Low Insulin-like Growth Factor-1 Levels Research Articles

The positive impact of smoking on poor sleep quality is moderated by IGF1 levels in cerebrospinal fluid: a case-control study among Chinese adults.

Previous research indicates associations between cigarette smoking, insulin-like growth factor-1 (IGF1), and sleep disturbances. This study aimed to examine the association between smoking and sleep quality and investigate the moderating role of IGF1. This case-control study involved 146 Chinese adult males (53 active smokers and 93 non-smokers) from September 2014 to January 2016. Sleep quality and disturbances were evaluated using the Pittsburgh Sleep Quality Index (PSQI), which includes seven scales. Pearson correlation analysis and logistic regression analysis were utilized to examine the link between IGF1 levels in cerebrospinal fluid (CSF) and PSQI scores. The effect of IGF1 was assessed using the moderation effect and simple slope analysis, with adjustments made for potential confounders. Active smokers exhibited significantly higher global PSQI scores and lower IGF1 levels in CSF compared to non-smokers. A significant negative correlation was observed between IGF1 and PSQI scores (â = -0.28, P < 0.001), with a stronger association in non-smokers (Pearson r = -0.30) compared to smokers (Pearson r = -0.01). Smoking was associated with higher global PSQI scores (â = 0.282, P < 0.001), and this association was moderated by IGF1 levels in CSF (â = 0.145, P < 0.05), with a stronger effect at high IGF1 levels (Bsimple = 0.402, p < 0.001) compared to low IGF1 levels (Bsimple = 0.112, p = 0.268). Four subgroup analysis revealed similar results for sleep disturbances (Bsimple = 0.628, P < 0.001), with a marginal moderation effect observed on subjective sleep quality (Bsimple = 0.150, P = 0.070). However, independent associations rather than moderating effects were observed between IGF1 and sleep efficiency and daytime disturbance. We provided evidence to demonstrate the moderation effect of IGF1 on the relationship between smoking and sleep in CSF among Chinese adult males.

Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major.

Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures. We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9years) with low serum IGF-1 (median value 52.4ng/ml, 38.5-83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder. Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%). Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.

An exploratory study of clinical factors associated with IGF-1 and IGFBP-3 in preterm infants.

Despite advances in parenteral nutrition, postnatal growth failure in very low birthweight (VLBW) preterm infants is common and associated with chronic health problems. Insulin-like growth factor 1 (IGF-1) is positively associated with improved infant growth, but factors which promote IGF-1 levels in this population have not been clearly identified. The objective of this study was to explore early factors that influence IGF-1 in VLBW preterm infants. VLBW infants were enrolled into a prospective, randomized controlled nutrition trial (N = 87). Outcome measures included IGF-1 and IGFBP-3 levels measured at 35 weeks PMA. Linear regression analyses tested the relationships between candidate clinical predictors and levels of IGF-1 and IGFBP-3. Higher protein intake, longer duration of parenteral nutrition, and lower IGFBP-3 levels at 1 week of life were associated with lower IGF-1 levels at 35 weeks PMA. Neither early markers of insulin resistance nor degree of illness were associated with IGF-1 levels at 35 weeks PMA. Optimization of early nutrient intake, and attention to route of delivery, may have a lasting influence on IGF-1/IGFBP-3, and in turn, long-term health outcomes. In very low birthweight preterm infants, early protein intake, duration of parenteral nutrition, and insulin-like growth factor binding protein 3 (IGFBP-3) levels at 1 week of life are positively associated with insulin-like growth factor 1 (IGF-1) levels at 35 weeks postmenstrual age. Data from this study highlight the influence of early nutrition on components of the endocrine axis in preterm infants. Strategies aimed at early initiation of enteral nutrition, as well as optimizing composition of parenteral nutrition, may bolster hormones involved in promoting preterm infant growth.

There is currently no evidence that high serum leptin and low insulin-like growth factor-1 levels characterise fibromyalgia.

There is currently no evidence that high serum leptin and low insulin-like growth factor-1 levels characterise fibromyalgia.

Insulin-like growth factor 1 associated with altered immune responses in preterm infants and pigs

BackgroundPreterm infants show low blood levels of insulin-like growth factor 1 (IGF-1), known to be negatively correlated with Interleukin-6 (IL-6). We hypothesized that circulating IGF-1 is associated with systemic immune-markers following preterm birth and that exogenous IGF-1 supplementation modulates immune development in preterm pigs, used as model for preterm infants.MethodsPlasma levels of IGF-1 and 29 inflammatory markers were measured in very preterm infants (n = 221). In preterm pigs, systemic immune development, assessed by in vitro challenge, was compared between IGF-1 treated (2.25 mg/kg/day) and control animals.ResultsPreterm infants with lowest gestational age and birth weight showed the lowest IGF-1 levels, which were correlated not only with IL-6, but a range of immune-markers. IGF-1 supplementation to preterm pigs reduced plasma IL-10 and Interferon-γ (IFN-γ), IL-2 responses to challenge and reduced expression of genes related to Th1 polarization. In vitro addition of IGF-1 (100 ng/mL) further reduced the IL-2 and IFN-γ responses but increased IL-10 response.ConclusionsIn preterm infants, plasma IGF-1 correlated with several immune markers, while supplementing IGF-1 to preterm pigs tended to reduce Th1 immune responses. Future studies should document whether IGF-1 supplementation to preterm infants affects immune development and sensitivity to infection.ImpactSupplementation of insulin-like growth factor 1 (IGF-1) to preterm infants has been proposed to promote postnatal growth, but its impact on the developing immune system is largely unknown.In a cohort of very preterm infants, low gestational age and birth weight were the primary predictors of low plasma levels of IGF-1, which in turn were associated with plasma immune markers. Meanwhile, in immature preterm pigs, experimental supplementation of IGF-1 reduced Th1-related immune responses in early life.Supplementation of IGF-1 to preterm infants may affect the developing immune system, which needs consideration when evaluating overall impact on neonatal health.

Regulation of IGF1R by MicroRNA-15b Contributes to the Anticancer Effects of Calorie Restriction in a Murine C3-TAg Model of Triple-Negative Breast Cancer.

Calorie restriction (CR) inhibits triple-negative breast cancer (TNBC) progression in several preclinical models in association with decreased insulin-like growth factor 1 (IGF1) signaling. To investigate the impact of CR on microRNAs (miRs) that target the IGF1/IGF1R pathway, we used the spontaneous murine model of TNBC, C3(1)/SV40 T-antigen (C3-TAg). In C3-TAg mice, CR reduced body weight, IGF1 levels, and TNBC progression. We evaluated the tumoral expression of 10 miRs. CR increased the expression of miR-199a-3p, miR-199a-5p, miR-486, and miR-15b. However, only miR-15b expression correlated with tumorigenicity in the M28, M6, and M6C C3-TAg cell lines of TNBC progression. Overexpressing miR-15b reduced the proliferation of mouse (M6) and human (MDA-MB-231) cell lines. Serum restriction alone or in combination with low levels of recombinant IGF1 significantly upregulated miR-15b expression and reduced Igf1r in M6 cells. These effects were reversed by the pharmacological inhibition of IGFR with BMS754807. In silico analysis using miR web tools predicted that miR-15b targets genes associated with IGF1/mTOR pathways and the cell cycle. Our findings suggest that CR in association with reduced IGF1 levels could upregulate miR-15b to downregulate Igf1r and contribute to the anticancer effects of CR. Thus, miR-15b may be a therapeutic target for mimicking the beneficial effects of CR against TNBC.

Insulin-like growth factor 1 predicts decompensation and long-term prognosis in patients with compensated cirrhosis.

Insulin-like growth factor 1 (IGF-1), which is primarily produced in hepatocytes and is associated with liver functional reserve, plays a crucial role in the pathological condition of cirrhosis. This study aimed to investigate the usefulness of serum IGF-1 levels for predicting the long-term prognosis and decompensation development in patients with cirrhosis. We retrospectively evaluated 148 patients with cirrhosis and divided them into three groups according to baseline IGF-1 levels: low (L)-, intermediate (I)-, and high (H)-IGF-1 groups. The cumulative survival rates were compared among these groups in compensated and decompensated cirrhosis, respectively. Significant and independent factors associated with mortality and decompensation development were identified using Cox proportional hazards regression analysis. The median observation period was 57.1 (41.7-63.2) months. Thirty (20.3%) patients died of liver disease-related events and 21 (22.3%) patients with compensated cirrhosis developed decompensation. Multivariate analysis identified low serum IGF-1 levels as a significant and independent factor associated with mortality (all patients: hazard ratio [HR], 0.967; p = 0.004; patients with compensated cirrhosis: HR, 0.927; p = 0.002). The cumulative survival rates were significantly lower in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (all patients: p < 0.001 and = 0.009; patients with compensated cirrhosis: p = 0.012 and 0.003, respectively). However, in decompensated cirrhosis, the cumulative survival rates demonstrated no significant differences among the three groups. The cumulative decompensation incidence rates were significantly higher in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (p < 0.001 and = 0.009, respectively). Low serum IGF-1 levels were significantly and independently associated with decompensation development (HR, 0.939; p < 0.001). Low serum IGF-1 levels were significantly and independently associated with decompensation development and poor long-term prognosis in patients with compensated cirrhosis. Therefore, IGF-1 may be useful for predicting decompensation-related events and should be regularly monitored in the management of compensated phase.

Long-term opioid treatment and endocrine measures in chronic non-cancer pain patients.

The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a public health problem. Endocrine dysfunction may be a complication of long-term opioid treatment (L-TOT), but the evidence is limited. This study aimed at investigating the associations between L-TOT and endocrine measures in CNCP patients. Cortisol (spot and after stimulation), thyrotropin (TSH), thyroxin (T4), insulin-like growth factor 1 (IGF-1), prolactin (PRL), 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEAS), sex hormone-binding globulin (SHBG), total testosterone (TT) and free testosterone (fT) were measured. Group comparisons were done between CNCP patients in L-TOT and controls as well as between patients on high- or low-dose morphine equivalents. Eighty-two CNCP patients (38 in L-TOT and 44 controls not receiving opioids) were included. Low TT (p = 0.004) and fT concentrations (p < 0.001), high SHBG (p = 0.042), low DEAS (p = 0.017) and low IGF-1 (p = 0.003) in men were found when comparing those in L-TOT to controls and high PRL (p = 0.018), low IGF-1 standard deviation score (SDS) (p = 0.006) along with a lesser, but normal cortisol response to stimulation (p = 0.016; p = 0.012) were found when comparing L-TOT to controls. Finally, a correlation between low IGF-1 levels and high opioid dose was observed (p < 0.001). Our study not only supports previous findings but even more interestingly disclosed new associations. We recommend future studies to investigate endocrine effects of opioids in larger, longitudinal studies. In the meanwhile, we recommend monitoring endocrine function in CNCP patients when prescribing L-TOT. This clinical study found associations between L-TOT, androgens, growth hormone and prolactin in patients with CNCP compared to controls. The results support previous studies as well as add new knowledge to the field, including an association between high opioid dose and low growth hormone levels. Compared to existing research this study has strict inclusion/exclusion criteria, a fixed time period for blood sample collection, and adjustments for potential confounders, which has not been done before.

Compensatory Growth Is Accompanied by Changes in Insulin-Like Growth Factor 1 but Not Markers of Cellular Aging in a Long-Lived Seabird.

AbstractDeveloping organisms often plastically modify growth in response to environmental circumstances, which may be adaptive but is expected to entail long-term costs. However, the mechanisms that mediate these growth adjustments and any associated costs are less well understood. In vertebrates, one mechanism that may be important in this context is the highly conserved signaling factor insulin-like growth factor 1 (IGF-1), which is frequently positively related to postnatal growth and negatively related to longevity. To test this idea, we exposed captive Franklin's gulls (Leucophaeus pipixcan) to a physiologically relevant nutritional stressor by restricting food availability during postnatal development and examined the effects on growth, IGF-1, and two potential biomarkers of cellular and organismal aging (oxidative stress and telomeres). During food restriction, experimental chicks gained body mass more slowly and had lower IGF-1 levels than controls. Following food restriction, experimental chicks underwent compensatory growth, which was accompanied by an increase in IGF-1 levels. Interestingly, however, there were no significant effects of the experimental treatment or of variation in IGF-1 levels on oxidative stress or telomeres. These findings suggest that IGF-1 is responsive to changes in resource availability but is not associated with increased markers of cellular aging during development in this relatively long-lived species.

Abstract #1404780: Implementing a Screening Protocol for Endocrinopathies in Patients with Secondary Hemochromatosis due to Sickle Cell Anemia

Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy characterized by hemolytic anemia, intermittent small vessel occlusion, and organ dysfunction. Red blood cell transfusions are a therapeutic mainstay in SCD, which can lead to iron overload and endocrine disease. However, due to diagnostic difficulties and lack of data, there is not a wide consensus in approach. This has led to many practitioners screening for endocrinopathies only once patients are symptomatic. In this study, we implemented a standardized protocol for screening of iron overload and certain endocrinopathies in a single-study cohort of patients with SCD to assess viability in real-world practice and to detect disease prior to significant burden. We studied 19 patients diagnosed with SCD or sickle-cell trait (SCT) at a single institution. Patients had serum testing for ferritin and a metabolic panel at usual clinical visits. Iron overload was diagnosed with serum ferritin levels of at least 1000 ng/mL. If iron overload was detected, additional testing for 25-Hydroxyvitamin D (OHD), Thyroid Stimulating Hormone (TSH), Parathyroid Hormone (PTH), and Insulin-Like Growth Factor-1 (IGF-1) was obtained. Nineteen patients (12 men and 7 women) were included with a mean age of 32 years old. Twelve patients and seven patients were diagnosed with SCD and SCT, respectively. The average ferritin levels of SCD and SCT patients were 4874 and 270 ng/mL, respectively. Nine patients had ferritin levels greater than 1000 ng/mL, eight of which were diagnosed with SCD, one was diagnosed with SCT, and seven of which were prescribed iron chelation therapy. Of these nine patients, the average random glucose was 103 ng/mL. The average serum calcium corrected for albumin levels was 9.3 ng/mL. Seven of eight patients were found to have low 25-OHD levels with two of four patients showing elevated serum PTH. One of six patients had abnormal thyroid testing, with an elevated TSH and normal free thyroxine. Three of five patients showed abnormal IGF-1 testing, with low IGF-1 levels and low IGF-1 binding protein levels. This study successfully implemented a protocol for screening for endocrinopathies in a cohort of SCD and SCT patients at a single institution. We showed evidence that many patients with iron overload demonstrated abnormalities in 25-OHD, PTH, TSH, and IGF-1. The few studies that have been done to analyze this topic have shown findings of growth failure, osteopenia, hypogonadism, hypothyroidism, and glucose intolerance in SCD and SCT patients. This study did not explore bone disease or sex hormone function due to difficulty in performing these tests and obtaining insurance payor coverage. An additional limitation includes low sample size. However, this study replicates real-world care for these patients due to these barriers, making these methods easily translatable to other clinical settings. Our findings suggest implementation of a standardized protocol for iron overload and endocrinopathy screening in SCD and SCT patients is not only viable but could also detect disease before symptom onset when intervention is more effective.

Association of Body Mass Index with Insulin-like Growth Factor-1 Levels among 3227 Chinese Children Aged 2–18 Years

Insulin-like growth factor-1 (IGF-1) levels are affected by nutritional status, yet there is limited research exploring the association between body mass index (BMI) and IGF-1 levels among children. This cross-sectional study included 3227 children aged 2-18 years without specific diseases, whose height, weight, and pubertal stages were measured and assessed by pediatricians. BMI standard deviation scores (BMISDS) were used to categorize children as underweight (BMISDS < -2); normal-weight (-2 ≤ BMISDS ≤ 1); overweight (1 < BMISDS ≤ 2); and obese (BMISDS > 2). Children were divided into low-level (<-0.67 SD) and nonlow-level (≥-0.67 SD) groups based on IGF-1 standard deviation scores (IGF-1SDS). The association between IGF-1 and BMI as categorical and continuous variables was explored by Binary logistic regression, the restrictive cubic spline model, and the generalized additive model. Models were adjusted by height and pubertal development. Recursive algorithm and multivariate piecewise linear regression were further utilized to assess the threshold of the smooth curve. IGF-1 levels varied by BMI categories, with the highest levels observed in the overweight group. The proportion of low IGF-1 levels in underweight, normal-weight, overweight, and obese groups was 32.1%, 14.2%, 8.4%, and 6.5%, respectively. The risk odds of low IGF-1 levels in underweight children were 2.86-, 2.20-, and 2.25-fold higher than in children with normal weight before adjustment, after adjustment for height, and after adjustment for height and puberty, respectively. When analyzing the association between BMI and low IGF-1 levels, dose-response analysis demonstrated an inverted J-shaped relationship between BMISDS and low IGF-1 levels. Lower or higher BMISDS increased the odds of low IGF-1 levels, and significance was retained in underweight children but not in obese children. When BMI and IGF-1 levels were used as continuous variables, the relationship between the BMISDS and IGF-1SDS followed a nonlinear inverted U shape. IGF-1SDS increased with the increase of BMISDS (β = 0.174, 95% CI: 0.141 to 0.208, p < 0.01) when BMISDS was less than 1.71 standard deviation (SD) and decreased with the increase of BMISDS (β = -0.358, 95% CI: -0.474 to -0.241, p < 0.01) when BMISDS was greater than 1.71 SD. The relationship between BMI and IGF-1 levels was found to depend on the type of variable, and extremely low or high BMI values could result in a tendency toward low IGF-1 levels, emphasizing the importance of maintaining a normal BMI range for normal IGF-1 levels.

Laron syndrome in South Indian children – A descriptive study

Objectives: The objectives of this study were to describe the clinical and biochemical features of five children with Laron syndrome (LS) from South India. Material and Methods: This is a prospective descriptive case series of five children with clinical and biochemical features of LS managed over 5 years. Results: Five children (two girls and three boys) with LS with the mean age group of 5.9 ± 1.7 years and the mean age at diagnosis of 2.7 ± 0.8 years are described. All children were born out of consanguinity and all had typical phenotypic facies of LS. The mean Z-scores of height, weight, and body mass index on follow-up for the cohort were −7.0 ± 1.6, −5.9 ± 2.8, and −0.1 ± 0.7, respectively, and they were within ± 2 SD of the mean for children in LS chart. The median basal growth hormone level for age was 13 ng/mL and the median growth hormone levels at 30 min, 60 min, 90 min, and 120 min post-stimulation test were 35 ng/mL, 35 ng/mL, 44 ng/mL, and 50 ng/mL, respectively. All of them had insulin-like growth factor-1 (IGF-1) levels less than the 3rd percentile and no increment during the IGF-1 generation test. The prevalence of micropenis was 100% and one child had symptomatic hypoglycemic episodes. Genetic analysis was performed in two boys and both harbored variants in the growth hormone receptor gene. Conclusion: LS should be suspected in children with clinical features of growth hormone deficiency along with elevated growth hormone levels and low IGF-1 levels with no increment of IGF-1 in the IGF-1 generation test.

Inflammation induces stunting by lowering bone mass via GH/IGF-1 inhibition in very preterm infants.

Sustained systemic inflammatory response (SIR) was associated with poor postnatal growth in very preterm infants (VPI). We hypothesize that VPI with sustained SIR will exhibit linear growth retardation related to lower bone mass accrual mediated by GH/IGF-1 axis inhibition at term corrected age (CA). C-reactive protein (CRP), procalcitonin (PCT), growth hormone (GH), insulin-like growth factor 1 (IGF-1), calcium, phosphorus, alkaline phosphatase, anthropometric, nutritional, neonatal and maternal data were collected prospectively in 23 infants <32 weeks gestational age. Body composition using dual-energy X-ray absorptiometry was performed at term CA. Analysis was undertaken with multiple linear regression models. At term CA 11 infants with sustained SIR compared with 12 infants without sustained SIR present significantly lower IGF-1, length z-score (LZS), bone mineral content (BMC) and lean mass (LM), and higher GH and fat mass (FM). LZS was associated significantly with PCT, BMC with IGF-1, FM and LM with CRP, GH with bronchopulmonary dysplasia and CRP, and IGF-1 with invasive mechanical ventilation, CRP and PCT. In addition to the known effect on linear growth failure, sustained SIR induces lower bone mass accrual related to higher GH and lower IGF-1 levels in VPI. Very preterm infants (VPI) with sustained systemic inflammatory response (SIR) compared with VPI without SIR present stunting, lower bone mass, higher GH and lower IGF-1 levels at term corrected age. SIR may help to explain the influence of non-nutritional factors on growth and body composition in VPI. SIR induces postnatal stunting related to lower bone mass accrual via GH/IGF-1 axis inhibition in VPI. VPI with SIR need special attention to minimize inflammatory stress, which could result in improved postnatal growth. Research on inflammatory-endocrine interactions involved in the pathophysiology of postnatal stunting is needed as a basis for new interventional approaches.

Association of umbilical cord insulin-like growth factor 1 levels with severe retinopathy in extremely preterm infants.

The association between umbilical cord blood insulin-like growth factor 1 (IGF-1) levels and retinopathy of prematurity (ROP) remains unclear. This study aimed to investigate whether umbilical cord blood IGF-1 levels can predict the development of severe ROP in extremely preterm infants. This hospital-based retrospective cohort study included infants born at <37 weeks gestational age (GA) between 2019 and 2021 and then classified them into the two GA groups: extremely preterm, <28 weeks and preterm infants, 28-36 weeks. Extremely preterm infants were further subclassified into two groups according to the laser treatment as follows: the severe ROP (ROP-Tx) and ROP (No ROP-Tx) groups. Median umbilical cord blood IGF-1 values were compared between the groups. Perinatal risk factors were identified by univariate and multivariate analyses. Finally, umbilical cord IGF-1 cut-off values requiring ROP treatment with laser were determined by receiver operating characteristic (ROC) curve analyses. A total of 205 infants were enrolled, with 32 being extremely preterm (ROP-Tx: n=11; No ROP-Tx: n=21) and 173 being preterm. IGF-1 levels were significantly lower in extremely preterm (13.5ng/mL) than preterm infants (36ng/mL, p<0.001). In extremely preterm infants, IGF-1 levels were significantly lower in the ROP-Tx group than the No ROP-Tx group (10 vs. 19ng/mL, respectively, p=0.024). Only GA, umbilical cord blood IGF-1 levels, birth head circumference, and birth chest circumference were identified as risk factors by univariate analysis (p<0.05). Multivariate analysis showed that only umbilical cord blood IGF-1 was an independent risk factor (odds ratio: 1.26, p=0.021). ROC curves revealed an IGF-1 cut-off value of 14ng/mL. The need of laser treatment for ROP was found to be associated with low umbilical cord blood IGF-1 levels in extremely preterm infants. Umbilical cord blood IGF-1 can be used as a biomarker for the risk of developing severe ROP.

The Role of Insulin-Like Growth Factor 1 in Delirium: A Systematic Review and Meta-Analysis

Background: The relationship between delirium and low levels of insulin-like growth factor 1 (IGF-1) is contradictory and uncertain. We hypothesised that low levels of IGF-1 are a predisposing factor for delirium in medical and abdominal surgical cohorts, in contrast to other surgical cohorts. Aims: Systematic review and meta-analysis investigating the association between peripheral levels of IGF-1 and delirium in medical and surgical patients to explore if there are distinct patterns of associations by using subgroup meta-analysis. Methods: PubMed, Scopus, CINAHL, Cochrane, and Embase databases were searched. Inclusion criteria were prospective studies in medical and surgical populations and available data. The following were collected: the setting (surgical/medical), the type (orthopaedic surgery, abdominal, cardiovascular, or medical), the number of participants, mean age, the number of delirious patients, scale/criteria for delirium, IGF-1 levels, and MMSE. Results: Thirteen studies were included and analysed. Low levels of IGF-1 are significantly associated with delirium in abdominal surgical samples and medical samples but not in the other surgical samples. Age, cognition, and the setting (medical vs. surgical) do not have any significant effect on the differences in IGF-1 levels between those with and without delirium. Discussion: Delirium in acute medical and abdominal surgery is triggered by low IGF-1 which may reflect chronic conditions like frailty/cachexia/sarcopenia, while in other surgeries perhaps from an inflammatory process. Conclusions: Low peripheral levels of IGF-1 are a predisposing factor for delirium only in acute medical and abdominal surgery. More studies are needed to confirm and to explore further this finding.

Влияние полиморфизма rs9939609 гена FTO на прибавку массы тела при беременности, уровни лептина и ИПФР-1 в грудном молоке и рост младенцев на грудном вскармливании

The search for possible ways of early prevention of obesity is an urgent task. Previous studies have provided evidence of the association of breast milk (BM) hormones with growth in young children. However, information on the influence of the mother’s genetic predisposition to obesity and her weight gain during pregnancy on their level is limited. Objective. To assess the effect of the rs9939609 polymorphism in the maternal FTO gene on body weight gain during pregnancy, the levels of leptin and insulin-like growth factor-1 (IGF-1) in BM, as well as the dynamics of the physical development of exclusively breastfed children. Patients and methods. The study involved 103 healthy women aged (M ± m) 32.2 ± 0.5 years, with a BMI of 19.8 ± 2.8 kg/m2 and their children living in Smolensk. Mothers gave informed consent to participate in the study. BM was taken on days 10–14, at 1 and 3 months of lactation. Levels of leptin and IGF-1 were determined in the morning midstream portion of BM serum by ELISA. Anthropometric data of children were assessed at birth, at 1 and 3 months of life using the WHO Anthro software (2009) by calculating the Z-scores of “weight-for-age” (WAZ) and “length-for-age” (LAZ). The women were genotyped for rs9939609 by real-time PCR. Results. Mothers with the TT genotype (frequency of occurrence – 62%) had higher body weight gain during pregnancy than carriers of the AT (22%) and AA (16%) genotypes, as well as significantly higher leptin and lower IGF-1 levels in BM during the entire observation period. Their infants had significantly lower WAZ at birth and at 1 month and LAZ at 3 months of life than children born to mothers with the AA and AT genotypes. Conclusion. Lower parameters of the physical development of infants born to mothers with the TT genotype of the rs9939609 polymorphism in the FTO gene can be explained by their low genetic predisposition to obesity. However, we cannot exclude the existence of an additional mechanism of growth restriction due to the influence of BM hormones on it, i.e., a reduced level of IGF-1 and the anorexigenic effect of an increased level of leptin, probably associated with a higher BMI and weight gain in mothers with the TT genotype over the period of pregnancy. Key words: anthropometry, breast milk, insulin-like growth factor-1, leptin, rs9939609 polymorphism, pregnancy weight gain

Insulin-Like Growth Factor -1 (IGF-1) and Glucose Dysregulation in Young Adult Patients with β-Thalassemia Major: Causality or Potential Link?

Insulin-like growth factor-1 (IGF-1) has been shown to lower blood glucose through stimulating glucose transport to fat and muscle and inhibiting hepatic glucose output. Although previous cross-sectional reports reported an association between low circulating concentrations of IGF-1 and glucose dysregulation (GD), its role is still debated. The present retrospective study was designed to assess the circulating IGF-1 levels in β-thalassemia major (β -TM) patients with normal oral glucose tolerance test (NGT-OGTT) and (GD) referred for an endocrine evaluation to explore the potential link between low IGF-1 and GD. Our study included 34 young adult patients with β-TM; 12 patients with NGT after OGTT, 7 with impaired glucose tolerance (IGT), 9 with impaired fasting glucose (IFG) plus IGT, and 6 patients with β-TM-related diabetes mellitus (β-TM- DM). Twenty-two β-TM patients with GD or β-TM- DM and 1 patient with NGT had IGF-1 levels below the 2.5th percentile. Correlation of IGF-1 with fasting plasma glucose, HOMA-IR (homeostatic model assessment for insulin resistance) and OGIS (oral glucose insulin sensitivity) was found. Moreover, a negative correlation was documented between ALT and the Insulinogenic Index (IGI) and a positive correlation between serum ferritin and PG 2-h after OGTT. This study reports for the first time an association between low levels of IGF-1 and GD in β-TM patients. Despite some limitations, our study can serve to generate proposals for more convenient and efficient methods to identify and treat early GD in patients with β-TM, and to conduct more extensive studies. www.actabiomedica.it).

Association Between Insulin-Like Growth Factor-1 and Social Cognition in Huntington's Disease.

Insulin-like growth factor 1 (IGF-1) seems to be involved in the neural circuits associated with social cognition and brain structure. To investigate the association of IGF-1 levels with social cognition and brain structure in Huntington's disease (HD). We evaluated social cognition using the Ekman test in 22 HD patients and 19 matched controls. Brain structure was assessed using standard volume-based voxel-based morphometry and surface-based cortical thickness pipeline. We analyzed the association of IGF-1 levels with social cognition and brain structure using adjusted regression analysis. Social cognition was worse in HD patients (P < 0.001), on antidopaminergic drugs (P=0.02), and with lower IGF-1 levels (P=0.04). In neuroimaging analyses, lower IGF-1 levels were associated with social cognition impairment and atrophy mainly in frontotemporal regions (P < 0.05 corrected). In HD, abnormal IGF-1 function seems to be associated with brain atrophy leading to clinical deficits in social cognition.

Insulin-like growth factor-1 levels are associated with high comorbidity of metabolic disorders in obese subjects; a Japanese single-center, retrospective-study

Insulin like growth factor-1 (IGF-1) plays important roles in metabolic functions, especially in adulthood. Additionally, obese subjects are reportedly predisposed to having low absolute IGF-1 levels. However, the prevalence and clinical characteristics of obese subjects with low IGF-1 levels are unknown. We examined 64 obese subjects with a body mass index (BMI) ≥ 35 kg/m2, with no history of endocrinological disorders, receiving inpatient care. IGF-1 levels were interpreted based on the IGF-1 standard deviation score (SDS) clinically used and standardized by age and sex (low IGF-1 group; ≤ − 2.0 SDS and standard IGF-1 group; − 2.0 < and < + 2.0 SDS). Notably, 26.6% of the subjects had low IGF-1. Body fat mass and percentage, but not BMI, were significantly higher in the low than in the standard IGF-1 group. Furthermore, natural log-transformed high-sensitivity C-reactive protein, and the frequencies of dyslipidemia and hyperuricemia were higher in the low IGF-1 group. Moreover, among the subjects without diabetes, fasting glucose levels were significantly higher in the low IGF-1 group. Stepwise variable selection procedure revealed body fat percentage to be a parameter most strongly associated with low IGF-1. Thus, low IGF-1 levels may be an important marker of adiposity-associated metabolic disorders in obese patients.

Insulin-like growth factor 1 and the hormonal mediation of sibling rivalry

In altricial animals, young are completely dependent on parents for provisioning. The ability to outcompete siblings to receive parental provisioning has clear fitness benefits, and may be mediated by hormones that influence growth. We analyzed the effects of insulin-like growth factor 1 (IGF-1) on body size, growth, and sibling rivalry in eastern bluebirds (Sialia sialis). To determine whether IGF-1 is upregulated in response to the competitive environment, we manipulated brood sizes and examined the effect on IGF-1 levels, nestling body size, growth rate, and behavior. In a separate experiment, we injected nestlings with exogenous IGF-1 to study its impacts on body size, growth rate, and sibling competition. Brood size manipulation did not influence endogenous IGF-1 levels, but male nestlings with higher IGF-1 levels early in the nestling period tended to have greater mass gain than males with lower IGF-1 levels. Nestlings with higher IGF-1 levels also tended to be fed more frequently by parents. In the injection experiment, IGF-1 injected individuals tended to be heavier than vehicle injected young by the end of the nestling period, which suggests that IGF-1 can influence mass gain in bluebirds. IGF-1 has been proposed to be a mediator of life-history strategies and post-hatching behavior. Our results suggest that although bluebird nestlings do not adaptively elevate IGF-1 in response to the presence or number of siblings, IGF-1 may influence growth during the nestling period. These findings shed light on sibling competition, life history strategies, and the hormones that underlie them.