Blood Levels Of Insulin-like Growth Factor-1 Research Articles

Insulin-like growth factor-1 (IGF-1) levels in multiple sclerosis patients: A systematic review and meta-analysis.

Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

Investigation of Igf-1, Igf-Bp3 and Igf-Bp5 levels in umbilical cord blood of infants with developmental dysplasia of the hip.

IGF-1 (insulin-like growth factor-1) is an important regulator of bone formation. Its deficiency has been associated with fetal growth disorders and hip dysplasia. The aim of this study was to evaluate whether IGF-1, IGF-BP3 (insulin like growth factorbinding protein 3), and IGF-BP5 levels in the umbilical cord blood can be predictive for early diagnosis of DDH. Umbilical cord blood samples were collected from 860 mothers with pregnancies at high risk for DDH between October 2020 and January 2021. Mothers at 37-42 weeks of gestation, with risk factors for DDH, who delivered healthy infants were included. Blood samples were collected during delivery. Each eligible infant was medically followed up and underwent a hip ultrasound in the postnatal 2nd or 3rd month. Infants diagnosed with DDH were matched with a healthy cohort in terms of sex, birth weight, maternal age, and gestational week, and the IGF-1, IGF-BP3 and IGF-BP5 levels were studied and compared. Evaluation was made of 20 infants diagnosed with DDH and 60 healthy infants. Of the total 80 infants, 72.5% were female.The umbilical cord blood levels of IGF-1 and IGF-BP3 were similar in both groups. The IGF-BP5 values were significantly lower in the DDH patient group. Except for DDH diagnosis, the other categorical variables of the study did not appear to influence the levels of any of the IGFs. Umbilical blood samples could potentially help diagnose DDH. The levels of IGF-BP5 were shown to be significantly lower in infants with DDH.

Insulin-like growth factor-1 blood levels and carotid artery remodeling in hypertensive patients with type 2 diabetes mellitus

Background and Aims: Insulin-like growth factor-1 (IGF-1) is an important link in the regulation of structural and functional changes in the vascular bed. We aimed to study the relationship between blood levels of IGF-1 and indicators of carotid artery remodeling in hypertensive patients with type 2 diabetes mellitus (T2DM).

Mechanistic study of the cause of decreased blood 1,25-Dihydroxyvitamin D in sepsis

BackgroundVitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency.MethodsWe studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function.ResultsWe demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver.ConclusionsBecause FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.

Maternal H. pylori seropositivity is associated with gestational hypertension but is irrelevant to fetal growth and development in early childhood

BackgroundHelicobacter pylori infection is known to alter growth-related hormones and affect growth in young children. However, it is still unknown whether maternal H. pylori infection has an impact on the levels of cord blood growth-related hormones and whether this can predict intrauterine growth restriction and poor physical and neurodevelopmental outcomes in children. This study aimed to examine associations between maternal H. pylori infection and pregnancy-related adverse events, fetal growth and early childhood development.MethodsIn this prospective cohort study, we recruited singleton pregnant women without major medical illnesses from January 2014 to January 2015. Seropositivity for H. pylori was defined as > 12 U/ml of anti-H. pylori IgG in maternal serum. Demographic data and pregnancy-related medical issues of the cohort were documented. Cord blood levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, and ghrelin were determined using ELISA. The growth of the included neonates was monitored annually for up to 3 years, and cognitive development was assessed using the comprehensive developmental inventory for infants and toddlers (CDIIT) test 3 years after birth.ResultsOf the 106 enrolled women, 25 (23.6%) were H. pylori-seropositive. Maternal H. pylori seropositivity was correlated with a higher risk of developing gestational hypertension (GH) (12% vs. 1.2%, p = 0.04) and lower cord blood levels of IGF-1 (< 35 ng/ml, 70.0% vs. 40.7%, p = 0.02) and IGFBP-3 (< 1120 ng/ml, 100.0% vs. 76.3%, p = 0.02) compared with the seronegative women. No significant impacts on birth weight, childhood growth and cognitive development were found to be correlated with maternal H. pylori seropositivity during pregnancy.ConclusionsMaternal H. pylori infection during pregnancy was more likely to lead to the development of GH, but was not correlated with fetal and childhood growth and development. In addition to close monitoring of hypertension, H. pylori eradication can be considered for mothers with H. pylori infection.

Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk

Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ERα(+) breast cancer and compared their IGF-1 blood levels with those of 178 ERα(+) and 83 ERα(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. ERα(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ERα status of women with BBD was taken into account, the difference in IGF-1 levels between ERα(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ERα(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ERα(+) breast cancer patients were compared with ERα(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. We found evidence in support of an interaction of IGF-1 with the expression of ERα in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer.

Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer

High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood levels and of it's main binding protein, IGFBP-3, on overall survival and occurrence of second primary breast tumors in breast cancer patients, as well as reproductive and lifestyle factors that could modify this risk. Patients were accrued from six hospitals in the Netherlands between 1998 and 2003. Total IGF-1 and IGFBP-3 were measured in 582 plasma samples.No significant association between IGF-1 and IGFBP-3 plasma levels and overall survival was found. However, in a multivariate Cox regression model including standard prognostic variables high IGF-1 levels were related to worse overall survival in patients receiving endocrine therapy (HR = 1.37, 95% CI: 1.11, 1.69, P 0.004). These data at least indicate that higher IGF-1 levels, and as a consequence most likely IGF-1-induced signaling, are related to a less favorable overall survival in breast cancer patients treated with endocrine therapy. Interventions aimed at reducing circulating levels of IGF-1 in hormone receptor positive breast cancer may improve survival.

Effects of administration of subtoxic doses of acetaminophen on liver and blood levels of insulin-like growth factor-1 in rats

Acetaminophen (APAP) is widely used in the treatment of pain. Toxic doses of APAP cause acute liver failure, but therapeutic doses are believed to be safe. The purpose of this study is to investigate the effects of administration of subtoxic doses of APAP on liver and blood levels of insulin-like growth factor-1 (IGF-1) in rats. Low dose (100 mg/kg) and high dose (250 mg/kg) of APAP were intraperitoneally injected into Wistar albino rats. Following administration of therapeutic doses of APAP, there were no significant changes in serum transaminases and liver glutathione levels. Both doses of APAP induced a decrease in liver and blood levels of IGF-1 when compared with the controls. There was no significant difference in liver IGF-1 levels between the high-dose and low-dose APAP groups; however, there was a significant difference in blood IGF-1 levels between both the groups. The histological examination showed that low dose of APAP induced mild degree of structural change, while high dose of APAP induced severe structural damage. In conclusion, these results suggest that blood IGF-1 levels may have a value in predicting hepatic damage resulting from therapeutic doses of APAP.

TK Inhibitor Treatment Disrupts Growth Hormone Axis: Clinical Observations in Children with CML and Experimental Data from a Juvenile Animal Model

Long-term treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) exerts off-target effects on bone growth by either impaired growth hormone (GH) action or osseous modelling impairment. Body height and the GH-related parameters insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3(IGFBP-3) were determined repetitively 3-monthly over 2 years in 21 pediatric CML-patients on standardized imatinib treatment. In an animal model 4-week-old male Wistar rats were exposed over 10 weeks to imatinib, dasatinib, or bosutinib at varying concentrations via the drinking water. Blood was collected at prepubertal age, pubertal age, and at adult age, respectively, and animals' serum levels of IGFBP-3 were measured. Independent from treatment duration patients exhibited IGF-1 and IGFBP-3 levels almost exclusively in the very low range when compared to age-matched references. No clear pattern of rising or falling IGF-1 and IGFBP-3 levels was observed. In rats, compared to controls, serum IGFBP-3 was significantly lowered for all TKIs tested, at all concentrations applied, and at all ages under investigation. Besides direct off-target effects on the growing skeleton, TKI treatment also results in lowered blood levels of IGF-1 and IGFBP-3.A juvenile rat model predicts this side effect for dasatinib and bosutinib. Thus, growth and GH- related parameters should be monitored regularly in pediatric patients with CML on TKIs.

Is a deceptive role of IGF-1 in Sirt1–PARP1 interactions the primary step of postnatal regression of hypertrophic cardiomyopathy in infants of diabetic mothers?

Is a deceptive role of IGF-1 in Sirt1–PARP1 interactions the primary step of postnatal regression of hypertrophic cardiomyopathy in infants of diabetic mothers?

Diet, insulin-like growth factor-1 and cancer risk.

Despite extensive research it has proved difficult to establish the role of diet in the aetiology of common types of cancer. Obesity and alcohol definitely increase the risk for several types of cancer, but the importance of particular foods and nutrients is not clear. Part of the difficulty is our poor understanding of the physiological changes that might mediate the effect of diet on cancer risk. Recent research in prospective studies with biobanks of stored blood samples has shown that the serum concentration of insulin-like growth factor-1 (IGF-1) is positively associated with the risk for both breast cancer in women and prostate cancer in men. It is also known that circulating IGF-1 concentrations can change in response to nutritional changes including energy and protein restriction, and some studies suggest that, even within well-nourished western populations, men and women with relatively high intakes of protein from dairy products have higher blood levels of IGF-1. These observations have led to the hypothesis that high intakes of protein from dairy products might increase the risk for some cancers by increasing the endogenous production of IGF-1. Further evaluation of this hypothesis requires clinical nutritional studies of the effects of diet on IGF-1 metabolism, and large epidemiological studies of cancer risk incorporating reliable measures of diet and serum IGF-1 concentrations.

Dietary Intervention of Flaxseed: Effect on Serum Levels of IGF-1, IGF-BP3, and C-Peptide

Higher levels of insulin and insulin-like growth factor 1 (IGF-1) increase cancer risk by stimulating cell proliferation and increasing survival of DNA-damaged cells through antiapoptotic mechanisms. Laboratory studies suggest that flaxseed added to the diet may lower circulating levels of insulin and IGF-1, but there is limited information on the effects of dietary flaxseed on these biomarkers of cancer risk in humans. The aim of this study was to determine the effect of flaxseed supplementation in postmenopausal women on serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGF-BP3), and C-peptide, a marker of insulin production. Forty-eight postmenopausal women participated in this 12-wk baseline to postintervention study. Participants were asked to consume 7.5 g per day of ground flaxseed for 6 wk and 15 g per day for an additional 6 wk. No significant changes were observed in blood levels of IGF-1, IGF-BP3, or C-peptide over the study intervention. Flaxseed supplementation did not impact circulating levels of IGF-1, IGF-BP3, or C-peptide. Longer duration of intake may be necessary to observe changes in these biomarkers of cancer risk.

Ageing and Longevity Are Related to Growth Hormone/Insulin-Like Growth Factor-1 Secretion

Background: It is known that the growth process is related to an individual’s life-span, but the role of growth hormone (GH) secretion in human ageing remains unknown. Objectives: This study has focussed on the influence of GH on ageing parameters and on its relationship with human longevity. Methods: To deal with the first issue, we compared ageing parameters of young (up to 39) and old (over 70) individuals having similar insulin-like growth factor-1 (IGF-1) blood levels. For the second one, the decline in IGF-1 levels was studied comparing its behaviour in the first half with that in the second half of adult life. The latter represents the period of life in which mortality progressively increases. Two hundred and five healthy individuals were chosen as subjects, well distributed by gender and age (between 19 and 93 years). Results: Old males with IGF-1 levels similar to young ones do not show the age-dependent decrease in serum testosterone and lean body mass, nor the increase in fat body mass. Other hormone-metabolic and nutritional parameters do not reveal any change compared with the results of all individuals. In females, the results do not allow to assume any IGF-1 influence. The behaviour of the linear regression in the second half of adult life of males, which becomes flat because old men having low IGF-1 blood levels die earlier, is consistent with these results. This effect, which is supported by predictive analysis, is not observed in females, i.e. the IGF-1 level declines in the second half of the women’s adult life are only a little flatter than in the first half. Finally, extrapolating the regressions obtained in the first half of adulthood, the age at which the curve crosses the x-axis is 110 years for males and 132 for females. Conclusion: The presented study of IGF-1 levels suggests that the GH secretion in adulthood plays a determinant role not only for some regressive manifestations, but also for life potential.