Importance of Plasma N-Terminal Pro B-Type Natriuretic Peptide, Epicardial Adipose Tissue, and Carotid Intima-Media Thicknesses in Asymptomatic Obese Children

This study aimed to analyze the variations of N-terminal pro B-type natriuretic peptide, epicardial adipose tissue thickness, and carotid intima-media thickness in childhood obesity. The study participants consisted of 50 obese children in the study group and 20 nonobese children referred for evaluation of murmurs who proved to have an innocent murmur and were used as control subjects. All the subjects underwent transthoracic echocardiographic examination for determination of left ventricular systolic function and mass index, myocardial tissue rates, and myocardial performance index. Epicardial adipose tissue thickness and carotid intima-media thickness also were measured during echocardiography. Serum N-terminal pro B-type natriuretic peptide levels were measured at the time of evaluation. The left ventricle mass index was 40.21 ± 10.42 g/m² in the obese group and 34.44 ± 4.51 g/m² in the control group (p > 0.05). The serum N-terminal pro B-type natriuretic peptide level was 109.25 ± 48.53 pg/ml in the study group and 51.96 ± 22.36 pg/ml and in the control group (p = 0.001). The epicardial adipose tissue thickness was 5.57 ± 1.45 mm in the study group and 2.98 ± 0.41 mm in the control group (p = 0.001), and the respective carotid intima-media thicknesses were 0.079 ± 0.019 cm and 0.049 ± 0.012 cm (p = 0.001). The left ventricular systolic and diastolic functions showed no statistically significant correlations with N-terminal pro B-type natriuretic peptide levels, carotid intima-media thickness, or epicardial adipose tissue thickness values. The results show that measurement of serum N-terminal pro B-type natriuretic peptide level, carotid intima-media thickness, and epicardial adipose tissue thickness in asymptomatic obese children is not needed.     

新基因NYGGF4在肥胖患儿脂肪组织中的表达验证及生物信息学分析

目的 验证新基因NYGGF4在肥胖患儿脂肪组织中的表达,初步探讨NYGGF4的生物信息学特征.方法 采用反转录聚合酶链反应(RT-PCR)技术验证肥胖与健康儿童脂肪组织中NYGGF4基因的表达差异,应用DNA Star、Blast、ProtParam、SOPMA、TargetP、TMHMM、ProtScale、SOSUI、InterproScan和SMART等软件或数据库分析NYGGF4的核苷酸基本特征、蛋白质理化性质、二级结构、信号肽、跨膜结构域、疏水性/亲水性、可溶性、结构域及亚细胞定位等.采用SPSS 11.0软件进行统计学分析.结果 NYGGF4基因是一个未知的新基因,差异高表达于肥胖患儿脂肪组织中,生物信息学分析该基因cDNA全长1 527 bp,开放阅读框(ORF)长753 bp,编码250个氨基酸,预测相对分子质量28 271,定位在胞质,蛋白序列分析显示无跨膜螺旋结构,为一非分泌、可溶的亲水性蛋白,蛋白结构域分析提示NYGGF4的N端有一较短的亲脂性靶向序列、C端有一PTB结构域.结论 NYGGF4基因是一差异高表达于肥胖患儿脂肪组织中的新基因,可能是胞质内一个信号转导分子,在肥胖的发生发展过程中发挥重要功能,有进一步研究的价值.     

抵抗素在肥胖大鼠白色脂肪组织中的表达

目的 观察抵抗素mRNA及蛋白在肥胖大鼠白色脂肪组织中的表达,探讨抵抗素与肥胖、胰岛素抵抗发生的相关性.方法 SD雄性大鼠30只,随机分为对照组(15只)和高脂组(15只).对照组大鼠给予普通饲料;高脂组大鼠予高脂肪和高能量型的大鼠饲料喂养,诱导肥胖伴胰岛素抵抗大鼠模型.11周后应用葡萄糖耐量试验检测其0、30、60、90、120 min时血糖值,采用双抗体放射免疫分析法检测其血浆胰岛素水平.全自动生化分析仪测定其血浆游离脂肪酸水平.取附睾周围及肾脏周围脂肪组织,采用RT-PCR半定量法及Western blot 技术检测脂肪组织中抵抗素mRNA和蛋白的表达.采用SPSS 11.5软件进行统计学分析.结果 高脂组大鼠高脂饮食11周,体质量明显增加,出现高胰岛素血症、高脂血症,同时胰岛素的抵抗指数升高、糖耐量出现异常,白色脂肪组织内抵抗素mRNA及蛋白的表达均显著高于对照组大鼠(Pa<0.05).结论 高脂饮食诱导大鼠产生了胰岛素抵抗,胰岛素抵抗的形成可能与高胰岛素状态下较高的抵抗素水平有关.抵抗素可能在肥胖引起胰岛素抵抗中发挥了作用,进而引起2型糖尿病.     

Evaluation oF Epicardial Fat and Carotid Intima-Media Thickness in Obese Children

Background:

Epicardial fat has a role in cardiovascular diseases.

Objectives:

To assess epicardial fat and its relation with carotid intima-media thickness (IMT) in obese adolescents with metabolic syndrome (MetS).

Patients and Methods:

The study included 60 obese adolescents and 25 control subjects. According to the presence or absence of MetS, obese subjects were divided into two subgroups. We measured weight, height, calculated Body Mass Index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure and biochemical parameters (fasting glucose, total cholesterol, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol, High sensitivity C-reactive protein, fasting insulin, a homeostasis model assessment index of insulin resistance. plus an echocardiographic examination with measurement of epicardial adipose tissue thickness (EATT).

Results:

Left ventricular mass index measurements were significantly higher in MetS group than both non-MS and control groups. The MetS and non-MetS obese patients had significantly higher carotid IMT in comparison to the control group. Carotid IMT measurements were significantly higher in MetS group had than both non-MetS and control groups. Also, EATT was significantly increased in patients with MetS compared to control group. Among MetS obese group, EATT was positively correlated with body mass index-standard deviation score, waist circumference, fasting glucose, fasting insulin, insulin resistance, triglyceride levels, left ventricular thickness, left ventricular mass index and myocardial performance index. EATT was found to be the only predictor of carotid IMT.

Conclusions:

EATT is closely related to carotid IMT and early cardiac dysfunction in obese adolescents with MetS.     

Early Subclinical Left-Ventricular Dysfunction in Obese Nonhypertensive Children: A Tissue Doppler Imaging Study

A direct effect of obesity on myocardial function has not been not well established. Our aim was to investigate the effect of body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA–IR) on left-ventricular (LV) myocardial function in normotensive overweight and obese children by tissue Doppler imaging (TDI). We calculated the mitral annular displacement index (DI) and myocardial performance index (MPI) using TDI indices of systolic and diastolic LV function. In this hospital-based, prospective cross-sectional study, we studied 60 obese (mean age 13.2 ± 2.0 years) and 50 normal children. Subjects were divided into three groups: group 1 (BMI < 25, n = 50, control), group 2 (BMI 25–29.9 kg/m², n = 30, overweight), and group 3 (BMI ≥ 30 kg/m², n = 30, morbidly obese). Standard echocardiography showed increased LV diameters and LV mass/index and preserved ejection fraction in obese children. By TDI, LV systolic and diastolic function showed that peak late myocardial velocity (Em = 15.4 ± 2 cm/s), peak early myocardial velocity (Am = 8.7 ± 1.3 cm/s), Em/Am ratio (1.8 ± 0.3), isovolumetric relaxation time (IVRT = 59.2 ± 8.2 ms), MPI (0.39 ± 0.03), and DI (25.5 ± 3.2 %) of the lateral mitral annulus in the obese subgroups were significantly different from those of control subjects (18.2 ± 1.2 cm/sn, 6.9 ± 0.6 cm/sn, 2.6 ± 0.2, 51.2 ± 9.6 ms, 0.34 ± 0.03, and 33.13 ± 5.0 %, respectively; p < 0.001). These structural and functional abnormalities were significantly related to BMI. There were positive correlations between HOMA–IR, septal MPI, and LV mass. DI and MPI data indicated impaired subclinical LV function in all grades of isolated obesity at a preclinical stage. Insulin resistance and BMI correlated significantly with indices of LV function.     

Right Ventricular Function in Children with Bronchial Asthma: A Tissue Doppler Echocardiographic Study

Asthma is the most common cause of respiratory disability among children. Patients with severe bronchial asthma can experience cor pulmonale later in life, but little is known about the function of the right ventricle early in the disease. This study aimed to investigate the right ventricular function in children with bronchial asthma as detected by tissue Doppler echocardiography. This case-control study compared 60 asthmatic children ages 5 to 15 years between attacks (study group) with 60 apparently healthy children (control group). All the children were subjected to full history-taking, complete physical examination, measurement of peak expiratory flow rate (PEFR), chest x-ray, electrocardiography (ECG), echocardiographic examination, and both conventional and tissue Doppler study. The results of the tissue Doppler study examining the right ventricular diastolic function showed that peak E′ velocity (10.08 ± 2.8 cm/s), peak A′ velocity (5.7 ± 2.5 cm/s), E′/A′ ratio (1.77 ± 0.58 m/s), and isovolumetric relaxation time (IVRT) of the lateral tricuspid annulus (138.9 ± 30.7 m/s) among the asthmatic patients differed significantly from those among the control subjects (12.4 ± 2.3, 7.8 ± 2.1 cm/s; 1.58 ± 0.32, and 91.1 ± 32.6 m/s, respectively). In addition, the E′ velocity and IVRT of the lateral tricuspid annulus were significantly different among the mild, moderate, and severe cases (P < 0.001). It is concluded that although the clinical and conventional echocardiographic findings of the asthmatic children were apparently normal, the tissue Doppler echocardiographic study showed right ventricular dysfunction that is positively correlated with the severity of asthma. These findings signify the diagnostic value of tissue Doppler echocardiography for the early detection and monitoring of such deleterious effects among asthmatic patients.     

Mineral Metabolism in Obese Children

ABSTRACT. Blood levels of glucose, insulin (IRI), Calcium (Ca), phosphorus (P), alkaline phosphatase (AP), osteocalcin (OC), parathyroid hormone (PTH), calcitonin (CT), 25-hydroxyvitamin D3 (2SOHD3), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and urinary excretion of Ca (Ca/Cr), P (TmP/GFR), hydroxyproline (OH-P/Cr) and cyclic AMP (cAMP/GFR) were determined in 16 obese children, aged 8 to 11 years, on a diet rich in calories and carbohydrates and in 15 controls of the same age. Blood glucose, IRI, Ca, P, PTH and CT were also determined in both groups of subjects, during an oral glucose tolerance test (OGTT). In basal conditions glucose, IRI, AP, OC, PTH, CT and 1,25(OH)2D3 levels were significantly higher, and 2SOHD3 levels lower, in obese children than in controls. Urinary Ca/Cr, TmP/GFR were lower in obese than in non obese children, while OH-P/Cr and cAMP/GFR were higher. Bone mineral content (BMC), measured by photon absorptiometry, and BMC/bone width ratio were lower in obese than in non obese children. During OGTT serum Ca and P decreased and serum PTH and CT increased less in obese than in non obese children. In obese children receiving a diet with high carbohydrate content, an alteration of mineral metabolism occurred, characterized by secondary increase of PTH and 1,25(OH)2D3. Ca decreased and PTH and CT increased less markedly during OGTT.     

肥胖儿童非酒精性脂肪肝炎

非酒精性脂肪肝炎(NASH)是指肝脏病理改变类似于酒精性脂肪肝炎而又无饮酒史的一类慢性肝脏疾病.肥胖儿童NASH与体质量指数(BMI)、高脂血症、稳态模型胰岛素抵抗指数(HOMA-IR)密切相关,是代谢综合征的肝脏表现.血清脂联素水平与肝细胞脂肪浸润呈负相关,基因的多态性对肝脏的脂类代谢和贮存功能有重要影响.肥胖儿童NASH多无症状,肝转氨酶升高,必须排除自身免疫性疾病、病毒性肝炎、药物性肝损害等.超声波检查可识别肝内脂肪浸润,帮助诊断肥胖儿童NASH.对肥胖儿童NASH的治疗仍以去除病因、控制饮食、加强锻炼、采取合理生活方式为主,也可用维生素E和葫芦素片治疗,合并2型糖尿病或代谢综合征的NASH儿童可应用胰岛素增敏剂盐酸二甲双胍治疗.     

Three-Dimensional Echocardiographic Measurement of Left Ventricular Stroke Volume in Children: Comparison with Doppler Method

Three-dimensional echocardiography (3DE) allows calculation of ventricular volumes without geometric assumption on the ventricular shape. Our aim was to apply 3DE in a normal pediatric population and to compare the left ventricular stroke volume measurements to the Doppler method. Twenty-four normal patients (median age 7 years) underwent Doppler echocardiography and 3DE for left ventricular stroke volume calculation. The left ventricular stroke volume by Doppler method was calculated as the product of the aortic Doppler flow mean velocity and the area of the aortic annulus. The 3DE method was performed using a transthoracic rotational probe (TomTec) and left ventricular volumes were calculated using the Simpson's rule. The mean time for 3DE acquisition was 90 seconds without any sedation. 3DE correlated well with the Doppler method for left ventricular stroke volume measurements (y= 0.8x− 0.2, r= 0.94). The mean difference between the average values of left ventricular stroke volume obtained by Doppler method and 3DE was 5 ± 4 ml. Intraobserver and interobserver variabilities in the left ventricular stroke volume measurement by 3DE were 2.6% and 4.4%. In conclusion, 3DE compared to the Doppler method is an accurate, noninvasive, and reproducible method to measure the left ventricular stroke volume in normal children.     

Epicardial Adiposity in Children with Obesity and Metabolic Syndrome

Objective: Obesity increases cardiac diseases by increasing tendency to atherosclerosis. Our aim was to define epicardial adipose tissue thickness, and its related factors in obese children. Methods: Total of 94 patients were divided into obesity with metabolic syndrome (MS) (n=30), obesity without MS (n=33), and control (n=31) groups. Auxological values with fasting glucose, fasting insulin, alanine transaminase, serum lipid levels, and high sensitive C-reactive protein levels were evaluated. Epicardial adipose tissue thickness, interventricular septum thickness and left ventricular mass were measured by echocardiography. Findings: Weight, body mass index, waist circumference, insulin, alanine transaminase, and high sensitive C-reactive protein values were markedly higher in obesity group when compared with controls (P<0.001). Epicardial adipose tissue thickness was 0.64±0.23 cm in obesity with MS; 0.60±0.20 cm in obesity without MS, and 0.27±0.12 cm in control group (P<0.001). Interventricular septum thickness and left ventricular mass values were markedly high in obesity without MS group (P<0.001 and P=0.002). Conclusion: Our study has indicated that obesity has unfavorable effects on heart starting in the adolescence.Key Words: Adipose Tissue, Insulin Resistance, Obesity, Metabolic Syndrome, Cardiovascular Diseases, Adolescence     

Cardiorespiratory Function during Exercise in Obese Children

ABSTRACT. Fifteen obese children, aged 4 to 16 years and ranging in body weight from 27.3 to 95 kg (median 67.5) and percentage overweight from 22 to 127% (median 40), underwent graded exercise testing on a treadmill and were compared with healthy peers of comparable age. Cardiorespiratory performance capacity was assessed by determination of the ventilatory threshold. This was defined as the highest oxygen uptake at which the pulmonary ventilation stops to increase linearly with increasing exercise intensity. The ventilatory threshold, expressed as ml O₂/min/kg, was significantly ( p <0.05) lower than in normal children and averaged 70.6±13.5% of the normal mean value, matched for age. The habitual level of physical activity, assessed by a questionnaire, was 27% lower ( p <0.01) in the obese children compared to healthy controls. As the ventilatory threshold was strikingly lower and also exceeded sooner in the majority of the obese children, compared with normal controls, it may be assumed that obese children avoid moderate or strenuous exercise, because of the higher degree of effort needed. This may contribute to the maintenance of overweight.     

肥胖儿童非酒精性脂肪肝炎54例

目的 观察不同程度肥胖儿童非酒精性脂肪肝炎(NASH)的发病状况,探讨其可能的发病机制.方法 体质量指数(BMI)≥23的7～16岁单纯性肥胖儿童123例.按BMI分为3组:BMI≥30组34例,25≤BMI＜30组57例,23≤BMI＜25组32例.分别进行肝脏B超检查,并检测血转氨酶、胆固醇、三酰甘油(TG)及空腹血糖/空腹胰岛素比值(FlGIR).将另24例仅有肥胖而无肝脂肪病变者设为对照组.结果 123例患儿中B超发现肝脂肪病变99例(80.49%),其中符合NASH诊断标准者54例(43.90%).所有患儿中,BMI≥30组脂肪肝炎及FGIR＜7的发生率均显著高于其他2组(Pa ＜0.01).相关分析表明,ALT和AST与BMI分级、血胆固醇、TG、FGIR均有相关性(r=0.413,0.290,0.379,-0.477 Pa ＜0.01;r=0.359,0.349,0.348,-0.369 Pa ＜0,01).NASH患儿与对照组血脂、FGIR、BMI比较差异均有统计学意义(X2=9.84,25.59 Pa ＜0.01;t=5.05P＜0.01).结论 BMI ≥30是肥胖儿童发生NASH的高危因素,且脂代谢紊乱和胰岛素抵抗可能与其发病有关.     

Fatty Acid Composition of Subcutaneous Adipose Tissue in Mother-Infant Pairs

ABSTRACT. The fatty acid composition of microsamples from 10 AGA term, 8 SGA term, 7 AGA preterm and 4 SGA preterm, 2–4 day old infants and their mothers were analyzed. In AGA preterm newborns the mean percent of palmitic and stearic acid was lower and the mean percent of linoleic acid was higher than in AGA term infants indicating that there is an increase in fatty acids derived by synthesis from glucose throughout gestation. SGA infants had relative amounts of palmitic and stearic acid similar to what was found in AGA term infants. This indicates that the enzymes involved in synthesis of fatty acids from glucose are intact in intrauterine growth retardation (IUGR). The absolute amount of adipose tissue and fatty acids, however, is smaller in SGA infants due to a reduced availability of glucose in IUGR gestation. No differences were found in the fatty acid composition of subcutaneous adipose tissue from the mothers in the 4 groups. All mothers had a lower mean percent of palmitic and stearic acid and a higher mean percent of oleic and linoleic acid than their infants, ensuring a transplacental gradient to the fetus of this latter essential fatty acid. The fatty acid composition of plasma free fatty acids generally reflected the composition of the subcutaneous adipose tissue in the infants.     

Five-hour Oral Glucose Tolerance Test in Obese Children

Concentrations of blood glucose, plasma free fatty acids, and plasma glycerol during a 5-hour oral glucose tolerance test on 46 obese children are reported.Seven children had unequivocally impaired glucose tolerance. However in the group as a whole, there was a delay in return of blood glucose to baseline levels after oral glucose, 27 children (60%) having a blood glucose concentration greater than 110 mg/100 ml at 2 hours. It was concluded that some degree of glucose intolerance is common in childhood obesity. No relation was seen among the following: impairment of glucose tolerance and age, degree or duration of obesity, or family history of diabetes.Fasting plasma free fatty acids and glycerol concentrations were high (mean ± 1SD, 1030 ± 221 μEq/litre FFA and 121 ± 44 μmol/l. glycerol). For all children, concentrations of FFA and glycerol decreased during the first hour after glucose, though minimal levels were not reached until 90-120 minutes (mean ± 1SD, 395 ± 170 μEq/litre FFA, 77 ± 24 μmol/l. glycerol). For those children (27) who had raised blood glucose at 2 hours, there was a positive correlation between fasting plasma glycerol concentration and glucose tolerance sum, suggesting that impaired glucose tolerance was associated with increased basal lipolysis.