Low Insulin-like Growth Factor-1 Levels Research Articles

Assessment of serum insulin-like growth factor 1 and serum insulin in children with congenital heart disease

Introduction Children with congenital heart disease (CHD) have been reported to show significant growth retardation both prenatally and postnatally. Different types of cardiac malformation can affect nutrition and growth to varying degrees. Objectives The aim of this study was to assess the relationship between insulin-like growth factor 1 (IGF-1) and age, height, weight, head circumference, and BMI of infants. Materials and methods This was a case-control study conducted on 45 infants and children. The study included 30 children with CHD attending the Pediatric Cardiology Unit in Benha University Hospital from December 2012 to May 2013 who constituted the diseased group (groups 1 and 2). Their ages exceeded the neonatal period. Fifteen healthy sex-matched and age-matched children served as the control group (group 3). The infants were subjected to history taking, complete clinical examination, and assessment of serum IGF-1, serum insulin, and random blood sugar. All data were recorded and analyzed in detail. Growth retardation in children with CHD was assessed. Results There was significant difference between cases of CHD and the healthy control group as regards weight and BMI. There was significant difference between infants with cyanotic and those with acyanotic CHD as regards the weight. The cyanotic group was underweight. A significant difference was found in the length between the cyanotic and the acyanotic group. Infants in the cyanotic group were of short stature. There was significant difference between the cyanotic group and the acyanotic group as regards IGF-1 concentration, with the cyanotic group having lower concentration compared with the acyanotic group. Conclusion In light of this study we found that infants with CHD had lower IGF-1 levels compared with controls. Cyanotic CHD in children caused more pronounced growth retardation in comparison with acyanotic CHD.

Role of CRP, TNF-a, and IGF-1 in Delirium Pathophysiology.

Delirium is a common and life-threatening neuropsychiatric syndrome. Diagnosing delirium can be challenging, which increases mortality and mortality rates and health care costs. The biologic model of delirium is not definite yet, but evidence supports a cholinergic deficiency model. Delirium may be the result of processes and drugs that trespass a compromised blood-brain barrier. We aimed to evaluate the possible diagnostic utilization and the role of certain biomarkers, such as C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and insulin like growth factor-1 (IGF-1), in delirium etiology. A total of 93 inpatients that planned to undergo cardiovascular surgery were informed; 35 of them completed the study. Medical history and current cognitive status were evaluated pre-operatively. Participants were followed using Delirium Rating Scale-Revised-98 Turkish (DRS-R98-T) for delirium symptoms, and blood samples were collected post-operatively. Delirium was developed more in participants who had worse pre-operative cognitive status. Also, low pre-operative IGF-1 levels were detected in the delirium group. Pre-operative CRP and TNF-α levels were not different between groups. Low IGF-1 levels can be used to predict delirium after surgery. However, the complex nature of cytokines and delirium itself make it difficult to utilize cytokines to predict delirium instead of psychometric tools.

Insulin-like Growth Factor-1 (IGF-1): Demographic, Clinical and Laboratory Data in 120 Consecutive Adult Patients with Thalassaemia Major.

IntroductionIGF-1 deficiency in TM patients in children and adolescents has been attributed to chronic anemia and hypoxia, chronic liver disease, iron overload and other associated endocrinopathies, e.g. growth hormone deficiency (GHD). Few data are available in the literature regarding adult TM patients and growth disorders. The aim of this study was to measure IGF-1 values and other clinical data in a large number of adult patients with TM to evaluate the possible relationships between them.Patients and MethodsA cohort of 120 adult patients with TM was studied for plasma levels of IGF-1. Plasma total IGF-1 was determined by chemiluminescent immunometric assay (CLIA) method. In eleven patients (3 females) the GH response during glucagon stimulation test (GST) was also evaluated.ResultsFifty percent of patients (33 males and 27 females) had IGF-1 levels <- 2 SDs below normative values for healthy subjects matched for age and sex. In these patients endocrine complications and elevations of aminotransferases (ALT) were more common compared to TM patients with IGF1 > -2SDs. In multivariate regression analyses, height, weight, BMI, serum ferritin, ALT, HCV serology and left ventricular ejection fraction (LVEF) were not significantly related to IGF-1, but a significant correlation was found in females between HCV-RNA positivity and IGF-1, ALT and serum ferritin. AGHD was diagnosed in 6 (4 males) out of 11 patients (54.5%) who had glucagon stimulation tests and in 5 out of 8 (62.5%) with IGF-1 <-2SD. The mean age of patients with GHD was 39.3 years (range: 25–49 years, median: 39 years) versus 35.8 years (range: 27–45 years, median: 37.5 years) in non-GHD patients. A positive correlation between GH peak after GST and IGF-1 level was found (r: 0.6409; p: < 0.05).ConclusionsIn 50% of TM patients the IGF-1 levels were 2SDs below average values for healthy individuals. IGF-1 deficiency was more common in TM patients with associated endocrine complications, and a significant correlation was found in HCV-RNA positive females among IGF-1, ALT, and serum ferritin. Further data in a larger group of patients are needed to confirm whether IGF-1 level <-2 SDs may be a potential criterion for additional studies in TM patients. This datum could avoid performing GH stimulation tests in the majority of them.

Correlation between serum insulin-like growth factor-1 and retinopathy of prematurity

Objective To determine the changes of serum levels of insulin-like growth factor-1 (IGF-1) in the premature infant,and to explore the correlation between serum IGF-1 and retinopathy of prematurity (ROP).Methods Premature infants with gestational age ＜34 weeks or birth weight ＜2000 g were enrolled in the study.They were divided into two groups,ROP group (with ROP) 30 cases,premature control group (without ROP) 30 cases.In the time of first week after delivery,corrected gestational age at 32,34,36 and 40 week,we collected peripheral venous blood and measured the levels of serum IGF-1.At the same time 30 cases of full term newborn were chosen as mature control group.Results Before corrected gestational age of 40 week,serum levels of IGF-lwere rising in ROP group and premature control group.IGF-1 levels of ROP group were significantly lower than those of the premature control group in the first week and corrected gestational age at 32,34,36 week (P ＜ 0.05).IGF-1 levels in ROP group and premature control group were both lower than those of the mature control group in the first week (P ＜ 0.05).At corrected gestational age of 40 week,there was no significant difference among three groups (P ＞ 0.05).Conclusion Low levels of IGF-1 in premature infant may lead to ROP generation in the early period after birth.Improving the serum level of IGF-1 may effectively control the occurrence of ROP during the critical period. Key words: Premature infant; Retinopathy of prematurity; Insulin-like growth factor-1

Evaluation of insulin like growth factor-1 (IGF-1) level and its impact on muscle and bone mineral density in frail elderly male

Decrease in IGF-1 level is a major endocrine dysregulation that has been implicated in frailty, disability, and mortality in older adults. Our aim was to clarify the effect of IGF-1 on muscle and bone mineral density (BMD) in frail males. One hundred elderly males were included and divided into frail group (n=50) and robust group (n=50) based on the study of osteoporotic fractures (SOF) frailty index. Anthropometric measures, femoral BMD, and serum IGF-1 level were measured. Our results showed that the IGF-1 level was significantly lower in the frail males in comparison to the robust with mean value 37.1±24.2 versus 68.5±18.4ng/ml (P<0.05). Receiver operating curve (ROC) analysis of the IGF-1 level revealed that sensitivity was 88.5%, specificity was 100%, cutoff value was 46.5ng/ml and area under the curve (AUC) was 0.897 (P<0.05). Participants with low IGF-1 percentile had significantly higher odds ratio of being frail compared to those with high IGF-1 percentile (odds ratio=12.8, 95% CI: 4.2–38.8, P-value<0.05). Subjects with low IGF-1 percentile had 13.5 times the odds of having an abnormal BMD than those with middle IGF-1 percentile (95% CI: 3.4–53.3, P<0.05). In multivariate analysis BMD, mid arm circumference (MAC), mid calf circumference (MCC), and handgrip strength were significantly affected by IGF-1 percentiles with age and co-morbid diseases adjustment. Male subjects with a low IGF-1 level may be at risk of being frail and having abnormal BMD. 16.8% and 15% of variability in MCC and BMD may be attributed to IGF-1 level respectively.

Low circulating insulin-like growth factor-1 levels are associated with high serum uric acid in nondiabetic adult subjects

Background and aimsLow insulin-like growth factor-1 (IGF-1) levels and high uric acid concentrations are associated with cardio-metabolic disorders. Acute IGF-1 infusion decreases uric acid concentration in healthy individuals. In this study, we aimed to examine the relationship between IGF-1 and uric acid levels. Methods and results1430 adult non diabetic subjects were stratified into quartiles according to their circulating IGF-1 values. Significant differences in uric acid concentration, measured by the URICASE/POD method were observed between low (quartile 1), intermediate (quartile 2 and 3), and high (quartile 4) IGF-1 levels groups after adjusting for age, gender, and body mass index (P = 0.02). These differences remained significant after adjustment for blood pressure, total cholesterol, high density lipoprotein, triglycerides, fasting and 2 h post-load glucose levels, HOMA-IR index (P = 0.005), liver enzymes (P = 0.03), glucose tolerance status (P = 0.02), growth hormone levels (GH) (P = 0.05), anti-hypertensive treatments (P = 0.04) or diuretics use (P = 0.04)). To clarify the molecular links between IGF-1 and uric acid, we performed an in vitro study, incubating human hepatoma cells with uric acid for 24 or 48 h in the presence of GH and observed a 21% and 26% decrease, respectively, in GH-stimulated IGF-1 mRNA expression (P = 0.02 and P = 0.012, respectively). This effect appears to be mediated by uric acid ability to down regulate GH intracellular signaling; in fact we observed a significant decrease of GH activated JAK2 and Stat5 phosphorylation. ConclusionsThese data demonstrate an inverse relationship between IGF-1 and uric acid levels in adults and suggest that uric acid might affect hepatic IGF-1 synthesis.

Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity.

Attenuated growth hormone and insulin-like growth factor-1 (GH/IGF-1) signaling is associated with extended lifespan in several animal models. However, the effect of diminished GH/IGF-1 activity on survival in humans has not been confirmed. We tested the hypothesis that IGF-1 levels in nonagenarians (n = 184), measured at study enrollment, predict the duration of their incremental survival. In the Kaplan–Meier analysis, females with IGF-1 levels below the median (≤ 96 ng mL−1) had significantly longer survival compared with females with levels above the median, P < 0.01. However, this survival advantage was not observed in males (P = 0.83). On the other hand, in both males and females with a history of cancer, lower IGF-1 levels predicted longer survival (P < 0.01). IGF-1 level remained a significant predictor of survival duration in linear regression models after multivariable adjustment in females (P = 0.01) and individuals with a history of cancer (P < 0.01). We show for the first time that low IGF-1 levels predict life expectancy in exceptionally long-lived individuals.

Serum Insulin-Like Growth Factor-1 Predicts Disease Progression and Survival in Patients with Hepatocellular Carcinoma Who Undergo Transarterial Chemoembolization

Insulin like-growth factor-1 (IGF-1) reflects hepatic synthetic function and plays a major role in the development and progression of various cancers. In the present study, we investigated whether baseline serum IGF-1 levels predict time-to-progression (TTP) and overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). A total of 155 consecutive treatment-naive patients with HCC who had undergone TACE as initial treatment were included from a prospective cohort. Baseline serum IGF-1 levels were analyzed with regard to their associations with disease progression and survival. During a median follow-up period of 41.8 months, patients with low IGF-1 levels showed significantly shorter TTP (median, 6.0 months; 95% confidence interval [CI], 4.5–7.6) than patients with high IGF-1 levels (median, 16.5 months; 95% CI, 4.9–28.1; p = 0.003). In the multivariate analysis, BCLC stage, serum vascular endothelial growth factorlevels, and IGF-1 levels were independent risk factors for disease progression. The hazard ratio (HR) of progression for each 10 ng/mL decrease in IGF-1 level was 1.072 (95% CI, 1.029–1.117; p = 0.001). Furthermore, together with tumor size, stage, and treatment response, IGF-1 levels were an independent predictor of poorer survival (for each 10 ng/mL decrease in IGF-1 level; HR, 1.057; 95% CI, 1.001–1.115; p = 0.045). In conclusion, low baseline IGF-1 levels independently correlated with shorter TTP and poorer OS in patients with HCC who underwent TACE.

Association between Noninvasive Fibrosis Markers and Chronic Kidney Disease among Adults with Nonalcoholic Fatty Liver Disease

Evidence suggests that nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are associated with an increased risk of chronic kidney disease (CKD). In this study we aimed to evaluate whether the severity of liver fibrosis estimated by NAFLD fibrosis score is associated with higher prevalence of CKD in individuals with NAFLD. To this end NAFLD fibrosis score and estimated glomerular filtration rate (eGFR) were assessed in 570 White individuals with ultrasonography-diagnosed NAFLD. As compared with subjects at low probability of liver fibrosis, individuals at high and intermediate probability showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein, fibrinogen, uric acid and lower insulin-like growth factor-1 levels. Individuals at high and intermediate probability of liver fibrosis have lower eGFR after adjustment for gender, smoking, glucose tolerance status, homeostasis model assessment index of insulin resistance (HOMA-IR index), diagnosis of metabolic syndrome, statin therapy, anti-diabetes and anti-hypertensive treatments (P = 0.001). Individuals at high probability of liver fibrosis had a 5.1-fold increased risk of having CKD (OR 5.13, 95%CI 1.13–23.28; P = 0.03) as compared with individuals at low probability after adjustment for age, gender, and BMI. After adjustment for glucose tolerance status, statin therapy, and anti-hypertensive treatment in addition to gender, individuals at high probability of liver fibrosis had a 3.9-fold increased risk of CKD (OR 3.94, 95%CI 1.11–14.05; P = 0.03) as compared with individuals at low probability. In conclusion, advanced liver fibrosis, determined by noninvasive fibrosis markers, is associated with CKD independently from other known factors.

The role of insulin-like growth factor-1 in development of coronary no-reflow and severity of coronary artery disease in patients with acute myocardial infarction.

IntroductionInsulin-like growth factor-1 (IGF-1) has atheroprotective effects via reduction in oxidative stress, cellular apoptosis, pro-inflammatory signaling, and endothelial dysfunction.AimWe hypothesized that low levels of IGF-1 may be associated with the severity and extent of coronary artery disease and development of the coronary no-reflow phenomenon in patients with acute ST-elevation myocardial infarction (STEMI) and investigated the role of the IGF-1 molecule in the coronary no-reflow phenomenon and severity of coronary artery disease (CAD) in patients with acute STEMI in a tertiary hospital.Material and methodsThe study was conducted among 113 patients undergoing primary percutaneous coronary intervention (PPCI) for STEMI, of whom 49 patients developed the no-reflow phenomenon. Coronary no-reflow was defined as Thrombolysis In Myocardial Infarction (TIMI) flow grade 2 or less after intervention. Insulin-like growth factor-1 levels were measured in both groups. The severity and extent of CAD were evaluated according to the Gensini and Syntax scores.ResultsAlthough IGF-1 levels were lower in the no-reflow group, there was not a statistically significant difference between the no-reflow group and the control group (116.65 ±51.72 vs. 130.82 ±48.76, p = 0.130). Gensini and Syntax scores were higher in the no-reflow group. There was no association between Gensini and Syntax scores and IGF-1 levels (r = –0.071, r = 0.479, r = –0.158, p = 0.113).ConclusionsIn this study, IGF-1 levels were not statistically different between patients developing the no-reflow phenomenon and controls. There was no association between development of the no-reflow phenomenon and severity of CAD or IGF-1 levels. Nevertheless, large scale studies are needed to verify these results.

Alkaline phosphatase and insuline-like growth factor-1 levels in Tayanç-Prasad syndrome: A case report

Tayanc-Prasad Syndrome is characterized by geophagia, iron defi ciency anemia, hepatosplenomegaly, skin changes, hypogonadism, and retardation of growth and development. A 13.5 year-old female patient who had geophagia for approximately 5–6 years, presented with an ongoing diarrhea 3–4 days a week for the last 4–5 years, headache, loss of appetite, palpitations, and pallor for one year. The patient had an iron defi ciency anemia, and low levels of ALP (alkaline phosphatase) and IGF-1 (insulin-like growth factor-1). The patient was treated with ferroglycine sulfate and zinc sulfate. After the 6 month follow-up, there were an increase in height of approximately 2 cm, a weight gain of 6.7 kg, a chest girth increment of 5.5 cm, and an increment of the upper mid-arm circumference of 4 cm. The hepatosplenomegaly disappeared. Anemia and ALP level improved signifi cantly. As a result, zinc defi ciency should be suspected in a patient with iron defi ciency anemia, low ALP levels, as well as geophagia. Although decreased levels of zinc, ALP and IGF-1 were detected in this particular case, more research is required in a larger number of patients.

Relationship between use of proton pump inhibitors and IGF system in older subjects.

to investigate the effects of proton pump inhibitors (PPIs) on the insulin-like-growth factor 1(IGF-1) system in the elderly. cross-sectional. InCHIANTI study. 938 older subjects (536 women, 402 men, mean age 75.7±7.4 years). complete data on age, sex, BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1 and -3 (IGFBP-1, IGFBP-3). Participants were categorized by PPI use, identifying 903 PPI non users and 35 users. After adjusting for age, male PPI users (107.0 ± 69.6 vs. 127.1 ± 55.8, p<0.001) and female PPI users (87.6 ± 29.1 vs. 107.6 ± 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1 levels were similar in the two groups in both sexes. In whole population, after adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1-113.8] than non-users 110 [77.8-148.6], p=0.02. After further adjustment for BMI, albumin, liver function, C-reactive protein, Interleukin-6, number of medications, ACE-inhibitors use, caloric intake, protein intake, physical activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and negatively associated with IGF-1 levels (β±SE = -19.60±9.83, p=0.045). Use of PPIs was independently and negatively associated with IGF-1 levels.

Abstract A11: Insulin-like growth factor vaccine for the global prevention of adult cancers

Abstract The purpose of this study is to develop a single vaccine that will prevent a variety of different cancers. It functions by reducing the supply of insulin-like growth factor (IGF) required for carcinogenesis. A safe, widely applicable preemptive treatment can greatly curtail cancer deaths. Primary prevention precludes the confounding problems associated with advanced cancer such as its resistance to treatment, its eventual recurrence and the progression to metastatic disease. This novel prevention strategy is based on studies of a small population of individuals in Ecuador who are cancer free their entire lifetime due to genetically low IGF levels. In contrast, 14% of their IGF-replete relatives succumbed to 20 different types of malignancy. That compelling human example of the benefit of reduced IGF activity suggests that the initiation or early progression of many cancers requires IGF. Thus, the objective is to develop protective vaccines to neutralize the multiple activities of IGF that promote oncogenesis. The ultimate goal is to vaccinate at risk adults and achieve the same protection from cancer experienced by the IGF-deficient Ecuadorians. The concept is predicated on the hypothesis that a lingering high level of IGF stimulation is superfluous after adolescence and, in later years, becomes detrimental to health. There are strong survival benefits for its simultaneous mitogenic, hypertrophic and antiapoptotic activities to operate during growth and development. Alas, there is no evolutionary pressure to develop a post-reproductive IGF shutoff mechanism. So, as science and medicine steadily extend the human lifespan, we find ourselves in the dilemma of having to accommodate a persistent pro-cancer hormone with little or no other purpose. This hypothesis fits with the age dependent increase of cancer incidence. Conventional and cutting-edge, nanofiber-based epitope vaccines have been produced to test this idea. They are designed to actively induce antibodies that either neutralize IGF directly or block a key enzyme that regulates IGF bioavailability. The continuous presence of such inhibitory antibodies would keep IGF activity at a constantly low level and thereby preemptively block the development of incipient cancers later in life. Antisera from mice immunized with those vaccines contained epitope-specific IgG antibodies that were reactive with recombinant IGF in ELISA studies. An ultrafiltration method was also used to demonstrate specific binding of recombinant 125I-IGF after incubation with undiluted antiserum versus non-immune control sera (conditions that mimic in vivo therapy). Exploratory tests indicated that the vaccine delayed the appearance of tumors in mice that develop sarcomas due to SV40 Tag expression. Safety is undeniably paramount for any new cancer prevention therapy and apprehension about targeting the ubiquitously expressed IGF is understandable. In terms of human health consequences however, the IGF-deficient Ecuadorians represent a worst-case scenario since they are severely depleted from birth onwards. Although very short due to their life-long IGF deficit, this cancer-free population is surprisingly healthy and long-lived (some &amp;gt;80 years old). Nevertheless, to further ensure safety the IGF-suppressive vaccines will be administered exclusively to fully grown and developed adults. Preemptive vaccination at 40-50 years old would be most effective since a majority of human malignancies occur beyond the age of 60 and because this postponement will circumvent impairment of normal growth or other juvenile functions. The prevention vaccines could be used; 1) for people with a genetic likelihood to develop familial cancer, 2) as an adjuvant following precancerous growth removal, 3) to inhibit relapse for patients in remission, and 4) as a general prophylactic to curtail sporadic, age-dependent cancers. Citation Format: Victor Raso. Insulin-like growth factor vaccine for the global prevention of adult cancers. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A11.

Study of Primary IGF-1 Deficiency in Egyptian Children with Idiopathic Short Stature

Background/Aims: Primary insulin-like growth factor-1 (IGF-1) deficiency (IGFD) is defined by low levels of IGF-1 without growth hormone (GH) deficiency and absence of secondary causes. The aim of this study was to evaluate IGF-1 in Egyptian children with idiopathic short stature (ISS) and describe patients with IGFD. Methods: This cross-sectional study included 50 children with ISS following up at the Diabetes Endocrine and Metabolism Pediatric Unit at Cairo University Pediatric Hospital. Children were included based on the following criteria: (1) short stature with current height standard deviation score (SDS) ≤-2.5; (2) age between 2 and 9 years in boys and 2 and 8 years in girls, and (3) prepubertal status. Exclusion criteria were: (1) identified cause of short stature and (2) pubertal children. IGF-1-deficient children were defined as children without GH deficiency and with IGF-1 levels below the 2.5th percentile. Results: Among 50 children with ISS, 14 (28%) patients had low IGF-1 levels, consistent with the diagnosis of primary IGFD. When compared with non-IGFD children, IGFD children had lower birth weight SDS (-1.8 vs. -0.7 SDS, p < 0.0001) and lower height SDS (-4.2 vs. -3.1 SDS, p < 0.05) and more delayed bone age (2.6 vs. 1.6 years, p = 0.001). Conclusion: Primary IGF-1 deficiency is found in 28% of children with ISS.

Increased IGF-1 serum levels and discordant protein and mRNA IGF-1 receptor expression in the small intestine of formula-fed piglets

The present investigation addresses the question whether feeding piglets on formulated milk alters the insulin-like growth factor-1 (IGF-1) system differently in normal versus low birth weight piglets. In this study, both types of piglets were either sow-fed until 28 days of age or until 3 days of age and subsequently formula-fed until day 28. Formula-fed piglets had higher serum IGF-1 levels compared to suckled piglets, whereas low birth weight piglets had lower IGF-1 levels in comparison with normal birth weight piglets. In contrast, the mRNA expression of IGF-1 receptor (IGF-1R) showed lower expression in formula-fed piglets versus suckled piglets. However, the opposite effect was observed for IGF-1R protein abundance. Moreover, birth weight did not markedly affect IGF-1R mRNA or protein abundance. In conclusion, formula-fed piglets have higher IGF-1 serum levels and altered gene and protein expression of IGF-1R in the small intestine, irrespective of their birth weight.

Insulin‐like growth factor‐1 predicts cognitive functions at 2‐year follow‐up in early, drug‐naïve Parkinson's disease

Cognitive impairment is common in Parkinson's disease (PD), even in the early stages. We aimed to assess the relationship between insulin-like growth factor-1 (IGF-1) and cognitive functions in early, drug-naïve patients with PD. Serum IGF-1 was measured in 65 early, drug-naïve patients with PD that underwent a complete neuropsychological battery at baseline and after 2 years. Linear regression analysis was used to evaluate the relationships between neuropsychological scores and IGF-1. Repeated-measures anova was applied to assess changes in neuropsychological variables over time. At baseline, IGF-1 levels were related to phonological fluency. At follow-up, IGF-1 levels were associated with the Rey auditory verbal learning test (RAVLT) - immediate and delayed recall, Frontal Assessment Battery, verbal span and Benton judgement of the line orientation test. Patients with low IGF-1 levels at baseline showed a significantly faster decline of performances than patients with high IGF-1 levels on immediate and delayed recall of the RAVLT and interference task of the Stroop test. Low serum IGF-1 levels are related to poor performance on executive tasks in early, drug-naïve patients with PD, and may predict poor performance on attention/executive and verbal memory tasks after a 2-year follow-up.

The GH/IGF-1 Axis in Chronic Heart Failure

The classic model of Chronic Heart Failure (CHF) is rooted in the overexpression of neurohormonal molecules. To complement this paradigm, increasing evidence indicates that a variety of hormones may be down-regulated in CHF patients. The list includes growth hormone (GH) and its tissue effector insulin-like growth factor-1 (IGF-1). The GH/IGF-1 axis regulates cardiac growth, stimulates myocardial contractility, and influences the vascular system. The relationship between the GH/IGF-1 axis and the cardiovascular system has been extensively demonstrated in numerous studies in animals models and confirmed by the cardiac derangements secondary to both GH excess and deficiency in humans. Impaired activity of the GH/IGF-1 axis in CHF has been described by several independent groups and includes a wide array of abnormalities, including low IGF-1 levels, GH deficiency (GHD), and GH resistance that may be related to the severity of heart disease. According to several observations, these derangements are associated with poor clinical status and outcome. Since the first study of GH therapy in CHF in 1996, several placebo-controlled trials have been conducted with conflicting results. These discordant findings are likely explained by the degree of CHF-associated GH/IGF-1 impairment that may impact on individual responsiveness to GH administration. Biological actions of GH and IGF-1, cardiovascular implication of GH deficiency and GH excess, relation between somatotrophic axis and CHF are discussed. Results from trials of GH therapy, emerging therapeutic strategies, safety issues, and lack in evidence are also reported.

IGF-1 and IGFBP-3 in patients with liver disease/IGF-1 und IGFBP-3 bei Patienten mit Lebererkrankungen

Abstract Background: Hepatic stellate cells are stimulated by insulin-like growth factor 1 (IGF-1) and high IGF-1 levels attenuate fibrogenesis and accelerate liver regeneration. This effect is mainly mediated by upregulation of hepatic growth factor and downregulation of transforming growth factor β1. Thus, decreased IGF-1 levels in patients point to an impaired regeneration potential in chronic liver failure. The objective of this study was to evaluate the relation between liver dysfunction and levels of IGF-1 and IGF-binding protein 3 (IGFBP-3) levels. Methods: One hundred and twenty-seven patients aged 45 to 60 years (36 women, 91 men) with diagnosed liver disease were recruited for the study. From the Study of Health in Pomerania (SHIP), 508 healthy individuals were matched for age and sex as the control group. Associations between laboratory parameters of liver failure and IGF-1 or IGFBP-3 were examined. Serum IGF-1 and serum IGFBP-3 levels were measured by automated two-site chemiluminescence immunoassays. Results: IGF-1 and IGFBP-3 levels were significantly lower in patients with liver diseases. There was no detectable homogeneous relation between liver transaminases and IGF-1 or IGFBP-3 levels in the patient group alone. Patients with a Child Pugh Score of C revealed lower levels of IGF-1 than patients with Child Pugh Scores of B or A. In IGFBP-3, this association was also apparent, but statistically not significant. In pooled analyses of patients and healthy controls, negative associations between aspartate aminotransferase (ASAT) and γ-glutamyltranspeptidase (GGT) activities and IGF-1 and IGFBP-3 levels, as well as between alanine aminotransferase (ALAT) activity and IGF-1 levels were detected. Conclusions: We demonstrated that compared with healthy controls patients with liver disease exhibited lower IGF-1 and IGFBP-3 levels.

A study of bone mineral density and its determinants in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) has been inconsistently associated with low bone mineral density (BMD) and increased fracture risk. 86 consecutive T1DM cases and 140 unrelated age and sex matched healthy nondiabetic controls were included in the study. After history and examination, BMD and body composition were assessed by dual energy X-ray absorptiometry (DXA). Serum samples were analyzed for calcium, phosphorus, albumin, creatinine, alkaline phosphatase, 25 (OH) vitamin D3, intact parathormone (PTH) levels (both cases and controls) and HbA1c, antimicrosomal and IgA tissue transglutaminase (IgA TTG) antibodies, cortisol, follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG), tetraiodothyronine (T4), thyroid stimulating hormone (TSH), growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP3) (cases only). T1DM cases had a lower BMD as compared to controls at both total body (TB) and lumbar spine (LS) (P < 0.05). Patients with celiac autoimmunity (CA) had significantly, lower BMD as compared to age, sex, and body mass index (BMI) matched T1DM controls. Linear regression analysis showed that low BMD in T1DM patients was associated with poor glycaemic control, lower IGF-1 levels, less physical activity (in total population as well as in male and female subgroups), and lower body fat percentage (in females) and higher alkaline phosphatase level (in males) (P < 0.05).

One‐hour post‐load plasma glucose and IGF‐1 in hypertensive patients

In normoglucose-tolerant subjects (NGT), 1-h post-load plasma glucose value ≥155 mg/dL, during an oral glucose tolerance test (OGTT), is associated with an increased risk of type-2 diabetes (T2D) and subclinical organ damage. Insulin-like growth factor-1 (IGF-1) is involved in the pathogenesis of insulin resistance (IR) and T2D. Moreover, hypertensives have different degrees of IR and different levels of IGF-1. Actually, there are no data supporting the association between post-load glucose and IGF-1; thus, the aim of the study was to investigate this relationship. We enrolled 1126 never-treated hypertensive subjects who underwent an OGTT and clinical characterization. Insulin sensitivity was assessed by the Matsuda index. IGF-1 was measured by a sensitive immunoradiometric assay. Among participants, 764 had NGT, 263 had impaired glucose tolerance (IGT) and 99 had T2D. According to the 1-h post-load plasma glucose cut-off point of 155 mg/dL, we divided NGT subjects into NGT < 155 mg/dL and NGT ≥ 155 mg/dL. NGT ≥ 155 in comparison with NGT < 155 had significantly reduced insulin sensitivity and IGF-1 levels. At multiple regression analysis, IGF-1 was the major determinant of 1-h post-load glucose in NGT ≥ 155 subjects, IGT and diabetics, accounting for 20·9%, 17·7% and 15·5% of its variation in the respective models. In hypertensive NGT ≥ 155 subjects, IGF-1 results strongly associated with 1-h post-load glucose, similarly to that observed in IGT and diabetics. This finding has clinical relevance because both low IGF-1 levels and 1-h post-load glucose in NGT subjects are associated with subclinical organ damage, an independent predictor of cardiovascular events.