Effects of alcohol on insulin-like growth factor I and insulin-like growth factor binding protein 3 in postmenopausal women

BACKGROUND: Increased circulating insulin-like growth factor I (IGF-I) concentrations, frequently adjusted for IGF binding protein 3 (IGFBP-3), have been associated with increased risk of several types of cancer, including colon, prostate, and breast. Studies have suggested that alcohol may affect IGF-I or IGFBP-3; however, controlled feeding studies to assess alcohol's effects on IGF-I or IGFBP-3 have not been conducted. OBJECTIVE: To determine whether chronic, moderate alcohol intake affects serum IGF-I or IGFBP-3 concentrations, we performed a controlled, crossover feeding study. DESIGN: Fifty-three postmenopausal women were randomly assigned to consume 0 g (control), 15 g (one drink), or 30 g (2 drinks) alcohol daily for 8 wk and were rotated through the other 2 intake levels in random order. All foods and beverages were provided during the intervention. Individuals were monitored and calories adjusted to maintain constant weight, and serum was collected at the end of each diet period. RESULTS: Compared with the effects of 0 g alcohol/d, IGF-I concentrations were nearly unchanged by 15 g alcohol/d (0.8%; 95% CI: -3.2%, 3.5%) but decreased significantly by 4.9% (95% CI: -8.0%, -1.6%) with 30 g alcohol/d. IGFBP-3 concentrations significantly increased by 3.0% (95% CI: 0.4%, 5.6%) with 15 g alcohol/d but did not increase significantly with 30 g/d (1.8%; 95% CI: -0.9%, 4.5%). CONCLUSIONS: To our knowledge, this is the first published controlled diet study to find that in postmenopausal women, when weight is kept constant, alcohol consumption reduces the amount of serum IGF-I potentially available for receptor binding. These findings suggest that the effect of alcohol intake should be considered in studies of IGF-I, IGFBP-3, and cancer in postmenopausal women.     

Anthropometric and behavioral correlates of insulin-like growth factor I and insulin-like growth factor binding protein 3 in middle-aged Japanese men

High levels of plasma insulin-like growth factor I (IGF-I) and low levels of insulin-like growth factor binding protein 3 (IGFBP-3) have been related to increased risk of several cancers. Little is known about the behavioral determinants of these biologic markers. The authors examined the relation of anthropometric and behavioral factors to plasma concentrations of IGF-I and IGFBP-3 in a cross-sectional study of 616 Japanese men aged 45-55 years in 1995-1996. In univariate analyses, body mass index was strongly, positively associated with both IGF-I and IGFBP-3. The waist/hip ratio was also linearly related to IGF-I and IGFBP-3 up to the third quartile level. Height was weakly, positively associated with IGF-I and IGFBP-3. Smoking was inversely associated with IGF-I and IGFBP-3. Alcohol use was associated inversely with IGF-I and positively with IGFBP-3. Neither IGF-I nor IGFBP-3 was related to physical activity. Results of the multivariate analysis were essentially the same as those of the univariate analyses. The findings regarding body mass index are in contrast to those of previous studies showing null or inverse associations, and they suggest that the relation of body mass index to IGF-I or IGFBP-3 may vary among populations. The study also indicates that smoking and alcohol use might affect plasma IGF-I and IGFBP-3.     

Maternal concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 1 during pregnancy and birth weight of offspring

Maternal concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 1 (IGFBP-1) may influence fetal growth. Offspring birth weight related to maternal IGF-I and IGFBP-1 measured in pregnancy was studied in 368 randomly selected women without preeclampsia who delivered a singleton liveborn child in Norway between 1992 and 1994. Maternal IGF-I concentrations were not consistently associated with birth weight, but a 1-standard deviation stronger increase in IGF-I from the first to second trimester was associated with an 82-g (95% confidence interval (CI): 11, 153) higher birth weight. IGFBP-1 concentrations were inversely associated with birth weight: Birth weight was 71 g (95% CI: 14, 128) lower per 1-standard deviation higher IGFBP-1 in the second trimester, and an increase in IGFBP-1 from the first (below median) to second (above median) trimester was associated with a 342-g (95% CI: 124, 560) lower birth weight, compared with having low IGFBP-1 (below median) in both trimesters. Conversely, low IGFBP-1 in both trimesters was associated with a 200-350-g higher birth weight compared with other combinations of IGFBP-1. In conclusion, persistently low IGFBP-1 in pregnancy is associated with relatively higher birth weight. Maternal insulin resistance may provide a link between IGFBP-1 and offspring birth weight.     

Insulin-like growth factor I,insulin-like growth factor binding protein 3, and urologic measures of benign prostatic hyperplasia

Laboratory studies suggest that insulin-like growth factor I (IGF-I) promotes prostatic growth. The authors evaluated the association between benign prostatic hyperplasia and IGF-I and its binding protein IGFBP-3 in community-dwelling men to determine whether this laboratory finding is manifest at the population level. Participants (n = 471) were Olmsted County, Minnesota, Caucasian males aged 40-79 years in 1990. Urologic measures were assessed from the International Prostate Symptom Score, peak urinary flow rates, prostate volume, and serum prostate-specific antigen (PSA), and serum IGF-I and IGFBP-3 levels were measured. After adjustment for age, the relative odds (odds ratios) of an abnormal urologic measure in men with high versus low serum IGF-I levels were 0.98 (95% confidence interval (CI): 0.66, 1.45) for a symptom score of >7, 1.14 (95% CI: 0.72, 1.80) for a peak urinary flow rate of <12 ml/second, 1.11 (95% CI: 0.72, 1.72) for a prostate volume of >30 ml, and 0.71 (95% CI: 0.46, 1.09) for a PSA level of >1.4 ng/ml. A low IGFBP-3 level was associated with an enlarged prostate (odds ratio = 1.72, 95% CI: 1.05, 2.82), after simultaneous adjustment for IGF-I and age, but not with other urologic measures. These data do not provide evidence for an association between benign prostatic hyperplasia and serum IGF-I.     

Markers of fetal growth and serum levels of insulin-like growth factor (IGF) I, -II and IGF binding protein 3 in adults

Fetal growth has been linked with increased risk of cancer and cardiovascular disease later in life. The insulin-like growth factor (IGF) axis has recently been proposed as a predictor of risk of subsequent cancer and cardiovascular disease. However, only few data are available on the possible association between fetal growth and levels of IGFs later in life. We examined the association between markers of fetal growth, i.e. birth weight, birth length and Ponderal Index, from birth records and serum IGF-I, IGF-II, and IGF binding protein 3 (IGFBP-3) levels in 545 middle-aged Danish men and women. We fitted separate multivariate models including birth weight, birth length, Ponderal Index and serum IGF-I, IGF-II, and IGFBP-3, respectively. After adjustment for age, alcohol intake, smoking, diabetes mellitus, systolic and diastolic blood pressure, serum total cholesterol and current height and weight, we found negative associations between birth weight and Ponderal Index, respectively, and serum IGF-II in men, i.e. the mean regression coefficients were -49.41 (95% CI: -87.06-11.77) (microg/l)/kg and -3.49 (95% CI: -6.73-0.25) (microg/l)/(kg/m3), respectively. Furthermore, in men birth weight was negatively associated with the (IGF-I + IGF-II)/IGFBP-3 and IGF-II/IGFBP-3 ratios, which are believed to be indicators of bioavailable IGF and IGF-II, respectively. However, no other associations were found in any of the models. Between 1 and 16% of the variance in serum IGF-I, IGF-II, and IGFBP-3, respectively, could be explained by the statistical models used in the analyses. We found very little support to the hypothesis of an association between fetal growth and the IGF axis throughout life.     

The potential role of insulin-like growth factor 1, insulin-like growth factor binding protein 3 and bone mineral density in patients with chronic hepatitis C virus in Cairo, Egypt

Insulin-like growth factor 1 (IGF-1) levels have been found to correlate with measurements of bone mineral density (BMD) in liver diseases. This study investigated the relationship between IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3) and BMD in patients with chronic hepatitis C virus. This study was conducted for 30 patients with chronic hepatitis C virus infection (16 patients without and 14 patients with cirrhosis) and 11 healthy controls. Serum levels of IGF-1 and IGFBP-3 and BMD of the proximal femur and lumbar spine were measured in all subjects. Osteoporosis of the proximal femur and lumbar spine was found in 42.9% and 21.4%, respectively, of the patients with cirrhosis. Patients with liver cirrhosis and osteoporosis of the proximal femur and lumbar spine had lower IGF-1 (P < 0.001, P = 0.04, P = 0.04 respectively). BMD of the proximal femur was lower in cirrhotic patients compared with controls (P < 0.01). Patients with liver cirrhosis had lower IGFBP-3 than patients without cirrhosis and controls (P < 0.001). Patients with osteoporosis of the proximal femur had lower IGFBP-3 than those without osteoporosis (P < 0.01). IGF-1 and IGFBP-3 levels were lower in patients with liver cirrhosis. IGF-1 and IGFBP-3 may play a role in hepatic osteoporosis.     

胰岛素样生长因子及其结合蛋白与妊娠期高血压疾病的相关性研究

目的:研究妊娠期高血压疾病患者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-1(IGFBP-1)的水平与病情程度及新生儿出生体重之间的关系。方法:采用放射免疫方法测定并比较38例妊娠期高血压疾病患者与38例正常血压妊娠妇女的血清IGF-1、IGFBP-1的水平。结果:子痫前期组IGF-1显著低于妊娠期高血压组和正常组,而IGFBP-1水平显著高于妊娠期高血压组和正常组;妊娠期高血压组与正常组间IGF-1、IGFBP-1的水平比较,差异均无统计学意义。IGF-1水平与收缩压、舒张压及平均动脉压呈显著负相关,与新生儿出生体重呈显著正相关,而IGFBP-1与收缩压、舒张压及平均动脉压呈显著正相关,与新生儿出生体重呈显著负相关。结论:妊娠期高血压疾病患者的发病及严重程度与IGF-1、IGFBP-1有明显的关系,IGF-1、IGFBP-1与胎儿的发育及新生儿出生体重有明显的相关性。     

先天性甲状腺功能减低患儿胰岛素样生长因子及其结合蛋白的变化

【目的】观察先天性甲状腺功能减低(CH)新生儿及经替代治疗的CH患儿血清中胰岛素样生长因子．1(IGF-1)及胰岛素样生长因子结合蛋白-3(IGFBP-3)的变化。【方法】收集22例CH新生儿、21例替代治疗后的CH患儿静脉血清，采用放射免疫分析法(RIA)测定ICF-1水平，免疫放射分析法(IRMA)测定IGFBP-3水平，并与20例正常新生儿做对照。【结果】与正常新生儿组比较，CH新生儿血清IGF-1和IGFBP-3水平显著降低；替代治疗1～6月后，CH患儿血清IGF-1和IGFBP．3水平较CH新生儿明显升高。各组内IGF-1与IGFBP-3呈正相关，CH新生儿血清IGF-1和IGFBP-3水平与T4、TSH无明显相关性。【结论】CH患儿治疗前血清中IGF-1和IGFBP-3水平明显降低，替代治疗后水平升高。     

Effect of lycopene supplementation on insulin-like growth factor-1 and insulin-like growth factor binding protein-3: a double-blind, placebo-controlled trial

OBJECTIVE: Studies have suggested a link between lycopene and insulin-like growth factor-1 (IGF-1). The aim of this study was to test the effect of lycopene supplementation on IGF-1 and binding protein-3 (IGFBP-3) status in healthy male volunteers. DESIGN, SETTING, SUBJECTS AND INTERVENTION: This was a 4 week randomized, double-blind, placebo-controlled study of lycopene supplementation (15 mg/day) in healthy male volunteers (n=20). Fasting blood samples were collected at baseline and after 4 weeks. Samples were analysed for lycopene by high-performance liquid chromatography (HPLC) and IGF-1 and IGFBP-3 by enzyme-linked immunosorbent assay (ELISA). Changes in end points from baseline were compared in those who received placebo versus those who received the lycopene supplement. RESULTS: Median change in lycopene from baseline (post-supplement - baseline) was higher in subjects in the intervention than those on placebo (lycopene group 0.29 (0.09, 0.46); placebo group 0.03 (-0.11, 0.08) micromol/l; median (25th, 75th percentiles), P<0.01). There was no difference in median change in IGF-1 concentrations (lycopene group -0.6 (-2.6, 1.9); placebo group -1.15 (-2.88, 0.95) nmol/l, P=0.52), or median change in IGFBP-3 concentrations (lycopene group 245 (-109, 484); placebo group 101 (-34, 234) nmol/l, P=0.55) between intervention and control groups. Change in lycopene concentration was associated with the change in IGFBP-3 in the intervention group (r=0.78; P=0.008; n=10). CONCLUSIONS: Lycopene supplementation in healthy male subjects has no effect on IGF-1 or IGFBP-3 concentrations in a healthy male population. However, the association between change in lycopene concentration and change in IGFBP-3 in the intervention group suggests a potential effect of lycopene supplementation on IGFBP-3.     

Insulin-like growth factor 1, insulin-like growth factor-binding protein 3, and testicular germ-cell tumor risk

Studies have consistently shown that taller men are at increased risk of testicular germ-cell tumors. Thus, it is plausible that factors associated with height may also influence risk of these tumors. The authors examined associations between testicular germ-cell tumor risk and circulating concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) among 517 cases and 790 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study (2002-2005). Odds ratios and 95% confidence intervals were estimated using logistic regression models, adjusting for age, race/ethnicity, height, and body mass index. All tests of significance were two-sided. Overall, there were no associations between IGF-1 or IGFBP-3 concentrations and risk of testicular germ-cell tumors (p > 0.05). However, when cases were separated by histologic type, there was a suggestion of a reduction in seminoma risk associated with the highest concentrations of IGF-1 as compared with the lowest concentrations (odds ratio = 0.66, 95% confidence interval: 0.40, 1.09). Although there were no overall associations with insulin-like growth factor, contrary to expectation, there was a suggestion that IGF-1 concentrations may be inversely associated with risk of seminoma.     

血清IGF-1、IGFBP-3水平和大肠癌关系的Meta分析

目的综合评价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)水平和大肠癌的关系。方法利用Meta分析法对6篇关于血清IGF-1、IGFBP-3水平与大肠癌关系的研究文献进行定量综合分析。结果对于IGF-1，合并OR=1．56(95％CI：1．14～2．13)；按实验方法不同分层，间接酶联免疫吸附试验(ELISA)合并OR=1．92(95％CI：1．26～2．93)，IRMA法合并OR=1．23(95％CI：0．78～1．94)；对于IGFBP-3，合并OR=0．78(95％CJ：0．43～1．44)；按实验方法不同分层，ELISA法合并OR=0．46(95％CI：0．29～0．74)，免疫放射测定法(IRMA)合并OR=1．44(95％CI：0．93～2．23)。结论血清IGF-1高水平为大肠癌的独立危险因子，IGFBP-3与大肠癌的关联不具有统计学意义；IGFBP-3与大肠癌关系的各研究之间异质性是由实验方法不同而引起，但该结论尚需大样本并同时进行两种方法的测量证实。     

学龄前肥胖儿童血清IGF-I、IGF-BP3与其他激素相互关系的研究

[目的]研究学龄前肥胖儿童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(IGF-BP3)与瘦素(Leptin)、胰岛素(Ins)、雌二醇(E2)及睾酮(T)的相互关系,探讨IGF-I在肥胖发病机制中的作用,为肥胖儿童的早期干预提供理论依据.[方法]对122例学龄前肥胖儿童及61例正常儿童血清IGF-I、IGF-BP3、LEI、in、Ins、E2和T水平进行测定,并分析IGF-I、IGF-BP3与其他激素的相互关系.[结果]学龄前肥胖儿童血清IGF-I、IGF-BP3、Lepfin、Ins和E2水平明显高于对照组(P值均＜O.001),两组间睾酮水平差异无显著性(P>O.05);血清IGF-I、IGF-BP3与Leptin、Ins、E2及睾酮水平显著正相关(P值均＜0.01),且Leptin与Ins、E2水平显著正相关(P值均＜0.001);多元线性回归分析显示IGF-BP3、Ins和E2是影响IGF-I的重要因素.[结论]学龄前肥胖儿童IGF-I、Leptin和Ins在调节机体能量代谢过程中不仅作为独立的外周因子发挥作用,同时提示IGF-I对儿童生长发育以及性发育的调控受Leptin、Ins及性激素多种激素水平的共同影响,IGF-I是儿童肥胖又一敏感检测指标.     

学龄前肥胖儿童血清IGF-Ⅰ、IGF-BP_3与其他激素相互关系的研究

【目的】研究学龄前肥胖儿童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（IGF-BP3）与瘦素（Leptin）、胰岛素（Ins）、雌二醇（E2）及睾酮（T）的相互关系,探讨IGF-I在肥胖发病机制中的作用,为肥胖儿童的早期干预提供理论依据。【方法】对122例学龄前肥胖儿童及61例正常儿童血清IGF-Ⅰ、IGF-BP3、Leptin、Ins、E2和T水平进行测定,并分析IGF-Ⅰ、IGF-BP3与其他激素的相互关系。【结果】学龄前肥胖儿童血清IGF-Ⅰ、IGF-BP3、Leptin、Ins和E2水平明显高于对照组（P值均〈0.001）,两组间睾酮水平差异无显著性（P〉0.05）;血清IGF-Ⅰ、IGF-BP3与Leptin、Ins、E2及睾酮水平显著正相关（P值均〈0.01）,且Leptin与Ins、E2水平显著正相关（P值均〈0.001）;多元线性回归分析显示IGF-BP3、Ins和E2是影响IGF-Ⅰ的重要因素。【结论】学龄前肥胖儿童IGF-Ⅰ、Leptin和Ins在调节机体能量代谢过程中不仅作为独立的外周因子发挥作用,同时提示IGF-Ⅰ对儿童生长发育以及性发育的调控受Leptin、Ins及性激素多种激素水平的共同影响,IGF-Ⅰ是儿童肥胖又一敏感检测指标。     

胰岛素样生长因子结合蛋白-1对延期妊娠引产时机选择的意义

目的:探讨胰岛素样生长因子结合蛋白-1(IGFBP-1)对延期妊娠引产时机选择的意义。方法:选择延期妊娠孕妇79例,检测宫颈分泌物IGFBP-1的同时进行宫颈Bishop评分,观察IGFBP-1与Bishop评分的相关性。根据IGFBP-1检测结果分为阳性组和阴性组,根据Bishop评分结果分为宫颈成熟组和未成熟组,按催产素点滴常规进行引产。观察各组引产效果成功率,评价IGFBP-1与Bishop评分对预测引产成功的敏感性、特异性、阳性预测值和阴性预测值。结果:IGFBP-1与Bishop评分呈正相关,其总体相关系数为0·98(P<0·05);IGFBP-1阳性组84h内引产成功率明显高于阴性组,差异有显著性(P<0·001);宫颈成熟组与未成熟组84h内引产成功率差异无显著性(P>0·05);Bishop评分≤3分且IGFBP-1阴性的10例孕妇无1例引产成功;IGFBP-1预测引产成功的敏感性、特异性、阳性预测值和阴性预测值优于Bishop评分。结论:IGFBP-1可作为延期妊娠引产时机选择的重要指标,IGFBP-1结合Bishop评分可提高延期妊娠引产成功率。     

IGFBP-1、CRP联合宫颈指数在早产预测中的价值

目的:探讨宫颈分泌物中高磷酸化IGFBP-1、血清中CRP、宫颈指数在早产预测中的价值。方法:对西丽人民医院诊治的91例先兆早产孕妇检测其宫颈分泌物中IGFBP-1、血清中C-反应蛋白,同时经会阴超声检测宫颈指数。随访至分娩,分析多指标联合应用在早产预测中的价值。结果:IGFBP-1、宫颈指数的阳性组中早产发生率明显高于阴性组(P<0.01),该两指标联合应用对早产的阳性预测值明显提高(P<0.01)。血清CRP在早产组与足月产组间无统计学差异(P>0.05)。结论:宫颈分泌物IGFBP-1联合宫颈指数可提高对早产预测的准确性。     

0～3个月早期干预对婴儿生长发育和GH、IGF-I水平的影响

【目的】　研究出生后即开始的早期干预对婴幼儿生长发育的影响及其影响机制。　【方法】　将186例刚出生的婴儿分为干预组和对照组,干预组在专业医师指导下采用在家庭与医院进行特殊训练的方法,持续3 个月,观察抬头、有意识发出微笑时间,3 个月、6 个月时身高、体重、心理发育指标变化及生长激素(gronth hormone,GH)和胰岛素样生长因子(isu lin like growth factor I,IGF I)水平。　【结果】　早期干预组婴儿抬头、有意识发出微笑时间较对照组明显提前,体重和身高大于对照组,心理发育综合评分高于对照组(P均<0.05 或0.01)。干预组婴儿3个月时IGF I水平明显高于对照组(P<0.05),而GH水平与对照组无差别(P>0.05),6个月时GH和IGF I水平均明显高于对照组(P均<0.01)。　【结论】　0~3个月早期干预对婴儿早期生长发育有明显促进作用,其可能通过影响生长激素和IGF I水平变化而起作用。     

Utility of insulin-like growth factor-I and its binding protein assays

Insulin-like growth factor-I circulates in serum either in free form or bound to insulin-like growth factor-binding proteins that modulate its bioavailability. Insulin-like growth factor-binding proteins interfere with insulin-like growth factor-I assay, which remains technically difficult. Many assays have been developed, but their results are somewhat discordant. The choice of separation method, standard and tracer considerably influences the results. The circulating concentration of insulin-like growth factor-I, however, is clearly dependent on nutritional status, and total levels are a valuable marker of nutritional status. The clinical utility of free insulin-like growth factor-I assay and simultaneous assay, in the same sample, of total insulin-like growth factor-I and its binding proteins (reflecting the bioavailable insulin-like growth factor-I fraction), remains to be evaluated.