Serum IGFBP-3 Levels Research Articles

The utility of Insulin Like Growth Factor Binding Proteins (IGFBPs-1, 2, 3) with genes expression in resistance to Imatinib and Nilotinib in chronic myeloid leukemia: a pilot study from Delta Egypt

Introduction: Resistance to tyrosine kinase inhibitors (TKIs) is an obstacle facing CML patients in spite of the high cure rate. In this context, a study association between IGFBP (1, 2, 3) genes expression and their proteins in CML with the response to TKI has been implicated. Patients and methods: 115 newly diagnosed CML in chronic phase (CP) followed up over 12 months under TKI. 116 apparently healthy individuals were used as a control. RT-qPCR amplification was used for detecting IGFBPs genes expression, and ELISA technique was used for measuring serum IGFBPs. Results: IGFBP-1 and IGFBP-3 genes expression, as well as their serum levels, were significantly higher in CML patients, whereas IGFBP-2 gene expression was not. Interestingly, IGFBP-1 gene expression and IGFBP-1 serum levels were significantly higher in resistant patients compared to responder patients. However, the expression of IGFBP-2, 3 genes and their serum were insignificant. Conclusion: IGFBP-1 gene expression and its serum were significantly correlated with resistance. It is currently recommended that IGF-receptor inhibitors be developed and utilized. We are hoping to optimize the cure rate for CML treated with TKIs. Keywords: IGFBP-1-3; Gene expression; CML; Imatinib; Nilotinib.

8015 Growth Hormone Axis Dysfunction in PMM2-CDG: Exploring the Role of Dynamic Tests for the Management of Short Stature in Two Pediatric Cases

Abstract Disclosure: G. Del Medico: None. E. Procopio: None. L. Ferri: None. A. Barbato: None. A. Morrone: None. S. Stagi: None. PMM2-CDG is the most prevalent congenital disorder of glycosylation (CDG) and is caused by defective phosphomannomutase2 (PMM2) activity. According to the 2019 guidelines, approximately half of PMM2-CDG patients exhibit short stature and low serum levels of insulin-like growth factor-1 (IGF-1), IGF binding protein 3 (IGFBP3), and acid-labile subunit (ALS). Despite this, there is no expert consensus on the endocrinological management of this condition. We investigated the growth hormone (GH) axis in two 12-year-old female patients with PMM2-CDG. The first patient was compound heterozygote for the most common PMM2 gene variants in Italy, p.(Leu32Arg) and p.(Arg141His). She presented with short stature (< 2 Standard Deviation Score, SDS) and low serum levels of IGF-1 and IGF-BP3 (< 2.5° for age and sex). Bone age was significantly delayed. Tanner stage was prepubertal. Somatotropic response to GH stimulation testing (Levodopa) was normal. After the IGF-1 generation test with recombinant GH, serum IGF-1 increased by 115%. The second patient was compound heterozygote for the known PMM2 pathogenetic variant p.(Ala108Val) and the novel p.(Thr171Asnfs*11) variant (only case described in literature). She presented short stature (< 2 SDS) with near-to-normal IGF-1 and IGF-BP3 serum levels (2.5° for age and sex). Bone age was slightly delayed. Tanner stage was prepubertal. She also exhibited severe obesity, hypertriglyceridemia, and hepatic steatosis. Her somatotropic response to two GH stimulation tests (Levodopa and Arginine) was deficient, probably because of her significant overweight. IGF-1 serum levels didn’t increase after the IGF-1 generation test. Hypoglycosylation in PMM2-CDG impairs the IGF1 system on multiple levels. It destabilizes the ternary complex formed by IGF-1 and glycoproteins IGFBP3 and ALS, therefore reducing the half-life of circulating IGF-1. Hypoglycosylation also reduces IGF1 production by impairing its precursor proIGF-1Ea and its cellular secretion. As a result, PMM2-CDG patients have GH insensitivity, with normal GH production but low levels of IGF-1. However, there is a lack of information in the literature on the use of dynamic tests and hormonal therapies (GH and rhIGF-1) in CDG. The IGF-1 generation test in our patients showed partial GH sensitivity in the first patient and GH insensitivity in the second patient. These observations suggest variability. Some PMM2-CDG patients may benefit from an extended trial with GH therapy, while for GH-insensitive patients a trial with recombinant IGF-1 might be considered. This is one of the first reports that explores the potential role of dynamic tests in PMM2-CDG. As the biochemical effects of hypoglycosylation on the GH-IGF1 pathway are becoming clearer more clinical research is needed to reach a consensus on the management and treatment of short stature in these patients. Presentation: 6/3/2024

Serum Insulin-like Growth Factor-Binding Protein-2 as a Prognostic Factor for COVID-19 Severity.

Insulin-like growth factor-binding protein (IGFBP)-2 is a regulator of anabolic pathways, which become inactivated in severe illness. Here, we measured the serum IGFBP-2 levels of COVID-19 patients with moderate and severe disease as well as healthy controls to identify the associations of serum IGFBP-2 levels with disease severity. Patients with severe COVID-19 had higher serum IGFBP-2 levels than those with moderate disease and healthy controls, who had similar levels. Non-survivors of COVID-19 tended to have elevated serum IGFBP-2 levels compared to survivors. Increased serum IGFBP-2 levels were observed in patients requiring dialysis and vasopressor therapy. Serum IGFBP-2 was positively correlated with procalcitonin in both patient groups. Bacterial co-infection in severe COVID-19 patients did not influence serum IGFBP-2 levels. Patients with liver cirrhosis and obesity, showing increased and decreased serum IGFBP-2 levels, respectively, were excluded from the study. The present analysis showed that higher serum IGFBP-2 levels are associated with increased disease severity in COVID-19 patients. The similarity in serum IGFBP-2 levels between patients with moderate COVID-19 and healthy controls suggests that elevated IGFBP-2 is associated with critical illness rather than SARS-CoV-2 infection itself.

Insulin-like growth factor-1 (IGF-1) levels in multiple sclerosis patients: A systematic review and meta-analysis.

Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

The effect of Nigella sativa on serum levels of insulin-like growth factor and its binding proteins in postmenopausal women with low bone density: A triple-blind randomized controlled trial

Animal studies have shown that Nigella sativa (NS) seed oil can increase Insulin-like growth factor (IGF-1) serum levels. This study aimed to investigate the effect of oral capsule NS on serum levels of IGF-1 and its binding proteins (IGFBP-1, IGFBP-3) in postmenopausal women with bone loss density. Sixty postmenopausal women of 50 to 65 years with bone loss density randomly received a soft capsule of NS oil 1000 mg or placebo once daily for six months with a 1:1 allocation ratio. DEXA method was used to measure bone density. Serum concentrations of IGF-1, IGFBP-1 and-3, ALT, AST, ALP, Cr, and urea were measured at baseline and after the intervention. There were no significant differences in serum levels of IGF1, IGFBP-1, urea, Cr, ALT, AST, and ALP between the two groups at the end of six months. However, a significant increase has been shown in IGFBP-3 between groups after the intervention (Adjusted mean difference: 95% CI: 1.65: 0.36 to 2.97; p=0.013). We observed a significant increase in IGFBP-3 serum levels without any side effects. Additional research with an increased number of participants may be needed for further clarification of its beneficial anabolic effects on the GH system.

Activity of granulomatosis with polyangiitis and its correlation with mTOR phosphoproteomics in neutrophils.

Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis with a complex pathomechanism. Organ damage in GPA is also mediated by extracellular trap formation (NETosis). We analyzed the functional status of phosphoproteins modulating NETosis in neutrophils by the mammalian target of rapamycin (mTOR) pathway in GPA along with NETosis biomarkers. Phosphoproteins levels measured in isolated neutrophils from 42 patients with GPA (exacerbation n=21; remission n=21) and 21 healthy controls were compared to serum biomarkers of the disease. Neutrophils in active disease manifested lowered levels of phosphorylated mTOR(Ser2448), PTEN(Ser380) and ULK1(Ser555), whereas phosphorylated GSK-3α/β(Ser21/Ser9) was elevated. Exacerbation of GPA was characterized by elevated neutrophil dsDNA in serum, circulating mitochondrial DNA, and DNA-MPO complexes. A significant negative correlation between mTOR or PTEN phosphoproteins and biomarkers of GPA activity was also present, reflecting the clinical activity score of GPA. Positive correlations between phosphorylated GSK-3 α/β and circulating mtDNA, DNA-MPO complexes, neutrophil-released dsDNA, or circulating proteins were also significant. Increased serum levels of IGFBP-2, TFF-3, CD147, and CHI3L1 accompanied GPA exacerbation, whereas DPP-IV levels were the lowest in active GPA. Using a principal component analysis basigin, PTEN and mTOR had the highest loadings on the discrimination function, allowing classification between active, remission, and control subjects with 98% performance. We present evidence that inhibited mTOR signaling accompanies NETosis in patients with GPA. The functional status of phosphoproteins suggests simultaneous activation of NETosis and autophagy. These results give rise to the study of autophagy as a mechanism underlying granuloma formation in GPA.

Normal range for acid-labile subunit in paediatric patients in Spain and its association with age, sex, pubertal stage and other growth factors

IntroductionThe acid-labile subunit (ALS) plays an important role in the endocrine effects of insulin-like growth factors (IGFs) on target tissues. Historically, it has attracted limited attention. The aim of our study was to describe the normal range of ALS in healthy children and its association with other growth factors. Patients and methodsWe designed a cross-sectional descriptive study. We collected data on age, height, body mass index, gestational age, anthropometry at birth and serum levels of ALS, IGF1 and IGFBP3 in healthy children aged 2–15 years with a normal height. The levels of ALS, IGF1 and IGFBP3 were measured by ELISA. We fitted GAMLSS normalization models to standardize the variables. ResultsSamples were collected from 446 children. In prepubertal children, the levels of ALS, IGF1 and IGFBP3 were positively correlated in both sexes and with age (P < .01). We found significant differences in the levels of ALS, IGF1 and IGFBP3 and the IGF1/IGFBP3 molar ratio between the sexes and higher levels in pubertal boys (P < .01). We generated normal probability plots for each sex for each of the components of the ternary complex and for the IGF1/IGFBP3 and IGFBP3/ALS molar ratios. In addition, we extracted equations from the models for the calculation of z-scores for age and sex. ConclusionsThis study may contribute age- and sex-specific reference values for IGF1, IGFBP3 and ALS levels and IGF1/IGFBP3 and IGFBP3/ALS ratios in Spanish children and suggests an association between age, sex, and pubertal stage.

Association of genetic and epigenetic changes of insulin like growth factor binding protein-1 in Egyptian patients with type 2 diabetes mellitus

BackgroundDiabetes is one of the global health threat. Type 2 Diabetes mellitus (T2DM) is associated with life-threatening complications. This work, aimed to study the association between T2DM and IGFBP-1 gene methylation, gene polymorphism and serum levels of IGFBP-1. MethodWe included 100 subjects with T2DM and 100 control. DNA methylation of IGFBP-1 was analyzed using pyrosequencing, IGFBP-1 gene polymorphism was analyzed using real time polymerase chain reaction and serum level of IGFBP-1 was measured by ELISA. ResultsThere was DNA hyper methylation levels of IGFBP1 gene at each of the six CpG sites in T2DM patients than control (P < 0.001). IGFBP-1 gene polymorphism (rs 2854843) CC pattern was significantly associated with DM, P = 0.002. Also, there was decrease in serum IGFBP-1 in patients with T2DM than control group (P < 0.001). ConclusionWe concluded that DNA hyper methylation of IGFBP-1 gene and CC polymorphism (rs 2854843) of IGFBP-1 gene are associated with T2DM in Egyptian patients, also, decrease serum level of IGFBP-1. Further cohort study is recommended with large sample size to detect which one, epigenetic changes or polymorphism of IGFBP-1 gene, is the cause of T2DM or even both.

Potential Effects of Oral Isotretinoin on Growth Plate and Height

Longitudinal growth and puberty are the result of a complex interaction of genetic, hormonal, nutritional, and environmental factors. Acne vulgaris is a chronic disease of the pilosebaceous unit that affects 85% of adolescents worldwide. Isotretinoin is a synthetic vitamin A derivative drug effective and is widely employed for the treatment of moderate and severe acne vulgaris. Premature epiphyseal closure has been reported in patients with neuroblastoma treated with high doses of isotretinoin as well as in patients with acne receiving lower doses. Although the mechanisms for these effects are not clear, it has been suggested that isotretinoin may have a negative impact on the GH-IGF-I axis, leading to a reduction in IGF-I and IGFBP3 serum levels. Although many of the isotretinoin adverse effects in pediatric patients are transient, premature epiphyseal closure and bone abnormalities can lead to transient abnormalities and permanent deformities with a negative impact on longitudinal growth and final height. The aim of this study was to review the potential effects of oral isotretinoin on the growth plate and growth during childhood and adolescence.

Exercise combined with lysine-inositol vitamin B12 promotes height growth in children with idiopathic short stature

ObjectiveThis study was aimed to systematically determine the effect of exercise combined with lysine-inositol vitamin B12 (VB12) therapy on the height of children with idiopathic short stature (ISS). MethodsSixty children with ISS were randomly divided into observation and control groups (N = 30). Each group was given lysine-inositol VB12 oral solution (10 mL bid). Simultaneously, the observation group exercised following the “ISS exercise instruction sheet”. The height (H), growth velocity (GV), height standard deviation score (HtSDS) and other indicators were compared after 6 and 12 months of intervention, respectively. After 12 months of intervention, the biochemical indicators of the two groups, together with the correlation between the average days of exercise per week and average minutes of exercise per day, GV and serum growth hormone were analyzed. ResultsAfter 6 and 12 months of treatment, the GV, serum GHRH, GHBP, GH, IGF-1, and IGFBP-3 levels in the observation group were significantly higher than those in the control group, and HtSDS was significantly lower than that in the control group (P<0.01). After 12 months of treatment, the height of the observation group was significantly higher than that of the control group (P<0.05). There was no significant difference in the biochemical indicators between two groups (P>0.05). Average days of exercise per week and average minutes of exercise per day were positively correlated with GV and GHBP levels. Serum GHRH, GH, IGF-1, and IGFBP-3 levels were negatively correlated. Average minutes of exercise per day were negatively correlated with GV and GHBP levels. Serum GHRH, GH, IGF-1, and IGFBP-3 levels were positively correlated. ConclusionRegular and moderate stretching exercises combined with lysine-inositol VB12 can effectively promote height growth of children with ISS, which is clinically safe. The mechanism promotes serum GHRH, GHBP, GH, IGF-1, and IGFBP-3 levels.

Rango normal de subunidad ácido-lábil (ALS) en niños españoles y su relación con la edad, el sexo, el estadio puberal y otros factores de crecimiento

IntroductionThe acid-labile subunit (ALS) plays an important role in the endocrine effects of insulin-like growth factors (IGFs) on target tissues. Historically, it has attracted limited attention. The aim of our study was to describe the normal range of ALS in healthy children and its association with other growth factors. Patients and methodsWe designed a cross-sectional descriptive study. We collected data on age, height, body mass index, gestational age, anthropometry at birth and serum levels of ALS, IGF1 and IGFBP3 in healthy children aged 2-15years with a normal height. The levels of ALS, IGF1 and IGFBP3 were measured by ELISA. We fitted GAMLSS normalization models to standardize the variables. ResultsSamples were collected from 446 children. In prepubertal children, the levels of ALS, IGF1 and IGFBP3 were positively correlated in both sexes and with age (P<.01). We found significant differences in the levels of ALS, IGF1 and IGFBP3 and the IGF1/IGFBP3 molar ratio between the sexes and higher levels in pubertal boys (P<.01). We generated normal probability plots for each sex for each of the components of the ternary complex and for the IGF1/IGFBP3 and IGFBP3/ALS molar ratios. In addition, we extracted equations from the models for the calculation of z-scores for age and sex. ConclusionsThis study may contribute to age- and sex-specific reference values for IGF1, IGFBP3 and ALS levels and IGF1/IGFBP3 and IGFBP3/ALS ratios in Spanish children and suggests an association between age, sex and pubertal stage.

Candidate Angiogenesis-Related Biomarkers in Patients with Laryngeal Carcinoma (AngLaC): A Prospective Cohort Study.

Angiogenesis is indeed a vital process in the progression of carcinomas, including that of larynx. Therefore, this study (AngLaC) aimed to identify candidate angiogenesis-related biomarkers in laryngeal carcinoma patients. Prospective controlled cohort study. Tertiary referral center. In silico analyses of angiogenesis-related genes in laryngeal carcinoma were performed to determine candidate biomarkers. Serum levels of candidate biomarkers were determined via enzyme-linked immunosorbent assay in laryngeal carcinoma patients as well as in an age and gender-matched control group. The associations of the biomarkers with clinical parameters were investigated. The study included 60 laryngeal carcinoma patients and 20 healthy controls. The serum levels of osteopontin, IGFBP-3, VEGF, sVEGFR-1, and VEGFR-2 were significantly higher in the patient group (p < .001, p ≤ .001, p < .001, p < .01, p < .01, respectively). High osteopontin and sVEGFR-1 levels were associated with locoregional-recurrence (p = .024, p = .016, respectively). IGFBP-3 had the highest diagnostic sensitivity (81.4%) and specificity (80%) among the molecules that were investigated (p < .001). High sVEGFR-1 and low VEGFR-2 levels were associated with poor overall-survival (p = .037, p = .027, respectively). High osteopontin and sVEGFR-1 levels were associated with poor disease-specific survival rates (p = .035, p = .018, respectively). High serum levels of sVEGFR-1 and osteopontin as well as low serum levels of VEGFR-2 proved to be poor prognostic in terms of survival in laryngeal carcinoma. VEGF, sVEGFR1, VEGFR2, IGFBP-3, and osteopontin levels were found to be significantly increased in larynx cancer patients compared to the normal population. Further studies on osteopontin and sVEGFR-1 are required in order to determine their associations with recurrence.

Expression of Concern: The Influence of Promoter -202 A/C Polymorphism (rs2854744) of the IGFBP-3 Gene on Erectile Dysfunction Risk and Serum Levels of IGF-I and IGFBP-3.

No AccessJournal of UrologyExpression of Concern10 Jan 2023Expression of Concern: The Influence of Promoter −202 A/C Polymorphism (rs2854744) of the IGFBP-3 Gene on Erectile Dysfunction Risk and Serum Levels of IGF-I and IGFBP-3is a expression-of-concern ofThe Influence of Promoter –202 A/C Polymorphism (rs2854744) of the IGFBP-3 Gene on Erectile Dysfunction Risk and Serum Levels of IGF-I and IGFBP-3 Mohammad Reza Safarinejad, Nayyer Shafiei, and Shiva Safarinejad Mohammad Reza SafarinejadMohammad Reza Safarinejad *Correspondence: P.O. Box 19395-1849, Tehran, Iran telephone: 0098 21 22454499; FAX: 0098 21 22456845; E-mail Address: [email protected] Financial interest and/or other relationship with Urology Journal. More articles by this author , Nayyer ShafieiNayyer Shafiei More articles by this author , and Shiva SafarinejadShiva Safarinejad More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003142AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail "Expression of Concern: The Influence of Promoter −202 A/C Polymorphism (rs2854744) of the IGFBP-3 Gene on Erectile Dysfunction Risk and Serum Levels of IGF-I and IGFBP-3." The Journal of Urology, Publish Ahead of Print, pp. – From the Clinical Center for Urological Disease Diagnosis and Private Clinic Specialized in Urological and Andrological Genetics, Tehran, Iran© 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology20 Nov 2012The Influence of Promoter –202 A/C Polymorphism (rs2854744) of the IGFBP-3 Gene on Erectile Dysfunction Risk and Serum Levels of IGF-I and IGFBP-3 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohammad Reza Safarinejad *Correspondence: P.O. Box 19395-1849, Tehran, Iran telephone: 0098 21 22454499; FAX: 0098 21 22456845; E-mail Address: [email protected] Financial interest and/or other relationship with Urology Journal. More articles by this author Nayyer Shafiei More articles by this author Shiva Safarinejad More articles by this author Expand All Advertisement PDF downloadLoading ...

ODP395 Relationship of serum total insulin-like growth factor-binding protein-3 with triglyceride to high-density lipoprotein cholesterol ratio and glucose tolerance in Korean children and adolescents

Abstract Objectives We investigated the relationships between serum IGF-I/ IGFBP-3 levels and degrees of triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio in Korean children and adolescents who underwentoral glucose tolerance test. Methods children and adolescents without known diabetes were checked an oral glucose tolerance test and collected the clinical and laboratory data. Serum IGF-I and total IGFBP-3 levels, TG/HDL ratio, total cholesterol, low-density lipoprotein cholesterol (LDL),AST, ALT, C-peptide levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, and glycated hemoglobin (HbA1c) levels were measured. Results Serum TG/HDL ratio and IGF-I/ total IGFBP-3 levels were significantly higher in individuals with type 2 diabetes (DM) than in those with normal glucose tolerance (NGT) (P&amp;lt;0. 05). TG/HDL ratio was not related with age and IGF-I levels and it was correlated with serum IGFBP-3 levels, HbA1c, C-peptide, HOMA-IR, and body mass index. However, these relationships were altered in patients with insulin resistance state, especially in those with DM. In the DM group, TG/HDL ratio and total IGFBP-3 levels were positively correlated stronger than no-DM groups. In addition,TG/HDL ratio and total IGFBP-3 levels were positively correlated with total cholesterol and LDL levels but not with age. Conclusions TG/HDL ratio, the marker of small dense LDL particles, is related with IGFBP-3, especially in patients with type 2 diabetes. The IGF-I-IGFBP-3 axis, especially IGFBP-3, may play roles in the pathogenesis and metabolic control of lipid metabolism. Presentation: No date and time listed

Elevated Serum IGFBP-2 and CTGF Levels Are Associated with Disease Activity in Patients with Dermatomyositis.

Background Insulin-like growth factor-binding proteins (IGFBPs) and connective tissue growth factor (CTGF) participate in angiogenesis. Dermatomyositis (DM) is characterized by microvasculopathy-derived skin lesions. Here, we investigated the clinical significance of serum IGFBP and CTGF levels in DM patients. Methods In this study, 65 DM patients and 30 healthy controls were enrolled. Serum IGFBP and CTGF levels were examined by ELISA, and their correlation with clinical and laboratory findings was analyzed by Spearman's correlation. Results Serum IGFBP-2, IGFBP-4, and CTGF levels were higher in DM patients than in healthy controls (median (quartile): 258.9 (176.4–326.1) ng/mL vs. 167.7 (116.1–209.4) ng/mL, p < 0.0001; 450.4 (327.3–631.8) ng/mL vs. 392.2 (339.0–480.2) ng/mL, p = 0.04; and 45.71 (38.54–57.45) ng/mL vs. 35.52 (30.23–41.52) ng/mL, p = 0.001, respectively). IGFBP-2 and CTGF levels were positively correlated with cutaneous (r = 0.257, p = 0.040 and r = 0.427, p = 0.015, respectively) and global (r = 0.380, p = 0.002 and r = 0.292, p = 0.019, respectively) disease activity in DM patients. Conclusion Serum IGFBP-2 and CTGF levels were increased in patients with DM and correlated with cutaneous and global disease activity.

Free Insulin-like Growth Factor (IGF)-I in Children with PWS.

In children with Prader–Willi syndrome (PWS), the standard growth hormone (GH) dose often results in high immunoreactive IGF-I levels. These high immunoreactive IGF-I levels lead to concern because their long-term effects are unknown. As a result, clinicians have to lower the GH dose, which worsens body composition and quality of life. As clinical features do not seem to correspond to immunoreactive IGF-I values, it is questionable whether immunoreactive IGF-I is a suitable marker for GH dosing, or whether another parameter better reflects IGF-I bioavailability and bioactivity. We, therefore, investigate serum immunoreactive IGF-I, free IGF-I and IGFBP-3 levels in 70 GH-treated children with PWS. Our study showed that, although immunoreactive IGF-I levels were high (>2 SDS) in the vast majority of prepubertal and pubertal children, free IGF-I SDS levels were <0 SDS in most and <1 SDS in all. Free IGF-I correlated with the immunoreactive IGF-I, IGFBP-3 and IGF-I/IGFBP-3 ratio. We conclude that there is a major discrepancy between immunoreactive and free IGF-I levels. While in the majority of GH-treated children with PWS, immunoreactive IGF-I levels were high, free IGF-I levels were <0 SDS in most. Our data appear to be very reassuring and suggest that free IGF-I levels should also be taken into consideration when the immunoreactive IGF-I levels are >2 SDS in GH-treated children with PWS.

Effects of high-dose all-trans retinoic acid on longitudinal bone growth of young rats

ObjectiveThe signaling axis consisting of GH-IGF1-IGFBP3 is the primary signal taht acts prepubertally to influence height development. Growth plate thinning and even premature closure have been reported in children with tumors treated with retinoid chemotherapy, resulting in long bone dysplasia. Growth failure may occur despite received GH treatment, but the reason is unknown. This study investigate the effect of high-dose all-trans retinoic acid (ATRA) on the development of long bones in growing SD rats. MethodsA total of 20 three-week-old male SD rats were randomly divided into a control group and an experimental group (n = 10). Rats were treated by gavage with or without high-dose ATRA for 10 days. The body weights of the rats were recorded daily. At the end of the experiment, we measured the length of nose-tail and tibia, stained the tibia and liver for pathological tissue and RT-PCR reaction, and measured the levels of serum GH, IGF1 and IGFBP3, and so on. ResultsCompared with controls, experimental rats exhibited reduced body weight and shortened nasal-tail and radial tibial length. Cyp26b1 enzyme activity in the liver was elevated, and histopathological staining revealed that the cartilaginous epiphyseal plate was narrowed, the medullary cavity of trabecular bone was sparse, the number of trabecular bones was decreased, trabecular separation was increased, bone marrow mineralization was enhanced, osteoclastic activity was increased, and circulating GH-IGF1-IGFBP3 levels were decreased. However, RT-PCR reaction results of localized proximal tibiae showed upregulation of IGF1 and downregulation of IGFBP3. ConclusionsHigh-dose ATRA intake over a short period of time can reduce GH-IGF1-IGFBP3 levels, affect cartilage and bone homeostasis, and inhibit bone growth in developing animals.

Wearables, Respiratory Rehabilitation, Acute Myocardial Infarction and Frailty, and High-Intensity Respiratory Muscle Training

Wearables, Respiratory Rehabilitation, Acute Myocardial Infarction and Frailty, and High-Intensity Respiratory Muscle Training

A Clinical Study on the Treatment of Children's Short Stature with Auxiliary Comprehensive Management Combined with Growth Patch.

Objective To explore the clinical effect of auxiliary comprehensive management combined with growth patch in the treatment of childhood idiopathic short stature (ISS). Methods From September 2017 to December 2019, 120 children with ISS who met the selection criteria were collected. Random number table method divided them into 2 groups: one group was given auxiliary comprehensive management and recorded as the routine group (n = 60), and the other group was given auxiliary comprehensive management and combined growth patch treatment and recorded as the combination group (n = 60). The course of treatment was 12 months. The effects of the two methods on children's height, bone age, body weight, and insulin-like growth factor (IGF)-1 and IGF-binding protein (IGFBP)-3 levels were compared. Results There was no statistical difference between the two groups in baseline height, genetic height, baseline bone age, baseline body weight, and body weight before and after treatment (P > 0.05). After treatment, the heights of the two groups were higher than before for the same group, the height growth values and predicted adult height of the combination group were higher than those of the routine group, and the predicted adult height of the combination group was higher than the genetic height of the same group (P < 0.001). There was no statistical difference in IGF-1 and IGFBP-3 levels before treatment between the two groups (P > 0.05). The levels of IGF-1 and IGFBP-3 after treatment in the two groups were higher than those in the same group before treatment, and the combination group was higher than that in the routine group (P < 0.05). Conclusion On the basis of auxiliary comprehensive management, combined with growth patch for the treatment of children with ISS, it can effectively increase the height of the children, improve the levels of serum IGF-1 and IGFBP-3, and have significant clinical effects, which is beneficial to the healthy growth of the children.

Evaluation of the effect of glycemic control on the Growth and its relation to Insulin like growth factor binding protein type 3 in a sample of prepubertal Egyptian children with type 1 Diabetes Mellitus

Abstract Background PrePubertal children with type 1 diabetes mellitus are shorter than their non- diabetic peers. we aimed to evaluate the role of HbA1c and IGFBP-3 in this phenomenon. Aim of the work: The aim of the study was to evaluate the effect of glycemic control on the growth and IGFBP-3, represented by height, weight, height and weight percentiles for age in a sample of prepubertal Egyptian children with T1DM. Patients and Methods This study was a cross sectional study conducted on 80 pre-pubertal Egyptian children, divided into 25 Males and 25 Females with T1DM and 30 age matched controls (15 Males and 15 Females), the participants were recruited from the Outpatient Clinic of the Pediatric Department of Ain Shams University Hospitals and the National Institute of Diabetes and Endocrinology in Cairo, Egypt during the period from July 2018 to August 2019. Anthropometric measures including height and weight were obtained and used to calculate the height and weight percentiles using the CDC calculators. HbA1c as well as IGFBP-3 levels were tested. Results The mean age (years) of the participants was (9.671±2.24) for male patients, (9.22 ± 2.19) for female patients and (8.39 ± 2.034) for controls. The height found to be lower in the children with T1DM when compared to the disease-free controls with median values of (129.287 ± 13.410) in male patients, (127.727 ±10.155) in female patients and (136.760 ± 13.431) in the controls. the height and weight percentiles (%) were found to be lower in the children with T1DM when compared to the disease-free controls, the height percentile with median values of 14.54 (IQR 27.95) in male patients, 17.93 (IQR 29.20) in female patients and 87.07 (IQR 20.48) in the controls. the weight percentile with median values of 40.68 (IQR 40.83) in male patients, 30.64(IQR 35.59) in female patients and 85.18 (IQR 20.17) in the controls. A negative correlation between HbA1c (%) and serum IGFBP-3 (ng/ml), height and height percentile were found with (0.014, 0.049 and 0.012) as well as a positive correlation between serum IGFBP-3 and height, height and weight percentiles (%), were found with (,0.004, 0.009 and 0.005 respectively). Serum IGFBP-3 levels were also found to be significantly lower in patients (P &amp;lt; 0.001) with a mean value of (198.6 ± 45.335) in male patients and (168.4 ± 44.317) in female patients and (285.333 ± 61.936) in the disease-free controls. Conclusion Serum IGFBP-3 levels (ng/ml) as well as growth are negatively affected in prepubertal children with T1DM in relation to the glycemic control.