scholarly journals Investigating the Relationship Between IGF-I, IGF-II, and IGFBP-3 Concentrations and Later-Life Cognition and Brain Volume

2021 ◽  
Author(s):  
Antoine Salzmann ◽  
Sarah-Naomi James ◽  
Dylan M Williams ◽  
Marcus Richards ◽  
Dorina Cadar ◽  
...  
Keyword(s):  
Processing Speed ◽  
Brain Volume ◽  
Later Life ◽  
Hippocampal Volume ◽  
White Matter Hyperintensity ◽  
Molar Ratio ◽  
Cognitive State ◽  
Igf I ◽  
Using Data ◽  
Igfbp 3

Abstract Background The insulin/insulin-like signaling (IIS) pathways, including insulin-like growth factors (IGFs), vary with age. However, their association with late-life cognition and neuroimaging parameters is not well characterized. Methods Using data from the British 1946 birth cohort, we investigated associations of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3; measured at 53 and 60-64 years of age) with cognitive performance [word-learning test (WLT) and visual letter search (VLS) at 60-64 years and 69 years of age] and cognitive state [Addenbrooke’s Cognitive Exam III (ACE-III) at 69-71 years of age], and in a proportion, quantified neuroimaging measures [whole brain volume (WBV), white matter hyperintensity volume (WMHV), hippocampal volume (HV)]. Regression models included adjustments for demographic, lifestyle, and health factors. Results Higher IGF-I and IGF-II at 53 years of age was associated with higher ACE-III scores [ß 0.07 95% confidence interval (CI) (0.02, 0.12); scoreACE-III 89.48 (88.86, 90.1), respectively). IGF-II at 53 years of age was additionally associated with higher WLT scores [scoreWLT 20 (19.35, 20.65)]. IGFBP-3 at 60 to 64 years of age was associated with favorable VLS score at 60 to 64 and 69 years of age [ß 0.07 (0.01, 0.12); ß 0.07 (0.02, 0.12), respectively], higher memory and cognitive state at 69 years of age [ß 0.07 (0.01, 0.12); ß 0.07 (0.01, 0.13), respectively], and reduced WMHV [ß −0.1 (−0.21, −0.00)]. IGF-I/IGFBP-3 at 60 to 64 years of was associated with lower VLS scores at 69 years of age [ß −0.08 (−0.15, −0.02)]. Conclusions Increased measure in IIS parameters (IGF-I, IGF-II, and IGFBP-3) relate to better cognitive state in later life. There were apparent associations with specific cognitive domains (IGF-II relating to memory; IGFBP-3 relating to memory, processing speed, and WMHV; and IGF-I/IGFBP-3 molar ratio related to slower processing speed). IGFs and IGFBP-3 are associated with favorable cognitive function outcomes.

scholarly journals Investigating the relationship between IGF-I, -II and IGFBP-3 concentrations and later-life cognition and brain volume

2020 ◽  
Author(s):  
Antoine Salzmann ◽  
Sarah-Naomi James ◽  
Dylan M. Williams ◽  
Marcus Richards ◽  
Dorina Cadar ◽  
...  
Keyword(s):  
Processing Speed ◽  
Brain Volume ◽  
Later Life ◽  
Hippocampal Volume ◽  
White Matter Hyperintensity ◽  
Molar Ratio ◽  
Cognitive State ◽  
Igf I ◽  
Using Data ◽  
Igfbp 3

AbstractBackgroundThe insulin/insulin-like signalling (IIS) pathways, including Insulin-like Growth Factors (IGFs), varies with age. However, their association with late-life cognition and neuroimaging parameters is not well characterised.MethodsUsing data from the British 1946 birth cohort we investigated associations of IGF-I, -II and IGFBP-3 (measured at 53 and 60-64 years) with cognitive performance (word learning test (WLT) and visual letter search (VLS) – at 60-64y and 69y) and cognitive state (Addenbrooke’s Cognitive Exam-III (ACE-III) - at 69-71y), and in a proportion, quantified neuroimaging measures (whole brain volume (WBV); white matter hyperintensity volume (WMHV); hippocampal volume (HV)). Regression models included adjustments for demographic, lifestyle and health factors.ResultsHigher IGF-I and IGF-II at 53y was associated with higher ACE-III scores (ß 0.07 95%CI [0.02,0.12]; scoreACE-III 89.48 [88.86,90.1], respectively). IGF-II at age 53y was additionally associated with higher WLT scores (scoreWLT 20 [19.35,20.65]). IGFBP-3 at 60-64y was associated with favourable VLS score at 60-64y and 69y (ß 0.07 [0.01,0.12]; ß 0.07 [0.02,0.12], respectively), higher memory and cognitive state at 69y (ß 0.07 [0.01,0.12]; ß 0.07 [0.01,0.13], respectively) and reduced WMHV (ß −0.1, [-0.21,-0.00]). IGF-I/IGFBP-3 at 60-64y was associated with slower VLS scores at 69y (ß −0.08, [-0.15,-0.02]).ConclusionsIncreased measure in IIS parameters (IGF-I, -II and IGFBP-3) relate to better cognitive state in later life. Furthermore, there were apparent associations with specific cognitive domains (IGF-II relating to memory; IGFBP-3 to memory, processing speed and WMHV; and IGF-I/IGFBP-3 molar ratio with slower processing speed). IGFs and IGFBP-3 are associated with favourable cognitive function outcomes.

scholarly journals Hyperlipidemia is associated with altered levels of insulin-like growth factor-I

2008 ◽  
pp. 919-925
Author(s):  
J Malík ◽  
T Štulc ◽  
D Wichterle ◽  
V Melenovský ◽  
E Chytilová ◽  
...  
Keyword(s):  
Growth Factor ◽  
Coronary Atherosclerosis ◽  
Molar Ratio ◽  
Insulin Like Growth Factor ◽  
Premature Atherosclerosis ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Mixed Hyperlipidemia ◽  
Igfbp 3

Previous studies revealed altered levels of the circulating insulin-like growth factor-I (IGF-I) and of its binding protein-3 (IGFBP-3) in subjects with coronary atherosclerosis, metabolic syndrome and premature atherosclerosis. Hyperlipidemia is a powerful risk factor of atherosclerosis. We expected IGF-I and IGFBP-3 alterations in subjects with moderate/severe hyperlipidemia but without any clinical manifestation of atherosclerosis. Total IGF-I and IGFBP-3 were assessed in 56 patients with mixed hyperlipidemia (MHL; cholesterol >6.0 mmol/l, triglycerides >2.0 mmol/l), in 33 patients with isolated hypercholesterolemia (IHC; cholesterol >6.0 mmol/l, triglycerides <2.0 mmol/l), and in 29 healthy controls (cholesterol<6.0 mmol/l, triglycerides<2.0 mmol/l). The molar ratio of IGF-I/IGFBP-3 was used as a measure of free IGF-I. IHC subjects differed from controls by lower total IGF-I (164+/-60 vs. 209+/-73 ng/ml, p=0.01) and IGF-I /IGFBP-3 ratio (0.14+/-0.05 vs. 0.17+/-0.04, p=0.04). Compared to controls, MHL subjects had lower total IGF-I (153+/-54 ng/ml, p=0.0002) and IGFBP-3 (2.8+/-0.6 mg/ml, p<0.0001), but higher IGF-I/IGFBP-3 ratio (0.25+/-0.06, p<0.0001). Differences remained significant after the adjustment for clinical and biochemical covariates, except for triglycerides. Patients with both IHC and MHL have lower total IGF-I compared to controls. The mechanism is presumably different in IHC and MHL. Because of prominent reduction of IGFBP-3 in patients with MHL, they have reduced total IGF-I despite the actual elevation IGF-I/IGFBP-3 ratio as a surrogate of free IGF-I.

scholarly journals Prenatal vitamin D and cord blood insulin-like growth factors in Dhaka, Bangladesh

2019 ◽  
Vol 8 (6) ◽  
pp. 745-753 ◽  
Author(s):  
Monika Bilic ◽  
Huma Qamar ◽  
Akpevwe Onoyovwi ◽  
Jill Korsiak ◽  
Eszter Papp ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cord Blood ◽  
Fetal Growth ◽  
Reference Population ◽  
Vitamin D Supplementation ◽  
Molar Ratio ◽  
Anthropometric Parameter ◽  
Blood Concentrations ◽  
Igf I ◽  
Igfbp 3

Fetal growth restriction is linked to adverse health outcomes and is prevalent in low- and middle-income countries; however, determinants of fetal growth are still poorly understood. The objectives were to determine the effect of prenatal vitamin D supplementation on the insulin-like growth factor (IGF) axis at birth, to compare the concentrations of IGF-I in newborns in Bangladesh to a European reference population and to estimate the associations between IGF protein concentrations and birth size. In a randomized controlled trial in Dhaka, Bangladesh, pregnant women enrolled at 17–24 weeks of gestation were assigned to weekly oral vitamin D3 supplementation from enrolment to delivery at doses of 4200 IU/week, 16,800 IU/week, 28,000 IU/week or placebo. In this sub-study, 559 woman–infant pairs were included for analysis and cord blood IGF protein concentrations were quantified at birth. There were no significant effects of vitamin D supplementation on cord blood concentrations of IGF-I (P = 0.398), IGF-II (P = 0.525), binding proteins (BPs) IGFBP-1 (P = 0.170), IGFBP-3 (P = 0.203) or the molar ratio of IGF-I/IGFBP-3 (P = 0.941). In comparison to a European reference population, 6% of girls and 23% of boys had IGF-I concentrations below the 2.5th percentile of the reference population. IGF-I, IGF-II, IGFBP-3 and the IGF-I/IGFBP-3 ratio were positively associated with at least one anthropometric parameter, whereas IGFBP-1 was negatively associated with birth anthropometry. In conclusion, prenatal vitamin D supplementation does not alter or enhance fetal IGF pathways.

scholarly journals Cognitive Correlates of MRI-defined Cerebral Vascular Injury and Atrophy in Elderly American Indians: The Strong Heart Study

2019 ◽  
Vol 26 (3) ◽  
pp. 263-275 ◽  
Author(s):  
Astrid Suchy-Dicey ◽  
Dean Shibata ◽  
Brenna Cholerton ◽  
Lonnie Nelson ◽  
Darren Calhoun ◽  
...  
Keyword(s):  
Executive Function ◽  
White Matter ◽  
Magnetic Resonance ◽  
Cerebrovascular Disease ◽  
Cognitive Functioning ◽  
American Indians ◽  
Processing Speed ◽  
Brain Volume ◽  
Hippocampal Volume ◽  
White Matter Disease

AbstractObjective:American Indians experience substantial health disparities relative to the US population, including vascular brain aging. Poorer cognitive test performance has been associated with cranial magnetic resonance imaging findings in aging community populations, but no study has investigated these associations in elderly American Indians.Methods:We examined 786 American Indians aged 64 years and older from the Cerebrovascular Disease and its Consequences in American Indians study (2010–2013). Cranial magnetic resonance images were scored for cortical and subcortical infarcts, hemorrhages, severity of white matter disease, sulcal widening, ventricle enlargement, and volumetric estimates for white matter hyperintensities (WMHs), hippocampus, and brain. Participants completed demographic, medical history, and neuropsychological assessments including testing for general cognitive functioning, verbal learning and memory, processing speed, phonemic fluency, and executive function.Results:Processing speed was independently associated with the presence of any infarcts, white matter disease, and hippocampal and brain volumes, independent of socioeconomic, language, education, and clinical factors. Other significant associations included general cognitive functioning with hippocampal volume. Nonsignificant, marginal associations included general cognition with WMH and brain volume; verbal memory with hippocampal volume; verbal fluency and executive function with brain volume; and processing speed with ventricle enlargement.Conclusions:Brain-cognition associations found in this study of elderly American Indians are similar to those found in other racial/ethnic populations, with processing speed comprising an especially strong correlate of cerebrovascular disease. These findings may assist future efforts to define opportunities for disease prevention, to conduct research on diagnostic and normative standards, and to guide clinical evaluation of this underserved and overburdened population.

scholarly journals Do Height-Related Variations in Insulin-Like Growth Factors Underlie the Associations of Stature with Adult Chronic Disease?

2004 ◽  
Vol 89 (1) ◽  
pp. 213-218 ◽  
Author(s):  
D. Gunnell ◽  
S. E. Oliver ◽  
J. L. Donovan ◽  
T. J. Peters ◽  
D. Gillatt ◽  
...  
Keyword(s):  
Disease Risk ◽  
Molar Ratio ◽  
Leg Length ◽  
Trunk Length ◽  
Increased Risk ◽  
Igf I ◽  
Disease Associations ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Tall people, particularly those with long legs, have an increased risk of developing cancer but a reduced risk of cardiovascular disease and type II diabetes. We examined associations of stature and body mass index with IGF-I, IGF-II, and IGF binding protein (IGFBP)-2 and IGFBP-3 in 274 men aged 50–70 yr to investigate whether variations in growth factor levels underlie associations of anthropometry with a number of adult diseases. Height and leg and trunk length were not strongly associated with circulating levels of IGF-I, IGF-II, or IGFBP-3. The molar ratio of IGF-I/IGFBP-3 increased with increases in the leg/trunk length ratio (P = 0.06). IGFBP-2 was positively associated with leg length and inversely associated with trunk length. Mean levels of IGFBP-2 (in nanograms per milliliter) across quartiles of increasing leg length were 504.4 493.6, 528.7, and 578.8 (Ptrend = 0.06), and for trunk length were 615.2, 507.2, 498.6, 488.5 (Ptrend &lt; 0.01), suggesting that variations in IGFBP-2, or a factor influencing its levels in the circulation, may contribute to biological mechanisms underlying height-disease associations. We conclude that whereas growth-influencing exposures during childhood, which may operate through effects on IGF-I levels, have long-term influences on disease risk, they do not necessarily program IGF-I levels throughout life. The associations of anthropometry with IGFBP-2 merit additional investigation.

scholarly journals Increased Insulin-Like Growth Factor (IGF)-II and IGF/IGF-Binding Protein Ratio in Prepubertal Constitutionally Tall Children

2002 ◽  
Vol 87 (12) ◽  
pp. 5455-5460 ◽  
Author(s):  
S. Garrone ◽  
G. Radetti ◽  
M. Sidoti ◽  
M. Bozzola ◽  
F. Minuto ◽  
...  
Keyword(s):  
Growth Velocity ◽  
Binding Protein ◽  
Molar Ratio ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Acid Labile Subunit ◽  
Igf Binding Protein ◽  
Acid Labile ◽  
Igfbp 3

Abstract The height of subjects with constitutionally tall stature (CTS) is at least 2 sd above the mean of subjects of the same age and sex. Apart from a few discordant data on the role of GH and its direct mediator, IGF-I, no studies have been conducted on other components of the IGF system, which also condition the bioavailability and activity of IGF-I. We, therefore, investigated the possibility that other components of the IGF system might play a role in determining the increased growth velocity seen in CTS. To this end, we evaluated the behavior not only of IGF-I but also of IGF-II, IGF-binding protein (IGFBP)-3, and acid-labile subunit, the subunits that constitute the main IGF complex in circulation (150-kDa complex), as well as of IGFBP-1 and IGFBP-2, which are negatively regulated by GH and, like IGFBP-3, able to influence the bioavailability of the IGFs. The study was performed on 22 prepubertal subjects affected by CTS (16 males and 6 females), aged 2.8–13.3 yr (6.8 ± 0.5 yr, mean ± sem). Thirty-seven normal prepubertal subjects (16 males and 21 females) aged between 2.2 and 13.3 yr (6.7 ± 0.5 yr), who were comparable in socioeconomic and nutritional terms, served as controls. From the auxological point of view, subjects with CTS differed significantly from controls only in terms of growth velocity (HV-sd score; CTS, 1.8 ± 0.3; controls, 0.4 ± 0.2; P &lt; 0.0001) and height (H-sd score; CTS, 3.1 ± 0.1; controls, 0.4 ± 0.2; P &lt; 0.0001). The results demonstrated that the concentrations of IGF-I (27.3 ± 2.0 nmol/liter), IGFBP-3 (66.9 ± 3.8), and acid-labile subunit (216.8 ± 13.6) in CTS-affected subjects were not significantly different from those determined in controls (25.0 ± 2.9, 74.4 ± 4.1, and 241.0 ± 11.9, respectively). By contrast, IGF-II levels proved significantly higher in CTS subjects (IGF-II: 87.2 ± 3.4 vs. 52.4 ± 2.3, P &lt; 0.0001). Chromatographic analysis, performed after acid treatment of pooled sera, showed only the presence of normal 7.5-kDa IGF-II in both CTS subjects and controls. In comparison with controls, CTS children showed a lower concentration of IGFBP-1 (1.6 ± 0.3 vs. 4.1 ± 0.7, P = 0.03) and a higher concentration of IGFBP-2 (14.3 ± 1.8 vs. 9.6 ± 1.1, P = 0.03). The IGFs (IGF-I and -II)/IGFBPs (−1 + −2 + −3) molar ratio was significantly higher (P &lt; 0.0001) in CTS children than in controls. In particular, the IGF-II/IGFBP ratio (P &lt; 0.0001) was responsible for the excess of the IGF peptide in relation to the concentrations of IGFBPs and, therefore, for the increase in the potentially bioactive free form of the IGFs. Moreover, the IGFBP-3/IGF molar ratio was significantly reduced, being less than 1 in CTS subjects (0.6 ± 0.1 vs. 1.1 ± 0.1), so that a quantity of IGF peptides lack sufficient IGFBP-3 to form the 150-kDa complex with which are normally sequestered in the vascular compartment. The data show that in CTS: 1) the most GH-dependent components of the IGF system are normal, consistent with the finding of a normal GH secretory state; 2) the less GH-dependent IGF-II is significantly increased, in agreement with the finding of a relationship between high levels of IGF-II and overgrowth in some syndromes; and 3) the IGF/IGFBP molar ratio is increased, and, therefore, a greater availability of free IGF for target tissues may be responsible for overgrowth in CTS.

scholarly journals Impact of nutrients on insulin-like growth factor-I, insulin-like growth factor binding protein-3 and their ratio in African American and white males

2007 ◽  
Vol 10 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Katharine M McGreevy ◽  
Brian D Hoel ◽  
Stuart R Lipsitz ◽  
David G Hoel
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
African Americans ◽  
Molar Ratio ◽  
Insulin Like Growth Factor ◽  
Nutritional Factors ◽  
White Males ◽  
Igf I ◽  
The Impact ◽  
Igfbp 3

AbstractObjectiveHigher levels of insulin-like growth factor-I (IGF-I) and lower levels of IGF binding protein-3 (IGFBP-3) have been associated with an increased risk of prostate cancer. Nutrition is known to partially regulate IGF levels and it is possible that nutritional factors mediate the impact of IGF levels on prostate cancer risk.DesignA cross-sectional analysis of the impact of nutritional factors measured by a dietary questionnaire on plasma levels of IGF-I, IGFBP-3 and their molar ratio. Multiple linear regression analysis was used to test for effects of nutrients on IGF levels.SettingProstate cancer screening at the Hollings Cancer Center in Charleston, South Carolina.SubjectsNinety-five African American and 138 white males aged 33–83 years attending the screening.ResultsIn whites, intakes of total, saturated and monounsaturated fats were positively associated with an increase in the molar ratio, while there was no association in African Americans. In African Americans, we found that increasing intake of calcium and dairy servings was positively associated with IGF-I levels. Increased vegetable intake was positively associated with IGFBP-3 in African Americans, while there was no effect in whites. A higher percentage of alcohol in the total diet was significantly associated with a decrease in the molar ratio and an increase in IGFBP-3 in both groups.ConclusionsOur results confirm previous findings of nutritional determinants of IGF levels. Additionally, we found the impact of several nutrients on IGF levels to be different in whites and African Americans, which warrants further investigation.

Influence of chronic naltrexone treatment on growth hormone secretion in normal subjects

1997 ◽  
pp. 631-634 ◽  
Author(s):  
P Villa ◽  
D Valle ◽  
L De Marinis ◽  
A Mancini ◽  
A Bianchi ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Normal Subjects ◽  
Molar Ratio ◽  
Normal Female ◽  
Gh Secretion ◽  
Igf I ◽  
Before And After ◽  
Ghrh Test ◽  
Igfbp 3

OBJECTIVE: To verify if a chronic opioid blockade could affect the GH/IGF-I axis. DESIGN: We have investigated the effects of naltrexone (NTX) treatment on GH response to GHRH in normal women. METHODS: GHRH test (50 micrograms i.v.) performed in seven normal female volunteers (age 25-38 years, with a body mass index ranging from 19.8 to 23.1 kg/m2) before and after 4-weeks NTX treatment (50 mg p.o. daily). RESULTS: Basal GH, IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3) plasma levels and the IGF-I/IGFBP-3 molar ratio remained unaffected by NTX. NTX significantly reduced the GH peak values (15.52 +/- 3.59 vs 4.78 +/- 0.49 micrograms/l; P < 0.01), and GH area under curve (918.93 +/- 253.96 vs 401.09 +/- 79.63 micrograms/l; P < 0.01). CONCLUSIONS: This finding suggests that the long-term opioid receptor blockade has an inhibitory role on GHRH-induced GH secretion. A central influence on neurotransmitter control of GH might be hypothesised. The inhibition of stimulated GH release, without interference with the basal level, could indicate an enhanced somatostatin secretion and/or activity. Opioids could be involved only in the regulation of GH dynamics and not in basal secretion. Nevertheless, a direct involvement of opioids at the pituitary level, which could be modified by NTX, cannot be excluded.

scholarly journals Relationship between IGF-I Concentration and Metabolic Profile in Children with Growth Hormone Deficiency: The Influence of Children’s Nutritional State as well as the Ghrelin, Leptin, Adiponectin, and Resistin Serum Concentrations

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Renata Stawerska ◽  
Joanna Smyczyńska ◽  
Maciej Hilczer ◽  
Andrzej Lewiński
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Body Mass ◽  
Metabolic Profile ◽  
Hormone Deficiency ◽  
Molar Ratio ◽  
Healthy Children ◽  
Serum Concentrations ◽  
Igf I ◽  
Igfbp 3

Background. Some, however not all, children with growth hormone deficiency (GHD) reveal a tendency towards metabolic disorders. Insulin-like growth factor I (IGF-I) is the main mediator of GH anabolic effects. Objective. The aim of the study was to compare ghrelin, adiponectin, leptin, resistin, lipid, glucose, and insulin concentrations in GHD children, depending on the IGF-I bioavailability. Methods. The analysis comprised 26 children with GHD, aged 5.7–15.3 yrs. Fasting serum concentrations of IGF-I, IGFBP-3, ghrelin, leptin, adiponectin, resistin, lipids, glucose, and insulin were measured. The GHD children were divided into two subgroups: (1) with lower IGF-I/IGFBP-3 molar ratio and (2) with higher IGF-I/IGFBP-3 molar ratio. The control group consisted of 39 healthy children, aged 5.1–16.6 yrs, of normal height and body mass. Results. GHD children with lower IGF-I/IGFBP-3 molar ratio were found to have a significantly lower body mass and insulin and triglyceride concentrations, as well as significantly higher ghrelin and adiponectin concentrations than GHD children with higher IGF-I/IGFBP-3. Conclusions. A better metabolic profile characterised GHD children with low IGF-I bioavailability. This phenomenon may be the result of high adiponectin and ghrelin concentrations in those children and their influence on adipose tissue, glucose uptake, and orexigenic axis.

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