Low Insulin-like Growth Factor-1 Research Articles

The relation between insulin-like growth factor 1 levels and risk of depression in ischemic stroke.

The aim of this study is to evaluate whether lower serum levels of insulin-like growth factor 1 (IGF-1) in the acute phase of ischemic stroke are associated with higher risk of post-stroke depression (PSD) over a 1-year period. The subjects were first-ever acute ischemic stroke (AIS) patients who were hospitalized from July 1, 2014 to August 31, 2015. The study also included 120 age-matched and sex-matched healthy controls from the same geographical area. Fasting blood samples were collected within 24hours of admission for IGF-I measurement. Neurological and neuropsychological evaluations were conducted at a 1-year follow-up. Two-hundred twenty-five patients were observed for a 1-year follow-up, and 74 of these patients (32.9%, 95%CI: 26.8%-39.0%) were diagnosed with PSD. The depression distribution across the IGF-1 quartiles ranged between 61.4% (first quartile) and 8.9% (fourth quartile). In a multivariate model using the first quartiles of the IGF-1 versus quartiles 2 through 4, together with the significant clinical variables, the marker displayed prognostic information, and the odds ratio (OR) for first quartile was 3.35 [95% CI, 1.88-6.79; P=0.001]. The data showed that low serum IGF-1 levels at admission are associated with a high risk of developing PSD, suggesting that these alterations might be involved in the pathophysiology of depression symptoms in stroke patients.

Genome-wide profiling of congenital insulin-like growth factor-1 deficient patients: translational implications in cancer prevention and metabolism

Laron syndrome (LS) is a rare genetic disorder identified in the 1950s by Professor Zvi Laron. LS results from mutation of the growth hormone receptor (GH-R) gene, leading to congenital insulin-like growth factor-1 (IGF1) deficiency and dwarfism. Recent epidemiological studies have shown that LS patients do not develop cancer, emphasizing the crucial role of the IGF1 axis in cancer biology. Genome-wide profiling of LS patients conducted in our laboratory led to the identification of genes and signaling pathways that are over- or under-represented in LS compared to healthy controls of the same age range and ethnic group. Differentially expressed genes may be responsible for the association between lifetime low IGF1 values and protection from cancer. This experiment of nature may provide invaluable information that might translate into novel therapeutic approaches in modern oncology.

Serum insulin-like growth factor-1 and its binding protein 3 as prognostic factors for the incidence, progression, and outcome of hepatocellular carcinoma: a systematic review and meta-analysis.

PurposePrevious studies have supported an association between serum insulin-like growth factor-1 (IGF1) and IGF-binding protein 3 (IGFBP3) levels and hepatocellular carcinoma (HCC), but the results were inaccurate. It has recently been proposed that IGF1 and IGFBP3 play roles in the time-to-progression (TTP) and overall survival (OS) of HCC patients. Our results revealed that serum IGF1 level is predictive of the progression and survival of HCC patients.ResultsHCC was associated with a significant reduction in serum IGF-1 and IGFBP-3 levels compared to cirrhosis (p = 0.037). Low serum IGF1 levels were predictive of a shorter TTP (OR, 2.74; 95% confidence interval [CI], 1.92–3.90) and poorer OS (odds ratio [OR], 2.20; 95% CI, 1.81–2.68) in HCC patients. The IGF1/IGFBP3 molar ratio was not significantly associated with the risk of HCC (OR, 1.311; 95% CI, 0.761–2.260).Materials and MethodsWe conducted a comprehensive literature search in PubMed, EMBASE, and the Cochrane Library. Twenty studies met the inclusion criteria and were subjected to statistical analysis. The geometric mean and standard deviation (SD) of serum IGF1 and IGFBP3 levels in the healthy, cirrhosis, and HCC groups were calculated. Pooled odds ratios (ORs) were calculated using a fixed-effects model to analyse the association of serum IGF1 level with the progression and survival of HCC patients.ConclusionsSerum IGF1 and IGFBP3 levels were positively associated with the incidence of HCC. Serum IGF1 level is an independent prognostic factor for the progression and survival of HCC patients.

Circulating Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-3 predict Three-months Outcome after Ischemic Stroke.

Reports on neuroprotective effects of Insulin-like growth factor-1 (IGF-1) and Insulin-like growth factor binding protein-3 (IGFBP-3) in ischemic brain tissue are inconsistent. The aim of this study was to determine if plasma levels of IGF-1 and IGFBP-3 in acute stroke patients are indicative of 3 months functional outcome. Plasma levels were measured via chemiluminescence immunoassay in heparin blood samples of patients included in the EARLY trial (NCT00562588). Plasma samples were drawn on admission and 8 days post-stroke. Neurological deficits were assessed via modified Rankin Scale (mRS) 3 months post-stroke, resulting in favorable (mRS=0-2) or unfavorable (mRS=3-6) outcome. A multiple binary logistic regression including IGF-1 and IGFBP-3 levels and confounders was conducted. Out of 404 included patients, 89 patients had an unfavorable outcome. Mean mRS on admission as well as 3 months post-stroke was 2 (±1). Low IGF-1 levels (day 8) were independently associated with a decreased risk of an unfavorable outcome (OR 0.61; 95%CI 0.37-0.99; p=0.044). Low IGFBP-3 levels (day 8) were independently associated with an unfavorable outcome (OR 2.75; 95%CI 1.56-4.84; p<0.001). Low IGFBP-3 levels and high IGF-1 levels in the subacute phase are predictive of unfavorable outcome 3 months after stroke.

Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke: The Framingham Study.

Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P=0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke (P<0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P=0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P=0.031) lower risk of incident ischemic stroke, respectively. IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance.

The role of serial measurements of serum insulin-like growth factor 1 levels in the development of retinopathy of prematurity.

To determine the role of serum insulin-like growth factor-1 levels in the development of retinopathy of prematurity, which is a major cause of childhood blindness worldwide. We prospectively studied newborn infants born at a postmenstrual age of <32 weeks and birth weights <1 500 gr, between January 1st, 2015, and December 31st, 2015. A total of 40 infants were enrolled in the study. The retinal examination time was determined in accordance with the American Academy of Pediatrics recommendations for retinopathy of prematurity screening and follow-up. Retinopathy of prematurity was classified according to the international classification of retinopathy of prematurity. Serum Insulin like growth factor 1 levels were measured serially in blood samples on the 1st, 3rd, 7th, 21st, and 28th day. Among the 40 infants, 11 (27.5%) constituted the retinopathy of prematurity group and 29 comprised the non-retinopathy of prematurity group. In the retinopathy of prematurity group, the mean gestational age and birth weight was significantly lower. The demographic features of the study cohort were similar. The duration of mechanical ventilation was significantly greater in the retinopathy of prematurity group compared with the non-retinopathy of prematurity group (p=0.036). In terms of neonatal morbidities such as respiratory distress syndrome, intraventricular hemorrhage, bronchopulmonary dysplasia, patent ductus arteriosus, and necrotizing enterocolitis, no differences were detected between the groups. The mean serum insulin-like growth factor-1 levels in retinopathy of prematurity group were significantly lower than those in the non-retinopathy of prematurity group at each time point (1st, 3rd, 7th, 21st, and 28th day of postnatal life) (p=0.001). This study demonstrated the low serum insulin-like growth factor-1 levels was associated with retinopathy of prematurity development.

Mice with infectious colitis exhibit linear growth failure and subsequent catch-up growth related to systemic inflammation and IGF-1

In developing communities, intestinal infection is associated with poor weight gain and linear-growth failure. Prior translational animal models have focused on weight gain investigations into key contributors to linear growth failure have been lacking. We hypothesized that murine intestinal infection with Citrobacter rodentium would induce linear-growth failure associated with systemic inflammation and suppressed serum levels of insulin-like growth factor-1 (IGF-1). We evaluated 4 groups of mice infected or sham-infected on day-of-life 28: uninfected-controls, wild-type C rodentium–infected, partially-attenuated C rodentium–infected (with deletion of 3 serine protease genes involved in colonization), and pair-fed (given the amount of daily food consumed by the wild-type C rodentium group). Relative to the uninfected group, mice infected with wild-type C rodentium exhibited temporal associations of lower food intake, weight loss, linear-growth failure, higher IL-6 and TNF-α and lower IGF-1. However, relative to the pair-fed group, the C rodentium–infected group only differed significantly by linear growth and systemic inflammatory cytokines. Between post-infection days 15–20, the infected group exhibited resolution of systemic inflammation. Between days 16–20, both wild-type C rodentium and pair-fed groups exhibited rapid linear-growth velocities exceeding the uninfected and mutant C rodentium groups; during this time levels of IGF-1 increased to match the uninfected group. We submit this as a model providing important opportunities to study mechanisms of catch-up growth related to intestinal inflammation. We conclude that in addition to known effects of weight loss, infection with C rodentium induces linear-growth failure potentially related to systemic inflammation and low levels of IGF-1, with catch-up of linear growth following resolution of inflammation.

Insulin-like growth factor 1 and metabolic parameters are associated with nonalcoholic fatty liver disease in obese children and adolescents.

Few studies have investigated the relationship between paediatric nonalcoholic fatty liver disease (NAFLD) and insulin-like growth factor 1 (IGF-1). This study, carried out from July 2013 to September 2015, aimed to fill the gap and added metabolic parameters to the analysis. This was a cross-sectional study of 168 obese children and adolescents (84% male), divided into two groups based on the presence (n=90) or absence (n=78) of NAFLD. All participants underwent clinical examinations, anthropometric and laboratory examinations and liver ultrasonography. Nonalcoholic fatty liver disease patients had significantly lower IGF-1 standard deviation score (IGF-1 SDS) and higher body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and uric acid levels than the control group. The prevalence rate of NAFLD was negatively correlated with the IGF-1 SDS. IGF-1 SDS was negatively associated with NAFLD, while BMI, HOMA-IR and uric acid were positively associated with NAFLD. The combined analysis of the area under the receiver operating characteristic curve for multiple variables, including IGF-1 SDS, BMI, HOMA-IR and uric acid, was 0.812, with a sensitivity of 78.89% and specificity of 74.36%. IGF-1, BMI, HOMA-IR and uric acid were useful markers of NAFLD in obese children and adolescents.

Forty Years Of Unrecognized Hypopituitarism Diagnosed By Physical Exam

AbstractObjective: To describe the diagnosis of a case of hypopituitarism that went undiagnosed for 40 years, having been masked by inhaled glucocorticoids.Methods: We present the clinical, laboratory, exam, and imaging findings, along with a review of the literature.Results: A 58-year-old man with a history of intermittent hyponatremia of unknown etiology and chronic abdominal cramps presented with worsening cramps, confusion, and serum sodium of 112 mmol/L (reference range, 135 to 145 mmol/L). His urine sodium and osmolality suggested the syndrome of inappropriate antidiuretic hormone (SIADH), but serum sodium did not normalize with hypertonic saline and fluid restriction. Exam revealed no axillary or pubic hair and no palpable testes. He reported 3 episodes of traumatic head injury around the age of 18 and an inability to have an erection since that time. Further testing found undetectable luteinizing hormone, undetectable testosterone, low free thyroxine, low insulin-like growth factor 1, and a failed cosyntropin stimulation test. Magnetic resonance imaging showed an empty sella. His sodium and cramping improved rapidly with hydrocortisone. He had not used his glucocorticoid inhaler for 3 days prior to admission. He had a similar admission after stopping his inhaler 4 years ago, leading us to the conclusion that the chronic inhaled glucocorticoid may have masked his hypopituitarism.Conclusion: This case highlights the common and life-threatening delay in diagnosis of adrenal insufficiency, the need to consider SIADH a diagnosis of exclusion, and the importance of a thorough physical exam and history, even in this era of digital medicine.Abbreviations:Siadhsyndrome of inappropriate antidiuretic hormoneT4thyroxine

Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

Introduction:Traumatic brain injury (TBI) is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population.Aims:The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality.Subjects and Methods:Forty-nine TBI patients (41 men and 8 women) were included in this study. Pituitary functions were evaluated within 24 h of admission.Results:Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3) and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality.Conclusions:Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening

Effect of growth hormone treatment on children with idiopathic short stature and idiopathic growth hormone deficiency.

PurposeThere are inconsistencies in the results reported in a small number of previous studies into growth hormone (GH) treatment in Korean children with idiopathic short stature (ISS) and idiopathic growth hormone deficiency (IGHD). Thus, the authors retrospectively compared the effects of GH in ISS and IGHD.MethodsFrom the medical records of 26 ISS and 30 IGHD children, auxological and biochemical changes including chronologic age (CA), bone age (BA), height standard deviation score (HT-SDS), predicted adult height (PAH), midparental height (MPH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) were compared.ResultsBefore treatment, IGHD group had younger BA, lower BA/CA ratio, and lower IGF-1 level than those in the ISS group. During GH treatment, the levels of IGF-1 and IGFBP-3 were not different. Although annual BA increment was higher in IGHD group, and annual PAH-SDS increment was higher in ISS group, annual HT-SDS increments were not different. Both HT-SDS and PAH-SDS in the ISS group increased significantly until the end of the second year, and then those were not significantly different from MPH-SDS. In the IGHD group, the HT-SDS showed a significant increase till the end of the second year, and the PAH-SDS was not significantly changed at each year, but both HT-SDS and PAH-SDS were not significantly different from MPH-SDS at the end of the third year.ConclusionDuring GH treatment, both HT-SDS and PAH-SDS approached the genetic target range of MPH-SDS after 2 years in ISS children and 3 years in IGHD children.

Changes in Insulin-like Growth Factor-1 Level in Patients with Sepsis and Septic Shock

Background: Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1) has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods: We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock) admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA). Results: Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively). Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029). Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038). IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions: Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.

Effects of prenatal micronutrient and early food supplementation on metabolic status of the offspring at 4.5 years of age. The MINIMat randomized trial in rural Bangladesh.

Background: Fetal nutritional insults may alter the later metabolic phenotype. We hypothesized that early timing of prenatal food supplementation and multiple micronutrient supplementation (MMS) would favourably influence childhood metabolic phenotype.Methods: Pregnant women recruited 1 January to 31 December 2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of either 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, and randomized to food supplementation (608 kcal) either with early invitation (9 weeks’ gestation) or usual invitation (at 20 weeks). Their children (n = 1667) were followed up at 4.5 years with assessment of biomarkers of lipid and glucose metabolism, inflammation and oxidative stress.Results: Children in the group with early timing of food supplementation had lower cholesterol (difference -0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95% CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; -0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale -0.141 µg/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 μg folic acid. There were no effects on markers of inflammation or oxidative stress.Conclusions: Findings suggest that in a population where malnutrition is prevalent, nutrition interventions during pregnancy may modify the metabolic phenotype in the young child that could have consequences for later chronic disease risks.

The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits

To investigate the effects of different doses of insulin-like growth factor 1 (IGF-1) on the cartilage layer and subchondral bone (SB) during repair of full-thickness articular cartilage (AC) defects. IGF-1-loaded collagen membrane was implanted into full-thickness AC defects in rabbits. The effects of two different doses of IGF-1 on cartilage layer and SB adjacent to the defect, the cartilage structure, formation and integration, and the new SB formation were evaluated at the 1st, 4th and 8th week postoperation. Meanwhile, after 1 week treatment, the relative mRNA expressions in tissues adjacent to the defect, including cartilage and SB were determined by quantitative real-time RT-PCR (qRT-PCR), respectively. Different doses of IGF-1 induced different gene expression profiles in tissues adjacent to the defect and resulted in different repair outcomes. Particularly, at high dose IGF-1 aided cell survival, regulated the gene expressions in cartilage layer adjacent defect and altered ECM composition more effectively, improved the formation and integrity of neo-cartilage. While, at low dose IGF-1 regulated the gene expressions in SB more efficaciously and subsequently promoted the SB remodeling and reconstruction. Different doses of IGF-1 induced different responses of cartilage or SB during the repair of full-thickness AC defects. Particularly, high dose of IGF-1 was more beneficial to the neo-cartilage formation and integration, while low dose of it was more effective for the SB formation.

IGF-1 and NT-proBNP in a black and white population: The SABPA study.

Black populations exhibit lower concentrations of the cardioprotective peptide, insulin-like growth factor-1 (IGF-1), and are more prone to develop hypertensive heart disease than whites. We therefore determined whether lower IGF-1 in black individuals relates to a marker of cardiac overload and systolic dysfunction, namely N-terminal prohormone B-type natriuretic peptide (NT-proBNP). We included 160 black and 195 white nondiabetic South African men and women (aged 44·4 ± 9·81 years) and measured ambulatory blood pressure, NT-proBNP, IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3). Although the black group presented elevated ambulatory blood pressure accompanied by lower IGF-1 compared to the white group (all P < 0·001), we found similar NT-proBNP concentrations (P = 0·72). Furthermore, in blacks we found a link between NT-proBNP and systolic blood pressure (SBP) (R(2) = 0·37; β = 0·28; P < 0·001), but not with IGF-1. In the white group, NT-proBNP was inversely associated with IGF-1 (R(2) = 0·39; β = -0·22; P < 0·001) after adjusting for covariates and potential confounders. As IGF-1 is attenuated in diabetes, we added the initially excluded patients with diabetes (n = 38), and the aforementioned associations remained robust. Contrary to the white group, we found no association between NT-proBNP and IGF-1 in black adults. Our findings suggest that SBP and other factors may play a greater contributory role in cardiac pathology in blacks.

Pituitary dysfunction after aneurysmal subarachnoid hemorrhage in Japanese patients

To elucidate the pituitary function of Japanese patients after aneurysmal subarachnoid hemorrhage (aSAH) and implicative factors related to growth hormone deficiency (GHD) after aSAH. We evaluated basal pituitary hormone levels among 59 consecutive aSAH patients with a modified Rankin Scale (mRS) ⩽4 at 3months after aSAH onset. Patients with low insulin-like growth factor 1 (IGF-1) SD score (SDS) or who seemed to develop pituitary dysfunction underwent provocative endocrine testing during a period of 3–36months after SAH onset. The relationship between IGF-1 SDS and clinical factors of the patients such as severity of SAH, aneurysm location, and treatment modalities, were assessed. Six patients (10.2%) demonstrated their IGF-1 SDS less than −2. Multiple logistic regression analyses revealed that patients who underwent surgical clipping had a significantly lower IGF-1 SDS (<−1SD) than patients who underwent endovascular embolization with an odds ratio of 5.83 (p=0.032). Thirty-three patients took provocative tests and five (15.6%) patients were identified as having GHD. The mean IGF-1 SDS of these five GHD patients was 0.08 SD. The aneurysms in all GHD patients were located in internal carotid artery (ICA) or anterior cerebral artery (ACA). To the best of our knowledge, this is the first report describing the prevalence of GHD in Japanese patients after aSAH, and it was not as high as that of previous European studies. We recommend that screening pituitary dysfunction for aSAH survivors with their aneurysms located in ICA or ACA.

Systemic inflammation, growth factors, and linear growth in the setting of infection and malnutrition

ObjectivesDeficits in weight gain and linear growth are seen frequently among children in areas where malnutrition and recurrent infections are common. Although both inflammation and malnutrition can result in growth hormone (GH) resistance, the interrelationships of infection, inflammation, and growth deficits in developing areas remain unclear. The aim of this study was to evaluate relationships between low levels of systemic inflammation, growth factors, and anthropometry in a case–control cohort of underweight and normal weight children in northern Brazil. MethodsWe evaluated data from 147 children ages 6 to 24 mo evaluated in the MAL-ED (Interactions of Malnutrition and Enteric Disease) case–control study following recruitment from a nutrition clinic for impoverished families in Fortaleza, Brazil. We used nonparametric tests and linear regression to evaluate relationships between current symptoms of infections (assessed by questionnaire), systemic inflammation (assessed by high-sensitivity C-reactive protein [hsCRP]), the GH insulin-like growth factor-1 (IGF-1) axis, and measures of anthropometry. All models were adjusted for age and sex. ResultsChildren with recent symptoms of diarrhea, cough, and fever (compared with those without symptoms) had higher hsCRP levels; those with recent diarrhea and fever also had lower IGF-1 and higher GH levels. Stool myeloperoxidase was positively associated with serum hsCRP. hsCRP was in turn positively associated with GH and negatively associated with IGF-1 and IGF-binding protein-3 (IGFBP-3), suggesting a state of GH resistance. After adjustment for hsCRP, IGF-1 and IGFBP-3 were positively and GH was negatively associated with Z scores for height and weight. ConclusionsInfection and inflammation were linked to evidence of GH resistance, whereas levels of GH, IGF-1, and IGFBP-3 were associated with growth indices independent of hsCRP. These data implicate complex interrelationships between infection, nutritional status, GH axis, and linear growth in children from a developing area.

Thermoprotective effect of insulin-like growth factor 1 on in vitro matured bovine oocyte exposed to heat shock

The role of insulin-like growth factor 1 (IGF1) on cellular function and developmental capacity of heat-shocked oocytes has not been completely understood. Therefore, the objective of this study was to determine the effect of IGF1 on apoptosis, mitochondrial activity, cytoskeletal changes, nuclear maturation, and developmental competence of bovine oocytes exposed to heat shock. Cumulus–oocyte complexes were submitted to control (38.5 °C for 22 hours) and heat shock (41 °C for 14 hours followed by 38.5 °C for 8 hours) in the presence of 0 or 100 ng/mL IGF1 during IVM. Heat shock increased the percentage of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)–positive oocyte and reduced oocyte mitochondrial activity. However, addition of 100 ng/mL IGF1 minimized these deleterious effects of temperature. Caspase activity was affected neither by heat shock nor IGF1. Exposure of bovine oocytes to 41 °C during the first 14-hour IVM affected cortical actin localization and microtubule organization at the meiotic spindle and reduced the percentage oocytes that reached the metaphase II stage. However, in the presence of IGF1, cortical actin and percentage of metaphase II oocytes were not different between control and heat-shocked oocytes, suggesting a partial beneficial effect of IGF1. There was no effect of IGF1 on microtubule organization. Heat shock also reduced the percentage of oocytes that reached the blastocyst stage, blastocyst cell number, and increased the percentage of TUNEL-positive blastomeres. However, there was no effect of 100 ng/mL IGF1 on oocyte development to the blastocyst stage and blastocyst quality. Therefore, 100 ng/mL IGF1 prevented some heat shock–induced cellular damage in bovine oocytes but had no effect on oocyte developmental competence. In contrast, a low IGF1 concentration (25 ng/mL) had a thermoprotective effect on oocyte developmental competence to the blastocyst stage. In conclusion, IGF1 prevented part of the damage induced by heat shock on oocyte function. This effect was modulated by IGF1 concentration.

EXAMINING THE ASSOCIATION BETWEEN CIRCULATING INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) AND BRAIN ACTIVITY IN OLDER ADULTS

With population aging, prevention of cognitive decline has become of paramount interest to the general public. Biomarkers, such as insulin-like growth factor 1 (IGF-1), decline with age and thus may be useful for predicting cognitive health in late life. Animal models have shown that IGF-1 plays a significant role in enhancing working memory and neurogenesis in the rodent brain. 1-2 An association between low IGF-1 levels and poor executive function has been found in human studies using neuropsychological measures.3 To date, there is a paucity of research evaluating the association between IGF-1 and brain activation while engaged in executive function processing. This study aims to determine whether circulating IGF-1 is associated with brain activation while preforming the Oddball task, a measure of executive function. A total of 90 community-dwelling older adults, aged 60 and above, were recruited as part of a larger study. Participants who met inclusion/exclusion criteria were asked to do the following: 1) provide a blood sample for measurement of IGF-1, 2) undergo neurocognitive testing, and 3) undergo an electroencephalography (EEG) protocol, which entails measurement of brain activation while at rest and while performing the Oddball task. Data was analyzed using Matlab R2012 and EEGLAB Toolbox version 7.14. Trials contaminated by eye blink and horizontal eye movements were rejected from EEG analyses. The P300 peak is of particular interest as it is indicative of novelty detection, a component of executive function. A simple regression analysis was conducted to examine the relationship between older adult’s IGF-1 level and their mean P300 amplitude. Preliminary analyses (based on n=45) reveal that increased circulating IGF-1 levels is assoicated with higher mean P300 amplitude of the posterior region, specifically in the P1 (R2 = 0.09, F (1, 36) = 3.68, p = .06) and Pz (R2 = 0.08, F (1,36) = 3.15, p = .08) channels. Results from this study may provide a basis for using IGF-1 as a biomarker for cognitive function in older adults, which may aid in the development of early detection and treatment protocols for cognitive impairment in late life. Future research and implications are further discussed.

Low insulin-like growth factor 1 is associated with low high-density lipoprotein cholesterol and metabolic syndrome in Chinese nondiabetic obese children and adolescents: a cross-sectional study.

BackgroundLow serum high-density lipoprotein cholesterol (HDL-C) is an independent risk factor for developing cardiovascular disease. Insulin-like growth factor 1(IGF-1) levels have been proven to be positively associated with HDL-C, but few studies were based on the dataset of children or adolescents. The aim of this study is to investigate the relationship among IGF-1, HDL-C and the metabolic syndrome in Chinese nondiabetic obese children and adolescents.MethodsAs a cross-sectional study, this study includes 120 obese Chinese children and adolescents and 120 healthy ones. The obese subjects were divided into two groups based on using 1.03 mmol/L as a threshold value for HDL-C. Clinical examination and laboratory examinations were assessed for all participants.ResultsObese subjects had significantly lower IGF-1SDS and higher Height SDS than those in the control group. Among 120 obese children and adolescents, 22 (18.3 %) subjects had an HDL-C level <1.03 mmol/L. IGF-1SDS was significantly lower (P = 0.001) in obese subjects with low HDL-C. According to the results of multivariate logistic regression analysis, IGF-1 SDS is significantly associated with low HDL-C(OR 0.518, 95 % CI 0.292–0.916; P = 0.024), after being adjusted for age, gender, pubertal status, BMI SDS, SBP, DBP, HOMR-IR, total cholesterol, low density lipoprotein-cholesterol, triglycerides, ALT and uric acid. In addition, IGF-1 SDS is significantly correlated with the level of serum HDL-C in study population (r = 0.19, P = 0.003). Based on logistic regression analysis with adjustment for age, gender and pubertal status, the increased IGF-1 SDS was associated with a decreased probability of metabolic syndrome (OR 0.555, 95 % CI 0.385–0.801; P = 0.002) and hypertriglyceridemia (OR 0.582, 95 % CI 0.395–0.856; P = 0.006), but no significant correlation with hypertension.ConclusionObese children had lower IGF-1SDS and taller stature compared with the control group. Low levels of IGF-1 SDS were associated with low levels of HDL-C in chinese nondiabetic obese children and adolescents, independent of insulin resistance, as well as other traditional cardiovascular disease risk markers.