Vltrasonie EvaIuation ofEarly Atherosclerosis in Children and

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Vltrasonie EvaIuation of Early Atherosclerosis in
Children and Adoleseents with Type 1 Diabetes M~llitus
Taner Yavuz!, Ahmet Akçar, Rukiye Eker Ömeroglu3, Rüveyde Bundak4 and Mine Sükür4
JDepartment of Pediatries, Düzce School of Medicine, Abant Izzet Baysal University, Düzce,
2Department of Pediatrics, Pamukkale School of Medicine, Pamukkale University, Denizli,
3Division of Pediatric Cardiology and 4Division of Pediatric Endocrinology,
Department of Pediatries, Istanbul School of Medicine, Istanbul, Turkey
,.'
ABSTRACT
KEY WORDS
Objective: To assess early atherosclerosis using
B-mode imaging of the carotid artery in children
and adolescents with type 1 diabetes mellitus
(TIDM)
and to evaluate the relationship
between various risk factors and intimal plus
medial thickness (lMT) in this population.
Methods: Fifty-two children and adolescents
(aged 3-18 years) with uncomplicated TIDM
and 43 age- and gender-matched healthy controls were examined. B-mode imaging was used
to determine the intimal plus medial thickness
(IMT) of the carotid artery in all subjects.
Patients witb T1DM.and control subjects were
divided into two groups according to age and
gender. Furthermore,
duration of DM was
considered for comparison.
Results: Patients and control subjects showed no
association between IMT and sex, systolic blood
pressure (sBP), diastolic blood pressure (dBP),
serum lipid levels or left ventricular ejection
fraction (L VEF). However, statistical analysis
indicated a good correlation between age and
carotid arterial wall thickness in both diabetic
and control groups. These findings were consistent with those in the literature. No correlation was found between IMT and the duration
of DM.
atherosclerosis, intimal plus medial thickness
(IMT), macroangiopathy,type 1 diabetes mellitus,
ultrasonography
Conclusions: This study indicates that there is
no association between TIDM and IMT in
children and adolescents with TIDM.
Reprint address:
Yrd, Doç. Dr. Taner Yavuz
Düzce Tip Fakültesi
Çocuk
Po!iklinigi
- Konuralp
INTRODUCTION
Type 1 diabetes mellitus (TlDM) is caused by
autoimmune destruction of insulin-producing Pcells of the pancreatic islets of Langerhans.
Absolute or relative insulIn deficiency leads to
metabolic alterations in carbohydrate, protein and
fat metabolism, and water/electrolyte disturbancesl.
TLDM is one of the most common chronic
diseases of childhood, with prevalence of approximately one in 300 children by the age of 18 years2.
As the disease progresses, chronic complications of
TLDM start to appear. Diabetic complications
related to micro- and macroangiopathy are .the main
causes of mortality and morbidity in patients with
DMJ. Macrovascular complications, clinically
evident as coronary, cerebrovascular, and peripheral arterial disease, are important causes of early
death in DM.
Although the effects of atherosclerosis do not
appear in most patients until middle age or Iater,
the process begins much earlier. Identification of
atherosclerosis can be made using high-resolution
B-mode imaging of the carotid arterl.5 which
enables direct in vi1'Omonitoring of carotid arteries
of living patients with Tl DM. Combined thickness
of the carotid intima and media is useful to examine
early stages of atherosclerosis and to give
information on the regression and progression of
atherosclerotic lesions6,7.
Düzce, Turkey
e-mail: [email protected]
VOLUM E 15. NO. 8. 2002
IDI
1132
T.YAVUZETAL.
Intimal plus medial thickness (IMT) values for
patients with TlDM have been shown- to be
significantly greater than those of age-matched nondiabetic subjects. Age and blood glucose control
have an important effect on IMT in young patients
with TlDM8-lo.
In the present study, we investigated early
atherosclerosis using B-mode imaging of the
carotid artery in children and adolescents with
Tl DM.
METHODS.
Fifty-two subjects (24 males, 28 females; mean
age 11.6 :t 3.8 years, range 3-18 years) with TlDM
were recruited at the pediatric endocrinology
outpatient clinie, Department of Pediatries, Istanbul
School of Medicine. All had a history of abrupt
onset of DM and at least one episode of diabetic
ketoacidosis. None had manifest macroangiopathy,
such as coronary artery disease or ischemic arterial
disease of the 100NerIimbs. Patients with li\-er or
renal function impairment \Yere excluded. All
patients with TlDM were under insulin therapy.
Forty-three non-diabetic volunteers of comparable
sex and age (19 males, 24 females; mean age 11.3 :t
3.3 years, range 3"-16years) were randomly selected
as control subjects. This study \Vasapproved by the
hospital's ethics committee and \\iritten informed
consent was obtained from parents.
Fasting blood was obtained for analysis of total
and HDL cholesterol, serum triglycerides. glycosylated hemoglobin (HbA1c) and urine microalbumin. LDL cholesterol was calculated using the
Friedewald formula, and determined by radioimmunoassay. Blood pressure was measured using
a random-zero sphygmomanometer after 5 min rest.
IMT defined by Pignoli et aL.1i was measured as
the distance from the leading edge of the first
echogenic line to the leading edge of the second
echogenic line. The first line represents the lumenintimal interface, and the second line is produced
by the collagen-containing upper layer of the tunica
adventitia (Fig. i). Ultrasonographic scanning of
the carotid arteries was performed using an
echotomographic system (Hewlett-Packard 1000)
with an electrical linear transducer (midfrequency
of 7.5 MHz). All studies were conducted by the
same researcher (R.E.Ö.) who is a pediatrician with
II years experience in vascular u1trasonography.
The comman carotid artery was chosen as it is
known to be rather elastic and easily accessible to
ultrasound. Subjects were examined in the supine
pasition, with the head turned 45° away from the
side being scarined. Three measurements of IMT
were. taken from the far wan of the right and left
comman carotid arteries at the maximum thickness
and the average of the six measurements was used.
Patients and non-diabetic subjects were divided
into two groups according to age and gender. IMT
values were correlated with sex, body mass index
(BMI), systolie blood pressure (sBP), diastolic
blood pressure (dBP), serum lipid Jevels, HbAle
and left ventricular ejection fraction (LVEF).
Furthermore, duration of DM was alsa eonsidered.
Differences between the patients and control subjeets were analyzed by the Mann- Whitney U test
and Student's t-test as needed; p values !ess than
0.05 were considered to be significant. LInear
regression analysis was also performed to carreIate
IMT with blood pressure, duration of DM, serum
lipid levels and LVEF.
.
RESULTS
There w<,s no significant correlation between
IMT values and sex, BMI, sBP, dBP, serum lipid
levels, HbA1cor LVEF (Table 1).
Patients with Tl DM less than 10 years of age
did not show a significant difference in IMT values
from non-diabetic subjects of similar age (0.38 ::!:
0.05 vs 0.37 ::!: 0.03 mm, NS). Patients 10 years of
age or older had greater IMT values than nondiabetic subjects of similar age (0.45 ::!:0.06 vs 0.42
::!: 0.04 mm): however, the difference was not
statistically significant (Fig. 2).
The mean ::!:SD duration of DM was 4.1 :t 2.8
years. IMT values did not have a good correlation
with the duratIon of DM (r = 0.30).
IMT values for children and adolescents with
TLOlv! showed a good correlation wIth age (r =
0.71). (Fig. 3). There was no correlation between
IMT and sex. BMI, sBP, dBP, serum lipid levels,
HbA1c or LVEF.
.
JOURNAL OF PEDIATRIC
ENDOCRINOLOGY
& METABOLlSM
EARL Y ATHEROSCLEROSIS
Fig.1:
i 133
IN TYPE I DIABETES MELLlTUS
Typical B-sean pattem of common carotid artery.
TABLEl
Comparison of the cl inical eharacteristies of patients with type i diabetes mellitus (Tl DM)
and health)' eontrols
TlDM
P
-13
52
-
Sex (M/F)
19/24
24/28
NS
Age (years)
IL.3 :1: 3.3
11.6:1:3.8
NS
EMI (kg/ml)
18.1 :1:3.4
17.9::1:3.0
NS
Total cholesterol (mg/di)
]53.6::1:28.5
162.4::1:33.9
NS
TG (ing/di)
89.8:!:: 31.6
90.9:I: 40.]
NS
HDL cholesterol (ing/di)
49.9::1: 12.9
54.3 :1:16.8
NS
LDL cholesterol (ing/di)
85.7:!::25.7
91.3::1:29.4
NS
107.1:1: 9
NS
Control
n
sEP (mmHg)
106
dEP (minHg)
66.2 ==9.5
68::!:7.5
NS
LVEF (%)
65.7:!:: 7.2
66.4::!: 7.7
NS
IMT (min)
0.40 :t 0.04
0.-12:t 0.06
NS
:!:: ] 1. ]
BM] = body mass index: TG = triglycerides: sBP = systolic blood pressure; dBP = diastolic b]ood
pressure: LVEF = lefi vemricular ejection fraction: IMT = intimal plus medial thickness; NS = not
.significanl.
VOLUME
15. NO. 8. 2002
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1134
T. YAVUZ ET AL.
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Controls
IOOM
Controls
age < 10
Fig.2:
IOOM
age ~ 10
IMT values (average :f: SEM) of controJs and patients with type J diabetes mellitus (IDDM), grouped by age < JO and 2:1O
years old.
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0.8 i
0.6
<>
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0.4
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5
10
15
20
Age (years)
Fig.3:
Relationship between JMT and age in children wIth type i diabetes melliius.
JOURNAL OF PEDIA TRIC ENDOCRINOLOGY
& MET ABOLlSM
!?h
EARL Y ATHEROSCLEROSiS
DISCVSSION
Our results indicate that IMT values have a
linear relationship with age, but no correlation with
sex, .BMI, sBP, dBP, serum lipid levels, HbAIc or
LVEF.
Patients with DM tend to suffer unduly from
premature and severe atherosclerosis. it was found
that patients with DM in general show an increased
morbidity and mortality from cardiovascular
causes3,12. DM, along with age, hyperlipidemia,
smoking, and hypertension, aggravates carotid
atherosclerosis 4.
B-mode imaging is a reliable method for
measuring IMT of human arteries in vivo and
evaIuation of IMT can be carried out more precisely
in the early stages of atherosclerotic disease7,1l. The
extent of carotid artery atherosclerosis as measured
by ultrasound B-mode imaging has been shown to
have a strong correlation with the presence of
coronary atherosclerotic diseasel3. In the present
study, we used this method to determine early
atherosclerosis in children and adolescents with
TlDM.
Only a few studies have been performed on IMT
in patients with Tl DM. Most of the studies on the
IMT value s of patients with Tl DM were carried out
in adolescents and young adults. Some of these
studies conc!uded that patients with TlOM have
significantly greater IMT values than non-diabetic
subjects
4,8.10.14-16.
Yamasaki et al.]O examined 105 patients with
TlOM ranging from 4 to 25 years of age. In their
study, patients less than 10 years of age showed
greater (but not significant) IMT values than nondiabetic subjects of similar age (0.454 :i: 0.079, n =
23 vs 0.382 :i: 0.056 mm, n = 5). In contrast to our
study, IMT values of their patients with TlOM of
lOto 19 years of age (0.525 :i: 0.124 mm, n = 68)
were significantly greater than those of age-
matched non-diabetic subjects (0.444 :i: 0.057mm,
n = 12, p = 0.01169). This may be due to a shorter
durationof the disease in our patients(5.5 :!: 4.7
years vs 4.1 :t 2.8 years in our study). Gunczler et
al,17 found no change in IMT in children and
adolescents with TIDM ofshort duration (3.4:i: 3.3
years). Only a few studies have investigated the
relationship between duration of DM and IMT in
patients with, Tl DM. IMT was related to duration
VOLUME
15, NO. 8, 2002
IN TYPE I DIABETES MELLlTUS
.
1135
.
. .10]4
of DM in two stud ies ' , wh ereas th is was not
confirmed in four studies in addition to our
study8,15,16,18,19.
IMT value s for children and adolescents with Tl DM showed a positive correlation
with age (r = 0.71). This finding was consistent
with those of the literature8.
In conclusion, we showed that in young children
with TlOM there was no association between the
DM and early macrovascular lesions, such as IMT
of the common carotid artery. IMT value s may
increase significantly after a certain age in patients
with Tl DM, which could only be revealed by
further studies in children with Tl DM.
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