Serum IGFBP-3 Levels Research Articles

IGF-1 and IGFBP-3 serum concentrations in patients undergoing programmed frozen-thawed embryo transfer of euploid PGT-A embryos

IGF-1 has been shown to induce embryonic development in vitro, but at high concentrations exhibits toxic effects by decreasing embryonic glucose uptake. IGFBP-3 binds IGF-1, modulating its bioavailability and is essential to its function. Prior reports have associated elevated follicular phase IGF-1 with pregnancy loss in frozen-thawed embryo transfer in natural cycles (n-FET), but an association in programmed (p-FET) cycles or in the luteal phase has not been analyzed. We sought to determine whether serum levels of IGF-1 and IGFBP-3 correlate with the outcome of p-FET cycles. Retrospective cohort study. Patients who underwent p-FET of single, good quality (Grade ≥2BB), PGT-normal embryos were included in the study. GnRH-agonist suppression was started in the preceding luteal phase, overlapped with estradiol patches, and stopped with the start of progesterone. Serum samples were collected on cycle day 2 (CD2), the day of progesterone start (CDP4), and cycle days 28 (CD28) and 30 (CD30). Embryo transfer occurred on the 7th day of P4 administration. Serum levels of IGF-1 and IGFBP-3 were compared between those who did not achieve pregnancy, those who had a live birth, and those who had a pregnancy loss. Serum IGF-1 and IGFBP-3 levels were measured by chemiluminescent immunoassays using the Immulite 2000 XPi. Statistical analysis was performed using Chi-square and Fisher’s exact test. P<0.05 was deemed statistically significant. A total of 102 patients who underwent p-FET of single euploid embryos over 2 years were analyzed. The mean age at retrieval was 35.7 ± 4.1 years, BMI 24.2 ± 4.8 kg/m2, gravity 1.8 ± 1.6, parity 0.4 ± 0.6 and peak endometrial thickness 9.7 ± 2.0 mm. 76.5% of patients were pregnant and 78.2% of those had a live birth. Among women who conceived, those who had a subsequent pregnancy loss had significantly higher serum IGF-1 levels on CDP4 and CD28 compared to those who achieved live birth when analyzing patients whose serum IGF-1 levels were above the mean value of IGF-1 level on CDP4 (136 ng/ml, p= 0.044) and CD28 (138 ng/ml, p=0.007), and between patients with CD28 IGF-1 levels one standard deviation above the mean (≥160 ng/ml, p=0.007). There was no significant difference in the serum levels of IGFBP-3 in any of the treatment cycle days.Tabled 1p-FET, Deliveredp-FET, Pregnancy losspIGF-1 CDP4 (≥ mean value)63.6%33%0.044IGF-1 CD 28(≥ mean value)58%14%0.044IGF-1 CD28 (≥ 160 ng/ml)70.8%14%0.007 Open table in a new tab In p-FET cycles with transfer of a single, euploid, high quality embryo, IGF-1 serum levels on day of progesterone start and CD28 are significantly higher in patients who subsequently had a pregnancy loss compared to those who had a live birth. This is in contrast to the findings of prior studies in n-FET.

The Eff ect of resistance training and growth hormone injection on circulating IGF-1 and IGFBP-3 levels in a rat model

Growth hormone has mitotic and anti-apoptotic effects which may increase proliferation and transformation of cells when it is expressed aberrantly. This study investigated the effects of resistance training and growth hormone injection on circulating IGF-1, IGFBP-3 levels and IGF-1/IGFBP-3 ratio in male Wistar rats. Thirty-two male Wistar rats were randomly assigned to a control group (C, n = 8), a resistance training group (RT, n = 8), a growth hormone injection group (GI, n = 8) and a resistance training + growth hormone injection group (RG, n = 8). The resistance training protocol comprised of climbing a ladder (5 days/week, 3 sets/5 reps) while carrying a weight suspended from the tail. The growth hormone (2 mg/kg/day, 5 days/week) was injected before an exercise session. Serum IGF-1, IGFBP-3 levels, and IGF-1/IGFBP-3 ratio were measured after 8 weeks. One-way ANOVA analysis was used for comparison of serum IGF-1 and IGFBP-3 levels between groups. Serum IGF-1 levels and IGF-1/IGFBP-3 ratio signifi cantly decreased, but serum IGFBP-3 levels showed no significant change in the RT group compared to the C group. Also, both serum IGF-1 and IGFBP-3 levels and IGF-1/IGFBP-3 ratio in GI and RG groups significantly increased compared to the other groups. In conclusion, resistance training decreases serum IGF-1 levels and/or IGF-1/IGFBP-3 ratio in normal condition. On the other hand, the growth hormone injection with and without the resistance training increases serum IGF-1 levels and IGF-1/IGFBP-3 ratio which could be noted as a condition with a higher risk of neoplasm.

The levonorgestrel-releasing intrauterine device induces endometrial decidualisation in women on tamoxifen

There is conflicting literature on whether the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena®) induces decidualisation in the tamoxifen-treated endometrium. The expression of the decidualisation marker IGFBP-1 was measured using immunohistochemistry in endometrial biopsies and in serum (using ELISA) of 20 postmenopausal women at the start of tamoxifen-treatment for breast cancer. Ten women were then fitted with LNG-IUS and the other ten received tamoxifen-treatment only and acted as controls. Samples were taken at baseline and after 12 months. At baseline, all endometrial samples were negative for IGFBP-1 and at 12 months, IGFBP-1 was only expressed in the endometria of women fitted with the LNG-IUS, confirming the observed histological features of decidualisation. By contrast, serum IGFBP-1 concentrations were increased by tamoxifen, but not in the group receiving LNG-IUS. In conclusion, tamoxifen induces a rise in serum IGFBP-1 suggesting a systemic, possibly hepatic effect, whilst LNG abrogates this in both the liver and endometrium.Impact statementWhat is already known on this subject? Previous reports of the use of LNG-IUS in women on tamoxifen have provided conflicting evidence as to whether the endometrium exhibited decidualisation or not. These reports were however based solely on histological examination and lacked supporting biochemical data.What do the results of this study add? After 12 months of treatment with LNG-IUS, the endometria of women on tamoxifen show histological features of decidualisation and the presence of the decidualisation marker IGFBP-1, suggesting that levonorgestrel protects the tamoxifen-treated uterus from additional pathology by causing decidualisation. Serum levels of IGFBP-1 were expected to be a reflection of uterine production, but contrary to expectations, higher levels were identified in women on tamoxifen alone. These data suggest that an inhibition of tamoxifen-induced serum IGFBP-1 production (possibly from a hepatic source) by LNG-IUS occurred and indicates independent systemic effects of both drugs in post menopausal breast cancer patients.What are the implications of these findings for clinical practice and/or further research? This research demonstrated a mechanism for endometrial protection in women on tamoxifen. It also alerts clinicians to the fact that both tamoxifen and LNG-IUS exert systemic effects in this patient group.

The Impact of Combined (Aerobic-resistance) Training on Serum Levels of IGF-I and IGFBP-3 in Men with Prostate Cancer

The Impact of Combined (Aerobic-resistance) Training on Serum Levels of IGF-I and IGFBP-3 in Men with Prostate Cancer

Prevalence of growth hormone (GH) deficiency in previously GH-treated young adults with Prader-Willi syndrome.

ObjectiveSome features of subjects with Prader‐Willi syndrome (PWS) resemble those seen in growth hormone deficiency (GHD). Children with PWS are treated with growth hormone (GH), which has substantially changed their phenotype. Currently, young adults with PWS must discontinue GH after attainment of adult height when they do not fulfil the criteria of adult GHD. Limited information is available about the prevalence of GHD in adults with PWS. This study aimed to investigate the GH/insulin‐like growth factor (IGF‐I) axis and the prevalence of GHD in previously GH‐treated young adults with PWS.DesignCross‐sectional study in 60 young adults with PWS.MeasurementsSerum IGF‐I and IGFBP‐3 levels, GH peak during combined growth hormone‐releasing hormone (GHRH)‐arginine stimulation test.ResultsSerum IGF‐I was <−2 standard deviation scores (SDS) in 2 (3%) patients, and IGFBP‐3 was within the normal range in all but one patient. Median (IQR) GH peak was 17.8 μg/L (12.2; 29.7) [~53.4 mU/L] and below 9 μg/L in 9 (15%) patients. Not one patient fulfilled the criteria for adult GHD (GH peak < 9 μg/L and IGF‐I < −2 SDS), also when BMI‐dependent criteria were used. A higher BMI and a higher fat mass percentage were significantly associated with a lower GH peak. There was no significant difference in GH peak between patients with a deletion or a maternal uniparental disomy (mUPD).ConclusionsIn a large group of previously GH‐treated young adults with PWS, approximately 1 in 7 exhibited a GH peak <9 μg/L during a GHRH‐arginine test. However, none of the patients fulfilled the consensus criteria for adult GHD.

SUN-245 Heterozygous GH1 p.R209H Variant within a Large Pedigree May Mimic a Growth Hormone Insensitivity Pattern

Isolated growth hormone deficiency (IGHD) is most frequently caused by mutations in the GH1 gene. Pathogenic mutations in the GHRHR and GHSR have also been reported to cause IGHD. Individuals with IGHD type II present with variable clinical phenotype. Autosomal dominant GH1 p.R209H variant impairs GH secretion despite normal GH synthesis. The aim of this work is to expand the clinical and biochemical phenotype of heterozygous GH1 p.R209H missense mutation (previously known as p.R183H) in a large Argentinean pedigree. We report a non-consanguineous 4 generation pedigree. Two affected members showed classical IGHD phenotype: short stature (height -4.13 and -2.6 SD), low GH peak after arginine/clonidine provocative tests (3.6 and 2.6 ng/ml, cut-off value 4.7 ng/ml, GH IS 98/574, Immulite), non-detectable IGF-1, and low IGFBP-3 (-2.83 and -2.28 SD). Brain MRI showed anterior pituitary gland of 3.3 mm and 2.5 mm, respectively. The use of a customized panel for congenital hypopituitarism using single molecule molecular inversion probes sequencing (smMIPS) revealed a c.626G>A transition in GH1 gene, predicted to result in p.R209H mutation. The variant was subsequently confirmed by Sanger sequencing. Parents affected with the same variant presented either short (-1.91 SDS) or normal stature (-0.72 SDS). The patients’ response to rhGH treatment was adequate (Δ heights were 2.49 and 1.37 SDS in 2.4 and 1.0 year of treatment, respectively). Additionally, 4/9 siblings within this pedigree had short stature (mean height -2.48 ± 0.62 SD) with mild or no clinical phenotype of GHD, normal GH response to provocative pharmacologic tests (maximum GH peaks 5.46 to 10.9 ng/ml), associated to low serum IGF-1 (mean -3.27 ± 0.89 SD) and IGFBP3 (mean -2.61 ± 0.42 SD), resembling a pattern of growth hormone insensitivity (GHI). IGF-1 generation tests (GH dose 33 µg/kg.day) showed a mean increment in IGF-1 of 3.25 times over basal, confirming adequate GH sensitivity. Despite the absence of complete GHD phenotype, data from the extended pedigree suggested GH1 as the initial candidate gene, identifying the same pathogenic GH1 variant in these four siblings. Brain MRI showed normal height of the anterior pituitary gland (range 3.9 to 4.6 mm). Their affected father had normal stature (-1.69 SDS) with low serum IGF-1 (64 ng/mL). We have shown that members of a large pedigree affected with the p.R209H GH1 variant showed either a classical clinical and biochemical pattern of GHD or an initial biochemical pattern resembling GHI. This variability could lead in certain cases to an elusive diagnosis of GHD when the classical phenotype is absent. Therefore, these results highlight the need to explore GH1 gene in children with short stature associated to low IGF-1 and IGFBP-3 serum levels even when GH response to pharmacological tests is normal.

Prevalence of low lean mass in patients with adult growth hormone deficiency with or without low-dose growth hormone therapy.

The importance of muscle mass has been emphasized in various studies, and growth hormone (GH) deficiency is tightly associated with lean mass loss. Therefore, we aimed to investigate the prevalence of low lean mass in patients with adult growth hormone deficiency (AGHD) who received or did not receive GH therapy. In this retrospective study, we included patients diagnosed with AGHD by using the insulin tolerance test (ITT) in our hospital. Patients without completed follow-up data were excluded, and data for 56 patients were analysed. Twenty-six patients who had received GH therapy for more than 6months, based on the medical record, were included in the GH group and received recombinant human growth hormone (rhGH) at a dose of 0.5IU/d. Thirty patients who had not previously received GH treatment were included in the non-GH group. Many anthropometric and blood biochemical indicators were measured. Body composition was measured on a dual-energy X-ray-absorptiometry (DXA) scanner. Low lean mass was defined as a skeletal muscle index (SMI) <7.0kg/m2 in males or 5.7kg/m2 in females. Statistical analyses were performed using GraphPad Prism 5.0. Compared to the non-GH group, the patients who received GH therapy had significantly lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and fasting plasma glucose (FPG). The percentage of patients with low lean mass in GH and non-GH groups was 30.77% and 60%, respectively. The percentage of total lean was lower in the GH group than in the non-GH group, but the difference in total lean mass was not statistically significant. Conversely, patients with GH treatment had significantly lower fat mass and percentage than non-GH-treated patients (P<0.05). The GH group had significantly higher serum levels of both IGF-1 and IGFBP3. Moreover, both IGF-1 and IGFBP3 were significantly correlated with SMI (r2 =0.275, P=0.003, and r2 =0.138, P=0.005, respectively). Our data showed that AGHD patients who received low-dose GH treatment had a lower prevalence of low lean mass than those who did not receive GH treatment. Patients with GH treatment had significantly lower cardiovascular risk factors, especially the lipid profile.

The Impact of Combined (Aerobic-resistance) Training on Serum Levels of IGF-I and IGFBP-3 in Men with Prostate Cancer

The Impact of Combined (Aerobic-resistance) Training on Serum Levels of IGF-I and IGFBP-3 in Men with Prostate Cancer

IGFBP-2 and aging: a 20-year longitudinal study on IGFBP-2, IGF-I, BMI, insulin sensitivity and mortality in an aging population

Objective Insulin-like growth factor-binding protein-2 (IGFBP-2) concentrations are low in subjects with metabolic syndrome and type 2 diabetes. Intriguingly, recent studies have demonstrated an association between high IGFBP-2 concentrations and increased mortality not only in populations with certain types of cancer, but also in relatively healthy populations. We evaluated the role of IGFBP-2 in relation to BMI and mortality. Design and Participants BMI, insulin sensitivity, insulin-like growth factor 1 (IGF-I) and IGFBP-2 were assessed repeatedly in 539 participants of the Baltimore Longitudinal Study of Aging around the ages of 55, 65 and 75 years. Results IGFBP-2 concentrations positively correlated with insulin sensitivity and inversely with BMI, both at baseline and follow-up. Independent of IGF-I, sex, BMI and insulin sensitivity, circulating IGFBP-2 levels positively correlated with age (P < 0.001). Changes over time in BMI were associated with an inverse correlation in IGFBP-2 concentrations. Furthermore, we found indications of a relationship between low baseline IGFBP-2 levels and mortality. Remarkably, after adjustment for insulin sensitivity, the opposite association was found, as a unit increase of log(IGFBP2) was associated with an increase in the log hazard by 1.43 (95% CI: 0.3-2.6). This accounted for both baseline (P = 0.02) as well as serial (P < 0.001) measurements of IGFBP2. Finally, in this longitudinal study, we found that IGF-I concentrations increased with age (0.82 ± 0.2 (µg/L)/year, P < 0.001). Conclusion This is the first study investigating the relationship between IGFBP-2 levels and age in a longitudinal setting. Serum IGFBP-2 levels increase with age after the age of 50 years and evolve in parallel with insulin sensitivity. IGFBP-2 may therefore be a potential marker for insulin sensitivity. We further show that IGFBP-2 levels can predict mortality in this aging population. However, its predictive value for mortality can only be interpreted in relation to insulin sensitivity. After adjustment for insulin sensitivity, high IGFBP-2 levels are predictive of increased mortality.

The insulin-like growth factor family and breast cancer prognosis: A prospective cohort study among postmenopausal women in Denmark

ObjectiveCirculating levels of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have been associated with breast cancer (BC) risk. The evidence in relation to BC prognosis is limited. We aimed to evaluate the association between pre-diagnostic serum levels of IGF-I, IGF-II, IGFBP-2, IGFBP-3 and BC prognosis (i.e. recurrence, BC specific mortality and all-cause mortality) among women diagnosed with BC. We hypothesized that higher serum levels of IGFs and IGFBPs were associated with poor BC prognosis and that the associations were modified by estrogen receptor (ER) status. DesignFrom the Danish Diet, Cancer and Health cohort, 412 postmenopausal women diagnosed with incident BC within 5 years of cohort baseline (1993–1997) were identified. Baseline serum samples were analyzed for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Follow-up was carried out through 2014 by linkage to national Danish registries. Exposures were related to BC prognosis by Cox Proportional Hazard models; effect modification by ER status was investigated and sensitivity analyses by follow-up time were made. ResultsDuring a median of 15 years, 106 women experienced recurrence and 172 died (118 due to BC). Overall, no associations were observed between IGF-I, IGF-II, IGFBP-2, IGFBP-3 and BC prognosis and no effect modification by ER status was observed. However, higher levels of IGF-II were associated with higher BC specific mortality [Hazard Ratio (HR) (95% Confidence Intervals (CI)): 1.43 (1.01–2.04)] within 10 years of follow-up. Likewise, higher levels of IGFBP-2 were associated with higher BC specific mortality [HR (95% CI): 1.87 (1.19–2.94)] within 5 years of follow-up. In contrast, higher levels of IGFBP-3 were associated with lower risk of recurrence [HR (95% CI): 0.76 (0.60–0.97)] at 5 years of follow-up and BC specific mortality [HR (95% CI): 0.80 (0.65–0.98)] within 10 years of follow-up. ConclusionsThe present study did not support an association between higher serum levels of IGFs, IGFBPs and adverse BC prognosis. However, it is possible that the role of the IGF family in the etiology of the 5–10 year BC prognosis is different from that of longer-term BC prognosis.

Abstract 3725: Pre-clinical evaluation of prostate specific membrane antigen (PSMA) nanobioconjugate encapsulating green tea polyphenol EGCG for prostate cancer

Abstract For prostate cancer green tea constituent (-)-epigallocatechin-3-gallate (EGCG) has shown promise in preclinical, geographical and epidemiological studies and more importantly in many clinical trials. However, concerns related to stability, poor intestinal absorption and extensive systemic and enteric metabolism have hampered its use in the clinic. We introduced the idea of nanotechnology to enhance the outcome of chemoprevention with EGCG and coined the term ‘Nanochemoprevention' and later reported the efficacy of chitosan nanoparticles encapsulating EGCG for PCa prevention and therapy. Here, we evaluated an aptamer conjugated prostate targeting nanobioconjugate encapsulating EGCG in two relevant pre-clinical mouse models of human PCa. We developed chitosan nanobioconjugates encapsulating EGCG, surface functionalized with the A10 2′-fluoropyrimidine RNA aptamers that recognize the extracellular domain of the prostate specific membrane antigen (PSMA), henceforth called chit-EGCG-Apt. Mice implanted with androgen sensitive CWR22Rν1 cells and treated with Chit-EGCG-Apt showed significant inhibition in tumor growth that was also associated with decreased serum PSA levels as compared to native EGCG. Tumor tissues from mice treated with Chit-EGCG-Apt exhibited significant (i) induction of PARP cleavage, (ii) increase in the protein expression of Bax with concomitant decrease in Bcl-2, (iii) activation of caspases and (iv) reduction in Ki-67 and PCNA. We further observed inhibition of markers of angiogenesis, invasion and metastasis in tumor tissues in these mice. We next evaluated the efficacy of Chit-EGCG-Apt in the prostate specific Pten knockout mouse model that recapitulates disease progression as seen in humans. Longitudinal MRI analysis suggested significant inhibition of PCa development and tumor growth in these mice. We observed a significant inhibition in tumor growth as evaluated by genitourinary and prostate tissue weight. We further observed a significant decrease in serum IGF-I levels with concomitant increase in serum IGFBP-3 levels in these mice. We analyzed tumor tissues isolated from the mice and observed significant (i) induction of apoptosis, (ii) modulation of Pten/PI3K/Akt, MAPK pathway, IGF-1 signaling and iii) inhibition of markers associated with angiogenesis, invasion and metastasis. These data support our hypothesis that target-specific nanobioconjugates enhance efficacy through boosting bioavailability, thus leading to a significant potential for possible clinical outcome. Targeted nano-encapsulation approach could be viewed as “precision chemoprevention” for PCa patients that are considered low-risk and put on active surveillance. Citation Format: Imtiaz A. Siddiqui, Vaqar M. Adhami, Islam Rady, Hasan Mukhtar. Pre-clinical evaluation of prostate specific membrane antigen (PSMA) nanobioconjugate encapsulating green tea polyphenol EGCG for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3725.

Association between IGF1/IGFBP3 with Lipid Metabolism and Chronic Low-Grade Inflammation and Alteration after Laparoscopic Sleeve Gastrectomy in Chinese Obese Subjects

Some studies have demonstrated the disturbance of IGF1/IGFBP3 axis in endocrine-metabolic diseases. We aimed to investigate the association between IGF1/IGFBP3 with glucose-lipid metabolism and chronic low-grade inflammation and the changes after laparoscopic sleeve gastrectomy (LSG) in Chinese obese patients. Thirty-six obese subjects were enrolled. Anthropometric data, routine laboratory biochemical parameters and IGF1/IGFBP3 levels were evaluated at baseline and 3 months after LSG. Serum total IGF1 and IGFBP3 levels were measured by enzyme-link immunosorbent assay and molar ratio of IGF1/IGFBP3 is represented as free IGF1 levels. In all subjects, total IGF1 was positively correlated with HDL-c (P&amp;lt;0.05), negatively with weight, BMI, waistline, hipline, waist/hip ratio, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) (P&amp;lt;0.or P&amp;lt;0.01). Free IGF1 was negatively correlated with hipline, triglyceride (TG), CRP and TNF-α (P&amp;lt;0.or P&amp;lt;0.01). IGFBP3 was positively correlated with TG and free fatty acids (FFA) (P&amp;lt;0.or P&amp;lt;0.01). Both total IGF1 and IGFBP3 levels were significantly decreased after LSG (from 166.54±64.44ng/ml to 143.02±69.09ng/ml, P=0.048 and from 2556.54±756.99ng/ml to 2051.89±618.61ng/ml, P&amp;lt;0.001, respectively, and more reduction in IGFBP3 levels of 19.74%), while an increased tendency of free IGF1 levels was observed. In addition, changes of total IGF1/free IGF1 were negatively related to changes of CRP and TNF-α (P&amp;lt;0.or P&amp;lt;0.01), and change of IGFBP3 was positively related to change of FFA (P&amp;lt;0.05). In conclusion, the IGF1/IGFBP3 axis is closely associated with lipid metabolism and chronic low-grade inflammation in Chinese obese patients. Decreased IGFBP3 and increased free IGF1 may partly account for the improved lipid metabolic and chronic low-grade inflammatory profiles after LSG. Disclosure L. Li: None. X. Wang: None. J. Gao: None. S. Qu: None.

Effects of Astragalus Extract Mixture HT042 on Height Growth in Children with Mild Short Stature: A Multicenter Randomized Controlled Trial.

HT042 is a standardized functional food ingredient approved by Korean Food and Drug Administration with a claim 'HT042 can help height growth of children'. We aimed to evaluate the safety and efficacy of HT042 on height growth in children with mild short stature. A multicenter, randomized, double-blind, placebo-controlled parallel study was performed on children aged 6-8years with height ranked below the 25th percentile. In 129 children, height gain was significantly higher in HT042 group than placebo group after 24weeks (mean difference, 0.29cm; 95% CI, 0.01 to 0.57cm; p=0.027). The difference was elevated when the efficacy analysis was restricted to children below the 10th percentile (mean difference, 0.45cm; 95% CI, 0.04 to 0.87cm; p=0.031). Because bone age advancement was lower in HT042 group, height standard deviation score gain for bone age was higher in HT042 group and the difference was significant in children below the 10th percentile (mean difference, 0.20 score; 95% CI, 0.00 to 0.39 points; p=0.045). Serum IGF-1 and IGFBP-3 levels were significantly increased compared with baseline within HT042 group, but group difference was not significant. HT042 supplementation helped to increase height growth in children without skeletal maturation and was more effective in much shorter children. The effects might be mediated by increases in serum IGF-1 and IGFBP-3 levels. Copyright © 2017 John Wiley & Sons, Ltd.

IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD – a pilot study

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. Advanced fibrosis (stage 3–4) is the most robust marker for future mortality, but diagnosis requires liver biopsy. Current non-invasive scoring systems aimed to identify advanced fibrosis are imperfect. Insulin-like growth factor I (IGF-I) and its binding protein IGFBP-1 are liver derived proteins, that are involved in various liver disorders. The aim of this study was to examine the possible association between advanced fibrosis and IGF-I and IGFBP-1 in NAFLD.Methods: Fasting blood samples were obtained from 52 patients diagnosed with NAFLD by liver biopsy. Total IGF-I and IGFBP-1 concentrations were determined in serum by in-house radio-immuno-assays. IGF-I levels were age-standardized (IGF-SD). A logistic regression model was used to investigate the association of IGF-SD and IGFBP-1 with advanced fibrosis (stage 3–4).Results: Patients with advanced fibrosis (stage 3–4 vs. 0–2) had lower IGF-SD (−1.17 vs. 0.11, p = .01) and higher mean levels of IGFBP-1 (29.9 vs. 18.8 µg/l, p = .02). IGFBP-1 was associated with presence of advanced fibrosis (OR 1.04 per unit increase, 95%CI 1.0–1.07, p = .05), while IGF-1 was negatively associated with advanced fibrosis (OR 0.63 per standard deviation, 95%CI 0.44–0.92, p = .02).Conclusions: This pilot study suggests an association between serum IGFBP-1 and IGF-I levels with advanced fibrosis in NAFLD patients. IGFBP1 and IGF-1 could be of interest as future biomarkers. Similar studies in larger cohorts are needed.

Association study of IGFBP1 and IGFBP3 polymorphisms with hypertension and cardio-cerebral vascular diseases in a Chinese Han population

Previous studies have showed that insulin-like growth factor (IGF) axis is involved in the development of hypertension. It is unclear whether genetic variants in the IGF-binding proteins (IGFBPs) contribute to the susceptibility to hypertension. Three single-nucleotide polymorphisms (SNPs) in IGFBP1 and four SNPs in IGFBP3 were selected for genotyping in 2,012 hypertension cases and 2,210 healthy controls and 4,128 subjects were followed up for a median of 5.01 years. Multiple logistic regression and Cox regression were performed to evaluate the association of these seven SNPs with hypertension and cardio-cerebral vascular disease (CCVD). In the case-control study, rs2132572 and rs3110697 at IGFBP3 were significantly associated with hypertension, and the odds ratios (ORs) of rs2132572 (CT+TT vs. CC) and rs3110697 (GA+AA vs. GG) were 1.235 (P=0.002) and 1.176 (P=0.013), respectively (PFDR<0.05). The association of rs2132572 (TT vs. CT+CC) with hypertension was further replicated in the follow-up population, with a hazard ratio (HR) of 1.694 (P=0.014). rs1874479 at IGFBP1 was significantly associated with CCVD, particularly with stroke, and the HRs of the additive model were 1.310 (P=0.007) and 1.372 (P=0.015). Moreover, the hypertension cases presented with lower serum IGFBP1 levels than the controls (P=0.011). The serum levels of IGFBP1 significantly varied among the genotypes of rs1065780, rs2854843 and rs13223993, both in the controls and in the hypertension cases (P<0.05). These findings suggest that the genetic variants of IGFBP1 and IGFBP3 were associated with an increased risk of stroke and hypertension, respectively. Lower serum IGFBP1 levels may predict an increased risk of hypertension.

MUSCLE STRENGTH, GH AND IGF-1 IN OLDER WOMEN SUBMITTED TO LAND AND AQUATIC RESISTANCE TRAINING

ABSTRACT Introduction: Aging leads to decline in multiple organ systems associated to hormone alterations and loss of muscle mass and strength. Objective: To evaluate the effects of land and water resistance training on muscle strength, basal serum levels of GH, IGF-1, and IGFBP3 in elderly women. Methods: Subjects were distributed in three groups: land resistance training (LRT; n=10; age: 66.10±2.77 years), water resistance training (WRT; n=10; age: 67.10±3.54 years) and control (CG; n=10; age: 68.80±5.41 years). Muscle strength was assessed with the 1-RM test in bench press (BP) and leg press (LP) exercises. Serum levels of GH, IGF-1, and IGFBP3 were analyzed by chemiluminescence. Results: Repeated measures ANOVA showed elevated muscle strength in the BP only in LRT (D%=60.2%; p=0.0001) when compared to the CG (D%=46.73%, p=0.0001) and WRT (D%=32.49%, p=0.004). LRT and WRT increased muscle strength in LP (D%LRT=57.14%; p=0.004; D%WRT=42.3%; p=0.033). There was an increase in LRT and WRT in the LP when compared to CG (D%=45.59%, p=0.019; D%=43.97%, p=0.026, respectively). IGF-1 was elevated only in LRT (D%=49.72%, p=0.004) from pre- to post-test and when compared to WRT (D%=56.76%, p=0.002) and CG (D%=74.63%, p=0.0001). IGFBP3 levels showed that only WRT increased (D%=26.79%, p=0.044) from pre- to post-test. The IGF-1/IGFBP3 ratio demonstrated that LRT reached intragroup elevation (D%=52.66%, p=0.002) and when compared to WRT (D%=94.11%, p=0.0001) and CG (D%=73.45%, p=0.0001). There was no significant difference in GH. Conclusion: Land resistance training may provide better anabolic effects in elderly women.

Serum insulin-like growth factor-1 and its binding protein 3 as prognostic factors for the incidence, progression, and outcome of hepatocellular carcinoma: a systematic review and meta-analysis.

PurposePrevious studies have supported an association between serum insulin-like growth factor-1 (IGF1) and IGF-binding protein 3 (IGFBP3) levels and hepatocellular carcinoma (HCC), but the results were inaccurate. It has recently been proposed that IGF1 and IGFBP3 play roles in the time-to-progression (TTP) and overall survival (OS) of HCC patients. Our results revealed that serum IGF1 level is predictive of the progression and survival of HCC patients.ResultsHCC was associated with a significant reduction in serum IGF-1 and IGFBP-3 levels compared to cirrhosis (p = 0.037). Low serum IGF1 levels were predictive of a shorter TTP (OR, 2.74; 95% confidence interval [CI], 1.92–3.90) and poorer OS (odds ratio [OR], 2.20; 95% CI, 1.81–2.68) in HCC patients. The IGF1/IGFBP3 molar ratio was not significantly associated with the risk of HCC (OR, 1.311; 95% CI, 0.761–2.260).Materials and MethodsWe conducted a comprehensive literature search in PubMed, EMBASE, and the Cochrane Library. Twenty studies met the inclusion criteria and were subjected to statistical analysis. The geometric mean and standard deviation (SD) of serum IGF1 and IGFBP3 levels in the healthy, cirrhosis, and HCC groups were calculated. Pooled odds ratios (ORs) were calculated using a fixed-effects model to analyse the association of serum IGF1 level with the progression and survival of HCC patients.ConclusionsSerum IGF1 and IGFBP3 levels were positively associated with the incidence of HCC. Serum IGF1 level is an independent prognostic factor for the progression and survival of HCC patients.

The timing of administration of exogenous glucocorticoid affects 24 hour growth hormone secretion in children

Exogenous glucocorticoids may suppress linear growth by affecting the diurnal secretory rhythm of GH. ObjectiveTo assess whether the timing of exogenous glucocorticoid administration affects GH secretion in children. DesignFour girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I–IV were studied in an open randomized 2-period cross-over trial, with a 1-day un-in, and two 4-day periods of 5mg prednisolone in the morning or in the evening, respectively, separated by a 3-week washout period. At run-in and on the last day of each treatment period serum was collected every 20min for 24h for assessment of GH. Secondary analyses were serum levels of IGF-I and IGFBP-3 (measured every 8h), and IGFBP-1, insulin, and collagen markers PICP, PINP, ICTP and PIIINP (measured every 2h). ResultsEvening prednisolone suppressed 24hour GH secretion (P=0.016), overnight GH secretion (P=0.023) and IGF-I (P=0.024) when compared to morning prednisolone, but not when compared to run-in. Evening prednisolone also increased nocturnal insulin levels as compared to run-in (P=0.010). Irrespective of time of day, prednisolone increased serum collagen markers PICP, PIINP, ICTP and PINP (all P<0.05). ConclusionsShort-term prednisolone 5mg administered in the morning may alleviate nocturnal GH suppression as compared to evening administration. In analogy, growth rates are less affected by morning as compared to evening administration of exogenous glucocorticoids. In contrast, collagen markers and metabolic indices were not affected by the timing of prednisolone administration.

The diagnostic value of serum AMH, IGF-1 and IGFBP-1 levels in polycystic ovarian syndrome

Objective To explore the relation between serum AMH, IGF-1 and IGFBP-1 levels and polycystic ovarian syndrome (PCOS) and its clinical significance. Methods Serum levels of AMH, IGF-1 and IGFBP-1 were measured by ELISA in 80 patients with PCOS and 80 healthy subjects. Results The levels of serum AMH, IGF-1, IGFBP-1 in PCOS group were (7.18±1.50)ng/L, (200.85±27.78)ng/L, (4.05±0.65)ng/L respectively, which in the control group were (3.70±1.01)ng/L, (110.58±12.50)ng/L, (8.16±1.39)ng/L.The serum levels of AMH, IGF-1 in the PCOS group were significantly higher than those in the control group(t=13.14, 26.80, P<0.01), while the serum level of IGFBP-1 in the PCOS group was significantly lower than that in the control group(t=16.28, P<0.01). The serum levels of AMH, IGF-1, IGFBP-1 in patients with obese group were (7.18±1.50)ng/L, (200.85±27.78)ng/L, (4.05±0.65)ng/L respectively, which in the non-obese group were (15.52±2.41)ng/L, (143.85±15.61)ng/L, (6.75±0.93)ng/L.The serum level of IGF-1 in the obese group was significantly higher than that in the non-obese group(t=10.87, P<0.01), while the serum levels of AMH and IGFBP-1 in the obese group were significantly lower than those in the non-obese group(t=18.98, 15.27, P<0.01). Conclusion Serum AMH, IGF-1 and IGFBP-1 may be involved in the pathogenesis and obesity of PCOS, which may be associated with the pathogenesis of PCOS. Key words: Polycystic ovarian syndrome; Anti-mullerian hormone; Insulin-like growth factor 1; Insulin-like growth factor binding protein1; Obesity

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