Blood pressure from childhood to adolescence in obese youths in relation to insulin resistance and asymmetric dimethylarginine

37

 

ORIGINAL ARTICLE

Blood pressure from childhood to adolescence in obese youths

in relation to insulin resistance and asymmetric dimethylarginine

T. de Giorgis1,2 · M. L. Marcovecchio1,2 · C. Giannini1,2 · V. Chiavaroli1,2 · F. Chiarelli1,2 · A. Mohn1,2

Abstract

Background and propose Hypertension is the most important cardiovascular complication of obesity, even dur-ing childhood. Several studies have demonstrated that there is a natural progression of hypertension from childhood to adulthood. However, there are no data reporting a potential worsening in blood pressure (BP) already moving from the pre-pubertal to the pubertal period in obese youths. The aim of this study was to evaluate early change in BP and its relation to insulin resistance (IR) and asymmetric dimethy-larginine (ADMA).

Methods Thirty obese children underwent a first assessment when they were pre-pubertal (visit_1) and were re-evaluated after a mean of 4.5 years (visit_2). At both visits, anthropo-metric parameters were assessed, blood samples were col-lected for measurement of insulin, glucose and ADMA and a 24-h ambulatory BP monitoring was performed.

Results At visit_2, the study participants presented increased HOMA-IR and ADMA compared to visit_1 (HOMA-IR: 3.6 ± 2.8 vs 2.8 ± 1.4, p = 0.01; ADMA: 1.57 ± 0.78 vs 0.77 ± 0.52 μmol/l, p < 0.001). Values of 24-h systolic and diastolic BP SDS (0.86 ± 0.79 vs 0.42 ± 0.83, p = 0.001; −0.45 ± 0.82 vs 0.08 ± 0.51, p = 0.001) were significantly increased at visit_2

Electronic supplementary material The online version of this article (doi:10.1007/s40618-015-0351-2) contains supplementary material, which is available to authorized users.

1\ Department of Pediatrics, University of Chieti, Ospedale Policlinico, Via dei Vestini 5, 66100 Chieti, Italy

2\ Clinical Research Center, ‘G. d’Annunzio’ Foundation, University of Chieti, Chieti, Italy

compared to visit_1. At both visits, BMI-SDS, HOMA-IR and ADMA were associated with 24-h BP. In addition, over-time changes in IR and ADMA influenced changes in systolic blood pressure and diastolic blood pressure from childhood to adolescence (p < 0.05).

Conclusions Changes in BP already occur moving from the pre-pubertal to the pubertal period in obese children, and modifications in insulin resistance and ADMA seem to be implicated in this early progression in BP.

Keywords Blood pressure · Puberty · Obesity · Insulin resistance · ADMA

Introduction

Hypertension represents one of the most important public health problems, and it undoubtedly plays a pivotal role in the pathogenesis of cardiovascular diseases [1]. Fur-thermore, obesity seems to be the underlying cause of the increased prevalence of essential hypertension in adults [2, 3]. During the last years, several epidemiological studies have reported an alarming increase in high blood pressure (BP) starting already in late infancy, which again has been correlated with the growing epidemic of childhood obesity [4, 5]. In addition, longitudinal studies have clearly demon-strated that there is a natural progression of BP and other cardio-metabolic risk factors from childhood to adulthood in obese subjects [6–8].

Recently, several lines of evidence have highlighted that puberty represents a critical window of life for the onset of cardiovascular complications, such as hypertension. Puberty is characterized by several physiological hormo-nal changes able to influence insulin resistance and oxida-tive stress, which in turn can increase cardiovascular risk

[9–11]. However, there are no studies reporting a possible trend of high BP from pre-puberty to puberty.

Although the pathogenesis of hypertension in obese sub-jects is not fully understood, insulin resistance [12, 13] and the emerging cardiovascular marker, asymmetric dimethyl-arginine (ADMA) [14], seem to be two main factors play-ing a crucial role in its development during adulthood. This is supported by the observation that both insulin resist-ance and ADMA lead to an increased absorption of renal sodium, an impaired autonomic nervous system activity and vascular smooth muscle growth. All these factors seem to be involved in the pathogenesis of hypertension [15–17].

The aim of the present study was to assess whether rele-vant changes in ambulatory blood pressure (ABP) might be found already moving from childhood to adolescence, and whether insulin resistance and ADMA might play a role in these overtime changes in BP.

Subjects and methods

Subjects

The study population included 30 Caucasian obese children (15 males) who had been referred to the Obesity Clinic of the Department of Paediatrics, University of Chieti, Italy. All sub-jects were defined obese on the basis of a body mass index (BMI) >95th percentile for age and sex. A detailed medical and family history was obtained for all subjects. None of them were taking any medication known to affect body com-position or blood pressure and none had any medical illness.

The 30 obese children underwent a first assess-ment when they were pre-pubertal (visit_1, mean age: 9.0 ± 1.2 years) and were then re-evaluated during puberty (visit_2, age: 14.1 ± 1.4 years), after a time interval of 4.5 ± 0.4 years, during which they did not perform any clinical and biochemical evaluation. All these patients were lost to regular follow-up after visit_1. In addition, they did not follow any specific lifestyle change. After a mean of 4.5 years, they were invited to have a new clinical, meta-bolic and instrumental evaluation.

At both study visits, anthropometric parameters and pubertal stage were assessed. In addition, fasting blood samples were collected to measure glucose, insulin, lipids and ADMA and a 24-h ABP monitoring was performed. Secondary causes of hypertension (renal and adrenal forms, thyroid problems, hyperparathyroidism) were excluded in obese children with blood pressure >95th percentile.

Anthropometric assessments

Weight and height were measured with the child in light clothing and without shoes. Body weight was determined

to the nearest 0.1 kg and height was measured with Harpenden stadiometer to the nearest 0.1 cm. BMI was cal-culated as weight/height2 and expressed as kg/m2. Height, weight and BMI standard deviation scores (SDS) were cal-culated based on the age and sex reference values for Ital-ian children, and using the LMS method [18].

In all subjects, pubertal stage was defined on the basis of breast development in girls and genital development in boys [19].

Biochemical evaluation

At both study visits, fasting blood samples were collected for measurements of glucose and insulin. Glucose lev-els were measured with the glucose oxidase method and plasma insulin was measured with a 2-site immuno enzy-mometric assay (AIAPACK IRI; Tosoh, Tokyo, Japan). The limit of detection was 0.5 mU/ml, with intra-assay and inter-assay coefficients of variation of 0.7 %.

Indexes of insulin sensitivity

The homeostasis model assessment of insulin resistance (HOMA-IR) was used as a surrogate index of insulin sen-sitivity derived from fasting blood samples. HOMA-IR was calculated using the formula: [fasting insulin (mU/ ml) × fasting glucose (mmol/l)]/22.5 [20].

Lipid analysis

Serum total cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG) concentrations were determined by calorimetric enzymatic method. LDL-cholesterol (LDL-

  1. was calculated according to the Friedewald formula (LDL-C = total cholesterol − HDL-C − TG/5).

ADMA determination

Plasma ADMA concentration was determined by an ELISA kit (Cusabio Biotech CO., LDT) which has recently been described and validated in detail. In brief, cross-reactivity was 1.2 % for symmetric dimethylarginine (SDMA) and <0.02 % for l-arginine. The limit of detection was 0.05 μmol/l. The intra- and the inter-assay variation was 8 and 10 (CV %), respectively. There is a good correlation of the values meas-ured by this ELISA and LC-tandem MS (n = 29; r = 0.984; p < 0.0001). Reference ranges for ADMA have been estab-lished by this technique recently [21].

Ambulatory blood pressure monitoring

At both study visits, ABP monitoring was performed with a portable non-invasive oscillometric recorder (SpaceLabs

model 90207; Redmond, Washington, USA). The repro-ducibility and validity of this monitor have been exten-sively studied. In our study population, the same protocol for ABPM monitoring was applied at both study visits using the same equipment.

The left arm was used during both evaluations because this is how the cuffs were designed and three different cuff sizes were used (10 × 13 cm, 13 × 24 and 24 × 32 cm), selected on the basis of the arm circumference of each subjects.

ABP monitoring was performed during a normal day with typical activities but children were asked to avoid vig-orous exercises and to keep their arm relaxed during each daytime inflation. Furthermore, children and parents were asked to record the time they went to bed and the time they awoke, as well as exercise periods and the quality of the sleep, in a diary.

Within each visit, the reproducibility was assessed by simultaneous measurements of BP with a mercury sphyg-momanometer at the beginning and at the end of the moni-toring period.

Blood pressure readings were obtained at 20 min inter-vals during daytime and at 30 min intervals during night-time. At the end of the ABP monitoring, the monitor was downloaded to a personal computer for the analysis of the measurements. All readings taken 24 h were used to cal-culate mean 24 h systolic blood pressure (SBP) and dias-tolic blood pressure (DBP), whereas readings from 8:00 until 20:00 were used to calculate mean daytime SBP and DBP and readings from 00:00 until 06:00 were used to calculate mean nighttime SBP and DBP, in accordance with the method by Soergel et al. [22]. Recordings were automatically rejected if systolic blood pressure was >240 or <70 mmHg if diastolic blood pressure was >150 or <40 mmHg.

The 24 h monitoring of BP was considered adequate when a minimum of 70 % of the measurements were avail-able without errors both for sleep and/or wake BP.

To characterize the circadian blood pressure rhythm, the percentage of nocturnal fall in SBP and DBP was cal-culated using the formula: daytime SBP [or DBP]—night-time SBP [or DBP]/daytime SBP [or DBP] ×100. Patients were classified as dippers if their daytime systolic and DBP decreased by at least 10 % during night; all other subjects were classified as non-dippers.

The BP SDS was calculated according to the LMS method, using published reference data and a validated equation [23]. In brief, the LMS method was used to define the distribution of a parameters Y by its median (M), the coefficient of variation (S), and a measure of skewness (L) required to transform the data to normality [18].

The equation is: (SDS): SDS [(Y/M(t))L(t) − 1]/ (L(t) × S(t)), where Y is the child’s individual systolic,

diastolic BP value, and L(t), M(t) and S(t) are the gender-specific values of L, M and S interpolated for the child’s height.

Statistical analysis

Analysis was performed using SPSS version 16 software for Windows (SPSS Inc., Chicago, IL, USA). All data are expressed as mean ± SD or median (interquartile range) unless otherwise specified. Data were analyzed for normal-ity, and log transformed where required to allow the use of parametric analysis. Two-tailed significance was set to p < 0.05.

Paired T test was used to evaluate differences in the study variables between study visit_1 and study visit_2, whereas unpaired T test was used to evaluate differences between genders.

A partial correlation analysis was used to establish asso-ciations between BP SDS and variables of interest, after adjusting for potential confounding factors (age, gender).

To evaluate which pre-pubertal factors could influence changes in BP from pre-pubertal to pubertal period, a linear regression analysis was performed.

Results

The clinical and biochemical characteristics of the study population (n: 30; 15 males) at visit_1 (pre-pubertal period) and visit_2 (post-pubertal period) are reported in Table 1.

Anthropometric and cardio‑metabolic parameters:

visit_1 vs visit_2

When comparing anthropometric parameters between the two visits, height SDS was higher at visit_1 compared to visit_2, whereas no changes were found between the two visits in weight SDS and BMI-SDS (Table 1).

No significant differences were found in total choles-terol, HDL-cholesterol, LDL-cholesterol and triglycerides between the two study visits. Levels of fasting glucose were not different between the two study visits. In contrast, fasting insulin and HOMA-IR increased significantly from visit_1 to visit_2. ADMA levels increased significantly increased over the study period (Table 1).

Blood pressure: visit_1 vs visit_2

As expected by the known age-related changes in BP, 24 h, daytime and night-time SBP and DBP values significantly increased from visit_1 to visit_2.

24 h and nighttime SBP and DBP SDS values were sig-nificantly higher at visit_2 compared to visit_1, whereas no

\ J Endocrinol Invest
Table 1  Clinical characteristics, biochemical parameters and ambulatory blood pressure in the whole study population
Visit_1 Visit_2 p
Clinical and biochemical parameters
Age (years) 9.0 ± 1.2 [5.9–10.5] 14.1 ± 1.4 [11.1–16.6] <0.001
Pubertal stage P1-B1/G1 P5-B4/5-P5-G4/5
Weight (kg) 55.9 ± 12.4 86.6 ± 14.3 <0.001
Weight SDS 2.2 ± 0.6 2.1 ± 0.6 0.67
Height (cm) 139.6 ± 8.9 163.9 ± 7.2 <0.001
Height SDS 1.1 ± 0.8 0.5 ± 0.6 <0.001
BMI (kg/m2) 28.3 ± 3.8 32.2 ± 4.1 <0.001
BMI SDS 2.2 ± 0.4 2.2 ± 0.6 0.71
Total cholesterol (mg/dl) 176.4 ± 41.0 172.3 ± 40.5 0.45
Triglycerides (mg/dl) 92.8 ± 34.5 105.7 ± 51.0 0.16
Glucose (mg/dl) 85.4 ± 7.7 84.1 ± 6.5 0.41
Insulin (mU/l) 13.2 ± 5.2 22.7 ± 6.5 <0.001
HOMA-IR 2.8 ± 1.4 3.6 ± 2.8 0.01
ADMA (μmol/l) 0.77 ± 0.52 1.57 ± 0.78 <0.001
Blood pressure
24 h
SBP (mmHg) 110 ± 5.9 120 ± 5.1 <0.001
SBP SDS 0.42 ± 0.83 0.86 ± 0.79 0.001
DBP (mmHg) 64 ± 4.5 67 ± 3.0 0.004
DBP SDS −0.45 ± 0.82 0.08 ± 0.51 0.001
Daytime
SBP (mmHg) 114 ± 5.2 120 ± 5.7 0.001
SBP SDS 0.14 ± 0.60 0.27 ± 0.75 0.19
DBP (mmHg) 66 ± 4.5 68 ± 3.0 0.610
DBP SDS −0.80 ± 0.69 −0.87 ± 0.40 0.50
Nighttime
SBP (mmHg) 106 ± 7.6 116 ± 8.4 <0.001
SBP SDS 1.04 ± 0.80 1.53 ± 0.76 0.005
DBP (mmHg) 59 ± 6.1 63 ± 4.8 0.039
DBP SDS 0.48 ± 0.68 0.75 ± 0.35 0.021

Data are mean ± SD

SDS standard deviation score, BMI body mass index, HOMA-IR homeostasis model assessment of insulin resistance, ADMA asymmetric dimeth-ylarginine, SDS standard deviation score, SBP systolic blood pressure, DBP diastolic blood pressure

differences were found in daytime SBP and DBP SDS val-ues between the two study visits (Table 1).

At visit 1, 14 out of the 30 children (40 %) did not pre-sent the physiological decline of BP during night. This number increased at visit 2, when 16 out of the 30 ado-lescents (53 %) were non-dipper and 2 of the 30 subjects developed blood pressure values above the 95th percen-tile. These subjects were excluded from further statistical analysis.

Associations of ambulatory blood pressure with clinical and biochemical parameters

At visit_1 BMI SDS, HOMA-IR, insulin and ADMA were significantly correlated with 24-h, daytime and nighttime BP SDS (Table 2). The same associations were found at visit_2 (Table 2).

No significant correlations were identified between fast-ing glycemia and BP at both study visits.

Table 2  Associations of blood pressure and other main variables at visit 1 and visit 2

24 h SBP-SDS 24 h DBP-SDS Day SBP-SDS Day DBP-SDS Night SBP-SDS Night DBP-SDS
VISIT_1
BMI-SDS r = 0.580 r = 0.522 r = 0.359 r = 0.374 r = 0.512 r = 0.484
HOMA-IR p = 0.001 p = 0.004 p = 0.042 p = 0.05 p = 0.005 p = 0.009
r = 0.472 r = 0.570 r = 0.435 r = 0.445 r = 0.555 r = 0.349
ADMA p = 0.011 p = 0.002 p = 0.021 p = 0.018 p = 0.002 p = 0.069
r = 0.580 r = 0.439 r = 0.423 r = 0.401 r = 0.564 r = 0.432
Insulin p = 0.001 p = 0.019 p = 0.025 p = 0.035 p = 0.002 p = 0.022
r = 0.440 r = 0.499 r = 0.282 r = 0.350 r = 0.383 r = 0.413
Glycemia p = 0.019 p = 0.007 p = 0.146 p = 0.05 p = 0.044 p = 0.029
r = 0.295 r = −0.087 r = −0.037 r = 0.206 r = −0.034 r = −0.357
VISIT_2 p = 0.128 p = 0.661 p = 0.850 p = 0.274 p = 0.863 p = 0.062
BMI-SDS r = 0.537 r = 0.400 r = 0.475 r = 0.483 r = 0.182 r = 0.390
HOMA-IR p = 0.003 p = 0.035 p = 0.011 p = 0.009 p = 0.354 p = 0.04
r = 0.731 r = 0.582 r = 0.584 r = 0.583 r = 0.399 r = 0.363
ADMA p = 0.0001 p = 0.001 p = 0.001 p = 0.001 p = 0.035 p = 0.05
r = 0.606 r = 0.399 r = 0.569 r = 0.435 r = 0.435 r = 0.622
Insulin p = 0.0003 p = 0.035 p = 0.002 p = 0.021 p = 0.021 p = 0.004
r = 0.551 r = 0.415 r = 0.399 r = 0.490 r = 0.367 r = 0.460
Glycemia p = 0.002 p = 0.028 p = 0.035 p = 0.006 p = 0.05 p = 0.014
r = 0.027 r = 0.332 r = 0.300 r = −0.103 r = 0.336 r = 0.004
p = 0.892 p = 0.084 p = 0.121 p = 0.602 p = 0.07 p = 0.983

All correlations have been adjusted for age and gender

SDS standard deviation score, BMI body mass index, HOMA-IR homeostasis model assessment of insulin resistance, ADMA asymmetric dimeth-ylarginine, SBP systolic blood pressure, DBP diastolic blood pressure

Influence of ADMA levels at pre‑pubertal period on ambulatory blood pressure and metabolic parameters during post‑pubertal period

To evaluate the potential influence of ADMA and HOMA-IR levels during the pre-pubertal period (visit_1) on BP during the post-pubertal period (visit_2), a partial correla-tion analysis was performed.

Values of 24 h, daytime and nighttime SBP and DBP at visit_2 were directly correlated with levels of ADMA and by insulin resistance status (fasting insulin and HOMA-IR) also after adjustment for potential confounding factors, such as age and gender (Table 3). Fasting glycaemia was not associated with different parameters of blood pressure.

Regression analysis

To investigate the potential independent contribution of the variation of different cardio-metabolic parameters from visit_1 to visit_2 on BP, a multiple regression anal-ysis was performed. Delta (difference from visit_ 1 and visit_2) BMI-SDS, Delta HOMA-IR, Delta ADMA and values of ADMA, HOMA-IR and BMI-SDS at visit_1 were

considered as independent variables, and the variation of SBP and DBP from the pre-pubertal to the pubertal period (Delta SBP-SDS 24 h and Delta DBP-SDS 24 h) was used as a dependent variables. In this model, Delta HOMA-IR, Delta ADMA and BMI SDS at visit_1 were independently associated with the variation in ABP (Table 4).

Discussion

In this study, we showed that changes in BP are already detectable moving from the pre-pubertal to the puber-tal period in obese children. In addition, for the first time, our study demonstrated that over-time variations in insulin resistance and ADMA influence changes in BP, suggesting a possible role of these factors in the pathogenesis of car-diovascular disease later in life.

Hypertension represents one of the most common car-diovascular risk factors in obese subjects. The epidemic increase in childhood obesity has caused an important shift from secondary forms of hypertension, once predominant in this age group, to primary hypertension, previously con-sidered rare in children [4, 5]. Interestingly, several studies

Table 3  Association between cardio-metabolic parameters at visit_1 and ambulatory blood pressure at visit_2

HOMA-IR (visit_1) ADMA (visit_1) Insulin (visit_1) Glycemia (visit_1)
24 h SBP-SDS_2 r = 0.539 r = 0.586 r = 0.451 r = 0.014
24 h DBP-SDS_2 p = 0.003 p = 0.001 p = 0.016 p = 0.940
r = 0.504 r = 0.387 r = 0.385 r = 0.318
Day SBP-SDS_2 p = 0.006 p = 0.042 p = 0.043 p = 0.100
r = 0.452 r = 0.705 r = 0.371 r = 0.141
Day DBP-SDS_2 p = 0.016 p = 0.0002 p = 0.05 p = 0.474
r = 0.347 r = 0.609 r = 0.403 r = −0.092
Night SBP-SDS_2 p = 0.07 p = 0.001 p = 0.033 p = 0.641
r = 0.439 r = 0.307 r = 0.457 r = 0.336
p = 0.152 p = 0.112 p = 0.014 p = 0.07
Night DBP-SDS_2 r = 0.534 r = 0.413 r = 0.442 r = 0.022
p = 0.003 p = 0.029 p = 0.019 p = 0.912

Results are adjusted for potential confounding factors (age at visit_1, gender and BMI SDS at visit_1)

SDS standard deviation score, HOMA-IR homeostasis model assessment of insulin resistance, ADMA asymmetric dimethylarginine, SBP systolic blood pressure, DBP diastolic blood pressure

Table 4  Linear regression analysis between changes of blood pres-sure and cardio-metabolic parameters from pre-pubertal to pubertal period

Delta SBP-SDS 24 h Delta DBP-SDS 24 h
Delta HOMA-IR β = 0.440; p = 0.008 β = 0.117; p = 0.326
Delta ADMA β = 0.380; p = 0.017 β = 0.455; p = 0.006
Delta BMI-SDS β = 0.086; p = 0.575 β = −0.158; p = 0.380
BMI-SDS_1 β = 0.335; p = 0.002 β = 0.024; p = 0.882
ADMA_1 β = −0.112; p = 0.521 β = 0.170; p = 0.323
HOMA-IR_1 β = 0.086; p = 0.724 β = 0.220; p = 0.175

Bold values indicate statistical significance at p < 0.05

SDS standard deviation score, BMI body mass index, HOMA-IR homeostasis model assessment of insulin resistance, ADMA asym-metric dimethylarginine, SBP systolic blood pressure, DBP diastolic blood pressure

have shown the existence of a trend in obesity and related cardio-metabolic risk factors from childhood/adolescence to adulthood [6–8, 24]. Although all these studies consid-ered large populations, up to now it has not been assessed whether these trends can already be detectable moving from childhood to adolescence. This is an important issue to clarify as it would allow the identification of a specific time point when dedicated intervention programs should be started to improve long-term cardiovascular outcomes.

Interestingly, the present study demonstrated changes in BP occurring from the pre-pubertal to pubertal period, therefore, suggesting that puberty might represent the critical window for the onset and consolidation of BP abnormalities.

Several metabolic risk factors have been associ-ated with the risk of hypertension in obese children and adults. Whereas in some studies, this association has

been attributed to obesity itself [12, 25]; in others, insu-lin resistance has emerged as an independent risk factor for increased BP [26, 27]. In our study, a direct effect of obesity on BP was excluded, given that no changes in BMI SDS were detected from childhood to adolescence.

Over the years, there has been an increasing interest in the role of insulin in the pathogenesis of hypertension. Insulin can induce renal sodium absorption, increase sym-pathetic nervous system activity and stimulate vascular smooth muscle growth [4, 12]. According to this hypothesis, in our population not only we found that insulin resistance was directly and independently associated with BP both during childhood and adolescence, but also that HOMA-IR and fasting insulin during childhood were directly related to SBP and DBP during adolescence, suggesting the long-term effect of pre-pubertal insulin resistance on BP. In addition, the regression analysis confirmed that BP during adoles-cence period was influenced by changes in HOMA-IR from the pre-pubertal to the pubertal period, further underlining the role of insulin resistance on BP.

Recently, there has also been growing interest on ADMA, as a new emerging cardiovascular disease marker, which is involved in the pathogenesis and progression of vascular lesions and hypertension [22, 23]. Increased lev-els of ADMA inhibit NO synthesis and, therefore, impair endothelial function and lead to the development of athero-sclerosis. ADMA levels are increased in people with hyper-cholesterolemia, atherosclerosis, hypertension, chronic heart failure, diabetes mellitus and chronic renal failure [28, 29]. However, up to now, no studies have evaluated the potential influence of ADMA on BP changes from child-hood to adolescence. For the first time, our study demon-strated that ADMA concentrations are not only associated with BP during the pre-pubertal and post-pubertal period,

but over-time changes in this marker (from childhood to late adolescence) are independently related with the increase in SBP and DBP. These results support the theory that ADMA might be implicated in the pathogenesis of hypertension and cardiovascular disease.

Some limitations of this study need to be acknowledged. In particular, the small sample size and the clinical-based design limit the possibility to generalize our results. Never-theless, our results seem to be a good starting point to plan new and larger studies to confirm our preliminary findings.

In conclusion, our data suggest that in obese youths, changes in BP already occur moving from the pre-pubertal period to late adolescence, and this trend in BP is influ-enced by modifications in cardio-metabolic parameters between these two periods of life. Further longitudinal studies are needed to better clarify the natural history of changes in BP from childhood to adolescence and to imple-ment early interventions in childhood and adolescence, which might help in preventing the burden associated with hypertension later in life.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Ethical approval This study was approved by Ethical Committee of University of Chieti. All procedures included in this study were performed in the respect of the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent Written informed consent was obtained from all parents and oral consent from children at visit_1. At visit_2, written informed consent was obtained both from all parents and adolescents.

References

\ 1.\ Berenson G, Wattigney W, Bao W et al (1995) Rationale to study the early natural history of heart disease: the Bogalusa heart study. Am J Med Sci 310 Suppl:SS22–SS28

\ 2.\ Bogaert Y, Linas S (2009) The role of obesity in the pathogenesis of hypertension. Nat Clin Pr Nephrol 5:101–111

\ 3.\ Landsberg L, Aronne LJ, Beilin LJ et al (2013) Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment-a position paper of the the obesity society and the American soci-ety of hypertension. Obesity 21:8–24. doi:10.1002/oby.20181

\ 4.\ Steinberger J, Daniels SR (2003) Obesity, insulin resistance, diabetes, and cardiovascular risk in children an american heart association scientific statement from the atherosclerosis, hyper-tension, and obesity in the young committee (council on cardio-vascular disease in the young) and t. Circulation 107:1448–1453. doi:10.1161/01.CIR.0000060923.07573.F2

\ 5.\ Cai L, Wu Y, Wilson R et al (2014) Effect of childhood obesity prevention programs on blood pressure: a systematic review and meta-analysis. Circulation 129:1832–1839

\ 6.\ Bao W, Threefoot SA, Srinivasan SR, Berenson GS (1995) Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa heart study. Am J Hypertens 7061:657–665

\ 7.\ Juhola J, Magnussen CG, Viikari JSA et al (2011) Tracking of serum lipid levels, blood pressure, and body mass index from childhood to adulthood: the cardiovascular risk in young finns study. J Pediatr 159:584–590. doi:10.1016/j.jpeds.2011.03.021

\ 8.\ Chen X, Wang Y (2008) Tracking of blood pressure from childhood to adulthood: a systematic review and meta-regres-sion analysis. Circulation 117:3171–3180. doi:10.1161/ CIRCULATIONAHA.107.730366

\ 9.\ Caprio S, Plewe G, Diamond M et al (1989) Increased insulin secretion in puberty: a compensatory response to reductions in

insulino. J Pediatr 114:963–967

\10.\ Tobisch B, Blatniczky LBL (2015) Cardiometabolic risk factors and insulin resistance in obese children and ado-lescents: relation to puberty. Pediatr Obes 10:37–44. doi:10.1111/j.2047-6310.2013.00202.x

11\.\ Day FR, Elks CE, Murray A et al (2015) Puberty timing associ-ated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study. Sci Rep 5:11208. doi:10.1038/srep11208

\12.\ Marcovecchio ML, Patricelli L, Zito M et al (2006) Ambu-latory blood pressure monitoring in obese children: role of insulin resistance. J Hypertens 24:2431–2436. doi:10.1097/ HJH.0b013e328010918b

13\.\ Lurbe E, Torro I, Aguilar F et al (2008) Added impact of obe-sity and insulin resistance in nocturnal blood pressure eleva-tion in children and adolescents. Hypertension 51:635–641. doi:10.1161/HYPERTENSIONAHA.107.099234

\14.\ Chiavaroli V, Giannini C, De Marco S et al (2011) Unbalanced oxidant-antioxidant status and its effects in pediatric diseases. Redox Rep 16(3):101–107

15\.\ Lind L, Berne C, Lithell H (1995) Prevalence of insulin resist-ance in essential hypertension. J Hypertens 13:1457–1462

\16.\ Taittonen L, Uhari M, Nuutinen M et al (1996) Insulin and blood pressure among healthy children. Cardiovascular risk in young Finns. Am J Hypertens 9:194–199

17\.\ Stühlinger MC, Abbasi F, Chu JW et al (2002) Relationship between insulin resistance and an endogenous nitric oxide syn-thase inhibitor. JAMA 287:1420–1426

\18.\ Cole TJGP (1992) Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 11:1305–1319

19\.\ Biro F (2007) Puberty. Adolesc Med State Art Rev 18:425–433

\20.\ Matthews D, Hosker J, Rudenski A et al (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabe-tologia 28:412–419

21\.\ Schulze F, Maas R, Freese R et al (2005) Determination of a refer-ence value for NG, NG- dimethyl-l-arginine in 500 subjects. Eur J Clin Invest 35:622–626. doi:10.1111/j.1365-2362.2005.01561.x

\22.\ Soergel M, Kirschstein M, Busch C et al (1997) Oscillomet-ric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial includ-ing 1141 subjects. J Pediatr 130:178–184. doi:10.1016/ S0022-3476(97)70340-8

23\.\ Wühl E, Witte K, Soergel M et al (2002) Distribution of 24-h ambulatory blood pressure in children: normalized reference val-ues and role of body dimensions. J Hypertens 20:1995–2007

\24.\ Deshmukh-Taskar P, Nicklas TA, Morales M et al (2006) Track-ing of overweight status from childhood to young adulthood: the Bogalusa Heart Study. Eur J Clin Nutr 60:48–57. doi:10.1038/ sj.ejcn.1602266

\ J Endocrinol Invest
\25.\ He Q, Ding ZY, Fong DY, Karlberg J (2000) Blood pressure is 28\.\ Zoccali C, Benedetto FA, Maas R et al (2002) Asymmet-
associated with body mass index in both normal and obese chil- ric dimethylarginine, C-reactive protein, and carotid intima-
dren. Hypertension 36:165–170 media thickness in end-stage renal disease. J Am Soc Nephrol
\26.\ Cruz ML, Huang TTK, Johnson MS et al (2002) Insulin sensitiv- 13:490–496
ity and blood pressure in black and white children. Hypertension \29.\ Zoccali C, Mallamaci F, Maas R et al (2002) Left ventricular
40:18–22. doi:10.1161/01.HYP.0000019972.37690.EF hypertrophy, cardiac remodeling and asymmetric dimethylargi-
\27.\ Sinaiko A, Steinberger J, Moran A et al (2002) Relation of nine (ADMA) in hemodialysis patients. Kidney Int 62:339–345.
insulin resistance to blood pressure in childhood. J Hypertens doi:10.1046/j.1523-1755.2002.00437.x
20:509–517

 

Comments are closed.