Insulin-Like Growth Factor Binding Protein 3

胰岛素样生长因子结合蛋白 3
  • 文章类型: Journal Article
    背景:关于老年人高血压相关参数与身体机能之间的关系的结果是相互矛盾的。这些不同结果的可能解释是,研究可能没有根据血管紧张素转换酶抑制剂(ACEI)的使用调整其分析。
    目的:为了检查高血压相关参数之间的关联,ACEI使用,和一组非常老的成年人的身体表现测试。
    方法:来自ilSIRNTE数据库的横断面研究。
    方法:Sirente地理区域的山区社区(L\'Aquila,阿布鲁佐,意大利)。
    方法:1924年1月1日之前出生在Sirente地区(13个城市)并在研究时居住在该地区的所有人员都被确定并邀请参加。最终样本包括364名老年人(平均年龄:85.8±标准偏差[SD]4.8)。
    方法:使用等距握力(IHG)评估物理性能,正常和快速的步行速度(WS),5次静坐试验(5STS),和肌肉力量措施。在休息20至40分钟后测量血压(BP),参与者以直立的姿势坐着。根据解剖治疗和化学代码对药物进行编码。ACEI分为中枢(ACEI-c)和外周(ACEI-p)作用。血液炎症标志物,游离胰岛素样生长因子1(IGF-1),并测定IGF结合蛋白3(IGFBP-3)。
    结果:结果表明5STS检验与舒张压值呈显著负相关。然而,当针对ACEI使用调整结果时,显著性丧失.与非ACEI使用者相比,服用ACEI的参与者更可能具有更大的特定肌肉力量和更高的IGFBP-3血液水平。当参与者根据ACEI亚型进行分类时,与ACEI-c使用者相比,ACEI-p使用者的血液IGF-1水平更高。
    结论:本研究的主要发现表明,使用ACEI可能会影响超龄成年人高血压相关参数与神经肌肉参数之间的关联。这些结果可能与ACEI-p对IGF-1途径的作用有关。
    BACKGROUND: Results regarding the associations between hypertension-related parameters and physical performance in older adults are conflicting. A possible explanation for these divergent results is that investigations may not have adjusted their analyses according to the use of angiotensin-converting enzyme inhibitors (ACEIs).
    OBJECTIVE: To examine the associations between hypertension-related parameters, ACEI use, and a set of physical performance tests in very old adults.
    METHODS: Cross-sectional study from the ilSIRENTE database.
    METHODS: Mountain community of the Sirente geographic area (L\'Aquila, Abruzzo, Italy).
    METHODS: All persons born in the Sirente area (13 municipalities) before 1 January 1924 and living in that region at the time of study were identified and invited to participate. The final sample included 364 older adults (mean age: 85.8 ± standard deviation [SD] 4.8).
    METHODS: Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at normal and fast pace, 5-time sit-to-stand test (5STS), and muscle power measures. Blood pressure (BP) was measured after 20 to 40 min of rest, while participants sat in an upright position. Drugs were coded according to the Anatomical Therapeutic and Chemical codes. ACEIs were categorized in centrally (ACEI-c) and peripherally (ACEI-p) acting. Blood inflammatory markers, free insulin-like growth factor 1 (IGF-1), and IGF-binding protein 3 (IGFBP-3) were assayed.
    RESULTS: Results indicated that 5STS test was significantly and negatively associated with diastolic BP values. However, significance was lost when results were adjusted for ACEI use. Participants on ACEIs were more likely to have greater specific muscle power and higher blood levels of IGFBP-3 than non-ACEI users. When participants were categorized according to ACEI subtypes, those on ACEI-p had higher blood IGF-1 levels compared with ACEI-c users.
    CONCLUSIONS: The main findings of the present study indicate that ACEI use might influence the association between hypertension-related parameters and neuromuscular parameters in very old adults. Such results may possibly be linked to the effects of ACEI-p on the IGF-1 pathway.
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  • 文章类型: Journal Article
    背景:主动监测(AS)越来越多地用于监测风险较低的前列腺癌(PCa)患者。前列腺癌积极生活方式研究(PALS)是一项随机对照试验,旨在确定体重减轻是否可以改善AS患者PCa进展的因果途径上的肥胖生物标志物。
    方法:招募被诊断为PCa并选择AS的超重/肥胖男性(体重指数>25kg/m2)。干预时间为6个月,单独交付,从糖尿病预防计划中调整的结构化饮食和运动计划,从基线开始达到7%的体重减轻目标。对照参与者参加了一次审查美国饮食和身体活动指南的会议。主要结果是从基线到6个月干预结束时的血糖调节变化,用空腹血糖测量,C-肽,胰岛素,胰岛素样生长因子1,胰岛素样生长因子结合蛋白-3,脂联素,和胰岛素抵抗的稳态模型评估。
    结果:在被随机分配的117名男性中,100人完成了审判。干预和控制组的平均体重减轻百分比分别为7.1%和1.8%,分别(调整后的组间平均差,-6.0kg;95%置信区间,-8.0,-4.0)。胰岛素相对于基线的平均百分比变化,C-肽,干预组胰岛素抵抗的稳态模型评估为-23%,-16%,和-25%,分别,与+6.9%相比,+7.5%,和+6.4%,分别,在控制臂中(干预效果的所有p≤0.003)。对于其他生物标志物没有检测到显著的臂之间差异。
    结论:参与基于生活方式的减肥干预的超重/肥胖PCa患者AS患者通过这种可重复的生活方式干预成功实现了减肥目标,并经历了与PCa进展相关的葡萄糖调节生物标志物的改善。
    BACKGROUND: Active surveillance (AS) is increasingly used to monitor patients with lower risk prostate cancer (PCa). The Prostate Cancer Active Lifestyle Study (PALS) was a randomized controlled trial to determine whether weight loss improves obesity biomarkers on the causal pathway to progression in patients with PCa on AS.
    METHODS: Overweight/obese men (body mass index >25 kg/m2) diagnosed with PCa who elected AS were recruited. The intervention was a 6-month, individually delivered, structured diet and exercise program adapted from the Diabetes Prevention Program with a 7% weight loss goal from baseline. Control participants attended one session reviewing the US Dietary and Physical Activity Guidelines. The primary outcome was change in glucose regulation from baseline to the end of the 6-month intervention, which was measured by fasting plasma glucose, C-peptide, insulin, insulin-like growth factor 1, insulin-like growth factor binding protein-3, adiponectin, and homeostatic model assessment for insulin resistance.
    RESULTS: Among 117 men who were randomized, 100 completed the trial. The mean percentage weight loss was 7.1% and 1.8% in the intervention and control arms, respectively (adjusted between-group mean difference, -6.0 kg; 95% confidence interval, -8.0, -4.0). Mean percentage changes from baseline for insulin, C-peptide, and homeostatic model assessment for insulin resistance in the intervention arm were -23%, -16%, and -25%, respectively, compared with +6.9%, +7.5%, and +6.4%, respectively, in the control arm (all p for intervention effects ≤ .003). No significant between-arm differences were detected for the other biomarkers.
    CONCLUSIONS: Overweight/obese men with PCa undergoing AS who participated in a lifestyle-based weight loss intervention successfully met weight loss goals with this reproducible lifestyle intervention and experienced improvements in glucose-regulation biomarkers associated with PCa progression.
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  • 文章类型: Journal Article
    骨质疏松症,一种以骨骼强度降低为特征的普遍骨骼疾病,与IGF系统密切相关,对骨骼代谢至关重要。然而,这种关系的确切性质仍然难以捉摸。在这项研究中,我们采用孟德尔随机化(MR)方法来揭示基因预测的血清IGF系统成员水平与骨质疏松症之间的关联.
    采用双样本MR方法基于两个单独的数据集来研究这些因果关联。在4,301名欧洲血统个体的队列中,使用11,036,163个相关单核苷酸多态性(SNP)对14个IGF系统成员的血清水平进行了预测。骨质疏松症的遗传关联估计来自两个公开的GWAS联盟:来自FinnGen生物库的芬兰联盟,包括212,778名芬兰裔人(3,203例病例和209,575名对照),和英国生物银行的英国财团,包括337159名欧洲血统的人(5266例和331893例对照)。
    根据英国数据集,IGF-1水平与骨质疏松症的风险降低有关,如加权中位数法所示(比值比[OR]=0.998,95%CI=0.997-1.000,P=0.032).此外,使用逆方差加权(IVW)方法(OR=0.999,95%CI=0.998-1.000,P=0.019),较高的IGFBP-3水平与骨质疏松症风险降低有关。CTGF水平与骨质疏松症呈负相关,通过加权中位数法确定(OR=0.998,95%CI=0.996-0.999,P=0.004)。在FinnGen数据集中,未发现IGF-1和IGFBP-3与骨质疏松症相关。同时,IGF-LR1水平与骨质疏松呈负相关,根据MR-Egger法(OR=0.886,95%CI=0.795-0.987,P=0.036),根据加权中位数和IVW方法,CYR61与骨质疏松风险增加相关(OR=1.154,95%CI=1.009-1.319,P=0.037,OR=1.115,95%CI=1.022-1.215,P=0.014).
    这项研究提供了令人信服的证据,表明某些IGF家族成员在不同数据集之间的骨质疏松症发病机制中发挥作用。表明IGF家族与骨质疏松症之间的人群特异性因果效应。尽管来自两个数据集的结果表明IGF家族参与骨质疏松症的发病机理,但是响应的关键分子可能在不同的人群中有所不同。随后的研究有必要评估这些生物标志物作为特定人群中骨质疏松症预防和治疗目标的潜力。
    Osteoporosis, a prevalent skeletal disorder characterized by reduced bone strength, is closely linked to the IGF system, crucial for skeletal metabolism. However, the precise nature of this relationship remains elusive. In this study, we employed Mendelian randomization (MR) to unravel the associations between genetically predicted serum IGF system member levels and osteoporosis.
    A two-sample MR approach was employed to investigate these causal associations based on two individual datasets. Predictions of 14 serum levels of IGF system members were made using 11,036,163 relevant Single Nucleotide Polymorphisms (SNPs) within a cohort of 4,301 individuals of European descent. Genetic association estimates for osteoporosis were derived from two publicly available GWAS consortia: the Finnish consortium from the FinnGen biobank, comprising 212,778 individuals of Finnish descent (3,203 cases and 209,575 controls), and the UK consortium from the UK Biobank, including 337,159 individuals of European descent (5,266 cases and 331,893 controls).
    According to the UK dataset, IGF-1 levels were associated with a reduced risk of osteoporosis, as indicated by the weighted median method (Odds Ratio [OR] = 0.998, 95% CI = 0.997-1.000, P = 0.032). Additionally, higher levels of IGFBP-3 were linked to a decreased risk of osteoporosis using the Inverse-Variance Weighted (IVW) method (OR = 0.999, 95% CI = 0.998-1.000, P = 0.019), and CTGF levels exhibited a negative association with osteoporosis, as determined by the weighted median method (OR = 0.998, 95% CI = 0.996-0.999, P = 0.004). In the FinnGen dataset, IGF-1 and IGFBP-3 were not identified to be associated with osteoporosis. While, IGF-LR1 levels displayed a negative association with osteoporosis, according to the MR-Egger method (OR = 0.886, 95% CI = 0.795-0.987, P = 0.036), while CYR61 was linked to an increased risk of osteoporosis based on both the weighted median and IVW methods (OR = 1.154, 95% CI = 1.009-1.319, P = 0.037, and OR = 1.115, 95% CI = 1.022-1.215, P = 0.014, respectively).
    This study provides compelling evidence that certain IGF family members play a role in the pathogenesis of osteoporosis between different datasets, indicating population specific causal effects between IGF family and osteoporosis. Although the results from both datasets demonstrated that IGF family involved in the pathogenesis of osteoporosis, but the responding key molecules might be various among different population. Subsequent research is warranted to evaluate the potential of these biomarkers as targets for osteoporosis prevention and treatment in specific population.
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  • 文章类型: Journal Article
    背景:重组人生长激素(rhGH)治疗对Prader-Willi综合征(PWS)儿童在改善身材矮小和新陈代谢方面有益,但是早期rhGH治疗对3岁以下PWS儿童的呼吸和睡眠参数的影响仍然难以捉摸。因此,本研究旨在探讨rhGH治疗对PWS幼儿睡眠相关呼吸障碍(SRBDs)的影响。
    方法:在2018年10月至2023年1月期间,共招募了17名年龄匹配的接受rhGH治疗的PWS患者(rhGH组)和17名未接受rhGH治疗的对照个体(非rhGH组)。收集与多导睡眠图(PSG)相关的数据以及胰岛素样生长因子(IGF-1)和胰岛素样生长因子结合蛋白3(IGFBP-3)的血清水平。
    结果:rhGH组的平均年龄为20.76±9.22个月,与非rhGH组(25.23±13.81个月)相当。治疗52周后,两组的人口统计学和人体测量参数相似。对幼儿施用rhGH不会对阻塞性呼吸暂停低通气指数(OAHI)产生不利影响,中枢呼吸暂停指数(CAI),氧饱和度指数(ODI),平均经皮氧饱和度(SpO2),最低SpO2,当SpO2低于90%时的持续时间,或SpO2低于90%的患者比例。此外,IGF-1z评分和IGFBP-3水平的升高并未使SRBD恶化.
    结论:用rhGH治疗52周对患有PWS的幼儿没有显示出对SRBD的有害影响。这进一步阐明了PWS患者早期开始rhGH治疗的重要性。
    Recombinant human growth hormone (rhGH) therapy is beneficial for children with Prader-Willi syndrome (PWS) in improving short stature and metabolism, but the effect of early rhGH treatment on respiratory and sleep parameters for PWS children under three years old remains elusive. Thus, this study aimed to investigate the impact of rhGH treatment on sleep-related breathing disorders (SRBDs) for toddlers with PWS.
    A total of 17 age-matched PWS patients receiving rhGH treatment (rhGH group) and 17 control individuals not receiving rhGH treatment (non-rhGH group) were recruited for this study between October 2018 and January 2023. Data related to polysomnography-polygraphy (PSG) and serum levels of insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) were collected.
    The mean age in the rhGH group was 20.76 ± 9.22 months, which was comparable to that of the non-rhGH group (25.23 ± 13.81 months). The demographic and anthropometric parameters were similar across the two groups after 52 weeks of treatment. Administration of rhGH to toddlers did not exert adverse effects on the obstructive apnea-hypopnea index (OAHI), central apnea index (CAI), oxygen desaturation index (ODI), mean percutaneous oxygen saturation (SpO2), lowest SpO2, duration when SpO2 is lower than 90%, or proportion of the patients with SpO2 lower than 90%. Furthermore, the increased IGF-1 z-score and IGFBP-3 level did not worsen SRBDs.
    Treatment with rhGH for 52 weeks on young toddlers with PWS showed no deleterious effects on SRBDs. This shed more light on the importance of initiating rhGH therapy early in PWS patients.
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  • 文章类型: Journal Article
    重组人生长激素(rhGH)是一种经批准的改善身材矮小儿童生长和改善行为问题的方法。然而,关于rhGH治疗对自发性脑活动的影响的数据仍不清楚.这项研究包括35名身材矮小的儿童,分为两组:治疗组(n=14)和未治疗组(n=21)。所有参与者在基线和一年随访结束时都接受了静息状态功能磁共振成像(rs-fMRI)和神经心理学评估。采用基于rs-fMRI的低频波动幅度(ALFF)分析方法评估自发性脑活动。使用混合效应分析检测rhGH和时间对ALFF的相互作用效应。此外,进行Pearson相关性分析以探讨ALFF值与重要临床指标之间的关联。治疗组表现出高度的显著改善,体重,胰岛素样生长因子-1(IGF-1)水平,胰岛素样生长因子结合蛋白3(IGFBP-3)水平,和从基线重新评估时的处理速度指数(PSI)。rhGH×时间的相互作用效应在右壳核(RPUT)中很明显,在rhGH治疗后,ALFF值显示显着增加,同时也显示出与身高的显着正相关。此外,时间的主要作用表现为未治疗组随访期间左额上背外侧回(LSFG)ALFF值明显下降,同时显示与年龄的正相关。总之,rhGH治疗不仅对生长有积极的影响,认知,和矮小儿童的行为,而且还改善和正常化自发的大脑活动。
    Recombinant human growth hormone (rhGH) is an approved method to improve the growth and ameliorate behavioral issues in children with short stature. However, the data concerning the effects of rhGH treatment on spontaneous brain activity remains unclear. This study included 35 children with short stature, categorized into two groups: the treated group (n = 14) and the untreated group (n = 21). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessments at baseline and at the end of a one-year follow-up. The rs-fMRI based amplitude of low frequency fluctuation (ALFF) analysis method was employed to assess spontaneous brain activity. Interaction effects between rhGH and time on ALFF were detected using a mixed-effects analysis. Additionally, Stepwise regression analysis was conducted to investigate the associations between ALFF values and significant clinical indicators. The treated group exhibited significant improvements in height, weight, insulin-like growth factor-1 (IGF-1) levels, insulin-like growth factor binding protein 3 (IGFBP-3) levels, and processing speed index (PSI) when reevaluated from baseline. The interaction effect of rhGH × time was evident in the right putamen (RPUT), where the ALFF value showed a significant increase following rhGH treatment, while also demonstrating a notable positive correlation with height. Moreover, The main effect of time was manifested as a significant decrease in the ALFF value of the left dorsolateral superior frontal gyrus (LSFG) within the untreated group during the follow-up period, concurrently displaying a positive correlation with age. In conclusion, rhGH treatment not only has a positive effect on the growth, cognition, and behavior of children with short stature, but also improves and normalizes spontaneous brain activity.
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  • 文章类型: English Abstract
    OBJECTIVE: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions.
    METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups.
    RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05).
    CONCLUSIONS: In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.
    目的: 探讨重组人生长激素(recombinant human growth hormone,rhGH)对不同垂体发育状况生长激素缺乏症(growth hormone deficiency,GHD)患儿的治疗效果。方法: 前瞻性选取2020年6月—2021年12月许昌市妇幼保健院收治的90例GHD患儿为研究对象,根据垂体正中矢状高径将患儿分为垂体发育不良组(45例)、垂体正常组(31例)、垂体发育增大组(14例)。分析比较各组身高、生长速率、身高标准差分值、血清胰岛素样生长因子结合蛋白-3、胰岛素样生长因子-1,以及治疗前后上述指标变化的差值(差值用△表示)。结果: 治疗后3组身高、生长速率、身高标准差分值及血清胰岛素样生长因子结合蛋白-3、胰岛素样生长因子-1水平均高于治疗前(P<0.05);垂体发育不良组、垂体发育增大组△身高、△生长速率、△身高标准差分值、△胰岛素样生长因子-1、△胰岛素样生长因子结合蛋白-3均大于垂体正常组(P<0.05);3组不良反应发生率比较差异无统计学意义(P>0.05)。结论: rhGH治疗不同垂体发育的GHD患儿均有促进骨生长、增加身高的作用,对垂体发育不良及增生患儿效果更明显,且安全性可靠。.
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  • 文章类型: Observational Study
    目的:本研究旨在探讨不同剂量重组人生长激素(rhGH)治疗儿童生长激素缺乏症(GHD)的疗效。
    方法:对我院2019年6月至2022年1月收治的174例GHD患者的病历进行回顾性分析。共有136名患者符合纳入标准,其中70例接受0.1U/(kg·d)(低剂量组),66例接受0.2U/(kg·d)剂量的rhGH治疗(高剂量组).生长发育状况[身高,体重,身高标准偏差(HtSDS),增长率],骨龄,骨密度,声速(SOS)作为桡骨远端骨量,生长和发育的生化指标[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)],比较两组患者治疗前后生长激素(GH)水平及不良反应发生率。
    结果:治疗后,高度,体重,HTSDS,与治疗前相比,两组的生长速度均增加,高剂量组明显高于低剂量组(p<0.05)。经过一年的治疗,进行了以下观察:与基线值相比,两组的骨龄增加,高剂量组的骨龄高于低剂量组(p<0.05).两组SOS均降低,但高剂量组明显高于低剂量组(p<0.05)。与基线值相比,两组血清IGF-1、IGFBP-3和GH水平均升高,高剂量组高于低剂量组(p<0.05)。高剂量组(8.6%)与低剂量组(6.1%)不良反应发生率差异无统计学意义(p>0.05)。
    结论:大剂量rhGH治疗GHD是安全的,可以更有效地上调IGF-1、IGFBP-3和GH,促进儿童的生长发育。
    The aim of this study was to explore the effects of different doses of recombinant human growth hormone (rhGH) treatment on children with growth hormone deficiency (GHD).
    Medical records of 174 GHD patients admitted to our hospital from June 2019 to January 2022 were retrospectively evaluated. A total of 136 patients met the inclusion criteria, of which 70 received 0.1 U/ (kg·d) (low-dose group) and 66 received 0.2 U/ (kg·d) dose of rhGH treatment (high-dose group). Growth and development status [height, weight, height standard deviation (HtSDS), growth rate], bone age, bone density, speed of sound (SOS) as distal radius bone mass, biochemical indicators of growth and development [insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3)], growth hormone (GH) levels and incidence of adverse reactions were collected and compared between the two groups before and after one year of the treatment.
    After the treatment, height, weight, HtSDS, and growth rate of the two groups increased compared to before the treatment and were significantly higher in the high-dose group than in the low-dose group (p<0.05). After one year of treatment, the following observations were made: the bone age of the two groups increased compared to the baseline values and was higher in the high-dose group compared to the low-dose group (p<0.05). The SOS of the two groups decreased but was significantly higher in the high-dose group compared to the low-dose group (p<0.05). Serum levels of IGF-1, IGFBP-3, and GH in both groups increased compared to the baseline values and were higher in the high-dose group than in the low-dose group (p<0.05). There was no significant difference in the incidence of adverse reactions between the high-dose group (8.6%) and the low-dose group (6.1%) (p>0.05).
    High-dose rhGH treatment for GHD is safe and can more effectively upregulate IGF-1, IGFBP-3, and GH, and promote the growth and development of children.
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  • 文章类型: Randomized Controlled Trial
    背景:胰岛素样生长因子(IGF)在调节细胞增殖中起着至关重要的作用,凋亡,和关键的代谢途径。IGF-1与IGF结合蛋白-3(IGFBP-3)的比例是决定IGF-1生物活性的重要因素。我们试图调查IGF-1和IGFBP-3与2型糖尿病患者心肾结局的关系。
    方法:从2627名2型糖尿病和慢性肾脏疾病患者中获得样本,这些患者被随机分配接受canagliflozin或安慰剂,并对偶发的心肾事件进行随访。主要结局定义为终末期肾脏疾病的复合,血清肌酐水平加倍,或肾/心血管死亡。在基线测量IGF-1和IGFBP-3,1年和3年。升高的IGF-1水平根据年龄特异性截止值定义。Cox比例风险回归用于研究IGF-1水平之间的关联,IGFBP-3和IGF-1/IGFBP-3的比值与临床结果。
    结果:IGF-1升高与基线时肾小球滤过率降低相关。canagliflozin治疗3年后未显著改变IGF-1和IGFBP-3浓度(p值>0.05)。在多变量模型中,升高的IGF-1(高于与低于特定年龄的临界值)与主要复合结局相关(发生率:17.8%与12.7%,风险比[HR]:1.52;95%置信区间1.09-2.13;P:0.01),肾脏综合结局(HR:1.65;95%CI1.14-2.41;P:0.01),和全因死亡率(HR:1.52;95%CI1.00-2.32;P;0.05)。IGFBP-3的对数升高与任何临床结果无关。IGF-1/IGFBP-3对数比值的增加也与主要复合结局的较高风险相关(每单位增加的HR:1.57;95%CI1.09-2.26;P;0.01)。
    结论:这些结果进一步表明IGF生物学在2型糖尿病心肾结局风险中的潜在重要性。SGLT2抑制对IGF的生物学没有影响,尽管它对结果有显著影响。
    背景:CREDENCE;ClinicalTrials.gov标识符:NCT02065791。
    The insulin-like growth factors (IGF) play a crucial role in regulating cellular proliferation, apoptosis, and key metabolic pathways. The ratio of IGF-1 to IGF binding protein-3 (IGFBP-3) is an important factor in determining IGF-1 bioactivity. We sought to investigate the association of IGF-1 and IGFBP-3 with cardio-renal outcomes among persons with type 2 diabetes.
    Samples were available from 2627 individuals with type 2 diabetes and chronic kidney disease that were randomized to receive canagliflozin or placebo and were followed up for incident cardio-renal events. Primary outcome was defined as a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal/cardiovascular death. IGF-1 and IGFBP-3 were measured at baseline, Year-1 and Year-3. Elevated IGF-1 level was defined according to age-specific cutoffs. Cox proportional hazard regression was used to investigate the association between IGF-1 level, IGFBP-3, and the ratio of IGF-1/IGFBP-3 with clinical outcomes.
    Elevated IGF-1 was associated with lower glomerular filtration rate at baseline. Treatment with canagliflozin did not significantly change IGF-1 and IGFBP-3 concentrations by 3 years (p-value > 0.05). In multivariable models, elevated IGF-1 (above vs below age-specific cutoffs) was associated with the primary composite outcome (incidence rate:17.8% vs. 12.7% with a hazard ratio [HR]: 1.52; 95% confidence interval CI 1.09-2.13;P: 0.01), renal composite outcome (HR: 1.65; 95% CI 1.14-2.41; P: 0.01), and all-cause mortality (HR: 1.52; 95% CI 1.00-2.32; P; 0.05). Elevations in log IGFBP-3 did not associate with any clinical outcomes. Increase in log IGF-1/IGFBP-3 ratio was also associated with a higher risk of the primary composite outcome (HR per unit increase: 1.57; 95% CI 1.09-2.26; P; 0.01).
    These results further suggest potential importance of IGF biology in the risk for cardio-renal outcomes in type 2 diabetes. SGLT2 inhibition has no impact on the biology of IGF despite its significant influence on outcomes.
    CREDENCE; ClinicalTrials.gov Identifier: NCT02065791.
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  • 文章类型: Randomized Controlled Trial
    目的:评估(a)每日预防性锌片(7mg;PZ)的影响,含锌的多种微量营养素粉末(10毫克锌,和13种其他微量营养素;MNP)或安慰剂,交付了9个月,对6-23个月老挝儿童胰岛素样生长因子1(IGF1)和IGF结合蛋白3(IGFBP3)的影响,(b)基线IGF1和IGFBP3是否改变了PZ和MNP对年龄长度z评分(LAZ)和年龄体重z评分(WAZ)的影响。
    方法:双盲,安慰剂对照试验(N=419)。
    方法:通过自动化学发光测定法分析基线和36周时的血浆IGF1和IGFBP3浓度。在基线时评估人体测量学,在18周和36周。使用ANCOVA估计干预效果。
    结果:在36周时,几何平均值IGF1(约39.0-39.2ng/mL;p=0.99)和IGFBP3(2038-2076ng/mL;p=0.83)在各组之间没有差异.在18周(但不是在36周),在最高基线IGF1三元组(相互作用的p=0.006)的儿童中,PZ组(-1.45)的LAZ高于MNP(-1.70)和对照组(-1.55)(p=0.01)。在36周(但不是在18周),PZ组的WAZ(-1.55)显著高于MNP组(-1.75)和对照组(-1.65)(p=0.03),在基线IGFBP3最低的儿童中(相互作用的p=0.06)。
    结论:虽然IGF1和IGFBP3对PZ和MNP没有反应,基线IGF1和IGFBP3显着改变了PZ对线性和成体生长的影响,提示IGF1的生物利用度可能推动补锌儿童的追赶生长.
    OBJECTIVE: To assess (a) the impact of daily preventive zinc tablets (7 mg; PZ), zinc-containing multiple micronutrient powder (10 mg zinc, and 13 other micronutrients; MNP) or placebo, delivered for 9 months, on Insulin-like Growth Factor 1 (IGF1) and IGF Binding Protein 3 (IGFBP3) among Laotian children 6-23 months, and (b) whether the effects of PZ and MNP on length-for-age z-scores (LAZ) and weight-for-age z-scores (WAZ) are modified by baseline IGF1 and IGFBP3.
    METHODS: A double-blind, placebo-controlled trial (N = 419).
    METHODS: Plasma IGF1 and IGFBP3 concentrations at baseline and 36 weeks were analyzed by automated chemiluminescent assay. Anthropometry was assessed at baseline, at 18 and 36 weeks. Intervention effects were estimated using ANCOVA.
    RESULTS: At 36 weeks, geometric mean IGF1 (~39.0-39.2 ng/mL; p = 0.99) and IGFBP3 (2038-2076 ng/mL; p = 0.83) did not differ by group. At 18 weeks (but not at 36 weeks), LAZ in the PZ group (-1.45) was higher than the MNP (-1.70) and control (-1.55) groups (p = 0.01) among children in the highest baseline IGF1 tertile (p for interaction = 0.006). At 36 weeks (but not at 18 weeks), WAZ in the PZ group (-1.55) was significantly higher than the MNP (-1.75) and control (-1.65) groups (p = 0.03), among children in the lowest baseline IGFBP3 tertile (p for interactions = 0.06).
    CONCLUSIONS: Although IGF1 and IGFBP3 did not respond to PZ and MNP, baseline IGF1 and IGFBP3 significantly modified the impact of PZ on linear and ponderal growth, suggesting that IGF1 bioavailability may drive catch-up growth in zinc-supplemented children.
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  • 文章类型: Journal Article
    探讨循环IGFBP-3,IL-6和骨密度之间的关系以及循环IGFBP-3和IL-6在绝经后妇女骨质疏松症中的潜在诊断作用。
    苏州大学附属第一医院85名绝经后妇女,骨质疏松症和更年期诊所,被招募。85名妇女中有45名被诊断患有骨质疏松症。循环IL-6,PTH,1,25(OH)2D3,骨钙蛋白(OST),在40名普通女性和45名骨质疏松女性中测量了IGF-1,IGFBP-3和腰椎(LS)和股骨颈(FN)的骨密度(BMD)。一个简单的回归分析计算了年龄之间的相关性,BMD,IL-6和IGFBP-3。进行多重逐步回归分析以确定哪些变量与BMD独立相关。使用受试者工作特征曲线下面积(ROC,AUC)。
    年龄,更年期多年来,和循环IL-6,PTH,与正常组相比,骨质疏松组的IGFBP-3明显升高。骨质疏松女性的LS和FN的BMD明显低于正常女性。发现IGFBP-3和IL-6与年龄相关的增加,而LS/FNBMD与年龄相关的减少。IGFBP-3和IL-6与LS和FNBMD均呈负相关。逐步回归分析显示IGFBP-3和IL-6是绝经后妇女骨密度的强预测因子。AUC临界值(IGFBP-3:3.65,IL-6:0.205)是诊断绝经后妇女骨质疏松症的最佳评估,循环IGFBP-3和IL-6的AUC分别为0.706(95%CI0.594-0.818)和0.685(95%CI0.571-0.798),分别。
    在这项对绝经后妇女的横断面研究中,IGFBP-3和IL-6与BMD呈负相干。循环IGFBP-3和IL-6可能是绝经后骨质疏松的重要预测因子,有助于预测骨质疏松性骨折。
    UNASSIGNED: To explore the relationship between circulating IGFBP-3, IL-6, and bone mineral density and the potential diagnostic role of circulating IGFBP-3 and IL-6 in postmenopausal women with osteoporosis.
    UNASSIGNED: Eighty-five postmenopausal women at Soochow University\'s First Affiliated Hospital, Osteoporosis and Menopause Clinics, were recruited. Forty-five of 85 women were diagnosed with osteoporosis. Circulating IL-6, PTH, 1,25(OH)2D3, osteocalcin (OST), IGF-1, IGFBP-3, and bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) were measured in 40 ordinary and 45 osteoporotic women. A simple regression analysis calculated the correlation between age, BMD, IL-6, and IGFBP-3. Multiple stepwise regression analyses were conducted to determine which variables were independently related to BMD. The potential role of IGFBP-3 and IL-6 in the diagnosis of postmenopausal osteoporosis was predicted using the area under the receiver operating characteristic curve (ROC, AUC).
    UNASSIGNED: Age, years since menopause, and circulating IL-6, PTH, and IGFBP-3 were significantly higher in the osteoporosis group compared to the normal group. Osteoporotic women had substantially lower BMDs of the LS and FN than normal women. Age-related increases were found for IGFBP-3 and IL-6, whereas age-related decreases were observed for LS/FN BMD. IGFBP-3 and IL-6 were both negatively correlated with LS and FN BMD. Stepwise multiple regression analysis showed that IGFBP-3 and IL-6 were strong predictors of BMD in postmenopausal women. AUC cut-off values (IGFBP-3: 3.65, IL-6: 0.205) were best evaluated for the diagnosis of postmenopausal women with osteoporosis, and the AUC for circulating IGFBP-3 and IL-6 were 0.706 (95% CI 0.594-0.818) and 0.685 (95% CI 0.571-0.798), respectively.
    UNASSIGNED: In this cross-sectional study of postmenopausal women, IGFBP-3 and IL-6 were negatively related to BMD. Circulating IGFBP-3 and IL-6 might be essential predictors of postmenopausal osteoporosis and can help predict osteoporotic fracture.
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