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.     

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

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.     

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。     

妊娠高血压综合征与小于胎龄儿的相关性研究

该文探讨妊娠高血压综合征(PIH)与小于胎龄儿(SGA)之间的关系。方法:研究对象为浙江省和江苏省4个县(市)1995—2000年期间单胎分娩且孕周在28～42周的93 743名妇女。首先计算并比较 PIH 组     

追赶生长胰岛素抵抗形成机制的新认识

追赶生长是机体一过性生长抑制后出现的快速生长现象,现已证实追赶生长与胰岛素抵抗存在高度相关性,但其形成的具体机制尚不明确.     

妊娠高血压综合征与小于胎龄儿的相关性研究

该文探讨妊娠高血压综合征（PIH）与小于胎龄儿（SGA）之间的关系。方法：研究对象为浙江省和江苏省4个县（市）1995—2000年期间单胎分娩且孕周在28-42周的93743名妇女。首先计算并比较PIH组（包括不同程度PIH组）与非PIH组孕妇的SGA发生率；采用logistic回归控制孕妇年龄、产次、职业、文化程度、体质量指数、孕期贫血严重程度、胎膜早破和新生儿性别等可能的混杂因素后，估计PIH与SGA的关联程度；并按照早产和足月分娩进行分层分析。     

成年期追赶生长对大鼠胰岛素敏感性与应激水平的影响

目的 观察成年期追赶生长对大鼠胰岛素敏感性和应激水平的影响,并探讨其胰岛素抵抗形成的可能机制。方法 将7周龄雄性SD大鼠分为6组（共2个时间点）,即4周时间点2组：热卡限制4周组(R4),正常饮食4周组(NC4)作为R4组对照;8周时间点4组：正常饮食追赶生长组(RN4)、高脂饮食追赶生长组(RH4)、持续高脂饮食8周组（HF8）、持续正常饮食8周组(NC8)。通过先热卡限制后恢复饮食的方法建立追赶生长大鼠模型。检测大鼠高胰岛素-正糖钳夹试验过程中葡萄糖输注率和骨骼肌2-脱氧葡萄糖摄取、胰岛素刺激后的骨骼肌胰岛素信号通路、血皮质酮、骨骼肌11β-羟类固醇脱氢酶1(11β-HSD1)表达水平。结果 热卡限制4周时,R4组大鼠血皮质酮和骨骼肌11β-HSD1 mRNA表达水平明显高于NC4组(P＜0.05),骨骼肌蛋白激酶B( Akt) Ser473磷酸化和糖摄取与NC4组相比差异无统计学意义。热卡限制后恢复饮食4周时,血皮质酮和骨骼肌11β-HSD1表达水平RN4组明显高于NC8组,RH4组明显高于NC8和HF8组,而骨骼肌Akt磷酸化和糖摄取RN4组明显低于NC8组,RH4组明显低于NC8组、HF8组和RN4组（均P＜0.05）。结论正常饮食和高脂饮食追赶生长大鼠均可导致整体和骨骼肌应激水平上调及胰岛素抵抗,尤以高脂饮食追赶生长大鼠更为明显。应激和饮食状况的交互作用可能是追赶生长胰岛素抵抗形成的重要原因。     

追赶生长:胰岛素抵抗研究的新领域

2型糖尿病等胰岛素抵抗相关疾病在亚洲国家呈急速蔓延之势,这很有可能与营养水平的快速提升所带来的追赶生长现象有关.从追赶生长现象入手,研究其胰岛素抵抗发生机制,将有助于深入理解亚洲2型糖尿病的发病特点,从中寻找有效预防手段,以期在一定程度上阻遏亚洲糖尿病流行趋势.     

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     

Pathophysiology of insulin resistance in subjects born small for gestational age

Over the last 15 years, a number of long-term health risks associated with reduced fetal growth have been identified, including cardiovascular diseases, hypertension, dyslipidaemia and type 2 diabetes. A common feature of these conditions is insulin resistance, which is thought to play a pathogenic role. However, despite abundant data in the literature, it is still difficult to trace the pathway by which fetal events, environmental or not, may lead to increased morbidity later in life. To explain this association, several hypotheses have been proposed pointing to the role of a detrimental fetal environment, a genetic susceptibility or an interaction between the two, and of the particular dynamic changes in adiposity that occur during catch-up growth. The relative impact of early postnatal events in relation to fetal growth has to be considered for designing health policy strategies for early interventions aimed at decreasing disease risk throughout life.     

The benefits of growth hormone therapy in patients with Turner syndrome, Noonan syndrome and children born small for gestational age

This review will summarize the effects of growth hormone (GH) on height, body composition, bone and psychosocial parameters in children with Turner syndrome or Noonan syndrome and those born small for gestational age. The safety of GH treatment in children with these diagnoses is also reported. Despite the reported efficacy and safety of GH in these indications, however, not all children achieve their target height potential, due in some part to poor adherence to GH therapy regimens; indeed up to 50% of children are less than fully compliant with treatment. With this in mind the present and future administration of GH therapy is discussed with respect to advances being made in the presentation of GH for injection and advances in GH injection devices. It is hoped that such progress, aimed at making the administration of GH easier and less painful for the patient will improve treatment adherence and outcome benefits.     

Impact of being born small for gestational age on onset and progression of puberty

Children born small for gestational age (SGA) are at higher risk for perinatal morbidity, mortality and chronic diseases in later life. There is increasing evidence for a link between prenatal growth and pubertal development, but studies concerning the timing, duration and progression of puberty in these children are scarce and the results are difficult to compare due to the various methodologies employed. Most boys born SGA have normal pubertal timing, but often attain an adult height below the target height. In girls, most studies document a relationship between intra-uterine growth retardation and earlier pubertal development or normal timing but with rapid progression. This chapter will discuss the factors that could influence pubertal development in children born SGA and the information reported to date.     

Efficacy and safety of the recombinant human growth hormone in short children born small for gestational age: A randomized,multicentre, comparative phase III trial

Objective:Growth hormone (GH) treatment is known to be effective in increasing stature in children with a short stature born small for gestational age (SGA). This multicentre, randomized, open-label, comparative, phase III study aimed to evaluate the efficacy and safety of Growtropin-II (recombinant human GH) and to demonstrate that the growth-promoting effect of Growtropin-II is not inferior to that of Genotropin in children with SGA (NCT ID: {"type":"clinical-trial","attrs":{"text":"NCT02770157","term_id":"NCT02770157"}}NCT02770157).Methods:Seventy five children who met the inclusion criteria were randomized into 3 groups in a ratio of 2:2:1 (the study group [Growtropin-II, n = 30], control group [Genotropin, n = 30], and 26-week non-treatment group [n = 15]). The study and control groups received subcutaneous injections of Growtropin-II and Genotropin, respectively for 52 weeks, whereas the non-treatment group underwent a non-treatment observation period during weeks 0 to 26 and a dosing period during weeks 27 to 52 and additional dosing till week 78 only in re-consenting children.Results:No significant differences in demographic and baseline characteristics between the groups were observed. The mean ± standard deviation change difference in annualized height velocity (aHV) (study group - control group) was 0.65 ±2.12 cm/year (95% confidence interval [CI], −0.53 to 1.83), whereas the lower limit for the 2-sided 95% CI was −0.53 cm/year. Regarding safety, treatment-emergent adverse events (TEAEs) occurred in 53.33% children in the study group and 43.33% children in the control group; the difference in the incidence of TEAEs between the 2 treatment groups was not statistically significant (P = .4383). A total of 17 serious adverse events (SAEs) occurred in 13.33% children in the treatment groups, and no significant difference in incidence between groups (P = .7065) was seen. Two cases of adverse drug reaction (ADR) occurred in 2 children (3.33%): 1 ADR (injection site swelling or pain) occurred in 1 child (3.33%) each in the study and control groups.Conclusions:This study demonstrates that the change in aHV from the baseline till 52 weeks with Growtropin-II treatment is non-inferior to that with Genotropin treatment in children with short stature born SGA. Growtropin-II is well-tolerated, and its safety profile is comparable with that of Genotropin over a 1-year course of treatment.     

Low serum adiponectin levels in subjects born small for gestational age: impact on insulin sensitivity

OBJECTIVE: Increasing evidence point to the role of the adipose tissue on the insulin resistance associated with reduced fetal growth. Since adiponectin, exclusively produced by the adipose tissue, exerts an important insulin-sensitizing activity, it appears critical to investigate the effect of being born small for gestational age (SGA) on adiponectin production in adulthood and its relationship with insulin sensitivity. SUBJECTS AND METHODS: Serum adiponectin concentrations were measured in 486 young adults born SGA, precisely selected on birth data, who were compared to 573 age-matched subjects born appropriate for gestational age (AGA). The relationship between serum adiponectin levels and insulin-resistance indices measured under OGTT were tested and compared between the two groups. RESULTS: The SGA group demonstrated significantly reduced serum adiponectin levels than controls (12.6 +/- 6.9 vs 13.2 +/- 6.4 microg/ml, P = 0.02) and the difference remained significant when the key regulatory factors were taken into account (P = 0.008). In the AGA group, fasting I/G taken as an insulin-resistance index negatively correlated with serum adiponectin concentrations (P = 0.02), while the relationship followed a U-shape with increased fasting I/G ratio despite high concentrations of serum adiponectin in the SGA group (P = 0.12). CONCLUSION: Subjects born SGA demonstrated significantly reduced serum adiponectin levels, which were not related to insulin-resistance indices in comparison to what observed in age-matched subjects born AGA. Although this defect in adiponectin production and in its insulin-sensitizing action remains to be elucidated at the molecular level, it strengthens the critical contribution of the adipose tissue in the metabolic complications associated with reduced fetal growth.