....... .... . 
65 
a-
b-
e-
d-
e. ¿Qué indicio lingüístico le permitió encontrar las respuestas? 
f. ¿Para qué se unieron las categorías, de manera que se asegurara que 
menos de 20% de las celdas qwedaran bajo los mínimos? 
g. ¿Qué indicio lingüistico le permitió encontrar la respuesta? 
8. ¿Cuál es el referente de la palabra/frase resaltada? 
REFERENTE (en español) 
Fifty-four survey items 
were clustered (r. 1 O) 
Additional demograehic 
guestions were included 
(r.18) 
A number of health-
related attributes were 
also included (r.21-22) 
This information enabled 
(r.26) 
9. Lea las siguientes frases, para completar las actividades a continuación: 
o LimeSurvey version 1.82 8 (r.3) 
o Diabetes Australia, Queensland (DAQ) information database (r.16-17) 
o SPSS stalistical software package version 19 (r.63) 
a chi-square goodness-of-fit (r.65- 66) 
o Pearson's chi-squared tests (r.72) 
a. ¿Conoce el significado de las frases del recuadro? 
b.¿Puede inferirlo del contexto? 
c. En los renglones 54-55 se encuentra la siguiente oración: "DAQ is 
Queensland's primary organization for support, advocacy and research for 
people with Type 2 diabetes." ¿Cuál es la función de esta oración? ¿Por 
qué se incluyó? 
d. El resto de las frases NO están explicadas en el texto. ¿Por qué? 
66 
e. Escriba el nombre de la herramienta/ procedimiento al lado de la 
definición/ descripción correcta. 
Descripción/ definición Herramienta 
lt Is an lntegrated family of products that addresses the entire 
analytical process, from planning to data collection to analysis, ' ... .. .... ..... ·· ···· ····· ..... . 
reporting and deployment. The software name stands for Statistical ' ......... ' ................. ... 
Package for the Social Sciences. 
htlp:liwww-01.ibm.comlsonware/analytlcsispss/products/statistlcs/ 
A statistical test that addresses the problem of fitting a statistical 
model to observed data. 11 is intended to test how likely it is that an ................................ 
observed distribution is due to chance ...................... ·· ········ 
hl lp://www.slatyalo.edu/Courses/1997•98/ 101/chlgf.hlm 
http://www.lingupenn.edu/-clight/chisquared.htm 
lt is a software that allows users to quickly create intuitiva, powerful, ................................ 
online question-and-answer surveys that can work for tens to .. ..... ······ .......... , ..... .. 
thousands of participants without much effort. 
The survey software itself is self-guiding for the respondents who are 
participating. 
https://manual,limesurvey.org/LimeSurvay_Manual 
lt is used to assess two types of comparison: tests of goodness of fil ....... ······ ......... ····· ···· 
and tests of independence. • ••• • ••• 1 • • • • • ••••••• • ••••••• • • 
• A test of goodness of lit establishes whether or not an 
observad frequency distribution differs from a theoretical dislribution. 
• A test of independence assesses whether pairad observations 
on two variables, expressed in a contingency ta ble, are independent 
of each other (e.g. polling responses from people of different 
nationalities to see if one's nationali ty is relatad t.o the response). 
http://en.wiklpedia.org/wikVPearson%27s_chi•squared_ test 
10. Vocabulario: Dé los equivalentes en español de las siguientes 
palabras/frases. 
Frases en inglés Equivalentes en español 
a. survey content (r.5) 
b. health insurance coverage (r.9-10) 
c. rationale (r.11 ) 
d. participan! pool (r.17) 
e. health care providers (r. 24) 
f. nutrition care (r. 27) 
g. initial survey piloting (r.39) 
h. tace validity (r. 40) 
i. support, advocacy and research 
(r.55) 
6,7 
a 
a 
a 
a 
11 
11 
11 
11 
11 
11 
11. la sección Metodología presenta gran variabilidad. las siguientes son 
características que puede presentar esta sección. Relea el texto, para decidir 
qué características cumple éste en particular. luego, resúmalo. El comienzo 
está hecho a modo de ejemplo. 
Provee explicaciones complementarias. Asume conocimientos previos del lector. 
Se divide en subsecciones. 
Se hace uso de siglas y citas vs uso de descripciones 
Presenta muchos/Q.ocos verbos por oración 
Provee ejemplos, definiciones e ilustraciones 
Presenta Q_ocoslmuchos enunciados de modo: how by + ing vs. 
Da QQ.cas/ muchas justificaciones de las decisiones metodológicas 
Se usan verbos volitivos o de voluntad (por ejemplo: decidimos) 
Existen pocas reiteraciones de los sujetos/ objetos de la investigación (énfasis en las 
técnicas usadas) 
Se usan de conectores 
En este texto no se proveen explicaciones sobre las herramientas utilizadas ........................ . 
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . ' ' . ' ' .. .. .. ' .. ...... ' ' ....... ' ............................... ' ............................................ . 
12. Complete el cuadro que resuma la información del texto. 
Herramienta: 
Detalles: ..................................... .... .... ... ..... ...... . 
Secciones: ........... ........ ...... ...... ........... .. ...... ... ... . 
Soporte: .... ........ .. ..... .... ..... ............. .... ......... ..... . 
Participantes : 
Pasos/ Etapas: Paso 1: ... ... .. .. ........ .. ......... .......... .. .... ... ....... ... . . 
Paso 2: .......................................................... . . 
Paso 3: .................. .. ............ ...... .. ..... ....... ... .... . 
Paso 4: .... ........ ..................... ... ..... ..... .. .... ... .... . 
Paso 5: . ..... .. ..... . .... ........ ... ........ .... .... .. ... .. ... .... . 
Paso 6: . .... ......... ........ ........... .... .... ....... .... ..... .. . 
68 
Análisis de datos: 
/ ACTIVIDADES DE PRÁCTICA DE ESCRITURA DE 
ABSTRACTs/ 
13.a. Establezca correspondencias entre las frases/palabras de la columna 
de la izquierda y las de la columna de la derecha. 
1- Previous o o a- inconsistent results studies 
2- Preterm birth o o b- was to determine 
3- These findings o o e- have suggested have 
4- ... have shown o o d- were obtained 
5- Our objective o o e- is associated 
6- Medication data 
□ □ 
f- important public 
health implications 
[Adaptado y Traducido de Weissberg, R. y S. Buker. (1990). Writing up research. Experimental 
research report writing for students of Engllsh. Nlew Jersey: Prentice Hall Regents.] 
13.b. Complete el texto a continuación con las frases que formó en el ejercicio 
anterior. 
Risk of Diabetes Among Young Adults Born Preterm in Sweden 
OBJECTNE- (1) ...................................................................... that pretenn bitth is 
associatc.-d witl1 diabetes later in lifc. Thesc studies 
(2) ...................................................................................... for late prcterm births and have 
had various limitations, including the inability to evaluate diabetic outpatients or to 
estima te risk across Lhe fttll range of gestational ages. 
(3) .................................................................................. whether preterm bi1th is associated 
with diabetes medication prescription in a 11ational cohort of young adults. 
RE.SEARCH OE.SlGN AND METHODS- This was a national cohort study of 
630,090 infants born in Sweden from1973 through 1979 (including 27,953 bon, pretern1, 
gestational age ,37 weeks), fo llowed for diabetes medication prescription in 2005- 2009 
(ages 25.5- 37.0 years). (4) .......................................... .................... from ali outpatient and 
inpatient pharmacies throughout Sweden. 
RESULTS- Individuals born preterm, including those born late preterm 
(gcstational age 35- 36 weeks), had modestly increased odds ratios (ORs) for diabetes 
medication prcscription relative to those bom ful) tcrm, after adjustiog for fetal growth 
69 
and other potential confounders. Insulit1 and/or oral diabetes medications were 
presctibed to 1.5% of individuals born pre1term compared ,'lith 1.2% of those born full 
terrn (adjusted OR 1.13 [95% CI 1.02- 1.26]). Insulin without oral diabetes medications 
was prescribed to 1.0% of individuals born preterrn compared with o.8% of those born 
ful! term (1.22 [1.08- 1.39)). 
CONCLUSIONS- (5) .................................................. , inclucling late preterm bhth, 
(5) .............................................. ,,.,.ith a modestly increased risk of diabetes in young 
Swedish adults. (6) ................................................................................................... given 
tbe increasing number of preterm bi1ths and the large disease burden of diabetes, 
particularly when diagnosed ill young adulthood. 
Diabetes Care 34:1109-1113, 2011 
70 
Crricllo « o/ úJrdrOW)JIC.Jor 010~1obgy 2014, 13 140 
ktt¡x//www,cardwb.comlcm ll!nl/ 1311 /l◄O 
T EXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
•
CARDIO 
VASC\JLAR 
DIASElOLOGY 
ORIGINAL INVESTIGATION Open Access 
The protective effect of the Mediterranean diet 
on endothelial resistanceto GLP-1 in type 2 
diabetes: a preliminary report 
Antor-.o Cenello1·, Kathe11ne Esposno2, Luc:,a La Sala1 Gemma P4adas. Valen.t De N19r1>1, Rd:lerto T~ta3, 
Loredana Bucdare1114, MauriZio Rord,netli4 and Steíano Genovese4 
1 Abstract 
Background: In type 2 diabetes, acute hyperglycennla worsens endothellal tunctlon and lnflammatlon, whlle 
resistance to GLP-1 action occurs. AII these phenomena seem to be relatad to the generation of oxidative stress. A 
Medlterranean dlel. supplemented wlth olive oll, lncreases plasma anttoxldant capaclty, suggesung that lts 
5 lmplementatlon can have a favorable effect on the af orementloned phenomena. In the present study, we test the 
hypothesls that a Mediterranean diet uslng olive oll can counteract the effects of acute hyperglycemla and can 
improve the resistance of the endothelium to GLP-1 action. 
Methods: Two groups of type 2 dlabetlc patlents, each conslstlng of twelve subjects, participated In a randomlzed 
trlal for three months, followlng a Medlterranean dlet uslng olive oll or a control low-fat diet. Plasma antloxidant 
10 capacity, endothelia l function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels were evaluated at baseline and at 
the end of the study. The eftect of GLP-1 durlng a hyperglycemlc clamp, was also studled at basellne and at the 
end of the study. 
Results: Compared to the control dlet, the Medlterranean dlet lncreased plasma antloxldant capaclty and lmproved 
basal endothelial functlon. nltrotyroslne, 8-lso-PGF2a, IL-6 and ICAM-1 levels. The Mediterranean diet also reduced 
15 the negatlve effects of acute hyperglycemla, lnduced by a hyperglycemic clamp, on endothellal functlon, 
nltrotyroslne, 8-lso-PGF2a, IL-6 and ICAM-1 levels. Furthermore, the Medlterranean diet lmproved the protectlve 
actíon of GLP-1 on endothelial function , nltrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels, also lncreasing GLP-1· 
induced lnsulln secretlon. 
Concluslons: These data suggest that the Mediterranean diet, using olive oil, prevents the acute hyperglycemia 
20 effect on endothellal functlon, lnflammatlon and oxldative stress, and lmproves the actlon of GLP-1, whlch may 
have a favorable effect on the management of type 2 diabetes, particularly for the prevention of card lovascular 
dlsease. 
Keywords: Diabetes mellitus, Acute hyperglycemla, GLP-1, 0xldatlve stress, Medlterranean dlet 
Gardiovascular disease Is a major oomplication of type 2 diabetes and cause of death (1]. Hyperglycemla seems 
25 to be an Importan! contrlbutor toward cardlovascular compllcatlons of diabetes, and lt has been suggested that lt 
produces such damage through the generation of oxldatlve stress (2). Particularly, there Is evldence that an acute 
71 
TEXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
lncrease In glycemla can produce oxldatlve stress, leadlng to endothella l dysfunctlon and lnflammatlon (2). Both 
endothelial dysfunction and inflammation are wellrecognized pathogenic factors for vascular disease, particularly 
In diabetes (2). 
30 Until recently, any intervention with antioxidants aiming to prevent cardiovascular complications in both 
nondlabetlc and dlabetlc people has ylelded dlsappolntlng results [3]. The PREDIMED trlal , however, showlng that 
a Mediterranean diet (MedDiet) enrl ched In monounsaturated fatty acids or polyunsaturated fatty aclds and 
polyphenols can prevent cardiovascular disease In both non-dlabetlc and dlabetic people, can be considered the 
flrst proof that an "antloxldant• lnterventlon can provlde certaln beneflts [4]. Thls hypothesls Is strongly supported 
35 by evldence In PREDIMED of a significan! lncrease In the antloxldant capaclty In the plasma of people recelvlng the 
MedDlet 151, and that thls lncrease Is partlcularly relevant when uslng olive oll 16]. 
Recently, a possible beneficia! effect of glucagon-like peptide-1 (GLP-1) analogues in the management of 
diabetes has been suggested (7). GLP-1 and lts analogues, In addltlon to thelr lnsulln-troplc actlon In allevlatlng 
hyperglycemia, have beneflclal effeots In protectlng fr,om the progresslve lmpairment of pancreatic J3-cell function, 
40 preservlng ¡3-cell mass and suppresslng glucagon secretlon, gastrlc emptylng and appettte, al i of whlch are 
characteristlcs that could prove beneficia! for the management of diabetes [7] . 
Apart from the well-documented lncretin effect of GLP-1, its role in the cardlovascular system also arouses 
lnterest. GLP-1 effects on the card lovascular system may lnclude a dlrect actlon on the endothellum, where the 
presence of speciflc receptors for GLP-1 has been demonstrated [8]. Conslstently, GLP-1 has demonstrated to 
45 lmprove endothellal functlon In diabetes 19,10], poss.lbly lncreaslng the antloxldant defenses of the endothellum 
(11) and decreasing oxidative stress generation (10]. However, it is worth mentioning that, in both type 1 and type 
2 diabetes. hyperglycemla Induces an endothellal reslstance to the act lon of GLP-1, wlth oxldatlve stress servlng as 
the mediator of this phenomenon 110,12,13]. 
The alm of thls study is to test the followlng In patlents wlth type 2 diabetes: 
50 - whether a MedDlet can counterbalance the effects of acute hyperglycemla on the generatlon of oxidative stress, 
endothellal dysfunction and inflammatlon; 
- and lf lt can also lmprove the effects of GLP-:!1. durlng acule hyperglycemla on endothellal dysfunctlon, 
inflammation and oxidative stress. 
Methods 
55 Sub]ects and dlets 
The study included 24 type 2 dlabetlc patlents. Basellne characteristícs of the study groups are shown in Table 1. 
The study was approved by the Ethlcs Commlttee, and lnformed wrltten consent was obtalned from the study 
subjects. 
Ali patlents were taklng metformln, whlch they contlnued durlng the study. None of the type 2 dlabetlc patlents 
60 presented retinopathy, nephropathy, or neuropathy. Ten patlents had hypertension treated wlth an ACE inhlbitor, 
whlch was wlthheld on the study days. None of the subjects was on statln or antloxidant supplements, and they 
were requested to malntaln thelr regular physlcal actlvlty and llfestyle and to record In a dlary any event that could 
affect the outcome of the study (e.g., stress, change In smoking hablts, alcohol consumption, or intake of foods not 
included in the experimental deslgn). None of the partlclpants showed evldence of hlgh alcohol consumptlon or 
65 was an act ive smoker. Furthermore, durlng the previous 6 months, particlpants could not have taken part In any 
welght-reductlon program or other nutrltlonal lnterventlon. 
At thelr flrst appolntment wlth the dletltlan, all particlpants were lnformed about the study, asked to keep a 30 
72 
TEXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
food dlary, and completed a baslc questlonnalre regardlng age, socloeconomlc status, medica! hlstory, famlly 
history, physical activity, smoking and alcohol cons111mp tion habits, which allowed identification of foods to be 
70 modlfled. 
75 
Participants were randomly assigned to two groups of twelve patients each, using a computer-generated 
random number sequence. Each group recelved, for a perlod of 12 weeks, elther a Mediterranean dlet (MedDlet) 
enriched in monounsaturated fatty acids (MUFAs) (50 ml, 4 tablespoons extra virgin olive oll/day; approximately 
1L/ week), ora control low-fat diet [4). 
The general Med0let guldelines that dietitlans provlded to partlcipants lncluded the following positiva 
recommendatlons (4): a) abundant use of olive oll for cooklng and dressing dlshes; b) consumpllon of :!:2 dally 
servlngs of vegetables (at least one of them raw, such as In a salad),not lncludlng slde dlshes; c) :!:2-3 dally 
servings of fresh fruits (including natural ju ices); d) :!:3 weekly servings of legumes; e) :!:3 weekly servings of fish or 
seafood (at least one them fatty fish}; f ) :!:1 weekly servlng of nuts or seeds; g) select whlte meats (poultrywlthout 
80 skln or rabbit) lnstead of red meats or processed meats (burgers, sausages); and h) cooklng regularly (at least 
twlce a week) wlth tomato, garllc and onlon, and dressing vegetables, pasta, rice and other dlshes wlth a sauce 
made by slowly simmerlng mlnced tomato, garlic and onlon wlth abundant olive oll. Negative recommendatlons 
were also given to eliminate or limit the consumpt ion of cream, butter, margarlne, cold cut meat, paté, duck, 
carbonated and/ or sugary beverages, pastrles, Industrial bakery products (such as cakes, donuts, or cookles), 
85 Industrial desserts (puddlngs, custard), French fries and/ or potato chips, and out-of-home pre-cooked cakes and 
sweets. The alm of the control dlet 14] was to reduce all types of fat, wlth particular emphasls on the consumptlon 
of lean meats, low-fat dairy products, cerea Is, potatoes, pasta, rice, fruits and vegetables. In the control diet, advice 
on vegetables, red meat and processed meats. hlgh.fat dalry products. and sweets concurred wlth the 
recommendations of the Medlterranean dlet, but the use of olive oil for cooking and dressing and the consumption 
90 of nuts, fatty meats, sausages. and fatty flsh were dlscouraged. 
Compllance by partlcipants was monltored through weekly telephone conversations wlth the dietitian and a 
check-list of the foods they consumed daily. 
Table 1 8-stllne chara<tetlitks of type 2 dlabetl< patltnu and tht ~IIKU of on• month followlng a Medltfflantan 
diet using olive oU, or followlng a control low-fat dlet 
Mtdlllft l>Meline IM-3 n,c,rnho Cotarol dle1 bueane Control clet. l fflONhl 
!><e OM 3f ·•,H• lM'f 8M• 
hMl«9fm1 198 r 14 2')61!] 1911.11 2'1lill 
ttl>Alc'ID 11.llOl ,SO 10• 110 t04 8.0i0.6 
lloAlc mmoVMol 6St l.l ott> t LO a,' JO 6HJJ 
ftstrq U~ oC-'IOd PINUt' mm 11q TTAt 11 186 t IJ 1116t IJ TThl • 
lll-,tm .,.,,o1.- blr>od P'"'"' .. "'"' -ig 116.H 1.3 1155 • IJ lt/1•1 4 116.1 • 15 
Tora1 "'°'"''"ol ,m,ol/1 • JOtOJ 4]0t0A "11tO• 4JlHOJ 
tngl\C~des rriml'I I.HO • Uto.5 UtaJ l,:HDl 
HOl-Cmmolll 141 Q.2 ••Jo.• 1.ha.l ).f t OA 
l DI.< ,,,"10111 2.1 J QJ l3 •O• 21 t04 JJ • 05 
fl,()1" SHO.S 19 ,o•· !IS ta.l S6l ~b 
8-6o-9Ub i¡,QI"' 1 61lH~ •IJtU• 81•110 oll.h. •I 
•i """'° .,.. µmola Qt',.I l ODl QJhO~• 116) 1 OIM 0.641 QD(¡ 
IUM-1 • rcv,nU IIOHll5 nos 101 · m a, 10s 1733 t 1¡.a 
1l-61P'l/fflt 2JO'JS1.o..1 !/O.JO, &.r Zi830 t IOJ 2li.5~ t 10.l 
f 1W' l¡ffl>VO 90l..2.t $1J 1.110.Ji .C.i~ 911.6.!.. !IS~ 9U.6B2.> 
1W l¡,rc!VQ 807.5 t ª'' lo;oe.J UO I' 1110.ll 7U 8113 l ma 
0.,11,etpM\fd •fntWniSl i, cO.OStnbiNtM. 
73 
T EXTO PARA A CTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
Study deslgn 
Before and at the end of the diet intervention, baseline glyoemia, insulin, endothelial function (flow mediated 
95 dllatatlon: FM0), plasma nltrotyroslne and S~so prostaglandln F2alpha (8-lso-PGF2a), GLP-1 (active 7-36), 
interleukin•6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), the ferric reducing antioxidant potential (FRAP)and 
the total radlcal-trapplng antloxldant parameter 
(TRAP) plasma levels were measured in each subject. 
Before and at the end of the diet lntervention, each subject underwent, In a randomlzed order and on dlfferent 
100 days, two hyperglycemic clamps (14], with or wlthout GLP-1. 
Synthetlc GLP-1 (7-36] amlde was purchased from PolyPeptlde Laboratorles (Wolfenbuttal Germany), and tha 
same lot number was used In all studles. GLP-1 was the rate of 0.4 pmol Kg- 1 mln-1, accordlng to Nauck et al. 
(15]. 0uring the hyparglycemic clamp, the level of glyoemia was levelled at 15 mmol/1. 
SubJects were admltted to the research centre the evenlng before the experlment. AII subjects recelved an 
105 evening meal and recelved a contlnuous low-dose lnfuslon of lnsulin to normaliza plasma glucosa. The lnsulin 
lnfuslon was adjusted ovarnlght to malntaln blood glucosa betwaen 4.4 and 7.2 mmoljl and stopped 2 hours 
before the start of each experiment. 
After a 12-hour overnight fast. subjects were placed In a supina comfortable position with a room temperatura 
between 20 º and 24 •c. lntravenous llnes were Insertad lnto a large antecubltal veln of 1 arm for lnfuslons and 
110 lnto a dorsal veln of the contralatera l arm for blood sampling. Patency was preservad wlth a slow salina lnfuslon 
(0.9% NaCI). The study began after the subjects had restad for 30 minutes. 
0uring each clamp, at baseline and at 1 and 2 hours, glycemia, insulin, FM0, plasma nitrotyrosine, 8-iso-
PGF2a.GLP-1 (active 7-36), IL-6 and ICAM-1 plasma levels were measured. 
Blochemlca/ Mea5urements 
115 Cholesterol and triglyoerldes were measured enzymatically (Roche 0iagnostics. Basal, wltzerland). H0L-C was 
estlmated after the precipitation of apolipoproteln B with phosphotungstate/ magneslum (16]. L0L-C was 
calculated after llpoproteln separatlon (16]. Plasma glucosa was measured by the glucosa-oxidase method, HbA1c 
by HPLC, and insulín by mlcropartlcle enzyme immunoassay (Abbott laboratorles, Wlesbaden, Germany). 
Nltrotyroslne plasma conoentratlon was assayed by enzyme~lnked lmmunosorbent assay (ELISA), recently 
120 validated by our laboratory (16]. Plasma 8-iso-PGF2a (Cayman Chemical, Ann Arbor, Michigan, USA.), ICAM-1 
(Brltlsh Blo-technology, Ablngton, 0xon, UK) and IL-6 (R&D Systems, Mlnneapolls, MN, USA), were determinad wlth 
commercially available kits. GLP-1 (active 7-36) was measured by a radioimmunoassay kit 
125 
(Península Laboratorles, Belmont. CA. USA). FRAP was measured accordlng to Benzle et al. (17Jand TRAP 
accordlng to Ghlselll et al. (18]. 
Endothelial functlon was evaluated measurlng the FMD of the brachlal artery (19). Al the end of each test, the 
subJects restad quletly for 15 min. Then, sublingual nltroglycerln (0.3 mg) was admlnlstered, and 3 mln later, the 
last measurements were performed. Response to nitroglycerln was used as a measure of endothellum-
lndependent vasodllatlon. 
Statlstlcal analysls 
130 Data are expressed as Mean ± SE. The sample slze was selected accordlng to previous studles (9,10,20,21). The 
Kolmogorov- Smlrnov test dld not show any slgnlflcant departure from normallty In the dlstrlbutlon of varlance 
values. Comparisons of basellne data among the groups were performed uslng an unpalred Student's t-tesl The 
changas In variables durlng the tests were assessed by two-way AN0VA wlth repeated measurements. lf 
74 
T EXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
dlfferences reached statlstlcal slgnlflcance, post hoc analyses wlth two-talled palred t test, uslng Bonferronl's 
135 correction for multiple comparisons, were used to assess differences at individual time periods during the study. 
Statistlcal slgnlflcance was deflned as p < 0.05. Ali analyses were conducted uslng SPSS verslon 9.0 (SPSS lnc, 
Chicago, IL, USA). 
Results 
With the MedDiet, FRAP, TRAP and FMD significantly increased, while nitrotyrosine, 8-iso-PGF2a, ICAM-1 and IL-
140 6 slgnlflcantly decreased {Table 1). There was no change wlth the control dlet (Table 1). 
At baseline, In both groups, during the clamps without GLP-1, the concentration of this hormone remalned 
unchanged, whlle lts concentratlon was constantly hlgh when lnfused (Figures 1 and 2). lnsulln concentratlon 
increased in both groups during the hyperglycemic clamp, and its increase was sign ificantly higher during GLP-1 
lnfusion (Figures 1 and 2). Durlng both clamps, wlth or wlthout GLP-1, an lncrease In nltrotyroslne, 8-lso-PGF2a, 
145 ICAM-1 and IL-6, and a decrease In FMD were observed at 1 h and 2 h (Figures 1 and 2). However, at both 1h and 
2h, the values of nltrotyroslne, 8-lso-PGF2a, ICAM-1 and IL-6 slgnlflcantly lncreased, whlle the values of FMD 
slgnlficantly decreased in the clamp wlthout GLP-1. as compared to the values observad during the clamp with 
GLP-1 (Figures 1 and 2). 
.. 
l • • 
.. 
t~ 
1 j" • •• ¡ 
• .. _ .. .. - .. . 
• n 
t " ~¡ --.. , e, l • ~ ~.( • C o., I .. 1/ 1 • "--i:f' <i •li r'~·--"t· 
' ., r-••-+--•, ¿ ___ ~ . {§ C§ • •• -- .. .. - .. • 
, .. • • § · t 
l ... /'1·---.¡ 1: r-~, • o / 0' o i. , ..o- --o ~ --/ J-----1 i NO // ¡ ___ ¡ ¡¿/ e e ¿ . . ~--·6 ----~-ét et 
i .. .,. • - .. .. - .. .. - A--i . . ~--•! i 1/4Q___(I rt 1"" ::--,or¡--·-Ó rt } no V-¿ • . ~--.... . . 
J .. ---·! ! J-----· -· . ~~ ' r---t --1s ¡..-?-·- " u t§ ... .. ...... .. ,. ..... . . 
Rew• 1 Glymffllt. a.,.1, fMO, rie,cnyrosste,, l,-IIO#Cifh.. hwu..lf\ ll~ Uld ICAM·1 dl.angu 4utngo büel,._ ti,pe,9'/Cewlll6t dMnp 
r,,t,w -glt):ludMb-,¡~dN!tp+<Ll'-1 !,,,.. _/,H-~•~-ModtliftlN._DOAl>lldt ot,nglt)¡ 
Hypttg~d ...... •Gl.JL1 at•MtdDlll lf'IIIM!fUln (bllldtMtllll't.f,01Qll.f,-l'I""◄~'! F 1 0" h~bt-a •,>< 1"'N1il p< 
"' ~ .,,.'f'!'Y e:a ""'l'1 
75 
TEXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
• • 
>'-----------
¡ IIO •t 
i •: ._I ____ -_ .... __ 
• , . •• 
• 
• .. ,. • • • .. 
... ... 
.. '------------• •• • ,. , . 
"" 
• • 
100 ,._ _________ _ 
b: • • , .. 1 1 111 JI 
n,... 2 Gl)oooffl-. a.l'• I, ,MO, IWIIOl)'IO>n-. a..to-PGfl4 lnoulf\ IL~ ord CAM-1 dlong .. dwlng: ~ no l,ypo,!h<fflllc damp 
{..t,i .. ,,_glotl; lloi«lnt hl'P"IJ!yoomlc clo"'I'• GU'-l ~ hoe i,quo.-1: H1'PO'll,,..,.,.. <lomp •'-' Con1rd d11tl-llon lblock lri"'!lle); 
HYl)89!y(,fmlc dlfflP-GU'-l .... Conaol el« 1-lblodt,q..,.¡. Ola .. ~ ....... E , o<O<ll .. bUli 'p<(J II Y1 .... 
lp o. "',.,,,.,_ canp 
Following the MedDiet intervention, similarly to the baseline, at both 1 h and 2 h, the values of nitrotyrosine, 8 -iso-
150 PGF2a, ICAM·1 and ll·6 slgnlflcantly lncreased, whlle the values of FMD slgnlflcantly decreased In the clamp 
without GLP-1, as compared to the values observed durlng the clamp with GLP-1 (Figure 1). However, the same 
values of glycemla were less effective In produclng oxldatlve stress and endothellal dysfunctlon after 1 month of 
the MedDlet. Slnce the basal values before and after the MedDlet were slgnlflcantly dlfferent, the t. between the 
basal value and the value at 1 h and 2 h during each clamp, with or wlthout GLP-1, were compared to that In the 
155 prevlous clamp (Figure 3). Of particular lnterest, hyperglycemla was less effectlve In worsenlng oxldatlve stress, 
FMD and inflammation after the MedDlet comparad to the previous clamp (Figure 3). At the same time, after the 
MedDlet, GLP-1 lnfuslon was more ettectlve In reduclng oxldatlve stress and lnflammatlon and In protectlng FMD 
from the acule effects of hyperglycemia. Furthermore, after the MedDlet, GLP-1 lnfusion was accompanled by a 
slgnlflcant lncrease In lnsulln secretlon at both 1 h and 2 h (Figure 3). 
160 There was no difference between the results of the clamps at baseline and after the control diet (Figure 2). No 
difference was found In endothellum-independent vasodllatatlon in all the studies. 
76 
TEXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
A 8 
• 
1 
l 
1 - ·- -- --, ,. H a 
º' º' 
cu 02 
o o ,. ,. 1. ,. 
,.., 100 
IO .. , . • 
o ~ • ,. 
1• ,. 2• 
>000 1000 • • 
no • • ''° ... -JSO uo 
o • ,. ,. ,. ,. 
110 110 
IS ts .. .. 
IO 
.. 11..:._ 11...:_ .. 
ID 
11, lh l h lh 
100 ,co 
lO !O • • 
• • ~ • •• , . '. ,. 
f19 .... JA Chon<JH b«to,un ba>elrl♦ Sld •llordlrt lnltNffltll01' A ,_11< ~ - lh ACI""' dWtgtJt'lf',f), ,,._..... 
....,.J'v,. "'·"' +.,.; C> .... d ""11 tia<•""' ~)P"'Q,......., ~...., 'f"' ""6TV!l arel "f:"WOMC<lamp••* V..0--"1 11\1 ....... 0I 
blln mi ""'l 8 "'""'r .. ~ t,,"'...,"" A el m• ctu,v• .., i'" tl MTOf\"omt> 8•<.>fGF)A ff.&,\ l~ • nd C.W d.uc;¡ ti-Ir~..., 
,.,.P"'!l'I<'•"""' .ll'"CI- QJ> t lg:fi eot.n,nJ -"'d ~.,,,,..,.,, dan'p • Gl"1 - ~•,rJO,t .,..,..,,,.,, t»ct a,I.Jrrri •p <0-01 
Dlscusslon 
Thls study shows that the MedDlet uslng olive oll can nmprove endothellal dysfunctlon, lnflammation a nd oxidative 
stress In type 2 diabetes. Whlle severa! papers are avallable on the effects of the MedDlet on these parameters In 
165 metabolic syndrome (22,23), In hypercholesterolemla (24) or In healthy subjects 125], lt Is quite surprislng that, 
untll now, only one paper has reported on the effects of the MedDlet on endothellal dysfunctlon In tYPe 2 diabetes 
121). Slmilarly, only one study, includlng only a small number of type 2 diabetic patlents, has reportad on the 
beneficia! effects of the MetDlet on lnflammatlon [26]. These papers, however, only almed to show the potentlal 
beneflts of the MedDlet on diabetes (2i,26]. However acute hyperglycemla alone can dlrectly produce damaging 
170 effects such as endothellal dysfunctlon and lnflammatlon, and Is consldered a n Importan! lndependent contrlbutor 
toward the development of dlabetlc compllcatlons, partlcularly cardlovascular compllcations (2-27]. Severa! 
studles confirm that acute hyperglycemla works by generatlng oxidative stress (2,10,28-30]. 0ur study, for the first 
time, shows that the MedDlet, uslng olive oll, can counteract the effects of acute hyperglycemla. The effects of the 
MedDlet are convlnclngly related to lts capaclty for lncreaslng antloxldant defensas. As already reported In a 
175 prevlous larger study 15], thls dlet lncreases both the plasma FRAP and TRAP In subJects. Thls effect could account 
77 
TEXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
for the reduced generatlon of oxldatlve stress observed durlng the hyperglycemlc clamp and, therefore, for the 
reduced impact of acute hyperglyoemia on endothelia I function and inflammation. 
Also of relevance, In our oplnlon, Is the effect of the MedDlet on GLP-1 actlon. 
lt is now well recognized that GLP-1 activity is partially reduced in poorly controlled diabetic patients. This has 
180 been reported for fnsulln secretlon and endothellal functlon (10,31). The actlon of GLP-1 can be restored by 
lmprovlng glycemic control (10, 31]. Two mechanisms have been suggested to explaln this resistance to GLP-1 
action in diabetes: the activation of PKCS, induoed by hyperglycemia, able to reduce the expression of GLP-1 
receptors [32); and the generatlon of oxldatlve stress by hyperglycemia (10). Nevertheless. the two proposed 
mechanlsms -PKCS actlvatlon leadlng to the reductlon of the expresslon of GLP-1 receptors, and oxldatlve stress 
185 generatlon- could be convlnclngly correlated, as lt Is well known that PKCS Is actlvated by the free radlcals [33]. 
Therefore, it has been suggested that hyperglycemia induces such a GLP-1 resistance, mainly through the 
generatlon of an oxldatlve stress [10). Thls hypothesls has been confirmad In vivo showlng that the GLP-1 actlon 
can be fmproved by an antioxldant, vltamln C (12,13). The results of the present study, In our opinlon, not only 
conflrm thls flndlng, but may also have a significan! cllnlcal lmpact. Whlle the chronlc use of vltamln C may not be 
190 a definitive solution (34), the evidence that the MedDlet lmproves GLP-1 action on both insulln secretion and 
endothelial dysfunction in diabetes might shed new light on the daily management of this disease. 
0ur study has several llmltatlons. The number of subjects was quite small (2 groups of 12 patlents each) and 
thelr lncluslon was very selective, requlrlng that particlpants be free of compllcatlons and not taking statlns, and 
that they be non-smokers and non-drlnkers. Thls llmlts the extrapolatlon of our research to the general populatlon, 
195 which is obviously much more heterogeneous. 
Genetlc lnfluences on our data cannot be excluded. The assoclation of the FTO-rs9939609 and MC4R-
rs17782313 polymorphisms with type 2 diabetes depends on diet, anda high adherence to the MedDiet is able to 
counteract a genetlc predisposltlon to cardlovascular disease (35). Moreover, the Med0iet. partlcuiarly when using 
virgln olive oll, can exert certaln health beneflts via changas In the transcriptomic response of certaln genes 
200 related to cardiovascular risk [36). 
In concluslon, thls study conflrms that a MedDlet uslng olive oil lmproves endothelia l dysfunctlon and 
lnflammation, concomltantly increasingantloxldant defensas and decreaslng oxldatlve stress. However, for the 
flrst time, thls study shows that a MedDiet can countert>alance the negatlve effects of acute hyperglycemia on 
endothelial function, inflammation and oxidative stress, and can recovar the protective action of GLP-1, not only on 
205 lnsulin secretlon, but, more lnterestlngly, also on endothellal functlon and lnflammatlon In type 2 diabetes. 
Considering that both acule hyperglycemia [21 and a reduced protective effect of GLP-1 (37) can impact the 
development of cardlovascular compllcatlons, these results can be considerad very relevant for the cllnlcal 
management of diabetes. Future studles are needed to conflrm thls hypothesls. 
Abbrevlattons 
Med0iet: Medlterranean diet; GLP-1: Glucagon llke peptlde•1; MUFAs: Monounsaturated fatty aclds; FM0: Endothellal flow 
medlated dllatatlon; 8-1so-PGF2a: 8-lso prostaglandln F2alpha; IL"6: lnterleukln-6; ICAM-1: lntercellular adheslon molecule-1: 
FRAP: Ferrlc-reduclng antloxldant potentlal; TRAP: Total radlcal-trapplng antloxldant para meter. 
Competlng lnterests 
The authors declare that they have no competlng lnterests. 
78 
T EXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
Author detells 
1I11stltut d' Investigación Blomédlques August PI I Sunyer (IDIBAPS) and Centro de Investigación Blomedlca en Red de 
Diabetes y Enfermedades Metabollcas Asociadas (CIBERDEM), Hospital Cllnlc. C/ Rosselló, 149-153, 08036 Barcelona, 
Spain. 2Divlsion of Metabolic Diseases, Center of Excellence for Cardlovascular Dlseases, 2ndUniversity of Naples SUN, 
Naples., ltaly. 3Experlmental Models In Cllnlcal Pathology, INRCA-IRCCS Natlonal lnstltute, Ancona, ltaly. 4Department of 
Cardlovascular and Metabollc Dlseases, IRCCS Gruppo Multlmedlca. Sesto San Glovannl, MI, ltaly. 
Received: 20 September 2014 Accepted: 3 October 2014 
References 
1. Chaturved i N: The burden of diabetes and its compllcatlons: trends and lmpllcatlons for lnterventlon. Diabetes Res Clln 
Pract 2007, 76(Suppl 1):53-512. 
2. Cerlello A: Hyperglycaemla and the vessel wall : the pathophysloIogIcaI aspects on the atherosclerotlc burden In patlents 
wlth diabetes. Eur J Cardlovasc Prev Rehabll 2010, 17(Suppl1):S15-S19. 
3. BJelakovlc G, Nlkolova D, Gluud LL, Slmonettl RG, Gluud C: MOftallty In randomlzed trlals of antloxldant supplements for 
prlmary and secondary preventlon: systematlc revlew and meta-analysls. JAMA 2007, 297:842-857. 
4. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracla E, Rulz-Gutlérrez V, Flol M, Lapetra J, 
Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñ.oz MA, Sorlí N , Martinez JA, Martínez-González MA, PREDIMED 
Study lnvestigators: Primary prevention of cardlovascular disease with a Mediterranean diet N Engl J Med 2013, 368:1279-
1290. 
5. Zamora-Ros R, Seraflnl M, Estruch R, Lamuela-Raventós RM, Martínez-González MA, Salas-Salvadó J, Flol M, Lapetra J, 
Arós F, Covas MI, Andres-Lacueva e, PREDIMED Study lnvestlgators: Medlterranean dlet and non enzymatlc antloxldant 
capaclty in the PREDIMED study: ellidence lor a mechanlsm of antloxidant tunlng. Nutr Metab Cardiovasc Dls 2013, 
23:1167-1174. 
6. Razquln C, Martinez JA, Martlnez-Gonzalez MA, Mltjavlla MT, Estruch R, Martl A: A 3 years follow-up of a Mediterranean dlet 
rich in vlrgin oilve oíi Is assocíated wlth high plasma antloxldant capaclty and reduced body welght gaín. Eur j Ciln Nutr 2009, 
63:1387 -1393. 
7. Peters A: lncretln-based therapies: review of current cllnlcal trial data. Am J Med 2010, 123(Suppl. 3):528- 537. 
8. Mudaliar S, Henry RR: Effects ol lncretin hormones on beta-cell mass and functlon, body weight, and hepatlc and 
myocardlal functlon. Am J Med 2010, 123(Suppl. 3):519-527. 
9. Nystrllm T, Gutnlak MK, Zhang Q, Zhang F, Holst JJ, Ahrén B, SJOholm A: Elfects of glucagon-llke peptlde-1 on endothellal 
functlon In type 2 diabetes patients wlth stable coronary artery dlsease. Am J Physlol Endocrino! Metab 2004, 287:E1209-
E1215. 
10. Ceriello A, Esposlto K, Testa R, Bonfigli AR, Marra M, Glugliano D: Toe posslble protectlve role of glucagon-like peptlde 1 
on endothellum durlng the meal and evldence for an ·endothellal reslstance · to glucagon-llke peptlde 1 In diabetes. Diabetes 
Care 2011, 34:697-702. 
1i Oeseburg H, de Boer RA, Bulkema H, van der Harst P, van Gllst WH, Sllljé HH: Glucagon-llke peptlde 1 prevents reactive 
oxygen specles-lnduced endothellal cell senescence through the activatlon of proteln klnase A. Arterioscler Thromb Vasc Biol 
2010, 30:1407- 1414. 
12. Cerlello A, Novlals A, Ortega E, Canlvell S, La Sala L. Pujadas G, Bucclarelll L,Rondlnelll M, Genovese S: Vltamln C further 
lmproves lhe protectlve effect of glucagon-llke peptlde-1 on acute hypoglycemla-lnduced oxldatlve stress, lnflammatlon, and 
endothellal dysfunction In type 1 
diabetes. Diabetes Care 2013, 36:4104- 4108. 
13. Cerlello A, Novia Is A, Ortega E, Canlvell S, Pujadas G, La Sala L, Bucclarelll L, Rondlnelll M, Genovese S: Vltamln e further 
lmproves the protectlve effect of GLP-1 on the lschemla-repeirfuslon-llke effect lnduced by hyperglycemla post-llypoglycemla 
In type 1 diabetes. Cardlovasc Dlabetol 2013, 12:97. 
14. De Fronzo RA, Toblt1 JO, Andres R: Glucosa clamp technlque: a method for quantlfylng lnsulln secretlon and reslstance. 
Am J Physlol 1979, 237:E214- E223. 
79 
TEXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
15. Nauck MA, Helmesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W: Preserved lncretln actlvlty of glucagon-llke peptlde 
1 (7-36 amlde) but not of synthetlc human gastrlc lnhlbltor)' polypeptlde In patlents wlth type-2 diabetes mellitus. J Clln 
lnvest 1993, 91:301- 307. 
16. Ceriello A, Mercuri F, Quagliaro L, Assaloni R, Motz E, Tonuttl L, Taboga C: Detection of nltrotyroslne In the diabetic 
plasma: evldence of oxldatlve stress. Dlabetologia 2001, 44:834- 838. 
17. 8enzle IF, Straln JJ: Ferrlc reduclng/antloxldant power assay: dlrect measure of total antloxldant actlvlty of blologlcal 
flulds and modlfled verslon for slmultaneous measurement of total antloxldant power and ascorblc acld concentratlon. 
Methods Enzymol 1999, 299:15-27. 
18. Ghlselli A, Serafinl M, Malani G, Azzinl E, Ferro-luzzl A: A fluorescencebased method for measuring total plasma 
antloxldant capablllty. Free Radie Blol Med 1995, 18:29- 36. 
19. Correttl MC, Anderson TJ, Benjamln El, Celermajer D, Charbonneau F, Creager MA, Deanfleld J, Drexler H, Gerhard-
Herman M, Herrlngton D, Vallance P, Vita J. Vogel R: lnternatlonal Brachlal Artery Reactlvlty Task Force: Guldellnes for the 
ultrasound assessment of endothelialdependent 
flow-mediated vasodilation of the brachial artery: a report of the lnternational Brachial Artery Reactivity Task Force. J Am Coll 
Cardlol 2002, 39:257- 265. 
20. Marln e, Ramlrez R, Delgado-Lista J, Yuberc>-Serrano EM, Perez-Martlnez P, carracedo J, Garcla-Rlos A, Rodrlguez F, 
Gutlerrez-Marlscal FM, Gomez P, Perez-Jlmenez F. Lopez-Mlranda J: Medlterranean dlet reduces endotellal damage and 
improves the regenerative capacity of endothelium. Am J Clin Nutr 2011, 93:267-274. 
21. Ryan M, Mclnerney D, Owens D, Collins P, Johnson A, Tomkin GH: Diabetes and the Medlterranean dlet: a beneficial 
effect of olelc acld on lnsulln sensltlvity, adlpocyte glucose transport and endothellum-c:lependent vasoreactlvlty. QJM 2000, 
93:85-91. 
22. Esposlto K, Marfella R. Clotola M. DI Palo C, Glugllano F, Glugllano G, D'Armlento M, D'Andrea F, Glugllano D: Effect of a 
mediterraneanstyle diet on endothelial dysfunctlon and marikers of vascular inflammation in the metabolic syndrome: a 
randomized tria l. JAMA 2004, 292:1440-1446. 
23. Glugllano D, Ceriello A. Esposito K: The effects of diet on tnflammation: emphasls on the metabolic syndrome. J Am Coll 
Cardlol 2006, 48:677-685. 
24. Fuentes F, López-Mlranda J, Sánchez E, Sánchez F, Paez J, Paz-Rojas E, Marín C, Gómez P, Jlmenez-Perepérez J, OrdovásJM, Pérez-Jiménez F: Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men. Ann lntern 
Med 2001, 134:1115-1119. 
25. Fuentes F, López-Mlranda J, Pérez-Martínez P, Jlménez Y, Marín C, Gómez P, Fernández JM, Caballero J, Delgado-Lista J, 
Pérez-Jlménez F: Chronlc effects of a hlgh.fat dlet enrlched wltlh vlrgln olive oll anda low-fat dlet enrlched wlth alpha~lnolenlc 
a cid on postprandlal endothellal functlon 
in healthy men. Br J Nutr 2008, 10:159-165. 
26. Salas-Salvadó J, Garcia-Arellano A, Estruch R, Marquez-Sandoval F, Corolla D, Fiol M, Gómez-Gracia E, Viñoles E, Arós F, 
Herrera C, Lahoz C, Lapetra J, Perona JS, Muñoz-Aguado D, Martínez-Gonuílez MA. Ros E, PREDIMED lnvestlgators: 
Components of the Medlterranean-type food pattern and serum lnflammatory markers among patlents at hlgh rlsk for 
cardlovascular dlsease. Eur J Clln Nutr 2008, 62:651-659. 
27. Cerlello A. Zarlch SW, Testa R: Lowering glucose to prevemt adverse cardlovascular outcomes In a crltlcal care setting. J 
Am Coll C<lrd iol 2009, 63(5 Suppl):S9- S13. 
28. Beckmim JA, Goldflne AB, Gordon MB, Creager MA: Ascorbate restores endothellum dependen! vasodllatlon lmpalred by 
acute hyperglycemla In humans. Clrculatlon 2001, 103:1618-1623. 
29. Marfella R, Quagllaro L, Nappo F, Cerlello A, Glugllano D: Acute hyperglycemla Induces an oxldatlve stress In healthy 
subJects. J Clln lnvest 2001, 108:635- 636. 
30. Grassl D, Deslderl G, Necozlone S, Rugglerl F, Blumberg JB. Stornello M,Ferrl C: Protectlve effects of fl avanol-rlch dark 
chocolate on endothellal functlon and wave reflectlon durlng acute hyperglycemla. Hypertenslon 2012, 60:827 - 832. 
31. Herzberg-Schiifer S, Henl M, Stefan N, Hiirlng HU, Frltsche A: lmpalrment of GLP1-lnduced lnsulln secretlon: role of 
genetlc background, lnsulln reslstance and hyperglycaemla. Diabetes Obes Metab 2012, 14{Suppl 3):85- 90. 
80 
TEXTO PARA ACTIVIDADES COMPLEMENTARIAS DE LAS GUIAS 3 Y 4 
32. Mima A, Hlraoka-Yamomoto J, LI Q, Kltada M, LI e, Geraldes P, Matsumoto M, Mlzutanl K, Park K, Cahlll C, Nlshlkawa SI, 
Rask-Madsen C, Klng GL: Protectlve effects of GLP-1 on glomerular endothellum and lts lnhlbltlon by PKCíl actlvatlon In 
diabetes. Diabetes 2012, 61:2967-2979. 
33. Quagliaro L, Piconi L., Assalonl R, Martinelli L, Motz E, Ceriello A: lntermittent high glucosa enhances apoptosis related to 
oxldatlve stress In human umbilical vein endothellal cells: the role of proteln klnase C and NAD(P) H-oxldase actlvatlon. 
Diabetes 2003, 52:2795-2804. 
34. Frel 8, Blrlouez-Aragon 1, Lykkesfeldt J: Authors' perspectiva: What Is the optlmum lntake of vitamln C In humans? Crlt 
Rev Food Sel Nutr 2012, 52:815-829. 
35. Ortega-Azorín C, Sorlí JV, Asensio EM, Col tell O, Martínez-Oonzález MÁ, Salas-Salvadó J, Covas MI, Arós F, Lapetra J, Sorra• 
Majem L, Gómez-Gracla E, Flol M, Sáez-Tormo G, Pintó X, Muñoz MA, Ros E, Ordovás JM, Estruch R, Corella D: Assoclatlons of 
the FTO rs9939609 and the MC4R rs17782313 polymorphlsms wlth type 2 diabetes are modulated by dlet, belng hlgher 
when adherence to the Medlterranean dlet pattern IS low. Cardlovasc Dlabetol 2012, 11:137. 
36. Castañer O, Corella D, Covas MI, Sorlí JV, Subirana I, Flores-Mateo G, Nonell L, Bulló M, de la Torre R, Portolés O, Filó M. 
PREDIMED study investigators: In vivo transcriptomic profile af1er a Mediterranean diet In highcardiovascular risk patients: a 
randomlzed controlled tria!. Am J Clln Nutr2013, 98:845-853. 
37. Slmsek S, de Galan SE: Cardlovascular protectlve propertles of lncretlnbased theraples In type 2 diabetes. Curr Opln 
Llpldol 2012, 23:540- 547. 
do,10. 1186/sl:1933-01•-0140-9 
ate thlunki. a,: Crt..io tt <JI Tho pnua,~ rft'tc:t of !he! 
Medltemnca, di" on ..-dothelal ,.,Jane• to GLP 1 In !)!)e 2 
d!l~ln. l p,cl!mlnl!y repon. CA,c,r,.l)k"'11 PJ\l<I, t,,,¡y ;'01• 13 l"ll 
8,1 
Submlt your next manuscrlpt to BloMed Central 
and take full advantage of: 
• Con~• Qfl,ll,w tubn11s1,on 
• Tho<ough _, rwlow 
• fito fS-W Cl>MV'at'1U CM' <olot- flour. ch.ttoet 
• 1rn1Mdilt• pubhc:atJOft on aa.pu1fla 
• lndutiaft., ,.,_ CAS. seo-Md Goool• -
• __,, "'hi<h Is lroely ••"""l,j• l ar ..dhtnbutlon 
Subn'lft yout nunu,alpt ~ 
wwwblomedcentralcCJrM.ttbmíl ( ) ... Me,I Cernnil 
Fa>ntueh , r al BMC Gamo,nrtrolo9y 2014, 14 19 
hnp://www.blomedcenual.com/1471•230X114119 
GUIAS 5 Y 6- TEXTO COMPLETO 
(a;c 
Gastroenterology 
RESEARCH ARTICLE Open Access 
Endoscopic findings in uninvestigated dyspepsia 
Jacob Jehuda Fa1n1uct,'.l', Fernando Marcuz Silva1, Tomás Nava,ro-Rodnguez2, Ricardo Conea Barbutr, 
Oaud,o Lyoul Hash1m010', Alessandra R11a Asayama Lopes Rossin?, Marcio Augusto D1n1z' and Jaime Natan Eisig2 
Abstract 
Background: lt 1s 1mportan1 to lnow 1he causes ol dyspepsia 10 cs1abbsh the 1herapeu11c approach. Dyspcps¡a ,s a 
frcquent syndrome 1n our country. where 1here are restnaions to endoscooy and high prevalence cl. Hetlcobocter 
f)'tlon /1-1. py/0<1) mfea10n. ThlS srudy a,med to assess 1he eodoscop1e flndlngs et 1he synclrome, 1n an ouipa11en1 
saeen ng drnlc el. a ·cruary hospi1al In Sáo Pauo. 
Methods: OJtpetJcnts w,th umnvestlgaied dyspepsla, acc.ordlng 10 Rome ftl cnteria, anWvered a dyspeps¡a 
questiOnnaue and underwent csophagogamoduodenoscopy. The Rapid Ureasc TeSI was applied 10 lragrnents of 
the antral mucosa and epidemlolog,cal daia were colleaed from the stud,ed popula110n. Oqarllc dyspeps,a 
fü-.:l,ngs were analyzcd with d,ffcrent variables to \<e<rfy statisticaJly sign1ficam assodations. 
Results: Three hundred and six patient:s wcre ,ncluded and 282 were analyzed in the srudy. Thc mean age was 
44 years and women comprlsed 6S% et the sample. Fony-flve percent or the patients reponed alarm symp¡oms. 
Funaional dyspep!.la was found 111 66% ol thc paucnu (20'llt with notmal endoscopy results and 46% w,th gasmLJ5), 
18% hade.ERO and 13% had ukers (ciiodenal ,n 9% and gastnc ,n 4%) Four cases of gasmc adenocarcinoma were 
1denotied (14%). one withoui alarm charaaens1ics, 1 case of aderiocaroroma oí 1he dtstal esophagus and 1 case c:J 
gasmc fymphoma The prevalence oí H fltlorl was 54% ard u,feaion. age and smolcing status were aSSOCJ.3red w,th 
organ1e dyspeps1a The age ci 48 years was ,ndicauve el. alarm srgns 
Conclusions: The endoscopc diagr,os,s oí uninvesngaied dyspepsia ,n cu SE'rnng showed a ¡redomlnance ol 
functlonal disease, whereas cancer was an uncommon ftnd1ng, desp,te the high prevalence of 1-l py/Ofl Organrc 
dyspepsla was assodared v.1th Infea10f\ age and smokJng sta1us. 
Keywords: Dyspepsra f,ndrngs, Esophagrns. Functlonal dyspeps,a. Gasinc cancer, Pept,c ufcer 
Background 
Dyspepsia ís a prevalent complaint ín general practicc 
and gastrointc<tinal clini~ [1•51, with a pre"alcnce of up 
to 40~ among adults In Braxil [ 6). O)'spep.<la represents 
up to 83"6 o( all prim•ry care physidan visits and cau_,es 
huge economic costs to patienis and to the economy 17). 
Rome UI guidellnc smtcs thnt dyspepsla is non-re0ux 
predominant pain or discomfort in the uppcr abdomen 
and the patlenis must also have one or more of the follow-
ing four symptonu: postprandial fullne,;s, c3rly !llltintion. 
ep,gastralgb and epigastric burnlng. Symptom onset musu 
• C'A•"'l>(¡rlo:-nc,, ~11r11d'l.,..pm.,._,, h< 
0Hn:10n tJ (In.al M('d,~ and ~lA<4 1ncofHcy.p_g tbi Clnt~ 
da hc<Ída:I• do MM< .... d.> U5P, Slo Paulo, Br,111 
\1<1spt11 do, º"~as .s., ra~ c1, Medi0N do u .. ,,...ltlx1c, "º 1.1o 
"""'1 Av o, l-d•úrvatlo /,qR, 155 • Co,quencesar ~Po~,;;, 
lfnvl 
fo lr.-r d a~o, •nfofl'Mm:Jn •$~»,ole-. me CM ofthc JndC 
have ocCUJTed at least sb: month.~ prior to dJagnosls [8]. 
Only 75'16 oí thc dyspcpsia expcrts, 73'lo of gastrocnlcrolo-
gists and 5~ of primary carc pmvidcr. adhere to dy.;pep-
sn best practiccs; so "dyspepsl3" means difTercnt thrngs 
to different prO\idcrs. Without a common diagnosnc lan-
guagc, genernl prnctitloners may ~ umbte to pmvide ad-
equate treaunent foUowing common dyspepsfa guldclines. 
(9]. The rapid introductionof ncw diagnostic crtcrb for 
dyspepsla has made very dlfllailt or vlnuall)' lmposslble to 
compare prcvalence rotes from different pcrlods or geo-
gn¡phic rt'glon.~ ( 101, Because ruucturnl upptt gaso-ointt,M;• 
tina! (UGI) tract dlseascs, such tlS pcptlc ulcer, ero!live 
c,;ophagitis, lummal strictures and malignanc:y CM coursc 
wih dyspcps!a, esophagogastroduodenoscopy (l:.GD) is 
the dbgnosdc proccdurc, of choice to differcnti~tc paticnu 
wrth orgnnlc from thosc w1th functJonal dyspcpsn 111] 
Although it is possible to propose endoscopy as the initial 
( ) BioMed Central 
OM.4 , .. uh.dldi!. lameil, lo~ Ú'l1tr.: Ud Til1-• '1 C'9I f..Cl!u.l"'tde ,JWlb.J.nJ .,. th:• tti~CC t' IJ" ~ 
ColintatS Awiluton l«rrw (h:11-,/A~,m~~ 't\l'IOl ocrmcs Jl~k:lrJtJ~ ~lllr b.Jaan.MU 
lnlfOd,.CJo(l f'l .litlJ meck,n\ ~',}\,'dt,J l_t,t tltiqNl'llr(Jk a '1~ cgd 
82 
Faintuch ~I ol BMC GartiwnttlO/ogy 2014, 14:19 
h11p://www.blomedcenwl.com/1471-230)(/1 <V19 
s1rntegy for d)-speps1a {J 2J, thc establishment of this pro-
cedure for every dyspeptic paliMI may not be practica! ap• 
proach, as the high pl'l'\'lllcnce of the ~dromc will result 
in very high costs to any health sr,tem l 13). Morcovcr. the 
diagnostic proccdw-e and its oost eff«tivcness musl be 
considenng that a lnrge number of uninvestigated dyspep-
sia are functional cases [14J. 'lhtL~. the use of endosoopy 
in the mnnagcmmL of uninvestigated d)':,pepsla rmutlns o 
contToversial issue worldwide l 11 J. l'he frequenc)' of unDl• 
,•estlgated dyspepsia varies conside:rably in dlfferent 
populations and such dilferences may be related to true 
diffürences m the frequency of the condlt1on or the critena 
~ to dl3gnosc dyspepsla l 15). 1 nternaUonal medica! 
practia- and academic association.~ h:J\'e rccommcndcd 
usmg alarm s1gns with or without age hmits. usually set at 
50--55 )"ro!S, to select dyspcptic patients for enda;oopy 
L16). The predictlve values to be 11$00 in the diagnosi,; of 
uppcr gastromtcstalal pathology have bccn extensi\'Cly 
studled. but the re,'lllts are lnconsistent. especially be-
cause the majoril)• oí previo\1$ studlc,s were can-icd out in 
Europe or North America 116-18). As for our countTy, the 
,·cry high prevalence of H. pylori infoction l 19-22), whlch 
requires a complcx and expcnsive treatment for a large 
number of 1nd1viduals and the low avaílabílity of noninva-
sive tests for the diagnosis of H. p)'lori mfection make the 
test and treaL approach unfcasible. The age lndlcation for 
endosmpy ha.~ not bren detenruned in our country and 
Lhe hmited avru.lability of this procedure does not allow it 
to be requestcd as thc initinl appmach. 
By prospc:ct.ively following consecutlve patlents wlth 
w,uivcstigated dyspepsi:I 111 an oulpaticnl scrccrung dime 
&om a tcrtiary hospitnl, this study aimcd to = thc 
diagnostic effecti,-encss of EGO, in a de\-eloping country. 
Methods 
Study padents and setting 
Thls prospecti,-e obscrvational study was carrled out in 
a tcrtfary hospital, which provides open-access service to 
cndoscopy. From Scptember 2008 and Septcmbcr 2011. 
conseculive adult outpatients who presentcd \\ith unlnves• 
og¡itcd dyspcpsia were scr~ned for el1gibility. AII study 
partiopants wcre S)'Slelnaticall)' e\"3luated before undergo-
ing endoscopy. The paticnts wcre intervlewed 10 detem1lne 
the presencc of alan-n s~toms, indudmg unintcnded 
wclght loss (defined as decruasc of more tlu1n S'K, of ori-
ginal body wt!ight in threc months), S)'tllptonu suggestive 
of upper gastrointestinal bleeding and dysphagl3. Oldcr 
age, pn.-sence of mass or lyrnphadcnopathy and family 
history of upper gastrointestinal cancrr wen, not indudoo 
as alarm charactcn.o;tiG. Symptom mumsity was detcr-
mínau, by the Leed., D~'Spepsia Qu~onnaire (23) and 
epig;istmlgo wns con&idered tJ'Pical whcn pain wa, re• 
hevcd by food or acid suppression or clockmg wns prcsent. 
lñc presenl study was carried out by only two physlclans, 
83 
GUIAS 5 Y 6- TEXTO COMPLETO 
l>age 2 of7 
who madc the lnterviews in person "1th the outpaoents 
using a stnndardized qucslioMaire. l'he upper digeslive 
endoscopy wa~ carricd out ",th a snmdard elcctronlc 
videoendo.~pe b)• two exper1enced cndoscoplsts. no later 
Lhan 20 dll)'S after thc lntc,rvicw, to allow tme for thc 
symptomatic use of antaods. H. pylon detcrmlnaoon wa~ 
performed by the Rapid Urea,;e Test, validated in our 
COWllry 124). 
lnduslon crlterla 
Epig;istralgin or epig:u;tric buming lasong for at lc:ist three 
months. w!th symptom on.~et having occun-ed at least 
six months beforc, at lcasi once a weck and/or at post• 
prandinl fullness or early satiation. for thrce months, with 
¡ymptom onset that st:arted at lrost six months bdore. at 
least once a weel.. Patlcnts should be yow1g~ than 90 and 
older th:in 13 )'l?ll1'5 old. 
Exdusion crlterla 
Exdusion criterla lnduded predominant symptoms of g:i.~-
trocsophageal rdlux dlsease (GERD), ~ymptoms outside 
thc cpigastrlum, othcr predominant d)'Smotillty syrnproms 
(na11$ea and vomiting), use of NSA10s (including low dOlie 
treatrnent) up to one week before srud)' lndLL~íon, use 
of proton pump inhibitors or H2-blockers for more 
than two wt-cks, bd'ore study enrollment, prescnce oí 
systemic decompensated dtsease (conge$t!,-e heart fail-
ure, coronary heatt dlscase, Liver frulure, dtabetcs melli-
tus. thyrold diseasc. acute or chronlc respiratory fuilure, 
hcmatologlcal diseases), presence of ma¡or psychlatnc 
disorders, impediment to endoscopy and difficulty for 
the patient to w,derstand the aims and procedul'l!S of 
the study, 
Ethks 
'loo study was approved by the 1:'.thics Comnuttee for 
Anruysis of Research Pmjeas - CAPPesq • Oinlcal Dirtttion 
of thc Hospital and the Fticulty of Medicine, Uroversity of 
SAo Paulo. Writtcn ,nfon-ned conscnt was obtain<.-d írom 
the patienls prior lo study particlpation. 
Statistlcal analysls 
Variables were mcasured as &equency and percenbge 
and thc as.'IOdation between organic dyspcptic ílndmss 
and the variables was deten-nined by fisher's !fil, with a 
p vnlue < O.OS being consldered ~tntistically significanL A 
cutoff for age was obtained though ROC cww. 
Org¡tnic dysp<.'PUC findlngs werc analyud with the var• 
hlbles by simple and multt>le binary logistic regrcssions 
then odd ratios and its 95'\i confidencr mtervals wcrc prc-
.M:nted. A soore for cndoscopy indicatlon was determlncd 
bascd on regrcssion coefficient valucs. Calculotions wcre 
performed usmg R ( !ne R foundation for Statisttcal 
Computing) , venlon 2.15.2. 
Fllntuch ti al. 8MC Gastr0ffltrrol"912014, 14:19 
http:J/www .blomedcentral.cornn 4/ 1·230Xl14/19 
Table 1 Demographlc lnfonnatlons of patients srudied 
P.u.,,,~ ,ndi.dtd 30<> 
Eod»<q,,,:, perfotTT,.d 1112 (!12'/,,j 
...,.,,~,.¡ pyt¡, 144 (~'IS! 
Ag,--rr «1n y.-..n .14 
R..,-.,,., 16 • l!1 
Ay" >4!1 121 (4.Ne,j 
M.tl• 9<" od-1 <'8 (-™!,) 
R.tc:e- wt1t~ .103(72'líl 
8om In s.;., P•ulo 110 (43'111 
Srnol;,rs IS (1911,) 
Results 
Jñree hundrcd slx patknts were includcd, of whkh 282 
were avaUable Cor analysis: 8 patients dropped from the 
study, 5 werc exduded, as tht,y were using of omepra-
zolc at t.he time of thc endoscopy, 4 had their endoscopy 
results lost, 3 refused to undergo endo.<K:opy, 3 under-
wcnt thc endoscopy aftcr more thnn 30 d.trs and one 
h:id a previous abdominal wrgery. 
Patient demographlc data are shown In Table I and 
symptoms are listcd in Table 2. 
GERO {18') and peptic ulcer {13')(,) were the mnjor 
causes of orgarue dyspepsm: there were six e.ases (2i) of 
uppcr gastromtestlnnl cancer (4 gastrlc carcinomas, 1 gas.-
trie l)1nphoma and I csophageal adenocarcinoma) charac-
teriz.ing a total of 96 (34'M patient5 as havmg organic 
Table 2 0escriprion of the symptoms 
5)fflPt0mS 01\><'1 
6 to II mo11hs 
lt03)'dS 
4 to 10 ~""" 
Mo<r lhY1 10 ')e,I> 
Tw,e OI >Vmpl00'6 
Eplg.1>1.r•ig•• 
p .i-prd\d141 rulb .;s 
lnte<1s,1y ol 9o<fn¡10tns 
1>' Id 
l>'odeU!e 
s.,.,..~ 
P,,n •Pf'Ch:lr,, 
T•P" 
A'lpic 
Al•nn 9(1T()t<>mS 
Wl'l9tciollS91~119 
D)'lph.,glol 
144 ()11¡6) 
,~ (2</Wil 
.!S (l}M,) 
28(1~ 
6i(221Q 
1'5 (44~) 
'M (33~ 
101 (3(11,,) 
14 (51111 
11 (4~J 
84 
GUIAS 5 Y 6- TEXTO COMPLETO 
Page J of 7 
Table 3 General endoscoplc findlng, 
f'uritD004 dvll)el>'-'d lllól~ 
NQ<m,I '""""'" ~ª~ 
G.,1111~ IJQ(~ 
Oga'"< ~p,,p,ia 9', 13 4'1fal 
Rdlux """""gllll !.2 08l0 
Pepu: Utt1 38 (Hll, 
w\tllC 12(4~ 
lluoddldl 21it9\llol 
Malgri.>ncy 6 Q,6) 
GdlCC 6<1onotdtdll0'0• 4(1~ 
G.&rot l)'mpt,om, t (0 4'lf,J 
E;o¡-;,49.,al ~ronaru I (O. 4ll,I 
dyspeps1a ('rabie 3 ). Reflux dlsease lncluded cases of ero--
slve csoph.,gitis, Barrett's esoph:igus and c,ophagcal ulccr. 
The spectfic finding, on upper digestive endoscopy are 
summarited In Table 4. Orgnnlc dyspepsla (determlned by 
Table 4 Speciflc endoS<oplc findlngs 
Elopl A!Jt'• 
Non""'""" ~ ¡¡< 
Er011ve í!$Clflhagll> 
11,,,, .. 
UICN 
Ott...,.·· 
.'jom.kch 
G.nn1~ 
fnJI 1lh-arl'\1t0tt, 
E,a.1.e 
Nodular 
Nrophc; 
Ulce, Id(~~ 
fundu1,, todv and •nuu,n 
l'r..pylo,K 
Md)g11.t11c:y 
"""""'di{ ilóm! 
LJIITlph}m• 
Oltlct> 
D.Kxlt-11um 
Ouodenltl, 
Er-..;nlh-m,tw, 
E,o,..., 
Ukl'f 
Olhm 
8~ 
41(1~ 
' in 1'11,¡ 
1 (Q4l,l 
10 14"'1 
186 (<> 111,) 
660~ 
as 001 
l816~ 
1 tn,) 
9(l~ 
H.1'16l 
S (U,w,) 
4 (1 4f,j 
l «J.41Q 
bP'I,) 
31 111\llol 
9 (3'11,) 
11 Ol'IQ 
6~ 
10 (4111) 
'ffon ••OII"' eoophagit6 tN_.,..,. c,oPhoglas: 6 ca,o~ •toPh"Olal 
""1dldla,i. 2<. ..... 
- C)toe" üepiw9"' ftndlny.. Hl>r>J htrnlA. 6 tm•• Polpll __ , """""'gldi: 
2 ..,,., Eiophag .. l ""'IL I Col"- Ret"'tlon cy-,; 1 ,__ 
F1lntuch ti ri BMC CiclsllOt'nltrOiq¡y 2014, 14·19 
hnpc//www blom~o,nlfll.a:im/1471-230)(/14/ 19 
Table S Otganlc dyspepsla In simple blnary loglstlc 
regressfon with variables 
Varloble G,oup OR 9sw, a 
Ger>dd Mole 154 0!;J - 1.SII 
~ > 48 IIS I .Cló - 2l!7 
Srrobng l'mlt111e 14 l.21 - 44 
Wo:lghlkru Pcbil,._.~ OJ 0A2 • 1.18 
Syw ¡,wn, ~,i.11,11y s.. .... MI> 0ld • 1.11 
Sy,i,pton d11.i,on > ,o,..,,, 0.61 0.2il - 1,62 
H~, J'osllNt 161 106- 2Jl7 
p Valut 
010 
003 
001 
0.18 
0.10 
0J7 
o.os 
the findmg of rdlux dlSeaSe or pcptlc u leer or malignancy) 
showed natistlcal s1gruflcance "ílh age, H. pylori posítlve 
status and smoking, but not wih wcight loss, symptom in• 
tensny W1d durauon. gcnder and cthmc,ty (Table 5~ 
Toe agc of patlents analyzed by ROC curve showed that 
the agc of 48 )"CalS had a 0.42 positivc and 0.72 ncgativc 
predictwe values for orgaruc dyspepsia (Figure 1). suggcst-
lng this agc is an afann chnractcristlc. 
Toe coef6cients of multiplc binary logistic regression 
of age, treated as a continuous variable, smoking status 
and pos1uvc H. pylori stntus (Table 6) allowed the con-
srruction oí a scorc, whcre ,-nlueli lower !han 46 (in a 
.scale of up lo 100 points) indicatn 1b@ non- nl!Ces.tjty of 
EGD with a high n~live pred,cth-e value for organk 
dyspeps1a (Figure 2). 
Discussion 
Ou r snrdi• shows results that are consistent with the 
meta-analysís by Ford ( 14), although (conslderlng the 
Rome criteria) our pm•alence of GERD wa~ somC\\i\at 
hlghcr than that of pepclc ulcer, whereas malignancy rates 
~ ROC Cutvo • Youclon c,1,-r1on 
o 
.. 
o 
o 
o 
00 OJ 
Figure I A9f lnclcadon ro, alarm fenure. 
r 
t111M•W1 
Ara OS:nfll M>t, O ... l 
01 
GUIAS 5 Y 6 • TEXTO COMPLETO 
P,s,ocof ? 
were somewhat highcr than those observcd In that study, 
lnese differenc,:s nuy be due ID lhe fnct th:u our ln51.1111• 
don Is an outpalient screcning cbnic In general pracoce of 
a tertiary hospital. In ¡xu,ents followed ,na three-)·ear pro-
specllvt! general praalcr srudy, thc prescnce of al:trrn 
5>mptoms signiflcantly lncrea~ the rlsk oí dl.,.-eloping 
peptlc ulccrs, but not gnso-olnt..-stlnal canar. Pnslth-e pre-
didh-e values for devclopmcnt oí canccr and uker werc 
4"' and 14'1\, respectlvely 1181, Patients "ilh peptic ulcer 
wcre more Ukcly to prescnt with gnso-ointC$tlnal bleeding 
125) and in our study, gastrointestinal blecding Wll$ an un• 
common alarm symptom (5%), "-hereas the prc.-valence of 
pcptic ulcer was 13"4 and malignancy, 2'\., lt was some-
what surpnsmg that more !han two fifths of our functional 
dyspepdc patients had alarm symptoms, whlle about 75\16 
oí lhe ulcer patients did not lt ia pcmibi! that our most 
frequmt alarm 5>mptom (\\e1ght loss) was not spcc1fic for 
serious digcstlve traa díiease.. 
Upper GI bl~ng and unintended wcight loss were 
alSQ assooated with malignancy 126), but the sensitmty 
oí alonn foatures in dmgnosing upper gMD'omt~tlnal ma• 
lignancy varied fmm 00/, to 100%, while specificity ranged 
from 16~ to 98'6 [27) This wide variation m sensiti,,ty 
may be du.e to the smnll numbcr of cancer cases drtected 
in man)· ofthc studies. Fhe in six patients with neoplasms 
had alarm sympcoms, inliming a sensimity o( 83% and 
specificiq• of 59'1. ln a srudy "~th unscd31ecl tmnsnasal 
esophagogastroduodenoscopy, c:ancer was found In 49- oí 
paticnts with alarm S)mptoms (in our study 1.7\1,) vtrnLS 
0.1'!1\ (in our study 0.6~) In the non-alnrm sympmm group 
127), Desp11e lhe difference between patients wnh and 
wllhout alarm 5>mptorns, lt Is kno,-n that 5>mptoms llave 
limitecl value m the d,agnoñs oí upper ganrointe,1:inal 
matignancy 128). 
--
AGE 
lotlm•I• 95"CI 
curoll 48 NA NA 
Se 0.55 0.4-4 065 
S¡, 0.61 0.53 0.68 
PPV 0.42 0.35 053 
NPV 0.11 0.63 O 78 
FP 73 NA NA 
FN ~ NA NA 
10 
85 
Folntu<h tr ol.BMC Gasrr~nwology 2014, 14:19 
hnpc//www.bl~central,a,m/1471•230X/l <!l19 
Table 6 Organic dyspepsia in multiple binary logistic 
regresslon 
Varlalw Gtoup OR 9S'H,CJ pValv~ 
fogt > 4$ 1.9} lU .us 0.02 
S11u!i19 fW.tve 23b 1.1g - 4J¡9 W)l 
H r,,'011 Po,ci.., 1.b8 0.99 - Uo ~ 
In this study, older age, mass or lymphadenopathy and 
f.unily history of upper g.tstrointest!nal cana,r were nol 
included os abrm fcatures. In llraz:11 therc •~ nn consen• 
sus on this maner and the AGA guidchnes are usually 
foUowed [16). In our sample, ali p31lenbl \\1th malignancy 
wcre older thnn 55 ycars, but consrdcring the finding of 
or~nic dyspepsia (reílux di,ease, peptic ulcer and malig-
nancy) our study suggests the agc of •J.8 as indicatiYc of 
alarm S)fflptom. 
Frequent ,-omitmg was not c;ons1dered an alarm symp-
tom, as rt was disregarded when reported as a chJef com• 
plaint in dyspeptic syndrome and thus, it is unlikely thal 
thls symptom, when present for a t least three months, 
wlll not result in weight loss. 
Tile presence of adcnopathy or abdominal tumor c:hnnges 
the diagnosis of undiagnosed dyspepsia lnto undiag• 
nos«! adenopathy or tunior nnd In lhese oises. lhe 
be~t approoch requlres imnging assessment and nat an 
esophagogastroduodcnoscopy. 
Famtly history of upper gastrointestinal cancer is a 
1:)-pe of inrormation lbat Is dillkult to obtaln, when pa-
ticnts lmow the cause of the discasc, they cannot proVldc 
informaaon on 1ts type and precise location. 
Primary g¡istrointestmnl lyn1phoma Is a rare disease, 
although thc stomach is the most frequent sitc of m• 
volvemcnl for thls neoplasm 129). Our samplc had only 
$coto ROC Curvo • Vouden Ctlterion 
/ 
? .., ..... 
""-O.ffl IO ~ . o lOOJ 
º "T'"-----, 
00 02 0<1 0,1 
, -Specijlclty 
Flgute 2 Upper Dlgttltlve Endosc:op~ (UOE) Sc0<e. 
ºª 
86 
GUIAS 5 Y 6- T EXTO COMPLETO 
Pq5of 7 
1 case of lymphoma; considering the small samplc sizc 
of our study, thrs finding was most hkely fonwtous. 
Thc prevalcncc of GERD has lncreased dnunaUcally in 
recent decades, mostly in the western world, where it nf-
fects aboul 19% to 30'.I. of the population, inacasing the 
risk ror esophageal adenocardnoma 130). In thls study, 
GERD was diagnoscd in 18'\í of paticnt.s, similru- to lhe 
6ndings of 11 rccent mctn-analysis, bascd on Romc aitcria 
114). In Oenmad., gastrlc inOanmiation was recently 
found in 11'\i of lhe paticnts ..,¡,h upper gas1rointestinal 
~>mptoms 127); our sa.1dy d,d not 1nclude lu~tological 
examinm:lon of the gastrlc mucosa, and thus. gastritls was 
ru, endosmplc dbgnosi.<;, which