IGF-binding Protein Research Articles

Insulin-Like Growth Factor, Inflammation, and MRI Markers of Alzheimer's Disease in Predominantly Middle-Aged Adults.

Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults. To investigate the association of serum IGF-1 and IGF binding protein 3 (IGFBP-3) concentrations with MRI markers of Alzheimer's disease in predominantly middle-aged adults, and further assess moderation by chronic inflammation. We included participants from the Framingham Heart Study (n = 1,852, mean age 46±8, 46% men) and the Study of Health in Pomerania (n = 674, mean age 50±13, 42% men) with available serum IGF-1, IFGBP-3, as well as brain MRI. IGF-1 and IFGBP-3 were related to MRI outcomes (i.e., total brain, cortical gray matter, white matter, white matter hyperintensities (WMH), and hippocampal volumes) using multivariable regression models adjusting for potential confounders. Subgroup analyses by C-reactive protein (CRP) concentrations were also performed. Cohort-specific summary statistics were meta-analyzed using random-effects models and corrected for multiple comparisons. Meta-analysis results revealed that higher IGF-1 concentrations were associated with lower WMH (estimate [β] [95% CI], -0.05 [-0.09, -0.02], p = 0.006) and larger hippocampal volumes (0.07 [0.02, 0.12], p = 0.01), independent of vascular risk factors. These associations occurred predominantly in individuals with CRP concentrations < 75th percentile. We did not observe associations between IGFBP-3 and MRI outcomes. Our findings suggest that IGF-1-related signaling may be implicated in brain health as early as midlife.

Molecular cloning and expression profiling of insulin-like growth factor 2 and IGF-binding protein 6 in Clarias magur (Hamilton 1822)

Growth is an important trait in aquaculture and the major genes that regulate it are Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs). In this study, the full-length coding sequences of IGF2 and IGFBP6 genes in the Indian catfish Clarias magur were cloned and characterized. The full-length cDNA sequences of IGF2 and IGFBP6 were 885 bp (ORF 642 bp) and 928 bp (ORF 600 bp), encoding 213 and 199 amino acids, respectively. Bioinformatics analyses revealed that the magur IGF2 and IGFBP6 proteins are hydrophilic and secretory in nature. Sequence alignment with other teleosts and mammalian orthologues shows conservation of the functional domains. Gene expression analysis in 6 individuals each of high (298 ± 5.0 g) and low (210 ± 6.0 g) growth performing families showed significantly (p < 0.05) higher expression (2.5–3 fold) of IGF2, and lower expression (∼2.5 fold) of IGFBP6 in liver and muscle of fast-growing fish. This study suggests that IGF2 could be playing a major role in the growth regulation of magur. These genes and their expression patterns could be developed into growth-associated markers for magur and other catfishes.

Insulin-like growth factor-I biocompartmentalization across blood, interstitial fluid and muscle, before and after 3 months of chronic resistance exercise.

This investigation examined the influence of 12-week ballistic resistance training programs on the IGF-I system in circulation, interstitial fluid, and skeletal muscle, at rest and in response to acute exercise. Seventeen college-aged subjects (11 women/6 men; 21.7 ± 3.7 yr) completed an acute ballistic exercise bout before and after the training program. Blood samples were collected pre-, mid-, and postexercise and analyzed for serum total IGF-I, free IGF-I, and IGF binding proteins (IGFBPs) 1-4. Dialysate and interstitial free IGF-I were analyzed in vastus lateralis (VL) interstitial fluid collected pre- and postexercise via microdialysis. Pre- and postexercise VL muscle biopsies were analyzed for IGF-I protein expression, IGF-I receptor phosphorylation (p-IGF-IR), and AKT phosphorylation (p-AKT). Following training, basal serum IGF-I, free IGF-I, IGFBP-2, and IGFBP-3 decreased whereas IGFBP-1 and IGFBP-4 increased. Training reduced basal dialysate and interstitial free IGF-I but had no effect on basal skeletal muscle IGF-I, p-IGF-IR, or p-AKT. Acute exercise elicited transient changes in IGF-I system concentrations and downstream anabolic signaling both pre- and posttraining; training did not affect this acute exercise response. Posttraining, acute exercise-induced changes in dialysate/interstitial free IGF-I were strongly correlated with the changes in intramuscular IGF-I expression, p-IGF-IR, and p-AKT. The divergent influence of resistance training on circulating/interstitial and skeletal muscle IGF-I demonstrates the importance of concurrent, multiple biocompartment analysis when examining the IGF-I system. As training elicited muscle hypertrophy, these findings indicate that IGF-I's anabolic effects on skeletal muscle are mediated by local, rather than systemic mechanisms.NEW & NOTEWORTHY In the first investigation to assess resistance training's effects on the IGF-I system in serum, interstitial fluid, and skeletal muscle, training decreased basal circulating and interstitial IGF-I but did not alter basal intramuscular IGF-I protein activity. Posttraining, acute exercise-induced interstitial IGF-I increases were strongly correlated with intramuscular IGF-I expression and signaling. These findings highlight the importance of multibiocompartment measurement when analyzing IGF-I and suggest that IGF-I's role in hypertrophic adaptations is locally mediated.

Effect of 10-hours Time Restricted Diet on Breast Cancer Risk in Pre and Postmenopausal Women with Overweight or Obesity: TRED Pilot Study

ObjectivesThis study examined the effect of 10-h time restricted diet on breast cancer risk, assessing changes in body weight, insulin, IGF-1, and IGF binding protein 1, 2, and 3 among pre and postmenopausal women with overweight and obesity.MethodsWomen with overweight or obesity (n = 25) were enrolled into a time-restricted diet for 6 months. Participants were instructed to eat only from 10am until 8pm and to record consumption on the TRED smartphone app. At weeks 1, 2, 12, and 24, participants were asked to complete food diaries. During the other weeks, participants simply recorded the category of food consumed (meal or snack). Compliance was calculated as percentage of days when food consumption was reported.Results25 women with a BMI between 25 and 40 (32.3 ± 4.2) and age between 18–65 years old (46.5 ± 11.0) were enrolled. Average weight loss was 0.8 ± 4.6 kg (−0.6%). Fat percentage, muscle mass remained unchanged. Insulin and IGFBP 2 significantly increased from baseline to post intervention and to follow up. However, the change is not clinically significant. IGF-1 and IGFBP1 significantly decreased from baseline to follow up. Average adherence to the diet protocol was high: 78% of participants recorded dietary intake on at least 77% of intervention days.ConclusionsThe TRED 10-hour eating window did not lead to weight loss, body fat loss, or decreasing waist circumference among pre and postmenopausal women with overweight or obesity. However, the intervention significantly improved some biomarkers of breast cancer risk (IGF-1, IGFBP 2 and IGFBP 3).Funding SourcesThis study was supported by NIH/NCI training grant T32 CA193193.

Combined diagnostic value of insulin-like growth factor-1, insulin-like growth factor binding protein-3, and baseline luteinizing hormone levels for central precocious puberty in girls.

The golden standard test for diagnosing central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test, which has many limitations. This study aimed to investigate the value of insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and basal luteinizing hormone (LH) levels in diagnosing CPP. Cross-sectional study of the levels of IGF-1, IGFBP-3, and basal LH in girls with a chief complaint of premature breast development. Seventy-nine girls with CPP and 37 girls with premature thelarche (PT) diagnosed at West China Second University Hospital from January 2016 to October 2018 were recruited. All patients underwent physical examination, laboratory tests, uterine and ovarian ultrasound, and bone age tests, only CPP patients underwent pituitary magnetic resonance imaging (MRI). Statistical analysis was performed using the SPSS software 21.0. A receiver operating characteristic curve was used to determine diagnostic value. The anthropometric data and hormone indicators between CPP and PT were statistically different (p<0.001), except for peak follicle stimulating hormone (FSH) levels (p=0.181). IGF-1, IGFBP-3, and basal LH levels were significantly higher in the subjects with CPP than in those with PT; IGF-1 and basal LH were positively correlated with peak LH and LH/FSH (peak) (p<0.001). The area under the curve (AUC) of IGF-1, IGFBP-3, and basal LH were 0.880, 0.853, and 0.915, respectively. When combined, the AUC reached the highest value of 0.978. IGF-1, IGFBP-3, and baseline LH levels were useful in diagnosing CPP. The combined analysis improved the diagnostic effectiveness.

Constant light exposure in early life induces m6A-mediated inhibition of IGF gene family in the chicken.

Insulin-like growth factor (IGF) family plays important roles in regulating the development of various organ systems through stimulating cell proliferation and differentiation. Photoperiod is an important factor affecting growth and development in the chicken, yet the effect of constant light exposure in early life on IGF1 and IGF2 expression in the chicken remains unclear. In this study, one-day-old chickens were kept in either constant light (24L:0D, LL) or natural photoperiod (12L:12D, LD) for the first week of life and then maintained in constant light from 8 to 21 d of age. Constant light exposure in early life reduced mRNA expression of IGF gene family, including mRNA expression of IGF1, IGF2, and IGF2 binding proteins, in the hippocampus, hypothalamus, and liver of chickens at both 7 and 21 d of age. Moreover, constant light exposure increased mRNA expression of genes involved in RNA methylation N6-methyladenosine (m6A) in a tissue-specific manner. Interestingly, higher m6A on 3'UTR of IGF2 mRNA coincides with lower IGF2 mRNA, indicating a possible role of m6A in the post-transcriptional regulation of IGF2 expression in the hippocampus, hypothalamus, and liver of chickens. These findings suggest a m6A-mediated gene regulation of IGF gene family in different organs of chicken and expand our knowledge on mechanism of gene regulation in response to early life experience.

Evaluation of apelin level in women with polycystic ovary syndrome at Al-Najaf Province

Hyperinsulinaemia is one of the most common clinical manifestations in women with PCOS. Here, hyperinsulinaemia may increase IGF- 1 expression and aggravate the effect of IGF1 by reducing the synthesis of IGF binding protein 1. IGF1 increases the expression of APLNR, and further promotes oestrogen synthesis and secretion via binding of APLN/APLNR. Patients with PCOS have high ovarian IGF1 levels. Therefore, IGF-1 and APLN may exhibit a compensatory increase in PCOS. Recently study found a high APLN/APLNR level in blood and ovary in PCOS (Liu et al., 2020). One of the first effects of APLN observed was its ability to lower glucose levels in both in fasting conditions and during a glucose tolerance test. Increased glucose uptake in target tissues such as skeletal muscle and adipose tissue was responsible for the decreased glycaemia (Yue et al., 2010).

Investigation of the relationship of growth hormone, insulin-like growth factor (IGF)-1, and IGF-binding protein-3 levels with graft viability in autograft-transplanted pediatric patients with major burns

BackgroundIn our study, we investigated graft viability, Growth Hormone (GH), Insulin-like growth factor (IGF)-1, and IGF-binding protein (IGFBP)-3 in autograft-transplanted pediatric major burn cases. MethodsThis descriptive study was conducted with the participation of pediatric patients with major burn wounds. The laboratory data and characteristics of the patients were accessed retrospectively, and the obtained data were recorded in the data form developed by the researchers. In the analysis of the data, descriptive statistical methods, chi-squared test, Wilcoxon signed-rank test, one-way ANOVA, and post hoc analyses were used. ResultsThe sample of our study consisted of 93 pediatric major burn patients with a total burnt body surface area of more than 20%. It was found that 65.59% of the patients were between the ages of 1 and 5, 63.43% of them were in the 41–55 percentile range, 58.06% had a hot liquid burn, 74.2% had a second-degree burn, 60.21% had a burn percentage in the range of 21–40 of their total body surface area. It was determined that the GH and IGF-1 levels of the patients who experienced loss after graft transplantation remained below the normal value in the first 14 days, and the differences in the GH and IGF-1 values between the patients with good functioning grafts and those with graft loss were statistically significant (p < 0.01). It was found that the IGFBP-3 value remained low on the 14th day in the patients with good functioning grafts, and the difference in the IGFBP-3 values between the patients with good functioning grafts and those with graft loss was statistically significant (p < 0.05). ConclusionToday, it is known that the parameters of GH, IGF-1, and IGFBP-3 are related to many problems. However, no study examining their relationships with graft viability in autograft-transplanted pediatric patients with major burns was encountered. Our study may be the first to determine that changes in these three laboratory parameters negatively affect the healing of burn wounds.

IGF-dependent dynamic modulation of a protease cleavage site in the intrinsically disordered linker domain of human IGFBP2.

Functional regulation via conformational dynamics is well known in structured proteins but less well characterized in intrinsically disordered proteins and their complexes. Using NMR spectroscopy, we have identified a dynamic regulatory mechanism in the human insulin-like growth factor (IGF) system involving the central, intrinsically disordered linker domain of human IGF-binding protein-2 (hIGFBP2). The bioavailability of IGFs is regulated by the proteolysis of IGF-binding proteins. In the case of hIGFBP2, the linker domain (L-hIGFBP2) retains its intrinsic disorder upon binding IGF-1, but its dynamics are significantly altered, both in the IGF binding region and distantly located protease cleavage sites. The increase in flexibility of the linker domain upon IGF-1 binding may explain the IGF-dependent modulation of proteolysis of IGFBP2 in this domain. As IGF homeostasis is important for cell growth and function, and its dysregulation is a key contributor to several cancers, our findings open up new avenues for the design of IGFBP analogs inhibiting IGF-dependent tumors.

Association of animal and plant protein intakes with biomarkers of insulin and insulin-like growth factor axis

Insulin and insulin-like growth factor (IGF)-1 signaling is a proposed mechanism linking dietary protein and major chronic diseases. However, it is unclear whether animal and plant proteins are associated with biomarkers of insulin and IGF axis. We analyzed a total of 14,709 participants from Nurses' Health Study and Health Professionals Follow-up Study who had provided a blood sample. Detailed dietary information was assessed using validated food frequency questionnaires. We assessed C-peptide, insulin, IGF-1, and IGF binding proteins (BP). Multivariable-adjusted linear regressions were used to examine associations of animal and plant protein intake with biomarkers after adjusting for confounders. The medians (5th-95th percentiles) of animal and plant protein intake (% of total energy) were 13% (8-19%) and 5% (4-7%), respectively. Compared to participants in the lowest quintile, those in the highest quintile of animal protein had 4.8% (95% CI: 1.9, 7.9; P-trend<0.001) higher concentration of IGF-1 and -7.2% (95% CI:-14.8, 1.1; P for trend=0.03) and-11.8% (95% CI:-20.6,-1.9; P-trend<0.001) lower concentration of IGFBP-1 and IGFBP-2, respectively, after adjustment for major lifestyle factors and diet quality. In contrast, no association was observed between animal protein intake and C-peptide, insulin and IGFBP-3. The associations were restricted to participants with at least one unhealthy lifestyle risk factor (i.e., overweight/obese, physical inactivity, smoking, and heavy alcohol intake). Plant protein tended to be strongly associated with numerous biomarkers in age-adjusted analyses but these became largely attenuated or non-significant in multivariable adjustment. Plant protein intake remained positively associated with IGF-1 (P-trend=0.002) and possibly IGFBP-1 (P-trend=0.02) after multivariable adjustment. Substitution of plant protein with animal protein sources was associated with lower IGFBP-1. In additional analysis, IGF-1 and IGFBPs were estimated to mediate approximately 5-20% of the association between animal protein and type 2 diabetes. Higher animal protein intake was associated with higher IGF-1 and lower IGFBP-1 and IGFBP-2, whereas higher plant protein intake was associated with higher IGF-1 and IGFBP-1.

MOLECULAR BASIS OF THE DEVELOPMENT OF INSULIN RESISTANCE IN OBESE ADOLESCENT AND ADULT MEN

The aim of this work was to study the association between the expression of glucose metabolism related genes and insulin resistance, which expression is changed in obese adolescents and adult men with and without insulin resistance, for better understanding the molecular basis of the development of obesity complications and evaluation of possible contribution of these genes in development of insulin resistance. Methods. The expression level of genes related to glucose metabolism and their regulations was studied by real-time qPCR in adipose tissue and blood cells using SYBRGreen Mix and specific for each mRNA forward and reverse primers. Total RNA was extracted using TRIZOL reagent. For reverse transcription of mRNAs we used Thermo Scientific Verso cDNA Synthesis Kit (Germany). The values of mRNA expressions were normalized to the level of ACTB mRNA and represented as percent of control (100 %). Results. It was shown that in obese patients with insulin resistance the expression level of IRS1 (insulin receptor substrate 1), HK2 (hexokinase 2), PFKFB2 (6-phosphofructokinase/fructose-2,6-bisphosphatase 2) and PFKFB3 as well as circadian factors CLOCK and ARNTL genes in subcutaneous adipose tissue is significantly decreased as compared to obese men with normal sensitivity to insulin. At the same time, the development of insulin resistance in obese patients leads to up-regulation of PFKFB4, PER1, HSPA6, ALDH1A3, COL5A1, TIMP1, TIMP2, SPARC, and VCAN gene expressions in subcutaneous adipose tissue. The expression level of IGF1 (insulin-like growth factor 1) and IGFBP5 (IGF binding protein 5) as well as ENO1 (enolase 1) and ENO2 is down-regulated in the blood of obese adolescent with insulin resistance, but IGFBP2 and IGFBP7 gene expressions are significantly increased in these patients. Conclusions. The results of this investigation provide evidence that the development of insulin resistance in obese patients is associated with gene specific changes in the expression of many very important regulatory genes, which are endoplasmic reticulum stress responsible.

The Origination of Growth Hormone/Insulin-Like Growth Factor System: A Story From Ancient Basal Chordate Amphioxus.

The growth hormone/insulin-like growth factor (GH/IGF) system, also called the pituitary-liver axis, has a somatotrophic role in the body. Although the GH/IGF system has always been regarded as a vertebrate-specific endocrine system, its actual origin remained unknown for a long time. The basal chordate, amphioxus, occupies an evolutionary position between vertebrates and invertebrates. Impressively, most of the members of the GH/IGF system are present in the amphioxus. The GH-like molecule in the amphioxus is mainly expressed in Hatschek’s pit. It functions similarly to vertebrate GH and has a GH receptor-like binding partner. The amphioxus IGF-like peptide shows mitogenic activity and an expression pattern resembling that of vertebrate IGF-I. The receptor of IGF-like peptide and IGF binding protein (IGFBP) have also been demonstrated to exist in the amphioxus. These results reveal the origin of the gene families in the GH/IGF system, providing strong evidence that this system emerged in the amphioxus.

Changes in circulating insulin-like growth factor-1 and its binding proteins in yearling rainbow trout during spring under natural and manipulated photoperiods and their relationships with gill Na+, K+-ATPase and body size

Smoltification in salmonids occurs during spring in response to increasing photoperiod to prepare for marine life. Smoltification is associated with increased hypo-osmoregulatory ability and enhanced growth potential, mediated by growth hormone and insulin-like growth factor (IGF)-1. Rainbow trout is uniquely insensitive to the induction of smoltification-associated changes by photoperiod, such as the activation of gill Na+,K+-ATPase (NKA). We measured the circulating IGF-1 and IGF-binding protein (IGFBP)-2b levels in yearling rainbow trout exposed to natural and manipulated photoperiods during spring and correlated these with gill NKA activity and body size. Although the effect of photoperiod manipulation on body size and circulating IGF-1 and IGFBP-2b was negligible, they were positively correlated with gill NKA activity in fish under simulated natural photoperiod. We next pit-tagged yearling rainbow trout and fed them a restricted ration or to satiation under a natural photoperiod. In April, gill NKA activity was higher in the satiation group than in the restricted group and positively correlated with body size and growth rate. In addition, circulating IGFBP-2b was positively correlated with gill NKA, size and growth, whereas circulating IGF-1 was correlated only with size and growth. The relationship between circulating IGF-1 and growth intensified from May to June, suggesting that the IGF-1–growth relationship was disrupted in April when gill NKA was activated. Two additional IGFBPs were related to growth parameters but not to gill NKA activity. The present study suggests that circulating IGFBP-2b and IGF-1 mediate the size-dependent activation of gill NKA in yearling rainbow trout during spring.

A local insulin reservoir in Drosophila alpha cell homologs ensures developmental progression under nutrient shortage

Insulin/insulin-like growth factor (IGF) signaling (IIS) controls many aspects of development and physiology. In Drosophila, a conserved family of insulin-like peptides called Dilps is produced by brain neurosecretory cells, and it regulates organismal growth and developmental timing. To accomplish these systemic functions, the Dilps are secreted into the general circulation, and they signal to peripheral tissues in an endocrine fashion. Here, we describe the local uptake and storage of Dilps in the corpora cardiaca (CC), an endocrine organ composed of alpha cell homologs known to produce the glucagon-like adipokinetic hormone (AKH). We show that Dilp uptake by the CC relies on the expression of an IGF-binding protein called ImpL2. Following their uptake, immunogold staining demonstrates that Dilps are co-packaged with AKH in dense-core vesicles for secretion. In response to nutrient shortage, this specific Dilp reservoir is released and activates IIS in a paracrine manner in the prothoracic gland. This stimulates the production of the steroid hormone ecdysone and initiates entry into pupal development. We therefore uncover a sparing mechanism whereby insulin stores in CC serve to locally activate IIS and the production of ecdysone in the PG, accelerating developmental progression in adverse food conditions.

Liver and muscle-specific effects of phoenixin-20 on the insulin-like growth factor system mRNAs in zebrafish

ObjectivePhoenixin-20 (Pnx-20) is a bioactive peptide with endocrine-like actions in vertebrates. Recent studies suggest Pnx-20 promotes growth hormone/insulin-like growth factors (Gh/Igf) axis, an important endocrine regulator of growth in mammals and fish. DesignIn this research, we determined whether Pnx-20 affects the different members of the Igf family, its binding proteins and receptors (Igf-system) in zebrafish liver and muscle. ResultsIn vivo administration of Pnx-20 downregulated igfs, igf receptors (igfrs) and igf binding protein (igfbp) 5 mRNA expression in the liver of male and female zebrafish at both 1 and 6 h post-intraperitoneal (IP) injection. Interestingly, this effect occurred at a relatively earlier timepoint in female zebrafish suggesting sex-specific differences in Pnx-20 action. Besides, either 6 or 24 h in vitro incubations with Pnx-20 downregulated the expression of all igfs, igfrs and igfbp5 mRNAs (except igf2a) analyzed in a zebrafish liver cell (ZFL) line. Moreover, siRNA-mediated knockdown of Pnx-20 upregulated all Igf-system mRNAs analyzed in ZFL cells. Together, these results (both in vivo and in vitro) revealed a general suppressive action for both endogenous and exogenous Pnx-20 on the hepatic Igf-system of zebrafish. In contrast, a general sex-specific upregulation of the Igf-system mRNAs analyzed was found in the muscle of Pnx-20 injected fish. Future research should explore the sex- and time-differences observed in the present study. ConclusionsCollectively, this research shows that Pnx-20 is a tissue-specific regulator of the liver (suppressor) and muscle (stimulant) Igf signaling in both male and female zebrafish.

Growth Hormone and Thyroid Function in Children With Attention Deficit Hyperactivity Disorder Undergoing Drug Therapy.

The trends in hormone indices of children with attention deficit hyperactivity disorder (ADHD) who received long-term medication treatment remains controversial. This prospective study aimed to examine the changes in the growth hormone and thyroid hormone systems among children with ADHD undergoing various medication treatments. In total, 118 children who were diagnosed with ADHD and were drug-naive were observed naturalistically over 12 months. Of them, 22 did not receive any medication, while 39, 40, and 17 were treated with low doses of short-acting methylphenidate (MPH) (14 ± 6.7 mg/day), osmotic-release oral system (OROS) long-acting MPH (32 ± 9.6 mg/day), and atomoxetine (29.2 ± 9.7 mg/day), respectively. Blood samples were obtained at both the baseline and the endpoint (month 12) to measure serum levels of insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), prolactin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and free T4. Trends for IGF-1, IGFBP-3, prolactin, TSH, T3, T4, and free T4 levels were similar among the 4 groups. Changes in serum levels of IGF-1 were positively correlated with changes in height and weight of all the children with ADHD. However, patients who received MPH treatment had less body weight gain than the nonmedicated group. The ratio of MPH doses to body weight was inversely correlated with the increment in height. There were no changes in thyroid or growth hormones associated with the low doses of ADHD medications used in this study within 1 year's duration. Nonetheless, patients' growth and the appropriateness of drug dosage should be closely monitored.

First Year Metabolic and Hormonal Behavior Define two Different Populations of SGA Newborn for Weight or Height.

ContextSmall-for-gestational-age (SGA) children have a particular metabolic and hormonal pattern at birth that changes rapidly.ObjectiveTo evaluate the linear and weight growth in the first year of life in SGA children.DesignProspective, monocentric cohort study.SettingReal-world data collected from April 2012 to January 2016.PatientsSGA newborns uniformly defined by either growth or length lower than -2 SDs for gestational age.InterventionsAll children were evaluated for 1 year after birth, at 3 days of life, then 3, 6, and 12 months after birth.Main outcome measuresAnthropometric parameters and biochemical variables, such as blood glucose, insulin, leptin, IGF-1, IGF binding protein-3 (IGFBP-3), and homeostasis model assessment - insulin resistance (HOMA-IR) index.ResultsA total of 133 SGA children were enrolled. Length significantly improved 1 month after birth, whereas weight significantly increased only at 3 months after birth. Biochemical variables increased during the first year of life, showing a prediction by IGFBP-3 and HOMA-IR index. Then, the variables were divided considering either weight, length, or both, showing a different incidence. The biochemical variable changes recorded in the first step were maintained considering SGA children for weight or length, whereas they disappeared when weight and length were considered together.ConclusionsOur study shows a specific catchup growth for weight and length in SGA children. Moreover, we highlight that weight and length should be considered as independent parameters in SGA children, defining 2 different metabolic-hormonal populations with different conceivable predictive role in early catchup growth and in later growth and metabolic status.

The role of IGF-pathway biomarkers in determining risks, screening, and prognosis in lung cancer.

Background: Detection rates of early-stage lung cancer are traditionally low, which contributes to inconsistent treatment responses and high rates of annual cancer deaths. Currently, low-dose computed tomography (LDCT) screening produces a high false discovery rate. This limitation has prompted research to identify biomarkers to 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.Main Body: Multiple biomarkers within the IGF family have been investigated, most notably IGF-I and IGF binding protein 3. However, newer studies seek to expand this search to other molecules within the IGF axis. Certain studies have demonstrated these biomarkers are useful when used in combination with lung cancer screening, but other findings were not as conclusive, possibly owing to measurement bias and non-standardized assay techniques. Research also has suggested IGF biomarkers may be beneficial in the prognostication and subsequent treatment via systemic therapy. Despite these advances, additional knowledge of complex regulatory mechanisms inherent to this system are necessary to more fully harness the potential clinical utility for diagnostic and therapeutic purposes.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.

Effects of Pilates with and without elastic resistance on health variables in postmenopausal women with low back pain.

Aim: To compare the effects of Pilates with and without accessories on biochemical markers, pain intensity, functional disability and muscle strength in postmenopausal women with nonspecific chronic low back pain. Materials & methods: Twenty-two participants were randomized to a group of Pilates without (PG; n=11) and with elastic resistance (PAG; n=11) for 8weeks, twice a week. We analyzed IGF-1, IGF-binding protein-3 (IGFBP-3), cortisol, creatine kinase, pain intensity, functional disability, abdominal and back strengths. Results: Both groups had lower pain intensity and functional disability and increased lumbar strength postinterventions. PAG exhibited an increase in IGF-1/IGFBP-3 ratio and reduction in creatine kinase compared with PG. Conclusion: Both interventions were effective in the treatment of low back pain. However, PAG presented better responses than PG. Clinical Trial Registration: Brazilian Clinical Trials Registry: ReBEC (RBR-9jwcykc), www.ensaiosclinicos.gov.br/rg/RBR-9jwcykc.

Interrelationships among growth hormone, thyroid function, and endocrine-disrupting chemicals on the susceptibility to attention-deficit/hyperactivity disorder.

Abnormal growth hormones and thyroid function may be linked to pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Phthalates and bisphenol-A (BPA), two endocrine-disrupting chemicals (EDCs), may affect the human endocrine system. In this study, we aimed to perform a comprehensive investigation of whether growth hormone, thyroid function, and EDCs exhibited differential levels between ADHD patients and healthy controls. In total, 144 children with ADHD and 70 healthy control subjects were enrolled. Their endocrine systems were evaluated using the serum levels of insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and Free T4. The urinary levels of EDCs, including monoethyl phthalate (MEP), mono-methyl phthalate (MMP), monoethylhexyl phthalate (MEHP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), and BPA, were also examined. Patients with ADHD had lower IGF-1 levels than healthy controls (p = 0.003), but we observed no significant difference in IGFBP-3, TSH, T3, T4, or Free T4. Compared to the control group, patients with ADHD demonstrated higher MEHP levels (p = 0.043), MnBP (p = 0.033), and MBzP (p = 0.040). Furthermore, MEHP levels (p < 0.001) and BPA levels (p = 0.041) were negatively correlated with IGF-1 levels, while IGF-1 levels were negatively correlated with principal components consisting of ADHD clinical symptoms and neuropsychological performance variables. We suggest that MEHP exposure may be associated with decreased serum levels of IGF-1 and increased risk of ADHD. The mechanism underlying this association may be important for protecting children from environmental chemicals that adversely affect neurodevelopment.