IGF Binding Protein-3 Ratio Research Articles

Effects of Pilates with and without elastic resistance on health variables in postmenopausal women with low back pain.

Aim: To compare the effects of Pilates with and without accessories on biochemical markers, pain intensity, functional disability and muscle strength in postmenopausal women with nonspecific chronic low back pain. Materials & methods: Twenty-two participants were randomized to a group of Pilates without (PG; n=11) and with elastic resistance (PAG; n=11) for 8weeks, twice a week. We analyzed IGF-1, IGF-binding protein-3 (IGFBP-3), cortisol, creatine kinase, pain intensity, functional disability, abdominal and back strengths. Results: Both groups had lower pain intensity and functional disability and increased lumbar strength postinterventions. PAG exhibited an increase in IGF-1/IGFBP-3 ratio and reduction in creatine kinase compared with PG. Conclusion: Both interventions were effective in the treatment of low back pain. However, PAG presented better responses than PG. Clinical Trial Registration: Brazilian Clinical Trials Registry: ReBEC (RBR-9jwcykc), www.ensaiosclinicos.gov.br/rg/RBR-9jwcykc.

Insulin/IGF-1 Signaling Is Downregulated in Barrett's Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial.

Obesity and associated insulin resistance (Ins-R) have been identified as important risk factors for esophageal adenocarcinoma development. Elevated calories and protein consumption are also associated with Ins-R and glucose intolerance. We investigated the effect of a 24-month moderate calorie and protein restriction program on overweight or obese patients affected by Barrett’s esophagus (BE), as no similar dietary approach has been attempted to date in this disease context. Anthropometric parameters, levels of serum analytes related to obesity and Ins-R, and the esophageal insulin/IGF-1 signaling pathway were analyzed. This study is registered with ClinicalTrials.gov, number NCT03813381. Insulin, C-peptide, IGF-1, IGF-binding protein 3 (IGFBP3), adipokines, and esophageal expression of the main proteins involved in insulin/IGF-1 signal transduction were quantified using Luminex-XMAP® technology in 46 patients who followed the restriction program (IA) and in 54 controls (CA). Body mass index and waist circumference significantly decreased in 76.1% of IA and 35.2% of CA. IGF-1 levels were reduced in 71.7% of IA and 51.8% of CA. The simultaneous reduction of glycaemia, IGF-1, the IGF-1/IGFBP3 ratio, and the improvement in weight loss-dependent insulin sensitivity, were associated with the downregulation of the insulin/IGF-1 signal on BE tissue. The proposed intervention program was an effective approach to counteract obesity-associated cancer risk factors. The improvement in metabolic condition resulted in a downregulation of the ERK-mediated mitogenic signal in 43.5% of patients, probably affecting the molecular mechanism driving adenocarcinoma development in BE lesions.

The effect of milk and rapeseed protein on growth factors in 7–8 year-old healthy children – A randomized controlled trial

Milk protein may stimulate linear growth through insulin-like growth factor-1 (IGF-1). However, the effect of plant proteins on growth factors is largely unknown. This study assesses the effect of combinations of milk and rapeseed protein versus milk protein alone on growth factors in children.An exploratory 3-armed randomized, double-blind, controlled trial was conducted in 129 healthy 7-8 year-old Danish children. Children received 35 g milk and rapeseed protein (ratio 54:46 or 30:70) or 35 g milk protein per day for 4 weeks. The primary outcome was difference in IGF-1 changes between intervention groups after 4 weeks. Secondary outcomes included changes in IGF-1 after 1 week and changes in insulin-like growth factor binding protein-3 (IGFBP-3), IGF-1/IGFBP-3, insulin, height, weight and body composition after 1 and 4 weeks. Results were analysed by multiple linear mixed-effect models.There were no differences in changes of plasma IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), IGF-1/IGFBP-3 ratio or insulin between groups after 1 or 4 weeks based on 89 complete cases (P > 0.10). IGF-1 increased by 13.7 (95% CI 9.7;17.7) ng/mL and 18.0 (14.0;22.0) ng/mL from baseline to week 1 and 4, respectively, a 16% increase during the intervention. Similarly, insulin increased by 31% (14; 50) and 33% (16; 53) from baseline to week 1 and 4. Fat-free mass index (FFMI) increments were higher with milk alone than rapeseed blends (P < 0.05), coinciding with a trend towards a lower height increment. Body mass index increased within all groups (P < 0.05), mainly due to an increase in FFMI (P < 0.01).There were no differences in changes of growth factors between the combinations of milk and rapeseed protein and milk protein alone in healthy, well-nourished children with a habitual intake of milk. Within groups, growth factors increased considerably. Future studies are needed to investigate how intakes of plant and animal proteins affect childhood growth.

Erratum to: "Age- and Sex-Specific Reference Intervals Across Life Span for Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 Ratio Measured by New Automated Chemiluminescence Assays".

Erratum to: "Age- and Sex-Specific Reference Intervals Across Life Span for Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 Ratio Measured by New Automated Chemiluminescence Assays".

The diagnostic and prognostic utility of insulin growth factor of squamous cell carcinoma in oral cavity.

Objective:The present study was conducted to find the utility of insulin growth factors (IGFs) as diagnostic and prognostic biochemical parameters in patients suffering from squamous cell carcinoma of oral cavity.Materials and Methods:A total of 360 male and female patients diagnosed with precancerous conditions (PCC) and oral squamous cell carcinoma (OSCC) of Stage I to IV were selected for the present study. Patients were interviewed using a structured questionnaire to ascertain their demographic and medical history. After completing the history and physical examination, patients were subjected to routine blood investigations along with determining insulin growth factor (IGF-1, IGFBP-3) levels. The data obtained were then subjected to statistical analysis using SPSS 20.0 version.Results:The mean values of IGF-1, insulin-like growth factor-binding protein-3 (IGFBP-3), and ratio of IGF-1 and IGFBP-3 were obtained. The intergroup comparison was done between PCC and all the stages of OSCC for all the IGFs. The result obtained was found to be statistically significant (P < 0.05).Conclusion:The present study concluded that a positive correlation was observed for various insulin growth factors (IGF-1, IGFBP-3; and ratio of IGF-1 and IGFBP-3) between OSCC and PCC such as erythroplakia and oral submucous fibrosis. Thus, the study highlighted the use of IGFs as diagnostic and prognostic parameters in patients suffering from cancerous conditions.

Relationship between growth velocity and change of levels of insulin-like growth factor-1, insulin-like growth factor binding protein-3 and, IGFBP-3 promoter polymorphism during GnRH agonist treatment.

Purpose This study aims to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) on the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis and to evaluate whether -202 A/C IGF binding protein-3 (IGFBP-3) promoter polymorphism affects growth velocity in females with central precocious puberty (CPP) during treatment.Methods Data was collected from 97 females younger than 9 years, diagnosed with precocious puberty and treated with GnRHa for at least 1 year at Kangdong Sacred Heart Hospital from 2014 to 2015. Their body height, weight, change in height standard deviation score (∆SDS), serum IGF-1, serum IGFBP-3, bone age, and -202 A/C IGFBP-3 promoter polymorphism were measured before and after GnRHa treatment. The interrelationships between the variables were calculated.Results During treatment, height SDS, IGF-1 SDS, IGFBP-3 SDS, and IGF-1/IGFBP-3 ratio significantly decreased. A significant correlation was observed between ∆IGF-1 SDS and ∆height SDS (r=0.405, P<0.001). The presence of the C allele was significantly correlated with IGF-1 SDS after treatment (P=0.049) and with IGFBP-3 SDS before and after treatment (P=0.012 and P=0.001), but not with ∆IGF-1 SDS, ∆IGFBP-3 SDS, ∆IGF-1/IGFBP-3 ratio, or ∆height SDS.Conclusions Growth velocity during GnRHa treatment is related to ∆IGF-1 SDS, indicating the apparent impact of GnRHa on the GH-IGF-1 axis. The -202 A/C IGFBP-3 promoter polymorphism does not affect the growth velocity of GnRHa in CPP girls.

Prognostic Significance of IGF-1 Signalling Pathway in Patients With Advanced Non-small Cell Lung Cancer.

Insulin-like growth factor 1 (IGF-1)-mediated molecular pathway has been implicated in non-small cell lung cancer (NSCLC) pathogenesis and progression. We aimed to evaluate serum levels of IGF-1, IGF-2 and IGF-binding protein 3 (IGF-BP3) before and after standard treatment in patients with advanced NSCLC and their prognostic and predictive correlations. Seventy-three patients were prospectively included. Analysis and quantification of circulating levels of IGF1, IGF2, IGFBP3 were performed by total ELISA in peripheral blood samples at baseline and 3 months post-treatment. The median values of IGF-1 and IGF-1/IGF-BP3 ratios (125.82 vs. 133.4 ng/ml, p=0.087 and 0.01006 vs. 0.01252, p=0.011) were both decreased after treatment. Importantly, the post-treatment value of the ratio was significantly reduced only among responders to treatment (0.01044 from 0.01255, p=0.02). Reduction of IGF-1/IGF-BP3 ratio was statistically significant only among patients with NSCLC who responded to first-line treatment. If validated in larger cohorts, IGF-1/IGFBP3 might be a useful predictive tool for response to chemotherapy in NSCLC.

Effects of Zinc Alone versus Zinc-Containing Multiple Micronutrient Powder on Insulin-Like Growth Factor 1 (IGF1) and IGF Binding Protein-3 (IGFBP3) in Laotian Children (OR07-05-19)

Abstract Objectives To assess a) the impact of daily preventive zinc tablets (7 mg; PZ), multiple micronutrient powder (10 mg zinc, 6 mg iron and 13 other micronutrients; MNP) or placebo on Insulin-like Growth Factor 1 (IGF1), IGF Binding Protein 3 (IGFBP3) and IGF1 bioavailability (indexed by molar IGF1: IGFBP3 ratio), among Laotian children aged 6–23 mo; b) potential effect modification by baseline physical growth status. Methods Plasma samples from 419 children participating in the parent trial (n = 3407) were collected at baseline and after ∼9 mo (endline). Determination of IGF1 and IGFBP3 were done via an automated chemiluminescent assay. Linear regression models were used to assess main and modifying effects of PZ and MNP on IGF1 and IGFBP3, controlling for age, sex, district and baseline values of each biomarker. Results The parent trial found no overall treatment effects on physical growth. In this subgroup, mean age at baseline was 14.2 ± 5.1 mo and ∼38% were stunted. IGF1 and IGFBP3 at baseline were 45.9 ng/ml and 2143.0 ng/ml, respectively. At endline, geometric mean IGF1 (∼39.0–39.2 ng/ml; P = 0.99), IGFBP3 (2038–2076 ng/ml; P = 0.83) and molar IGF1: IGFBP3 ratio (0.071–0.073; P = 0.74) did not differ by group. Baseline weight-for-age z-score (WAZ) modified the treatment effect on IGFBP3 (p for interaction = 0.05) and molar IGF1: IGFBP3 (p for interaction = 0.04). In non-underweight children (WAZ ≥ -2), mean IGFBP3 in the PZ group (2000 ng/ml) was significantly lower than in the placebo (2148 ng/ml; P = 0.03) and MNP (2157 ng/ml; P = 0.03) groups. In underweight children, however, the IGFBP3 in the PZ group (2039 ng/ml) was higher than the placebo (1774 ng/ml; P = 0.05) but not the MNP (1881 ng/ml; P = 0.15) group. PZ (relative to placebo and MNP) appeared to reduce the bioavailability of IGF1 in underweight children, while increasing IGF1 bioavailability in non-underweight children (p interaction = 0.04). Conclusions IGF1 in this population did not respond to PZ or MNP. PZ (relative to placebo and MNP) was associated with higher endline IGFBP3 concentrations in underweight children but lower values in non-underweight children. These results suggest that PZ affected activity in the GH-IGF axis in these children, but additional evidence is needed to understand long term implications for growth in this population. Funding Sources By The Thrasher Research Fund, with support from the Mathile Institute for the Advancement of Human Nutrition, Nutrition International and the Bill &amp; Melinda Gates Foundation.

SUN-267 Relationship between Height Velocity and Change of Serum Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Concentrations during Gonadotropin-Releasing Hormone Agonist Treatment in Korean Girls with Idiopathic Central Precocious Puberty

Purpose : This study aims to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) on the growth velocity during treatment in Korean girls with idiopathic central precocious puberty (ICPP). Methods : Data was collected from 97 girls, diagnosed under 9 year of age and treated by GnRHa for at least 1 year between 2014 and 2015. Their body height, weight, ∆ Height standard deviation score (SDS), serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations and bone age were measured at the start and after a year of GnRHa treatment. Possible correlations between the variables were calculated. Results : During the treatment, height SDS, IGF-1 SDS, IGFBP-3 SDS and IGF-1/IGFBP-3 ratio significantly decreased. There were significant correlations between serum IGF-1 level and ∆ Height SDS (r=0.405, p=0.000), and between serum IGFBP-3 level and ∆ Height SDS (r=0.228, p=0.025). C allele had significant correlation with IGFBP-3 level (p=0.004) but had no significant correlation with ∆ Height SDS (p=0.947). Conclusions : The results suggest that the height velocity during GnRHa treatment may be related to serum IGF-1 and IGFBP-3 concentration thus GnRHa may affect GH-IGF-1 axis.

Relation of IGF-1 and IGFBP-3 with prevalent and incident atrial fibrillation in a population-based study

Insulin-like growth factor 1 (IGF-1) and its main binding protein insulin-like growth factor binding protein 3 (IGFBP-3) have been related to several cardiovascular diseases. The relation with atrial fibrillation (AF) is largely unknown. The objective of this study was to investigate the association of IGF-1 and IGFBP-3 levels with prevalent and incident AF in a large population-based study. Data from the Study of Health in Pomerania (SHIP) were collected. At presentation, a medical examination, standardized electrocardiographic assessment, and measurements of serum IGF-1 and IGFBP-3 levels were performed. Incident AF was assessed in individuals without AF at baseline (SHIP-1) who developed AF during follow-up (SHIP-2; after a mean of 5.2 years). Of 3160 participants, 66 (2.1%) exhibited AF at baseline. IGF-1 levels and IGF-1/IGFBP-3 ratios were significantly lower in individuals with AF than in those without AF (IGF-1: 104.2 ± 41.6 ng/mL vs 142.9 ± 53.5 ng/mL, P < .001 and IGF-1/IGFBP-3: 0.031 ± (0.009 ng/mL vs 0.036 ± 0.010 ng/mL, P = .006, respectively). Multivariable-adjusted logistic regression models showed that a low IGF-1/IGFBP-3 ratio was associated with prevalent AF (odds ratios 0.67; 95% confidence interval 0.48-0.94; P = .021). Of 1817 individuals without AF at baseline, 27 (1.5%) developed AF during follow-up. In these participants, IGF-1 levels, but not IGF-1/IGFBP-3 ratios, were significantly lower (IGF-1: 113.3 ± 38.6 ng/mL vs 147.2 ± 51.6 ng/mL, P = .013 and IGF-1/IGFBP-3: 0.033 ± 0.008 ng/mL vs 0.036 ± 0.010 ng/mL, P = .176). Low IGF-1/IGFBP-3 ratios are associated with a higher prevalence of AF. There seems to be a similar impact in incident AF.

Insulin-like growth factor-1 (IGF1) in systemic lupus erythematosus: relation to disease activity, organ damage and immunological findings.

Background Insulin growth factor-1 (IGF1) activates cell proliferation pathways and inhibits apoptosis. IGF1 is involved in tumour growth and required for T-cell independent activation of B cells. Activated B cells and autoantibody production are a hallmark of systemic lupus erythematosus (SLE). To investigate the possible role of IGF1 in SLE, we studied IGF1 across clinical characteristics, immunological biomarkers, disease activity and organ damage in SLE patients. Method In a cross-sectional study, we collected clinical characteristics, medication, disease activity (SLEDAI-2K) and organ damage (SDI) for 94 SLE patients. Autoantibodies and cytokines were measured by ELISA, and levels of IGF1 and IGF binding protein 3 (IGFBP3) by chemiluminescence. Free IGF1 was estimated by the IGF1:IGFBP3 ratio. Healthy controls served as a comparator group. Results There was a significant age-related decline in IGF1, IGFBP3 and free IGF1 (IGF1:IGFBP3 ratio) that was similar in SLE patients and controls with very few outliers. Free IGF1 was inversely related to blood pressure (Rs -0.327, p < 0.01) and HbA1c (Rs -0.31, p < 0.01). Free IGF1 was higher in disease-modifying antirheumatic drug-treated patients ( p < 0.01), but there was no significant association between the IGF1 axis and autoantibody profiles, cytokine levels or SLEDAI-2K or SDI categories. IGF1 correlated inversely with BAFF level and B, natural killer and CD8 + cell counts. Conclusion Free IGF1 levels in SLE patients declined appropriately with age. IGF1 levels were not associated with disease activity, severity or autoantibody levels in SLE. Free IGF1 had positive metabolic effects in SLE and may play an indirect role in dampening the cellular immune response by downregulating B- and T-cell activity.

Combined sprint and resistance training abrogates age differences in somatotropic hormones.

The aim of this investigation was to compare serum growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in response to a combined sprint and resistance training (CSRT) program in young and middle-aged men.Thirty-eight healthy, moderately trained men participated in this study. Young and middle-aged men were randomly assigned to, a young training group (YT = 10, 21.4±1.2yrs) ora young control group (YC = 9, 21.6±1.8 yrs), a middle-aged training group (MAT = 10, 40.4±2.1 yrs) or a middle-aged control group (MAC = 9, 40.5±1.8 yrs). Participants performed the Wingate Anaerobic Test (WAnT) before and after a 13-week CSRT program (three sessions per week). Blood samples were collected at rest, after warm-up, immediately post-WAnT, and 10 min post-WAnT. CSRT induced increases in GH at rest and in response to the WAnT in YT and MAT (P<0.05). CSRT-induced increases were observed for IGF-1 and IGFBP-3 at rest in MAT only (P<0.05). Pre-training, GH, IGF-1 and IGFBP-3 were significantly higher at rest and in response to the WAnT in young participants as compared to their middle-aged counterparts (P<0.05). Post-training, YT and MAT had comparable basal GH (P>0.05). In response to the WAnT, amelioration of the age-effect was observed between YT and MAT for IGF-1 and IGF-1/IGFBP-3 ratio following CSRT (P>0.05). These data suggest that CSRT increases the activity of the GH/IGF-1 axis at rest and in response to the WAnT in young and middle-aged men. In addition, CSRT reduces the normal age-related decline of somatotropic hormones in middle-age men.

Discordance Between Gh and Igf-1 Levels in Turkish Acromegalic Patients

Discordance between insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels is an important problem in the follow-up of patients diagnosed with acromegaly. Our aims were to evaluate the discordance between IGF-1 and GH levels and compare the performance of different cut-off levels for the nadir in GH (GHn) in acromegalic patients. The study included 63 acromegalic patients in a follow-up at a tertiary care university hospital facility. Levels of IGF-1, IGF binding protein-3 (IGFBP-3), and GH were investigated. The baseline GH and GHn levels were evaluated after an oral glucose tolerance test (cut-offs of 0.4 and 1 ng/mL, respectively). The discordance rates between GHn and IGF-1 levels, and IGF-1/IGFBP-3 ratios were determined. We first adopted a GHn cut-off value of 1 ng/mL and found that 27 patients (42.9%) exhibited biochemical remission (BR) (IGF-1 <95th percentile, GH <1), and 25 patients (39.7%) had no BR (NBR) (IGF-1 ≥95th percentile, GH >1). Discordance in the presence of normal IGF-1 and nonsuppressed GH (DC1) occurred in 2 of 63 (3.2%) patients; discordance in the presence of high IGF-1 and suppressed GH (DC2) occurred in 9 of 63 (14.3%) patients. If the GHn cut-off value adopted was 0.4 ng/mL, the distributions were 17 of 63 (27.0%) patients in BR, 29 of 63 (46.0%) patients in NBR, 12 of 63 (19.0%) in DC1, and 5 of 63 (7.9%) patients in DC2. If only the baseline GH values were considered, the distributions were very similar to those with a GHn cut-off value of 0.4 ng/mL. The IGF-1/IGFBP-3 ratio was lowest in the BR group. Adopting a GHn cut-off value of 0.4 ng/mL did not increase the test performance compared with baseline GH only. In contrast, in the follow-up of acromegalic patients, the IGF-1/IGFBP-3 ratio might be a useful measurement when discordance between IGF-1 and GH levels occurs. We propose that these values be considered in clinical practice. BR = biochemical remission DC1 = discordance group 1 DC2 = discordance group 2 DM = diabetes mellitus GH = growth hormone GHn = nadir in GH IGF-1 = insulin-like growth factor-1 IGFBP-3 = IGF binding protein-3 LAR = long-acting release NBR = not in biochemical remission OGTT = oral glucose tolerance test.

Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor-Binding Protein 3 in Relation to the Risk of Type 2 Diabetes Mellitus: Results From the EPIC-Potsdam Study.

Higher levels of insulin-like growth factor-binding protein 3 (IGFBP-3) might raise the risk of type 2 diabetes mellitus (T2DM) via binding of insulin-like growth factor 1 (IGF-1), an insulin-like hormone that is involved in glucose homeostasis. We investigated serum concentrations of IGF-1 and IGFBP-3 and their molar ratio in relation to T2DM incidence in a nested case-cohort study within the European Prospective Investigation Into Cancer and Nutrition-Potsdam Study. We included a randomly selected subcohort of persons without T2DM at the time of blood sampling (n = 2,269) and 776 individuals with incident T2DM identified between 1994 and 2005. For the highest quartile versus lowest, the multivariable-adjusted hazard rate ratios were 0.91 (95% confidence interval (CI): 0.68, 1.23; P for trend = 0.31) for IGF-1, 1.33 (95% CI: 1.00, 1.76; P for trend = 0.04) for IGFBP-3, and 0.77 (95% CI: 0.57, 1.03; P for trend = 0.03) for IGF-1:IGFBP-3 ratio. IGFBP-3 level remained positively associated with T2DM incidence-and the ratio of IGF-1 to IGFBP-3 was inversely related with T2DM incidence--in models that included adjustment for IGF-1 concentrations (P for trend < 0.05). Therefore, our findings do not confirm an association between total IGF-1 concentrations and risk of T2DM in the general study population, although higher IGFBP-3 levels might raise T2DM risk independent of IGF-1 levels.

Abstract 15552: Insulin-Like Growth Factor-1 is Lower in Acute Stroke but is Not Related to Recovery

Purpose: Insulin-like growth factor 1 (IGF1) sampled within ten days of stroke has resulted in inconsistent findings. When compared to control participants, one study found elevated levels of IGF1 while another reported lower values. Despite these reported differences, there is evidence to suggest that IGF1 may have a neuroprotective effect and may be related to admitting stroke severity and functional independence at one month post-stroke. The possibility exists that a large sampling window and no consideration for insulin-like growth factor binding protein 3 (IGFBP3), may account for the differing results. The purpose of this study was to: 1) determine the difference in IGF1, IGFBP3, and IGF1 ratio in individuals with acute stroke and controls; and 2) determine the relationship of IGF1, IGFBP3, and IGF1 ratio to admission stroke severity and functional independence at one month post stroke. Methods: Blood was collected from 12 individuals with a diagnosis of acute stroke (4 males; 63.9 + 8.4 years) between 7:30 and 9:00 am, after an overnight fast, and within 72 hours of hospital admission. Blood was obtained from 12 age and gender matched healthy controls (4 males; 64.8 + 9.8 years) after an overnight fast during similar hours. Plasma was obtained from blood samples, aliquoted, and frozen within 1 hour of collection. IGF1 and IGFBP3 were quantified using standard procedure ELISAs (Alpco, Salem, NH). Admission NIH Stroke Scale and the modified Rankin Scale (mRS) at one month post stroke was obtained from the electronic medical record. Results: IGF1 (stroke: 113 ng/mL; control: 123 ng/mL, p = .59) and IGFBP3 (stroke: 2350 ng/mL; control: 2593 ng/mL, p = .33) were lower in the acute stroke patients, but not significantly. IGF1 ratio was not different (stroke: .06; control: 05; p = .55) in acute stroke compared to controls. There were no significant relationships between any IGF marker and stroke severity (p &gt; 0.50), nor mRS (p &gt; 0.50). Conclusion: We report that IGF1 and IGFBP3 is lower in acute stroke patients. A single time point of IGF1 and IGFBP3 during acute stroke may not demonstrate a neuroprotective relationship to stroke recovery. Future work should examine percent change in the IGF family to determine whether this may be a more valuable biomarker of stroke recovery.

Circulating levels of IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio and colorectal adenomas: A meta-analysis

Insulin-like growth factor-1(IGF-1) promotes cell proliferation and inhibits apoptosis, and is thereby implicated in carcinogenesis. Insulin-like growth factor binding protein-3 (IGFBP-3) may antagonize IGF-1 action, leading to inhibition of the potential tumorigenicity of IGF-1. We conducted this meta-analysis to estimate the association between IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio and the risk of colorectal adenomas (CRAs). Further, we investigated whether this association was different between occurrent and recurrent CRA, by adjustment for obesity, and by advanced CRA. Pubmed and Embase were searched up to April, 2015 to identify relevant observational studies and summary odds ratio (OR) and the corresponding 95% confidence interval (95% CI) was estimated using a random-effects model. A total of 12 studies (11 studies including 3038 cases for IGF-1, 12 studies including 3208 cases for IGFBP-3, and 7 studies including 1867 cases for IGF-1/IGFBP-3 ratio) were included in this meta-analysis. The summary ORs of occurrent CRA for the highest versus lowest category of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio were 1.13 (95% CI: 0.95-1.34), 0.99 (0.84-1.16), and 1.05 (0.86-1.29), respectively. Higher IGF-1 and IGF-1/IGFBP-3 ratio were significantly associated with decreased risk of recurrent CRA (OR for IGF-1=0.60 [95% CI: 0.42-0.85]; IGF-1/IGFBP-3 ratio=0.65 [0.44-0.96]). A stratified analysis by advancement of occurrent CRA produced a significant summary OR of IGF-1 for advanced CRA (OR=2.21 [1.08-4.52]) but not for non-advanced CRA (OR=0.89 [0.55-1.45]). We did not find significant publication bias or heterogeneity. Circulating levels of IGF-1, IGFBP-3 and their molar ratio were not associated with the risk of occurrence of CRA, but IGF-1 was associated with the increased risk for occurrence of advanced CRA.

Bioavailable IGF-1 and its relationship with endothelial damage in a bi-ethnic population: The SABPA study

Insulin-like growth factor-1 (IGF-1) has vasculoprotective effects and can directly oppose endothelial dysfunction in several ways. To improve our understanding on the potential contribution of reduced IGF-1 to the development of vascular endothelial damage, we investigated the link between bioavailable IGF-1 and von Willebrand factor (vWF) as a marker of endothelial damage. We performed this study in black South African school teachers, known to be prone to hypertension. From the larger Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study we included 179 black and 207 white non-diabetic men and women (aged 44.5 ± 9.96 years). We measured ambulatory blood pressure and determined IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3) and vWF antigen from blood samples. We used the molar IGF-1/IGFBP-3 ratio as an estimate of bioavailable IGF-1. Black individuals presented higher blood pressure and vWFag and lower IGF-1 than the white group (all p < 0.001). In multivariate-adjusted analyses, vWFag was inversely associated with IGF-1 (R(2) = 0.18; β = -0.17; p = 0.044) and IGF-1/IGFBP-3 (R(2) = 0.18; β = -0.17; p = 0.030) in blacks, with no associations in whites. Since IGF-1 is attenuated and vWFag elevated in diabetes, we included patients with diabetes (n = 38) and the aforementioned associations found in blacks remained robust. The inverse association between bioavailable IGF-1 and vWF in black South Africans suggests that suppressed IGF-1 may result in endothelial damage independent of traditional risk factors.

Preweaning GH Treatment Normalizes Body Growth Trajectory and Reverses Metabolic Dysregulation in Adult Offspring After Maternal Undernutrition.

Maternal undernutrition (UN) results in growth disorders and metabolic dysfunction in offspring. Although dysregulation of the GH-IGF axis in offspring is a known consequence of maternal UN, little is known about the efficacy of GH treatment during the period of developmental plasticity on later growth and metabolic outcomes. The present study investigated the effect of preweaning GH treatment on growth, glucose metabolism, and the GH-IGF axis in adult male and female offspring after maternal UN. Female Sprague Dawley rats were fed either a chow diet ad libitum (control [CON]) or 50% of ad libitum (UN) throughout pregnancy. From postnatal day 3, CON and UN pups received either saline (CON-S and UN-S) or GH (2.5 μg/g·d CON-GH and UN-GH) daily throughout lactation. At weaning, male and female offspring were randomly selected from each litter and fed a standard chow diet for the remainder of the study. Preweaning GH treatment normalized maternal UN-induced alterations in postweaning growth trajectory and concomitant adiposity in offspring. Plasma leptin concentrations were increased in UN-S offspring and normalized in the UN-GH group. Hepatic GH receptor expression was significantly elevated in UN-S offspring and normalized with GH treatment. Hepatic IGF binding protein-2 gene expression and plasma IGF-1 to IGF binding protein-3 ratio was reduced in UN-S offspring and elevated with GH treatment. GH treatment during a critical developmental window prevented maternal UN-induced changes in postnatal growth patterns and related adiposity, suggesting that manipulation of the GH-IGF-1 axis in early development may represent a promising avenue to prevent adverse developmental programming effects in adulthood.

Age- and Sex-Specific Reference Intervals Across Life Span for Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 Ratio Measured by New Automated Chemiluminescence Assays

Measurement of IGF-binding protein-3 (IGFBP-3) can aid the diagnosis of GH-related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I to IGFBP-3 ratio are associated with clinical end points like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals. The objective of the study was the establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I to IGFBP-3 ratio by newly developed automated immunoassays. This was a multicenter study with samples from 11 cohorts from the United States, Canada, and Europe. A total of 14 970 healthy subjects covering all ages from birth to senescence participated in the study. Concentrations of IGFBP-3 and the IGF-I to IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays were measured. Both the concentration of IGFBP-3 and the IGF-I to IGFBP-3 ratio are mainly determined by age. IGFBP-3 concentrations increase until the age of 22 years, with a plateau being visible between 15 and 25 years. Determined by the high peripubertal peak in IGF-I, the peak in the IGF-I to IGFBP-3 ratio occurs already around the age of 15 years, with a slightly earlier and higher peak in females. Beyond the age of 60 years, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I to IGFBP-3 ratio remains significantly higher in males. We present an extensive set of assay-specific age- and sex-adjusted normative data for concentrations of IGFBP-3 and the molar IGF-I to IGFBP-3 ratio and demonstrate distinct sex specific differences across the life span.

Effects of Exogenous Growth Hormone on Growth Hormone-Insulin-Like Growth Factor Axis of Human Gastric Cancer Cell

Aim: To study effects of recombinant human growth hormone (rhGH) on growth hormone-insulin-like growth factor axis (GH-IGFs) of human gastric cancer cell in vivo in order to reveal part mechanism of growth effects of rhGH on gastric cancer. Methods: Nude mice were randomly divided into control group, cisplatin (DDP) group, rhGH group and DDP + rhGH group after human gastric cancer xenograft model of node mice was successfully founded and drugs were used for 6 days. We investigated volume of tumor, inhibitory rate of tumor and cell cycle by slide gauge and flow cytometry. In addition, We also respectively investigated insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) of blood serum of nude mice, IGF-ImRNA, insulin-like growth factor-I receptor (IGF-IR) mRNA and IGFBP-3 mRNA of xenograft of nude mice by enzyme linked immunosorbent assay (ELISA) and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on the first day of completing use of drugs later. Results: Tumor grew obviously slowly and tumor inhibitory rate obviously rose in DDP group and DDP + rhGH group compared with control group and rhGH group (p p p < 0.05). Expressions of IGF-I mRNA and IGF-IR mRNA were not obviously different in all groups. But expression of IGFBP-3 mRNA obviously increased in rhGH group, DDP group and DDP + rhGH group compared with control group; meanwhile, expression of IGFBP-3 mRNA also obviously increased in DDP + rhGH group compared with control group, DDP group and rhGH group. Conclusion: Our results indicated rhGH in short-time use did not improve proliferation of human gastric cancer cells and its mechanism was possible that rhGH in short-time use raised simultaneously IGF-I and IGFBP-3 of blood serum and increased IGFBP-3 mRNA, but degraded ratio of IGF-I and IGFBP-3 of blood serum in human gastric cancer cells.