Kucera Radek, Topolcan Ondrej, Pecen Ladislav, Kinkorova Judita, Svobodova Sarka, Windrichova Jindra, Fuchsova Radka
Laboratory of Immunoanalysis, Faculty Hospital Pilsen, Czech Republic; Medical Faculty Pilsen, Charles University, Prague, Czech Republic.
Laboratory of Immunoanalysis, Faculty Hospital Pilsen, Czech Republic; Medical Faculty Pilsen, Charles University, Prague, Czech Republic.
Clin Chim Acta. 2015 Apr 15;444:271-7. doi: 10.1016/j.cca.2015.02.036. Epub 2015 Mar 2.
IGF1 is responsible for regulation of growth, metabolism and differentiation of human cells. IGFBP3 is the most abundant of the carrier proteins for IGF1 in the blood. IGF1/IGFBP3 molar ratio is an indicator of IGF1 bioavailability. We decided to create a file of reference ranges of IGF1, IGFBP3 and IGF1/IGFBPP3 ratio for the adult Czech population across the age spectrum.
We selected a group of 1022 subjects, 467 males and 555 females (ages 20-98 years), from several regions in the Czech Republic. The group consisted of blood donors and patients undergoing regular preventive examinations. Serum levels of IGF1 and IGFBP3 were measured using the following radioimmunoassay kits: IRMA IGF1 (Immunotech, Marseille, France) and IRMA IGFBP3 (Immunotech, Prague, Czech Republic). The IGF1/IGFBP3 ratio was also calculated. The following groups of patients were excluded: patients with diabetes, high blood glucose, high insulin levels, post-surgery patients, polymorbid patients, and subjects with oncological diseases. Subjects were divided into seven age-groups. Changes in the levels of observed analytes in each decade across the age spectrum were evaluated. All statistical analyses were performed by SAS 9.3 (Statistical Analysis Software release 9.3; SAS Institute Inc., Cary, NC, USA).
All three parameters IGF1, IGFBP3 and IGF1/IGFBP3 decreased in parallel with decrease in age: p<0.0001, r=-0.64, -0.35 and -0.54, respectively. The dynamics of the decline was different between males and females. Linear regression models with age as independent variable fitted by gender are displayed in Fig. 1. Non-parametric reference interval curves (medians and 2.5th-97.5th percentiles) for IGF1, IGFBP3 and IGF1/IGFBP3 ratio as function of age by gender are displayed in Fig. 2(a,b,c). All medians and 2.5th-97.5th percentiles were plotted by cubic spline. For males, linear regression models were as follows: IGF1=291.34619-2.41211 × age, IGFBP3=2931.62778-6.11659 × age, IGF1/IGFBP3=0.02897-0.00021213 × age. For females, we plotted the following: IGF1=241.67406-1.98466 × age, IGFBP3=3688.60561-16.39560 × age, IGF1/IGFBP3=0.02029-0.00013233 × age. IGF1 was statistically significantly higher in males with p<0.0001 (Wilcoxon test) but decreased faster (p=0.0121). IGFBP3 was statistically significantly higher in females with p=0.0004 (Wilcoxon test) but decreased faster (p<0.0001). IGF1/IGFBP3 was statistically significantly higher in males with p<0.0001 (Wilcoxon test) but decreased faster (p<0.0001).
Authors recommend using of a linear regression model based reference ranges for IGF1, IGFBP3 and IGF1/IGFBP3 ratio and using different reference ranges for genders.
胰岛素样生长因子1（IGF1）负责调节人体细胞的生长、代谢和分化。胰岛素样生长因子结合蛋白3（IGFBP3）是血液中IGF1最丰富的载体蛋白。IGF1/IGFBP3摩尔比是IGF1生物利用度的一个指标。我们决定建立一个涵盖各个年龄段的成年捷克人群IGF1、IGFBP3及IGF1/IGFBP3比值参考范围的文件。
我们从捷克共和国的几个地区选取了一组1022名受试者，其中467名男性和555名女性（年龄在20 - 98岁之间）。该组包括献血者和接受定期预防性检查的患者。使用以下放射免疫分析试剂盒测量血清IGF1和IGFBP3水平：IRMA IGF1（Immunotech，法国马赛）和IRMA IGFBP3（Immunotech，捷克布拉格）。同时计算IGF1/IGFBP3比值。排除以下几组患者：糖尿病患者、高血糖患者、高胰岛素水平患者、术后患者、患有多种疾病的患者以及患有肿瘤疾病的受试者。受试者被分为七个年龄组。评估了各年龄段每十年观察分析物水平的变化。所有统计分析均使用SAS 9.3（统计分析软件版本9.3；SAS Institute Inc.，美国北卡罗来纳州卡里）进行。
IGF1、IGFBP3和IGF1/IGFBP3这三个参数均随着年龄的降低而平行下降：p<0.0001，r分别为 -0.64、 -0.35和 -0.54。男性和女性的下降动态有所不同。图1展示了以年龄为自变量按性别拟合的线性回归模型。图2（a、b、c）展示了IGF1、IGFBP3和IGF1/IGFBP3比值随年龄变化的非参数参考区间曲线（中位数和第2.5 - 97.5百分位数），按性别绘制。所有中位数和第2.5 - 97.5百分位数均通过三次样条绘制。对于男性，线性回归模型如下：IGF1 = 291.34619 - 2.41211×年龄，IGFBP3 = 2931.62778 - 6.11659×年龄，IGF1/IGFBP3 = 0.02897 - 0.00021213×年龄。对于女性，我们绘制如下：IGF1 = 241.67406 - 1.98466×年龄，IGFBP3 = 3688.60561 - 16.39560×年龄，IGF1/IGFBP3 = 0.02029 - 0.00013233×年龄。男性的IGF1在统计学上显著更高，p<0.0001（Wilcoxon检验），但下降速度更快（p = 0.0121）。女性的IGFBP3在统计学上显著更高，p = 0.0004（Wilcoxon检验），但下降速度更快（p<0.0001）。男性的IGF1/IGFBP3在统计学上显著更高，p<0.0001（Wilcoxon检验），但下降速度更快（p<0.0001）。
作者建议使用基于线性回归模型的IGF1、IGFBP3和IGF1/IGFBP3比值参考范围，并针对不同性别使用不同的参考范围。
