Growth Factor Binding Protein-3 Levels Research Articles

Minipuberty period of children with atopic dermatitis compared to healthy children.

Atopic dermatitis (AD) is an inflammatory, pruritic, noncontagious, chronic relapsing skin disease. Skin barrier abnormalities, excessive T helper 2 activity, and immune dysregulation are held responsible. Androgens have a negative effect on the integrity of the epidermal skin barrier, while estrogen has a positive effect. We aimed to investigate whether hormones make a difference between healthy children and children with AD during minipuberty. A total of 96 infants (postnatal 4-13 weeks), 48 diagnosed with AD and 48 controls, were included. Each group consisted of 23 girls (47.9%) and 25 boys (52.1%). Anthropometric examinations and hormone measurements were compared. The two groups, having similar age, sex, body mass index, and weight-for-length standard deviation scores, were compared. Serum free thyroxine (FT4) levels were found to be lower and insulin-like growth factor binding protein-3 (IGFBP3) levels were found to be higher in children with AD (p < 0.001 and p = 0.038, respectively). In girls with AD, estradiol, FT4, and insulin-like growth factor-1 (IGF-1) levels were found to be lower, but thyroid-stimulating hormone (TSH) levels were found to be higher (p = 0.023, p < 0.001, p = 0.038, and p = 0.034, respectively). In boys with AD, the FT4 level was found to be lower (p = 0.023). Serum FT4 and TSH levels were within normal reference ranges in all comparisons. Especially in girls with AD, decreased estradiol and IGF-1 levels were observed compared to the controls during minipuberty. In the logistic regression model, decreased levels of serum estradiol, dehydroepiandrosterone sulfate, FT4, and IGF-1, and increased levels of IGFBP3 were associated with an increased likelihood of exhibiting atopic dermatitis.

Association of Body Mass Index and Weight Gain With Obesity-Related Breast Cancer Risk Biomarkers in Adult Chinese Women

To investigate the associatiojn of body mass index (BMI) at different stages of life and weight gain in adulthood with obesity-related breast cancer risk biomarkers and to provide evidence for formulating policies concerning the prevention and control of breast cancer. A cross-sectional study was designed based on the follow-up cohort of southwest China community-based breast cancer screening of women. Using sequential sampling, eligible participants were enrolled from the cohort as the subjects of the study. Information on the basic risk factors was collected and the height, weight, and plasma biomarker levels were measured. Multiple linear regression model was applied to analyze the associations of early adulthood BMI (defined as the BMI of the participant at age 20), adulthood BMI (defined as the BMI measured at the time of enrollment), and weight gain in adulthood with the biomarkers. The concentrations of the biomarkers were incorporated in the model after log transformation. The average age of the 442 participants was 49 (45, 54) years old, the average early adulthood BMI and adulthood BMI were 21.47 (19.56, 23.11) and 24.10 (22.59, 25.97) kg/m 2, respectively, and the average weight gain in adulthood was 6.60 (2.00, 11.00) kg. Adulthood BMI was negatively associated with adiponectin level ( β=-0.026, 95% CI: -0.045--0.008, P=0.006), and positively associated with C-reactive protein level ( β=0.095, 95% CI: 0.054-0.137, P<0.001) and leptin receptor level ( β=0.090, 95% CI: 0.063-0.117, P<0.001). No association was found between adulthood BMI and resistin levels or between adulthood BMI and insulin-like growth factor-binding protein-3 levels. BMI in early adulthood was found to be negatively associated with only insulin-like growth factor-binding protein-3 levels ( β=-0.039, 95% CI: -0.068--0.010, P=0.009). Further analysis of adulthood weight gain after the age of 20 revealed that average annual weight gain in adulthood was negatively associated with adiponectin levels and positively associated with 4 other biomarkers. Furthermore, compared with those of women whose weight remained stable, the adiponectin level of women whose weight gain in adulthood exceeded 5.00 kg was much lower ( β=-0.185, 95% CI: -0.320--0.049, P=0.008), while their insulin-like growth factor-binding protein-3 ( β=0.389, 95% CI: 0.183-0.594, P<0.001) and leptin receptor ( β=0.245, 95% CI: 0.048-0.442, P=0.015) levels were higher. Weight gain in adulthood is strongly associated with the changes in obesity-related breast cancer risk biomarkers. Women should maintain a stable weight throughout adulthood and it is preferred that their weight gain should not exceed 5.00 kg.

Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors.

Antiangiogenic tyrosine kinase inhibitors (TKIs) provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma (HCC). However, patients with HCC often develop resistance toward antiangiogenic TKIs, and the underlying mechanisms are not understood. The aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in HCC. We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC patients. We evaluated the prognosis, therapeutic response, and serum insulin-like growth factor-binding protein-1 (IGFBP-1) levels of 31 lenvatinib-treated HCC patients. Based on the array of results, a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were conducted. Additionally, in vivo genetic and pharmacological gain- and loss-of-function experiments were performed. In the patient cohort, IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall survival. Mechanistically, antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor signaling. IGFBP-1 stimulated angiogenesis through activation of the integrin α5β1-focal adhesion kinase pathway. Consequently, loss of IGFBP-1 and integrin α5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib treatment. Together, our data shed light on mechanisms underlying acquired resistance of HCC to antiangiogenic TKIs. Antiangiogenic TKIs induced an increase of tumor IGFBP-1, which promoted angiogenesis through activating the IGFBP-1-integrin α5β1 pathway. These data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors.

Etiological study of short stature in children and role of insulin like growth factor-1 and insulin like growth factor binding protein-3 as screening markers for growth hormone deficiency.

To determine aetiological factors in children with short stature, and to evaluate the role of insulin like growth factor-1 and insulin like growth factor binding protein-3 as screening markers for growth hormone deficiency. The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2020 to July 2021, and comprised children with short stature. Evaluation protocol included complete history and examination, baseline laboratory investigations, X-ray for bone age and karyotyping. Growth hormone status was assessed using growth hormone stimulation tests, and serum insulin like growth factor-1 and insulin like growth factor binding protein-3 levels were also assessed. Data was analysed using SPSS 25. Of the 649 children, 422(65.9%) were boys and 227(34.9%) were girls. The overall median age was 11 years (interquartile range: 11 years). Of the total, 116(17.9%) children had growth hormone deficiency. Familial short stature was present in 130(20%) children and constitutional delay in growth and puberty in 104(16.1%). There was no significant difference in levels of serum insulin like growth factor-1 and insulin like growth factor binding protein-3 in children who had growth hormone deficiency and those who had other causes of short stature (p>0.05). Physiological variants of short stature were found to be more common in the population followed by growth hormone deficiency. Serum insulin like growth factor-1 and insulin like growth factor binding protein-3 levels alone should not be used to screen children with short stature for growth hormone deficiency.

The Association Between the Serum Level of IGF-1 and IGFBP-3 and the Risk of Breast Cancer among Women in the Gaza Strip.

The purpose of this research was to look at the relationship between insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels and the risk for breast cancer (BC) among women in the Gaza Strip. This case-control study, which included 334 participants (112 women with BC as cases, and 222 women without BC as control), was conducted between January 2021 and August 2022. Research data for the cases were gathered at the Oncology Departments of the Gaza Strip's two hospitals, "Al- Shifa Hospital and Turkish Palestinian Friendship Hospital," as well as from the electronic records of the Screening Mammogram Unit at Al- Remal Clinic for controls. The information about the participants was gathered using a standardized questionnaire. The key variables related to BC were identified using multivariate logistic regression. According to multivariate logistic regression, participants' age was associated with an increase in the risk of BC (OR= 1.03; 95%CI, 1.007-1.060). There was an association between serum concentrations of fasting blood glucose (FBG) (OR= 1.027; 95% CI, 1.013-1.042), IGF-1 (OR= 1.010; 95% CI, 1.006-1.015), and the risk of BC, while there was no link between IGFBP-3 and the risk of BC. In an analysis of the risk according to menopausal status, premenopausal women were associated with an approximate 0.5 time decrease in risk of BC compared to women in post-menopause (OR= 0.428, 95% CI, 0.258, 0.710). Dairy product was also related to a decreased risk of BC. The results suggest that age, lower physical activity, increased levels of FBG, and IGF- 1 increase the BC risk among females in the Gaza Strip. Meanwhile, premenopausal women and dairy products are linked to a reduction in the risk of BC. Furthermore, no link was found between IGFBP-3 and BC risk. Improving early BC detection rates in the Gaza Strip necessitates preventative interventions and screening for BC in the public and healthcare sectors.

The relationship between serum leptin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels and clinical parameters in primary fibromyalgia patients.

The aim of this study was to investigate the levels of leptin, growth hormone, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 and their relations with clinical parameters in patients with primary fibromyalgia and healthy controls. Our study was performed on 30 female patients with primary fibromyalgia and 30 healthy controls. The levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured by a two-site immunoradiometric assay. The serum level of leptin was measured by the ELISA kit. The serum level of leptin was significantly higher, but the serum levels of insulin-like growth factor-1 were significantly lower in patients with fibromyalgia syndrome than healthy controls (p<0.001). The leptin level was positively correlated with the Visual Analog Scale, Fibromyalgia Impact Questionnaire score, Beck Depression Inventory score, tender point count, age, and duration of disease (p<0.001), but it was negatively correlated with insulin-like growth factor-1 (p<0.001). The insulin-like growth factor-1 level was negatively correlated with age, Visual Analog Scale, Fibromyalgia Impact Questionnaire and Beck Depression Inventory scores, duration of disease, and tender point count (p<0.001). Our results indicate that high levels of serum leptin and low levels of serum insulin-like growth factor-1 may play a role in the physiopathogenesis of fibromyalgia and may be related to some symptoms.

Effects of high-dose recombinant human growth hormone treatment on IGF-1 and IGFBP-3 levels in idiopathic dwarfism patients.

Objective:To investigate the effects of high-dose recombinant human growth hormone(rhGH) treatment on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in patients with idiopathic dwarfism.Methods:This study retrospectively investigated records of idiopathic dwarfism patients treated at Anhui Children’s Hospital or the Affiliated Hospital of Xuzhou Medical University between May 2019 and October 2020. The study identified 76 patients, which were divided based on rhGH treatment dosage into high- and low-dose groups.Results:The high-dose group showed a total efficacy of 95.3%, which was significantly higher than the 79.41% observed in the low-dose group (P<0.05). Moreover, height, weight, IGF-1 levels, and IGFBP-3 levels were all significantly elevated in the high-dose group compared to the low-dose group (P<0.05). No significant difference in adverse reaction incidence was observed between high- (9.5%) and low-dose (8.8%) groups (P>0.05).Conclusions:Higher doses of rhGH can provide improved curative effects in patients with idiopathic short stature, likely via elevated levels of IGF-1 and IGFBP-3.

Origin of the X-chromosome influences the development and treatment outcomes of Turner syndrome

Turner syndrome (TS) affects 1/2,500 live-born female infants. In the present study, we attempted to clarify the relationship between genetic factors (especially the X-chromosome origin), clinical features, body/sexual development, and treatment outcomes. We enrolled 39 female infants aged between 3 and 14 years. General demographic and clinical features were documented, and laboratory analysis of blood samples was performed. Subject karyotype was determined by G-banding of 50 peripheral white blood cells, and the parenteral origin of the retained X-chromosome was determined. Next, growth hormone (GH) treatment was prescribed for 12 months, with follow-ups performed as determined. For patient groups separated according to X-chromosome origin, the basal height, bone age, insulin-like growth factor (IGF)-1, and insulin-like growth factor binding protein-3 (IGFBP-3) levels were comparable; however, after the 12-month treatment, significant differences in the height increase and IGF-1 levels were observed. If the X-chromosome (or chromosomes) originated from both parents, the increase in height was less substantial, with lower serum IGF-1 levels. The uterine size, prolactin level, increased weight after treatment, and bone age difference after treatment negatively correlated with the mother’s age at the time of birth. The mother’s height at the time of birth demonstrated a negative correlation with the basal bone age difference and a positive correlation with the IGF-1 level. In summary, the retained X-chromosome derived from both parents is associated with poorer response to GH therapy. The mother’s age and height at the time of birth can strongly impact the patient’s body/sexual development and the response to GH treatment. Thus, the mother’s age and height at the time of birth and the parental origin of the X-chromosome should be carefully considered before developing a treatment plan for TS.

Malnutrition in children associated with low insulin-like growth factor binding protein-3 (IGFBP-3) levels

ObjectiveThis study aimed to compare serum levels of Insulin-like Growth Factor Binding Protein-3 in children with malnutrition and good nutritional status. MethodThis cross-sectional study included 41 participants consisting of 31 malnourished, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. IGFBP-3 levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method. ResultMedian serum IGFBP-3 levels in malnourished children were found to be lower i.e. 0.35mcg/mL (minimum–maximum: 0.04–1.52mcg/mL) compared to well-nourished children 1.52ng/mL (minimum–maximum 0.47–3.17mcg/mL). ConclusionSerum IGFBP-3 levels can be used as indicators to assess nutritional status.

The effects of physical activity on physiological markers in breast cancer survivors: A meta-analysis.

Background:To systematically evaluate the effects of physical activity on physiological markers in breast cancer survivors.Methods:A systematic search of the PubMed, Wed of Science, Medline, CNKI and Wanfang Database was performed to identify eligible randomized controlled trials to explore physical activity on physiological markers in breast cancer survivors. STATA version 13.0 (Stata Corp LP, College Station, TX) was used for all statistical analyses.Results:A total of 11 articles with 941 cases were eligible in this meta-analysis. The results of the meta-analysis showed that physical activity could decrease the levels of insulin (SMD = −1.90, 95%CI: −3.2 to −0.60; I2 = 92.3%, P < .001), insulin-like growth factor 1 (IGF-I) (WMD = −4.67, 95%CI: −23.14 to 13.79; I2 = 96.2%, P < .001), insulin-like growth factor binding protein-3 (IGFBP-3) (WMD = −20.09, 95%CI: −47.15 to 6.97; I2 = 93.3%, P < .001). However, compared with the control group, there was not the significant change of insulin-like growth factor 2 (IGF-II), insulin-like growth factor binding protein-1 (IGFBP-1), leptin, adiponectin, glucose, C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-ɑ) levels after the intervention.Conclusions:Physical activity could improve the insulin function that might be associated with decreasing the levels of IGF-I, IGFBP-3 and insulin in breast cancer survivors.

Association of Growth Velocity with Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Levels in Children with a Vegan Diet

Background: The vegan diet in children provides the benefit of reducing the risk of being overweight and improving the fat profile. The risk that can occur in the provision of a vegan diet in children is anthropometric size below reference and low caloric intake. Growth hormone (GH) and Insulin like Growth Factors (IGFs) are powerful stimulators for longitudinal growth of bone and require insulin-like growth factor binding protein (IGFBPs) which acts as a transport protein for IGF-1. A vegan diet with lower calorie intake in children has lower IGF-I levels than children with an omnivorous diet.Objective: Examining the effect of vegan diets on IGF-1 levels, IGFBP-3 levels, and growth velocity.Methods: This study was done with a prospective cohort design. The study subjects were divided into two groups, namely the vegan group and the omnivorous group, then matched based on age and sex. During the study, anthropometric data collection, IGF-1 and IGFBP-3 levels measurements were done in both vegan children and omnivorous children.Results: During 6 months of observation, 22 subjects were divided into two groups, namely children with a vegan diet and children with an omnivorous diet. IGF-1 (ng / mL) in vegan children was 105.5 ± 47.3 compared to 102.7 ± 42.3 in omnivorous children with a value of p = 0.89. IGFBP-3 (ng / mL) in vegan children was 2146.4 ± 595.1 compared to 2142 ± 609.1 in omnivorous children with value of p = 0.99 and Growth Velocity (cm / 6 months) was 3.0 in vegan children (1.0-5.30), and 3.2 (2.6-6.5) in omnivorous children with value of p = 0.41.Conclusion:Children with vegan diet had IGF-1 level, IGFBP-3 level, and growth velocity that were the same as children with an omnivorous diet.

Association between serum insulin like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 levels and chronic kidney disease in diabetic patients

Introduction: Insulin-like growth factor-1 (IGF-1) is a potent mitogen for glomerular mesangial cells which can stimulate cell migration and the production of fibronectin, proteoglycan, and type IV collagen, thereby promoting the development of the chronic kidney disease (CKD) in patients with diabetes. Objectives: The aim of the study was to assess the associations between serum levels of IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3) and CKD in diabetic patients. Patients and Methods: We investigated 102 Belarusian men and women with diabetes type 2 aged 56.67±0.81 years. Control group included 68 healthy people the same age. We estimated GFR with the use of the CKD-EPI creatinine-cystatin C equation to determine eGFRcr_cys. Serum total IGF-1 and IGFBP-3 levels were measured using immunoradiometric assay (IRMA) (Beckman Coulter, Czech Republic s.r.o.). Results: Patients with diabetes had significantly lower level of IGF-1 than controls. However, IGFBP-3 levels were similar in the two groups. Diabetic patients with CKD had significantly higher levels of IGF-1 and IGFBP-3 than diabetic patients without CKD (P=0.0031). However, according to multivariate analysis, only IGF-1 and cystatin C were associated with renal impairment. In detail, the odds of having eGFR&lt;60 mL/min/1.73 m2 increased with rising IGF-1 levels (OR: 1.025, [CI 1.002-1.048]). Conclusion: Our study revealed that higher serum IGF-1 levels were positively associated with CKD in patients with diabetes. We suggest that IGF-1 might be a predictor of CKD in patients with diabetes. Further research is necessary to confirm the observed this association and to detect the causal relations.

Does insulin-like growth factor influence prognosis ten months after myocardial infarction?

Background: We investigated the levels of insulin-like growth factor-1 (IGF-1) in acute myocardial infarction (AMI) patients, and we determined whether a decrease in IGF-1 could influence long-term prognosis.Methods: In total, 65 patients who were admitted to our hospital for AMI and 25 healthy controls were included in this study. Fasting blood samples were obtained from all patients immediately after AMI and 10 months later to determine their IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels. Fasting blood samples were obtained from the control group. The patients were also evaluated for cardiac events 10 months after AMI.Results: The IGF-1 levels were higher in the AMI patients than in the healthy controls (p=0.002); after 10 months, both the IGFBP-3 and IGF-1 levels were higher. No differences were found in cardiac event occurrence between patients with low and high IGF-1 and IGFBP-3 levels (for both the baseline and 10-month values).Conclusions: The serum total IGF-1 and IGFBP-3 levels were higher in the AMI patients compared to the control patients; however, there was no correlation between the IGF-1 and IGFBP-3 levels and cardiac events during the 10-month period after AMI. Additional studies are needed to clarify the time required for IGF-1 and IGFBP-3 level normalization after AMI, and to determine the effects of IGF-1 and IGFBP-3 on the long-term prognosis of patients after AMI.

Serum phosphate: Does it more closely reflect the true state of acromegaly?

An increased serum phosphate (P) level is common in acromegaly patients, however, the relationships among P, growth hormone (GH), insulin-like growth factor 1 (IGF-1) and disease status remain unknown. To reveal these relationships, we examined the association of P with comprehensive clinical data. We measured the serum P, calcium, GH, oral glucose tolerance test-GH (OGTT-GH), IGF-1, and insulin-like growth factor binding protein-3 (IGBP-3) levels in 103 acromegaly patients. SAGIT® was used to assess the disease status comprehensively. Spearman’s rank correlation coefficient was obtained to evaluate the associations among the above parameters. Stepwise multiple linear regression analysis was performed to investigate factors independently associated factors with the SAGIT scores. The area under the receiver operating characteristic curve (AUCROC) was used to evaluate the efficacy of the percentage change in the serum phosphate level in predicting remission in patients with postoperatively discordant GH and IGF-1 levels. Hyperphosphatemia was found in 68.9% of patients at baseline. The serum P level was higher in the non-remission group, but no correlation was found between hyperphosphatemia and remission. We revealed a significant correlation between the P level and SAGIT® score in patients both preoperatively (r = 0.659, p = 0.000) and 1-year postoperatively without remission patients (r = 0.534, p = 0.027). All biochemical levels decreased significantly postoperatively, and the GH and OGTT-GH levels achieved early stability (1 month); however, the P, IGF-1 and IGBP-3 levels showed a gradual decline. A percentage change in P of −8.12% is recommended as a cut-off value for predicting remission in patients with postoperatively discordant GH and IGF-1 levels. As a metabolic product which affected by the GH/IGF-1 axis, serum P appears to more closely reflect the comprehensive disease status in acromegaly. When the GH and IGF-1 levels are discordant during follow-up, perioperative change in the P level may be a potential predictor of remission.

Gonadotropin versus Follicle-Stimulating Hormone for Ovarian Response in Patients Undergoing in vitro Fertilization: A Retrospective Cohort Comparison

Poor ovarian responders generally refer to patients who respond poorly to ovarian stimulation for assisted reproductive techniques (ART) such as in-vitro fertilization (IVF) and hence experience low live birth rate. Various controlled ovarian stimulation (COS) protocols have been developed during the past 3 decades for IVF/ICSI to improve oocyte quality and ultimately live birth rate, to increase ovarian response in POR patients, and to reduce the risk of ovarian hyperstimulation syndrome. Both highly puri?ed human menopausal gonadotropin (hp-hMG) and recombinant follicle-stimulating hormone (rFSH) have been widely used for COS during IVF/ICSI. Their in?uence on treatment outcome in women undergoing IVF/ICSI hasbeen actively debated. To compare highly purified human menopausal gonadotropin (hp-hMG) and recombinant follicle-stimulating hormone (rFSH) in patients with poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection with a gonadotropin-releasing hormone antagonist protocol. This retrospective cohort study included 60 patients with poor ovarian response (30 received hp-hMG and 30 received rFSH) undergoing in vitro fertilization/intracytoplasmic sperm injection with a gonadotropin-releasing hormone antagonist protocol. Pregnancy-related outcomes, ovarian response, oocyte, and embryo parameters were compared between the 2 groups. Additionally, serum insulin-like growth factor-1 and insulin-like growth factor binding protein-1 levels on the day of oocyte retrieval were compared between the 2 groups. The 2 treatments resulted in comparable numbers of oocytes retrieved and embryos, comparable oocyte retrieval rate, mature oocyte rate, and fertilization rate, and also comparable clinical pregnancy rates, implantation rates, and miscarriage rate. However, hp-hMG led to statistically insignificant higher viable embryo rate (54.0% vs 44.8%; P = 0.174) and live birth rate per pregnancy (16.7% vs 10%) versus rFSH. Finally, statistically significantly higher serum insulin-like growth factor-1 level (178.53 [13.70] ng/mL vs 164.93 [12.17] ng/mL; P = 0.01) and statistically insignificantly lower serum insulin-like growth factor binding protein-1 level (19.53 [3.56] ng/mL vs the lower insulin-like growth factor binding protein-1 level SD is (2.76 [20.83] ng/mL; P > 0.05) on the day of oocyte retrieval were associated with hp-hMG versus rFSH. hp-HMG and rFSH did not lead to significantly different treatment outcomes in patients with poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection with a gonadotropin-releasing hormone antagonist protocol, although significantly higher serum insulin-like growth factor-1 level and insignificantly lower serum insulin-like growth factor binding protein-1 level on the day of oocyte retrieval associated with hp-HMG might suggest a beneficial endocrine environment. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Elevated levels of IL-6 and IGFBP-1 predict low serum IGF-1 levels during continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants

ObjectiveSteady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels. MethodsNineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3. ResultsThirty seven percent of IGF-1 values during active treatment were <20 μg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.30 (95% CI 1.03–1.63), p = .026, and 1.57 (95% CI 1.26–1.97), p < .001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.74 (95% CI 1.19–2.53), p = .004. ConclusionIn preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels.The trial is registered at ClinicalTrials.gov (NCT01096784).

Up-regulation of Insulin-like Growth Factor Binding Protein-3 Is Associated with Brain Metastasis in Lung Adenocarcinoma.

The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-β (TGF-β)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.

Copeptin and insulin-like growth factor binding protein-1 during follow-up after an acute myocardial infarction in patients with type 2 diabetes: A report from the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction 2 cohort.

Copeptin and insulin-like growth factor binding protein-1 analysed at admission for a myocardial infarction in patients with type 2 diabetes mellitus predicts cardiovascular events. The present aim was to study the association between copeptin and insulin-like growth factor binding protein-1, the development of the levels over time, and if the predictive value remained when measured at hospital discharge and 3 months thereafter. Copeptin and insulin-like growth factor binding protein-1 were analysed in patients (median age = 70, male = 68%) with type 2 diabetes mellitus + myocardial infarction at admission (n = 393), discharge (n = 309) and 3 months later (n = 288). The primary endpoint was cardiovascular event (cardiovascular death/non-fatal myocardial infarction/stroke) with the three time points as separate baselines. The median copeptin levels were 21.8 pmol/L at admission, 8.5 pmol/L at discharge and 8.4 pmol/L after 3 months, while insulin-like growth factor binding protein-1 levels continued to increase. There were significant correlations between the biomarkers at all occasions. During an average follow-up of 2.5 years, copeptin, but not insulin-like growth factor binding protein-1, predicted cardiovascular event at all occasions in unadjusted analyses. Copeptin remained as a predictor at discharge and after 3 months in the final multiple model (including: heart failure/age/creatinine clearance). The relationship between copeptin and insulin-like growth factor binding protein-1 during the initial phase of a myocardial infarction persisted in a less-stressful situation, and copeptin remained as a prognostic indicator at discharge and 3 months later.

The correlation between birth weight and insulin-like growth factor-binding protein-1 (IGFBP-1), kisspeptin-1 (KISS-1), and three-dimensional fetal volume

Purpose: This study aimed to determine the relationship between birth weight, and maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) and kisspeptin-1 (KISS-1) levels, and first-trimester fetal volume (FV) based on three-dimensional ultrasonography. Materials and methods: The study included 142 pregnant women at gestational week 11°–136. All fetuses were imaged ultrasonographically by the same physician. Maternal blood samples were collected at the time of ultrasonographic evaluation and analyzed for IGFBP-1 and KISS-1 levels via enzyme-linked immunosorbent assay (ELISA). Maternal and neonatal weights were recorded at birth. Birth weight ≤10th and the >90th percentiles was defined as small and large for gestational age (SGA and LGA), respectively. Results: Median crown-rump length (CRL), FV, and maternal serum IGFBP-1 and KISS-1 levels were 58.2 mm (35.3–79.2 mm), 16.3 cm3 (3.8–34.4 cm3), 68.1 ng mL−1 (3.8–377.9 mL−1), and 99.7 ng L−1 (42.1–965.3 ng L−1), respectively. First-trimester IGFBP-1 levels were significantly lower in the mothers with LGA neonates (p < .05). There was a significant positive correlation between CRL and FV, and between the IGFBP-1 and KISS-1 levels. IGFBP-1 levels and maternal weight at delivery were negatively correlated with neonatal birth weight. There was no correlation between CRL or FV and maternal IGFBP-1 or KISS1 levels (p > .05). The maternal IGFBP-1 level during the first trimester was a significant independent factor for SGA and LGA neonates (Odds ratio (OR): 0.011, 95%CI: 1.005–1.018, p < .001; and OR: 1.297, 95%CI: 1.074–1.566, p = .007, respectively). There was no significant relationship between SGA or LGA, and CRL, FV, or the KISS-1 level. Conclusions: As compared to the maternal KISS-1 level, the maternal IGFBP-1 level during the first trimester might be a better biomarker of fetal growth. Additional larger scale studies are needed to further delineate the utility of IGFBP-1 as a marker of abnormal birth weight.

Pilot Mechanistic Study of Insulin Modulation of Somatotrophic Hormones, Inflammation, and Lipid Metabolism During Critical Illness in Children.

To evaluate the mechanism of insulin modulation on somatotrophic response, inflammation, and lipid metabolism in critically ill children. Open-label randomized mechanistic study. Two-center, tertiary PICU study. Thirty critically ill children between 1 month and 14 years old, requiring mechanical ventilation and with evidence of two or more organ system failures. Randomized physiologic design of hyperinsulinemic-euglycemic clamp using continuous insulin infusion at 0.1 U/kg/hr versus conventional management. Thirteen children underwent hyperinsulinemic-euglycemic clamp. Blood samples for somatotrophic, inflammatory, and metabolic evaluation were obtained before randomization, and 24 and 72 hours later. A growth hormone oscillation profile was obtained during the first night. There was no difference between groups at baseline. Growth hormone resistance, increased proinflammatory cytokines, and increased lipolysis with low lipoprotein levels were present in all patients. Hyperinsulinemic-euglycemic clamp did not affect growth hormone, insulin-like growth factor-1 or insulin-like growth factor binding protein-3 levels. By day 2, insulin reduced insulin-like growth factor binding protein-1 levels. Tumor necrosis factor-α and interleukin-1β were similar in both groups, whereas interleukin-6 levels reduced over time only in children receiving hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamp also decreased free fatty acid levels, which was accompanied by increased low-density lipoprotein cholesterol and relative increase in high-density lipoprotein levels. Total cholesterol and triglycerides were unchanged. Insulin does not reverse most of the somatotrophic changes induced by the stress of critical illness. Rather, it may improve lipid metabolism and down-regulate some markers of the inflammatory response.