甲状腺功能减退症患儿血清生长激素、胰岛素样生长因子-Ⅰ、胰岛素样生长因子结合蛋白-3水平的变化

目的通过监测甲状腺功能减退症患儿生长激素(GH)、胰岛素样生长因子-Ⅰ(IGF-Ⅰ)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平变化,探讨甲状腺功能减退症患儿GH-IGF轴与甲状腺素的变化规律。方法对56例甲状腺功能减退症(14例先天性甲状腺功能减退症和32例桥本病)患儿治疗前后血GH、IGF-Ⅰ、IGFBP-3水平和50例健康儿童血GH、IGF-Ⅰ、IGFBP-3水平进行监测。结果先天性甲状腺功能减退症新生儿9例患儿IGF-Ⅰ、IGFBP-3水平显著降低,经治疗后甲状腺功能逐渐恢复正常;5例先天性甲状腺功能减退症患儿和32例桥本病患儿无显著变化。结论先天性甲状腺功能减退症患儿存在GH-IGF轴功能紊乱,是导致身材矮小的重要原因,早期予甲状腺素治疗有利于维持患儿正常生长发育。     

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·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。     

正常儿童、青少年血清胰岛素样生长因子结合蛋白-3水平的变化

目的测定正常儿童、青少年血清胰岛素样生长因子结合蛋白-3(IGFBP-3)水平。方法对北京市东城区190名(男102名,女88名)健康的4.0~18.9岁儿童、青少年,应用放射免疫分析法(RIA)测定空腹血清IGFBP-3水平。结果随着年龄的增加,血清IGFBP-3水平逐渐升高,到青春期达到峰值。女性血清IGFBP-3水平达峰值时间较男性早1~2年,男、女性达峰时间分别为13.0~14.9及11.0~14.9岁,峰值分别为(4.58±0.64)、(4.67±0.93)mg/L。达峰值后血清IGFBP-3水平逐渐下降至各自9.0~10.9岁水平。血清IGFBP-3水平分别与身高和血清胰岛素样生长因-子1(IGF-1)水平呈显著正相关。结论血清IGFBP-3水平与年龄、青春发育期、身高及血清IGF-1水平明显相关。同年龄血清IGFBP-3水平无性别差异。     

Insulin-Like Growth Factors (IGFs) and IGF Binding Proteins in Chronic Renal Failure: Evidence for Reduced Secretion of IGFs

To test the hypothesis that growth hormone (GH) insensitivity is responsible, amongst other mechanisms, for impaired growth in uraemic children, insulin-like growth factor I (IGF-I), IGF-II, IGF binding protein-1 (1GFBP-1), IGFBP-2 and IGFBP-3 were measured by radioimmunoassay in normal control children, in patients with end-stage renal failure (n = 51) and in patients with preterminal chronic renal failure (n = 11) and the production rate of IGF was calculated. A unique pattern of normal IGF-I and IGF-II levels and markedly increased levels of all three IGFBPs was present in uraemia. Measurement of free IGF-II binding capacity, and affinity cross-linking experiments showed that the excess immuno-reactive IGFBP was able to bind IGFs. To explain the excess of unoccupied IGF binding sites in uraemia, a mathematical model was developed which describes the production of IGFs and their interaction with IGFBP. Calculations of IGF secretion rates suggested that production of IGF is two orders of magnitude lower in uraemic children than in control children, despite normal GH secretion. It is concluded that in uraemia there is a relative GH insensitivity with respect to IGF production.     

病毒性心肌炎小鼠不同时点胰岛素样生长因子-1及其相关蛋白的表达

目的探讨胰岛素样生长因子-1（IGF-1）及其相关蛋白在病毒性心肌炎病程中的作用。方法取Balb／C小鼠60只，随机分为病毒实验组40只，腹腔感染CVB3病毒，分别于实验d3、7、15、30采血、取心肌组织；空白对组（未感染CVB3病毒小鼠）20只。用酶联免疫吸附测定法（ELISA）检测其血浆IGF-1的表达，用免疫组织化学法和逆转录酶多聚链反应（RT-PCR）技术检测其心肌组织IGF-1及相关蛋白的表达。结果病毒性心肌炎小鼠血浆IGF-1及相关蛋白表达均较空白对照组高，且在感染病毒后表达渐增高，15d达最高峰，30d表达降低，但仍维持一较高水平，与对照组比较仍有显著差异（F=19．53 P〈0.05），其在心肌组织中的表达与血浆中的表达变化规律一致。结论IGF-1及其相关蛋白可能参与小鼠CVB3病毒性心肌炎的病理生理过程。     

新生儿血清瘦素、生长激素、胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3水平与宫内发育的关系

目的 探讨瘦素(leptin)、生长激素(GH)、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)在不同宫内发育状况胎儿中的变化,及对胎儿生长发育调控的作用.方法 2004年1月-2006年6月出生早产小于胎龄儿(A组)30例,早产适于胎龄儿(B组)36例,足月小于胎龄儿(C组)32例,足月适于胎龄儿(D组)37例.生后24 h内抽取患儿静脉血,用放射免疫法(RIA)检测其血清leptin、GH、IGF-1、IGFBP-3水平,组间比较采用及多元回归相关分析.结果 各组新生儿血清leptin、GH、IGF-1、IGFBP-3水平均存在明显差异(Pa<0.05,0.01),各指标基本呈C、A、B、D组次序由低到高,但A组IGF-1与C组差异无统计学意义(P>0.05);在A、B和C组,出生体质量与leptin、IGF-1、IGFBP-3呈正相关(Pa<0.01),而D组出生体质量与IGF-1呈正相关(P<0.01),与其他激素无相关性.结论 leptin、IGF-1、IGFBP-3参与宫内发育迟缓儿和早产儿宫内生长发育的调控.IGF-1在早产适于胎龄儿的宫内生长发育中也起调控作用,而leptin、GH、IGFBP-3均不是足月适于胎龄儿生长发育的主要调节因素.     

Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or recuperation

OBJECTIVE: To study the influence of dietary intervention on plasma ghrelin levels in obese children and adolescents with anorexia nervosa (AN).Study design Prepubertal obese children (n=16) and 16 anorexic adolescents were studied at three different points: clinical diagnosis and after a reduction or recuperation of 25% and 50% of the initial BMI SD score. Controls included 21 Tanner growth stage 1 and 36 Tanner growth stage 5 subjects. We analyzed plasma ghrelin levels and their correlation with plasma levels of leptin, insulin, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 1 (IGFBP-1), insulin-like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor binding protein 3 (IGFBP-3), and integrated concentration of growth hormone (ICGH) before and after dietary intervention. RESULTS: At diagnosis, ghrelin levels were significantly decreased in obese children (52% of control levels) and significantly increased in adolescents with AN (164% of control levels). After dietary intervention, ghrelin increased in obese patients but without reaching control levels even after a 50% reduction in body mass index (BMI). In adolescents with AN, ghrelin levels normalized after a 25% increase in BMI. Ghrelin correlated negatively with the BMI and positively with IGFBP-1 levels in controls but not in obese patients or in patients with AN at diagnosis. The positive correlation between ghrelin and IGFBP-1 was recovered after dietary intervention. CONCLUSIONS: Plasma ghrelin levels present opposite changes in obesity and AN after dietary intervention, suggesting that ghrelin is a good marker of nutritional status.     

儿童I型糖尿病青春发育前及青春期血清IGF-I和IGFBP-3水平监测

目的：研究儿童Ⅰ型糖尿病青春发育前及青春期血清胰岛素样生长因子I(IGF-I),胰岛素样生长因子结合蛋白3(IGFBP-3)水平变化,探讨生长激素 胰岛素样生长因子I(GH-IGF-I)轴与血糖控制的关系。方法：分别采用ELISA和免疫放射法测定63例Ⅰ型糖尿病患儿和47例正常对照血清IGF-I,IGFBP-3水平,用胶乳凝集法测定Ⅰ型糖尿病患儿的糖化血红蛋白(HbAIC)。结果：①青春发育前糖尿病患儿血IGF-I为(75.4±26.6) ng/ml,IGFBP-3为(2 756.1±763.8) ng/ml,与对照组［(103.9±46.5) ng/ml,(2 717.1±480.2 ng/ml)相比无统计学差异(P>0.05);但青春期糖尿病患儿血IGF-I和IGFBP-3［(178.2±65.9) ng/ml,(2 956.0±847.6) ng/ml］均低于对照组［(229.6±54.5) ng/ml,(3 393.2±748.9) ng/ml］］P<0.05。②新发病的I型糖尿病患儿胰岛素治疗后血IGF-I为(143.0±67.5) ng/ml,IGFBP-3为(2 740.0±449.8) ng/ml,较治疗前［(54.8±44.3) ng/ml, (2 233.8±336.2) ng/ml］明显升高(P<0.05)。③糖尿病组HbA IC与血IGF-I,IGFBP-3之间存在负相关关系(r=-0.32,-0.29,P<0.01或0.05)。④糖尿病组青春期HbAIC为(9.0±1.8)%,每日胰岛素用量为(0.86±0.30)U/kg,均高于青春期前［(7.8±1.8) %,(0.64±0.38) U/kg］(P<0.05)。结论：儿童Ⅰ型糖尿病血IGF-I,IGFBP-3水平较正常儿降低,尤其青春期患儿比正常同龄儿降低的程度更为显著,提示此类患者青春期存在GH IGF-I轴的严重紊乱,可能是导致这一时期血糖控制不良的重要原因。     

脐血IGF-1及IGFBP-3与胎儿生长发育的关系研究

目的探讨胰岛素样生长因子-1（IGF—1）及胰岛素样生长因子结合蛋白-2（IGFBP-3）与胎儿宫内生长发育的关系。方法将新生儿根据出生体重与胎龄的关系分为大于胎龄儿（IAG）、适于胎龄儿（AGA）、小于胎龄儿（SGA）三组,分别测定三组新生儿出生时身长、体重及胎盘重量,同时取脐血采用EUSA法测定IGF-1及IGFBP-3水平。结果①三组新生儿出生时身长、体重及胎盘重量3个指标比较差异均有统计学意义（P均〈0．05）。②脐血IGF-1及IGFBP-3水平在SGA、AGA、LGA三组间比较,LGA组〉AGA组〉SGA组,各组间比较差异均有统计学意义（P均〈0.05）。③胎儿发育的重要指标出生体重、身长及胎盘重量与IGF-1及IGFBP-3水平均呈正相关。结论IGF-1及IGFBP-3与胎儿生长发育密切相关,对胎儿的生长发育起重要的调节作用。     

Diagnostic markers in combination improve the identification of growth-restricted neonates

Background

The identification of growth-restricted neonates is hampered by the lack of an appropriate diagnostic tool.

Aim

To determine the value of combining diagnostic markers in detecting growth-restricted neonates.

Methods

A set of anthropometric indices, nutritional status and placental weight were assessed in the study population soon after birth. Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) were assayed in cord blood. Babies having low values (≤25th centile for gestational age) in 0, 1 or more of four anthropometric indices were classified as Group₂₅0, Group₂₅1 and Group₂₅2, respectively. For statistical evaluation the Mann-Whitney test and a multiple regression analysis were performed.

Results

One hundred-eighty (180) singleton babies of over 36 weeks of gestational age (GA) were studied. IGF-I, IGFBP-3 levels and placental weight were significantly lower in Group₂₅2 than both Group₂₅0 (P < 0.0001) and Group₂₅1 (p < 0.0001 to p = 0.03). Group₂₅1 and Group₂₅0 did not differ significantly regarding IGF-I and IGFBP-3 levels (p values 0.09 and 0.13, respectively). The combination of anthropometric indices enhanced their ability to predict IGF-I, IGFBP-3 levels and placental weight; the nutritional status of the babies added power to all individual models in predicting the three outcome variables. Analogous results were obtained when the 10th (instead of the 25th) centile for GA was used for the anthropometric indices.

Conclusion

The combination of simple diagnostic markers of growth restriction can define a reference test with enhanced diagnostic potential compared to the potential of the same markers in isolated use.