Insulin-Like Growth Factor Binding Proteins in Kidney Disease

The seven members of the insulin-like growth factor (IGF) binding protein family (IGFBPs) were initially considered to be the regulatory proteins of IGFs in the blood circulation, mainly as the subsequent reserve for bidirectional regulation of IGF function during environmental changes. However, in recent years, IGFBPs has been found to have many functions independent of IGFs. The role of IGFBPs in regulating transcription, inducing cell migration and apoptosis is closely related to the occurrence and development of kidney disease. IGFBP-1, IGFBP-3, IGFBP-4 are closely associated with diabetes and diabetic nephropathy. IGFBP-3, IGFBP-4, IGFBP-5, IGFBP-6 are involved in different kidney disease such as diabetes, FSGS and CKD physiological process as apoptosis proteins, IGFBP-7 has been used in clinical practice as a biomarker for early diagnosis and prognosis of AKI. This review focuses on the differential expression and pathogenesis of IGFBPs in kidney disease.

Insulin-like growth factor ternary complex components as biomarkers for the diagnosis of short stature

Objective The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature. Design Boys and girls (n = 429, 0.7–16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis. Results All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups. Conclusion Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.

Investigating whether serum IGF-1 and IGFBP-3 levels reflect the height outcome in prepubertal children upon rhGH therapy: LG growth study database

Serum insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3) levels can be used to monitor the safety of recombinant human growth hormone (rhGH) therapy. In this study, we evaluated the changes in serum IGF-I and IGFBP-3 levels during rhGH therapy as a marker of height outcome in prepubertal children. Totally, 705 prepubertal children with short stature were enrolled from the LG Growth Study Database. Data for three groups of subjects were obtained as follows: Idiopathic GH deficiency (IGHD; n = 486); idiopathic short stature (n = 66); small for gestational age (n = 153). Serum IGF-I and IGFBP-3 levels at the baseline and after the 1st and 2nd year of rhGH therapy, as well as the Δheight standard deviation score (SDS), were obtained. Δheight SDS after the 1st and 2nd year of rhGH therapy had notably increased compared to that at the baseline for all three groups. IGF-I and IGFBP-3 levels in all three groups were significantly increased compared to those at the baseline (p <0.001). Δheight SDS was positively correlated with ΔIGF-1 SDS after the 1st year of therapy, ΔIGFBP-3 SDS after the 2nd year of therapy in the IGHD group, and ΔIGF-I SDS and ΔIGFBP-3 SDS after the 2nd year of therapy (p < 0.05), regardless of whether the height at the baseline was a covariate. The increase in IGF-I and IGFBP-3 levels during rhGH therapy was related to the growth response in children with IGHD. Therefore, it may be valuable to measure the change in serum IGF-I and IGFBP-3 levels, especially the latter, during rhGH treatment to predict the growth response upon long-term treatment.

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.

Effects of COVID-19 Lockdown on Weight, Body Composition, and Behavior of Children, Adolescents, and Young Adults with Prader–Willi Syndrome

To reduce transmission of the coronavirus disease 2019 (COVID-19), many countries implemented lockdowns, causing the closure of childcare services. This study was designed to evaluate the impact of the COVID-19 lockdown in March–April 2020 on children, adolescents, and young adults with Prader–Willi syndrome (PWS) living in Germany. We recruited 180 participants with a genetically confirmed PWS. All families completed a questionnaire, and participants underwent a post-lockdown assessment; the last examination before the lockdown was determined as the pre-lockdown assessment. We used bivariate analyses to compare pre- and post-lockdown outcomes. Weight standard deviation scores (SDSPWS) and body mass index (BMI)-SDSPWS remained stable or even decreased in some age groups. A statistically significant gain in lean body mass (LBM) was found in all groups <18 years of age. We observed an increase in IGF-I and IGFBP-3 concentrations without a significant change in growth hormone (GH) dosage. Most families (95.4%) reported set mealtimes and implementation of structured activities (72.2%) during the lockdown period. We therefore suggest that the favorable development of weight/BMI and LBM was caused by an interplay of a suspected enhanced GH administration and continuous parental commitment. However, more intense behavioral problems were observed in 45.7%, which persisted post-lockdown in 33.7%.

The Role of IGF-Pathway Biomarkers in Determining Risks, Screening, and Prognosis in Lung Cancer: A Systematic Review.

Background: Detection rates of early-stage lung cancer are traditionally low, which contributes to inconsistent treatment responses and the highest rates of annual cancer deaths in the U.S. Currently, age and smoking history are the primary factors that qualify patients for low-dose computed tomography (LDCT) screening, which contributes heavily to a high false discovery rate. This limitation to the current screening paradigm has prompted research to identify biomarkers that will help more clearly define eligible patients for LDCT screening, differentiate indeterminate pulmonary nodules, and select individualized cancer therapy. Biomarkers within the Insulin-like Growth Factor (IGF) family have come to the forefront of this research. Methods: Literature available through PubMed and Google Scholar sources was cataloged using keywords: {Lung Cancer} AND {IGF} AND {Risk OR Diagnosis OR Prognosis OR Prognostication OR Treatment}. The results were summarized and provided herein.Results: Multiple biomarkers within the IGF family (or axis) have been investigated, most notably IGF-I and IGF binding protein 3 (IGFBP-3). However, newer studies seek to expand this search to other molecules within the IGF axis. Results have differed, however, due to features such as the pre-disease variable expression of IGF-I and IGFBP-3, likely promoted by factors such as obesity and smoking history. Certain studies have demonstrated these biomarkers are useful as a companion test alongside lung cancer screening, but other findings were not as conclusive, possibly owing to measurement bias from pre-analytical variables and non-standardized assay techniques. Research also has suggested IGF biomarkers may be beneficial in the prognostication and subsequent application of treatment via systemic therapy. Despite these advances, however, additional knowledge as to the intricacies of regulatory mechanisms inherent to this system are necessary to more fully harness the potential clinical utility for diagnostic tests and to identify novel targets for therapeutic intervention. Conclusions: The IGF system likely plays a role in multiple phases of lung cancer; however, there is a surplus of conflicting data, especially prior to development of the disease and during early stages of detection. IGF biomarkers may be valuable in the screening, prognosis, and treatment of lung cancer, though their exact application requires further study.

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

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 &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.

Application Value of Combined Detection of Serum IGF-I and IGFBP-3 in the Diagnosis of Bladder Cancer

Objective. To investigate the application value of the combined detection of serum IGF-I and IGFBP-3 in the diagnosis of bladder cancer (BC). Methods.Sixty BC patients in our hospital (January 2019-January 2020) were chosen as group A, while sixty healthy people during the same period were chosen as group B. The serum IGF-I and IGFBP-3 levels of the subjects were detected to explore the relationship between the two levels (serum IGF-I and IGFBP-3) and BC.Results.Compared with group B, the two levelsof group A were lower while IGF-l/IGFBP-3 was higher. Compared with low-grade BC group, non-muscle invasive BC (NMIBC) group and non-lymph node metastasis group, the two levels were lower in high-grade BC group, muscle-invasive BC (MIBC) group and lymph node metastasis group (P<0.05). No notable difference in IGF-l/IGFBP-3 was found among patients with high-grade or low-grade BC, with or without lymph node metastasis, andwith or without muscular invasion (P>0.05). Conclusion. The serum IGF-I and IGFBP-3 levels of BC patients are obviously different compared with healthy people, and vary in patients with different types of BC, indicating the two factors can be applied in clinical diagnosic of BC.