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目的探讨单纯性肥胖儿童的生长与其血清胰岛素(Ins)、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)浓度的关系。方法2004-03中山大学附属二院对31例单纯性肥胖儿童及48例同龄正常儿童的生长参数及空腹Ins、IGF-1、IGFBP-3浓度进行测定,并进行比较及相关性分析。结果肥胖组血清Ins、IGFBP-3浓度显著高于对照组(P<0·05,P<0·01),而两组间IGF-1差异则无显著性意义,血清Ins浓度与BMI、IGFBP-3呈正相关,肥胖儿童身高SDS与1NS、IGF-1正相关。结论肥胖儿童存在有非生长激素(GH)依赖性生长的代偿机制。其中高胰岛素血症可能参与了这一过程,它既可以通过增加IGFBP-3的合成来间接提高IGF-1的生物活性,又可以直接发挥促生长作用。     

血清胰岛素浓度的变化与肥胖儿童生长关系的探讨

目的探讨单纯性肥胖儿童的生长与其血清胰岛素(Ins)、胰岛素样生长因子 1(IGF 1)、胰岛素样生长因子结合蛋白 3(IGFBP 3)浓度的关系。 方法2004 03中山大学附属二院对31例单纯性肥胖儿童及48例同龄正常儿童的生长参数及空腹Ins、IGF 1、IGFBP 3浓度进行测定,并进行比较及相关性分析。 结果肥胖组血清Ins、IGFBP 3浓度显著高于对照组(P<005,P<001),而两组间IGF 1差异则无显著性意义,血清Ins浓度与BMI、IGFBP 3呈正相关,肥胖儿童身高SDS与1NS、IGF 1正相关。 结论肥胖儿童存在有非生长激素(GH)依赖性生长的代偿机制。其中高胰岛素血症可能参与了这一过程,它既可以通过增加IGFBP 3的合成来间接提高IGF 1的生物活性,又可以直接发挥促生长作用。     

复合刺激试验对单纯性肥胖儿童下丘脑-垂体 GH轴和性腺轴功能的评价

目的 探讨肥胖儿童下丘脑-垂体轴分泌生长激素（GH）及促性腺激素（Gn）功能。方法 采用复合刺激试验检测27例单纯性肥胖儿童和19例对照儿童：生长激素（GH）用放免法检测,促卵泡生成素（FSH）、促黄体生成素（LH）采用全自动荧光免疫分析系统测定。结果肥胖儿童的GH峰值（PGH）明显低于对照组（,J〈0.01）;PGH〈10μg／L者占肥胖儿童总数的88.89％。所有受试儿童血LH峰值（PLH）／LH基础值（BLH）均〉3;PLH／PFSH（FSH峰值）比值在青春期肥胖和对照组均〉0．7,但在青眷期前肥胖组有4例〉0.7;PLH值达到性腺轴发育标准者,在青春期肥胖组7例、对照组lO例、青春期前肥胖组l例。有4例青春期前肥胖儿存在中枢性性早熟,占30．77％。结论 肥胖儿垂体分泌GH功能和反应能力低下,但其身高正常,提示肥胖儿的生长调控机制较为复杂。采用PLH／PFSH比值和／或PLH值作为性腺轴功能成熟的判断标准较为理想。     

儿童单纯性肥胖血清瘦素水平分析

目的：比较单纯性肥胖儿童与正常健康儿童血清瘦素的水平，分析血清瘦素与空腹胰岛素之间的关系。方法：选择单纯性肥胖儿童30例，健康非肥胖儿童30例作对照组，分别测定其空腹胰岛素与瘦素水平。结果：单纯性肥胖组血清瘦素明显高于对照组（P＜0．001），瘦素与空腹胰岛素呈显著性相关（r=0.854，P＜0．001）。结论：单纯性肥胖儿童体内存在高胰岛素血症，同时存在瘦素抵抗，胰岛素与瘦素的调控是双向的。     

营养对男性儿童生长及性成熟的影响

对98例肥胖男孩及183例同龄正常体重男孩的身高、身高生长速度、性成熟、骨龄及生长激素结合蛋白（GHBP）进行对比调查。结果肥胖儿童身高、身高生长速度及GHBP较正常体重男孩明显增高，肥胖儿童性成熟较正常体重者提前。提示营养状态可通过生长激素（GH）铀受体途径对生长产生调控作用，营养对生长及性成熟有促进作用。     

长期吸入糖皮质激素对支气管哮喘儿童血清生长激素与身高的影响

目的探讨长期吸入糖皮质激素对支气管哮喘儿童生长激素（GH）及身高的影响。方法支气管哮喘患儿22例于治疗前、治疗后6、12、24个月抽取空腹静脉血约5ml，离心10min，留取血清，用放射免疫分析法（RIA）测定GH值。同时测定用药前及用药24个月患儿的身高，应用标准法测避并记录.结果支气管哮喘儿童用药前及用药6、12、24个月后其血清GH水平差异无显著性（F=0．6625 P〉0.05）。观察组身高治疗前、用药24个月与正常年龄相匹配儿童身高比较无显著差异（t=1．022,0．612P均〉0．05）。结论长期吸入糖皮质激素对哮喘儿童的GH及身高发育无明显影响。     

儿童单纯性肥胖与纤维蛋白原及其Bβ-148C/T基因多态性的关系研究

探讨儿童单纯性肥胖与纤维蛋白原（Fg）及其Bβ-148C/T基因多态性的关系, 为儿童单纯性肥胖的防治提供理论依据。方法　选取2004年6月至2007年9月华北煤炭医学院附属医院单纯性肥胖儿童及正常对照组儿童各106例,抽取空腹静脉血5 mL,测定Fg水平和分子功能;采用聚合酶链反应及限制性酶切方法对Fg Bβ-148C/T位点的基因型进行测定。结果　单纯性肥胖儿童血浆Fg水平及分子功能明显高于健康对照组（ P < 0.05） , 儿童单纯性肥胖T等位基因频率明显高于健康对照组 （P < 0.05） ,而且儿童单纯性肥胖组CT与TT基因型个体的血浆Fg水平及Fg单体聚合速度（FMPV）明显高于CC基因型组（P < 0.05）。结论　儿童肥胖能引起血浆Fg水平增高,分子功能增强,FgBβ-148C/T基因多态性通过影响Fg水平及单体聚合速率可能为儿童单纯性肥胖的一个累效基因。     

单纯性肥胖儿童有氧活动能力的研究

单纯性肥胖症对儿童健康的危害在国内外尚有较大争论，我们于1994年5～6月对45名儿童进行观察，旨在探讨单纯性肥胖症对儿童有氧活动能力的影响。一般资料：从北京市某小学中筛选单纯性肥胖儿童31名（男16，女15），按超标准体重的20％、30％～50％、大于50％，分别为轻、中、重度肥胖的标准进行判定。其中轻度肥胖为10名、中度为14名，重度为7名。从肥胖儿童所在班级随机选择非肥胖儿童14名（男8，女6）作为对照组。两组年龄（岁）均值分别为10．1±1．2、10．1±1．3（P＞0．05）。身高（厘米）均值分别为146.7±8．6、145.5±8.1（P＞0…     

血清胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3在矮小症儿童诊断和疗效判断中的价值

目的探讨胰岛素样生长因子-1（IGF-1）及其结合蛋白-3（IGFBP-3）在矮小症儿童诊断及疗效判断中的价值。方法1．对124例青春发育前矮小症患儿用精氨酸激发试验和可乐定激发试验检测其血清生长激素（GH）水平，并根据患儿GH峰值分为生长激素缺乏组（GHD组，40例）、特发性矮小组（1SS组，84例）。选取20例健康儿童作为健康对照组。对所有儿童采用酶联免疫吸附法检测血清IGF—1和IGFBP-3。对GHD组、ISS组和健康对照组儿童血清IGF-1和IGFBP-3水平进行两两比较。2．对15例GHD和30例ISS患儿予国产重组人生长激素（rhGH）0．1IU／（kg&#183;d）治疗6个月，于治疗前及治疗6个月分别测定其身高、体质量、骨龄及血清IGF-1、IGFBP-3，并进行治疗前后的对照。结果1．GHD组和ISS组患儿血清IGF-1和IGFBP-3水平明显低于健康对照组（Pa〈0．01），GHD组与ISS组患儿血清IGF-1和IGFBP-3水平比较均有显著差异（Pa〈0．01），GHD组患儿治疗前后血清IGF-1、IGFBP-3比较有显著差异（Pa〈0．01）；诊断GHD，IGF-1的特异性为67．8％，敏感性为75％；IGFBP-3的特异性为88％，敏感性为85％。2．rhGH治疗后身高增长速度明显加快，血清IGF-1、IGFBP-3水平显著升高；治疗前血清IGF-1与治疗6个月生长速度呈显著负相关（r=-0．78P〈0．01）；治疗6个月后IGF-1的变化与治疗后生长速度呈显著正相关（r=0．82P〈0．01）。结论IGF-1、IGFBP-3可用于儿童矮小症的诊断及疗效评价。     

单纯性肥胖儿童外周血单核细胞载脂蛋白E基因的表达

目的　探讨单纯性肥胖儿童外周血单核细胞载脂蛋白E基因表达及其与血脂、脂蛋白、载脂蛋白的相关关系。方法　采用竞争性逆转录 聚合酶链式反应方法分析 3 2例单纯性肥胖儿童和 3 2例正常健康儿童外周血单核细胞的载脂蛋白E基因表达。结果　载脂蛋白E基因能在儿童外周血单核细胞表达 ,与健康儿童比较 ,单纯性肥胖儿童外周血单核细胞载脂蛋白E基因表达水平显著下调 (P <0 0 1) ,重度肥胖儿童尤其明显 ,载脂蛋白E基因表达水平与肥胖度呈负相关 (P <0 0 5)。肥胖儿童存在明显的血脂代谢紊乱 ,载脂蛋白E基因表达水平与低密度脂蛋白 胆固醇呈负相关 ,与血载脂蛋白E浓度呈正相关 (P <0 0 5) ,与血总胆固醇、甘油三酯、高密度脂蛋白 胆固醇、脂蛋白 (a)、载脂蛋白AⅠ水平无明显相关 (P >0 0 5)。结论　单纯性肥胖儿童外周血单核细胞载脂蛋白E基因表达水平明显下调 ,并与肥胖程度及血脂代谢异常相关联 ,提示载脂蛋白E基因表达变化可能与肥胖的发生发展及肥胖的心血管病变相关联     

Children with Craniopharyngioma

ABSTRACT. Pre- and postoperative growth was analyzed in 22 children with craniopharyngioma. In 19 children a growth failure preceded the diagnosis by a mean of 4 years. Six children were obese preoperatively. During the first 3 postoperative months relative weight increased 7gt;10% in 14/21 children (there was one surgical death). One year after surgery 13/21 were obese. Neither the size of the tumor nor the mode of surgery was decisive in the development of the obesity. Serum insulin and insulin-like growth factor I (IGF-I) were assessed in four children with growth hormone deficiency (GHD) who, after surgery for craniopharyngioma, were growing normally without GH substitution. One of them was normal in weight and had normal insulin and IGF-I levels; the others were obese and had supranormal insulin and subnormal IGF-I levels. One of the four and two other children with unsubstituted GHD reached final height SDS -0.8, -2.0 and -2.4. One child with normal postoperative GH response reached final height SDS -0.7. Final height SDS ≧-2.5 was gained with GH substitution by 6/11 children. It was >2.0 SD below the height SDS expected from the heights of the parents in 7/11. An adequate monitoring of children's growth would lead to earlier diagnosis and probably better outcome.     

Children with craniopharyngioma. Early growth failure and rapid postoperative weight gain

Pre- and postoperative growth was analyzed in 22 children with craniopharyngioma. In 19 children a growth failure preceded the diagnosis by a mean of 4 years. Six children were obese preoperatively. During the first 3 postoperative months relative weight increased greater than 10% in 14/21 children (there was one surgical death). One year after surgery 13/21 were obese. Neither the size of the tumor nor the mode of surgery was decisive in the development of the obesity. Serum insulin and insulin-like growth factor I (IGF-I) were assessed in four children with growth hormone deficiency (GHD) who, after surgery for craniopharyngioma, were growing normally without GH substitution. One of them was normal in weight and had normal insulin and IGF-I levels; the others were obese and had supranormal insulin and subnormal IGF-I levels. One of the four and two other children with unsubstituted GHD reached final height SDS -0.8, -2.0 and -2.4. One child with normal postoperative GH response reached final height SDS -0.7. Final height SDS greater than or equal to -2.5 was gained with GH substitution by 6/11 children. It was greater than 2.0 SD below the height SDS expected from the heights of the parents in 7/11. An adequate monitoring of children's growth would lead to earlier diagnosis and probably better outcome.     

Caloric restriction for 24 hours increases mean night growth hormone.

In obesity, serum growth hormone (GH) is usually low, confounding GH assessment of short obese children. We evaluated whether 24-h caloric restriction would permit better discrimination between normal GH secretion and GH deficiency (GHD) by elevating night GH levels. DESIGN AND PATIENTS: Serum was obtained every 20 minutes 2000-0800 h before and 2200-0400 h after 24 hours of caloric restriction (8% of usual calories) in 24 normal height children [14 normal (weight for height 10-90th percentile); 10 obese (weight for height > 95th percentile)] and in 31 short children (height shorter than -2.0 SD below mean for age). All samples from both nights per child were assayed for GH simultaneously to eliminate interassay variability. RESULTS: Mean GH increased significantly in all groups after caloric restriction (P < 0.01). Obese children had lower baseline mean GH and GH amplitude compared to normal (P < 0.01); GH increased into normal range after restriction. Basal GH studies in short children were not significantly below normal. Surprisingly, some with low stimulated GH increased their night GH into the normal range after caloric restriction. CONCLUSIONS: Caloric restriction for 24 h enhances night GH similarly in short and in normal children, and thus does not increase the diagnostic utility of night GH studies in non-obese short children. Caloric restriction reverses suppressed GH secretory state of obese children, perhaps by decreasing diet-dependent somatostatin inhibition of GH secretion.     

Growth hormone and premature atherosclerosis in childhood obesity

BACKGROUND: The role of growth hormone (GH) in obesity is controversial. Childhood obesity is characterized by reduced GH secretion. Low, high and normal serum insulin-like growth factor-I (IGF-I) levels have been described in obese children in the face of low GH secretion. There is conflicting information on the interaction of GH and obesity upon components of the GH-IGF-I-insulin-like growth factor binding proteins (IGFBPs) system and its relationship to cardiovascular risk factors. OBJECTIVE: This review highlights the role of GH modulating cardiovascular risk factors, including lipid levels, inflammatory markers, cardiac and endothelial function in children and adolescents with obesity and insulin resistance. CONCLUSIONS: The interplay between GH secretion, NO production, IGF-I, IGFBP-1, and IGFBP-3 levels, lipid profile, insulin sensitivity and the degree of visceral obesity necessitates further study. These metabolic parameters may be useful markers of premature atherosclerosis in children with obesity. Further studies should address the question of optimal dose and duration of GH therapy in non-GH deficient obese patients with metabolic disturbances at risk for premature atherosclerosis.     

Differential impact of simple childhood obesity on the components of the growth hormone-insulin-like growth factor (IGF)-IGF binding proteins axis

Simple childhood obesity is characterized by normal or even accelerated growth in spite of reduced growth hormone (GH) secretion. There are conflicting reports on the effects of obesity upon components of the GH-insulin-like growth factor-I (IGF-I)-IGF binding proteins (IGFBPs) system. In the present study we aimed to determine GH, IGF-I, IGFBP-3 and IGFBP-2 as well as some of the less explored components of this axis (IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments, and total acid labile subunit [ALS]) in 22 obese and 17 age-matched control children. We also evaluated not only total GH binding protein (GHBP) serum levels but also GHBP bound to GH (complexed) in both groups. Obese and control groups strongly differed in BMI (obese: 4.7 +/- 0.36 vs control: 0.37 +/- 0.25 SDS, p <0.0001). In the obese group, we found lower GH serum levels, but normal serum levels of GH-GHBP complex, IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments and total ALS. Obese children presented higher total circulating GHBP (6.0 +/- 0.44 vs 2.9 +/- 0.29 nmol/l, p <0.001) and insulin levels (10.5 +/- 1.5 vs 5.1 +/- 0.8 mU/l, p <0.001), while IGFBP-2 (4.6 +/- 0.5 vs 6.6 +/- 0.7%, p <0.05) and the ratio IGFBP-2/IGF-I (0.032 +/- 0.019 vs 0.095 +/- 0.01, p = 0.013) were lower than in controls. BMI and insulin were directly, and IGFBP-2 serum levels inversely, correlated to total GHBP serum levels when multiple regression analysis was performed (r = 0.74, p <0.001). By stepwise regression analysis, insulin (r = -0.37, p <0.05) and BMI (r = -0.52, p <0.01) inversely determined IGFBP-2. In summary, obese children present normal growth in spite of reduced GH secretion, probably because the combination of increased total GHBP and normal GH-GHBP complex serum levels (suggesting increased GH receptor [GHR] number and a normal serum GH reservoir, respectively) allow for the achievement of normal levels of IGF-I, IGFBP-3, IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments and total ALS. Reduced IGFBP-2 serum levels and a lower ratio of IGFBP-2/IGF-I in obese children may suggest an increase of tissue IGF-I bioavailability, thus promoting its action. Normal IGF-I and GH availability may be contributing to maintain normal growth in obese children.     

Food-induced thermogenesis in obese children

In 11 obese children aged 12.5 (±0.7) years with normal glucose tolerance and 7 lean, control children aged 11.9±0.7 years the preload resting energy expenditure and thermogenic response to a standardised meal was measured by indirect calorimetry. Preload energy expenditure was higher in obese children when expressed in absolute terms than in controls, but was not different when corrected for lean body weight. Four children with obesity of recent onset had lower food-induced thermogenesis and insulin response then seven overweight children with long-standing obesity. Food-induced thermogenesis and insulin response showed a significant positive correlation.It is concluded that food-induced thermogenesis is reduced in the early phase of childhood obesity but increased in the later phase when hyperinsulinaemia develops, pointing towards an important role of insulin in food-induced thermogenesis.Abbreviations EE energy expenditure - LBW lean body weight - FIT food-induced thermogenesis - IRI immunoreactive insulin - GH growth hormone - FFA free fatty acids - LR low responder - HR high responder - RO respiratory quotient     

Serum levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3 and insulin in obese children.

In simple obesity, spontaneous and stimulated growth hormone (GH) secretions are diminished. However, this diminished GH secretion does not result in decreased somatic growth in obese children. Although the increased insulin level, low insulin-like growth factor binding protein (IGFBP)-1 and the resulting increase of bioavailability of insulin-like growth factor I (IGF-I) have been suggested as being involved, the exact mechanism has not yet been established. We investigated serum IGF-I, free IGF-I, IGFBP-1, IGFBP-3 and insulin levels in 36 obese and 39 non-obese healthy children. Insulin and IGFBP-3 were significantly higher in the obese group than in the control group (p < 0.05, p = 0.001, respectively). IGF-I, free IGF-I, free IGF-I/IGF-I and IGFBP-1 levels in the obese children were not significantly different from those in the control group. A positive correlation was found between body mass index (BMI) and IGF-I in the obese children (r = 0.30, p = 0.05). IGFBP-3 levels correlated positively with IGF-I (r = 0.44, p < 0.005), and free IGF-I levels (r = 0.37, p = 0.05) in the obese children. A negative correlation was found between IGFBP-1 and insulin levels (r = -0.30, p = 0.05) in the obese children. We concluded that normal growth in obese children might be maintained through normal IGF-I and increased IGFBP-3 levels, which are stimulated by increased insulin levels or nutritional factors or by increased responsiveness to GH.     

综合减肥对超重和肥胖女学生性激素和生长激素的影响

目的探讨综合减肥处方对单纯性超重和肥胖女学生性激素和生长激素(GH)的影响。方法对超重和肥胖女学生采取有氧运动、合理饮食、心理矫正等疗法进行为期10个月的减肥活动,采用放射免疫法分别测定试验前、中、后性激素和GH的变化。结果超重和肥胖女学生血GH、雌二醇(E2)水平明显低于正常同龄人,而睾酮(T)水平明显高于正常同龄人(P<0.05),减肥后GH、E2水平显著升高,而T水平显著降低(P<0.05)。结论综合减肥处方可升高超重和肥胖女学生体内雌激素和GH含量,降低雄激素含量,起到调节生殖内分泌代谢紊乱的作用。     

Decreased prolactin secretion in childhood obesity

Twelve obese patients and 7 control subjects, age and sex matched, whose weights were greater than 200% of ideal weight and 100% of ideal body weight, respectively, underwent intravenous insulin and thyroid releasing hormone (TRH) tests. Serial prolactin growth hormone, insulin, blood sugar, cortisol, glucagon, thyrotropin stimulating hormone, thyroxine, and triiodothyronine were obtained by RIA. Obese patients showed no significant differences from controls in basal and nadir glucose, basal and peak glucagon, cortisol, and thyroid responses to both tests. Basal insulin levels were higher (36 +/- 9.4 vs 10 +/- 2.3 microU/ml, P less than 0.05) and peak growth hormone responses after insulin were lower in the obese group (6.1 +/- 1.1 vs 12.7 +/- 3.7 ng/ml, P less than 0.05) than in controls. Whereas all control subjects had prolactin responses to both tests, five of 12 obese patients had no responses to insulin. Obese patients had lower prolactin responses at 30 minutes after insulin (5.4 +/- 0.7 vs 12.9 +/- 3.7 ng/ml, P less than 0.05) and lower prolactin responses at 60 minutes after TRH (9.9 +/- 1.7 vs 20.4 +/- 5.9 ng/ml, P less than 0.05). Maximum prolactin responses after TRH were lower in obese patients (9.9 +/- 2.0 vs 28.8 +/- 10.9 ng/ml, P less than 0.05). Maximum prolactin responses after insulin were lower in obese patients (6.2 +/- 4.1 vs 28.9 +/- 18.3 ng/ml). Thus prolactin secretion in childhood obesity is decreased after both stimuli, but more so after IV insulin that TRH, and suggests that, as in adult hypothalamic obesity, neuroendocrine regulation of prolactin release in obese children is impaired.     

The efficacy of grwoth hormone in different types of growth failure

One hundred and one children with GH deficiency, prenatal growth disorders, growth-retarding diseases, or normal variant short stature received GH for at least one year. Responders were observed in all groups. In the whole series of 72 prepubertal children the increments in height velocity showed negative correlations with the highest serum GH levels obtained in provocation tests.In the prepubertal children with normal growth potential the velocity SDSs during the first year of therapy showed positive correlations with initial ages and BAs, and negative correlations with height SDSs. In the 5 children with cartilage-hair hypoplasia the mean velocity increased from -1.9 to -0.6 SD. In the 8 children with Mulibrey nanism the mean velocity increased from -2.0 to 0.8 SD. The 4 children with various chromosome anomalies also showed an acceleration.The therapy brought about a significant increase in predicted final height only in the groups with normal growth potential. Final heights were known for 16 patients. Their heights were fairly accurately predicted by the RWT method, but the IPH method gave overpredictions. Both predictions showed strong correlations with the final heights.Additional low-dose androgen therapy in 10 boys, started at ages 9.5 to 18.9 years and after 1.4 to 4.7 years of GH therapy, accelerated growth without substantially affecting predicted height. The acceleration was mostly of the growth of sitting height.Abbreviations BA bone age - CHH cartilage-hair hypoplasia - GHD GH deficiency, GH deficient - iGHD isolated GHD - IPH index of potential height (height SDS for adjusted BA) adult height prediction method [23] - Maximal GH highest plasma GH level during an insulin or insulin-arginine test - MPHD multiple pituitary hormone deficiency - RWT the adult height prediction method of Roche, Wainer and Thissen [39] - SDS height standard deviation score - SDS SDS corrected for parental height