Diabetes Research and Clinical Practice 74 (2006) 3340 www.elsevier.

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Arterial wall thickening and stiffening in children and adolescents with type 1 diabetes
Mehmet Emre Atabek a,*, Selim Kurtoglu b, Ozgur Pirgon a, Murat Baykara c
a b

Department of Pediatric Endocrinology and Diabetes, School of Medicine, Selcuk University, Konya, Turkey Department of Pediatric Endocrinology and Diabetes, School of Medicine, Erciyes University, Kayseri, Turkey c Department of Radiology, School of Medicine, Erciyes University, Kayseri, Turkey Received 12 November 2005; accepted 9 March 2006 Available online 18 April 2006

Abstract Objective: We evaluated structural and functional characteristics of the common carotid artery (CCA), a marker of early carotid atherosclerosis, and investigated their relation to metabolic and anthropometric parameters in children and adolescents with type 1 diabetes. Materials and methods: Non-invasive ultrasonographic measurements were made in 45 type 1 diabetic patients and 33 controls. Age, sex, and body mass index were matched between patients and controls. We investigated intima-media thickness (IMT), compliance, distensibility, diastolic wall stress (DWS) and incremental elastic modulus (IEM) of the CCA. Metabolic and anthropometric parameters such as serum lipids, plasma glycated haemoglobin, body mass index, waisthip ratio and blood pressure were assessed. Results: The diabetic patients had signicantly higher CCA-IMT than the controls (0.48 0.06 mm versus 0.33 0.07 mm; p < 0.001). The diabetic children had signicantly higher values than the controls for DWS (1.18 0.29 mmHg 102 versus 0.81 0.25 mmHg 102; p < 0.001) and for IEM (1.26 0.57 mmHg 103 versus 0.77 0.28 mmHg 103; p < 0.001). The difference was not signicant between patients and controls for arterial compliance and for distensibility ( p > 0.05). In a multivariate regression model for all subjects, diabetic state was the best predictor of IMT ( p < 0.001), DWS ( p < 0.001) and IEM ( p = 0.001). Conclusion: Our results suggested that children and adolescent patients with type 1 diabetes are associated with early impairment of CCA structure and function and that diabetic state may be the main risk factor for CCA wall stiffening and thickening, which are of considerable concern as possible early events in the genesis of atheroma. # 2006 Elsevier Ireland Ltd. All rights reserved.
Keywords: Type 1 diabetes; Early atherosclerosis; Common carotid artery

Abbreviations: CCA, common carotid artery; IMT, intima-media thickness; DWS, diastolic wall stress; IEM, incremental elastic modulus; LCSA, lumen cross-sectional area; WCSA, intima-media crosssectional area; CSC, cross-sectional compliance; CSD, cross-sectional distensibility; HDL-cholesterol, high-density lipoprotein-cholesterol; LDL-cholesterol, low-density lipoprotein-cholesterol; HbA1c, plasma glycated haemoglobin * Corresponding author at: Selcuk Universitesi Meram Tip Fakultesi, Cocuk Sagligi ve Hastaliklari, 42080 Konya, Turkey. Tel.: +90 332 223 63 50; fax: +90 332 223 61 81. E-mail address: meatabek@hotmail.com (M.E. Atabek).

1. Introduction Diabetes mellitus is established as an independent risk factor for cardiovascular morbidity and mortality in adults and children with type 2 diabetes [1,2]. Although it is well known that adolescents with type 1 diabetes are at risk for developing microvascular disease [3], the effects of diabetes on larger vessels have not been extensively studied. Large vessel dysfunction and its

0168-8227/$ see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2006.03.004

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relation to leptin, insulin-like growth factor-1 and magnesium in diabetic adolescents have been reported previously [46]. The role of glycemic control is of particular interest. The few data available relating glycemia to cardiovascular disease in type 1 diabetes are controversial. The DCCT results suggested a borderline salutary effect of intensive treatment on combined macrovascular events [7]. A follow-up report by the Stockholm Diabetes Intervention Study suggested that intensive treatment leads to reduced intima-media thickness (IMT) and less stiffening of the carotid arteries [8], although the results were not uniformly supportive. The recent study did not support an association between HbA1c at the time of carotid ultrasonography during the 6.5 years of the DCCT and IMT [9]. Autopsy studies in adolescents and young adults document that atherosclerosis begins in adolescence and that the traditional risk factors are associated with its development [10]. This emphasizes the importance of evaluating the development of macrovascular changes in children and adolescent patients with type 1 diabetes. IMT is the structural feature of common carotid artery (CCA), and distensibility, compliance, diastolic wall stress and incremental elastic modulus are functional features of CCA. Arterial stiffness and thickness include decreased distensibility, decreased compliance, increased diastolic wall stress (DWS), increased the incremental elastic modulus (IEM), and increased IMT detected by ultrasonography [11]. The aim of our study was to evaluate whether children and adolescent patients with type 1 diabetes showed early abnormalities of the CCA structure and function and to assess their relationship to metabolic and anthropometric parameters in children and adolescents with type 1 diabetes. This study is the rst to assess both structural and functional changes of CCA, which is the preclinical atherosclerotic markers, in the same group of subjects.

2. Materials and methods 2.1. Study population The baseline study population consisted of 45 patients (23 female, 22 male, mean age: 14.8 2.5 years, age range: 919 years) with type 1 diabetes diagnosed according to the World Health Organization denition and a control group of 33 age, sex and body mass index matched healthy children (17 female, 16 male, mean age: 14.1 1.9 years, age range: 1017 years) (staff members children). The study population had been presented earlier [5]. Inclusion criteria was >1 year period from diagnosis of type 1 diabetes which was detected

19 years of age and requiring insulin treatment. None of the individuals studied had diseases known to affect CCA functions such as hypertension, hyperlipidemia and other cardiovascular diseases, and no one was under any medication other than antidiabetic drugs. All patients and controls had never smoked. The patients were seen for period of 3 months. Moreover, the patients were divided into two categories as 05 years (n: 24) and more than 5 years (n: 21) according to duration of diabetes and CCA functions were evaluated between groups. Blood pressure, body weight, fasting blood glucose, HbA1c, total cholesterol, high-density lipoprotein-cholesterol (HDL-cholesterol), triglycerides, low-density lipoproteincholesterol (LDL-cholesterol), daily insulin dose, and urinary albumin excretion were determined. Moreover, we looked for correlation between CCA functions, metabolic, and anthropometric parameters in both groups. In our center, 24 h urine samples were obtained and estimated for albuminuria after excluding proteinuria due to urinary tract infection. Microalbuminuria was dened as 24 h. Urinary albumin excretion >30 mg, and overt clinical nephropathy was recorded when urinary albumin excretion exceeded 300 mg/24 h in at least two urine samples evaluated within a 12 weeks interval. None of the patients had a diagnosis of renal disease unrelated to diabetes during the follow up. Ophthalmoscopy through dilated pupils was carried out in all diabetic patients to assess the presence of retinopathy, by the ophthalmologist. Neuropathy was tested once in all subjects by the same standard clinical method. In brief, the specic symptoms of somatic peripheral symmetrical polyneuropathy (neuropathy) were pain, paresthesia, tickling and muscle weakness. Knee and ankle jerks and vibration sense over the lateral malleoli (using a tune fork of 256 Hz) were tested. The patients were considered to have neuropathy if they had typical symptoms and impaired vibratory sensation. Hyperlipidaemia was dened as serum lipids higher than 95% for age and sex and/or receiving lipid-lowering therapy [12]. Arterial blood pressure was monitored under standard conditions after at least 5 min at rest in triplicate at 5 min intervals. Subjects were considered as hypertensive if their systolic blood pressure and/or their diastolic blood pressure were >95% for age and sex, or if they were receiving antihypertensive treatment [13]. Anthropometric data were obtained by trained research personnel. Height was measured using a wall-mounted stadiometer, and weight was determined using a balance scale. Body mass index was calculated as the ratio of weight (kg) to the square of height (m2). Hip circumference and waist circumference were recorded. Our institutional review board approved the study. Before the study, written informed consent was obtained from the older children and from both parents of all children. 2.2. Analytical methods Blood samples were collected after an overnight fast from the diabetic and control children. Serum glucose, lipid con-

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centrations and urine microalbumin were assayed on autoanalizator of the Konelab 60i analyser (Konelab, Espoo, Finland). Plasma HbA1c concentrations were determined from samples taken during outpatient visit by automated high-performance liquid chromatography (reference rate < 6.05%) (LC/MS, Thermo Finnigan, Basel, Switzerland). 2.3. CCA ultrasonography The subjects were studied in the early afternoon under standardized conditions, in a quiet room at a comfortable temperature. All fasted before testing and were asked to refrain from strenuous exercise or drinking alcohol or caffeine containing beverages for 24 h before the study. Upon arrival at the investigation unit, the subjects were equipped with measurement devices and then rested supine for about 1520 min until the absence of evident heart rate and mean blood pressure trends demonstrated that satisfactory baseline conditions had been achieved. Arterial blood pressure, carotid artery values were measured during the last 5 min of the resting period. The same sonographer, who was blinded to the participants case status and risk factor levels, did all examinations. High-resolution B-mode ultrasonography of the right CCA was performed with an Acuson Sequoia (Acuson, Mountain View, CA) with a linear 7.5 MHz transducer. The participants were examined in the supine position with the head turned slightly to the left. Longitudinal images of the CCA were obtained by combined B-mode and color Doppler ultrasound examinations. The IMT of the CCA far wall was measured with the electronic calipers of the machines, as described by Pignoli et al. [14]. On a longitudinal, twodimensional ultrasound image of the carotid artery, the posterior (far) wall of the carotid artery are displayed as two bright white lines separated by a hypoechogenic space. The distance between the leading edge of the rst bright line of the far wall and the leading edge of the second bright line indicates the IMT. The IMT was measured during end diastole. The IMT measurements were performed online. The mean IMT was calculated for each patient as the average of three consecutive measurements of maximum far wall thickness obtained from the CCA; 20 mm below the carotid bulb. M-mode ultrasound examinations were recorded on-line. The maximal end-diastolic carotid lumen diameter was measured at the R wave of the electrocardiogram. Three measurements each of systolic and diastolic diameters were averaged. The diameter change was calculated as the difference between the systolic and diastolic averages [11]. Lumen cross-sectional area was calculated as pdD2/4 and wall cross-sectional area as p(dD/2 + IMT)2 p(dD/2)2. Cross-sectional compliance and distensibility of the CCA were calculated from diameter changes during systole and from simultaneously measured pulse pressure (DP) according to the following formulae: cross-sectional compliance = p(sD2 dD2)/4DP; cross-sectional distensibility = (sD2 dD2)/(dD2DP) Diastolic wall stress was calculated as mean

arterial pressure multiplied by dD/2IMT. Whereas compliance provides information on elasticity of the artery as a hollow structure, incremental elastic modulus provides information on the properties of the wall material independently from arterial geometry. This variable was calculated as 3/(1+lumen cross-sectional area/wall cross-sectional area) divided by cross-sectional distensibility. Repeatability of measurements was assessed as previously described [11,15]. In order to assess structural and functional characteristics of CCA, two observers examined the CCA of eight healthy children on two occasions, separated by a periods of 2 weeks. The various formula given for the functional changes were automated by online calculations. Data were expressed as mean S.D. The Kolmogorov Smirnov test was applied separately for boys and girls to check the normality of the variables. Differences between data were studied using the Students t-test. Statistical correlation was assessed using the Pearson test (r). Multiple linear regression analysis was performed in standard, and forward stepwise selection to identify independent factors affecting CCA-IMT, distensibility, compliance, diastolic wall stress and the incremental elastic modulus and to estimate the nal predictors of their variability. Statistical signicance was taken as p < 0.05. The intra-observer and the inter-observer reliability of IMT, CSC, CSD and DWS were determined by calculating the correlation coefcient (Pearsons r). All statistical analysis was performed using the Statistical Package for Social Sciences (SPSS/Windows version 11 0, SPSS Inc., Chicago, IL, USA).

3. Results The characteristics of the study population are shown in Table 1. The groups were matched for age, sex, and body size. No signicant differences were observed in the values of weight, height, body mass index, waisthip ratio, systolic blood pressure and diastolic blood pressure between the both groups. The values of total cholesterol, triglycerides and LDL-cholesterol in diabetics, which were all within the range of normal values, were slightly higher than those in controls, but not signicantly so. There were no signicant sex differences in view of metabolic and anthropometric data in both groups. All but four subjects with diabetes had a urinary albumin excretion in the normoalbuminuric range (normal, <30 mg/24 h). The urinary albumin excretion of the patients was 11.6 14.6 mg/24 h. The other four patients had only modest microalbuminuria. None of the patients with diabetes had evidence of the microvascular complications, such as diabetic retinopathy (background and proliferativ), clinical neuropathy and overt nephropathy. At the time of the study, we were using conventional insulin therapy in most of the diabetic patients.

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Table 1 Characteristics of patients with type 1 diabetes and healthy controls Diabetic patients Number of subjects (boys) Age (years) Weight (kg) Height (m) Body mass index Waisthip ratio Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Total cholesterol (mg/dl) Triglycerides (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) Duration of diabetes (years) Daily insulin dose (U/kg/24 h) HbA1c (%) Urinary albumin excretion (mg/24 h) Data are mean S.D.; NS = non-signicant. 45 (22) 14.8 2.5 49.1 13.3 1.5 0.1 19.7 3.2 0.79 0.01 116.3 6.9 69.5 4.7 151.9 26.2 90 32.6 52.4. 18.1 81.5 22.4 4.4 2.5 1.02 0.2 10.5 2.6 11.6 14.6 Controls 33 (16) 14.1 1.9 48.3 9.6 1.5 0.1 19.4 1.6 0.78 0.01 113.9 6 69.2 4.5 149.7 23.3 90 24.2 57.2 7 78.4 22.8 p-value NS NS NS NS NS NS NS NS NS NS NS

Pearsons r was 0.96, 0.95, 0.95 and 0.96 for the intra-observer reliability of IMT, CSC, CSD and DWS, and 0.89, 0.87, 0.88 and 0.87 for the inter-observer reliability of IMT, CSC, CSD and DWS, respectively. The carotid artery IMT of patients and controls ranged from 0.4 to 0.6 and 0.20.5 mm, respectively. The diabetic patients had signicantly higher CCAIMT than the controls (0.48 0.06 mm versus 0.33 0.07 mm; p < 0.001). The difference was not signicant between patients and controls for arterial compliance (0.16 0.06 mm2 mmHg1 versus 0.19 0.06 mm2 mmHg1; p > 0.05) and for distensibility (0.78 0.28 mmHg1 102 versus 0.92 0.33 mmHg1 102; p > 0.05). The diabetic children had signicantly higher values than the controls for DWS (1.18 0.29 mmHg 102 versus 0.81 0.25 mmHg 102; p < 0.001) and for IEM (1.26 0.57 mmHg 103 versus 0.77 0.28 mmHg 103; p < 0.001) (Table 2).

Within the diabetic patients, those who have diabetic duration of equal or less than 5 years had signicantly different CCA-IMT and CSC than those who have diabetic duration of more than 5 years (0.46 0.06 mm versus 0.50 0.06 mm, p = 0.01 and 0.18 0.06 mm2 mmHg1 versus 0.14 0.05 mm2 mmHg1, p = 0.05, respectively). The correlations between carotid function and other measurements are shown in Table 3, for children with diabetes. In patients with diabetes, carotid IMT correlated signicantly with age, body mass index, waisthip ratio, systolic blood pressure, triglycerides and diabetes duration. Arterial compliance correlated signicantly with diabetes duration. Distensibility correlated signicantly with systolic blood pressure, total cholesterol and LDL-cholesterol. Arterial wall stress correlated signicantly with age, body mass index, waisthip ratio, systolic and diastolic blood pressure, triglycerides and diabetes duration. IEM

Table 2 Structural and functional characteristics of the CCA in patients with type 1 diabetes Diabetic patients, n = 45 Systolic diameter (mm) Diastolic diameter (mm) IMT (mm) CSC (mm2 mm Hg1) CSD (mm Hg1 102) DWS (mm Hg 102) IEM (mm Hg 103) LCSA (mm2) WCSA (mm2) 6 0.7 5.2 0.7 0.48 0.06 0.16 0.06 0.78 0.28 1.18 0.29 1.26 0.57 21.6 5.7 8.7 1.9 Controls, n = 33 6.1 0.8 5.2 0.8 0.33 0.07 0.19 0.06 0.92 0.33 0.81 0.25 0.77 0.28 22 7.1 5.9 1.8 p-value NS NS <0.001 NS NS <0.001 <0.001 NS <0.001

Data are mean S.D.; NS, non-signicant; CSC, cross-sectional compliance; CSD, cross-sectional distensibility; DWS, diastolic wall stress; IEM, incremental elastic modulus; LCSA, lumen cross-sectional area; WCSA, intima-media cross-sectional area.

M.E. Atabek et al. / Diabetes Research and Clinical Practice 74 (2006) 3340 Table 3 Pearson correlation coefcient between CCA functions and metabolic and anthropometric parameters in patients with type 1 diabetes Variable IMT Age Body mass index Waisthip ratio Systolic blood pressure Triglycerides Diabetes duration CSC Diabetes duration CSD Systolic blood pressure Total cholesterol LDL-cholesterol DWS Age Body mass index Waisthip ratio Systolic blood pressure Diastolic blood pressure Triglycerides Diabetes duration IEM Total cholesterol Triglycerides Diabetes duration Regression coefcient (r) 0.31 0.42 0.45 0.48 0.37 0.42 0.28 0.30 0.33 0.30 0.43 0.52 0.50 0.56 0.36 0.32 0.29 0.33 0.343 0.29 p-value 0.03 0.004 0.002 0.001 0.01 0.003 0.03 0.04 0.02 0.04 0.003 <0.001 <0.001 <0.001 0.01 0.03 0.04 0.02 0.02 0.04

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Table 4 Forward stepwise multivariate regression analyses of IMT, CSC, CSD, DWS and IEM in patients with type 1 diabetes Dependent variable Independent variable IMT Systolic blood pressure Waisthip ratio Diabetes duration Total cholesterol HDL-cholesterol Body mass index Waisthip ratio Triglycerides b-coefcient p-value 0.38 0.34 0.28 0.38 0.30 0.25 0.32 0.34 0.002 0.005 0.02 0.009 0.03 0.03 0.008 0.02

CSD DWS IEM

IMT, intima-media thickness; CSC, cross-sectional compliance; CSD, cross-sectional distensibility; DWS, diastolic wall stress; IEM, incremental elastic modulus.

IMT, intima-media thickness; CSC, cross-sectional compliance; CSD, cross-sectional distensibility; DWS, diastolic wall stress; IEM, incremental elastic modulus.

correlated signicantly with total cholesterol, triglycerides and diabetes duration. In control subjects, carotid IMT correlated signicantly with age (r = 0.38, p = 0.02), systolic blood pressure (r = 0.36, p = 0.03), weight (r = 0.35, p = 0.04) and body mass index (r = 0.35, p = 0.04). IEM correlated signicantly with triglycerides (r = 0.38, p = 0.02). DWS correlated signicantly with age (r = 0.37, p = 0.03) and triglycerides (r = 0.35, p = 0.04). In a multivariate regression model for all subjects, the independent correlates for IMT were diabetic state ( p < 0.001), systolic blood pressure ( p < 0.003), and waisthip ratio ( p = 0.03), with the total variance explained being 70%, the independent correlates for distensibility was total cholesterol ( p = 0.04), with the total variance explained being only 33%, the independent correlates for DWS were diabetic state ( p < 0.001), HDL-cholesterol ( p = 0.001), waisthip ratio ( p = 0.01), body mass index ( p = 0.02), total cholesterol ( p = 0.02), and LDL-cholesterol ( p = 0.04), with the total variance explained being 70%, the

independent correlates for IEM were diabetic state ( p = 0.001) and total cholesterol ( p = 0.04), with the total variance explained being only 36%. No independent correlates for CSC were found in the model. The stepwise multiple regression analysis between carotid function and other measurements are shown in Table 4, for children with diabetes. We included age, systolic blood pressure, diastolic blood pressure, body mass index, waisthip ratio, diabetes duration, HbA1c, urinary albumin excretion, daily insulin dose and serum lipids as independent variables in the model for CCA-IMT in patients with diabetes, but systolic and diastolic blood pressure were not included in the model for CCA functions. Systolic blood pressure, waisthip ratio and diabetes duration emerged as independent correlates for mean IMT in children with diabetes, the total variance explained being 46%. Waisthip ratio and body mass index emerged as independent correlates for DWS in children with diabetes, the total variance explained being 60%. In controls, age was the best predictor of IMT (b = 0.38, p = 0.02). 4. Discussion Type 1 diabetes in children predicts a broad range of later health problems including an increased risk of cardiovascular morbidity and mortality [36]. Thus, diabetes-related abnormalities that increase the risk of macrovascular disease may begin in childhood. Consistent with this possibility, our study provided evidence that type 1 diabetes is associated with early CCA wall stiffening and thickening. This increased IMT and arterial stiffness in children with type 1 diabetes may be an early step in the development of atherosclerosis. Far wall common carotid computerized measurement was preferred because this super-

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cial and straight segment offers the best geometric conditions for obtaining a high precision and reproducibility rate of ultrasound IMT measurement [16]. Measuring carotid IMT with ultrasonography correlates well with pathological measurements and is reproducible [17]. Increased carotid IMT is signicantly related to known cardiovascular risk factors and to carotid plaque, a more advanced atherosclerotic lesion [18]. Yamasaki et al. [19] performed studies in juvenile patients with type 1 diabetes to investigate possible risk factors for carotid atherosclerosis. In their study, the IMT values (mean = 0.52 mm) for patients with type 1 diabetes, aged 1019 years, were signicantly greater than for age-matched non-diabetic individuals. They showed a signicant positive correlation between IMT and both duration of diabetes and age as seen in the present study. In another study, the IMT values (mean = 0.47 mm) for patients with type 1 diabetes, aged 714 years, were signicantly greater than for agematched non-diabetic individuals. They also found that type 1 diabetes was an independent risk factor for increased IMT [20]. Our results are consistent with these studies. In contrast to our study, Yavuz et al. [21] reported that children and adolescents with type 1 diabetes (aged 318 years) had not increased carotid IMT (mean = 0.40 mm), compared with controls. Moreover, Gunczler et al. [22] found no change in IMT in children and adolescents with type 1 diabetes of short duration (mean = 3.4 years). It is possible that the difference between the ndings of our study and those of Yavuz et al. [21] and Gunczler et al. [22] also relate to differences in age range of patients and in severity, duration, or metabolic control of diabetes in the study populations. The earliest histological atherosclerotic vascular changes, i.e. fatty streaks, are commonly found in the arteries of adolescent, whereas the development of raised lesions mainly occurs after the age of 20 years [23]. Case-control studies of children and young adults demonstrate that familial hypercholesterolemia and borderline hypertension are associated with greater IMT [2426]. Young adults with diabetes have also shown higher carotid IMT than controls [20,27]. In the present study, all patients had normal LDL-cholesterol concentration. Despite this; total cholesterol, LDLcholesterol and triglycerides concentrations were correlated with CCA wall stiffening and thickening. Consistent with previous studies systolic blood pressure was correlated with the measurements of carotid artery IMT in the present study. The relationship between systolic blood pressure and increased IMT suggested that smooth muscle proliferation also played a role in the early diffuse thickening of the arterial wall.

Epidemiologic and clinical evidence has emphasized the role of hyperglycemia in explaining the increased cardiovascular morbidity and mortality in diabetes [28]. Chronic state of hyperglycemia may induce atherogenesis by increasing oxidative stress, leading to increased LDL oxidation and decreased nitric oxide bioavailability, including endothelial dysfunction [20,29]. In the present study, although HbA1c levels in the adolescent patients with type 1 diabetes was more than twice that of normal ranges, we were unable to show a relationship between HbA1c and carotid artery changes. The fact that HbA1c has only reects a short period of glycemia may be a reason. Moreover, it has been reported that fasting plasma glucose should be used with caution as a measure of long-term glycemia. Fasting plasma glucose tended to progressively underestimate HbA1c at increasing plasma glucose levels [30]. Our data suggest that postmeal plasma glucose may contribute appreciably to HbA1c. There may be other factors causing this discrepancy, such as improper meter use, laboratory error, a physical condition that alters red cell life span, or variant hemoglobin interfering with the HbA1c assay method. The HbA1c assay was not standardized to Diabetes Control and Complications Trial HbA1c norms. Because, HbA1c level was restricted to a relatively narrow range, it may have been difcult to detect an impact of HbA1c levels on arterial wall thickening and stiffening. Our ndings also suggested that daily insulin dose and fasting glucose concentrations did not affect CCA wall stiffening and thickening at a childhood age. Although, reduction in body mass index slows the yearly rate of increase in carotid-wall thickness [31], the thickness of the arterial wall increasing with proportional to body mass index is still a matter of debate. The incremental elastic modulus, which reects the properties of the arterial wall independently of arterial geometry, was increased in our diabetic patients. These ndings suggest a rearrangement of the wall material in diabetic children. In the present study, the increase in diastolic wall stress and in IMT was related to the waist hip ratio and to the body mass index. Truncal fat includes the intra-abdominal fat located around the viscera, which is the type of body fat related to metabolic cardiovascular risk factors [32]. Our results suggested that an android pattern of fat distribution might be associated with CCA wall stiffening and thickening in diabetic patients. Lambert et al. [33] reported that in adults with type 1 diabetes, those with microalbuminuria had decreased carotid artery distensibility compared with those without microalbuminuria and a control group. In Parikh et al.s study [34], despite a normal urinary

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albumin excretion in 31 of 35 subjects with diabetes, decreased carotid artery distensibility was still detectable. In our study, urinary albumin excretion in 41 of 45 subjects with diabetes (the other four having only modest microalbuminuria) was normal, and we did not nd correlation between microalbuminuria and the structural and functional changes of carotid artery. The study included relatively small numbers of participants. However, children with diabetes who participated in this study were representative of the total number of eligible children with diabetes treated in our clinic with regard to age, disease duration, glycemic control and lipids. Our study show that there were increased IMT, increased diastolic wall stress and increased the incremental elastic modulus in children and adolescents with type 1 diabetes although they had normoalbuminuric range, normal lipid levels and normal blood pressure except for poorly metabolic control. Arterial wall stiffening and thickening, begun in childhood age, may be an important step in the development of atherosclerosis in type 1 diabetes.

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