Serum Insulin-like Growth Factor-1 Levels Research Articles

Genetic Polymorphism and serum levels of Insulin like Growth Factor-1 (Igf-1) in patients of rheumatoid arthritis.

Insulin like growth factor-1(IGF-1), is a modulator of immunity and inflammation, it promotes the anabolic role of growth hormone (GH) on bone and skeletal tissue. Genetic polymorphism in IGF-1 gene is reported to affect the transcriptional efficiency affecting its serum level. In this study we aim: 1) To study the presence of 192bp polymorphism of IGF-1 gene in patients of rheumatoid arthritis (RA), 2) To study the association of 192 bp polymorphism of IGF-1 gene with serum IGF-1 levels and disease severity in patients of RA. A cross-sectional study was carried out at University of Health Sciences (UHS), Lahore. Diagnosed RA cases who fulfilled the American College of Rheumatology (ACR) criteria were recruited from Fatima Memorial Hospital (FMH) and Behbud Rheumatology Clinics, Lahore during 2018-2019. Serum IGF-1 levels were determined by ELISA in blood samples of 200 RA patients and 200 healthy individuals. DNA was extracted and genetic polymorphism was determined. The serum IGF-1 level in RA group was significantly lower compared to healthy group. Our study shows presence of 192bp allele of IGF-1in 77% of the studied population. Carriers of 192bp allele of IGF-1 had a significantly higher serum level of IGF-1 as compared to non-carriers in the RA patients. Rheumatoid factor (RF) positive patients had a higher number of 192bp carriers in comparison to RF negative patients. Significant difference was also seen in severity of disease between carrier and non-carriers of 192bp allele with the disease being more severe in male carriers. There is an association of IGF-1gene polymorphism with variation in serum IGF-1 levels and severity of RA.

Associations between insulin-like growth factor-1 standard deviation score and overall nutritional parameters in patients with maintenance hemodialysis: a cross-sectional study.

This study investigated the association between insulin-like growth factor-1 and nutritional status indicators in patients undergoing maintenance hemodialysis (MHD). Patients undergoing MHD for > 3months were included in this single-center cross-sectional study in March 2021. Clinical, demographic, and body mass data and blood samples were collected before the hemodialysis sessions. Serum insulin-like growth factor-1 (IGF-1) levels were measured using a radioimmunoassay, and serum IGF-1 standard deviation score (SDS) was calculated for MHD patients according to age and sex. The nutritional status of patients was assessed using serum albumin, serum prealbumin, handgrip strength, pinching strength, upper arm muscle circumference, lean body mass, phase angle, seven-point subjective global assessment (SGA) score, and geriatric nutritional risk index (GNRI). The patients were divided into groups according to tertiles of serum IGF-1 SDS levels. Spearman correlation analyses and univariate and multivariate binary logistic regression analyses were used to determine the association between serum IGF-1 SDS and nutritional status parameters. A total of 155 MHD patients (male: female = 90:65) were enrolled in the study, witha median dialysis vintage of 28.0 (11.0, 55.0)months, and an average age of66 (65.5 ± 13.0)years. The median of IGF-1 SDS was - 0.1 (- 0.6 to 0.6). Compared to patients with higher IGF-1 SDSs, patients with lower IGF-1 SDSs had lower levels of serum ceruloplasmin (341.0 [287.5, 416.0] vs 395.0 [327.0, 451.0] vs 409.0 [349.5, 507.5], p = 0.002), serum albumin (34.7 ± 3.0 vs 37.0 ± 3.1 vs 37.8 ± 2.6, p < 0.001), serum prealbumin (270.3 [233.7, 327.8] vs 326.0 [279.3, 355.6] vs 363.0 [324.2, 398.2], p < 0.001), handgrip strength (13.8 [10.0, 20.7] vs 17.7 [10.7, 22.5] vs 23.3 [16.6, 27.8], p < 0.001), pinch strength (4.6 [3.9, 6.0] vs 4.9 (3.9, 6.9) vs 6.5 [4.7, 8.7], p = 0.002), phase angle (3.3 [3.0, 3.8] vs 3.9 [3.4, 4.7] vs 4.3 [3.6, 5.2, p < 0.001), modified Creatinine Index (83.1 ± 19.7 vs 93.1 ± 23.4 vs 113.9 ± 24.3, p < 0.001), intracellular water (14.5 ± 4.4 vs 16.1 ± 4.9 vs 16.9 ± 4.4, p = 0.031), higher extracellular water (26.9 ± 5.8 vs 25.7 ± 5.5 vs 25.1 ± 3.1, p = 0.042), and higher malnutrition risk as defined by GNRI (49.0% vs 15.7% vs 11.5%, p < 0.001) and SGA (53.9% vs 23.5% vs 7.7%, p < 0.001). Lower IGF-1 SDSs are independently associated with higher malnutrition risk in patients with MHD.

Insulin-like growth factor-1 on cycle day 2 and assisted reproductive techniques outcome: A cross-sectional study.

Individualized assisted reproductive techniques (ART) can improve ART outcomes. Some studies suggested using insulin-like growth factor-1 (IGF-1) level on cycle day 2 for individualized ART. To investigate the relationship between serum levels of IGF-1 on day 2 of the cycle and ART outcomes. In this cross-sectional study, cycle day 2 serum levels of IGF-1 were measured in 175 women aged between 18-44 yr as candidates for in vitro fertilization or intracytoplasmic sperm injection. All participants received antagonist protocol, and the relationship between serum levels of IGF-1 and ART outcomes according to the number of oocytes were investigated; poor responders (oocytes 5), normal responders (oocytes 5-15), and hyper responders (oocytes 15). Poor responders had higher serum level of IGF-1 when compared with normal and hyper-responders; however,this difference was not statistically significant (p = 0.41). The serum levels of IGF-1 in women with zero retrieved oocytes and those cycles that were canceled for the inappropriate ovarian response were not significantly different compared to other women in the group of poor responders. An inverse relationship was observed between the serum level of IGF-1 and anti-Mullerian hormone. Furthermore, no significant relationship between serum level of IGF-1 with age, body mass index, number of 2 pronucleus, and number of embryos was observed. According to our results, the serum levels of IGF-1 may not be able to predict ART outcomes. It seems necessary to conduct more studies with larger sample size.

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.

Serum cortisol and insulin-like growth factor 1 levels in major depressive disorder and schizophrenia

The pathophysiology underlying major depressive disorder (MDD) and schizophrenia is related to endocrine system functions and includes changes in the blood levels of cortisol and insulin-like growth factor 1 (IGF-1). However, these hormones have not been investigated simultaneously in patients with MDD and schizophrenia. We investigated the differences in serum cortisol and IGF-1 levels among patients with MDD and schizophrenia and controls. We included 129 patients with MDD, 71 patients with schizophrenia, and 71 healthy volunteers. Blood tests were performed between 6:00 am and 11:00 am after fasting. Serum cortisol levels were significantly higher in patients with schizophrenia than in patients with MDD and controls. Serum cortisol levels were significantly higher in patients with MDD than in controls. Serum IGF-1 levels were higher in both patient groups than in controls, whereas there was no significant difference between patients with MDD and schizophrenia. Both cortisol and IGF-1 levels were positively correlated with the Hamilton Rating Scale for Depression score in patients with MDD, whereas cortisol level was positively correlated and IGF-1 level was negatively correlated with the Brief Psychiatric Rating Scale score in patients with schizophrenia. The differences in the level of these hormones suggest pathophysiological differences between these disorders.

Umbilical cord serum insulin-like growth factor-1 levels of infants of diabetic mothers are correlated with diastolic dysfunction detected by tissue Doppler echocardiography.

To our knowledge, this is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. A weak correlation was found between IGF-1 levels and IVS and LVPW thicknesses in M-Mode and LV e' and LV e'/a' parameters in TDI, revealing diastolic dysfunction in IDMs. • The umbilical cord blood serum IGF-1 level of IDMs is higher than in infants of healthy mothers. • Diastolic dysfunction is a well-studied and frequently observed consequence in IDMs. • This is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. • A weak correlation was detected between the median cord serum IGF-1 level of IDMs and the median values of IVS, LVPW, LV e', LV a', LV e'/a' ratio.

Proposed reference intervals of serum insulin-like growth factor-1 (IGF-1) levels in older Japanese populations.

Measurements of serum insulin-like growth factor 1 (IGF-1) levels are useful surrogate markers for the diagnosis and management of patients with growth hormone-related disorders. We have previously published normative data of serum IGF-1 levels for the Japanese population aged 0-77 years by combining and analyzing previously reported references, which were separately and independently constructed, to properly reflect data in the transition period. Although the reference is widely used in both clinical and research settings, the reference did not include data for those aged >77 years, raising the question of how we would evaluate patients over those ages. In this study, we extended the age- and sex-specific reference ranges of serum IGF-1 levels to the age of 80 years by reanalyzing combined data on serum IGF-1 levels from previously published references. Based on our results, we proposed that individuals aged >80 years can be evaluated using the references set at the age of 80 years. However, our proposal was based on a very limited number of participants. Therefore, physicians should exercise caution when interpreting IGF-1 standard deviation scores for those aged >80 years because they are not exactly correct but acceptable.

The Influence of Body Mass Index on Growth Factor Composition in the Platelet-Rich Plasma in Patients with Knee Osteoarthritis.

An abnormally high body mass index is strongly associated with knee osteoarthritis. Usually, obese patients are excluded from clinical trials involving PRP intra-articular injections. Growth factors have been demonstrated to have a disease-modifying effect on KOA treatment, even though data on their influence on treatment effectiveness in obese patients are lacking. To prospectively compare the level of selected growth factors including transforming growth factor-b (TGF-β), epidermal growth factor (EGF), fibroblast growth factor, insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) in platelet-rich plasma (PRP) in obese patients and patients with normal BMI. A total of 49 patients were included in the study according to inclusion and exclusion criteria. The groups strongly differed in body mass index (median values 21.6 vs. 32.15). Concentrations of growth factors were measured with an enzyme-linked immunosorbent assay. Statistical significance was determined with the Mann-Whitney U test. The compliance of the distribution of the results with the normal distribution was checked using the Shapiro-Wilk test separately for both groups. There were no statistically significant differences in median marker levels between groups. Statistically significant Pearson correlations were observed between IGF-1 serum level and age (weak negative, r = -0.294, p = 0.041) and gender (moderate positive, r = 0.392, 0.005). BMI does not influence the level of selected growth factors in patients with knee osteoarthritis. Obese and non-obese patients had similar compositions of PDGF, TGF-β, EGF, FGF-2, IGF-1, and VEGF. PRP can be used in both groups with similar effects associated with growth factors' influence on articular cartilage.

Correlation analysis of serum IGF-1 and IL-6 and urinary albumin/creatinine ratio in patients with type 2 diabetic kidney disease.

Diabetic kidney disease (DKD) is one of the most common chronic complications in diabetic patients, and there are major limitations in its pathological diagnosis. This study's objectives were to examine the changes in serum insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) levels in DKD patients with various urinary albumin/creatinine ratio (ACR) and to evaluate the utility of these two biological markers in the clinical diagnosis of the condition. We chose 80 type 2 diabetic patients as the experimental group and 20 healthy normal participants as the control group. The experimental group was split into three groups based on the ACR range: diabetes without nephropathy group (ACR < 30 mg/g), microalbuminuric group (30 < ACR < 300 mg/g), and macroalbuminuric group (ACR > 300 mg/g). The levels of serum IL-6 and IGF-1 were assessed in each trial participant. Serum IGF-1 was higher in the experimental group than in the control group (P < 0.01), and serum IL-6 levels were also higher than in the control group (P < 0.001). In DKD patients, serum levels of IL-6 and IGF-1 tended to rise when ACR levels rose. By Pearson correlation analysis, serum IGF-1 and IL-6 were positively correlated with ACR (r = 0.765 and r = 0.651, all P < 0.001) and negatively correlated with eGFR (r = -0.389 and r = -0.364, all P < 0.01). Additionally, the receiver operating characteristic (ROC) characteristic curve showed that the area under the curve (AUC) values for serum IGF-1 and IL-6 were 0.9056 and 0.7850, respectively, while the AUR value for both combined was 0.9367. Serum IGF-1 and IL-6 levels can be used to diagnose DKD, and the combined analysis of these two indicators can improve the sensitivity and specificity of the disease diagnosis.

Effects of Protein-Chelated Zinc Combined with Mannan-Rich Fraction to Replace High-Dose Zinc Oxide on Growth Performance, Nutrient Digestibility, and Intestinal Health in Weaned Piglets.

A total of 168 weaned piglets (average initial body weight of 7.70 ± 0.75 kg) were used in a 4-week feeding trial to investigate the effects of dietary supplementation with protein-chelated zinc (Zn-Pro) alone or combined with a mannan-rich fraction (MRF) to replace high-dose zinc oxide (ZnO) for weaned piglets. The dietary treatments included a basal diet as control (CON), a ZnO diet (basal diet + 1600 mg Zn/kg from ZnO), a Zn-Pro diet (basal diet + 60 mg Zn/kg from Zn-Pro), and a MRF plus Zn-Pro diet (MRP, basal diet + 800 mg/kg MRF + 60 mg Zn/kg from Zn-Pro). The average daily gain of piglets in the MRP group was higher (p ≤ 0.05) than that in CON and Zn-Pro groups during d 15-28 and d 1-28 of experiment. The apparent total tract digestibility of dry matter, organic matter, and crude protein in the MRP group was higher (p ≤ 0.05) than that in the CON group. The serum insulin-like growth factor-1 level in the MRP group was markedly higher (p ≤ 0.05) than that of piglets in the other three treatment groups. Piglets fed the Zn-Pro and ZnO diets had greater (p ≤ 0.05) acetic acid in cecal digesta than those fed the CON diet, while the MRP diet had higher (p ≤ 0.05) cecal propionate concentration than those that were fed the CON diet on d 28 of experiment. Moreover, the villus height of ileum in the MRP group tended to be greater than the CON group (p = 0.09). Compared with the CON and MRP groups, the relative abundance of Lactobacillaceae (p = 0.08) and Lachnospiraceae (p = 0.09) in the Zn-Pro group showed an increasing trend. The relative abundance of Prevotellaceae in the Zn-Pro group was significantly lower (p ≤ 0.05) than that in the MRP group. In conclusion, the combined addition of MRF and Zn-Pro acted as a suitable alternative to ZnO to beneficially support the growth performance and intestinal health of weaned piglets, as well as contribute to a lower diarrhea rate and environmental pollution from fecal zinc excretion.

Meta-analysis of peripheral insulin-like growth factor 1 levels in schizophrenia.

We aimed to investigate if there is a significant difference in peripheral insulin-like growth factor 1 (IGF-1) levels between schizophrenia patients and healthy controls and to determine whether a difference exists before and after initiation of antipsychotics. PubMed/MEDLINE, Scopus, and Web of Science were searched up to March 27, 2022. Original clinical studies of any type that reported peripheral blood, serum or plasma IGF-1 levels measured after fasting in schizophrenia patients and/or healthy control group were selected based on inclusion and exclusion criteria. Data were analyzed using Meta-Essentials: Workbooks for meta-analysis and pooled through random-effects meta-analyses. Twelve publications met eligibility criteria. Schizophrenia patients under antipsychotic treatment had significantly lower peripheral IGF-1 levels compared to healthy controls (n=632, Hedges' g -0.42, 95% CI from -0.79 to -0.04, p=.006, I2 =70.38%), while no significant difference was found between schizophrenia patients regardless of the antipsychotic treatment status and healthy controls, as well as between antipsychotic naïve or free schizophrenia patients and healthy controls, and before and after initiation of antipsychotic treatment. However, high heterogeneity was observed and its potential sources in some of the subgroup analyses included sample type and region. Schizophrenia patients under antipsychotic treatment seem to have lower peripheral IGF-1 levels compared to healthy controls. Additional studies with larger and more homogenous samples are needed to confirm these findings.

Prognostic Impact of Hepatic Steatosis Evaluated by CT on Immunotherapy for Gastric Cancer: Associations with Sarcopenia, Systemic Inflammation, and Hormones

Introduction: Immune checkpoint inhibitors (ICIs) are expected to improve the prognosis of gastric cancer (GC). Also, hepatic steatosis has been reported to be associated with cancer cachexia and is expected to be a cancer biomarker. The purpose of this study was to evaluate prognostic impact of hepatic steatosis in ICI therapy for GC. Methods: Unresectable or recurrent GC treated with ICIs was investigated. Using unenhanced CT, the liver-to-spleen CT attenuation ratio (LSR) was calculated as a parameter of hepatic steatosis. LSR was compared with the presence of sarcopenia and inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). These parameters were also compared with disease-specific survival (DSS) and progression-free survival (PFS). Associations of LSR with insulin-like growth factor 1 (IGF-1) and growth hormone were also evaluated. Results: A total of 70 patients were investigated. LSR of sarcopenia patients was significantly lower than that of non-sarcopenic ones (p = 0.02). LSR showed significant negative correlations with NLR, PLR, and MLR (p = 0.003, 0.03, 0.01, respectively). Lower LSR was significantly associated with a higher level of serum IGF-1 (p = 0.03). In univariate analysis, LSR was significantly correlated with DSS and PFS (both p < 0.0001), and multivariate analysis demonstrated that LSR was the independent prognostic factor for both DSS and PFS (both p = 0.01). ROC analysis demonstrated that LSR >1.263 was a good predictive marker for favorable DSS (>5.3 months) with an AUC of 0.80. Conclusion: Hepatic steatosis can be a promising prognostic biomarker for ICI therapy of GC, associated with sarcopenia and the elevation of inflammatory markers. Our data suggested that GC with steatohepatitis might be less responsive to ICI therapy.

ODP386 Growth Velocity and Growth Hormone Deficiency During Puberty

Abstract Background A subnormal growth velocity (GV) is a characteristic feature of growth hormone deficiency (GHD). During puberty growth hormone (GH) levels increase markedly in response to sex hormone secretion. The normal range for GV declines during childhood, increases during puberty with peak levels at mid-puberty. Hence, pubertal status rather than age alone must be considered in the evaluation of GV in children and adolescents. In most cases, a diagnosis of GHD is established by a subnormal response in GH levels following a stimulation with two pharmacological agents. Objective We determined the reliability of GV as a predictor of GHD during puberty. Methods We conducted a retrospective study of pubertal children and adolescents who underwent a GH stimulation test in our pediatric endocrinology clinic. Seventy-nine subjects (57 boys and 22 girls) were included in this study. Bone age was determined for all patients. Serum levels of insulin like growth factor-1 (IGF-1) were obtained prior to GH stimulation test. Serum IGF-1 levels, expressed as a standard deviation score were compared to the IGF-1 levels expected chronological age (CA), height age (HA), and bone age (BA). Serum GH levels were determined following the administration of arginine and levodopa. GHD was established by a peak GH level &amp;lt;10 ng/mL. IBM SPSS Statistics software version 28. 0. 0. 0 (190) was used for data analysis. Results Subjects ranged in age from 7.3-17.9 years. Thirty-nine patients (49.4%) had GV &amp;lt; 10 th percentile for CA; Forty patients (50.6%) had GV &amp;lt;10 th percentile for BA. Sixty percent of patients with GV &amp;lt;10 th percentile for CA had GHD. A similar number (59%) of patients with normal GV for CA also had GHD. Among patients with GV &amp;lt;10 th percentile for BA, 72.5% of subjects had GHD. By contrast, the percentage of patients who had normal GV for bone age and GHD (46.2%) was significantly less than that of subjects with GV &amp;lt;10 th percentile for BA (p = 0. 015). Positive predictive value, negative predictive value, sensitivity and specificity for GV &amp;lt;10 th percentile for BA in the diagnosis of GHD were 72.5%, 53.8%, 61.7%, and 65.6%, respectively. With respect to the diagnostic value of serum IGF-1, when the area under the ROC curve was used to measure how well the serum IGF-1 standard deviation score distinguished between GHD and normal, serum IGF-1 standard deviation score for CA, HA, and BA were not predictive of GHD (p = 0.1, 0.47, and 0.27, respectively). Conclusions During puberty, slow growth velocity for bone age (but not slow growth velocity for chronological age) was useful to predict a diagnosis of growth hormone deficiency. Presentation: No date and time listed

PMON68 Effect of an Amino-Acid Based Blend on Human Growth Hormone (hGH) and Fibromyalgia (FM) Symptoms

Abstract Fibromyalgia is a chronic pain sensitivity disorder that affects approximately 3-8% of the general population with symptoms that include fatigue and widespread musculoskeletal pain. Psychological and physical stressors are frequent drivers of fibromyalgia, and additional lockdown-associated stressors may worsen symptoms. Reduced production of human growth hormone (hGH) is evident in approximately 30% of individuals with fibromyalgia, which is hypothesized to contribute to common fibromyalgia symptoms. An orally administered amino acid supplement has been previously shown to improve endogenous hGH status in adults. We investigated if daily administration of the supplement would increase levels of endogenous insulin-like growth factor 1 (IGF-1), a surrogate marker of the body's hGH levels, and improve symptoms related to low-normal hGH production in a cohort of 84 individuals being treated for fibromyalgia. This is the full-cohort analysis of an open-label, single-arm study that investigated the effects of 24 weeks of daily oral administration of the supplement in individuals with low-normal hGH production. The primary endpoint was the change from baseline to endpoint (Week 24) in serum IGF-1. Additional endpoints included the change in body weight, clinical symptoms (assessed with the Revised Fibromyalgia Impact Questionnaire [FIQR], range 0-100, and Perceived Stress Scale [PSS], range 0-40), fasting cardiometabolic markers, tolerability, and safety. Participants continued to receive standard care. The study enrolled 84 fibromyalgia patients with low-normal age-adjusted IGF-1 serum levels. High mean±SD baseline FIQR and PSS scores of 76±16 and 32±5, respectively, indicated poor to moderate symptom management with standard care. All individuals completed 24 weeks of treatment. Serum IGF-1 levels increased with a Week 24 mean±SE change of 28.4±3.0 ng/mL (paired t-test p&amp;lt;0.001). Body weight was reduced with a Week 24 mean±SE change of -5.5±0.3 kg (p&amp;lt;0.001). The change from baseline in FIQR and PSS scores were -29.1±1.1 and -20.0±0.8, respectively (both p&amp;lt;0.001), indicating a substantial improvement. Statistically significant improvements from baseline were also observed for systolic and diastolic blood pressure, HbA1c, LDL and HDL cholesterol, and triglycerides (all p&amp;lt;0.001). The supplement was well tolerated; no adverse events were reported. Sustained augmentation of IGF-1 with the supplement may represent a unique method of improving clinical symptoms of fibromyalgia in individuals with low-normal hGH production. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Hyperbaric Oxygen Therapy Promotes Hearing Gain with Increases in Serum IGF-1 and HSP70 in Patients with Idiopathic Sudden Sensorineural Hearing Loss.

Hyperbaric oxygen therapy (HBOT) has been recommended for the initial and salvage treatment of patients with idiopathic sudden sensorineural hearing loss (ISSHL), but its underlying mechanisms remain unclear. In this study, we investigated whether HBOT alters serum levels of insulin-like growth factor 1 (IGF-1) and heat shock protein 70 (HSP70) in patients with ISSHL. Then, we identified the relationship between hearing recovery and changes in serum IGF-1 and HSP70 levels. Moderately severe to profound unilateral ISSHL patients (n = 70) and healthy control participants (n = 30) were enrolled. The ISSHL patients were randomly assigned to receive medical therapy alone (MT group, n = 35) or both HBOT and medical therapy (HBOT + MT group, n = 35). Audiometric testing was performed before and after treatment. Serum IGF-1 and HSP70 levels were assessed by ELISA in ISSHL patients pre-and posttreatment and healthy controls. Before treatment, compared with the healthy controls, serum IGF-1 and HSP70 were lower in ISSHL patients. After treatment, serum IGF-1 and HSP70 increased in both the HBOT + MT and MT groups, although they were significantly higher in the HBOT + MT group (p < 0.01). In the HBOT + MT group, these increases were associated with hearing gains. In addition, IGF-1 was strongly associated with HSP70 (r = 0.621, p = 0.001). No such association was found in the MT group (p = 0.757). Administering HBOT in addition to medical therapy can improve the hearing of patients with moderately severe to profound unilateral ISSHL. The improvement is related to the upregulation of IGF-1 and HSP70.

Insulin-like growth factor 1 serum levels in different stages of gastric cancer and their association with Helicobacter pylori status

High serum insulin-like growth factor 1 (IGF-1) and positive Helicobacter pylori (H. pylori) may increase the risk of gastric cancer (GC). We aimed to investigate IGF-1 serum levels in different stages of GC patients and their association with H. pylori status. A total of 90 participants, including 60 GC patients and 30 noncancerous (NC) individuals, were included in the present study. IGF-1 serum levels and candidate proteins were assessed using enzyme-linked immunosorbent and immunohistochemistry techniques. Likewise, Giemsa staining was applied to detect H. pylori infection. The candidate genes' expression, including IGF-1R, PI3KCA, AKT1, mTOR1, KRAS, BRAF, and ERK1, was also evaluated by a real-time PCR assay. The results of advanced GC stages indicated a significantly high IHC score for IGF-1R and phosphorylated AKT, mTOR, and ERK proteins compared to the early stages. Moreover, IGF-1 serum levels and the expression of candidate genes were considerably increased in the advanced GC patients compared to the early stages and the positive H. pylori status compared to the negative H. pylori status (P < 0.05). As a result, high IGF-1 serum levels and positive H. pylori status may be correlated with gastric tumor progression, and the inhibition of IGF-1 and the eradication of H. pylori infection might be new therapeutic targets in GC patients.

The IGF1/FSH Ratio Correlates with Sperm Count and Testicular Volume

BACKGROUND. Several studies have already investigated the relationship between IGF1 and semen parameters. However, clinical studies rarely concluded on the existence of a relationship between IGF1 and the sperm number, and whether the IGF1 serum levels have a practical value in the diagnostic work-up of patients with oligozoospermia is still unclear. OBJECTIVE. Molecular evidence reported that IGF1 and FSH belongs to the same molecular pathway. The aim of this study is to assess whether insulin-like growth factor-1 (IGF1)/follicle-stimulating hormone (FSH) ratio has an impact on testicular function and, specifically, on sperm number and testicular volume in a cohort of unselected men. METHODS. This is a cross-sectional study on 59 patients who attended the Seminology laboratory of the Division of Endocrinology of the University of Catania (Catania, Italy) for semen analysis. Data were analyzed to evaluate the relationships between IGF1 or IGF1/FSH ratio and sperm concentration, total sperm count (TSC), and testicular volume (TV). We also evaluated the occurrence of any difference in IGF1 and FSH serum levels and the IGF1/FSH ratio in patients with oligozoospermia and those with a TSC &gt; 39 million/ejaculate. MAIN RESULTS AND ROLE OF CHANGE. Patients had a mean age of 31.0 ± 8.5 years. The mean FSH and IGF1 levels were 3.95 ± 2.55 mIU/mL and 232.59 ± 65.13 ng/mL, respectively. IGF1 serum levels did not correlate with sperm concentration, TSC, and TV. The IGF1/FSH ratio showed a positive correlation with sperm concentration (r = 0.408; p = 0.004), TSC (r = 0.468; p = 0.001), and TV (0.463; p = 0.002). Patients with oligozoospermia (Group 1, 23.7%, n = 14) had a significant lower IGF1/FSH ratio (57.9 ± 9.5 vs. 94.1 ± 8.7; p = 0.03) compared to those with TSC &gt; 39 million/ejaculate (Group 2, 76.3%, n = 45). They did not differ significantly for neither IGF1 nor FSH serum levels. CONCLUSION. We found a positive correlation between the IGF1/FSH ratio and sperm concentration, TSC and TV. Furthermore, patients with oligozoospermia showed a significantly lower ratio compared to those with a normal TSC, while neither IGF1 nor FSH differed significantly in the two groups. Our results may reflect the existence of a molecular pathway to which IGF1 and FSH belongs. However, further studies are needed.

Population pharmacokinetic/pharmacodynamic analysis of PEG-rhGH enhances confidence in exploring dosing schemes with longer intervals

Background and objectivesPEG-rhGH (Jintrolong®, 0.2 mg/kg/week) is approved in China for the treatment of growth hormone deficiency (GHD) in children. Although 0.2 mg/kg/2 weeks PEG-rhGH failed the non-inferiority threshold of 20% compared with 0.2 mg/kg/week PEG-rhGH, it notably increases serum IGF-1 levels and height velocity in a phase IV trial. In the absence of investigation on the relationship between pharmacokinetics and pharmacodynamics, this analysis aimed to build a population pharmacokinetic/pharmacodynamic (PopPK/PD) model to characterize the relationship between serum PEG-rhGH concentration and serum insulin-like growth factor-1 (IGF-1) levels after subcutaneously administration of PEG-rhGH and to explore the possibility of flexible dosing schemes and improve the clinical monitor practice of IGF-1 levels. MethodsA total of 41 subjects were included for the PopPK analysis, consisting of 30 healthy adults (single dose of 0.1–0.4 mg/kg) and 11 GHD children (multiple doses of 0.2 mg/kg/2 weeks for 26 consecutive weeks). Only GHD children were included for the PopPK/PD analysis. The time courses of serum PEG-rhGH concentrations in healthy adults and GHD children and those of serum IGF-1 levels stimulated by serum PEG-rhGH were well developed with non-linear mixed-effects modeling. ResultsSerum PEG-rhGH pharmacokinetics after subcutaneous administration were adequately described by a one-compartment model with a zero-order input into the absorption compartment followed by first-order absorption dictating absorption into the central compartment, with a dual elimination process consisting of a capacity limited process and a non-capacity limited process. Body weight was a significant covariate. The drug effects on IGF-1 levels were adequately described by a turnover model with saturable effect relationship. IGF-1 responses at the various dosing scheme scenarios were simulated, and illustrated that dosing schemes with intervals longer than the approved one week could be promising, which may provide comparable peaks and average IGF-1 levels and IGF-1 SDS to dosing schemes that have been clinically proven to be tolerated and effective. An accurate prediction of the time course of the effect of various dosing schemes may assist the clinical monitoring practice. ConclusionsThis pharmacokinetic/pharmacodynamic analysis suggested that longer intervals or higher dosing strengths (e.g., 0.3 mg/kg/10 days) in children with GHD are promising compared with the approved dosing scheme (0.2 mg/kg/week). Our simulation may assist the clinical monitoring of the PEG-rhGH therapy.

Serum IGF-1 Scores and Clinical Outcomes in the Phase III IMbrave150 Study of Atezolizumab Plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma.

PurposeChild-Turcotte-Pugh class A (CTP-A) in unresectable hepatocellular carcinoma (HCC) is the standard criterion for active therapy and clinical trial enrollment. We hypothesized that insulin-like growth factor-1 (IGF-1) derived scores may provide improved survival prediction over CTP classification. This study aimed to evaluate the potential prognostic and predictive effects of IGF-1 derived scores in the phase III IMbrave150 study.Patients and MethodsBaseline and on-treatment serum IGF-1 levels from 371 patients were subjected to central analysis. Patients’ IGF-1 score (1/2/3) and IGF-CTP score (A/B/C) were determined based on pre-specified cutoffs. Outcomes were analyzed by baseline and by on-treatment changes of the IGF-1 and IGF-CTP scores within and between the two treatment arms. The interaction between these scores and outcomes was assessed using univariate and multivariate analyses.ResultsBaseline IGF-CTP score (A vs B/C) showed prognostic significance for OS in both the atezolizumab-bevacizumab (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.20–0.56; P<0.001) and sorafenib (HR, 0.32; 95% CI, 0.16–0.65; P=0.002) arms. Baseline IGF-1 score (1 vs 2/3) also showed prognostic significance for OS in both the atezolizumab-bevacizumab (HR, 0.33; 95% CI, 0.20–0.55; P<0.001) and sorafenib (HR, 0.48; 95% CI, 0.26–0.89; P=0.02) arms. HRs for PFS were consistent with those for OS. No significant predictive effects were observed for either score between the two arms. Kinetic analysis revealed that patients with increased IGF-1 score (1-> 2/3) at 3 weeks post treatment had shorter OS than patients with stable IGF-1 score of 1 in both the atezolizumab-bevacizumab (HR, 3.70; 95% CI, 1.56–8.77; P=0.003) and sorafenib (HR, 5.83; 95% CI, 1.88–18.12; P=0.0023) arms.ConclusionBaseline and kinetic change of IGF-CTP and IGF-1 scores are independent prognostic factors for patients with unresectable HCC treated with atezolizumab-bevacizumab or sorafenib. These novel scores may provide improved patient stratification in future HCC clinical trials. IMbrave150 ClincialTrials.gov number, NCT03434379.

Effect of Lingnan Chen's acupuncture on postmenopausal osteoporosis and serum GH and IGF-1

To compare the therapeutic effect on postmenopausal osteoporosis (PMOP) between Lingnan Chen's needling technique and calcitriol soft capsules and investigate the effect mechanism in view of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Seventy patients of PMOP were randomized into an observation group (35 cases, 4 cases dropped off ) and a control group (35 cases, 3 cases dropped off ). The patients of both groups were treated with calcium carbonate D3 tablets orally (600 mg each time, once daily). In the observation group, acupuncture was delivered at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Sanyinjiao (SP 6), etc. with the specific reinforcing-reducing technique and qi-conducting technique of Lingnan Chen's acupuncture, once every two days, three times a week. In the control group, calcitriol soft capsules were taken orally, 0.25 μg each time, twice a day. The intervention measures of two groups all lasted 12 weeks. Before and after treatment, the bone mineral density (BMD), the levels of serum GH and IGF-1 were assessed in two groups. Before treatment and 4, 8 and 12 weeks after treatment, TCM symptoms score and the MOS item short form health survey (SF-36) score were evaluated and the therapeutic effects were compared between groups. In both within-group and between-group comparisons, the difference in BMD was not significant before and after treatment (P>0.05). After treatment, the levels of serum GH and IGF-1 were increased in the observation group (P<0.05), and higher than the control group (P<0.05). After 4, 8 and 12 weeks of treatment, the scores of TCM symptoms were reduced in both groups compared with those before treatment (P<0.05), and the score in the observation group was lower than that in the control group (P<0.05). After 4, 8 and 12 weeks of treatment, except the score of general health 4 weeks after treatment in the control group, the scores of the other domains in SF-36 were increased in both groups compared with those before treatment (P<0.05). After 12 weeks of treatment, except the score for the general health and social functions, the scores of the other domains of SF-36 in the observation group were all higher than those in the control group (P<0.05). The total effective rate was 83.9% (26/31) in the observation group, higher than 59.4% (19/32) in the control group (P<0.05). Lingnan Chen's needling technique is effective on postmenopausal osteoporosis. This therapy may relieve the symptoms of osteoporosis and improve the quality of life, better than calcitriol soft capsules, and the effect mechanism may be related to the up-regulation of serum GH and IGF-1 in the patients.