Serum IGF-binding Protein-3 Research Articles

Clinical significance of epidermal growth factor receptor mutations and insulin-like growth factor 1 and its binding protein 3 in advanced non-squamous non-small cell lung cancer

This study of patients with advanced non-squamous non-small cell lung cancer (NSCLC) evaluated epidermal growth factor receptor (EGFR) mutation status and two serum markers, serum insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3), for their associations to response to gefitinib therapy and for their prognostic impact. An immunoradiometric assay determined levels of IGF1 and IGFBP3 in serum from 68 patients with advanced non-squamous NSCLC. The peptic nucleic acid locked nucleic acid clamp method determined their EGFR somatic mutation status. We evaluated the relationship between each independent clinicopathological variable and the response to gefitinib therapy and the risk factors associated with prognosis. Having IGF1-positive serum as determined by the 75th percentile and having wild-type EGFR were both independent negative predictive factors for geftinib treatment by multivariate logistic regression model analysis. Both having serum positive for IGF1 as determined by the 25th percentile and having wild-type EGFR were significant independent negative prognostic factors for survival based on multivariate analysis. We demonstrated that having IGF1-positive serum predicts a negative response to gefitinib therapy independent of EGFR mutational status. We also demonstrated that both IGF1-positive serum and wild-type EGFR were independent poor prognostic factors in patients with non-squamous NSCLC who received gefitinib therapy.

Serum IGF-1 and IGFBP-3 Levels in Healthy Children Between 0 and 6 Years of Age - Original Article

Objective: Along with growth hormone (GH) levels, measurements of serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) are used in the diagnosis of GH deficiency and in monitoring the efficacy and safety of long-term GH treatment. The purpose of the present study was to establish reference values for serum IGF-1 and IGFBP-3 in healthy Turkish children less than 6 years of age.Methods: This study was designed as a multicenter project. Five hundred sixty-seven healthy children younger than 6 years of age from different geographical regions of Turkey, with weight and height values between the 10th and 90th percentiles according to the national standards were included in the study. In addition to anthropometric parameters, serum IGF-1 and IGFBP-3 levels were measured in all subjects.Results: Although not statistically significant, the serum IGF-1 levels in infants at age 6 months were lower than those in infants at age 3 months. The IGF-1 levels showed a slow increase with age. Serum IGF-1 levels were lower in girls as compared to boys only at age 6 months. No correlation was found between either serum IGFBP-3 levels and body mass index (BMI) or serum IGFBP-3 and weight and height standard deviation scores (SDS). A weak correlation was observed between serum IGF-1 and IGFBP-3 concentrations.Conclusions: The age- and gender-specific reference values for serum IGF-1 and IGFBP-3 reported in this study will aid in the diagnosis of GH deficiency and in the monitoring of children receiving GH treatment.Conflict of interest:None declared.

Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks in trisomy 21 and trisomy 18 pregnancies

ObjectiveTo investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 in first-trimester screening for fetal aneuploidies. Study designMaternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks of gestation were measured and compared in 30 trisomy 21, 30 trisomy 18 and 120 euploid pregnancies. ResultsThe median multiple of the normal median (MoM) values of maternal serum IGF-I, IGFBP-1 and IGFBP-3 in trisomy 21, trisomy 18 and euploid pregnancies were not significantly different (IGF-I: 1.10, 1.14 and 1.0 MoM, respectively; IGFBP-1: 1.10, 1.01 and 1.0 MoM; IGFBP-3: 0.90, 1.16 and 0.98 MoM). ConclusionMeasurement of maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks of gestation is unlikely to be useful in screening for trisomies 21 and 18.

Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I, and IGFBP-3

The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between IGFBP-3 gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). DNA isolation was performed in peripheral blood samples obtained from all participants. Required areas were amplified with polymerase chain reaction restriction fragment length polymorphism (PCR–RLFP) technique by using proper primers belonging to this gene area. We also measured serum IGF-I and IGFBP-3 levels. The IGFBP-3 −202 A/C polymorphism genotype frequencies showed a significant difference between PCa patients and controls (χ2=6.27, df=2.0, P=0.026), as well as between BPH patients and controls (χ2=11.57, df=4.0, P=0.014). The AA genotype frequency was significantly decreased in PCa and BPH patients compared to control group and the risk of PCa and BPH occurrence of this genotype was decreased accordingly (PCa; OR=0.28, 95% CI=0.17–0.44, P=0.0001; BPH: OR=0.48, 95% CI=0.29–0.77, P=0.001). Age-adjusted mean serum IGFBP-3 concentrations were highest in the individuals with the AA genotype and diminished significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4577ng/ml, 3929ng/ml and 3349ng/ml, respectively). Patients with PCa and BPH had lower serum IGF-1 (P=0.001, and P=0.01, respectively) and IGFBP-3 levels (P=0.001, and P=0.01, respectively) compared with controls. The AA genotype at IGFBP-3 gene polymorphism is associated with reduced risks of PCa and BPH. Both IGF-I and IGFBP-3 concentrations, are associated with modified risks of PCa and BPH.

GH receptor blocker administration and muscle–tendon collagen synthesis in humans

ContextThe growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans. ObjectiveWe hypothesised, that a GH blockade would decrease IGF-I and collagen synthesis in the connective tissue of skeletal muscle and tendon. DesignThe study was randomised and double blinded. Participants20 healthy young males completed the study. InterventionThe participants were randomised to 2weeks of GH receptor blocker supplementation (pegvisomant, 5mg/day, n=9) or placebo (n=11). Main outcome measuresSerum levels of GH, IGF-I and IGF-binding protein 3 (IGFBP-3) were measured before and after pegvisomant/placebo supplementation. Fractional synthesis rates (FSR) for collagen and myofibrillar protein were determined with stable isotopes in tendon and muscle, and mRNA for collagen (COL1A1 and COL3A1) as well as IGF-I isoforms (Ea and Ec) were measured in skeletal muscle. ResultsPegvisomant decreased serum IGF-I by 20% (p<0.01) and serum IGFBP-3 by 10% (p<0.05). Pegvisomant supplementation had no effect on collagen synthesis in tendon and skeletal muscle, nor was muscle myofibrillar protein synthesis affected. Similarly, pegvisomant supplementation had no effect on mRNA expression of IGF-I and collagen in skeletal muscle. ConclusionGH receptor blocker administration in healthy humans resulted in a moderate decrease in serum IGF-I. Collagen synthesis in tendon and skeletal muscle, as well as skeletal muscle IGF-I and collagen mRNA expression, was unaffected by GH receptor blocker supplementation.

Serum concentrations of insulin-like growth factor-I, insulin-like growth factor binding protein-3 and cardiovascular risk factors in adolescents

The risk association between the insulin like growth factor-I (IGF-I) system and cardiovascular risk is inconclusive in adults and under-explored in adolescents. We aimed to investigate the associations between serum concentrations of IGF-I and IGF binding protein-3 (IGFBP-3) and cardiovascular risk factors in adolescents. This was a cross-sectional, population-based, observational study in a school setting with 2102 Hong Kong Chinese adolescents aged 12-19 years. Serum IGF-I and IGFBP-3 concentrations were measured by chemiluminescence immunoassays. Anthropometric indices and traditional cardiovascular risk factors were assessed. After excluding participants with abnormal thyroid and liver test results, 765 boys and 877 girls, mean (±SD) age of 15.3 (±2.0) and 15.7 (±2.0) years, respectively, were included in the analysis. Multivariable regression analyses revealed that both IGF-I and IGFBP-3 concentrations were independently associated with waist circumference, fasting insulin and haemoglobin concentrations in boys (all P < 0.05), systolic blood pressure, serum creatinine, fasting insulin and haemoglobin concentrations in girls (all P < 0.05). In girls, IGF-I was also associated with C-reactive protein concentration (P < 0.001) and IGFBP-3 was associated with fasting triglyceride concentration (P < 0.001). Compared with adolescents with the lowest tertile, the top tertile of both IGF-I and IGFBP-3 concentrations were associated with increased odds of having overweight/obesity, top tertiles of insulin and haemoglobin in both boys and girls (P for trend, all <0.05). The associations between serum IGF-I, IGFBP-3, obesity, cardiovascular risk factors, insulin and haemoglobin suggest that dysregulation of the IGF system may play a linking role for the clustering of cardiovascular risk factors.

Growth Hormone Deficiency in Children and Adolescents with Cerebral Palsy: Relation to Gross Motor Function and Degree of Spasticity

Children with Cerebral Palsy (CP) often have poor linear growth during childhood with short final height. Thus, we aimed to assess serum growth hormone (GH), insulin like growth factor-1 (IGF-1) and insulin like growth factor binding protein-3 (IGFBP-3) levels among CP patients and their relation to each of gross motor function and degree of spasticity. Fifty CP children and adolescents were studied in comparison to 50 healthy age-, sex- and pubertal stage-matched children and adolescents. All subjects were subjected to clinical evaluation, Intelligence Quotient (IQ) assessment and measurement of serum GH, IGF-1 and IGFBP-3. All auxological and hormonal parameters were significantly lower among cases. Fifty two% of cases were GH-deficient and 62% had reduced IGF-land IGFBP-3 levels. Gross Motor Function Measure- 88 (GMFM-88) score correlated negatively with each of basal (r = -0.71, p = 0.02) and peak stimulated GH (r =-0.88, p = <0.001); IGF-1 (r = -0.64, p = 0.04) and IGFBP-3 (r = -0.69, p = 0.031). There were significant negative correlations between the degree of spasticity assessed by Modified Ashworth Scale and each of basal (r = -0.61, p = 0.032) and peak stimulated GH (r = -0.78, p = 0.01); IGF-1 (r = -0.65, p = 0.041) and IGFBP-3 (r = -0.62, p = 0.035). Growth Hormone Deficiency (GHD) is prevalent in children with CP and could be one of the causes of their short stature.

Maternal serum insulin-like growth factor-binding protein-3 (IGFBP-3) at 11–13 weeks in preeclampsia

The objective of this study was to determine if the maternal serum concentration of insulin-like growth factor-binding protein-3 (IGFBP-3) at 11-13 week's gestation is altered in pregnancies that subsequently develop preeclampsia (PE). Maternal serum concentration of IGFBP-3, pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (PI) were measured in 60 cases that developed PE, including 20 that developed early-PE requiring delivery before 34 weeks, and compared with 120 unaffected controls. In the unaffected pregnancies, the median multiple of the normal median (MoM) values of serum IGFBP-3, PAPP-A and uterine artery PI were 1.0 MoM. In late-PE, but not in early-PE, serum IGFBP-3 was significantly increased (1.16 and 1.06 MoM, respectively), whereas in early-PE, but not in late-PE, uterine artery PI was increased (1.41 and 1.11 MoM, respectively) and serum PAPP-A was decreased (0.53 and 0.87 MoM, respectively). In the PE group, there was no significant association between IGFBP-3 and either uterine artery PI (P=0.775) or maternal serum PAPP-A (P=0.275). First-trimester serum IGFBP-3 is increased in pregnancies that subsequently develop late-PE in a mechanism that is unrelated to impaired placentation, as reflected in uterine artery PI and serum PAPP-A.

The emerging role of NO and IGF‐1 in early renal hypertrophy in STZ‐induced diabetic rats

Diabetic nephropathy (DN) is a major complication of diabetes mellitus, and the most common cause of end-stage renal disease. DN is characterized by early hyperfiltration and renal hypertrophy, which are associated with increased renal insulin-like growth factor-1 (IGF-1) levels. The relationship between IGF-1 and nitric oxide (NO) in DN is not established. The aim of this study was to investigate the effects of NO system modulation on the IGF-1-mediated hypertrophy and hyperfiltration during the first week after diabetes induction. Diabetes was induced in rats by streptozotocin (STZ) injection. Diabetic rats were treated with NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME). Various serum IGF-binding proteins (IGFBPs) and renal IGFBP1 expression was evaluated. Urine and plasma NO(2) + NO(3) level analysis was also performed. STZ induced hyperglycaemia decreased plasma insulin levels and brought about a decrease in body weight. L-NAME administration to diabetic rats significantly prevented renal hypertrophy and hyperfiltration. Serum IGFBP3, IGFBP4 and 30-kDa IGFBP fraction were all significantly reduced in diabetic rats, compared with those in non-diabetic control rats. However, the renal IGFBP1 mRNA expression in diabetic rats was significantly higher. These changes were accompanied by an increased in NO production. L-NAME administration prevented the serum IGFBP decline, without significantly affecting the renal IGFBP1 mRNA expression. We have shown that increased renal IGF-1 and increased NO production during the very early stages of STZ-induced DN are associated with renal hypertrophy and hyperfiltration in diabetic rats. Modulating the IGF-1 availability to the kidney by nitric oxide synthase inhibition significantly reduced renal hypertrophy and hyperfiltration during the first week of STZ-induced diabetes mellitus.

The association between bladder cancer and a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) gene

Insulin-like growth factors (IGF) regulate growth and development and enhance cellular proliferation. IGF-binding protein-3 (IGFBP-3) inhibits IGF action by competitively binding IGFs that prevents their binding to the IGF cell surface receptor. Altered expression and serum levels of IGFBP-3 are associated with a number of malignancies. Study addressing the effect of IGFBP-3 gene polymorphism on bladder cancer is lacking. The aim of this study was to examine the effect of -202 A/C polymorphism of IGFBP-3 gene on development of bladder transitional cell carcinoma (TCC) and its correlation with serum concentration of IGF-1 and IGFBP-3 and with clinicopathological characteristics. One single nucleotide polymorphism (rs2854744) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) technique. One hundred and sixty-two bladder cancer patients were genotyped for this SNP. The genotypes were compared with those of a random sample of 324 age-matched controls of the general population. Serum levels of IGF-I and IGFBP-3 were also determined. We found statistically significant differences in the genotypic distribution between the cases and the control subject (χ(2)=6.43, df=2.0, P=0.028). Using CC genotype as a reference, the odds ratio for the subjects with AC genotype was 1.76 (95% CI: 1.27-2.84; P=0.038). We detected a significantly decreased risk of bladder cancer associated with the AA genotype (adjusted OR=0.48; 95% CI=0.24-0.64; P=0.001) compared with the CC genotype. This decreased risk was more pronounced for invasive bladder cancer. Age-adjusted mean serum IGFBP-3 levels were lowest in the individuals with the CC genotype. We found a positive correlation between age-adjusted serum IGFBP-3 levels and circulating IGF-1 concentrations (16% difference in IGFBP-3 in top vs. bottom tertiles of IGF-1, P for trend=0.001), which was comparable across genotypes at the -202 IGFBP-3 locus (interaction term, F=0.10, P=0.87). Genetic polymorphism of the IGFBP-3 gene may be involved in the etiology of bladder TCC, and our results need further confirmation by larger studies.

Maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) at 11-13 weeks in pre-eclampsia

The aim of this study was to determine the maternal serum concentration of insulin-like growth factor-binding protein-1 (IGFBP-1) at 11-13 weeks' gestation in pregnancies that subsequently develop pre-eclampsia (PE) and to examine the possible association with uterine artery pulsatility index (PI). Maternal serum concentration of IGFBP-1 and uterine artery PI were measured in 60 cases that developed PE, including 20 that required delivery before 34 weeks (early-PE) and 120 unaffected controls. The measured IGFBP-1 concentration and uterine artery PI were converted into a multiple of the expected median (MoM) in unaffected pregnancies and median MoM values were compared in the outcome groups. Regression analysis was used to determine the significance of association of IGFBP-1 MoM with uterine artery PI MoM. In the early- and late-PE groups, the median IGFBP-1 was decreased (0.63 and 0.67 MoM, respectively) and uterine artery PI was increased (1.31 and 1.19 MoM, respectively). In the group that developed PE there were no significant associations between serum IGFBP-1 with uterine artery PI (p = 0.210). In pregnancies that develop PE, the serum IGFBP-1 is decreased from the first trimester suggesting that IGFBP-1 may be implicated in the pathogenesis of PE in a mechanism unrelated to impaired placental perfusion.

Longitudinal association between IGFBP-1 levels and parameters of the metabolic syndrome in obese children before and after weight loss

Insulin-like growth factor binding protein 1 (IGFBP-1) is a marker of insulin resistance. We hypothesized that IGFBP-1 is associated with the metabolic syndrome (MetS), which is related to insulin resistance. We examined 51 obese Caucasian children (mean age 12.1 ? 2.3, 55% male, mean body mass index [BMI] 31.8 ? 4.8 kg/m(2)). Anthropometrical markers, pubertal stage, hepatic ultrasound, waist circumference, blood pressure, fasting serum IGFBP-1, IGFBP-3, IGF-I, adiponectin, leptin, transaminases, glucose, insulin, triglycerides, and HDL-cholesterol concentrations were determined at onset and the end of the one-year lifestyle intervention. In contrast to IGF-I and IGFBP-3, IGFBP-1 correlated significantly to most parameters of the MetS in cross-sectional (waist circumference: r = -0.45, triglycerides: r = -0.29; insulin: r = -0.31; HOMA: r = -0.30) and longitudinal analyses (? triglycerides: r = ?0.22; ? Insulin: r = ?0.25; ? HOMA: r = ?0.62). The association between changes of HOMA and changes of IGFBP-1 was stronger than the associations between changes of leptin or adiponectin, and changes of HOMA. The risk for the MetS was inversely related to IGFBP-1 levels (odds ratio:-0.05 per additional IGFBP-1 unit; 95% confidence interval: -0.08 up to -0.02; p = 0.019) in a multiple logistic regression analyses adjusted to BMI, pubertal stage, age, and gender. The nine obese children with the MetS had significantly lower IGFBP-1 levels (1.6 ? 1.3 ngm/l) than the 42 obese children without the MetS (4.0 ? 3.8 ng/ml). The eleven obese children with fatty liver assessed by ultrasound had significantly lower IGFBP-1 levels (1.5 ? 1.3 ngm/l) than the 40 obese children without fatty liver (4.2 ? 4.1 ng/ml). The strong relationships between IGFBP-1, insulin resistance, and the MetS suggest that IGFBP-1 might be a promising marker for these entities in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

Evaluation of Growth Status Using Serum IGF-I and IGFBP-3 in Children with Subclinical Hypothyroidism

Purpose : The aim of this study was to evaluate growth status using the insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) concentrations in children with subclinical hypothyroidism (SCH). Methods : The study included 93 SCH patients (33 males and 60 females, age 8.1±1.9 years) and 94 healthy control subjects (31 males and 63 females, age 8.0±0.7 years). Patients’ height and weight were measured, and their body mass index (BMI) and Z-scores were calculated. The relationship between growth parameters, including IGF-I and IGFBP-3 concentrations and thyroid functions (thyroid-stimulating hormone (TSH) and free thyroxine 4 (fT4) was explored. Results : Although weight and BMI were greater in SCH patients, the Z-score of height, weight and BMI, and serum IGF-I and IGFBP-3 levels in SCH children were not significantly different compared to the control. In SCH patients, TSH showed a negative correlation with weight Z-scores (r =-0.23, P =0.028) and BMI Z-scores (r =-0.21, P =0.048). FT4 showed a positive correlation with IGFBP-3. Conclusion : The positive correlation of fT4 and IGFBP-3 and the negative relationship between TSH and weight and BMI Z-scores in SCH children suggest that subnormal thyroid functions could be related to growth impairment. (J Korean Soc Pediatr Endocrinol 2011;16:31-37)

The effect of corrective surgery on serum IGF-1, IGFBP-3 levels and growth in children with congenital heart disease

The aim of this study is to evaluate growth and insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels in infants with congenital heart disease (CHD) pre- and postoperatively over a period of a year. Anthropometric values and serum levels of IGF-1 and IGFBP-3 of 40 infants with CHD (20 cyanotic and 20 acyanotic) were compared with 32 healthy controls. Acyanotic infants and infants with pulmonary hypertension (PH) presented significantly more growth failure. Preoperatively, serum IGF-1 and IGFBP-3 levels were lower in the acyanotic group than the cyanotic and the control groups (p = 0.22; p < 0.01). The upward trend in IGF-1 and IGFBP-3 levels in this year-long study demonstrated that the values in the third month and the first year were higher than the preoperative values (p < 0.05). The parallel increase of weight gain and IGF-1, IGFBP-3 levels were the best evidence that these parameters are good nutritional indicators. Timing the corrective surgery before chronic malnutrition or PH develops is an important issue to maintain a normal growth for children with CHD.

Yetişkin Sağlıklı Bir Türk Toplum Örnekleminde İnsülin-Benzeri Büyüme Faktörü-I ve IGF-Bağlayıcı Protein-3 Seviyeleri

Amaç: İnsülin benzeri büyüme faktörü-I (IGF-I) ve IGF-bağlayıcı protein-3 (IGFBP 3) seviyeleri büyüme hormonu (GH) ilişkili hastalıkların tanısında önemli belirteçlerdir. Normal IGF-I ve IGFBP- 3 seviyeleri farklı etnik gruplar arasında değişkenlik göstermektedir ve farklı populasyonlara göre belirlenenen referanslar bazı tanı, tedavi ve izlemde bazen yanlış yönlenmeye neden olabilmektedir. Biz bu amaçla sağlıklı yetişkin Türk toplum örnekleminde IGF-I ve IGFBP-3 düzeylerini inceledik. Gereç ve Yöntemler: Sekiz yüz otuz üç olgu (512 kadın, 321 erkek) çalışmaya alındı. Serum IGF-I ve IGFBP-3 seviyeleri tüm olgularda bir immünoradyometrik tetkikle ölçüldü. Çalışma populasyonu yaş grupları (18-20, 21-23, 24-25, 26-30, 31-40, 41-50, >50 yaş) ve cinsiyet gruplarına (<30 yaş populasyon kadın ve erkekler olarak ayrılırken >30 yaş grubunda birlikte) ayrıldı ve sonuçlar üretici firmanın referans bir toplumu temsil eden referans değerleri ile karşılaştırıldı. Bulgular: Serum IGF-I değerleri ≤30 yaştaki bütün kadın yaş gruplarında referans seviyelerinden istatistiksel olarak anlamlı düzeyde daha yüksekti (p< 0.05). Erkeklerde sadece 26-30 yaş arası grupta IGF-I seviyeleri istatistiksel olarak anlamlı düzeyde daha yüksekti (p< 0.05). Otuz yaş üstündeki cinsiyet yönünden birlikte ele alınan gruplarda IGF-I seviyeleri referans seviyelerinden istatistiksel olarak daha yüksekti (p< 0.05). Serum IGFBP-3 seviyeleri 24-25 yaş arası grupta her iki cinsiyette, 18-20 yaş arası grupta ise erkeklerde referans değerlerinden daha düşüktü (p< 0.05). Serum IGFBP-3 seviyeleri 26-30 yaş arası grupta erkeklerde ve >30 yaş üstünde cinsiyet yönünden birleşik gruplarda istatistiksel açıdan anlamlı derecede daha yüksekti (p< 0.05). Sonuç: Çalışma populasyonumuzdaki serum IGF-I konsantrasyonları ticari kitin referans değerlerinden genelde daha yüksekti. GH'la ilişkili bozukluklarla ilgilenen merkezlerin tanı ve izlemde olası hatalardan kaçınabilmek amacıyla kendi populasyonlarının normal IGF-I ve IGFBP-3 değerlerini belirlemeleri yararlı olabilecektir.

The relationship between serum ghrelin levels and hair zinc concentrations in children

Background: Zinc (Zn) plays a central role in the activation of numerous enzyme systems that synthesize and degrade bioactive peptides. Some of these bioactive peptides, also called neuropeptides, are involved in the regulation of food intake.Objective: In this study we aimed to demonstrate the relationship between serum ghrelin and hair Zn concentrations in children. Methods: Prepubertal children brought to our outpatient clinics by their parents because of signs and symptoms of pica, poor appetite, poor growth, and other complaints were included in the study. The children were divided into two groups according to Zn hair concentrations. Group 1 consisted of children with low (< 70 μg/g) hair Zn levels, and group 2 of children with normal ( ≥ 70 μg/g) hair Zn levels. Hair Zn concentrations, serum ghrelin, insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels were measured in all children.Results: There were 10 children with low hair Zn levels (group 1) and 15 with normal levels (group 2). Serum IGF-I, IGFBP-3 and ghrelin concentrations of group 1 (103.1 ± 71.8 ng/mL, 1412.8 ± 615.7 ng/mL and 0.96 ± 0.22 ng/mL, respectively) were lower than in group 2(164.9 ± 40.5 ng/mL, 2398.5 ± 295.5 ng/mL and 1.21 ± 0.23 ng/mL, respectively). In univariate analysis, Zn hair concentration was positively associated with serum IGF-I (r=0.424, p=0.035) and IGFBP-3 (r=0.671, p < 0.001) concentrations. The correlation between ghrelin and hair Zn concentrations was not significant (r=0.202, p=0.333).Conclusion: Serum ghrelin concentrations might be affected by low hair Zn concentrations in children.Conflict of interest:None declared.

Insulin‐like growth factor axis (insulin‐like growth factor‐I/insulin‐like growth factor‐binding protein‐3) as a prognostic predictor of heart failure: association with adiponectin

Insulin-like growth factor (IGF)-I is a regulator of glucose/fatty acid metabolism and may be involved in the pathophysiology of cardiovascular disease, but it remains unclear whether endogenous IGF-I is associated with the prognosis of heart failure (HF). We investigated whether the IGF axis, the ratio of IGF-I to IGF-binding protein-3 (IGFBP-3), was a predictor of clinical outcomes in HF. The association of IGF axis with serum adiponectin level, a prognostic marker of HF as well as a regulator of glucose/fatty acid metabolism, was also analysed. We measured serum IGF-I and IGFBP-3 in 142 HF patients with left ventricular systolic dysfunction and 63 control subjects. Patients with HF underwent clinical assessment and measurement of adiponectin and B-type natriuretic peptide (BNP). Compared with controls, HF patients showed significantly decreased serum IGF axis values [median (inter-quartile ranges), 0.114 (0.063-0.150) vs. 0.099 (0.052-0.158), P = 0.042]. In HF patients, the log-transformed IGF axis values were inversely correlated with the log-transformed serum adiponectin levels (r = -0.35, P < 0.0001) and plasma BNP levels (r = -0.25, P = 0.0028). The IGF axis was lower in patients with New York Heart Association (NYHA) functional class III/IV than those with class I/II [0.071 (0.044-0.145) vs. 0.107 (0.068-0.161), P = 0.022]. Furthermore, a decrease in IGF axis was associated with increased rates of all-cause mortality (P = 0.013), cardiac death (P = 0.035), and a composite of cardiac death and re-hospitalization (P = 0.0085). Insulin-like growth factor axis is a significant predictor of clinical outcomes in HF and is significantly associated with serum adiponectin levels.

Abstract PR-1: Genetic African ancestry and race differences in blood insulin-like growth factor 1 (IGF-1), IGF-2, and IGF binding protein 3 (IGFBP-3)

Abstract Purpose: We have previously reported that African American women have significantly higher IGF-1 levels, and lower IGF-2 and IGFBP-3, compared to white women. This investigation aims to determine if genetic African ancestry is associated with these racial differences in blood IGF levels. Methods: The Southern Community Cohort Study (SCCS) is a prospective cohort study of 86,000 men and women, with two-thirds African American recruitment, designed to investigate racial disparities in cancer. We randomly selected 1000 African American and 1000 non-Hispanic white female participants to support focused investigations of racial differences in biomarkers possibly related to breast cancer. Serum IGF-1, IGF-2, and IGFBP-3 levels were measured by ELISA. We estimated African and European admixture using a panel of 276 ancestry informative genetic markers. Final analyses included 821 African American women and 816 white women after excluding women taking hormone replacement therapy or insulin for diabetes. White women had a low African ancestry (median = 0.4%, range=0.1 % to 17.1 %) and thus were considered as a single ancestry category. For African Americans, cutpoints of &amp;lt;85% (n=149), 85%-95% (n=230), and ≥95% (n=442) defined “low,” “medium,” and “high” African ancestry. Using multivariable linear regression, we estimated differences in IGF levels across ancestry categories while adjusting for age, body mass index (BMI), height, menopausal status, and BMI at age 21 years. Results: African American women having 85% African ancestry. For example, IGF-2 levels among white women and African American women with &amp;lt;85%, 85%-95%, and ≥95% African ancestry were 1771.9 ng/ml, 1713.5 ng/ml, 1620.3 ng/ml, and 1620.6 ng/ml, respectively. African American women with &amp;lt; 85% African ancestry had IGF-2 levels that were about 5.8% higher than African American women with 85%-95% (p=0.03) or ≥95% (p=0.01) ancestry. IGF-1 levels among white women and African American women with &amp;lt;85%, 85%-95%, and ≥95% African ancestry were 134.7 ng/ml, 143.8 ng/ml, 147.8 ng/ml, and 147.4 ng/ml, respectively, while IGFBP-3 levels were 3871.8 ng/ml, 3816.9 ng/ml, 3629.0 ng/ml, and 3693.9 ng/ml, respectively. African American women with 85% African ancestry, but these differences in IGF-1 and IGFBP-3 levels between African American ancestry groups were not statistically significant. We also calculated the molar ratio of IGF-1 to IGFBP-3 as an index of biologically available or free IGF-1. Differences in free IGF-1 among white women and African American women with &amp;lt;85%, 85%-95%, and ≥95% African ancestry were 0.126,0.137,0.148, and 0.145, respectively. Free IGF-1 levels were significantly lower among African American women with &amp;lt;85% compared to women with 85%-95% (p=0.02) or ≥95% (p=0.05) ancestry. Conclusion: Estimates of African ancestry are significantly associated with IGF-2 and free IGF-1, and suggest inherited genetic traits associated with African ancestry contribute to racial differences in IGF levels. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PR-1.

Elevated Insulin-Like Growth Factor-I Values in Children with Prader-Willi Syndrome Compared with Growth Hormone (GH) Deficiency Children over Two Years of GH Treatment

Children with Prader-Willi syndrome (PWS) are routinely treated with GH and have a response comparable with that observed in children with GH deficiency (GHD). The objective of the study was to compare changes in serum IGF-I, IGF binding protein 3 (IGFBP-3), IGF-I to IGFBP-3 molar ratio, and growth velocity during the first 2 yr of GH therapy in PWS and GHD children. Thirty-three children with PWS (14 boys, 4.9 ± 3.8 yr) and 591 with GHD (351 boys, 9.6 ± 3.6 yr), all naive to GH treatment, were included in this study. Serum IGF-I and IGFBP-3 were measured at 0, 6, 12, and 24 months of GH therapy. The mean initial dose of GH was 0.9 and 1 mg/m(2) · d in the PWS and GHD groups, respectively. Mean ± SD IGF-I sdscore (SDS) and IGFBP-3 SDS were significantly higher in PWS compared with GHD. The IGF-I to IGFBP-3 molar ratio was significantly lower at baseline and subsequently not different. Despite significantly lower GH doses in PWS children at 6, 12, and 24 months (P = 0.021, P = 0.021, P = 0.001), IGF-I reached 2.8 ± 1.2 SDS at 24 months (72% of values > 2 SDS), and remained at 0.7 ± 1.6 SDS in GHD children (17% of values > 2 SDS). IGFBP-3 did not exceed 2 SDS in either group. There was no significant change in the IGF-I to IGFBP-3 molar ratio. IGF-I SDS increases to a greater extent in PWS than GHD. Bioavailable IGF-I is apparently not different, suggesting that any possible safety issues related to elevated IGF-I are similar in both groups.

Serum concentrations of insulin‐like growth factor‐i and insulin‐like growth factor binding protein‐2 and ‐3 in eight hoofstock species

The somatotropic axis, which includes growth hormone, insulin-like growth factor (IGF)-I, and IGF binding proteins (IGFBP), is involved in the regulation of growth and metabolism. Measures of the somatotropic axis can be predictive of nutritional status and growth rate that can be utilized to identify nutritional status of individual animals. Before the somatotropic axis can be a predictive tool, concentrations of hormones of the somatotropic axis need to be established in healthy individuals. To begin to establish these data, we quantified IGF-I, IGFBP-2, and IGFBP-3 in males and females of eight threatened hoofstock species at various ages. Opportunistic blood samples were collected from Bos javanicus (Java banteng), Tragelaphus eurycerus isaaci (bongo), Gazella dama ruficollis (addra gazelle), Taurotragus derbianus gigas (giant eland), Kobus megaceros (Nile lechwe), Hippotragus equines cottoni (roan antelope), Ceratotherium simum simum (white rhinoceros), and Elephas maximus (Asian elephant). Serum IGF-I and IGFBPs were determined by radioimmunoassay and ligand blot, respectively. Generally, IGF-I and IGFBP-3 were greater in males, and IGFBP-2 was greater in females. In banteng (P = 0.08) and male Nile lechwe (P < 0.05), IGF-I increased with age, but decreased in rhinoceros (P = 0.07) and female Nile lechwe (P < 0.05). In banteng, IGFBP-3 was greater (P < 0.01) in males. In elephants (P < 0.05) and antelope (P = 0.08), IGFBP-2 were greater in females. Determination of concentrations of hormones in the somatotropic axis in healthy animals makes it possible to develop models that can identify the nutritional status of these threatened hoofstock species.