宫内发育迟缓与胰岛素样生长因子及其结合蛋白关系的研究

为探讨宫内发育迟缓（IUGR）的发生机制,检测了86例新生儿脐血胰岛素样生长因子－1（IGF－1）、胰岛素样生长因子结合蛋白－3（IGFBP－3）水平,并分析上述指标变化与胎儿期生长的关系。将86例新生儿分为两组,IUGR（即小于胎龄儿）组22例,适于胎龄儿（AGA）组64例,采用竞争性放射免疫分析法（RIA）测定两组脐血IGF－1水平,非竞争性免疫放射分析法（IRMA）测定IGFBP－3水平。结果显示,与AGA组相比,IUGR组脐血IGF－1和IGFBP－3水平显著降低（P＜0．001）;IGF－1水平随胎龄及出生体重增加而增加（P＜0．01）;IGFBP－3水平与胎龄及出生体重呈相关（P＜0．01）;IGF－1与IGFBP－3呈正相关（P＜0．01）。认为IUGR与IGF－1及其结合蛋白密切相关,不论何种原因引起的IUGR,其脐血IGF－1、IGFBP－3水平均低,IGF－1水平下降与IGFBP－3下降相伴随;脐血IGF－1、IGFBP－3水平与胎龄及出生体重呈正相关,随着胎龄的增加和出生体重的增长,IGF－1、IGFBP－3水平不断升高。     

胰岛素-胰岛素样生长因子代谢轴在胎儿生长发育中的作用

目的探讨胰岛素-胰岛素样生长因子（IGF）代谢轴在胎儿宫内生长发育中的作用。方法连续收集266名单胎足月新生儿基本资料,采用放免法检测脐血胰岛素和IGF水平。结果（1）脐血胰岛素水平与出生体重、BMI、身长和胎盘重量均呈正相关（P〈0．01）。（2）脐血IGF水平与出生体重、BMI、身长和胎盘重量均呈正相关（P〈0．01）。（3）脐血胰岛素水平和IGF水平呈显著正相关（P〈0．01）。结论脐血胰岛素、IGF水平可作为评价胎儿宫内生长发育情况的参考指标。     

血清胰岛素样生长因子及其结合蛋白诊断儿童生长激素缺乏症的价值

为了解血清胰岛素样生长因子1（IGF－1），胰岛素样生长因子结合蛋白－3（IGFBP－3）浓度与生长激素缺乏症（GHD）患儿生长激素（GH）激发试验中血清生长激素峰值的关系，以确定血清IGF－1，IGFBP－3浓度诊断GHD的价值，为其代替GH激发试验提供依据，选择GHD患儿62例（男39例，女23例）为GHD组，60例健康儿童（男38例，女22例）为对照组。分别用放射免疫分析（RIA）法，免疫放射分析（IRMA）法检测GHD组血清IGF－1，IGFBP－3浓度，同时被GH激发试验，测定血清GH峰值，并比较其与IGF－1，IGFBP－3的关系，测定对照组血清IGF－1，IGFBP－3。结果显示，GHD组血清IGF－1，IGFBP－3均显著低于对照组（t分别为3.116,11.579,p均＜0．01）；GHD组血清IGF－1，IGFBP－3浓度与GH激发试验中的GH峰值呈显著正相关（r分别为。331，0。347，P均＜0．01）；GHD组血清IGF－1，IGFBP－3降低的阳笥率分别为97．58％，98．38％，与激发试验的阳性率（100％），比较无统计学意义（x^2分别为.3074,2.033,P均＞0．05）。表明血清中IGF－1，IGFBP－3浓度检测对诊断GHD有重要价值，认为检测血清中IGF－1，IGFBP－3浓度可以替代GH激发试验。     

胰岛素样生长因子和胰岛素样生长因子结合蛋白在人类胎儿生长中的作用

尽管人类胎儿生长的激素作用机制还不清楚，但研究表明，胰岛素样生长因子（IGFs)和胰岛素样生长因子结合蛋白（IGFBPs)起了重要作用。其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（IGFBP）－3的水平与胎儿的身长和体重呈正相关，而IGFBP－1的水平与胎儿的身长和体重呈负相关。     

小于胎龄儿的血清低胰岛素样生长因子I和C肽水平

目的　动态观察轻度和重度小于胎龄儿 (SGA)血清胰岛素样生长因子 I(IGF I)和C肽 (CP)水平 ,并与适于胎龄儿 (AGA)的水平进行比较 ,以探讨SGA的可能发病机制。方法　用放射免疫分析法测定了SGA和AGA出生时脐血、生后 3～ 7天和 2 2～ 2 8天外周血IGF I和CP浓度。结果　 (1)AGA出生时、出生后 3～ 7天和 2 2～ 2 8天的IGF I水平无明显差异 ,分别为 (10 .7± 4.5 )、(10 .8± 3.5 )和 (11.1± 3.4)nmol/L ;出生时和出生后 3～ 7天的CP水平相似〔(0 .43± 0 .13)和 (0 .41± 0 .12 )nmol/L〕 ,于出生后 2 2～ 2 8天下降〔(0 .32± 0 .11)nmol/L〕。 (2 )重度和轻度SGA出生时的IGF I〔(6 .1± 1.8)和 (8.9± 2 .8)nmol/L〕和CP〔(0 .2 6± 0 .0 9)和 (0 .33± 0 .11)nmol/L〕水平均低于AGA出生时水平 ;重度SGA出生后 3～ 7天和 2 2～ 2 8天的IGF I〔(6 .8± 2 .4)和 (6 .6± 1.9)nmol/L〕和CP〔(0 .2 7± 0 .10 )和 (0 .2 5± 0 .12 )nmol/L〕水平仍相当于其出生时水平 ;轻度SGA出生后IGF I和CP水平则明显上升 ,于 1周内达到AGA水平〔(11.4± 3.4)和 (0 .41± 0 .11)nmol/L〕 ,3～ 4周超过AGA水平〔(14.0± 3.5 )和 (0 .40± 0 .14)nmol/L〕。 (3)AGA出生时、出生后 3～ 7天和 2 2～ 2 8天的IGF I和CP之间存     

血清IGF—1、IGFBP—1，GH水平与糖尿病慢性并发症关系的研究

目的：揭示胰岛素样生长因子－1,胰岛素样生长因子结合蛋白－1,生长激素对糖尿病慢性并发症的发生,发展的影响。方法：测定20例健康对照者和62例2例糖尿病,10例1例糖尿病患者的胰岛素样生长因子－1（IGF－1）,胰岛素样生长因子结合蛋白－1（IGFBP－1）,生长激素（GH）及血浆胰岛素（INS）,C肽（C－P）,糖化血红蛋白（HbAlc)指标,结果：（1）IGF－1水平,1型糖尿病患者显著低于对照组（P＜0．05）,2型糖尿病患者显著低于对照组（P＜0．05）,（2）IGFBP－1水平,1型糖尿病患者显著高于对照组（P＜0．05）,2型糖尿病肥胖型伴高胰岛素血症者显著低于对照组（P＜0．05）;（3）GH水平,1型糖尿病患者显著高于对照组（P＜0．05）,2型糖尿病与对照组无显著差异（P＞0．05）,（4）合并糖尿病肾病及视网膜病变患者IGF－1水平均较对照组增高（P＜0．05）,（5）IGF－1水平与HbAlc间呈负相关（P＜0．01 2型r=-0.62 1型r=-0.73)。结 论：IGF－1,IGFBP－1,GH水平的检测对糖尿病慢性并发症,特别是微血管病变的发生,发展有重要的临床意义。     

早产儿、小于胎龄儿体质量追赶生长及其与IGF－1的相关性

目的：探讨早产儿和小于胎龄儿（ SGA）体质量追赶生长的规律及其与IGF－1的相关性。方法选择早产SGA 13例、早产适于胎龄儿（ AGA）80例、足月SGA 23例、足月AGA 177例，记录各组体质量，计算标准差单位（SDS）和SDS的变化值（ΔSDS），并进行统计学分析。结果①足月SGA 42 d时体质量的ΔSDS值＞0，提示其出生后即出现体质量追赶生长。9个月时体质量与足月AGA无显著差异（ P＞0．05），提示已达到完全追赶生长。②早产AGA生后42 d时体质量SDS值降至最低，其后体质量SDS值出现缓慢上升，3月龄时体质量ΔSDS值＞0，提示42 d前存在持续宫外发育迟缓，42 d后出现体质量追赶生长。③早产SGA的体质量追赶生长出现最晚，生后SDS值在3月龄时降至最低，此后开始上升，到6月龄时体质量的ΔSDS值＞0，提示其宫外发育迟缓持续至3月龄，3月龄后出现体质量追赶生长，18月时体质量仍与足月AGA存在显著差异，提示尚未达到体质量完全追赶生长。④早产和SGA的IGF－13月龄时均出现显著上升，与其体质量追赶生长趋势相吻合。结论早产儿均存在宫外发育迟缓现象，体质量追赶生长开始的时间依次为足月SGA、早产AGA、早产SGA。1岁时足月SGA和早产儿AGA体质量基本达到完全追赶生长；IGF－1水平变化与追赶生长的趋势一致。     

新生儿脐血血脂水平及胎心率检测分析

目的探讨新生儿脐血血脂水平及胎心率的变化。方法选取头胎顺产新生儿87例,测定小于胎龄儿(SGA)14例、适于胎龄儿(AGA)63例、大于胎龄儿(LGA)10例脐血血脂水平,记录胎儿娩出前5 min胎心率。并使用全自动生化分析仪测定脐血甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和载脂蛋白AI(ApoAI)和载脂蛋白B(ApoB)水平。结果SGA组脐血TG、TC、LDL-C、ApoB水平均高于AGA组和LGA组,HDL-C、ApoAI水平低于AGA组和LGA组,差异有统计学意义(P<0.05);新生儿血脂指标与胎心率回归分析未发现明显相关性(P>0.05)。结论不同的宫内环境引起胎儿代谢的改变,胚胎生长受限的新生儿存在血脂代谢障碍。     

IGF—I、IGFBP与肺癌

胰岛素样生长因子－I（IGF－I）具有类似胰岛素的代谢作用和促有丝分裂作用。IGF－I的生物学活性受胰岛素样生长因子结合蛋白（IGFBP，包括IGFBP－1－6）的调节。近年的研究表明测量肺部各种标本的IGF－I、IGFBP的水平有助于肺癌的早期诊断、病理分期，IGF－I抑制剂和IGFBP－3，6增强剂可望成为肺癌的有用的治疗手段。     

子痫前期患者与新生儿脐带血中IGF-Ⅰ及GH水平分析（附30例报告）

选择子痫前期患者30例（研究组）及同期住院单胎妊娠、元内外科并发症32例孕妇（对照组）为研究对象，用放射免疫法测定两组孕妇血清及新生儿脐静脉血清中胰岛素样生长因子-Ⅰ（IGF-Ⅰ）及生长激素（GH）的水平，并观察两组新生儿体重与胎盘重量及其与前两者之间的相关性。结果研究组新生儿体重及胎盘重量均明显低于对照组，孕妇血清及脐血中IGF-Ⅰ均低于对照组；两组母血与脐血IGF—Ⅰ水平均呈正相关；两组新生儿出生体重及胎盘重量均与母血GH水平呈正相关；研究组新生儿体重与脐血GH呈负相关、在对照组则元相关性，胎盘重量在两组间与脐血GH均元相关性。认为子痫前期状态下孕妇及胎儿体内IGF—Ⅰ及GH水平改变与胎儿生长发育有关。     

Impact of Insulin Resistance on Insulin-Like Growth Factor-1/Insulin Like Growth Factor-Binding Protein-3 Axis and on Early Weight Gain in Small for Gestational Age Infants

Objective: To assess insulin-like growth factor-1 (IGF-1)/IGF-binding protein-3 (IGFBP-3) axis and insulin resistance (IR) and the relationship of these parameters with growth in appropriate for gestational age (AGA) and small for gestational age (SGA) infants at birth and in early infancy.Methods: Postnatal blood samples for measurement of glucose, insulin, IGF-1, and IGFBP-3 were taken from 60 infants (30 AGA and 30 SGA) at birth and at one, three, and six months of age. Both SGA and AGA infants were divided into two groups: growing well and not growing well. Blood glucose, insulin, IGF-1, and IGFBP-3 values were assessed in all infants.Results: Homeostasis model assessment-IR (HOMA-IR) values in well-growing SGA infants in the third and sixth months were found to be higher than in not well-growing SGA infants (3.9±0.8 vs. 1.0±0.3 at 3 months and 3.3±0.9 vs. 2.4±0.9 at 6 months, p<0.05). IGF-1 levels in well-growing SGA infants at 3 and 6 months were found to be higher than those in not well-growing SGA infants (83.80±44.50 vs. 73.50±17.60 ng/mL at 3 months and 95.12±50.74 vs. 87.67±22.91 ng/mL at 6 months, p<0.05). The IGF-1 values were significantly lower in well-growing SGA infants than in well-growing AGA infants (83.80±44.50 vs. 103.31±30.81 ng/mL at 3 months and 95.12±50.74 vs. 110.87±26.44 ng/mL at 6 months, p<0.05).Conclusions: This study demonstrates the effects of accelerated early infant growth on IGF-1/IGFBP-3 axis in SGA-born infants.Conflict of interest:None declared.     

Serum levels of adiponectin and IGFBP-1 in short children born small for gestational age

OBJECTIVE: The aim of this study was to quantify serum adiponectin concentrations in short children born small for gestational age (SGA) compared with those in children born appropriate for gestational age (AGA), and to assess the relationship between the serum levels of adiponectin and insulin-like growth factor binding protein-1 (IGFBP-1) known as a predictor of the development of type 2 diabetes mellitus and cardiovascular disease. SUBJECTS AND METHODS: Sixteen prepubertal short children born SGA and 20 short children born AGA, matched for age, body mass index, height, pubertal status, gestational age, bone age and midparental height, were included in the study. The serum levels of adiponectin, IGFBP-1, insulin and insulin-like growth factor-I (IGF-I) were measured in the fasting state. RESULTS: The levels of serum adiponectin were significantly lower in the SGA than in AGA children (10.5 +/- 4.2 vs. 13.9 +/- 5.1 micro g/ml, P < 0.05). The levels of serum IGFBP-1, insulin and IGF-I were all similar in both groups. Overall, there was a significant positive correlation between adiponectin and IGFBP-1 (r = 0.40, P < 0.05). CONCLUSIONS: Our results suggest that hypoadiponectinaemia in short SGA children without catch-up growth may reflect insulin resistance and imply a higher risk of developing type 2 diabetes mellitus. Additionally, adiponectin may be a more sensitive indicator for latent insulin resistance than IGFBP-1 in short SGA children.     

Phosphoisoforms of insulin-like growth factor binding protein-1 in appropriate-for-gestational-age and small-for-gestational-age fetuses

We analysed phosphoisoforms of insulin-like growth factor binding protein-1 (IGFBP-1) in maternal and cord sera from preterm and term fetus with different growth status. Phosphoisoforms were separated by non-SDS-polyacrylamide gel electrophoresis and detected by immunoblot. Phosphoisoforms were also analysed by anion exchange chromatography on HPLC. The proportion of non-phosphorylated IGFBP-1 to total IGFBP-1 was significantly higher in preterm fetus than in their mothers, however, the relative amounts of each IGFBP-1 isoforms were similar between preterm and term fetus. The levels of non-phosphorylated IGFBP-1 were similar between appropriate for gestational age (AGA) and small for gestational age (SGA) fetus at term, however, phosphorylated isoforms of IGFBP-1 were increased in SGA fetus compared to those of AGA fetus and the proportion of non-phosphorylated IGFBP-1 to total IGFBP-1 was lower in SGA fetus than those in AGA fetus. Thus, the profiles of non-phosphorylated and phosphorylated IGFBP-1 in the fetus varies corresponding to fetal growth suggesting that not only total amounts of IGFBP-1 but also the proportion of phosphoisoforms of IGFBP-1 is important for fetal growth.     

Ghrelin in small-for-gestational age (SGA) newborn babies: a cross-sectional study

Background  Small-for-gestational newborn babies may have long-term metabolic consequences. Among the main hormones possibly involved in foetal growth regulation are the IGFs, IGFBPs and the recently described ghrelin.
Objective  To examine the levels of desacyl-ghrelin, IGF-1, IGFBP-1 and IGFBP-3 in children Small-for-gestational age (SGA) and children adequate-for-gestational age (AGA).
Design  This was a cross-sectional and comparative study.
Subjects  We included 40 children SGA and 40 children AGA.
Measurements  Blood sample was taken a week after birth and measuring hormonal levels were done by ELISA.
Results  SGA babies had lower IGF-1, IGFBP-3 and leptin levels, but higher ghrelin and IGFBP-1 levels. Birth weight was associated independently with ghrelin and IGFBP-1 (negatively) and IGFBP-3 (positively). Ghrelin circulating levels were associated negative and independently with IGFBP-3 and triglycerides in the mother.
Conclusions  We interpreted these findings to indicate that diminished body weight in newborns induce different adaptive signals, some of them mediated by IGF-1/IGFBP-3, ghrelin or by IGFBP-1. This regulation is congruent with the proposed role of ghrelin to adaptation to under-nutrition favouring lipid accumulation. CONCyTEG grant number 05-16-K117-028.     

A prospective study of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 in 942 healthy infants: associations with birth weight, gender, growth velocity, and breastfeeding

CONTEXT: Many aspects of hormonal regulation and mechanisms of normal infancy growth are poorly understood. OBJECTIVE: The objective of this study was to establish the determinants of serum growth factor levels in infancy and their association with growth. DESIGN: A prospective, longitudinal, population-based birth cohort between 1997-2001 was studied. PARTICIPANTS: Study participants were 942 healthy appropriate weight for gestational age (AGA) infants (538 boys and 404 girls) and 49 small for gestational age (SGA) children (29 boys and 20 girls). Interventions: Interventions were anthropometrical measurements (0, 3, 18, and 36 months) and serum samples (3 months). MAIN OUTCOME MEASURES: Height, weight, and serum IGF-I and IGF-binding protein-3 (IGFBP-3) were the main outcome measures. RESULTS: IGF-I levels showed no gender difference [boys, 92 ng/ml (confidence interval, 49, 162); girls, 91 ng/ml (47, 149); P = 0.50]. IGFBP-3 levels were significantly higher in females [2174 ng/ml (1295, 3330)] than in males [2103 ng/ml (1266, 3143); P = 0.04]. Infants receiving breast milk had lower IGF-I levels [90 ng/ml (48, 154)] than infants receiving formula [n = 62; 97 ng/ml (58, 165)] or both [n = 123; 94 ng/ml (48, 169); P < 0.001]. IGF-I and IGFBP-3 levels were positively associated with weight gain and height gain from birth to 3 months of age in AGA, but not in SGA, children. SGA children had significantly lower IGF-I [88.0 ng/ml (28, 145); P = 0.05] and IGFBP-3 [1835 ng/ml (1180, 2793); P < 0.001] levels than AGA children. CONCLUSION: We found a significant, but weak, association between IGF-I and IGFBP-3 levels at 3 months and postnatal growth in AGA, but not SGA, children. Factors other than IGF-I must contribute to the regulation of normal postnatal growth, and these may differ between AGA and SGA children. IGFBP-3, but not IGF-I, showed a gender difference, which may reflect an influence of the postnatal activation of the pituitary-gonadal axis on binding protein levels.     

Smallness for gestational age is associated with persistent change in insulin-like growth factor I (IGF-I) and the ratio of IGF-I/IGF-binding protein-3 in adulthood

CONTEXT: Implication of the IGF-IGF-binding protein (IGFBP) axis in the development of metabolic and cardiovascular diseases has been well documented. It has also been shown that an adverse intrauterine environment alters the IGF-IGFBP axis during childhood. OBJECTIVE: The objective of this study was to investigate whether these alterations persist into adulthood. DESIGN AND METHODS: Fasting serum IGF-I, IGFBP-3, and insulin concentrations were measured, and their determinants were analyzed in a cohort of young adult subjects (22 yr of age) born either small (SGA; n = 461) or appropriate (AGA; n = 568) for gestational age. RESULTS: In adulthood, subjects born SGA had significantly lower mean serum IGF-I (320 +/- 137 vs. 348 +/- 143 microg/liter; P = 0.0015), IGFBP-3 (4700 +/- 700 vs. 4800 +/- 800 microg/liter; P = 0.04), and IGF-I/IGFBP-3 ratio (0.067 +/- 0.026 vs. 0.072 +/- 0.025; P = 0.01) than those born AGA. The fasting IGF-I concentration and the IGF-I/IGFBP-3 ratio were significantly inversely associated with age, body mass index, smoking, and oral contraception and were positively related to birth weight and fasting insulin levels. The IGFBP-3 concentration was significantly negatively correlated to age and smoking and was positively related to insulin concentration and oral contraception. After adjustment for age, height, body mass index, gender, smoking, and oral contraception, the mean IGF-I concentration and the mean IGF-I/IGFBP-3 ratio remained significantly lower in the SGA compared with the AGA group (P = 0.003 and P = 0.01, respectively). CONCLUSIONS: Serum IGF-I concentrations and the IGF-I/IGFBP-3 ratio are lower in adult subjects born SGA. Although the origin of this persisting alteration of the IGF-IGFBP axis in adulthood needs to be elucidated, its potential contribution to the long-term metabolic and cardiovascular complications associated with fetal growth restriction is important to consider in the future.     

小于胎龄儿青春前期线性生长方式与血清胰岛素水平关系的研究

目的 探讨小于胎龄儿(small for gestational age,SGA)出生后生长追赶状态与血清胰岛素水平的关系.方法 青春前期30例有生长追赶SGA(catch-up growth SGA,CUG-SGA组)、37例无生长追赶SGA(NCUG-SGA组)和42例适于胎龄儿(appropriate for gestational age,AGA组),测定空腹血糖、空腹胰岛素(FINS)和血清胰岛素样生长因子I(IGF-I).结果 (1)与NCUG-SGA和AGA组比较,CUG-SGA组FINS和稳态模型评估的胰岛素抵抗指数(HOMA-IR)显著为高(P<0.01或P<0.05),而NCUG-SGA组与AGA组则无显著性差异(P>0.05).CUG-SGA组血清IGF-I水平较NCUG-SGA组显著为高[(212.61±17.81对137.40±14.66)ng/ml,P=0.001],但与AGA组无显著性差异(P=0.095).(2)SGA组HOMA-IR与年龄、身高标准差分值增值(AHtSDS)和体重指数分别正相关;≤6岁SGA组FINS与△HtSDS呈正相关,>6岁组FINS与体重标准差分值增值呈正相关.结论 生后早期胰岛素可能以生长因子角色参与了SGA儿的生长追赶;胰岛素抵抗程度与生长追赶程度相随.

Abstract：

Objective To evaluate the association between two different linear growth patterns with the levels of serum insulin in children bem small for gestational age(SGA).Methods Serum fasting glucose,fasting insulin,and insulin-like growth factor-I(IGF-I)concentrations were determined in 30 catch-up growth(CUG)children bern SGA [CUG-SGA,16 females,14males,(6.62±0.66)year],37 non-catch-up growth(NCUG)children born SGA[NCUG-SGA,15 females,22 males,(5.97±0.56)year],and42 appropriate for gestational age(AGA)children with normal height[AGA,16females,26males,(7.05±0.39)year].Results (1) Basal fasting insulin and homeostasis model assessment for insulin resistance(HOMA-IR)were significantly higher in CUG-SGA group than in NCUG-SGA and AGA group(P<0.01 or P<0.05).But there was no difference in fasting insulin between NCUG-SGA group and AGA group.IGF-I levels in CUG-SGA were significantly higher than in NCUG-SGA group[(212.61±17.81 vs 137.40±14.66)ng/ml,P=0.001],but showed no difference from AGA group(P=0.095).(2)In the SGA group,HOMA-IR showed positive correlation with age,△height SDS,and current body mass index.Fasting insulin showed positive correlation with △height SDS(r=0.500,P=0.002)in≤6 year group as well as with △weight SDS(r=0.496,P=0.030)in>6 year group.Conclusions Insulin as a growth factor may participate in postnatal catch-up growth accompanied with increased insulin resistance in SGA children.     

IGFBP-1 levels in adult women born small for gestational age suggest insulin resistance in spite of normal BMI

OBJECTIVE: Impaired fetal development may contribute to decreased insulin sensitivity. This study was designed to characterize serum markers of insulin resistance in adults born small for date or born prematurely. STUDY DESIGN: Fifty subjects, all women, were evaluated at a mean age +/- SD of 26 +/- 2 years (range: 23-30 years). They were allocated to three groups: (i) born fullterm with birth weight <2600 g (n = 18) (small for gestational age, SGA), (ii) born before gestational week 32 (n = 15) (ex-preterm), and (iii) controls, born fullterm with appropriate birth weight (n = 17). Anthropometric data as well as fasting serum samples of plasma B-glucose, serum lipids, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) levels were determined. RESULTS: In the SGA group final height was lower and they weighed less compared with the controls. Fasting insulin and glucose levels did not differ amongst the groups. Triglycerides were lower in the SGA group and in the ex-preterm group compared with the controls (P < 0.05). The SGA group showed lower IGFBP-1 levels compared with the controls median 17 (range 3-121) vs. 26 (7-67) microg L-1; P < 0.05]. The IGF-I levels in the SGA, ex-preterm and control groups were 212 +/- 58, 259 +/- 37 and 216 +/- 32 microg L-1, respectively, corresponding to a mean SD score of -0.8 +/- 1.0, 0.1 +/- 0.6 and -0.6 +/- 0.6. CONCLUSION: As IGFBP-1 is a marker of insulin sensitivity, the low levels observed in adult women with normal BMI, born small for date, suggest relative insulin resistance in spite of normal BMI.     

Influence of catch-up growth on IGFBP-2 levels and association between IGFBP-2 and cardiovascular risk factors in Korean children born SGA

Small for gestational age (SGA) at birth and postnatal growth pattern may have an impact on insulin resistance and body composition in their later life. Emerging evidence has indicated that insulin-like growth factor binding protein-2 (IGFBP-2) may be related to insulin sensitivity. The aim of this study was to evaluate insulin resistance and IGFBP-2 levels in SGA children, and to identify the effect of catch-up growth on IGFBP-2 concentration. Serum IGFBP-2 levels were measured in 103 Korean SGA children including 49 prepubertal and 54 pubertal subjects. Anthropometric values, fasting serum levels of metabolic parameters and insulin sensitivity indices were determined. Each prepubertal or pubertal group was subgrouped based on height or weight catch-up growth. The subgroups with weight catch-up showed higher values of BMI, body fat mass, percent body fat, and total cholesterol. Particularly in pubertal children, IGFBP-2 concentration was lower in the subgroup with weight catch-up. Catch-up growth in height did not affect insulin resistance and metabolic parameters. IGFBP-2 levels were inversely correlated with BMI, body fat mass, percent body fat, insulin and leptin levels in both prepubertal and pubertal groups. Additionally in the pubertal group, systolic blood pressure, cholesterol levels were related to IGFBP-2. A strong relationship between IGFBP-2, the insulin sensitivity index, and some cardiovascular risk factors was observed in children born SGA, suggesting that IGFBP-2 might be a promising marker for early recognition of insulin resistance, particularly in children with weight catch-up.     

Relationship of intracellular magnesium of cord blood platelets to birth weight

Magnesium (Mg(2+)) has an important role in insulin action, and insulin stimulates Mg(2+) uptake in insulin-sensitive tissues. Impaired biologic responses to insulin are referred to as insulin resistance. Diabetic patients and obese subjects are reported to have intracellular magnesium ([Mg(2+)](i)) deficiency. Many epidemiologic studies have disclosed that restricted fetal growth has been associated with increased risk of insulin resistance in adult life. We studied the relationship of [Mg(2+)](i) in cord blood platelets to birth weight. The subjects were 19 infants who were small for gestational age (SGA) and 45 who were appropriate for gestational age (AGA). By using a fluorescent probe, mag-fura-2, we examined the basal and insulin-stimulated [Mg(2+)](i) of platelets in the cord blood. Cord plasma insulin-like growth factor-1 (IGF-1)and leptin levels were determined with the use of enzyme-linked immunosorbent assay (ELISA). Birth weight was correlated with cord plasma IGF-1 (P < .001) and leptin (P < .005). Mean basal [Mg(2+)](i), but not plasma Mg(2+), was lower in the SGA than in the AGA group (291 +/- 149 micromol/L v 468 +/- 132 micromol/L, P < .001). The basal [Mg(2+)](i) was significantly correlated with the birth weight (P < .001) as well as birth length (P < .001). At 60 seconds after stimulation with insulin, there was no significant difference in stimulated [Mg(2+)](i) between the SGA and AGA groups. Although the SGA group had low [Mg(2+)](i), the platelets had good potentiality to compensate for low [Mg(2+)](i). [Mg(2+)](i) reflects the extent of fetal growth. Decreased [Mg(2+)](i) in SGA might underlie the initial pathophysiologic events leading to insulin resistance.