Low Insulin-like Growth Factor-1 Levels Research Articles

5-ARI induces autophagy of prostate epithelial cells through suppressing IGF-1 expression in prostate fibroblasts.

Objectives5α‐reductase inhibitor (5‐ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment.Materials and MethodsProstate specimens from patients were collected. Insulin‐like growth factor 1 (IGF‐1), Beclin‐1, LC3 levels, was analysed by immunohistochemistry. The role IGF‐1 on autophagic flux in prostate epithelial cells was studied. Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated.ResultsWe demonstrated that IGF‐1 expression is down‐regulated in prostate fibroblasts after long‐term 5‐ARI application. A decrease in IGF‐1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF‐1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long‐term 5‐ARI application reduces IGF‐1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression.ConclusionsFocusing on the autophagy induced by low levels of IGF‐1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development.

Change in the content of titin and nebulin and their phosphorylation level in the quadriceps femoris muscle in chronic alcoholic myopathy

Objective : to assess the structural and functional state of skeletal muscles in the hip, as well as changes in the content of the sarcomere cytoskeleton proteins titin and nebulin and their phosphorylation level in patients with chronic alcohol intoxication. Patients and methods . Thirteen patients (4 men and 9 women; mean age, 38.9±9.9 years) with chronic alcohol intoxication were examined. The average duration of regular consumption of alcoholic beverages was 7.6±3.7 years. The mean amount of alcohol consumed per week was 48.2±13.1 units. A control group included 10 healthy volunteers matched for age and sex. A neurological examination was performed according to the generally accepted scheme. Laboratory tests involved blood biochemical analysis estimating the levels of liver enzymes, creatine phosphokinase (CPK), and insulin-like growth factor-1 (IGF-1). All the patients underwent hip magnetic resonance imaging (MRI), followed by assessment of the degree of muscle tissue damage and by determination of the volume of anterior and posterior thigh muscles. The content of titin and nebulin and their phosphorylation level were determined in the muscle tissue samples obtained by an open biopsy from the lateral head of the quadriceps femoris muscle. Results and discussion . Four (30.8%) patients were found to have proximal leg muscle weakness; the degree of paresis was the same in the anterior and posterior thigh muscles. There was a significant increase in the plasma level of liver enzymes; the CPK level remained within the reference values; there was a tendency towards lower IGF-1 levels. Analysis of MRI data showed that 7 (53.8%) patients had fatty degeneration in the thigh muscles. Quantitative evaluation ascertained a significant symmetrical decrease in the volume of anterior thigh muscles and a tendency towards a symmetrical reduction in that in the posterior thigh muscle compared to the control. Analysis of the content of titin and nebulin in the lateral head of the quadriceps femoris muscle revealed a significant decrease in the percentage of nebulin (81.1%; p < 0.01) and intact titin-1 (T1) isoforms (83.6%; p < 0.01). The percentage of proteolytic titin-2 (T2) fragments in the muscle of patients did not differ significantly from that in the control group. Estimating the phosphorylation level of the structural muscle proteins showed no significant differences when compared to the control. Conclusion . Anterior and posterior thigh muscle weakness should be considered as the main clinical manifestation of chronic alcoholic myopathy (CAM) in the absence of biochemical and neurophysiological markers of the disease. Lower extremity muscle MRI that can reveal a lower muscle volume concurrent with fatty degeneration is a non-invasive informative diagnostic technique for CAM. The pathogenesis of skeletal muscle atrophy in chronic alcohol intoxication involves the sarcomere structural proteins titin and nebulin, which regulate the interaction of the major contractile proteins actin and myosin, and whole muscle contraction.

Pesticide Exposure and Stunting among Children in Agricultural Areas.

Background: The prevalence of growth disorders among school-aged children in Indonesia is high (30.7%). Pesticides have been massively used in Indonesian agricultural areas. Objective: Objective: To determine if exposure to pesticides is associated with stunting among children in agricultural areas. Methods: This case-control study included 160 children (48 cases and 112 controls) aged 8–12 years. Exposure to pesticides was measured based on the history of the exposure since perinatal period, infancy, and childhood of the participants. Stunting was determined as a height for age z-score (HAZ) < -2 SD. Other variables measured were levels of thyroid stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1), hemoglobin, zinc, albumin, nutrient adequacy level (energy and protein), and history of infection, low-birth weight (LBW), and mother's height. Results: There were no significant difference between the cases and controls in terms of in the baseline characteristics, except for the median IGF-1 level; it was significantly (p<0.001) lower in the cases (66.73 ng/mL) than the controls (112.57 ng/mL). High level of pesticide exposure (p=0.029) and low IGF-1 levels (p<0.001) were significantly associated with stunting. After adjusting for confounding variables, these variables were found to be independent risk factors for stunting in children (aOR 3.90, 95% CI 1.15 to 13.26; and aOR 8.35, 95% CI 3.65 to 19.14, respectively). Conclusion:Pesticide exposure could be a risk factor for the occurrence of growth disorders in children living in agricultural areas. Necessary actions should be taken to protect children living in agricultural areas from exposure to pesticides.

The Association of IGF-1 with Clinical Symptoms in Female Patients With Fibromyalgia Syndrome

Introduction: Fibromyalgia syndrome (FMS) is a disease of unknown etiology, which is characterised by chronic pain. Disturbed growth hormone response, low serum insulin-like growth factor-1 (IGF-1) may play a role in etiopathogenesis of fibromyalgia and may be related to the severity of some symptom. The aim of this study is to investigate serum IGF-1 levels and relationship of clinical symptoms in female patients with fibromyalgia syndrome. Materials and Methods: Thirty-seven patients with FMS and thirty healthy subjects were included in this study. All individuals were assessed for clinical findings, widespread pain (Visual Analogue Scale), functional disability and health state (health assesment questionnarie and fibromyalgia impact questionnarie), anxiety (anxiety State and Trait Anxiety Inventory) and depression (Beck depression inventory). Likert scale was used for evaluate morning stiffness, level of fatigue, pain, muscle spasm and tenderness. Results: In this study, serum IGF-1 levels of patients with fibromyalgia were significantly lower compared to the control group (p=0.004). The IGF-1 levels were significantly correlated with age (r=-0.496; p<0.01), muscle spasm (r=-0.333; p<0.05), tender points (r=-456; p<0.01) and morning stiffness (r=-0.463; p<0.01). Conclusion: Low levels of serum IGF-1 in female patients with fibromyalgia syndrome were associated with number of tender points, muscle spasm and stiffness. We have concluded that low levels of serum IGF-1 might play role in the pathogenesis of fibromyalgia and might be related to severity of symptoms.

Serum insulin-like growth factor 1 (IGF-1) in multiple sclerosis: relation to cognitive impairment and fatigue

BackgroundMultiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease. Changes in insulin growth factor 1 (IGF-1) input to the brain can affect survival of myelin and CNS cells. The study aims to investigate the relation of serum IGF-1 levels with cognitive impairment and fatigue in MS patients.MethodsThis study was conducted on 46 MS patients and 46 healthy controls. All participants were subjected to clinical assessment, serum IGF-1 levels, expanded disability status scale (EDSS), modified fatigue impact scale (MFIS), and Montreal cognitive assessment (MoCA) scale.ResultsThere was no significant difference between patients and controls regarding serum IGF-1 levels (P = 0.19). However, low serum levels of IGF-1 have significantly greater odds for fatigue (P = 0.002) and cognitive impairment (P < 0.001). Also, serum IGF-1 levels have a significant negative correlation with MFIS (r = − 0.701 and P < 0.001) and a significant positive correlation with MoCA scale (r = + 0.84 and P < 0.001).ConclusionsThe results, specifically that low levels of serum IGF-1 was associated with cognitive impairment and fatigue in MS, suggest that IGF-I may be involved in the pathogenesis of cognitive deficits and fatigue in MS disease.

Low lean tissue mass can be a predictor of one-year survival in hemodialysis patients

Purpose: Nutritional status has a significant impact on the outcomes in the dialysis population. The aim of this study was to evaluate the association between body composition and a one-year survival of hemodialysis patients.Methods: Forty-eight patients with chronic kidney disease stage V treated with hemodialysis for more than three months were included. Body composition was assessed by bioimpedance spectroscopy (Body Composition Monitor, Fresenius Medical Care). Blood samples for serum creatinine, serum albumin, serum prealbumin, high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), insulin-like growth factor 1(IGF-1) concentrations were taken before the midweek dialysis session.Results: Over the course of a one-year observation, seven patients died. We observed a significantly lower lean tissue index (LTI) (p = .013) and higher IL-6 (p = .032) and hsCRP levels (p = .011) among the patients who died. The remaining biochemical markers did not differ between these two groups. Kapplan–Meier analysis revealed a worse survival rate in patients with sarcopenia (lower than the 10th percentile for their age and gender) in comparison with those with normal LTI. However, it was not of statistical significance (p = .055). LTI inversely correlated with age and IL-6 and positively with IGF-1.Conclusions: Sarcopenia defined as decreased LTI, is a relatively common condition among patients undergoing maintenance hemodialysis, it can also be associated with a lower one-year survival rate. Decreased lean tissue mass can be associated with old age, lower IGF-1 levels and higher IL-6 levels. Body composition assessment may provide prognostic data for hemodialysis patients.

Preoperative Serum Insulin-Like Growth Factor 1 Level as a Prognostic Factor in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma.

In this study, preoperative serum levels of insulin-like growth factor 1 (IGF-1) were determined in 216 hepatocellular carcinoma (HCC) patients who underwent hepatic resection to investigate a possible contribution of IGF-1 to the increased risk for HCC recurrence and mortality. During January 2010 and December 2013, 216 HCC patients receiving hepatectomy were recruited. The primary endpoint was the HCC recurrences within the 3-year follow-up. The secondary endpoint was all-cause mortality. The multivariate analyses with Cox regression model were applied to explore the clinical significance of IGF-1 serum levels and associated parameters on death and recurrence of HCC patients. The IGF-1 levels of included patients were determined, with a median value of 75.5 ng/mL (IQR, 40.3-93.0 ng/mL). The preoperative serum level of IGF-1 was negatively correlated with tumor size, Child-Pugh class, or tumor stage (P < 0.001 for all). In multivariate models comparing the first, second, and third quartiles with the fourth quartile of IGF-1, the levels of IGF-1 in Q1 and Q2 were associated with HCC recurrence, with an increased risk of 216% [hazard ratios (HR) = 3.16 (95% CI: 1.79-4.28)] and 106% [3.02 (1.36-3.11)]. Similarly, concentrations of IGF-1 in Q1 and Q2 were also related to all-cause mortality, with an increased recurrence risk of 238% [HR = 3.38 (95% CI: 1.85-4.36)] and 117% [3.02 (1.40-3.21)], respectively. Poor prognosis in HCC patients receiving hepatectomy could be indicated by low preoperative serum levels of IGF-1, which would be applied as a predictor.

Vitamin D in children with growth hormone deficiency due to pituitary stalk interruption syndrome

BackgroundRecent studies have shown a relationship between vitamin D status and growth hormone (GH) and insulin-like growth factor 1 (IGF1). The objective of this study was to assess vitamin D status in children with GH deficiency due to pituitary stalk interruption syndrome (PSIS) and to investigate the relationship between 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25 (OH) 2D) serum levels and patient characteristics.MethodsA retrospective single-center study of 25OHD and 1,25(OH)2D serum concentrations in 50 children with PSIS at the initial evaluation before treatment.ResultsMean concentrations of 33.2 ± 18.0 ng/mL for 25OHD and 74.5 ± 40.7 ng/L for 1,25(OH)2D were measured. Additionally, 25OHD concentrations were significantly higher in boys than in girls (p = 0.04) and lower in the cold season than in the sunny season (p = 0.03). Significant positive correlations were observed between the GH peak and serum 1,25 (OH) 2D concentrations (Rho = 0.35; p = 0.015) and the 1,25(OH)2D/25OHD ratio (Rho = 0.29; p < 0.05). No correlation was found for other characteristics, including IGF1.ConclusionsVitamin D status in children with hypothalamic-pituitary deficiency due to PSIS was similar to that reported in national and European studies in healthy children. The positive significant correlations between the GH peak and the 1,25 (OH)2D concentration as well as with the 1,25 (OH)2D/25OHD ratio suggest that even in these patients who had severely impaired GH secretion and low IGF1 levels, an interplay between the GH/IGF1 axis and the vitamin D system still exists.

Whole Body Vibration Retards Progression of Atherosclerosis via Insulin-Like Growth Factor 1 in Apolipoprotein E-Deficient Mice.

Whole body vibration (WBV) has a marked impact on lipid metabolism and the endocrine system, which is related to the progression of atherosclerosis (AS). To investigate the effects of WBV, we measured the atherosclerotic plaque area of apolipoprotein E-knockout (ApoE−/−) AS mice, which were trained by WBV (15 Hz, 30 min) for 12 weeks. Simultaneously, serum levels of lipids, insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF-1R), interleukin 6 (IL-6), and the mRNA and protein levels of the same in the aorta were compared between the control and WBV groups. The results indicated that WBV significantly reduced the atherosclerotic plaque area with lower very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (ox-LDL) in the blood. Moreover, the levels of IGF-1 in serum and expression of IL-6, IGF-1R, and p-IGF-1R protein in the mice aorta decreased significantly in the WBV group. In addition, we found that serum IGF-1 in mice increased to the highest concentration in 30 min after WBV for 10, 30, 60, and 120 minutes. These results suggested that appropriate WBV may delay the progression of AS, which was associated with acutely elevated serum IGF-1 and lower levels of IGF-1 and IL-6 in the aorta for long-term treatment.

Has acromegaly been diagnosed earlier?

PurposeWe investigated whether acromegaly has been diagnosed earlier at the Niigata Medical and Dental University Hospital. MethodsPatients with acromegaly (n = 81) who underwent their first transsphenoidal surgery from 2006 to 2015 were reviewed. Two groups were compared: those who underwent surgery between 2006 and 2010 (n = 35) and those who underwent surgery between 2011 and 2015 (n = 46). We compared clinical features and serum levels of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1), hypertension (HT) and diabetes mellitus (DM) prevalence between the two groups. ResultsCompared with the early group, microadenomas (<10 mm) were more prevalent in the late group (0% vs. 15.2%, p < .05). Serum IGF-1 standard deviation score (SDS) was significantly lower in the late group (8.57 ± 2.50 vs. 6.44 ± 2.30, p < .001). In both groups, mean IGF-1 SDS was significantly lower in patients without DM than in those with DM (6.9 ± 2.6 vs. 8.3 ± 2.4, p = .02). Logistic regression analysis showed that serum GH and IGF-1 levels were significantly higher in patients with DM than in those without DM. ConclusionRegarding operated cases of GH-producing pituitary adenoma, acromegaly clinical manifestations tended to be milder at diagnosis in later years of the decade, and acromegaly was diagnosed at lower IGF-1 levels and in smaller lesions. Further study is mandatory for the generalization of this trend.

Growth and endocrine function in children with Dravet syndrome

PurposeDravet syndrome is an intractable childhood epilepsy syndrome most often associated with an SCN1A mutation. In our clinical practice, several patients with Dravet syndrome were noted to have short stature and endocrine dysfunction. This has not been reported in the literature. Our study aim was to describe growth measurements and endocrine abnormalities in children with Dravet syndrome. MethodA retrospective chart review was performed at a single institution. Eligibility criteria included clinical and genetic (SCN1A) diagnosis of Dravet syndrome. Records were reviewed for height and weight measurements and serologic evidence of endocrine abnormality, as well as patient demographics, anti-seizure medication, and family history. Age and gender specific trend of height and weight measurements, using z-scores, were compared to CDC growth curves (Centers for Disease Control and Prevention [1]). ResultsSixty-eight children were identified, 46% male, age 1–21 years, taking an average of 2.9 anti-seizure medications per patient. Mean growth parameter measurements were significant for decrease in height z-score of 0.10 (p=<0.001) and decrease in weight z-score of 0.09 (p=<0.01) for every year increase in age, such that with increasing age the cohort moved farther away from the mean. The average group height and weight z-score, at age 8, was −0.45 and −0.09, respectively. After adjusting for age, neither gender, family history, or anti-seizure medication was associated with height or weight z-score. Serologic endocrine results were available for 26 children (38%). This identified low insulin-like growth factor 1 (IGF-1) in 7/15 and low testosterone in 2/10. Two children received growth hormone supplementation. TSH testing was abnormal <10% of the time. ConclusionsComorbidities in children with Dravet syndrome may involve more systems than previously reported. We report a cohort of children with Dravet syndrome with reduced height and weight growth trend, as well as a subset with endocrine dysfunction evidenced by low IGF-1 and testosterone levels. Additional prospective research is needed to further define the significance of this relationship.

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.

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.

Association between frailty and carotid intima media thickness and inflammatory marker in an elderly population.

Frailty is a highly prevalent geriatric syndrome, characterized by increased vulnerability to subsequent morbidity and mortality. The association between frailty and preclinical atherosclerosis remains uncertain. The aim of the present study was to clarify the relationship between frailty, preclinical atherosclerosis and inflammatory markers in older adults. We enrolled 1798 inhabitants of I-Lan County of Taiwan (855 men, 47.5%; mean age 64±9years, range 50-92years). Assessment of frailty was based on the Cardiovascular Health Study criteria. Common carotid artery intima-media thickness (CIMT) was determined using carotid Doppler ultrasonography. Overall, 955 participants (53.1%) were non-frail, 724 (40.2%) were pre-frail and 119 (6.7%) were frail. Frail and pre-frail participants had significantly increased CIMT, high-sensitivity C-reactive protein, glycated hemoglobin and urine albumin-to-creatinine ratio, but had lower insulin-like growth factor-1 level and decreased femoral neck bone mineral density (BMD). By multivariate analysis, age (OR 2.53, 95% CI 1.92-3.33), C-reactive protein (OR 1.19, 95% CI 1.00-1.42), CIMT (OR 1.27, 95% CI 1.04-1.55) and femoral neck BMD (OR 0.49, 95% CI 0.38-0.65) were independently associated with frailty. The present study showed the epidemiology of frailty, and the strong connection to aging, increased CIMT, enhanced inflammation and decreased femoral neck BMD. These results suggested that preclinical atherosclerosis, inflammation and femoral neck BMD were potentially modifiable risk factors for frailty. Geriatr Gerontol Int 2017; 17: 2449-2454.

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.

Circulating IGF-1, IGFB-3, GH and TSH levels in multiple sclerosis and their relationship with treatment

Objectives: Improving the proficiency of oligodendrocytes in their ability to repair myelin damage is one of the major goals of multiple sclerosis treatment. Insulin-like growth factor-1 (IGF-1) is one of several polypeptides that are considered to have potential benefits in that sense. In the present study, we aimed to determine serum levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3), thyroid stimulating hormone (TSH) and growth hormone (GH) among treated and non-treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and a healthy control group.Methods: The study enrolled 100 RRMS patients and 100 age- and sex-matched control subjects diagnosed with definite multiple sclerosis (MS). Serum GH, IGF-1, IGFBP-3, and TSH levels were studied.Results: The number of relapses and Expanded Disability Status Scale were negatively correlated and IGFBP-3 and GH were positively correlated with IGF-1. A statistically significant difference was not observed when patients were divided into two subgroups as patients treated with a MS-specific therapy (n = 54) and non-treated patients (n = 46). TSH and IGFBP-3 values were significantly lower in patient group vs. control group.Conclusion: While no difference was determined with in IGF-1 levels, low levels of IGF-1 was in correlation with the least levels of IGFBP-3. To understand the relation between IGF-1 and IGFBP-3, the role of low levels of IGFBP-3 and TSH may be studied with clinic isolated syndrome patients and the evolution of these patients to definite MS.

Associations between levels of insulin-like growth factor 1 and sinusoidal obstruction syndrome after allogeneic haematopoietic stem cell transplantation

Allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) is challenged by severe adverse events, as cytotoxic effects of the conditioning may result in systemic inflammation, leaky epithelial barriers and organ toxicities, contributing to treatment-related morbidity and mortality. We hypothesised that insulin-like growth factor-1 (IGF-1), a mediator of growth and proliferation of various tissues, may attenuate chemotherapy-induced tissue damage after HSCT. We prospectively measured plasma levels of IGF-1 and its binding protein 3 (IGFBP-3) in 41 patients undergoing myeloablative HSCT. IGF-1 and IGFBP-3 levels were inversely correlated with C-reactive protein and interleukin-6 levels post HSCT. In multivariate analyses, low levels of IGF-1 and IGFBP-3 before conditioning were associated with increased risk of developing sinusoidal obstruction syndrome (SOS; OR=5.00 per 1 SDS decrease in IGF-1 (95% CI: 1.45-16.67), P=0.011 and OR=5.00 (1.37-20.00), P=0.015, respectively). Furthermore, low pre-transplant levels of IGF-1 and IGFBP-3 were associated with increased fluid retention during the first 21 days post transplant (OR=7.69 (95% CI: 1.59-33.33), P=0.012, and OR=2.94 (1.03-8.33), P=0.045). These data suggest that high levels of IGF-1 and IGFBP-3 may have a protective effect against fluid retention and SOS, possibly by attenuating systemic inflammation, and may prove useful as predictive biomarkers of SOS.

Bone mineral density and insulin-like growth factor-1 in children with spastic cerebral palsy.

Children with cerebral palsy (CP) have significant decrease linear growth rate and low bone mineral density (BMD). This study is to evaluate BMD in children with CP and its relation to the levels of insulin-like growth factor-1 (IGF-1). This cross-sectional study was carried out on 58 children suffering from spastic CP with the age range 4-12years compared to 19 controls. All assessed by dual energy x-ray absorptiometry (DXA) to measure BMD, serum level of IGF-1, and serum vitamin D. The patients were classified according to their GMFCS. Fractures were reported in seven (12.1%) of cases. Our study demonstrated that, IGF-1 level and BMD decrease in correlation with the severity of CP. IGF-1correlates positively with serum vitamin D, BMI, and BMD. CP children with severe GMFCS level or who use anticonvulsive drugs are at a high risk for low BMD and low levels of IGF-1. Both BMD and IGF-1 were significantly in low children with spastic CP; IGF-1 negatively correlates with the severity of osteopenia in children with spastic. Children with CP who are not independently ambulant or with severe GMFCS level or who use anticonvulsive drugs are at a high risk for developing low BMD.

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.

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.