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The Course Of IGF-1 Levels and Nutrient Intake in Extremely and Very Preterm Infants During Hospitalisation.
Yumani, DFJ, Calor, AK, van Weissenbruch, MM
Nutrients. 2020;(3)
Abstract
BACKGROUND Insulin-like growth factor 1 (IGF-1) plays an important role in the complex association between nutrition, growth, and maturation in extremely and very preterm infants. Nevertheless, in this population, research on associations between IGF-1 and nutrition is limited. Therefore this study aimed to evaluate the possible associations between the course of IGF-1 levels and nutrient intake between preterm birth and 36 weeks postmenstrual age (PMA). METHODS 87 infants born between 24 and 32 weeks gestational age were followed up to 36 weeks PMA. Actual daily macronutrient intake was calculated, and growth was assessed weekly. IGF-1 was sampled from umbilical cord blood at birth and every other week thereafter. RESULTS There was an inverse relationship between the amount of parenteral nutrition in the second week of life and IGF-1. Total protein, fat, and carbohydrate intake, as well as total energy intake, primarily showed a positive association with IGF-1 levels, particularly between 30 and 33 weeks PMA. Gestational age, bronchopulmonary dysplasia (BPD), and weight were significant confounders in the association between nutrient intake and IGF-1 levels. CONCLUSION Parenteral nutrition was found to be a negative predictor of IGF-1 levels, and there could potentially be a time frame in which macronutrient intake is unable to impact IGF-1 levels. Future research should aim to narrow down this time frame and to gain more insight into factors enhancing or decreasing the response of IGF-1 to nutrition, e.g., age and inflammatory state, to align nutritional interventions accordingly.
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Bazedoxifene effects on osteoprotegerin, insulin-like growth factor, tumor necrosis factor and bone mineral density.
Ma, Y, Chai, Z, Ren, L, Hu, Q
Cellular and molecular biology (Noisy-le-Grand, France). 2020;(3):109-112
Abstract
UNLABELLED To observe the clinical effect of estrogenic drugs (Bazedoxifene) on bone targeting in the treatment of osteoporosis and explore its mechanism. METHODS 112 patients with postmenopausal osteoporosis who received Bazedoxifene drugs in our hospital from January to December 2018 were collected as a study group, and 56 patients treated with calcium alone were collected as a control group. the risk of adverse events such as bone mineral density, osteoprotegerin (OPG), insulin-like growth factor (IGF), tumor necrosis factor (TNF-α), and fracture after treatment were analyzed before and after treatment. RESULTS There was no significant difference in the mean lumbar positive position (L2-4) and right femoral neck bone density and OPG, IGF, TNF-α level between the two groups before treatment (P>0.05). The total effective rate of clinical treatment in the study group was 88.39%, the control group was 23.21%, the difference between the two groups was statistically significant (P˂0.05). After treatment, the mean lumbar positive position (L2-4) and the right femoral neck bone density and OPG, IGF in the study group were higher than those in the control group, lower than those in the control group (P<0.05). the occurrence of adverse events such as fracture, spinal deformation and fatigue in the study group after 12 months of treatment was significantly lower than that in the control group (P<0.05), but there was no significant difference in the occurrence of hot flashes and venous thromboembolism between the two groups (P>0.05). CONCLUSION Bazedoxifene is an effective drug for the treatment of postmenopausal osteoporosis. It can not only prevent the rapid loss of bone mass, effectively relieve the symptoms of menopause, but also improve bone density and reduce the risk of fracture.
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Associations of IGF-1 and Adrenal Androgens with Cognition in Childhood.
Mäntyselkä, A, Haapala, EA, Lindi, V, Häkkinen, MR, Auriola, S, Jääskeläinen, J, Lakka, TA
Hormone research in paediatrics. 2019;(5):329-335
Abstract
BACKGROUND Little is known about the association between adrenarche and cognition in general populations of children. We therefore studied the associations of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), testosterone, insulin-like growth factor-1 (IGF-1), and adrenarche with cognition among prepubertal children. METHODS These cross-sectional analyses are based on baseline data of the Physical Activity and Nutrition in Children Study. A total of 387 children (183 girls, 204 boys) were included in the analyses. Raven's Coloured Progressive Matrices (CPM) score was used to assess nonverbal reasoning. Serum adrenal androgens and IGF-1 concentrations were measured and clinical signs of androgen action were evaluated. RESULTS Higher IGF-1 among boys (β = 0.149, p =0.033) was related to a better Raven's CPM score after adjustment for age and parental education. Adrenal androgens in girls or boys or IGF-1 in girls were not associated with the score. There were no differences in Raven's CPM score between children with biochemical adrenarche (DHEAS ≥1.08 µmol/L; ≥40 µg/dL) or with clinical signs of androgen action and children without them. CONCLUSION The results suggest that higher serum IGF-1 among boys is related to better cognition in prepubertal children. We could not provide evidence for the associations of adrenal maturation with cognition in prepubertal children.
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rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial.
Ley, D, Hallberg, B, Hansen-Pupp, I, Dani, C, Ramenghi, LA, Marlow, N, Beardsall, K, Bhatti, F, Dunger, D, Higginson, JD, et al
The Journal of pediatrics. 2019;:56-65.e8
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Abstract
OBJECTIVE To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. STUDY DESIGN This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 230/7 weeks to 276/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 296/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 404/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28-109 µg/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. RESULTS Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. CONCLUSIONS rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. TRIAL REGISTRATION ClinicalTrials.gov: NCT01096784.
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The Influence of Maternal Obesity and Breastfeeding on Infant Appetite- and Growth-Related Hormone Concentrations: The SKOT Cohort Studies.
Larnkjær, A, Ong, KK, Carlsen, EM, Ejlerskov, KT, Mølgaard, C, Michaelsen, KF
Hormone research in paediatrics. 2018;(1):28-38
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BACKGROUND/AIMS: Exposure to obesity during pregnancy may lead to adverse changes in the offspring's metabolic profile. We compared appetite- and growth-related hormones in a cohort of infants born to obese mothers (SKOT-II) with infants born mainly to nonobese mothers (SKOT-I). METHODS Infants from SKOT-I (n = 273) and SKOT-II (n = 132) were examined including anthropometric measurements and blood samples analyzed for glucose, insulin, insulin-like growth factor-I (IGF-I), adiponectin, and leptin. Information on breastfeeding and parental characteristics were also collected. RESULTS At 9 months of age, SKOT-II infants were 3.6% heavier and 1.2% longer than SKOT-I infants even though their mothers were shorter. There was no difference in body mass index (BMI). SKOT-II infants had higher levels of insulin, adiponectin, and leptin but lower levels of IGF-I compared to SKOT-I infants (all p ≤ 0.015). These differences remained, except for leptin, when adjusted for current weight. Breastfeeding versus nonbreastfeeding at 9 months was associated with lower concentrations of all hormones (all p ≤ 0.003). In adjusted models, maternal BMI at 9 months was positively associated with insulin and adiponectin and negatively with IGF-I. CONCLUSIONS Pre-pregnancy obesity confers symmetrically larger infant body size and higher levels of most growth- and appetite-related hormones but surprisingly lower levels of IGF-I, suggesting other possible infant growth-promoting effects through insulin.
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Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.
Kindler, JM, Pollock, NK, Laing, EM, Oshri, A, Jenkins, NT, Isales, CM, Hamrick, MW, Ding, KH, Hausman, DB, McCabe, GP, et al
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2017;(7):1537-1545
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Abstract
IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect = 0.200, p < 0.001) versus normal (βIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research.
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Insulin-Like Growth Factors and Metabolic Syndrome in Obese Children.
Inzaghi, E, Baldini Ferroli, B, Fintini, D, Grossi, A, Nobili, V, Cianfarani, S
Hormone research in paediatrics. 2017;(6):400-404
Abstract
BACKGROUND/AIMS: Insulin-like growth factor (IGF)-I is related to cardiometabolic risk in adults, whereas the metabolic role of IGF-II is unclear. The aim of this study was to assess IGFs in obese children and correlate them with metabolic syndrome (MetS) components. METHODS This is a retrospective study including 574 obese children (11.34 ± 3.16 years). All subjects underwent complete anthropometry and biochemical assessment. In a subgroup of 136 subjects, body composition was evaluated. IGF-I was measured in 300 obese subjects and IGF-II in 77 obese and 15 lean children. 177 subjects were divided according to the presence of 1 or more MetS criteria: group 1, subjects with 1 MetS criterion; group 2, subjects with 2 components; and group 3, subjects with MetS diagnosis. RESULTS IGF-I, IGF-II, and IGF-I/insulin-like growth factor-binding protein-3 ratio were not different among subjects with an increasing number of MetS criteria and were not associated with single components of MetS as well as with body composition parameters. In children younger than 10 years, IGF-I directly correlated with high-density lipoprotein cholesterol (p < 0.005) even after controlling for confounders. IGF-II was significantly higher in obese children and correlated with parameters of insulin sensitivity (p < 0.05). CONCLUSION IGFs were neither related to MetS nor to body composition parameters in obese children. Further studies are needed to clarify the mechanisms underlying the relationship between IGF-II and insulin sensitivity.
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Carotid Intima-Media Thickness in Children Treated with Growth Hormone: A Follow-Up Study over Three Years.
Rothermel, J, Knop, C, Lass, N, Toschke, C, Wunsch, R, Reinehr, T
Hormone research in paediatrics. 2017;(2):73-80
Abstract
BACKGROUND There is an ongoing discussion whether high doses of growth hormone (GH) may lead to cardiovascular diseases. Therefore, we studied the longitudinal relationships between GH treatment and carotid intima-media thickness (cIMT), which is predictive of the development of atherosclerosis. METHODS We measured blood pressure, lipids, hemoglobin HbA1c, IGF-1, IGFBP-3, and cIMT in 28 children treated with supraphysiological doses of GH (mean age 9.8 ± 2.2 years, 39% males) and 36 children suffering from GH deficiency (GHD) and treated with physiological doses of GH (mean age 9.7 ± 2.2 years, 72% males) in a longitudinal study over 3 years. RESULTS The cIMT values did not change significantly in the observation period in children with GHD (Δmaximum and Δmean cIMT 0.0 ± 0.1 mm). The mean (+0.1 ± 0.1 mm) but not the maximum cIMT (0.0 ± 0.1 mm) increased significantly (p = 0.049) in the children treated with supraphysiological doses of GH. Blood pressure, lipids, and HbA1c were not related to cIMT, while IGF-1, IGFBP-3, body mass index expressed as a standard deviation score, and treatment duration correlated significantly with cIMT. CONCLUSIONS We did not find any robust evidence that GH treatment is associated with changes in cIMT. Further studies are necessary to analyze the impact of IGF-1 and IGFBP-3 concentrations on cIMT.
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Bioavailable IGF-1 and its Relation to the Metabolic Syndrome in a Bi-Ethnic Population of Men and Women.
Koegelenberg, AS, Schutte, R, Smith, W, Schutte, AE
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2016;(2):130-6
Abstract
Insulin-like growth factor 1 (IGF-1), an insulin sensitivity and vasculoprotective factor, associates negatively with the metabolic syndrome. However, IGF-1 is reduced by factors such as inflammation, oxidative stress and liver dysfunction. We investigated the relationship between bioavailable IGF-1 and the number of metabolic syndrome components and determined whether this relationship is independent of inflammation, oxidative stress and gamma glutamyl transferase (γ-GT; a marker of liver dysfunction). This study included 907 black and white participants stratified by sex (aged 43.0±11.8 years). Among them 63 participants had fasting glucose levels of ≥+7.0+mmol/l and/or used diabetes medication. Via standard methods we determined waist circumference, fasting glucose, triglycerides, high-density lipoprotein cholesterol and blood pressure. We also determined high-sensitivity C-reactive protein (CRP), reactive oxygen species (ROS), γ-GT, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3). IGF-1/IGFBP-3 was used as an estimate of bioavailable IGF-1. Total IGF-1 was similar between men and women (p=0.10), however, bioavailable IGF-1 was lower in women (p<0.001). In multivariate-adjusted analyses, IGF-1/IGFBP-3 was inversely associated with the number of metabolic syndrome components in both sexes (men: β=- 0.11; p=0.013 and women: β=- 0.17; p=0.003). Upon inclusion of ROS, γ-GT and CRP, significance was lost. In patients without diabetes, the results for men changed marginally, but were consistent for women. We found an inverse association between bioavailable IGF-1 and the number of metabolic syndrome components. But the relationship was dependent on oxidative stress, liver dysfunction and inflammation, suggesting underlying processes by which the metabolic syndrome attenuates IGF-1.
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Women with osteoarthritis have elevated synovial fluid levels of insulin-like growth factor (IGF)-1 and IGF-binding protein-3.
Hooshmand, S, Juma, S, Khalil, DA, Shamloufard, P, Arjmandi, BH
Journal of immunoassay & immunochemistry. 2015;(3):284-94
Abstract
The present study explores the possible connection between synovial fluid concentrations of insulin like growth factor (IGF-1), IGF-binding protein (IGFBP-3), leptin, and C-reactive protein (CRP) in osteoarthritis (OA). Synovial fluid specimens were obtained from a total of thirty-four individuals with and without OA. Protein-normalized measurements of IGF-1, IGFBP-3, and leptin concentrations in synovial fluid showed significantly (P < 0.05) elevated levels in women with knee OA but not in men. This study provides initial evidence that protein normalized IGF-1 and IGFBP-3 and leptin levels increase in synovial fluid of women but not in men with OA versus those without OA.