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。     

足月小于胎龄儿胃饥饿素、胰岛素样生长因子-1及瘦素关系的研究

目的探讨胃饥饿素(Ghrelin)、胰岛素样生长因子-1(IGF-1)及瘦素(Leptin)在足月小于胎龄儿(SGA)中的作用及其关系。方法本院产科出生的足月SGA和适于胎龄儿(AGA)各30例,生后测量体重、身长、头围,并计算体重指数(BMI),生后第3天测定血Ghrelin、IGF-1及Lep-tin水平。结果 SGA组体重、身长、头围、BMI均明显低于AGA组[(2280±190)g比(3220±320)g,(46.3±1.8)cm比(50.5±2.0)cm,(31.8±1.1)cm比(33.6±1.1)cm,(10.6±0.8)cm比(12.6±0.9)cm,P均<0.05]。SGA组血清IGF-1及Leptin水平均低于AGA组[(49.6±10.3)μg/L比(55.3±9.9)μg/L,(2.4±0.8)μg/L比(3.0±1.0)μg/L],血浆Ghrelin水平高于AGA组[(25.2±11.0)μg/L比(17.3±7.4)μg/L],P均<0.05。两组IGF-1与体重呈正相关,Leptin与体重、身长呈正相关,Ghrelin与体重、BMI呈负相关,P均<0.05。两组Ghrelin水平与IGF-1呈负相关,IGF-1与Leptin呈正相关;SGA组Ghrelin水平与Leptin呈负相关,P均<0.05。结论生后早期SGA新生儿存在高Ghrelin、低IGF-1、低Leptin水平状态。Ghrelin、IGF-1及Leptin共同参与胎儿宫内营养的调节,相互起协同及拮抗作用。     

足月小于胎龄儿胃饥饿素、胰岛素样生长因子-1及瘦素关系的研究

目的探讨胃饥饿素（Ghrelin）、胰岛素样生长因子-1（IGF-1）及瘦素（Leptin）在足月小于胎龄儿（SGA）中的作用及其关系。方法本院产科出生的足月SGA和适于胎龄儿（AGA）各30例,生后测量体重、身长、头围,并计算体重指数（BMI）,生后第3天测定血Ghrelin、IGF-1及Lep-tin水平。结果 SGA组体重、身长、头围、BMI均明显低于AGA组[（2280±190）g比（3220±320）g,（46.3±1.8）cm比（50.5±2.0）cm,（31.8±1.1）cm比（33.6±1.1）cm,（10.6±0.8）cm比（12.6±0.9）cm,P均〈0.05]。SGA组血清IGF-1及Leptin水平均低于AGA组[（49.6±10.3）μg/L比（55.3±9.9）μg/L,（2.4±0.8）μg/L比（3.0±1.0）μg/L],血浆Ghrelin水平高于AGA组[（25.2±11.0）μg/L比（17.3±7.4）μg/L],P均〈0.05。两组IGF-1与体重呈正相关,Leptin与体重、身长呈正相关,Ghrelin与体重、BMI呈负相关,P均〈0.05。两组Ghrelin水平与IGF-1呈负相关,IGF-1与Leptin呈正相关;SGA组Ghrelin水平与Leptin呈负相关,P均〈0.05。结论生后早期SGA新生儿存在高Ghrelin、低IGF-1、低Leptin水平状态。Ghrelin、IGF-1及Leptin共同参与胎儿宫内营养的调节,相互起协同及拮抗作用。     

母血及脐血IGF-1、C肽和IGFBP-1质量浓度与新生儿出生体重的关系

目的探讨母体和脐血血清胰岛素样生长因子-1(IGF-1)、C肽(CP)及胰岛素样生长因子结合蛋白-1(IGFBP-1)质量浓度对新生儿出生体重的影响.方法选择12例大于胎龄儿(LGA)、15例适于胎龄儿(AGA)和20例小于胎龄儿(SGA),分为3组,分别抽取脐血和其母外周静脉血,分离血清.采用ELISA法测定IGF-1、CP和IGFBP-1.结果 (1)LGA组脐血IGF-1、CP、IGFBP-1质量浓度(ng·mL-1)分别为59.76±14.50,1.36±0.58,53.78±19.67;AGA组为33.65±12.74,0.90±0.45,104.79±27.60;SGA组为17.05±8.10,0.52±0.22,169.21±55.30;3组间差异有显著性意义(P<0.01).(2)LGA组新生儿母亲血清IGF-1、CP、IGFBP-1质量浓度(ng·mL-1)分别为267.15±99.43,2.84±0.93,158.50±51.25;AGA组母亲分别为237.34±105.56,2.71±0.72,170.78±63.69;SGA组分别为229.53±94.17,2.59±0.83,188.90±74.04;3组间比较差异均无显著性.但同组患儿母血IGF-1、CP及IGFBP-1均显著高于脐血水平(除SGA组母血与脐血IGFBP-1差异无显著性外).(3)新生儿出生体重与脐血IGF-1、CP呈正相关(r分别为0.814、0.654,P<0.01);与IGFBP-1呈负相关(r=-0.759,P<0.01);而与母血IGF-1、CP及IGFBP-1无明显相关性.结论脐血IGF-1、CP及IGFBP-1与胎儿生长关系密切.营养物质-胰岛素-胰岛素样生长因子轴是调节胎儿宫内生长发育的重要因素.     

小于胎龄儿血nesfatin-1水平及其与生长发育的关系

目的探讨nesfatin-1与新生儿能量代谢的关系。方法 113例新生儿分为早产儿53例、足月儿60例。足月儿分为适于胎龄(AGA)儿,32例、小于胎龄(SGA)儿28例。检测其空腹血浆nesfatin-1、生长激素释放肽(ghrelin)、胰岛素样生长因子-1(IGF-1)、胰岛素和血糖水平,并进行比较。结果 SGA组空腹血浆nesfatin-1、ghrelin、胰岛素水平及胰岛素抵抗指数(HOMA-IR)均高于AGA组(P=0.035 8,0.016 3,0.000 1,0.005 1);IGF-1、胰岛素敏感指数(HOMA-ISI)低于AGA组(P=0.033 0,0.000 1)。与出生0 d相比,出生7 d 2组nesfatin-1水平均明显降低(P<0.000 1),尤其是SGA组下降幅度更大。然后逐渐上升,到第28天,AGA组上升至出生时水平(P=0.284 8),但SGA组仍低于出生0 d的水平(P<0.000 1)。出生0 d,nesfatin-1水平在SGA组高于AGA组(P=0.035 8),但出生7 d及28 d,SGA组低于AGA组(P=0.000 2,0.048 8)。SGA组nesfatin-1与经口摄入热卡呈负相关(r=-0.446,P=0.017 0),与HOMA-ISI亦呈负相关(r=-0.398,P=0.036 0),与HOMA-IR呈正相关(r=0.43,P=0.023 0)。结论 nesfatin-1参与调控SGA儿摄食及能量代谢。nesfatin-1与SGA儿胰岛素敏感性有一定关系。     

脂联素、瘦素及胰岛素样生长因子-Ⅰ在胎儿生长发育中的作用

目的探讨脂联素、瘦素及胰岛素样生长因子-Ⅰ(IGF-Ⅰ)在胎儿生长发育中的作用。方法选择2006年10月-2007年10月在本院产科出生的新生儿86例。胎龄31~42周;男57例,女29例。根据不同出生体质量分为小于胎龄儿(SGA)组(16例),适于胎龄儿(AGA)组(41例)及大于胎龄儿(LGA)组(29例)。胎儿娩出后立即断脐留脐血20 mL,采用放射免疫分析法测定血清脂联素、瘦素及IGF-Ⅰ水平,同时检测其血脂水平,测量新生儿生长参数,计算体质量指数(BMI)。结果1.新生儿脐血瘦素、脂联素及IGF-Ⅰ水平无显著性别差异。2.脐血瘦素水平在SGA、AGA、LGA3组间有显著差异(P<0.001),LGA组显著高于AGA及SAG组(P<0.01,0.001);脐血瘦素水平与体质量、胎龄、头围、身长、足长及胎盘质量均呈显著正相关(Pa<0.01)。3.脐血脂联素水平与出生体质量、头围、足长、BMI水平均呈显著正相关(Pa<0.05)。脐血脂联素水平在SGA、AGA、LGA3组间有显著差异(P<0.001),LGA组高于AGA及SAG组(Pa<0.01)。4.LGA组脐血IGF-Ⅰ水平显著高于AGA及SAG组,3组间有明显差异(P<0.001);脐血IGF-Ⅰ水平与体质量、头围、身长、足长及胎盘质量均呈显著正相关(Pa<0.01)。5.脐血瘦素与脂联素、IGF-Ⅰ水平呈显著正相关(Pa<0.01),脐血脂联素与IGF-Ⅰ水平无明显相关关系(P>0.05)。6.SGA、AGA、LGA3组血脂水平比较无显著差异(Pa>0.05)。脐血IGF-Ⅰ水平与三酰甘油水平呈明显负相关(P<0.05),脐血脂联素、瘦素水平与血脂各指标间均无明显相关性(Pa>0.05)。结论瘦素与脂联素、IGF-Ⅰ在胎儿宫内生长和发育过程中起重要的调节作用,可作为评价胎儿生长发育及营养状态的临床指标之一。     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白3与胎儿宫内生长发育的关系

目的　通过测定新生儿脐血中胰岛素样生长因子 1(IGF 1)和胰岛素样生长因子结合蛋白 3(IGF BP 3)水平 ,研究其与出生体质量、身长及胎盘质量等生长参数间的关系 ,探讨影响胎儿宫内生长发育的内分泌因素。方法　将新生儿根据出生体质量与胎龄的关系分为适于胎龄儿 (AGA)组与小于胎龄儿 (SGA)组 ,分别测定两组出生时身长、体质量和胎盘质量 ,同时取新生儿脐血用免疫放射法测定IGF 1和IGFBP 3含量。结果　1) 10 5例新生儿中 79例AGA和 2 6例SGA ,其出生时身长、体质量和胎盘质量 3个参数比较均存在显著差异(P <0 .0 0 1) ,AGA组显著高于SGA组 (P <0 .0 0 1) ;2 )两组脐血IGF 1和IGFBP 3比较 ,AGA组IGF 1和IGF BP 3水平均高于SGA组 (P <0 .0 1和P <0 .0 0 1) ;3)出生时身长、体质量和胎盘重质 3个生长参数均与IGF 1和IGFBP 3呈显著正相关 (P均 <0 .0 0 1)。结论　 1.出生时身长、体质量和胎盘质量可用来评价AGA和SGA的生长发育。 2 .AGA脐血中IGF 1和IGFBP 3明显高于SGA。 3.胎儿自身分泌IGF 1和IGFBP 3与上述生长参数密切相关 ,其对胎儿的生长发育起重要调节作用。IGF 1和IGFBP 3可作为胎儿宫内生长发育的指标     

6个月内婴儿血清生长激素、胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3变化与体格发育的关系

目的 探讨6个月内婴儿血清生长激素(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)水平变化与体格发育值的关系.方法 对85例低出生体质量儿(LBWI)及29例足月适于胎龄儿于生后3 d、3个月、6个月时进行放射免疫法检测血清GH、IGF-1、IGFBP-3,同时测量婴儿体质量、身长、头围、胸围.结果 生后3 d小于胎龄儿的体格发育值和血清GH、IGF-1、IGFBP-3均分别低于适于胎龄儿(P均＜0.05),早产儿均小于足月适于胎龄儿(P＜0.05).3、6个月时LBWI的体格发育值和血清GH、IGF-1、IGFBP-3浓度均低于足月适于胎龄儿(P＜0.05).生后3 d、3个月、6个月时各体格发育值与各激素浓度均呈正相关.结论 新生儿血清GH、IGF-1、IGFBP-3浓度水平与胎儿生长发育有密切关系.LBWI生后6个月血清GH、IGF-1、IGFBP-3仍存在相对低水平状态,体格发育值仍落后于正常足月儿.     

骨钙素、Ⅰ型前胶原羧基端前肽、胰岛素样生长因子-1及其相关激素与胎儿骨发育的关系

目的 探讨骨钙素(OC)、Ⅰ型前胶原羧基端前肽(PICP) 及胰岛素样生长因子.1(IGF.1)等激素水平与胎儿骨生长发育的关系.方法 选择本院2008年10月-2009年10月收治的新生儿80例.男41例,女39例;胎龄28～42周.根据不同出生体质量分为小于胎龄(SGA)儿组22例,适于胎龄(AGA)儿组36例及大于胎龄(LGA)儿组(22例).胎儿娩出后,胎盘娩出前抽取其脐静脉血6 mL,采用放射免疫分析法测定其血清OC、IGF.1及甲状旁腺激素水平,酶联免疫吸附法检测其脐血PICP水平;同时检测其血钙、磷、ALP水平,测量新生儿生长参数,计算体质量指数(BMI).结果 1.脐血OC水平在SGA儿组、AGA儿组、LGA儿组间比较差异有统计学意义(P=0.000),LGA儿组显著高于AGA儿及SAG儿组(P＜0.01,0.001);脐血OC水平与出生体质量、头围、BMI呈正相关(Pa＜0.05),与身长无明显相关性(P＞0.05).2.LGA儿组脐血IGF.1水平显著高于AGA儿及SAG儿组,3组间比较有统计学差异(P=0.002);脐血IGF.1水平与出生体质量、头围、BMI水平均呈正相关(Pa＜0.05),与身长无明显相关性(P＞0.05).3.AGA儿组、LGA儿组脐血PICP水平明显高于SGA儿组,但3组间无统计学差异(P=0.070).脐血PICP、PTH水平与生长参数各指标水平均无直线相关关系(Pa＞0.05),偏相关分析脐血PICP与出生体质量、头围、BMI均呈正相关(r=0.239、0.250、0.306,Pa<0.05).4.脐血OC水平与PICP、IGF.1水平均呈正相关(Pa＜0.05),OC、PICP与PTH、ALP水平之间均无明显相关(Pa＞0.05).5.3组脐血钙、血磷、ALP水平均无统计学差异(Pa＞0.05).结论 SGA儿低血清OC、PICP水平与骨形成活动下降相关,脐血OC、PICP及IGF.1可作为评价胎儿骨骼生长发育的临床指标之一.     

脐血瘦素、胰岛素样生长因子-Ⅰ与胎儿生长发育

目的 揭示脐血瘦素及胰岛素样生长因子-Ⅰ(IGF-Ⅰ)与胎儿生长发育的关系,探讨其在胎儿生长发育方面的相互作用及临床意义.方法 采用放射免疫法测定86例新生儿脐血瘦素、IGF-Ⅰ水平,根据胎龄及出生体重百分位数的关系分为:小于胎龄儿(SGA)组16例、适于胎龄儿(AGA)组41例及大于胎龄儿(LGA)组29例.同时测量新生儿的出生体重、身长、头围、足长、胎盘重量并计算体质指数(BMI).结果 ①脐血瘦素水平SGA组与AGA组间差异有统计学意义(P<0.05);脐血IGF-Ⅰ水平AGA与LGA组间差异有统计学意义(P<0.05).②脐血瘦素及IGF-Ⅰ水平分别与新生儿出生体重、身长、头围、足长、BMI及胎盘重量呈显著正相关(P<0.01),脐血瘦素与IGF-Ⅰ水平亦呈显著正相关(P<0.01).③脐血瘦素水平与新生儿性别及分娩方式间差异均无统计学意义(P>0.05);脐血IGF-Ⅰ水平与新生儿性别差异无统计学意义(P>0.05),与新生儿分娩方式差异有统计学意义(P<0.05).结论 脐血瘦素、IGF-Ⅰ在调节胎儿生长发育方面起着重要作用,参与胎儿的生长发育过程,可作为评价胎儿生长发育及营养状态的临床指标之一.脐血瘦素、IGF-Ⅰ水平异常可能是引起胎儿宫内生长迟缓和巨大儿发生的原因之一.     

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。     

Growth hormone insensitivity syndromes: a preliminary report on changes in insulin-like growth factors and their binding proteins during treatment with recombinant insulin-like growth factor I

Serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) 1, 2 and 3 were studied by radioimmunoassay in 29 patients with growth hormone (GH) insensitivity syndromes (GHIS) before and during treatment with IGF-I. As in normal subjects, there was a highly significant correlation between IGFs and IGFBP-3 but not between IGFs and the other binding proteins, though IGFBP-3 represented only about one-third of the total IGFBP concentration. In 6 patients with GH deficiency and in 5 patients with GHIS, the pharmacokinetic profile of IGF-I after a single injection was strongly dependent on the IGFBP-3 concentration. A slight but significant increase in IGFBP-3 was observed coincident with the IGF-I peak, whereas IGFBP-2 increased after a delay of about 10 hours. In the patients with GHIS, chronic IGF-I treatment, with twice-daily injections for 6 months, caused a significant steady decline of IGF-II and an increase in IGFBP-2, but had no effect on IGFBP-1 and IGFBP-3 levels. During IGF-I treatment, an inverse relationship between baseline IGF-I and GH levels was observed. The data suggest that total IGF-I and IGF-IL serum levels are determined mainly by IGFBP-3, even in extreme situations such as GHIS, while other IGFBPs are less important. The IGFBP-3 concentration seems to be a major regulator of the pharmacokinetics of exogenous IGF-I, which, in turn, influences IGFBP-3 levels. This effect of IGF-I on IGFBP-3 is not through induction of IGFBP-3 synthesis, but possibly by reduction of IGFBP-3 clearance. Finally, IGF-I administration suppresses GH secretion.     

Improvement of diagnostic criteria in growth hormone insensitivity syndrome: solutions and pitfalls

A survey to identify children and adolescents with primary growth hormone insensitivity syndrome (GHIS) yielded 38 patients who were positively identified using a scoring system that included five criteria: height, basal growth hormone (GH), GH binding protein, basal insulin-like growth factor 1 (1GF-I) and the increase of IGF-I after 4 days of GH administration (IGF generation test). Because of an overlap of the accepted and excluded groups with respect to points scored, an attempt was made to improve the scoring system. The new criteria were: height below –3 SDS, basal GH 4 mU/I or above, GH binding below 10%, basal IGF-I and basal IGF binding protein-3 (IGFBP-3) below the 0.1 centile for age, an increase of IGF-I in the IGF generation test less than 15 μg/1, and the increase of IGFBP-3 less than 0.4 mg/1. With this scoring system, a clear separation between the accepted and the excluded groups was obtained. IGFBP-3 was included to give the GH-dependent parameters of the IGF system more weight and because the accuracy of IGFBP-3 in the IGF generation tests was greater than the accuracy of IGF-I, when the group of patients with GHIS was compared with a group of patients with GH deficiency. Unexpectedly, the IGF generation test was unable to segregate both cohorts completely. In the GHIS-positive group, a significant correlation was found between basal IGF-I or IGFBP-3 levels corrected for age (SDS) and height SDS ( r = 0.49, p < 0.002 and r = 0.61, p < 0.0001, respectively). There was also a significant correlation between the changes of IGF-I or IGFBP-3 in the IGF generation test and height SDS. That is, the patients with a slight response to GH were those with the least growth retardation, suggesting the existence of partial GH insensitivity.     

Effects of insulin-like growth factor I treatment on the molecular distribution of insulin-like growth factors among different binding proteins

The molecular distribution of insulin-like growth factor I (IGF-I) and IGF-II among the IGF binding proteins (IGFBPs) was studied before and during IGF-I therapy in Ecuadorean adults with growth hormone receptor deficiency (GHRD). Of the total circulating IGF-I and IGF-II, 70% was carried by the 150 kDa complex in normal subjects, while in patients with GHRD, 50% of serum IGF-I, but only 30–35% of serum IGF-II, was measured within the 150 kDa IGFBP-3 region. Administration of IGF-I altered the concentration of IGF-I and IGF-II, although the percentage of total IGF measured within each IGFBP region was not affected, as the increase in IGF-I and the decrease in IGF-II were proportional. Similarly, serum concentrations of IGFBP-3 and the acid-labile subunit, measured by radioimmunoassay, were unaltered. Thus, administration of IGF-I to patients with GHRD was unable to correct the aberrant distribution of IGFs among the IGFBPs.     

Insulin-Like Growth Factor II Effects Mediated through Insulin-Like Growth Factor II Receptors

ABSTRACT. Insulin-like growth factor II (IGF-II) resembles the homologous peptide insulin-like growth factor I (IGF-I) in that it stimulates cellular growth in vitro. This effect is generally believed to be mediated through IGF type 1 receptors; the role of the IGF type 2 receptor remains, as yet, unknown. IGF-II has been shown to stimulate clonal expansion in cells from the human erythroleukaemia cell line K562, which displays binding of IGF-II and insulin but not IGF-I. This IGF-II effect was dose-dependent and correlated to the amount of specific binding; IGF-I did not stimulate growth. A similar effect on clonal growth was observed in the human T-cell line Jurkat. Furthermore, IGF-II was found to stimulate the cytotoxic activity of natural killer cells (as does interleukin 2). This effect was not inhibited by addition of IGF binding protein 1. Thus, it can be concluded that IGF-II, besides demonstrating standard IGF properties, exhibits unique biological effects in certain cells.     

儿童青少年血清胰岛素生长因子-1及胰岛素因子结合蛋白-3的正常参考值研究

目的 建立中国6～18岁年龄段血清胰岛素生长因子-1(IGF-1)和胰岛素因子结合蛋白-3(IGFBP-3)水平的正常参考值,并探讨其与年龄、性别、发育阶段及体质指数的关系.方法 选取了大庆市、北京市、上海市不同中小学校的837名体检正常的儿童、青少年(男416名,女421名),由内分泌医师记录其发育状况.用化学发光法(IMMULITE 1000)测定血清IGF-1和IGFBP-3.用t检验和线性回归方法研究IGF-1及IGFBP-3与年龄、性别、发育阶段及体质指数(BMI)的关系.结果 男孩血清IGF-1于13岁组时出现峰值,女孩11岁组出现峰值;男孩血清IGFBP-3值14岁组时达到峰值,女孩11岁组达到峰值;高峰值出现后,IGF-1和IGFBP-3水平随年龄增长缓慢下降或维持高峰值在平台期;同年龄组相比,男孩血清IGF-1值高于女孩,女孩的IGFBP-3值高于男孩.发育阶段对血清IGF-1水平的影响大于对ICFBP-3的影响,而BMI对血清IGF-1及IGFBP-3水平无明显影响.结论 建立了与年龄、性别、发育阶段相关的儿童青少年血清IGF-1及IGFBP-3水平的正常参考值,这些数据对于生长监测、临床诊断及GH治疗后随访有重要参考价值.     

The effects of co-therapy with recombinant human insulin-like growth factor I and insulin on serum leptin levels in adolescents with type 1 diabetes mellitus

We previously demonstrated that in patients with type 1 diabetes mellitus (DM), co-therapy with subcutaneous (s.c.) recombinant human insulin-like growth factor I (rhIGF-I) and insulin improves glycemic control and reduces daily insulin requirements without inducing a significant change in body weight. However, it has been postulated that treatment with IGF-I may promote beneficial changes in body composition. Consequently, we assayed serum leptin, a peptide highly correlated with total fat mass, before and during chronic rhIGF-I administration. We studied 14 adolescents with type 1 DM (age range 12-19 yr). All patients were treated for 12 weeks with twice daily (BID) sc rhIGF-I in combination with standard BID split-mix insulin. At baseline, leptin concentrations were positively correlated with body mass index (BMI) (r(2) = 0.52, p = 0.004), as previously described for non-diabetic individuals. Leptin levels in diabetic females were higher than in diabetic males, and more than two times higher than in non-diabetic female controls. Baseline leptin levels did not correlate with patient age, duration of DM or hemoglobin A1c (HbA1c) measurements. The relationship between leptin concentrations and gender was maintained throughout treatment; however, average leptin levels did not change during 12 weeks of IGF-I + insulin co-therapy. These data suggest that despite treatment-induced improvements in HbA1c and serum IGF-I levels, serum leptin concentrations are unchanged by co-therapy with IGF-I + insulin. Moreover, these results suggest that improved metabolic control with IGF-I therapy is not obtained at the expense of increasing adiposity, a complication seen frequently with intensive insulin therapy.     

Insulin-like growth factor binding protein-3 proteolysis and growth of athyreotic infants in the first weeks of life

To gain a better understanding of the growth of athyreotic newborns in the first weeks of life, we evaluated auxological parameters and determined the serum levels of growth hormone (GH), insulin-like growth factor I (IGF-I) and free IGF-I, and IGF-binding protein-3 (IGFBP-3) in 15 hypothyroid infants (10 females) at a mean age of 25 d of life, immediately before the beginning of L-thyroxine therapy, and at 3 and 6 mo of life. Fourteen normal infants (9 females) of the same age were studied as controls. IGFBP-3 proteolytic activity was evaluated in 8 patients and in 8 controls at 25 d and 6 mo of life. There was no significant difference concerning weight and length between the patients and controls at birth, 25 d, 3 and 6 mo of life. The blood GH, IGF-I and IGFBP-3 levels were significantly lower in patients at diagnosis than in controls of the same age (p < 0.01 for all parameters), as well as IGFBP-3 studied by Western blotting. At diagnosis, the patients' free IGF-I level was within the control range, but the free IGF-I percentage of total IGF-I was higher than in the controls (p < 0.01). IGFBP-3 proteolytic activity was found to be greater in the patients (p < 0.01). At 6 mo of life, after therapy, none of these parameters was different from those of the controls. CONCLUSION: Increased IGFBP-3 proteolytic activity in our patients at diagnosis, favouring IGF-I bioavailability, could account for normal free IGF-I levels and in turn for their normal growth pattern during the first weeks of life and before the start of treatment.     

A cross-sectional study of growth, puberty and endocrine function in patients with thalassaemia major in Hong Kong

Methodology: A cross-sectional study of growth, puberty and endocrine function was performed on 35 girls and 33 boys with thalassaemia major.
Results Despite regular transfusion and chelation therapy, 75% of the girls and 62% of the boys over the age of 12 years were below the third percentile for height. Hypogonadotropic hypogonadism was found in a similar percentage of patients. Moderate to marked zinc deficiency secondary to chelation therapy was considered unlikely because normal serum zinc levels were found in all but three of our patients, but we could not exclude the possibility of a marginal status of zinc nutrition causing growth failure. Growth hormone deficiency and diabetes mellitus were sometimes encountered but hypothyroidism, hypoparathyroidism and adrenal insufficiency were rare among our patients. Most of the patients with growth failure had normal growth hormone (GH) response to insulin induced hypoglycaemia. The serum insulin-like growth factor-1 (IGF-1) levels were low in our patients and no significant difference in the serum IGF-1 levels was found between prepubertal children with or without growth failure (0.4±0.1 mU/mL vs 0.37±0.11 mU/mL, P = 0.39). Similarly, no difference in the serum IGF-1 levels was found between pubertal children with or without growth failure (0.48 ± 0.2 U/mL vs 0.56 ±0.14 U/mL, P= 0.26).
Conclusions Delayed sexual maturation and a possible defect in growth unrelated to the GH-IGF-1 axis may be responsible for the growth failure in adolescent children with thalassaemia major.     

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。