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Cardiovascular risk factors in children with type 1 diabetes and their relationship with the glycemic control

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Abstract

Diabetics have an increased risk of cardiovascular disease (CVD). The objective of this work was to evaluate the cardiovascular risk factors in infant-juvenile type 1 diabetics and their association with the degree of glycemic control. A total of 52 patients, aged 5-15 years, were studied and compared with 37 control subjects. The degree of glycemic control, lipid profile, plasma fibrinogen, microalbuminuria and blood pressure were investigated. The patients were grouped in diabetics with good glycemic control [DGGC, glycosilated hemoglobin (HbA1c) < 8%] and poor glycemic control [DPGC, HA1c > or = 8%]. Diabetic patients presented incremented values of total cholesterol (4.1 +/- 0.9 vs. 3.1 +/- 0.7 mmol/l, p = 0.0008), LDL-cholesterol (2.4 +/- 0.9 vs. 1.7 +/- 0.7 mmol/l, p = 0.0001), HDL-cholesterol (1.2 +/- 0.3 vs. 1.0 +/- 0.2 mmol/l, p = 0.0002), with respect to control group. Eighty three per cent of diabetics showed a poor glycemic control. There were not significant differences in lipid profile between DGGC and DPGC, excepting HDL-cholesterol which was higher in DPGC group (p = 0.007). Plasma fibrinogen levels were similar in diabetics and controls, but they were higher in DPGC than in DGGC (265 +/- 46 vs. 229 +/- 22 mg/dl, p = 0.02). Three patients with microalbuminuria and none with hypertension were detected. In these patients the most pronounced risk factors for CVD were dyslipidemia and hyperglycemia, which justify the need for the early detection of these factors as well as strict metabolic control.
RIESGO CARDIOVASCULAR EN DIABETES TIPO 1
385
ARTICULO ORIGINAL
MEDICINA (Buenos Aires) 2005; 65: 385-389
ISSN 0025-7680
FACTORES DE RIESGO CARDIOVASCULAR EN NIÑOS CON DIABETES TIPO 1
Y SU RELACION CON EL CONTROL DE LA GLUCEMIA
ADELA V. ABREGU, TERESITA DEL R. CARRIZO, MARIA M. PRADO, MARIA S. VELARDE,
ELBA I. DIAZ, ROSSANA C. PEREZ AGUILAR, MARIA C. FONIO,
MARIA C. BAZAN
1
Cátedra de Práctica Hospitalaria, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional
de Tucumán;
1
Servicio de Endocrinología, Hospital del Niño Jesús, San Miguel de Tucumán
Resumen Los pacientes con diabetes tienen un riesgo incrementado de desarrollar enfermedad cardiovascular
(ECV). El objetivo de este trabajo fue evaluar factores de riesgo de ECV en niños con diabetes
tipo 1 y su asociación con el grado de control glucémico. Se estudiaron 52 pacientes, entre 5 y 15 años, trata-
dos con insulina corriente y NPH, comparados con 37 controles. Se investigó el grado de control glucémico,
perfil lipídico, fibrinógeno plasmático, microalbuminuria y presión arterial. Los pacientes se agruparon en diabé-
ticos con buen control glucémico [DBCG: hemoglobina glicosilada (HA
1c
) < 8%] y con pobre control glucémico
(DPCG, HA
1c
> 8%). La población con diabetes presentó valores incrementados de colesterol total (4.1 ± 0.9
vs. 3.1 ± 0.7 mmol/l, p = 0.0008), LDL-colesterol (2.4 ± 0.9 vs. 1.7 ± 0.7 mmol/l, p = 0.0001), HDL-colesterol
(1.2 ± 0.3 vs. 1.0 ± 0.2 mmol/l, p = 0.0002), respecto a los sujetos controles. El 83% mostró un pobre control
glucémico. No hubo diferencias significativas en el perfil lipídico entre DBCG y DPCG, excepto para HDL-
colesterol que fue mayor en los DPCG (p = 0.007). Los niveles de fibrinógeno fueron mayores en DPCG que
en DBCG (265 ± 46 vs. 229 ± 22 mg/dl, p = 0.02). Se detectaron tres pacientes con microalbuminuria y ningu-
no con hipertensión arterial. En la población estudiada los factores de riesgo cardiovascular más pronunciados
fueron la dislipemia y la hiperglucemia, evidenciando la necesidad de la detección temprana de estos factores
y un control metabólico riguroso.
Palabras clave: diabetes tipo 1, riesgo cardiovascular, dislipemia, fibrinógeno
Abstract Cardiovascular risk factors in children with type 1 diabetes and their relationship with the
glycemic control. Diabetics have an increased risk of cardiovascular disease (CVD). The objective
of this work was to evaluate the cardiovascular risk factors in infant-juvenile type 1 diabetics and their association
with the degree of glycemic control. A total of 52 patients, aged 5-15 years, were studied and compared with 37
control subjects. The degree of glycemic control, lipid profile, plasma fibrinogen, microalbuminuria and blood
pressure were investigated. The patients were grouped in diabetics with good glycemic control [DGGC,
glycosilated hemoglobin (HbA
1c
)
< 8%] and poor glycemic control [DPGC, HA
1c
> 8%]. Diabetic patients presented
incremented values of total cholesterol (4.1 ± 0.9 vs. 3.1 ± 0.7 mmol/l, p = 0.0008), LDL-cholesterol (2.4 ± 0.9
vs. 1.7 ± 0.7 mmol/l, p = 0.0001), HDL-cholesterol (1.2 ± 0.3 vs. 1.0 ± 0.2 mmol/l, p = 0.0002), with respect to
control group. Eighty three per cent of diabetics showed a poor glycemic control. There were not significant
differences in lipid profile between DGGC and DPGC, excepting HDL-cholesterol which was higher in DPGC
group (p = 0.007). Plasma fibrinogen levels were similar in diabetics and controls, but they were higher in DPGC
than in DGGC (265 ± 46 vs. 229 ± 22 mg/dl, p = 0.02). Three patients with microalbuminuria and none with
hypertension were detected. In these patients the most pronounced risk factors for CVD were dyslipidemia and
hyperglycemia, which justify the need for the early detection of these factors as well as strict metabolic control.
Key words: type 1 diabetes, cardiovascular risk, dyslipidemia, fibrinogen
Recibido: 15-XI-2004 Aceptado: 18-V-2005
Dirección postal: Dra. Adela V. Abregu, Cátedra de Práctica Hospita-
laria, Jujuy 316, 4000 San Miguel de Tucumán, Argentina.
Fax: (54-0381) 4310994 e-mail: vabregu@arnet.com.ar
La diabetes tipo 1 es una enfermedad frecuente en la
población infanto-juvenil y su incidencia se ha incremen-
tado en el mundo en las últimas décadas
1
.
La diabetes constituye per se un factor de riesgo
cardiovascular, estimándose que en relación a la pobla-
ción general, el riesgo de desarrollar enfermedad
coronaria, es de 2 a 4 veces mayor en los pacientes con
diabetes. Sin embargo en niños y adolescentes con dia-
betes tipo 1 las evidencias clínicas de ateroesclerosis
son escasas
2, 3
.
Está bien establecido que las complicaciones
vasculares aparecen a mediana o avanzada edad, no
obstante, estudios realizados en autopsias han demos-
trado que el proceso de ateroesclerosis comienza en la
niñez y se acelera en presencia de factores de riesgo
MEDICINA - Volumen 65 - Nº 5, 2005
386
independientes y modificables, tales como hiperglucemia,
dislipemia, microalbuminuria, hipertensión arterial y va-
lores elevados de fibrinógeno
4-8
.
La hiperglucemia induce la disfunción endotelial a tra-
vés del estrés oxidativo, alterando las propiedades anti-
aterogénicas y anti-trombóticas del endotelio
9, 10
. La
dislipemia y la hipertensión arterial también están aso-
ciadas con la morbimortalidad en la diabetes. Diferentes
trabajos evidenciaron que la reducción de la presión san-
guínea y de los niveles de colesterol, disminuyen el ries-
go de complicaciones cardiovasculares en adultos con
diabetes
11-13
. Sin embargo, sólo recientemente se ha pres-
tado atención al control de la presión arterial en la pobla-
ción infantil
4, 14, 15
. Asimismo, la microalbuminuria define
entre los pacientes con diabetes a un grupo de alto ries-
go de mortalidad cardiovascular prematura
16
.
Los niveles aumentados de fibrinógeno plasmático
también están relacionados con la génesis de la enfer-
medad arterial, aunque los mecanismos fisiopatológicos
involucrados en esta asociación no están totalmente
esclarecidos
8
.
Por otro lado, los pacientes púberes con diabetes tipo
1 presentan un riesgo mayor de hiperglucemia debido a
la disminución en la sensibilidad a la insulina y una redu-
cida vasodilatación dependiente del endotelio, por ac-
ción de la hormona de crecimiento, aumentando así el
riesgo cardiovascular
3, 17
.
Debido a que los estudios de los factores de riesgo
de enfermedad cardiovascular en niños con diabetes tipo
1 son escasos, el objetivo de este trabajo fue evaluar
dichos factores en una población infanto-juvenil con dia-
betes tipo 1 y su asociación con el grado de control
glucémico.
Materiales y métodos
Se estudiaron 52 pacientes con diabetes tipo 1 (25 varones
y 27 mujeres) de edades comprendidas entre 5 y 15 años,
los que fueron atendidos en el Servicio de Endocrinología del
Hospital del Niño Jesús de San Miguel de Tucumán. A to-
dos los pacientes se les confeccionó una detallada historia
clínica consignando: edad cronológica, edad ósea, peso, ta-
lla, índice de masa corporal (IMC), estadio de Tanner, tiem-
po de evolución de la diabetes, presión arterial, anteceden-
tes familiares de diabetes y enfermedad cardiovascular.
Todos los pacientes fueron tratados con insulina corrien-
te y NPH y una dieta acorde a las necesidades de cada uno.
La población con diabetes se comparó con 37 controles
sanos, de edades y sexos semejantes, sin antecedentes fa-
miliares de diabetes que fueron seleccionados de una pobla-
ción escolar. En ambos grupos se tomaron muestras de san-
gre previo ayuno de 12 horas, que se procesaron en el La-
boratorio de la Cátedra de Práctica Hospitalaria de la Facul-
tad de Bioquímica de la Universidad Nacional de Tucumán.
Las extracciones se efectuaron previo consentimiento escri-
to de los padres o responsables.
El grado de control glucémico se evaluó mediante las
determinaciones de glucemia en ayunas, (método enzimático,
Wiener Lab, Argentina), fructosamina (método cinético de
NBT, BioSystems) y hemoglobina glicosilada (HA
1c
, sistema
DCA 2000, Bayer, EE.UU.).
El perfil lipídico incluyó las mediciones en suero de
colesterol total, HDL-colesterol, LDL- colesterol y triglicéridos
empleando métodos enzimáticos (Wiener Lab, Argentina) y
el cálculo del cociente CT/HDL-colesterol. Las lecturas se
realizaron en un espectrofotómetro Metrolab 1600 plus.
Los niveles de fibrinógeno plasmático se determinaron em-
pleando el método de Clauss (Diagnostica Stago, Francia).
Para la investigación de microalbuminuria se utilizó un
método inmunoturbidimétrico (DCA 2000, Bayer, EE.UU.) en
muestras de orina de 12 horas de recolección nocturna, con-
siderándose microalbuminuria a la excreción urinaria de al-
búmina comprendida entre 30 y 299 mg/24 horas, en al me-
nos dos de tres muestras consecutivas.
Los resultados se expresaron como la media ± una des-
viación estándar (X
± DS). El test-t de Student se aplicó para
analizar las diferencias entre grupos no apareados, conside-
rando significativos valores de p < 0.05. El coeficiente de
Pearson se empleó para investigar el grado de correlación
entre dos variables.
El protocolo del presente trabajo fue aprobado por el Co-
mité de Docencia e Investigación del Hospital del Niño Jesús.
Resultados
La Tabla 1 muestra las características clínicas y la distri-
bución de los pacientes con diabetes según el estadio
de Tanner. El 21% de los niños presentó un estadio II de
Tanner, observándose en los mismos diferencias signifi-
cativas en los niveles de fructosamina (4.5 ± 0.8 vs. 3.5 ±
0.7 mmol/l, p = 0.004) y en la dosis de insulina NPH ne-
cesaria (0.80 ± 0.2 vs. 0.57 ± 0.22 U/kg/día, p = 0.004).
Veinticuatro niños tenían antecedentes familiares de
diabetes tipo 2, 4 pacientes mostraron asociación con
enfermedad celíaca y en 2 se detectó retinopatía.
No se observaron diferencias significativas entre la
edad cronológica y la edad ósea en los niños con diabe-
tes (p = 0.20).
La Tabla 2 muestra comparativamente las característi-
cas clínicas y bioquímicas entre pacientes y controles
sanos. Se encontraron diferencias significativas en el IMC
(p = 0.04) y los valores de colesterol total (p = 0.0008),
HDL- colesterol (p = 0.0002) y LDL- colesterol (p = 0.0001).
De acuerdo con las pautas fijadas para niños con dia-
betes
4, 15
se consideraron como niveles óptimos para co-
lesterol total < 4.4 mmol/l, HDL- colesterol > 0.9 mmol/l,
LDL-colesterol < 2.6 mmol/l y triglicéridos < 1.7 mmol/l.
En la población enferma la incidencia de valores no de-
seables fue: 40.4% para colesterol total; 14.2% para HDL-
colesterol, 42.8% para LDL-colesterol y del 9.5% para
triglicéridos.
Los niveles de fibrinógeno plasmático no mostraron
diferencias significativas entre enfermos y controles (p =
0.15).
Los pacientes fueron agrupados según las concen-
traciones de HA
1c
en: diabéticos con buen control
glucémico (DBCG, HA
1c
< 8%) y diabéticos con pobre
control glucémico (DPCG, HA
1c
> 8%).
RIESGO CARDIOVASCULAR EN DIABETES TIPO 1
387
La Tabla 3 muestra los parámetros bioquímicos de
los pacientes de acuerdo al grado de control glucémico.
El 83% de la población presentó un pobre control
glucémico, puesto en evidencia por las diferencias sig-
nificativas en los niveles de glucemia, fructosamina y
HA
1c
entre ambos grupos. Los pacientes del grupo
DPCG fueron los que presentaron mayor tiempo de evo-
lución de enfermedad (3.9 ± 2.9 vs. 1.1 ± 1.0 años,
p = 0.0003).
Al analizar el perfil lipídico no se observaron diferen-
cias significativas entre los grupos DBCG y DPCG, ex-
cepto para HDL-colesterol que fue mayor en los DPCG
(0.9 ± 0.29 vs. 1.3 ± 0.3 mmol/l, p = 0.007).
Los niveles de fibrinógeno plasmático fueron más ele-
vados en los DPCG que en los DBCG (p = 0.02).
En el grupo DPCG y con un tiempo de evolución de la
enfermedad entre 4 y 10 años, se detectaron 3 pacien-
tes con microalbuminuria. Al mismo grupo pertenecían
los dos niños con retinopatía.
Tabla 2.– Parámetros clínicos y bioquímicos de niños con diabetes y controles
Niños diabéticos Controles p
n5237
Varones/mujeres (%) 25/27 19/18 ***
Edad cronológica (años) 11.3 ± 2.3 10.4 ± 1.7 0.071
Duración de la diabetes (años) 3.4 ± 2.9 *** ***
IMC (kg/m
2
) 16.9 ± 1.7 18.2 ± 2.7 0.04
Glucemia en ayunas (mmol/l) 8.4 ± 4.2 3.3 ± 0.4 0.0006
HA1c (%) 11.8 ± 2.9 5.4 ± 0.2 0.00005
Fructosamina (mmol/l) 3.7 ± 0.8 1.9 ± 0.2 0.00005
Fibrinógeno plasmático (mg/dl) 260 ± 46 252 ± 21 0.151
Colesterol total (mmol/l) 4.1 ± 0.9 3.1 ± 0.7 0.0008
HDL-Colesterol (mmol/l) 1.2 ± 0.3 1.0 ± 0.2 0.00002
LDL-Colesterol (mmol/l) 2.4 ± 0.9 1.7 ± 0.7 0.0001
HA1c: Hemoglobina glucosilada
Tabla 3.– Parámetros bioquímicos de niños con diabetes de
acuerdo al grado de control glucémico
DBCG DPCG p
n 9 43 ****
% 17 83 ****
Glucemia (mmol/l) 5.5 ± 2.2 8.8 ± 4.3 0.007
Fructosamina (mmol/l) 2.7 ± 0.7 3.8 ± 0.8 0.013
HbA1c (%) 7.2 ± 0.8 11.9 ± 1.9 0.0008
Colesterol total (mmol/l) 3.7 ± 0.8 4.1 ± 0.9 0.246
HDL-colesterol (mmol/l) 0.9 ± 0.2 1.3 ± 0.3 0.007
LDL-colesterol (mmol/l) 2.2 ± 0.9 2.3 ± 0.8 0.768
Triglicéridos (mmol/l) 1.1 ± 0.3 1.0 ± 0.7 0.518
Fibrinógeno (mg/dl) 229 ± 22 265 ± 46 0.020
DBCG: diabéticos con buen control glucémico
DPCG: diabéticos con pobre control glucémico
Tabla 1.– Características clínicas de la población con
diabetes tipo 1 estudiada
n52
Varones/mujeres 25 / 27
Edad cronológica (años) 11.3 ± 2.3
Edad ósea (años) 10.6 ± 2.2
Duración de la diabetes (años) 3.4 ± 2.9
IMC (kg/m
2
) 16.9 ± 2.1
Velocidad de crecimiento (cm/año) 4.4 ± 2.3
Presión sistólica (mm Hg) 110 ± 11
Presión diastólica (mm Hg) 67 ± 8
NPH humana (U/kg/día) 0.63 ± 0.23
Estadios de Tanner I........ 19 pacientes
II....... 12 pacientes
III ..... 12 pacientes
IV ..... 7 pacientes
V ...... 2 pacientes
IMC: Indice de masa corporal
MEDICINA - Volumen 65 - Nº 5, 2005
388
Discusión
Diversos estudios han demostrado que el riesgo de de-
sarrollar ECV aumenta con el grado de hiperglucemia,
ya que ésta provoca alteraciones vasculares que acele-
ran el proceso de ateroesclerosis. Esta relación no se
limita a los rangos diabéticos de hiperglucemia sino que
aun ligeros aumentos de glucemia en ayunas o post-
prandial han sido asociados a riesgo de enfermedad
cardiovascular
18-20
.
La pubertad es un período de intensos cambios hor-
monales y metabólicos, que tienen un papel preponde-
rante en el desarrollo de las complicaciones diabéticas.
En este trabajo se encontró que 21 pacientes presenta-
ron estadio de Tanner II, en los cuales el requerimiento
de insulina NPH y los niveles de fructosamina fueron
mayores que en el resto de la población estudiada. Es-
tos resultados podrían deberse a un aumento de la hor-
mona del crecimiento, la cual promueve una mayor ne-
cesidad de insulina.
En la población con diabetes analizada, se encontró
que el 83% presentaba un pobre control glucémico, lo
que indica el riesgo incrementado de estos pacientes a
desarrollar complicaciones vasculares a mediano o lar-
go plazo. Las dificultades para mantener a este grupo de
pacientes con un buen control glucémico estarían rela-
cionadas con cambios hormonales, desórdenes alimen-
tarios y/o terapéuticos propios de la edad
21, 22
.
El perfil lipídico mostró valores incrementados de
colesterol total, LDL-colesterol y HDL-colesterol respec-
to a los controles. Estos resultados concuerdan con los
de Gunczler y col
22
en los valores de LDL-colesterol y
triglicéridos, mientras que los de HDL-colesterol coinci-
den con otros autores
6, 23, 24
. Considerando los criterios
establecidos para el manejo de los lípidos en niños con
diabetes
4, 12
, observamos una elevada incidencia de va-
lores no deseables especialmente para colesterol total y
LDL-colesterol.
No se observaron diferencias significativas en el per-
fil lipídico entre los grupos DBCG y DPCG, excepto en
los niveles de HDL-colesterol, que fueron más elevados
en aquellos con pobre control glucémico. A pesar de esta
paradoja, el riesgo de ECV es elevado en estos pacien-
tes, y de acuerdo con Valabhji y col. la causa sería dife-
rencias cualitativas en las moléculas de HDL y cambios
en su capacidad antioxidante
25
.
Son numerosos los estudios que consideran que ni-
veles elevados de fibrinógeno plasmático constituyen un
factor de riesgo independiente de ECV
26, 27
. En un traba-
jo previo de nuestro grupo, se encontraron valores ele-
vados de fibrinógeno en diabéticos tipo 2
28
, en coinci-
dencia con otros autores. Similares resultados fueron ha-
llados por Ceriello y col. en adultos con diabetes tipo 1
29
.
Los datos sobre fibrinógeno en niños diabéticos son es-
casos y discordantes. Así, mientras Cam y col
30
señala-
ron niveles elevados, en el presente trabajo no se obser-
varon diferencias significativas entre niños con diabetes
y controles. Los valores de fibrinógeno más elevados
encontrados en el grupo DPCG indicarían un mayor ries-
go cardiovascular de estos pacientes. Sin embargo, con-
sideramos que son necesarias más investigaciones en
este grupo etáreo acerca de ese factor de riesgo.
En el grupo DPCG se detectaron tres sujetos con
microalbuminuria, los cuales presentaban un tiempo de
evolución de la diabetes superior a 4 años. Estos datos
al igual que los de Meigs y col
7
, sugieren que la hiperglu-
cemia de larga duración incrementa el riesgo de
microalbuminuria.
En la población estudiada sólo dos pacientes del gru-
po DPCG presentaron retinopatía. La aparición de esta
complicación en la diabetes estaría directamente rela-
cionada con la duración de la enfermedad y el grado de
control glucémico.
La hipertensión arterial junto a la dislipemia son facto-
res de riesgo sinérgicos para el desarrollo de ECV. En la
población estudiada no se encontraron niños hiper-ten-
sos; sin embargo, es recomendable que todo niño diabé-
tico sea controlado para detectar hipertensión en cada vi-
sita al médico y así, establecer un tratamiento precoz
14, 15
.
Entre los pacientes diabéticos hubo 24 niños con his-
toria familiar de diabetes tipo 2. Al respecto, Erbey y col.
sostienen que este antecedente es un factor de riesgo
de enfermedad arterial coronaria en diabéticos tipo 1 y
proponen que la insulinorresistencia puede contribuir a
su desarrollo, coexistiendo en estos pacientes una “do-
ble diabetes”
31
.
En conclusión, en la población estudiada, los factores
de riesgo de ECV más destacados fueron la dislipemia y
el nivel de hiperglucemia.
Teniendo en cuenta que en la actualidad la diabetes
es considerada una enfermedad cardiovascular, se
enfatiza la importancia de la detección y control precoz
de dichos factores de riesgo en la población infanto-ju-
venil con diabetes.
Agradecimientos: A Laboratorios Wiener Lab y a la Fun-
dación Infantil de Endocrinología (FIDE), por la donación de
reactivos empleados en la realización de este trabajo.
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LA PORTADA
Une salle de l'Hôtel Dieu au 15
ème
siècle
Enluminure extraite du Livre de Vie Active de l' Hôtel Dieu de Paris, de Jehan Henry, 15
ème
siècle.
Una sala del Hôtel Dieu en el siglo XV
Estampa iluminada del Libro de la Vida Activa del Hôtel Dieu de Paris, por Jehan Henry, siglo XV
(Inscripción al pie, sobre el muro).
Fotografìa de la reproducción existente en el muro de la galería, primer piso, Hôtel Dieu, place du
Parvis - Notre Dame, Paris, noviembre 2004.
... Youth with T1DM have proteomic alterations in their HDL compared peers without diabetes and are at increased risk of CVD [30]. Corroborating this, our [31]. Lipids levels are very important in predicting adverse cardiovascular outcomes [32]. ...
... These results highlight the importance to engage in regular physical exercise for persons living with T1DM. Importantly, very small volumes of physical activity appear to have significant health benefits [1,31]. ...
Article
Full-text available
Background Type 1 diabetes mellitus (T1DM) is associated with an increased risk for cardiovascular disease (CVD) related morbidity and premature mortality. Regular physical activity plays an important role in the primary and secondary prevention of CVD, improving overall health and wellbeing. Previous observational studies have examined the associations between self-reported physical activity and CVD risk factors in largely adult Caucasian populations. However, limited work has evaluated the relationship between objectively measured physical activity and CVD risk factors in other ethnicities, particularly Chinese youth living with T1DM. Methods This cross-sectional study assessed CVD risk factors, physical activity, and aerobic fitness (and their associations) in Chinese youth living with T1DM (n = 48) and peers (n = 19) without T1DM. Primary outcomes included blood pressure, lipid profiles, and physical activity (accelerometry). Statistical differences between groups were determined with chi-square, independent-samples t-tests, or analysis of covariance. The associations between aerobic fitness, daily physical activity variables, and CVD risk factors were assessed with univariate and multivariate linear regression analyses. Results Results were summarized using means and standard deviation (SD) for normally distributed variables and medians and 25–75th quartile for non-normally distributed variables. In comparison to peers without diabetes, youth living with T1DM showed higher levels of total cholesterol (3.14 ± 0.67 vs. 4.03 ± 0.81 mmol·L ⁻¹ , p = 0.001), low-density lipoprotein cholesterol (1.74 ± 0.38 vs. 2.31 ± 0.72 mmol·L ⁻¹ , p = 0.005), and triglycerides (0.60 ± 0.40 vs. 0.89 ± 0.31 mmol·L ⁻¹ p = 0.012), and lower maximal oxygen power (44.43 ± 8.29 vs. 35.48 ± 8.72 mL·kg ⁻¹ ·min ⁻¹ , p = 0.003), total physical activity counts (451.01 ± 133.52 vs. 346.87 ± 101.97 counts·min ⁻¹ , p = 0.004), metabolic equivalents (METs) (2.41 ± 0.60 vs. 2.09 ± 0.41 METs, p = 0.033), moderate-to-vigorous intensity physical activity [MVPA: 89.57 (61.00–124.14) vs (53.19 (35.68–63.16) min, p = 0.001], and the percentage of time spent in MVPA [11.91 (7.74–16.22) vs 8.56 (6.18–10.12) %, p = 0.038]. The level of high-density lipoprotein cholesterol was positively associated with METs (β = 0.29, p = 0.030, model R ² = 0.168), and the level of triglycerides was negatively associated with physical activity counts (β = − 0.001, p = 0.018, model R ² = 0.205) and METs (β = − 0.359, p = 0.015, model R ² = 0.208), and positively associated with time spent in sedentary behaviour (β = 0.002, p = 0.041, model R ² = 0.156) in persons living with T1DM. Conclusions Chinese youth with T1DM, despite their young age and short duration of diabetes, present early signs of CVD risk, as well as low physical activity levels and cardiorespiratory fitness compared to apparently healthy peers without diabetes. Regular physical activity is associated with a beneficial cardiovascular profile in T1DM, including improvements in lipid profile. Thus, physical activity participation should be widely promoted in youth living with T1DM.
... Corroborating this, our results showed that youth living with T1D have increased total cholesterol, LDL-C, and triglycerides compared to healthy controls. Similarly, a previous study showed that youth with T1D (5-15 years) had elevated values of total cholesterol and LDL-C compared to healthy controls [21]. Lipids levels are very important in predicting adverse cardiovascular outcomes [22]. ...
Preprint
Full-text available
Background: Type 1 diabetes (T1D) is associated with a high risk of cardiovascular disease (CVD) and an increased rate of premature mortality from CVD. Regular physical activity can improve overall health and wellbeing and plays an important role in primary and secondary prevention of CVD. Methods: This cross-sectional study assessed cardiovascular risk factors, physical activity, and fitness (and their associations) in young individuals living with T1D and healthy controls. Primary outcomes included blood pressure, lipid profiles, and physical activity (accelerometry). We included a total of 48 individuals living with T1D and 19 healthy controls, aged 12 to 17 years. Statistical differences between groups were determined with chi-square, independent-samples t-tests or analysis of covariance. The associations between aerobic fitness, daily physical activity variables and cardiovascular risk factors were assessed with univariate and multivariate linear regression analysis. Results: In comparison to healthy controls, youth living with T1D showed higher levels of total cholesterol (4.03 ± 0.81 vs. 3.14 ± 0.67 mmol·L⁻¹, p = 0.001), low-density lipoprotein cholesterol (LDL-C) (2.31 ± 0.72 vs. 1.74 ± 0.38 mmol·L⁻¹, p = 0.035), and triglycerides (0.89 ± 0.31 vs. 0.60 ± 0.40 mmol·L⁻¹ p = 0.012), and lower maximal oxygen power (VO2max) (35.48 ± 8.72 vs. 44.43 ± 8.29 mL·kg⁻¹·min⁻¹, p = 0.003), total physical activity counts (346.87 ± 101.97 vs. 451.01 ± 133.52 counts·min⁻¹, p = 0.004), metabolic equivalents (METs) (2.09 ± 0.41 vs. 2.41 ± 0.60 METs, p = 0.033), moderate to vigorous intensity physical activity (MVPA), and the percentage of time spent in MVPA. The level of HDL-C was positively associated with METs (β = 0.29, p = 0.030, model R² = 0.17), and the level of triglycerides was negatively associated with physical activity counts (β = -0.001, p = 0.018, model R² = 0.205) and METs (β = -0.359, p = 0.015, model R² = 0.208) in persons living with T1D. Conclusions: Youth with T1D, despite their young age and short duration of diabetes, present early signs of CVD risk, as well as low physical activity levels and cardiorespiratory fitness compared to healthy controls. Regular physical activity is associated with a beneficial cardiovascular profile in T1D, including improvements in lipid profile. Thus, physical activity participation should be widely promoted in youth living with T1D.
Article
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A subclinical inflammation state was detected in the early step of diabetes, which increases the serum levels of cytokines that induce acute-phase protein synthesis as C-reactive protein (PCR) and fibrinogen (Fg), stimulating the endothelial disfunction of adhesion molecules. Thirty patients (15 boys, 15 girls) with type 1 diabetes (DT1), without vascular complications, were studied. Their mean age and duration of diabetes were 11.8 +/- 2.1 and 3.9 +/- 3.2 years, respectively. The laboratory parameters evaluated were: blood leukocytes count, globular sedimentation velocity, fasting glycemia, glycosylated hemoglobin (HbA1c), high sensitivity PCR (uPCR), plasma soluble E-selectin (sE-S), sVCAM-1 and microalbuminuria. Increased levels of uPCR, sE-S and VCAM-1 were found, compared with the control group control [0.60 (0.30-1.25) vs. 0.20 (0.20-0.65) mg/l, p = 0.013], [108 (60-150) vs. 68 (56-82) ng/ml, p = 0.0031] y [750 (708-826) vs. 721 (674-751) ng/ml, p = 0.039] respectively. When diabetic patients were grouped according to duration of disease (3 and > de 3 years), uPCR values were higher in the second group. uPCR levels were better correlated with sE-S (r = 0.44, p = 0.03) and VCAM-1 (r = 0.49, p = 0.02). These results suggest the presence of pro-inflammatory and endothelial activation states, which are strongly associated with DT1.
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The chronic hyperglycemic state in diabetic patients produces an aggression to the vascular endothelium leading to a premature development of atherosclerosis. The objective of this paper was to determine the soluble E-selectin (sE-S) levels in children with type 1 diabetes (DT1) and its relationship with glycemic control and lipid profile. Thirty patients with DT1, (16 girls and 14 boys), age between 6 and 15 years were studied, whose data were compared with 20 control subjects. In both groups sE-S was determined as well as fasting glycemia, glycosylated hemoglobin (HbAlc), total cholesterol (TC), HDL-C, LDL-C, non-HDL-C and triglycerides (TG). sE-S values were 66% higher in diabetics than in control subjects (p = 0.001). Patients were grouped in: good glycemic control diabetics (GGCD, HbA1c < or = 8%) and poor glycemic control diabetics (PGCD, HbA1c > 8%). sE-S concentratios were in PGCD an GGCD respectively. 111.3 +/- 40.5 vs 68.0 +/- 11.3 ng/ml, p = 0.02. In the diabetic group, the incidence of non desirable values in the lipid profile parameters were: TC 50%; HDL-C 14%; LDL-C 52%, non-HDL-C 26.7% and TG 14%. sE-S values were better correlated with HbA1c (r = 0.53, p = 0.0001) than fasting glycemia (r = 0.36, p = 0.008), and CT (r = 0.36, p = 0.009). These results suggest that sE-S is an early marker of endothelial dysfunction and a probable risk marker of atherosclerosis in children with DT1.
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Early development of coronary disease in Non Insulin Dependent Diabetes Mellitus (NIDDM), plasma fibrinogen levels and its relatios with other risk markers were determinated in diabetic patients of San Miguel de Tucumán. 97 NIDDM patients of both sex, and aged from 37 to 65 years, were studied and matched with a control group of 50 healthy subjects, in which plasma Fg, glycemia, fructosamine and lipid profile were determinated. Plasma Fg levels in diabetic patients were 320 ± 87 mg/dl and 328 ± 73 mg/dl in women. There were significant difference with control group (men: 257 ± 48, p< 0,005; women: 256 ± 38, p< 0.005). Lipid profile of diabetic men showed that total cholesterol and LDL-cholesterol values were statistically lower than diabetic women (p< 0,005 and p< 0,05 respectively), in wich an significant and inverse relation between Fg and triglicerides was observed. Fg was higher in hypertensive patients than those normal arterial tension (men: 324 ± 49 vs 317 ± 57 mg/dl; women: 328 ± 46 vs 309 ± 54 mg/dl). Significant variations were not observed between Fg and age, neither evolution time of disease, smoker and nor smoker, alcohol drinker and not drinker diabetic men. We concluded that increased Fg levels in NIDDM confirm that it is an independent risk marker of cardiovascular disease associated to diabetes.
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Both type I and type II diabetes are powerful and independent risk factors for coronary artery disease (CAD), stroke, and peripheral arterial disease. Atherosclerosis accounts for virtually 80% of all deaths among diabetic patients. Prolonged exposure to hyperglycemia is now recognized a major factor in the pathogenesis of atherosclerosis in diabetes. Hyperglycemia induces a large number of alterations at the cellular level of vascular tissue that potentially accelerate the atherosclerotic process. Animal and human studies have elucidated three major mechanisms that encompass most of the pathological alterations observed in the diabetic vasculature: 1) Nonenzymatic glycosylation of proteins and lipids which can interfere with their normal function by disrupting molecular conformation, alter enzymatic activity, reduce degradative capacity, and interfere with receptor recognition. In addition, glycosylated proteins interact with a specific receptor present on all cells relevant to the atherosclerotic process, including monocyte-derived macrophages, endothelial cells, and smooth muscle cells. The interaction of glycosylated proteins with their receptor results in the induction of oxidative stress and proinflammatory responses 2) oxidative stress 3) protein kinase C (PKC) activation with subsequent alteration in growth factor expression. Importantly, these mechanisms may be interrelated. For example, hyperglycemia-induced oxidative stress promotes both the formation of advanced glycosylation end products and PKC activation.
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In Brief Emerging research emphasizes the importance of an integrative approach to treating type 1 diabetes among adolescent females. This review discusses important biological, psychological, behavioral, and sociocultural factors that must be considered when providing diabetes care. A summary of recommendations to assist health care professionals in delivering care to their patients is provided.
Conference Paper
Patients with diabetes have a 2-fold higher risk of developing cardiovascular disease than non-diabetic individuals. Moreover, recent epidemiologic studies have shown that this risk rises with the degree of hyperglycaemia, so that diabetic patients with poorly controlled glucose levels have a higher risk of cardiovascular disease than those with well-controlled glucose levels. Thus, in patients with diabetes, glucose level appears to be a continuous risk factor for cardiovascular disease. Several epidemiologic studies also suggest that this relationship is not confined to the diabetic range; non-diabetic levels of fasting and postprandial hyperglycaemia, that may even be lower than those associated with impaired glucose tolerance, are also associated with an increased risk of cardiovascular disease. Evidence is therefore accumulating that dysglycaemia (i.e. raised glucose levels above some low, as yet undefined, threshold) is a continuous risk factor for cardiovascular disease. This relationship is similar to that of smoking, blood pressure and dyslipidaemia to cardiovascular risk. Whether glucose lowering in diabetic or non-diabetic individuals will prevent cardiovascular disease remains to be determined.
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The concern for early cardiovascular morbidity and mortality is becoming increasingly more common in the pediatric arena due to the continually increasing incidence of type 1 and type 2 diabetes mellitus, as well as the rise in obesity in this population. Currently the only treatment recommendations are derived from adult guidelines, due to a lack of evidence-based data in children. Independent risk factors for cardiovascular disease are similar in children and adults: obesity, presence of diabetes, hyperglycemia, insulin resistance, hypertension, and hyperlipidemia. Postmortem studies in children have shown that atherosclerotic plaques begin in childhood, and coronary artery lesions can be seen as early as 10 years of age. The development of atherosclerotic plaques appears to be due to endothelial dysfunction as a result of inflammatory changes from the above listed cardiovascular risk factors. Currently there are several serum markers of inflammation that are predictive of cardiovascular disease in adults, but the significance of changes in the levels of these markers in children is currently unknown. Additionally, there are several noninvasive techniques to measure endothelial dysfunction, including brachial artery reactivity and ECHO Doppler carotid intima-medial thickness, which may ultimately prove to be predictive for cardiovascular disease in children. The management of hypertension in adult patients has been a critical aspect of prevention of cardiovascular disease, but treatment of hypertension in pediatric patients is difficult due to the lack of trials of safety and efficacy in children, as well as lack of universally accepted standards for the appropriate age and blood pressure level for starting treatment. However, data from adult studies of cardiovascular risk suggest that there would be benefit to early, aggressive control of elevated blood pressure in children. Future studies will be needed to determine which antihypertensive medications will be safe and effective in children, as well as to determine starting points for treatment of hypertension in this population. The treatment of dyslipidemia in adults has resulted in significant risk reduction for cardiovascular morbidity and mortality, but there is a paucity of information available about the long-term safety of using lipid-lowering medications in growing children. Currently, bile acid sequestrants are the only lipid-lowering medication approved for children of all ages, while other lipid-lowering medications are only approved for use in children age 10 and above, and for use in familial hypercholesterolemia. Short-term studies of the statin medications in small groups of male children have shown excellent compliance with no adverse effects on growth, sexual maturation, or hormone levels, but longer-term, more comprehensive studies are needed in the pediatric population. Both the statins and the thiazolidinediones have been shown to have pleotropic effects on the endithelium, which may confer a cardioprotective environment. Treatment of cardiovascular risk factors in childhood consists of a step-wise approach, including lifestyle modification and pharmacologic therapy. Therapy must be individualized based on number of risk factors, family history, and existing complications. Although further longitudinal studies of medications are needed in children, there may be benefit to following adult guidelines, especially in high-risk adolescents, and instituting early, aggressive treatment for modifiable risk factors.
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Lipoprotein abnormalities may well contribute to the increased risk of coronary heart disease, cerebrovascular disease and peripheral vascular disease observed in type 1 (insulin-dependent) diabetes mellitus. The spectrum of diabetes-associated changes in lipoprotein metabolism is discussed. The plasma levels of lipoprotein cholesterol and triglycerides are largely influenced by the degree of glycaemic control. With poor metabolic control, plasma cholesterol and triglycerides are frequently elevated. In contrast, in well-regulated patients without micro- and macrovascular complications lipid levels are generally normal or even favourable, although lipoprotein composition abnormalities can persist despite intensified insulin treatment. With the development of diabetic nephropathy the cardiovascular risk increases markedly and this complication is associated with increased concentrations of cholesterol and of the atherogenic lipoprotein species, lipoprotein(a), and low levels of high-density lipoprotein cholesterol. The rationale for treatment of lipid disorders in diabetes mellitus is based upon results of trials conducted primarily in non-diabetic populations. It is hoped that with increased recognition of dyslipidaemia and aggressive therapeutic measures the overkill in diabetes mellitus from macrovascular diseases will be reduced.
Article
In order to examine the relationship between serum lipids and apolipoproteins and macrovascular disease in patients with Type 1 diabetes mellitus, 50 patients with Type 1 diabetes mellitus attending the diabetic clinics at St Mary's and St Charles' Hospitals, London were recruited into a cross-sectional study. B-mode ultrasound was used to measure intima-media thickness and define an arterial ultrasound score for each patient as a non-invasive indicator of atherosclerotic change. Intima-medial (i-m) thickness was significantly higher in those subjects with clinical evidence of macrovascular disease compared to those without macrovascular disease (0.865 +/- 0.191 vs 0.695 +/- 0.162 mm, p = 0.0038). In the study group there were significant correlations between i-m thickness and age (r = 0.65, p < 0.01), total serum cholesterol (r = 0.32, p < 0.01), and serum fibrinogen (r = 0.43, p < 0.01) but no other lipid or apolipoprotein variable. When i-m thickness was corrected for age there were significant correlations with total cholesterol (r = 0.43, p < 0.01) and LDL-cholesterol (r = 0.42, p < 0.01). Whereas total and LDL-cholesterol and serum fibrinogen concentrations were related to the extent of atherosclerotic disease by ultrasound techniques, there was no relationship with high density lipoprotein (HDL) or subfraction cholesterol concentrations. HDL-cholesterol may not be a useful marker for cardiovascular disease in Type 1 diabetes.
Article
In IDDM or NIDDM, the total plasma cholesterol and triglycerides are usually within normal limits when the blood glucose is controlled. Marked hypertriglyceridemia can develop with loss of glycemic control and is often due to superimposed genetic abnormalities in lipoprotein metabolism. Tight control in IDDM usually reduces LDL and VLDL to normal levels and may raise HDL above the normal range. Low HDL cholesterol and mild to moderate elevations of VLDL triglyceride are common in NIDDM if obesity or proteinuria is also present. Both HDL and LDL may be smaller and more dense and may be enriched with triglyceride as compared with cholesterol. These abnormalities may require weight loss for control. The increased incidence of cardiovascular disease in diabetes is unexplained but is amplified by the well-defined cardiovascular risk factors. The new American Diabetes Association guidelines call for treatment of high triglycerides and LDL cholesterol to be aggressively reduced. Triglycerides should be under 200 mg/dL, are considered borderline high between 200 and 400 mg/dL, and high when above 400 mg/dL. Low HDL is defined as less than 35 mg/dL. Control of obesity with diet and exercise and reduced intake of saturated fat and cholesterol are important first steps. If needed, drug therapy is appropriate to reduce LDL to levels below 130 mg/dL in all adult diabetics and below 100 mg/dL in those with cardiovascular disease.