Low Insulin-like Growth Factor-1 Levels Research Articles

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.

Insulin-like growth factor 1 and hearing impairment in older adults: results from the English Longitudinal Study of Ageing

BackgroundAge-related hearing impairment is the most common hearing disorder, affecting two-thirds of people aged over 70 years in the UK. It is a major cause of disability, with considerable social and health implications, accompanied by a major economic burden. With the condition essentially incurable, the focus becomes identification of risk factors. The biological determinants of hearing impairment remain poorly understood. Despite a suggestion from animal studies that insulin-like growth factor 1 (IGF-1) is implicated in the development of hearing impairment, we know of no studies in human beings. Methods4398 participants with no missing data (mean age at baseline 64·2 years [SD 8·1], 55% women) from the English Longitudinal Study of Ageing provided serum concentrations of IGF-1 in 2008 and 2012. We used the average of these two measurement when available, one if not. Hearing acuity was measured with a HearCheck Screener (Siemens, Erlangen, Germany) in 2014. Hearing impairment was defined as hearing fewer than all six tones, three with decreasing intensity at two frequencies (1 kHz and 3 kHz). Logistic regression models were used to estimate odds ratios (OR) of hearing impairment across five quintiles of IGF-1 concentration. Presence of interaction and non-linearity were assessed by likelihood ratio tests. FindingsMean IGF-1 was 16·1 nmol/L (SD 5·2). In the full analytical sample, IGF-1 was not associated with subsequent hearing impairment (OR per 5 nmol increase in IGF-1 1·01, 95% CI 0·94–1·09). However, this association differed by age (pinteraction=0·03). Thus, in participants younger than 60 years (n=1402), IGF-1 was linearly associated with a lower risk of hearing impairment (0·85, 0·73–0·99) after adjustment for age, sex, smoking, height, body-mass index, cognitive function, education, and self-reported hearing at baseline. Among participants 60 years and older, there was some evidence of a J-shaped association (pcurvature=0·02). Compared with the lowest quintile of IGF-1, ORs for quintiles 2, 3, 4, and 5 were 0·94 (0·72–1·22), 1·13 (0·86–1·48), 0·97 (0·74–1·27), and 1·24 (0·95–1·62), respectively, but associations were not statistically significant. InterpretationIn people at the lower end of the older-age spectrum, there was some support for lower levels of IGF-1 being linked with hearing impairment. These results warrant replication and then testing in trials of IGF-1 supplementation. FundingThe English Longitudinal Study of Ageing is supported by the National Institute on Aging (grant numbers 2RO1AG7644 and 2RO1AG017644-01A1) and a consortium of the UK government departments coordinated by the Economic and Social Research Council. The funding bodies had no role in the study design; collection, analysis, and interpretation of data; writing of the abstract; and decision to submit the abstract for publication.

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.

Association between Cognition and Serum Insulin-Like Growth Factor-1 in Middle-Aged & Older Men: An 8 Year Follow-Up Study.

Low levels of insulin-like growth factor-1 (IGF-1), an essential neurotrophic factor, have been associated with worse cognitive function in older adults. However, few studies have assessed the prospective association of serum IGF-1 with cognitive function. We aimed to determine the association between serum IGF-1 on concurrent and prospective cognitive function in a population sample of men aged 40–80 years. Blood samples were assessed for IGF-1 levels at baseline and neuropsychological assessments were performed at baseline (n = 400) and at follow-up after a mean duration of 8.3 years (n = 286). Linear regression analyses were carried out to determine the associations between quintiles of IGF-1 and cognitive function at the baseline and follow-up visits. Results showed that those in the top quintile of IGF-1 had lower processing capacity and global cognition scores at follow-up after controlling for cognitive function at baseline and other confounding factors. Additional analyses exploring associations with IGF-1 separately in middle-aged and older participants, and with quartiles of IGF-1 produced similar results. In those older than 60 years, high IGF-1 levels were also associated with lower baseline processing capacity. These results suggest that high IGF-1 levels are associated with worse long-term cognition in men. Together with past studies, we suggest that both, high and low levels of IGF-1 may be associated with poor cognitive function and that optimum levels of IGF-1 (quintile 2 and 3 in current study) may be associated with better cognitive function.

IGF-1 Levels are Inversely Associated With Metabolic Syndrome in Obstructive Sleep Apnea.

This study examined insulin-like growth factor-1 (IGF-1) production and its association with the metabolic syndrome (MS) in men with obstructive sleep apnea (OSA). In total, 47 overweight and obese men who had been referred for suspected OSA underwent polysomnography and were classified based on the apnea-hypopnea index (AHI) into three groups: no OSA, < 5 events/h (n = 11); mild OSA, ≥ 5 to < 15 events/h (n = 8); and moderate-severe OSA, ≥ 15 events/h (n = 28). The assessment of the somatotropic axis function included IGF-1 measurement. MS was diagnosed according to the National Cholesterol Education Program guidelines. IGF-1 level in the moderate-severe OSA group was lower than in the no-OSA group (156.8 ± 54.3 μg/L versus 225.5 ± 80.5 μg/L; p = 0.013). IGF-1 level was negatively correlated with body mass index, waist circumference (WC), AHI, and sleep duration with oxygen (O2) saturation < 90% and positively correlated with the average and minimum O2 saturation (p = 0.027). In a multivariable linear regression, considering WC and minimum O2 saturation as independent variables, only the minimum O2 saturation was a predictor of low IGF-1 levels. The proportions of patients with MS were different between the three groups (18.2% in no OSA; 25% in mild OSA, and 57.1% in moderate-severe OSA; p = 0.047). Furthermore, in the lowest tertile of IGF-1 value, 66.7% of patients were affected by MS (p = 0.049). Hemoglobin (Hb)A1c correlated negatively with the minimum O2 saturation and IGF-1 levels. However, in multivariable linear regression only IGF-1 levels were a predictor of HbA1c levels. The occurrence of OSA is associated with a reduction in IGF-1 levels. IGF-1 alterations in OSA also seem to be associated with a higher prevalence of MS.

MP39-10 SERUM INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) WAS A VALUABLE BIOMARKER TO PREDICT THE HIGH GRADE PROSTATE CANCER IN FINAL PATHOLOGY IN PATIENTS WHO HAD LOW TO INTERMEDIATE DISEASE ON BIOPSY.

You have accessJournal of UrologyProstate Cancer: Detection & Screening V1 Apr 2016MP39-10 SERUM INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) WAS A VALUABLE BIOMARKER TO PREDICT THE HIGH GRADE PROSTATE CANCER IN FINAL PATHOLOGY IN PATIENTS WHO HAD LOW TO INTERMEDIATE DISEASE ON BIOPSY. Myong Kim, Myungchan Park, Jong Won Kim, Donghyun Lee, Won Hee Park, In Gab Jeong, Cheryn Song, Jun Hyuk Hong, Choung-Soo Kim, Tai Young Ahn, and Hanjong Ahn Myong KimMyong Kim More articles by this author , Myungchan ParkMyungchan Park More articles by this author , Jong Won KimJong Won Kim More articles by this author , Donghyun LeeDonghyun Lee More articles by this author , Won Hee ParkWon Hee Park More articles by this author , In Gab JeongIn Gab Jeong More articles by this author , Cheryn SongCheryn Song More articles by this author , Jun Hyuk HongJun Hyuk Hong More articles by this author , Choung-Soo KimChoung-Soo Kim More articles by this author , Tai Young AhnTai Young Ahn More articles by this author , and Hanjong AhnHanjong Ahn More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.135AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES High level of Insulin-like growth factor-1 (IGF-1) was reported to be positively associated with low grade prostate cancer but not to high grade disease. We evaluated the role of preoperative serum IGF-1 level in predicting high grade disease (Gleason score [GS] ≥ 8) in the prostatectomy specimen in patients with low (GS ≤ 6) or intermediate grade (GS = 7) disease on biopsy. METHODS We analyzed the data from 793 patients who received radical prostatectomy. The serum testosterone, IGF-1, and IGF binding protein-3 (IGFBP-3) level were measured immediately before operation. Multivariate analyses were performed to find out predictive parameters for high grade disease in prostatectomy specimen in patients with low or intermediate disease on prostate biopsy. RESULTS Low, intermediate, and high grade disease on final pathology were observed in 159 (20.1%), 502 (63.3%), and 132 (16.6%) patients. Mean IGF-1 levels of patients with low, intermediate, and high grade disease were 151.7 (± 49.8), 144.1 (± 50.0), and 132.9 (± 46.4) ng/mL (p = 0.006). Patients with low preoperative IGF-1 level tended to have high grade disease on final pathology (OR = 0.680; p = 0.013). Serum IGF-1 level was significantly correlated with age (r = -0.313), diabetes mellitus (r = -0.165), serum testosterone level (r = -0.130), and serum IGFBP-3 level (r = 0.583; all p < 0.05). On multivariate analyses, low serum IGF-l level was an independent predictor for high grade disease on final pathology in patients with biopsy GS ≤ 6 (OR = 5.439; p = 0.016), and GS ≤ 7 (OR = 2.489; p = 0.030) after controlling preoperative variables such as age, PSA, prostate volume, percentage of positive core, clinical T stage, serum testosterone, and serum IGFBP-3 level. CONCLUSIONS Serum IGF-1 was a valuable biomarker to predict the high grade disease in final pathology in patients with low to intermediate disease on biopsy. Especially, low serum IGF-1 level in patient with low grade disease on biopsy portends the high grade disease on final pathology. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e545 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Myong Kim More articles by this author Myungchan Park More articles by this author Jong Won Kim More articles by this author Donghyun Lee More articles by this author Won Hee Park More articles by this author In Gab Jeong More articles by this author Cheryn Song More articles by this author Jun Hyuk Hong More articles by this author Choung-Soo Kim More articles by this author Tai Young Ahn More articles by this author Hanjong Ahn More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Perfluoroalkyl Substances, Sex Hormones, and Insulin-like Growth Factor-1 at 6-9 Years of Age: A Cross-Sectional Analysis within the C8 Health Project.

Background:Exposure to some perfluoroalkyl substances (PFAS), such as perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA), may alter levels of sex hormones and insulin-like growth factor-1 (IGF-1) in animals. Human studies on this topic are scarce, and none have been conducted in young children.Objectives:We investigated the relationship between levels of PFAS and estradiol, total testosterone, and IGF-1 in 2,292 children (6–9 years of age) from the C8 Health Project who lived near a chemical plant in the Mid-Ohio Valley (USA) with local contamination from PFOA.Methods:Serum samples were collected in 2005–2006 and analyzed for PFAS, sex hormones, and IGF-1. Results from regression models were expressed as the adjusted percentage difference (95% CI) per sex-specific interquartile range (IQR) increment of each PFAS serum concentration. Analyses by PFAS quartiles were also conducted.Results:Median concentrations of PFHxS, PFOA, PFOS, and PFNA were 8, 35, 22, and 1.7 ng/mL in boys and 7, 30, 21, and 1.7 ng/mL in girls. In boys, PFOA concentrations were significantly associated with testosterone levels (–4.9%; 95% CI: –8.7, –0.8%); PFOS with estradiol (–4.0%; 95% CI: –7.7, –0.1%), testosterone (–5.8%; 95% CI: –9.4, –2.0%), and IGF-1 (–5.9%; 95% CI: –8.3, –3.3%); and PFNA with IGF-1 (–3.5%; 95% CI: –6.0, –1.0%). In girls, significant associations were found between PFOS and testosterone (–6.6%; 95% CI: –10.1, –2.8%) and IGF-1 (–5.6%; –8.2, –2.9%); and PFNA and IGF-1 (–3.8%; 95% CI: –6.4, –1.2%). In both sexes, the magnitudes of the associations decreased monotonically across quartiles for both testosterone and IGF-1 in relation to PFOS, and for IGF-1 and PFNA in girls.Conclusions:To our knowledge, this is the first study suggesting that PFAS are associated with lower levels of IGF-1 and sex hormones in young children.Citation:Lopez-Espinosa MJ, Mondal D, Armstrong BG, Eskenazi B, Fletcher T. 2016. Perfluoroalkyl substances, sex hormones, and insulin-like growth factor-1 at 6–9 years of age: a cross-sectional analysis within the C8 Health Project. Environ Health Perspect 124:1269–1275; http://dx.doi.org/10.1289/ehp.1509869

Growth factors in cystic fibrosis

Introduction: Cystic fibrosis is one of the most common autosomal recessive diseases that affects sweat glands and mucosa. CF is a hereditary disease with annual incidence of about 2500 new cases in United Kingdom. Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 levels decrease in CF. The aim of this study was to assess the role of growth peptides in patients with CF. Method: We searched PubMed, Google scholar, IranMedex, and Scientific Information Database (SID) in September 2012 to April 2014. We included clinical studies with available abstracts and full texts that were in English or Persian languages. Manual searching was conducted within the reference lists of articles. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data.Result: The earliest study was published in 1997 and the most recent one was in 2014. Study participants were adults in 3 studies (20%) and 12 studies (80%) were conducted in children. Patients with CF have lower levels of IGF-1 and there is a significant correlation between IGF-1 levels and growth index in patients with CF.Conclusions: IGF-1 decreases in children with CF and might be the cause of poor growth and low body mass index in these children.

Mental disorders in patients with acromegaly

To study mental disorders in acromegaly due to somatotropinoma. The study included 115 consecutively recruited patients with acromegaly (95 female and 20 male, aged from 21 to 78 years). Acromegaly was diagnosed by endocrinologists according to current guidelines based on clinical, laboratory data and brain MRI. All patients underwent a clinical psychiatric interview based on ICD-10 criteria. The Mini-Mental State Examination scale and Hypomania-Checklist (HCL-32) were used. Mental disorders were diagnosed in 79.1% of patients. Organic spectrum disorders were found in 46.1%, bipolar spectrum disorders in 35.7%, schizophrenia spectrum disorders in 4.3%. The patients with bipolar spectrum disorders had significantly lower serum insulin-like growth factor 1 (IGF-1) levels compared to patients with organic spectrum disorders (p=0.01). The presence of organic spectrum disorders was associated with older age and number of somatic comorbidities (р=0.0001 and 0.001). The prevalence of bipolar, organic and schizophrenia spectrum disorders in patients with acromegaly exceeds that in the general population. Significantly lower IGF-1 levels in acromegalic patients with bipolar disorders, compared to those with organic disorders, can have some implications to their pathogenesis.

Effects of Somatostatin Analogues on Glucose Metabolism in Acromegaly: Friend of Foe?

Effects of Somatostatin Analogues on Glucose Metabolism in Acromegaly: Friend of Foe?

Prognostic significance of serum insulin-like growth factor-1 in patients with hepatocellular carcinoma following transarterial chemoembolization.

Insulin-like growth factor-1 (IGF-1) is an effective survival factor that is involved in the development and progression of various tumors. The aim of the present study was to investigate whether baseline serum IGF-1 levels are associated with time to progression (TTP) and overall survival (OS) in patients with hepatocellular carcinoma (HCC) who have undergone transarterial chemoembolization (TACE). A total of 145 patients with HCC who underwent TACE as an initial treatment were enrolled in the study. Baseline serum IGF-1 levels were detected using enzyme-linked immunosorbent assay (ELISA) kits. The patients were followed up for a median follow-up period of 47 months (range, 10.6-69.3 months). During the follow-up, 98 patients (76.6%) experienced disease progression and 59 patients (46.1%) succumbed. The serum IGF-1 level was found to be significantly associated with hepatitis infection status, Child-Pugh class, bilirubin level, tumor size and nodularity, vascular invasion and the Barcelona Clinic Liver Cancer (BCLC) stage. Multivariate analysis was conducted, which indicated that BCLC stage, vascular invasion and serum IGF-1 were independent risk factors for disease progression. When clinical factors were examined as potential independent risk factors for OS, only advanced BCLC stage and low serum IGF-1 levels were found to be significantly associated with poorer OS. These results suggest that serum IGF-1 may serve as a predictor of the prognosis of patients with HCC undergoing TACE.

IGF-1 and VEGF can be used as prognostic indicators for patients with uterine fibroids treated with uterine artery embolization.

The aim of the present study was to investigate the association between serum vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) levels and the prognosis of patients with uterine fibroids following uterine artery embolization (UAE) treatment. A total of 70 patients with uterine fibroids and 20 healthy controls were enrolled in this study between 2012 and 2014. The serum levels of IGF-1 and VEGF were measured using ELISA. Multiple-factor analysis was performed to assess the association between serum levels of IGF-1/VEGF and certain clinical characteristics, including size, location, number of uterine fibroids and adenomyosis. Progression-free survival curves were analyzed using the Kaplan-Meier method. The serum levels of IGF-1 and VEGF in patients with uterine fibroids prior to UAE treatment were significantly higher than those in controls (P<0.05). At 1 week after UAE treatment, the serum levels of IGF-1 and VEGF were significantly lower compared with those prior to UAE treatment. The serum levels of IGF-1 and VEGF at 1 or 3 months after UAE treatment were significantly higher than those at 1 week after UAE treatment. The serum levels of IGF-1 and VEGF were significantly correlated with the clinical characteristics of uterine fibroids (P<0.05). Lower levels of IGF-1 and VEGF in the serum following UAE treatment were associated with an enhanced progression-free survival of patients. In conclusion, the levels of IGF-1 and VEGF in the serum following UAE treatment can be used as indicators of prognosis in patients with uterine fibroids.

The Effect of Recombinant Growth Hormone Treatment in Children with Idiopathic Short Stature and Low Insulin-Like Growth Factor-1 Levels.

Objective:Idiopathic short stature (ISS) constitutes a heterogeneous group of short stature which is not associated with an endocrine or other identifiable cause. Some ISS patients may have varying degrees of insulin-like growth factor-1 (IGF-1) deficiency. Recombinant growth hormone (rGH) treatment has been used by some authors with variable results. Reports on long-term rGH treatment are limited.Methods:In this study, 21 slowly growing, non-GH-deficient ISS children who received rGH treatment for 3.62±0.92 years were evaluated at the end of a 5.42±1.67-year follow-up period. The study group included patients with low IGF-1 levels who also responded well to an IGF generation test. The patients were divided into two groups as good responders [height increment >1 standard deviation (SD)] and poor responders (height increment <1 SD) at the end of the follow-up period.Results:The height of the patients improved from -3.16±0.46 SD score (SDS) to -1.9±0.66 SDS. At the end of the follow-up period, mean height SDS was -1.72. Eleven of the patients showed a good response to treatment. Clinical parameters were essentially similar in the good responders and the poor responders groups. A female preponderance was noted in the good responders group.Conclusion:rGH treatment can safely be used in ISS children. Long-term GH treatment will ameliorate the height deficit and almost 40% of patients may reach their target height.

A cohort study of insulin-like growth factor 1 and mortality in haemodialysis patients

BackgroundProtein-energy wasting (PEW) is highly prevalent in haemodialysis (HD) patients and associated with increased mortality and cardiovascular disease (CVD). Insulin-like growth factor 1 (IGF-1) correlates to markers of PEW and CVD. Disturbances in the growth hormone axis in end-stage renal disease (ESRD) could have an impact on survival through increased PEW and CVD.MethodsA cohort of 265 incident HD patients (median age 68 years, 59% males) was followed for 3 years. Subjects were categorized according to IGF-1 levels at dialysis initiation. Outcome and comorbidity data were retrieved from national registers. The Kaplan–Meier diagram and Cox proportional hazards model were used for the analysis of survival.ResultsPatients with IGF-1 levels in the lowest tertile were characterized by female sex, low creatinine, hypoalbuminemia and high C-reactive protein (CRP) levels. IGF-1 levels within the lowest tertile were associated with increased mortality [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.7–3.4]. This association persisted when corrected for demographic factors (age, sex) and comorbidities (diabetes mellitus, CVD, heart failure) in multivariable analysis. Including high-sensitivity C-reactive protein (hs-CRP) and serum creatinine in the model had a small effect on the magnitude of the hazard. When serum albumin was added to the model, the HR declined from 2.2 to 1.6, but remained significant (P = 0.02).ConclusionLow IGF-1 levels associate with increased mortality in HD, independent of biomarkers of inflammation (hs-CRP) and PEW (creatinine, albumin). Serum albumin modulates the relationship between IGF-1 levels and mortality, indicating shared pathophysiological pathways with IGF-1.

Insulin-like Growth Factor 1 and Adiponectin and Associations with Muscle Deficits, Disease Characteristics, and Treatments in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with low muscle mass and density. The objective of our study was to evaluate associations between 2 serum biomarkers [insulin-like growth factor 1 (IGF-1) and adiponectin] and skeletal muscle in RA. Whole-body dual energy X-ray absorptiometry measures of the appendicular lean mass index (ALMI; kg/m(2)) and total fat mass index (kg/m(2)), as well as the peripheral quantitative computed tomography measures of the lower leg muscle and fat cross-sectional area (CSA; cm(2)) and muscle density (an index of fat infiltration) were obtained from 50 participants with RA, ages 18-70 years. Multivariable linear regression analyses evaluated associations between body composition and levels of adiponectin and IGF-1, adjusted for age, sex, and adiposity. Greater age was associated with higher adiponectin (p = 0.06) and lower IGF-1 (p = 0.004). Eight subjects had IGF-1 levels below the reference range for their age and sex. These subjects had significantly lower ALMI and muscle CSA in multivariable models. Lower IGF-1 levels were associated with greater clinical disease activity and severity, as well as low ALMI, muscle CSA, and muscle density (defined as 1 SD below normative mean). After adjusting for age and sex, greater adiponectin levels were associated with lower BMI (p = 0.02) as well as lower ALMI, and lower muscle CSA, independent of adiposity (p < 0.05). Only greater Health Assessment Questionnaire scores were significantly associated with lower adiponectin levels. Low IGF-1 and greater adiponectin levels are associated with lower muscle mass in RA. Lower IGF-1 levels were seen in subjects with greater disease activity and severity.

Reduced utility of serum IGF-1 levels in predicting retinopathy of prematurity reflects maternal ethnicity

AimsTo validate known risk factors and identify a threshold level for serum insulin-like growth factor 1 (IGF-1) in the development of severe retinopathy of prematurity (ROP) in an ethnically diverse...

Düşük Insulin-Like Growth Factor-1 düzeyleri olan bir akromegalik hasta: IGF-1 akromegali tanısında her zaman yüksek bulunmayabilir

The diagnosis of acromegaly is based on demonstration of excess growth hormone (GH) and Insulin-Like Growth Factor-1 (IGF-1) secretion. IGF-1 is the most reliable biochemical indicator of activity of acromegaly. However, there are some pitfalls in the interpretation of change of plasma IGF-1 levels. We aim to report a case with acromegaly that has low IGF-1 levels and elevated GH levels associated with poorly controlled type 2 diabetes mellitus and malnutrition. A 38-years-old woman was admitted to emergency departmant due to hyperglycemia, weakness, cough, dyspnea, high fever. She has been complaining for enlargement of her hands and feet for ten years and she was cachectic for a long time. During oral glucose tolerance test (OGTT), serum growth hormone levels were found to be higher than normal range according to the matching age and sex subjects but IGF-1 and IGFBP-3 levels were measured lower than the reference range. A macroadenoma of 3x2.5 cm diameter was determined in magnetic resonance imaging of the pituitary gland. As a conclusion, determining elevated IGF-1 levels are very important for the diagnosis and activity of acromegaly, but careful interpretation of IGF-1 levels is necessary in type 2 diabetic patients with acromegaly. Key Words: Acromegaly, IGF-1, malnutrition, type 2 diabetes mellitus.

Postoperative Insulin-Like Growth Factor 1 Levels Reflect the Graft's Function and Predict Survival after Liver Transplantation.

BackgroundThe reduction of insulin-like growth factor 1 (IGF-1) plasma levels is associated with the degree of liver dysfunction and mortality in cirrhotic patients. However, little research is available on the recovery of the IGF-1 level and its prognostic role after liver transplantation (LT).MethodsFrom April 2010 to May 2011, 31 patients were prospectively enrolled (25/6 M/F; mean age±SEM: 55.2±1.4 years), and IGF-1 serum levels were assessed preoperatively and at 15, 30, 90, 180 and 365 days after transplantation. The influence of the donor and recipient characteristics (age, use of extended criteria donor grafts, D-MELD and incidence of early allograft dysfunction) on hormonal concentration was analyzed. The prognostic role of IGF-1 level on patient survival and its correlation with routine liver function tests were also investigated.ResultsAll patients showed low preoperative IGF-1 levels (mean±SEM: 29.5±2.1), and on postoperative day 15, a significant increase in the IGF-1 plasma level was observed (102.7±11.7 ng/ml; p<0.0001). During the first year after LT, the IGF-1 concentration remained significantly lower in recipients transplanted with older donors (>65 years) or extended criteria donor grafts. An inverse correlation between IGF-1 and bilirubin serum levels at day 15 (r = -0.3924, p = 0.0320) and 30 (r = -0.3894, p = 0.0368) was found. After multivariate analysis, early (within 15 days) IGF-1 normalization [Exp(b) = 3.913; p = 0.0484] was the only prognostic factor associated with an increased 3-year survival rate.ConclusionIGF-1 postoperative levels are correlated with the graft’s quality and reflect liver function. Early IGF-1 recovery is associated with a higher 3-year survival rate after LT.

Prospective multicenter cohort study of estrogen and insulin-like growth factor system in BRCA mutation carriers.

Major clinical characteristics of BRCA1/2-related cancers include association with estrogen and metabolic consequences. We aimed to evaluate serum estradiol (E2) and insulin-like growth factor 1 (IGF-1) levels as a marker of insulin resistance in BRCA1/2 mutation carriers and high-risk, BRCA-negative controls. Eligible cancer-free women (age 18-42 with regular menstrual cycles) who had been screened for BRCA1/2 mutations between 2005 and 2013 completed a questionnaire and underwent a single blood draw. E2 was measured with radioimmunoassay, and IGF-1 was measured with enzyme-linked immunosorbent assay. Eighty-six women participated (44 carriers and 42 non-carriers) in this study. BRCA mutation carriers were significantly younger than non-carriers (p=0.0002). Age-adjusted basal (menstrual cycle days 2-5) serum E2 level was not significantly different between BRCA mutation carriers and non-carriers (30.4 vs. 24.7pg/mL, p=0.07). BRCA mutation carriers have significantly lower age-adjusted serum IGF-1 levels compared to non-carriers (89.7 vs. 112.6ng/mL, p<0.001). In women with BRCA mutations, the risk of having low serum IGF-1 level (IGF-1: ≤85ng/mL) was 10.7 times as great as that of women without BRCA mutations (95% CI 2.5, 46.2). There was a significant inverse association between basal E2 and IGF-1 levels in BRCA mutation carriers after adjusting age and BMI (p=0.03). IGF-1 level is significantly lower in cancer-free BRCA mutation carriers versus BRCA-negative controls, and there is a potential association between E2 and IGF-1 in cancer-free BRCA mutation carriers. Our findings may instigate future studies evaluating the role of both E2 and IGF-1 in BRCA mutation carriers.

Abstract MP46: Growth Factors Are Associated With Imaging Markers of Brain Aging in Young Adults

Metabolic and vascular dysregulation are related to stroke, cognitive decline and dementia. Growth factor biomarkers of these processes, such as Insulin-like Growth Factor 1 (IGF1) and Vascular Endothelial Growth Factor (VEGF) have been associated with risk of neurodegeneration and stroke in middle-aged and older Framingham participants. Additionally, hepatocyte growth factor (HGF) and angiopoietin 2 are novel biomarkers of interest as they have been related to cardiovascular events. As abnormal brain changes probably start years before clinical symptoms, we hypothesize that circulating growth factors are related to MRI endophenotypes of brain aging. We included 1,877 individuals aged 46±8 years from the Framingham Study. Blood samples were collected during 2008-2011, and used to measure IGF1, VEGF, HGF, angiopoietin 2 and its receptor tyrosine kinase (TIE2). Participants underwent brain MRI examination (2009-2013) from which brain volumes and white matter hyperintensities were estimated. We related growth factor levels to brain MRI markers adjusting for age, sex, time between blood draw and MRI, and cardiovascular risk factors. Lower IGF1, as well as higher HGF and angiopoietin 2 levels were associated with higher ventricular volumes indicative of brain shrinkage. Higher TIE2 levels were associated with lower total brain and gray matter volumes, while higher angiopoietin 2 levels were associated with lower white matter volumes. Lower IGF1 levels were also associated with reduced hippocampal volumes. Finally, higher TIE2 levels were associated with larger white matter hyperintensities. Our results suggest that growth factors are associated with neurodegenerative and cerebrovascular markers of brain aging in healthy young adults. Whereas IGF1 seems protective, higher levels of HGF, angiopoietin 2 and TIE2 were associated with greater subclinical brain injury. These associations expand our understanding of the earliest stages of brain aging. We will extend our findings by analyzing cognitive outcomes.