Serum Insulin-like Growth factor-I Concentrations Research Articles

Association between serum insulin-like growth factor I or IGF-binding protein 3 and estimated glomerular filtration rate: results of a population-based sample

BackgroundInsulin-like growth factor I (IGF-I), which is mostly carried in blood by IGF-binding protein 3 (IGFBP-3), was associated to the glomerular filtration rate and chronic kidney disease in a multiethnic study among US adults. The aim of the present study was to investigate whether serum IGF-I or IGFBP-3 are associated with estimated glomerular filtration rate (eGFR) in a population-based study of Caucasian adults.MethodsData from 4028 subjects (2048 women) aged 20 to 81 years from the Study of Health in Pomerania (SHIP) were analyzed. Total serum IGF-I and IGFBP-3 concentrations were determined by chemiluminescence immunoassays and categorized into sex- and age-specific quartiles.ResultsAfter adjusting for age, waist circumference and type 2 diabetes mellitus, analysis of variance (ANOVA) revealed inverse associations between serum IGF-I concentrations and eGFR in men as well as between serum IGFBP-3 concentrations and eGFR in men and women. Logistic regression analyses confirmed these findings and showed that high IGF-I or IGFBP-3 concentrations were associated with an increased risk of decreased eGFR (<60 mL/min/1.73 m2) in men or women. These relations became stronger when lower eGFR cut-offs were used for the analyses.ConclusionOur data revealed associations of increased serum IGF-I concentrations and decreased eGFR in men but not in women and an association of increased serum IGFBP-3 concentrations and decreased eGFR in both sexes.

Acute Effects of Blood Transfusion on Spermatogenesis and Pituitary Gonadal axis in Eugonadal Males with Beta Thalassemia Major (pilot study)

AbstractAbstract 1027 Objective:To evaluate semen parameters and measure serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and insulin-like growth factor-I (IGF-I) concentrations before and 7 days after packed red cell transfusion (PCTx) in young adults with thalassemia major (TM). Design:Prospective study. Setting, Patients, Interventions:We studied the effect of blood transfusion on semen parameters, the endocrine functions in 10 young adults with TM, aged from 17 to 32 years, with full pubertal development (Tanner’s stage 5) (euogonadal),and capacity to ejaculate. They were regularly transfused since early childhood and underwent chelation therapy using desferrioxamine which was replaced by deferasirox for the last 4 –5 years. At the time of the study their serum ferritin levels ranged from 500 to 5922 ng/ml (mean2686 ng/ml). Basal serum concentrations of FSH, LH, T and IGF-I were evaluated before and 7 days after packed red cell transfusion (PCTx). Main Outcome Measures and Results:After PCTx significant increase of Hb from 8.7 +/− 0.86 g/dl to 11.1 +/− 0.82 g/dl was associated with increased testosterone (from 16.5 +/− 8 nmol/L to 20 +/− 8.8 nmol/L, IGF-I (from 173 +/− 46ng/ml to 214 +/− 61ng/ml) and gonadotropins’ concentrations. Total sperm count increased significantly from 57.8 +/− 38.3 million/ml to 166 +/− 132 million/ml and rapid progressive sperm motility progressive motility increased from 20.6+/− 16.6 % to 79.7 +/− 67.4 %. After PCTx, LH concentrations were correlated significantly with T concentrations (r = 0.434, p < 0.001) and sperm volume and count (r = 0.439 and r = 0.376 respectively, p: 0.01). The increase of IGF-I concentration was correlated significantly with Hb level after PCTx (r = 0.535, p < 0.001) and negatively with ferritin concentration (r = −0.458, p < 0.001). Significant correlation were found between serum T concentrations and semen parameters before and after PCTx including sperm count (r = 0.658 and r = 0.73 respectively, p < 0.001)rapid progressive motility (r = 0.675 and r = 0.758 respectively p < 0.001), and the number of sperms with normal morphology (r = 0.752 and r = 0.834 respectively, p < 0.001) IGF-I levels and seminal parameters. No correlations were found between serum FSH and IGF-I concentrations and seminal parameters. Conclusion:Our study suggests that in thalassemic males blood transfusion is associated with significant acute enhancement of sperm parameters and with an increased concentrations of serum testosterone, LH, FSH and IGF-I. These “acute” effects on spermiogenesis are reached with an unknown mechanism/s and suggest a number of pathways that need further human and/or experimental studies.Table 1Hormonal and sperm data before versus after blood transfusion in thalassemic malesBeforeAfterP valuen = 10n = 10Hb (g/dl)8.7 +/− 0.8611.1 +/− 0.82 *0.000046LH (IU/L)2.5 +/− 1.653.8 +/− 1.87*0.049FSH (IU/L)3.3 +/− 2.454.4 +/− 2.27*0.008Testosterone (umol/L)16.5 +/− 820 +/− 8.8*0.0018Basal GH (ng/ml)0.88 +/− 1.3NDPeak GH (ng/ml) after clonidine6.7 +/− 2.66NDIGF-I (ug/L)173 +/− 46214 +/− 61*0.003Seminal parametersVolume (ml)1.65 +/− 0.782.1 +/− 0.58*0.0406Total sperm count (mil/ml)57.8 +/− 38.3166 +/− 132*0.0059Rapid progressive motility (%)23.9 +/− 15.364.9 +/− 12.6*0.0026Normal forms (%)41.7 +/− 17.648.3 +/− 12.4*0.045ND= not done.Table 2Correlations (R values) between serum testosterone level and sperm parameters before (1) and after (2) blood transfusionTestosterone (1)Testosterone (2)Sperm count (million/ml)10.660.73Volume (ml)10.430.47total PM (%) 10.680.76RPM (%) 10.690.71Normal morphology (%) 10.750.73Sperm count (million/ml)20.680.75Volume (ml)20.460.51Total PM 20.660.74RPM (%) 20.680.73Normal morphology (%) 20.750.83Abbreviations: TPM = Total progressive motility (%); RPM= Rapid Progressive motility (%); 1= before blood transfusion; 2 = after blood transfusion. Disclosures:Yassin:Hamad medical corporation MRC: Employment, Research Funding. Soliman:Hamad medical corporation MRC: Employment, Research Funding. Elawa:Hamad medical corporation MRC: Employment, Research Funding.

Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety

In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP. In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h. Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded. In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.

352 Longitudinal Infusion of Insulin-Like Growth Factor-I and Igf-Binding Protein-3 Complex to Five Preterm Infants - Pharmacokinetics and Short Term Safety

IntroductionIn preterm infants, low levels of insulin like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP).Treatment with IGF-I/IGFBP-3...

Biomarker detection of rhGH Doping: an excretion study

The purpose of this research is to validate the biomarker-based approach for the detection of doping with recombinant human growth hormone (rhGH) in sport. The GH-2000 project proposed an indirect method for the detection of exogenously administered growth hormone (GH) based on the measurement of the GH-dependent markers: insulin-like growth factor-I (IGF-I) and Type III pro-collagen (P-III-P). These markers rise in a dose-dependent manner after GH application. In this study, the concentrations of IGF-I, IGF-BP3, and P-III-P in serum were determined to provide further incentives for the implementation of this detection assay in modern anti-doping programmes. This paper reports on an administration study of rhGH involving 25 Chinese male volunteers at a dose of 0.1 IU /kg/day for a continuous 14-day period. We observed that the serum IGF-I concentration increased rapidly in the rhGH treatment group and showed significantly higher levels compared to baseline between days 4 and day 16 after administration. Although the response of P-III-P to rhGH administration was delayed compared to the IGF-I axis, the P-III-P concentration remained increased for a longer period (from day 4 to day 28). Statistical analysis was carried out to establish a discriminant formula with Statistical Product and Service Solutions (SPSS) concluding that the biomarker methodology is valid and universally applicable.

The pregnancy-associated plasma protein A and insulin-like growth factor system in response to cigarette smoking

Objective: Maternal smoking during pregnancy is associated with a reduction in birth size but the mechanism by which this occurs still remains unclear. The purpose of this study was to evaluate the effect of tobacco smoking on concentrations of pregnancy-associated plasma protein A (PAPP-A), insulin-like growth factor I (IGF-I), II (IGF-II) and binding proteins BP-3 and BP-4 in pregnant women and correlations between these parameters. Methods: Sixty healthy pregnant women were divided into smoking and tobacco-abstinent group according to results of serum cotinine concentration. The current smokers were defined as those who had smoked five or more cigarettes per day during pregnancy. Results: The mean serum concentrations of PAPP-A, IGF-I and IGF–II were significantly lower in smoking than in non-smoking pregnant women (p < 0.01). The level of PAPP-A correlated positively with the IGF-II concentration in both studied group (non-smoking: r = 0.54; p < 0.001; smoking: r = 0.40; p < 0.05). In tobacco-abstinent group negative correlation between IGF-II and IGFBP-4 concentrations was found (r = −0.35; p < 0.05). Conclusion: Tobacco smoking during pregnancy decreases the pregnancy-associated plasma protein A and insulin growth factors I and II levels. The correlation between PAPP-A and IGF-II may suggest function of this protein as a protease and regulator in the IGF system.

Female recruits sustaining stress fractures during military basic training demonstrate differential concentrations of circulating IGF-I system components: A preliminary study

ObjectiveStress fracture injuries sustained during military basic combat training (BT) are a significant problem and occur at a higher rate in female recruits than male recruits. Insulin-like growth factor-I (IGF-I) is an easily measured biomarker that is involved in bone formation and positively correlated with bone mineral density, especially in women. This study examined the response of the IGF-I system between female soldiers that sustained a stress fracture (SFX, n=13) during BT and female soldiers who did not (NSFX, n=49). DesignFemale soldiers (n=62, 18.8±0.6yr) from 2 companies of a gender-integrated combat battalion in the Israeli Defense Forces participated in this study. Height, weight and blood draws were taken upon entry to BT (preBT) and after a four-month BT program (postBT). Stress fractures were diagnosed by bone scan. Serum was analyzed for total IGF-I, free IGF-I, IGF binding proteins (IGFBP)1–6, BAP, calcium, CTx, IL1β, IL6, PINP, PTH, TNFα, TRAP, and 25(OH)D. Statistical differences between SFX and NSFX groups and time points were assessed by RM ANOVA with Fisher post-hoc (p≤0.05). ResultsThe SFX group was significantly taller and had lower BMI than NSFX (p≤0.05). Serum concentrations of total IGF-I, bioavailable IGF-I, other bone biomarkers, and cytokines were not significantly different between SFX and NSFX preBT. Serum IGFBP-2 and IGFBP-5 were significantly higher in the SFX compared to the NSFX preBT (p≤0.05). In both groups, total IGF-I increased pre to postBT (p≤0.05). Additionally, a significant difference was observed in the bioavailable IGF-I response pre to postBT for both groups. The SFX group demonstrated a significant decrease in bioavailable IGF-I pre to postBT (preBT: 0.58±0.58ng/mL; postBT 0.39±0.48; p≤0.05) whereas the NSFX group demonstrated a significant increase in bioavailable IGF-I pre to postBT (preBT: 0.53±0.37ng/mL; postBT: 0.63±0.45; p≤0.05). ConclusionsOur study demonstrated that serum IGF-I changes during basic training and that women sustaining stress fractures during BT significantly decreased bioavailable IGF-I, whereas their uninjured counter parts increased bioavailable IGF-I. These results suggest that stress fracture susceptibility may be related to differential IGF-I system concentrations and response to physical training.

Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age

BackgroundPrenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1) has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate pesticides. A common polymorphism, PON1 Q192R, affects both properties, but a potential interaction between PON1 genotype and pesticide exposure on cardiovascular risk factors has not been investigated. We explored if the PON1 Q192R genotype affects cardiovascular risk factors in school-age children prenatally exposed to pesticides.MethodsPregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype was determined for 141 children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex specific Z-scores.ResultsPrenatally pesticide exposed children carrying the PON1 192R-allele had higher abdominal circumference, body fat content, BMI Z-scores, blood pressure, and serum concentrations of leptin and IGF-I at school age than unexposed children. The effects were related to the prenatal exposure level. For children with the PON1 192QQ genotype, none of the variables was affected by prenatal pesticide exposure.ConclusionOur results indicate a gene-environment interaction between prenatal pesticide exposure and the PON1 gene. Only exposed children with the R-allele developed adverse cardiovascular risk profiles thought to be associated with the R-allele.

Maternal serum insulin-like growth factor (IGF-I) and binding proteins IGFBP-1 and IGFBP-3 at 11–13 weeks’ gestation in pregnancies delivering small for gestational age neonates

To 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 at 11-13 weeks' gestation in the prediction of small-for-gestational age (SGA) neonates. Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks were measured in 60 cases that subsequently delivered SGA neonates in the absence of pre-eclampsia, and compared to 120 non-SGA controls. In the SGA group, compared to the non-SGA group, there was significantly lower median IGF-I (61.8, IQR 43.4-93.4 ng/mL vs 94.9, IQR 56.7-131.2 ng/mL, p=0.002) and IGFBP-1 (58.2, IGR 39.8-84.9 ng/mL vs 81.4, IGR 57.3-105.5 ng/mL, p=0.002) but not IGFBP-3 (54.5, IGR 45.6-61.5 ng/mL vs 55.4, IGR 47.4-64.9 ng/mL, p=0.402). However, after multiple regression analysis and adjustment for maternal characteristics, these biomarkers were not useful in predicting SGA. Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks are unlikely to be useful biochemical markers for early prediction of SGA.

The association between insulin-like growth factor-I and cardiac repolarization

ObjectivePrevious studies reported associations between insulin-like growth factor I (IGF-I) serum concentration and cardiac morbidity and mortality, but the association between IGF-I serum concentration and cardiac repolarization has not been investigated in a population-based study so far. Therefore, we analyzed the impact of IGF-I concentrations on QTc, QT and RR intervals in two population based studies, The Study of Health in Pomerania (SHIP) and the Rotterdam Study. Design457 individuals from SHIP and 155 individuals from the Rotterdam Study older than 55years and without cardiovascular diseases and a left ventricular hypertrophy were investigated. IGF-I was determined by automated two-site chemiluminescence immunoassays and electrocardiograms were recorded by an ACTA electrocardiograph at a sampling frequency of 500Hz. The association of IGF-I with QTc, QT and RR intervals was investigated by multivariable linear regression analyses adjusted for age, gender, diabetes mellitus, myocardial infarction, hypertension, body mass index, serum potassium and calcium in both studies separately and in pooled analysis. ResultsThere were no significant associations between log-transformed IGF-I and QTc interval in the single populations, whereas a significant inverse association was detectable in the pooled population (β, −15.6; 95%-confidence interval, −25.7, −5.5). The QTc interval was significantly higher in the first tertile of IGF-I compared to the third tertile (β, 5.4; 95%-confidence interval, 9.5–1.3) in the pooled analysis. ConclusionThe inverse association between IGF-I serum concentrations and QTc interval in our study is suggestive of a higher risk for cardiac arrhythmias and thus might provide additional evidence for increased cardiovascular mortality in subjects with low IGF-I secretion.

Population Pharmacokinetic and Pharmacodynamic Modeling of Pegvisomant in Asian and Western Acromegaly Patients

Pegvisomant is a growth hormone (GH) receptor antagonist that normalizes insulin-like growth factor I (IGF-I) levels in patients with acromegaly. Although the dose of pegvisomant is determined by the IGF-I level, the pharmacokinetic and pharmacodynamic (PK/PD) model for pegvisomant concentration and IGF-I reduction has not been established. This study was conducted to characterize PK/PD of pegvisomant, and to determine the influence of covariates on the pegvisomant PK/PD. Based on the data from 5 phase III studies in 168 acromegaly patients, models were developed to characterize the PK/PD of pegvisomant. The PD variables were IGF-I serum concentrations. The modeling was performed with a nonlinear mixed-effects approach using NONMEM. After subcutaneous dosing, the PK of pegvisomant was described by a steady state PK model with dose- dependent clearance. Baseline GH and age were significant covariates for the clearance. A sigmoid E(max) model adequately described the relationship between IGF-I and pegvisomant concentrations. Baseline GH was found to be a significant covariate for the baseline effect (E(0)) and IC(50). The PK/PD properties of pegvisomant were not significantly different between Asian and Western patients.

Reference values for serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in Korean children and adolescents

ObjectiveMeasurements of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) are utilized in the diagnostic work-up and clinical management of children with growth disorders. We designed this study to establish the reference values of serum IGF-I and IGFBP-3 levels according to age, sex and pubertal stage in Korean children and adolescents. MethodsFor the study, 1378 healthy Korean children and adolescents aged 0 to 17years (722 boys, 656 girls) were randomly selected. Blood samples were collected, and the stored sera were assayed for IGF-I and IGFBP-3 using immunoradiometric assay (IRMA, Immunotech). The R 2.8.1 program (Bell Laboratories) was used to generate reference percentile curves for IGF-I and IGFBP-3 according to age, sex, and pubertal stage ResultsSerum IGFBP-3 level was higher in girls compared to that in boys of the same ages throughout the pubertal period, whereas IGF-I was only higher for girls younger than 13years of age. Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal stage, followed by a progressive decline thereafter. Peak levels of serum IGF-I and IGFBP-3 were observed two years earlier in girls compared to those in boys (13 vs. 15years of age, respectively). Serum IGF-I and IGFBP-3 concentrations were highest at Tanner stage IV in boys and girls, with a subsequent decline. ConclusionsOur reference value model based on age, sex, and pubertal stage can improve the diagnostic utility of IGF-1 and IGFBP-3 levels in the evaluation and management of Korean children and adolescents with growth disorders.

Molecular cloning, expression analysis of insulin-like growth factor I (IGF-I) gene and IGF-I serum concentration in female and male Tongue sole (Cynoglossus semilaevis)

Insulin-like growth factor I (IGF-I) is a polypeptide hormone that regulates growth during all stages of development in vertebrates. To examine the mechanisms of the sexual growth dimorphism in the Tongue sole (Cynoglossus semilaevis), molecular cloning, expression analysis of IGF-I gene and IGF-I serum concentration analysis were performed. As a result, the IGF-I cDNA sequence is 911 bp, which contains an open reading frame (ORF) of 564 bp encoding a protein of 187 amino acids. The sex-specific tissue expression was analyzed by using 14 tissues from females, normal males and extra-large male adults. The IGF-I mRNA was predominantly expressed in liver, and the IGF-I expression levels in females and extra-large males were 1.9 and 10.2 times as much as those in normal males, respectively. Sex differences in IGF-I mRNA expressions at early life stages were also examined by using a full-sib family of C. semilaevis, and the IGF-I mRNA was detected at all of the 27 sampling points from 10 to 410 days old. An increase in IGF-I mRNA was detected after 190 day old fish. The significantly higher levels of IGF-I mRNA in females were observed after 190 days old in comparison with males (P<0.01). The IGF-I concentrations in serum of mature individuals were detected by ELISA. The IGF-I level in the serum of females was approximately two times as much as that of males. Consequently, IGF-I may play an important role in the endocrine regulation of the sexually dimorphic growth of C. semilaevis.

Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels with risk of malignant melanoma

We examined the relationship of insulin-like growth factor-I (IGF-I) and its primary growth factor, IGF binding protein-3 (IGFBP-3) with malignant melanoma using interview data and sera from cases (n = 286) and controls (n = 289) in a population-based case-control study conducted in 1986-1992 on Oahu, Hawaii. Serum IGF-I and IGFBP-3 concentrations were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression and adjusting for age, sex, education, number of blistering sunburns, ability to tan, hair color, energy intake, BMI, height, smoking status, and drinking status. An inverse relationship was found between IGF-I concentration and melanoma (OR for upper vs. lower tertile: 0.44, 95% CI: 0.25-0.79), but clear associations were not observed between malignant melanoma and upper tertiles of IGFBP-3 and the IGF-1/IGFBP-3 molar ratio. The inverse association with IGF-I was strongest among subjects who did not report a history of non-melanoma skin cancer (NMSC) (OR for ≥ vs. < median: 0.39, 95% CI: 0.24-0.65), and a positive association was found among those with such a history (OR: 3.6, 95% CI: 1.0-13; p (interaction) = 0.0035). Our findings observed here between serum IGF-I and malignant melanoma warrants replication in studies with a larger sample size and a prospective design.

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.

Association between linear growth patterns with serum insulin levels in pre-pubertal children born small for gestational age

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 6 year group.Conclusions Insulin as a growth factor may participate in postnatal catch-up growth accompanied with increased insulin resistance in SGA children. Key words: Catch-up growth; Insulin resistance; Small for gestational age

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.

Bone quality and vitamin K2 in type 2 diabetes: Review of preclinical and clinical studies

Type 2 diabetic patients are at high risk of bone fractures even if their bone mineral density is normal or high. This is likely explained by poor bone quality and extraskeletal factors. The present review was conducted to provide an overview of the currently available preclinical and clinical evidence on the effect of vitamin K(2) on bone quality in persons with type 2 diabetes. Vitamin K(2) stimulates γ-carboxylation of osteocalcin and can increase bone formation through steroid and xenobiotic receptors. Clinical studies of type 2 diabetic patients have shown detrimental collagen cross-links in bone; low serum insulin-like growth factor-I and osteocalcin concentration are associated with an increased risk of fractures. A therapeutic strategy for preventing fractures in type 2 diabetic patients remains to be established. One recent preclinical study showed that vitamin K(2) administration in a type 2 diabetic rat model had the following skeletal benefits: increased serum osteocalcin, improved collagen cross-link profiles, and increased bone strength. These new findings suggesting a possible beneficial effect of vitamin K(2) supplementation on bone quality in type 2 diabetes warrant further investigation.

Progesterone and Insulin‐Like Growth Factor I Levels in Blood of Boer Goats During Puerperium Out‐of‐Season in a Mild Climate Region

The aims of this study were to compare insulin-like growth factor-I (IGF-I) and progesterone concentrations as indicators of cycle activity in the blood of Boer goats during puerperium out-of-season in mild climate conditions and to investigate the influence of parity and litter size on the concentration of IGF-I and progesterone in serum during the study period. Twenty Boer (8 primiparous and 12 pluriparous) goats were examined in this study. Blood samples were taken every 4 days starting on the 3rd day and up to the 40th day of puerperium. IGF-I and progesterone (P4) blood levels were determined using radio immune assay (RIA). Results indicated cyclic ovarian activity outside the breeding season in 18 of 20 Boer goats. IGF-I levels in blood sera followed oestrus and cyclic ovarian activity. IGF-I concentrations correlated significantly with P4 concentrations. The IGF-I peak preceded the P4 peak by approximately 8 days in cycling goats. IGF-I and P4 blood levels were not influenced by parity or litter size. Changes in blood serum P4 and IGF-I concentrations levels during puerperal period can assist in the evaluation of reproductive status of goats.

Chronic supplementation of beta-hydroxy-beta methylbutyrate (HMβ) increases the activity of the GH/IGF-I axis and induces hyperinsulinemia in rats

Objective Beta-hydroxy-beta-methylbutyrate (HMβ) is a metabolite of leucine widely used for improving sports performance. Although HMβ is recognized to promote anabolic or anti-catabolic effects on protein metabolism, the impact of its long-term use on skeletal muscle and/or genes that control the skeletal protein balance is not fully known. This study aimed to investigate whether chronic HMβ treatment affects the activity of GH/IGF-I axis and skeletal muscle IGF-I and myostatin mRNA expression. Design Rats were treated with HMβ (320 mg/kg BW) or vehicle, by gavage, for 4 weeks, and killed by decapitation. Blood was collected for evaluation of serum insulin, glucose and IGF-I concentrations. Samples of pituitary, liver, extensor digitorum longus (EDL) and soleus muscles were collected for total RNA or protein extraction to evaluate the expression of pituitary growth hormone (GH) gene (mRNA and protein), hepatic insulin-like growth factor I (IGF-I) mRNA, skeletal muscle IGF-I and myostatin mRNA by Northern blotting/real time-PCR, or Western blotting. Results Chronic HMβ treatment increased the content of pituitary GH mRNA and GH, hepatic IGF-I mRNA and serum IGF-I concentration. No changes were detected on skeletal muscle IGF-I and myostatin mRNA expression. However, the HMβ-treated rats although normoglycemic, exhibited hyperinsulinemia. Conclusions The data presented herein extend the body of evidence on the potential role of HMβ-treatment in stimulating GH/IGF-I axis activity. In spite of this effect, HMβ supplementation also induces an apparent insulin resistance state which might limit the beneficial aspects of the former results, at least in rats under normal nutritional status and health conditions.