Elevated Serum Insulin-like Growth Factor Research Articles

Machine learning analysis of the UK Biobank reveals IGF-1 and inflammatory biomarkers predict Parkinson's disease risk.

Parkinson's disease (PD) is the most common movement disorder, and its prevalence is increasing rapidly worldwide with an ageing population. The UK Biobank is the world's largest and most comprehensive longitudinal study of ageing community volunteers. The cause of the common form of PD is multifactorial, but the degree of causal heterogeneity among patients or the relative importance of one risk factor over another is unclear. This is a major impediment to the discovery of disease-modifying therapies. We used an integrated machine learning algorithm (IDEARS) to explore the relative effects of 1,753 measured non-genetic variables in 334,062 eligible UK Biobank participants, including 2,719 who had developed PD since their recruitment into the study. Male gender was the highest-ranked risk factor, followed by elevated serum insulin-like growth factor 1 (IGF-1), lymphocyte count, and neutrophil/lymphocyte ratio. A group of factors aligned with the symptoms of frailty also ranked highly. IGF-1 and neutrophil/lymphocyte ratio were also elevated in both sexes before PD diagnosis and at the point of diagnosis. The use of machine learning with the UK Biobank provides the best opportunity to explore the multidimensional nature of PD. Our results suggest that novel risk biomarkers, including elevated IGF-1 and NLR, may play a role in, or are indicative of PD pathomechanisms. In particular, our results are consistent with PD being a central manifestation of a systemic inflammatory disease. These biomarkers may be used clinically to predict future PD risk, improve early diagnosis and provide new therapeutic avenues.

Prevalence of sleep apnea and lung function abnormalities in patients with acromegaly.

Background:Sleep apnea (SA) is highly prevalent in acromegaly. Ethnicity influences the prevalence of SA in the general population. We studied the prevalence of SA and other respiratory comorbidities in North Indian patients with active acromegaly.Design:Prospective, observational.Materials and Methods:Consecutive adult patients with active acromegaly (n = 35, age 39.7 ± 13.2 years) and hypersomatotropism (nonsuppression of serum growth hormone after oral glucose and elevated serum insulin-like growth factor-1 [IGF-1]) were evaluated for respiratory symptoms, scoring for SA (Epworth Sleepiness Score [ESS] and STOP-BANG), pulmonary function tests (PFT), high-resolution computerized tomography (HRCT) of the thorax, polysomnography (PSG), and transthoracic echocardiography. Age- and sex-matched healthy individuals (n = 34) served as controls.Results:Acromegaly subjects had dyspnea (34%), cough (37%), excessive daytime somnolence (43%), and fatigue (49%). Clinically significant ESS (>10) and STOP-BANG score (≥3) were present in 41% and 68.6% of subjects, respectively. PFT showed restrictive and obstructive patterns in 45.7% and 11.4% of acromegalics respectively; with higher total lung capacity (TLC), thoracic gas volume (TGV), and residual volume (RV). PSG revealed significantly higher SA events in acromegalics (central [acromegaly 24.63 ± 37.82 vs. control 3.21 ± 5.5], mixed [11 ± 19.46 vs. 3.50 ± 5.96], obstructive [34.86 ± 44.37 vs. 9.71 ± 10.48], and mean apnea-hypopnea index [AHI] [16.91 ± 18.0 vs. 7.86 ± 7.84]). Acromegalics had significantly higher prevalence of obstructive SA (71.4% [mild 31.4%, moderate 20%, severe 20%]) as compared to controls (38.2%). There was no correlation of AHI with serum IGF-1 and disease duration.Conclusion:Acromegaly subjects have a significantly higher prevalence of respiratory symptoms, SA, and abnormalities in PFT. Screening for respiratory comorbidities should be routinely recommended in all patients with acromegaly.

Insulin-like growth factor-1 and site-specific cancers: A Mendelian randomization study.

Insulin‐like growth factor‐1 (IGF‐1) is involved in several processes relevant to carcinogenesis. We used 416 single‐nucleotide polymorphisms robustly associated with serum IGF‐1 levels to assess the potential causal associations between this hormone and site‐specific cancers through Mendelian randomization. Summary‐level genetic association estimates for prostate, breast, ovarian, and lung cancer were obtained from large‐scale consortia including individuals of European‐descent. Furthermore, we estimated genetic associations with 14 site‐specific cancers in European‐descent individuals in UK Biobank. Supplementary analyses were conducted for six site‐specific cancers using summary‐level data from the BioBank Japan Project. Genetically predicted serum IGF‐1 levels were associated with colorectal cancer. The odds ratio (OR) per standard deviation increase of IGF‐1 levels was 1.11 (95% confidence interval [CI] 1.01‐1.22; P = .03) in UK Biobank and 1.22 (95% CI 1.09‐1.36; P = 3.9 × 10−4) in the BioBank Japan Project. For prostate cancer, the corresponding OR was 1.10 (95% CI 1.01‐1.21; P = .04) in UK Biobank, 1.03 (95% CI 0.97‐1.09; P = .41) in the prostate cancer consortium, and 1.08 (95% CI 0.95‐1.22; P = .24) in the BioBank Japan Project. For breast cancer, the corresponding OR was 0.99 (95% CI 0.92‐1.07; P = .85) in UK Biobank and 1.08 (95% CI 1.02‐1.13; P = 4.4 × 10−3) in the Breast Cancer Association Consortium. There was no statistically significant association between genetically predicted IGF‐1 levels and 14 other cancers. This study found some support for a causal association between elevated serum IGF‐1 levels and increased risk of colorectal cancer. There was inconclusive or no evidence of a causal association of IGF‐1 levels with prostate, breast, and other cancers.

Effects of dietary inulin supplementation on growth performance, intestinal barrier integrity and microbial populations in weaned pigs.

Here, we explored the influences of dietary inulin (INU) supplementation on growth performance and intestinal health in a porcine model. Thirty-two male weaned pigs (with an average body weight of 7·10 (sd 0·20) kg) were randomly assigned to four treatments and fed with a basal diet (BD) or BD containing 2·5, 5·0 and 10·0 g/kg INU. After a 21-d trial, pigs were killed for collection of serum and intestinal tissues. We show that INU supplementation had no significant influence on the growth performance in weaned pigs. INU significantly elevated serum insulin-like growth factor-1 concentration but decreased diamine oxidase concentration (P < 0·05). Interestingly, 2·5 and 5·0 g/kg INU supplementation significantly elevated the villus height in jejunum and ileum (P < 0·05). Moreover, 2·5 and 5·0 g/kg INU supplementation also elevated the villus height to crypt depth (V:C) in the duodenum and ileum and improved the distribution and abundance of tight-junction protein zonula occludens-1 in duodenum and ileum epithelium. INU supplementation at 10·0 g/kg significantly elevated the sucrase activity in the ileum mucosa (P < 0·05). INU supplementation decreased the expression level of TNF-α but elevated the expression level of GLUT 2 and divalent metal transporter 1 in the intestinal mucosa (P < 0·05). Moreover, INU increased acetic and butyric acid concentrations in caecum (P < 0·05). Importantly, INU elevated the Lactobacillus population but decreased the Escherichia coli population in the caecum (P < 0·05). These results not only indicate a beneficial effect of INU on growth performance and intestinal barrier functions but also offer potential mechanisms behind the dietary fibre-regulated intestinal health.

Associations between circulating bone-derived hormones osteocalcin, lipocalin 2, and glucose metabolism in patients with acromegaly

Objective The aim of this study was to examine the change of serum bone-derived hormones osteocalcin and lipocalin 2 (LCN2) level in patients with active acromegaly, and to further investigate the potential role of osteocalcin and LCN2 in glucose metabolism. Methods Fifty consecutive patients diagnosed as acromegaly in Nanjing Drum Tower Hospital from December 2016 to August 2018 were recruited. Of those, 41 patients after operations with complete follow-up data were also included. 30 sex, age, and body mass index matched healthy persons as normal controls. Serum osteocalcin and LCN2 levels were compared between controls and patients with acromegaly, as well as at pre- and post- operation periods. Univariate and multivariate linear regression analyses were used to investigate the correlation between bone-derived hormones and glucose metabolism indexes and to determine the independent associations between variables. Results Compared with normal controls, serum osteocalcin increased [(55.45±34.02 vs 19.46±6.69)ng/ml, P 0.05). After operation, with the decrease of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1), serum osteocalcin level decreased [24.79(18.39, 32.59) vs 43.51(26.73, 65.66)ng/ml, P<0.01] and LCN2 level increased [(45.15±15.33 vs 37.03±9.73)ng/ml, P<0.05] significantly compare to pre-operation levels. In a multivariate linear stepwise regression analysis, lean mass was shown to be the only positive predictor for LCN2 (β=0.44, P=0.015) and elevated serum IGF-1 was a positive predictor for osteocalcin (β=0.512, P<0.01). In the multivariate models, low LCN2 (β=-0.398, P=0.017) and elevated serum osteocalcin (β=0.553, P=0.001) were predictors for AUCINS, osteocalcin was a positive predictor of HOMA- β (β=0.519, P=0.004). GH (β=0.294, P=0.029) and IGF-1(β = 0.428, P=0.002) were all identified as positive predictors of HOMA-IR during multivariate testing in acromegaly patients. Conclusions Acromegaly patients had increased osteocalcin and decreased LCN2 serum levels, and corresponding alteration was detected with the correction of biochemical abnormalities. Serum osteocalcin and LCN2 were predictors of β-cell function in acromegaly patients. This study adds new evidence for the role of bone in regulating glucose metabolism in acromegaly. Key words: Acromegaly; Osteocalcin; Lipocalin 2; Glucose metabolism

Role of insulin-like growth factor 1 in pathogenesis of acne vulgaris: relation to acne severity and body mass index

&lt;div class="Section1"&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Acne vulgaris is a multifactorial skin disease. A potential role for insulin-like growth factor-1 (IGF-1) has been suggested in the pathogenesis of acne. Several studies have shown that elevated levels of serum IGF-1 correlate with overproduction of sebum and acne. Objective: Measurement of the serum level of IGF-1 in acne patients in comparison to normal controls and evaluating the relationship of these levels to severity of acne and body mass index (BMI), in order to investigate the role of this factor in the pathogenesis of acne.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Fifty-four patients with acne vulagaris and 42 healthy controls were included. History taking, dermatological examination, clinical assessments of acne severity, calculation of BMI were performed for patients. Blood samples were collected from all participants for estimation of serum IGF-1 level using enzyme linked immunosorbant assay.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; There was a significantly higher serum IGF-1 level in acne patients (p&amp;lt;0.05) than controls. Authors didn’t find a relation of significance between elevated serum IGF-1 level and degree of acne severity and BMI (p&amp;gt;0.05). There was a significant positive correlation between serum IGF-1 level and age of the patients.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; There is a significantly higher serum IGF-1 in acne patients than controls not related to acne severity and BMI. That is adding to the scientific evidence of IGF-1 role in pathogenesis of acne vulgaris.&lt;/p&gt;&lt;/div&gt;

Can the sFLC assay help on the optimization of the use of 24h urines in patients with monoclonal gammapathies?

Acromegaly is typically caused by a growth hormone–secreting pituitary adenoma, driving excess secretion of insulin-like growth factor 1. Acromegaly may result in a variety of cardiovascular, respiratory, endocrine, metabolic, musculoskeletal, and neoplastic comorbidities. Early diagnosis and adequate treatment are essential to mitigate excess mortality associated with acromegaly.PubMed searches were conducted using the keywords growth hormone, acromegaly, pituitary adenoma, diagnosis, treatment, pituitary surgery, medical therapy, and radiation therapy (between 1981 and 2021).The diagnosis of acromegaly is confirmed on biochemical grounds, including elevated serum insulin-like growth factor 1 and lack of growth hormone suppression after glucose administration. Pituitary magnetic resonance imaging is advised in patients with acromegaly to identify an underlying pituitary adenoma.Transsphenoidal pituitary surgery is generally first-line therapy for patients with acromegaly. However, patients with larger and invasive tumors (macroadenomas) are often not in remission postoperatively. Medical therapies, including somatostatin receptor ligands, cabergoline, and pegvisomant, can be recommended to patients with persistent disease after surgery. Select patients may also be candidates for preoperative medical therapy. In addition, primary medical therapy has a role for patients without mass effect on the optic chiasm who are unlikely to be cured by surgery. Clinical, endocrine, imaging, histologic, and molecular markers may help predict the response to medical therapy; however, confirmation in prospective studies is needed. Radiation therapy is usually a third-line option and is increasingly administered by a variety of stereotactic techniques. An improved understanding of the pathogenesis of acromegaly may ultimately lead to the design of novel, efficacious therapies for this serious condition.

Relationship between serum levels of osteoproteins, inflammatory cytokines and coronary heart disease and disease severity

To explore the relationship between serum levels of osteoprotein (OPG), soluble nuclear factor-κB receptor activator ligand (sRANKL), inflammatory factors and coronary heart disease (CHD) and its severity. The patients who underwent coronary angiography (CAG) due to chest pain admitted to department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled, and they were divided into CHD group and non-CHD group according to the CAG results. The gender, age, history of hypertension, smoking history, diabetes, the levels of cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB), lipoprotein (a) [Lp (a)], MB isoenzyme of creatine kinase (CK-MB) and other clinical data of patients were collected. The serum levels of OPG, sRANKL, matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). According to the results of CAG, the patients with CHD were divided into single-, double-, triple-branch coronary artery lesion groups, and the relationship between the levels of serum OPG, sRANKL, inflammatory factors and the degree of coronary artery lesions was observed. Multivariate Logistic regression was used to analyze the risk factors of CHD, and receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of main risk factors for CHD. A total of 472 patients were enrolled in the final analysis during the study period, including 264 patients in the CHD group, 208 patients in the non-CHD group, 79 patients in the CHD group with single-branch disease, 75 patients with double-branch disease, and 110 patients with three-branch disease. (1) Compared with the non-CHD group, the CHD group had more older male patients, as well as higher proportion of hypertension and diabetes, the levels of serum Lp (a) and CK-MB were significantly increased, and the levels of serum HDL-C and apoAI were significantly lowered. There was no statistically significant difference in serum TC, LDL-C, or apoB between the two groups. The levels of serum OPG, MMP-9, MCP-1, IGF-1 and IL-6 in the CHD group were significantly higher than those in the non-CHD group [OPG (μg/L): 1.79±0.50 vs. 1.50±0.30, MMP-9 (μg/L): 57.91 (33.50, 130.46) vs. 38.33 (29.43, 109.78), MCP-1 (μg/L): 298.30 (207.96, 537.16) vs. 252.73 (165.22, 476.01), IGF-1 (μg/L): 734.03±486.11 vs. 217.75±126.45, IL-6 (ng/L): 64.76±40.25 vs. 48.60±15.80, all P < 0.05], and the levels of serum sRANKL was significantly lower than that in the non-CHD group (ng/L: 344.31±122.14 vs. 378.74±109.27, P < 0.05). (2) The serum OPG level showed a slight upward tendency with the increase in the number of coronary artery lesions, and the sRANKL level showed a slight downward tendency [OPG (μg/L) in the single-, double-, triple-branch coronary artery lesion groups was 1.74±0.49, 1.76±0.50, 1.85±0.52, and sRANKL (ng/L) was 354.96±116.64, 340.05±124.24, 339.57±125.03, respectively) without statistically significant differences (all P > 0.05). The levels of IGF-1 and IL-6 were increased with the number of coronary artery lesions [IGF-1 (μg/L) in the single-, double- and triple-branch coronary artery lesions groups was 372.13±258.42, 676.06±350.29, 1 033.47±468.06, and IL-6 (ng/L) was 48.87±16.72, 65.36±18.84, 75.76±22.72, respectively], and the differences among different lesion groups were statistically significant (all P < 0.01). Correlation analysis showed that IGF-1 level was significantly positively correlated with the number of coronary artery lesions (r = 0.612, P < 0.01), while IL-6 was not correlated with the number of coronary artery lesions (r = 0.185, P > 0.05). (3) Multivariate Logistic regression analysis showed that elevated serum OPG and IGF-1 levels were risk factors for CHD [OPG: odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.936-2.067, P = 0.012; IGF-1: OR = 1.009, 95%CI = 1.004-1.015, P = 0.001]. (4) ROC curve analysis showed that the area under ROC curve (AUC) of OPG and IGF-1 was 0.716 and 0.867, respectively. When the cut-off value of OPG was 1.13 μg/L, the sensitivity was 81.7%, the specificity was 58.1%; when the cut-off value of sRANKL was 401.20 μg/L, the sensitivity was 69.7%, the specificity was 95.7%. CHD was associated with increased in OPG, related inflammatory cytokines including MMP-9, MCP-1, IGF-1 and IL-6, and decreased in sRANKL. The level of IGF-1 was positively correlated with the severity of CHD. The serum levels of OPG and IGF-1 were risk factors for CHD, which had good predictive value for CHD.

SAT-467 Gigantism Caused by Growth Hormone-Secreting Pituitary Macroadenoma: A Case Report

Background Gigantism is a rare condition where excessive secretion of growth hormone (GH) occurs before fusion of the epiphyseal growth plates. Clinical Case A 23-year-old Sri Lankan male presented to the Endocrine clinic with extreme tall stature, and was diagnosed to have pituitary gigantism. He had been the tallest in his class since 5 years old. Pubertal development from 12 years of age was normal. There was no history of headache, visual disturbance, galactorrhea or any hypogonadal symptoms. Family history was non-contributory. On examination, there were clinical features of frontal bossing, prognathism, and prominence of supra-orbital ridge. He was 196cm in height (calculated midparental height of 171cm) and at Tanner stage 5. Initial medical treatment was started with cabergoline for 1 year, before decision for surgical treatment was sought in Singapore. Initial laboratory investigations revealed an elevated serum insulin-like growth factor-1 (IGF-1) value of 577ng/mL (RR: 116-358ng/mL), and failure of GH suppression during an oral glucose tolerance test, with GH nadir of 3.99 ng/mL (RR: <1 to 13.4ng/mL, no gender nor age-specific cut offs were provided). Prolactin was 132 mIU/L (RR 77-274mIU/L) and total testosterone was 11 nmol/L (RR 5-30nmol/L). Basal cortisol, thyroid function test, and calcium levels were normal. Pituitary magnetic resonance imaging showed a hypo-enhancing focus in the left lateral aspect of the pituitary gland with extension into the sphenoid sinus, measuring 12mm in size at largest diameter, which was suspicious for a pituitary adenoma. He subsequently underwent transphenoidal surgery, and there were no immediate complications post operatively. During a follow up visit 3 months after surgery, laboratory investigations showed normalization of GH (0.33 ng/mL), IGF-1 (212 ng/mL) levels, and normal GH suppression during OGTT. Conclusion Pituitary gigantism occurs during the pre-pubertal period of active linear growth, where elevated GH and IGF-1 levels result in extreme growth acceleration and tall stature (1). The treatment of choice for well-circumscribed pituitary adenomas is transphenoidal surgery, which may be curative (2).

Elevated insulin-like growth factor-1 in Cushing's disease.

To determine if patients with untreated Cushing's disease have higher serum insulin-like growth factor-1 (IGF-1) compared to matched controls, and if IGF-1 decreases following remission of Cushing's disease. Retrospective case-control study matching Cushing's disease cases to control patients for adenoma size, age, sex, diabetic and gonadal status, body mass index and serum IGF-1 measured within one year. Paired analysis of pre-operative (untreated) and >3months post-operative (remission) serum IGF-1 for cases. All patients were investigated at the Princess Alexandra Hospital Endocrine Unit between 2005 and 2017. Serum IGF-1 was measured in 25 cases and 49 controls, 23 case-control pairs and 13 cases pre- and post-operatively. Mean serum IGF-1 in cases was significantly higher compared to controls-32±12nmol/L compared to 25±8nmol/L, (P=0.005). The proportion of cases with elevated serum IGF-1 above an age-adjusted reference range was higher compared to 1:1 matched controls (8/23 (35%) vs 1/23 (4%), P=0.02). In 13 cases in remission post-operatively, serum IGF-1 decreased significantly from 31 (IQR 29-40.5)nmol/L to 23 (IQR 15-28.5)nmol/L, (P<0.001), despite no difference in the prevalence of pre- vs post-operative pituitary hormone dysfunction (P=0.47). Patients with untreated Cushing's disease may have elevated IGF-1, which decreases following remission. Mildly elevated IGF-1 in Cushing's disease does not imply pathological growth hormone (GH) excess.

Elevated serum insulin-like growth factor 1 in recurrent aphthous stomatitis.

Over 100 million Americans experience recurrent aphthous stomatitis (RAS) at some point in life. To develop targeted drugs for RAS treatment, it is critical to identify its etiology. We determined if serum insulin‐like growth factor 1 (IGF‐1) and related factors are associated with RAS, because both RAS prevalence and IGF‐1 are highest during puberty. We analyzed data from 1,480 Third National Health and Nutrition Examination Survey participants aged 20–40 years. Participants with a history of diabetes or lupus, cotinine levels 6 ng/ml or higher or glycemia 110 mg/dl or higher were excluded. We compared levels of IGF‐1, IGFBP‐3, leptin, and insulin in participants with a positive vs. negative RAS history in the prior 12 months. We used logistic regression in SAS/SUDAAN to account for the complex sampling design. The odds of a positive RAS history were 1.31 times higher for every 100 ng/ml increase in serum IGF‐1. This association persisted after adjustment for age, race/ethnicity, medication intake, body mass index, insulin, leptin, glycemia, and income (adjusted OR = 1.30, 95% CI [1.06, 1.60]; p = 0.013). The odds of a positive RAS history were also higher among non‐Hispanic white compared with non‐Hispanic black participants (adjusted OR = 4.37, 95% CI [3.00, 6.38]). Leptin, IGFBP‐3, and insulin levels did not differ by RAS status. The significantly higher IGF‐1 levels in participants with a positive RAS history compared with controls suggest a possible role of the IGF‐1 pathway in RAS etiology.

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.

Gene Expression and Clinical Manifestations in Iraqi Patients with Acromegaly

Introduction Acromegaly is initiated by extreme growth hormone (GH) secretion and secondary elevation of insulin-like growth factor-1 (IGF-1). The occurrence of acromegaly is deliberate to be 3 to 4 cases per million for every year.1 Because GH secretion is pulsatile, elevated serum IGF-1 levels

C-reactive protein and insulin-like growth factor-1 in differential diagnosis of ascites.

Insulin-like growth factor-1 (IGF-1) and C-reactive protein (CRP) are produced mainly by the liver; the output of these markers in response to inflammatory processes may be affected in patients with hepatic dysfunction. This may explain the differences in IGF-1 and CRP values in patients with non-portal and portal hypertension ascites. We aimed to evaluate serum and ascitic fluid IGF-1 and CRP as diagnostic markers in the differential diagnosis of benign and malignant ascites. In this prospective study, 398 consecutive patients with ascites were included. Serum and ascitic fluid levels of IGF-1 and CRP were measured using an enzyme-linked immunosorbent assay. Patients were divided into group 1, due to benign ascites (n = 324), and group 2, due to malignant ascites (n = 74). Serum and ascitic IGF-1 were significantly increased in malignant ascites than benign ascites group [305 ± 65.7 ng/mL vs 95 ± 53.8 ng/mL; P < 0.001 and 288 ± 54.7 ng/mL vs 83.2 ± 36.7 ng/mL; P < 0.001], respectively. Serum and ascitic CRP were significantly higher in malignant ascites than benign ascites patients [12.8 ± 6.3 mg/mL vs 6.1 ± 4.9 mg/mL; P < 0.001 and 5.1 ± 2.2 mg/mL vs 1.6 ± 1.3 mg/mL; P < 0.001], respectively. At a cutoff value of 309.4 ng/mL and 7.8 mg/mL, serum IGF-1 and CRP had (95.1%, 81%) sensitivity and (88.6%, 75.5%) specificity for detecting malignant ascites [area under the curve: 0.932, 0.845], respectively. At a cutoff value of 291.6 ng/mL and 2.6 mg/mL, ascitic IGF-1 and CRP had (94.6%, 84%) sensitivity and (83.2%, 80.3%) specificity for detecting malignant ascites (area under the curve: 0.911, 0.893) correspondingly. Elevated serum and ascitic fluid IGF-1 and CRP levels were associated with malignant ascites.

Elevated IGF-1 with GH suppression after an oral glucose overload: incipient acromegaly or false-positive IGF-1?

To report the evolution of patients with a suggestive clinical scenario and elevated serum insulin-like growth factor-1 (IGF-1), but growth hormone (GH) suppression in the oral glucose tolerance test (OGTT), in whom acromegaly was not initially excluded. Forty six patients with a suggestive clinical scenario, who had elevated IGF-1 (outside puberty and pregnancy) in two measurements, but GH < 0.4 µg/L in the OGTT, were selected. Five years after initial evaluation, the patients were submitted to clinical and laboratory (serum IGF-1) reassessment. Patients with persistently elevated IGF-1 were submitted to a new GH suppression test and magnetic resonance imaging (MRI) of the pituitary. Four patients were lost to follow-up. During reassessment, 42 patients continued to show no "typical phenotype" or changes in physiognomy. Fifteen of the 42 patients had normal IGF-1. Among the 27 patients with persistently elevated IGF-1 and who were submitted to a new OGTT, GH suppression was confirmed in all. Two patients exhibited a lesion suggestive of microadenoma on pituitary MRI. In our interpretation of the results, acromegaly was ruled out in 40 patients and considered "possible" in only 2. Our results show that even in patients with a suggestive clinical scenario and elevated IGF-1, confirmed in a second measurement and without apparent cause, acromegaly is very unlikely in the case of GH suppression in the OGTT.

Elevated Serum Insulin-Like Growth Factor 1 Levels in Patients with Neurological Remission after Traumatic Spinal Cord Injury.

After traumatic spinal cord injury, an acute phase triggered by trauma is followed by a subacute phase involving inflammatory processes. We previously demonstrated that peripheral serum cytokine expression changes depend on neurological outcome after spinal cord injury. In a subsequent intermediate phase, repair and remodeling takes place under the mediation of growth factors such as Insulin-like Growth Factor 1 (IGF-1). IGF-1 is a promising growth factor which is thought to act as a neuroprotective agent. Since previous findings were taken from animal studies, our aim was to investigate this hypothesis in humans based on peripheral blood serum. Forty-five patients after traumatic spinal cord injury were investigated over a period of three months after trauma. Blood samples were taken according to a fixed schema and IGF-1 levels were determined. Clinical data including AIS scores at admission to the hospital and at discharge were collected and compared with IGF-1 levels. In our study, we could observe distinct patterns in the expression of IGF-1 in peripheral blood serum after traumatic spinal cord injury regardless of the degree of plegia. All patients showed a marked increase of levels seven days after injury. IGF-1 serum levels were significantly different from initial measurements at four and nine hours and seven and 14 days after injury, as well as one, two and three months after injury. We did not detect a significant correlation between fracture and the IGF-1 serum level nor between the quantity of operations performed after trauma and the IGF-1 serum level. Patients with clinically documented neurological remission showed consistently higher IGF-1 levels than patients without neurological remission. This data could be the base for the establishment of animal models for further and much needed research in the field of spinal cord injury.

Serum IGF-1 and IGFBP-3 levels as clinical markers for patients with lung cancer.

Insulin-like growth factor-1 (IGF-1) and its essential binding protein-3 (IGFBP-3) exhibit significant roles in cellular proliferation, differentiation and apoptosis in numerous malignancies, including lung cancer. The aim of the present study was to determine the clinical roles of the serum IGF-1 and IGFBP-3 levels in lung cancer patients. A total of 80 patients with lung cancer were enrolled in the study. Serum IGF-1 and IGFBP-3 concentrations were determined by ELISA methods. The median age of patients was 58.5 years old, with a range of 36-80 years. The majority of the patients had non-small cell lung cancer (NSCLC) (85%) and metastatic disease (56%). No significant differences were observed in serum IGF-1 levels between lung cancer patients and healthy subjects (P=0.403). However, baseline serum IGFBP-3 levels of the lung cancer patients were significantly lower compared to the control group (P<0.001). The male patients had elevated serum IGF-1 concentrations compared to females (P=0.025). Furthermore, patients with NSCLC histology and metastatic stage in NSCLC had elevated serum IGF-1 (P=0.022 and P=0.039, respectively) and IGFBP-3 (P=0.005 and P=0.043, respectively) levels compared with those with SCLC histology and non-metastatic stage in NSCLC. However, none of the other clinical variables, including age of patient, tumor histology and chemotherapy responsiveness, were observed as correlated with serum assays of IGF-1 and IGFBP-3 (P>0.05). There was a significant association found between IGF-1 and IGFBP-3 serum levels in lung cancer patients (P<0.001). Neither serum IGF-1 nor IGFBP-3 concentrations were associated with outcome (P=0.552 and P=0.471, respectively). In conclusion, serum concentrations of IGFBP-3 may have a diagnostic predictor in patients with lung cancer compared to serum IGF-1 concentrations. However, predictive and prognostic values of the two serum assays were not observed.

The prevalence of acromegaly in hospitalized patients with type 2 diabetes.

The prevalence of acromegaly is estimated to be 8-24/100,000, but several recent studies suggest it is underestimated. In particular, acromegaly is considered more prevalent in patients with type 2 diabetes mellitus (T2DM) than in the normal population. This study aimed to evaluate the prevalence of acromegaly in hospitalized patients with T2DM. A total of 327 hospitalized patients with T2DM were recruited as subjects. If serum insulin-like growth factor 1 (IGF-1) levels were found to be elevated, random GH level was measured or oral glucose tolerance test (OGTT) was performed. Five patients with elevated serum IGF-1 levels and random GH level or inadequate suppression of GH in the OGTT underwent pituitary magnetic resonance imaging. Of those patients, pituitary adenoma was detected in 2 patients. These 2 patients were diagnosed with acromegaly, as they also exhibited mild acromegalic features. Intriguingly, both these patients exhibited severe macroangiopathy and an absence of microangiopathy. The prevalence of acromegaly in the hospitalized patients with T2DM in this study was therefore 0.6%, suggesting a higher prevalence than that predicted. Although a large-scale prospective study is required to clarify the precise prevalence of acromegaly in hospitalized patients with T2DM, the present study shows that it is useful to screen hospitalized patients with T2DM for acromegaly by measuring their serum IGF-1 level.

ω-3 fatty acid differentially modulated serum levels of IGF1 and IGFBP3 in men with CVD: A randomized, double-blind placebo-controlled study

ObjectiveStudies have reported elevated serum insulin-like growth factor (IGF)-1 levels followed by ω-3 supplementation in various groups. Considering decreased level of IGF1 in patients with cardiovascular disease (CVD) and protective effects of IGF1 against CVD progression and myocardial infarctions mortality, this study was performed with the aim of determining effects of ω-3 supplementation on serum levels and gene expression of IGF1 and IGF binding protein-3 (IGFBP3) in men with CVD. MethodsSixty-two middle-aged (55.9 ± 6.5 y) non-obese men with CVD followed the study protocol in two groups of ω-3 (n = 31) or placebo (n = 31) supplementation. Participants took ω-3 supplement or placebo (edible paraffin) for 8 wk and were asked not to change their diet or physical activity plan. Anthropometric and lipid profile characteristics, serum IGF1, serum IGFBP3 and also IGF1 and IGFBP3 gene expression in peripheral blood mononuclear cells (PBMCs) were measured in all participants before and after the intervention. Statistical analyses were performed using SPSS software. ResultsThere were no significant differences between the two study groups in age and body mass index at baseline. The groups also had no difference in baseline serum low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, triacylglycerols, and IGF1. Compared with placebo, ω-3 supplementation increased serum IGF1 levels (P = 0.01), and decreased serum level of IGFBP3 (P = 0.02). There was a trending toward an increase in IGF1 expression and nonsignificant decrease in IGFBP3 expression. Conclusionsω-3 supplementation in patients with CVD increases serum IGF1 levels and decreases serum IGFBP3. Further research is warranted to investigate the underlying mechanisms.

Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with breast cancer.

Insulin-like growth factor-1 (IGF-1) and its primary binding protein-3 (IGFBP-3) play an important role in cellular proliferation, differentiation and apoptosis in many tumors, including breast cancer (BC). The objective of this study was to determine the clinical significance of the serum levels of IGF-1 and IGFBP-3 in BC patients. A total of 96 patients with a pathologically confirmed diagnosis of BC were enrolled into this study. Serum IGF-1 and IGFBP-3 levels were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) methods. Age- and sex-matched 30 healthy controls were included in the analysis. The median age of diagnosis was 48 years (range: 29-80). Thirty-seven (39 %) consisted of metastatic disease. No significant difference in baseline serum was found in both IGF-1 and IGFBP-3 levels between BC patients and healthy controls (p = 0.92 and p = 0.26, respectively). None of the prognostic parameters analyzed was correlated significantly with the serum assay concentrations. Likewise, no correlations were also found between these serum concentrations and response to chemotherapy. No significant correlation was found between serum IGF-1 and IGFBP-3 levels in BC patients (r s = 0.048, p = 0.66).The patients with elevated serum IGF-1 levels had favorable in survival than those with lower levels (p = 0.05). However, serum IGFBP-3 concentrations were found no prognostic role for outcome (p = 0.35). In conclusion, elevated serum IGF-1 level is afavorable prognostic factor for overall survival in BC patients.