scholarly journals IGF1 and its binding proteins 3 and 1 are differentially associated with metabolic syndrome in older men

2010 ◽  
Vol 162 (2) ◽  
pp. 249-257 ◽  
Author(s):  
Bu B Yeap ◽  
S A Paul Chubb ◽  
Ken K Y Ho ◽  
Johnson W S Setoh ◽  
Kieran A McCaul ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Binding Proteins ◽  
Older Men ◽  
Community Dwelling ◽  
Igf Binding Proteins ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Igf Binding ◽  
Response Gradient ◽  
Sectional Analysis

ObjectiveCirculating IGF1 declines with age, and reduced circulating IGF1 is associated with increased cardiovascular mortality in some but not all studies. The relationship between IGF-binding proteins 3 and 1 (IGFBP3 and IGFBP1) with risk of cardiovascular disease remains unclear. We sought to examine associations between IGF1, IGFBP3 and IGFBP1 with metabolic syndrome in older men.DesignCross-sectional analysis of 3980 community-dwelling men aged ≥70 years.MethodsMorning plasma levels of IGF1, IGFBP3 and IGFBP1 were assayed. Metabolic syndrome was defined according to National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria.ResultsFor IGF1 and IGFBP3, there was a U-shaped relationship, with middle quintiles possessing the lowest odds ratios (OR) for metabolic syndrome (reference Q1, Q3 IGF1: OR 0.74, 95% confidence intervals 0.57–0.96, Q3 IGFBP3: OR 0.67, 0.51–0.87). Increasing IGFBP1 was associated with reduced risk of metabolic syndrome with a dose–response gradient (reference Q1, OR for Q2 to Q5 IGFBP1: 0.56, 0.33, 0.22 and 0.12 respectively, P<0.001). IGF1 was associated with two, IGFBP1 with four and IGFBP3 with all five components of the metabolic syndrome. The ratio of IGF1/IGFBP3 was not associated with metabolic syndrome.ConclusionsIn older men, both lower and higher IGF1 and IGFBP3 levels may be metabolically unfavourable. IGFBP1, as a marker of insulin sensitivity, is relevant in the assessment of metabolic syndrome, while the IGF1/IGFBP3 ratio is less informative. Longitudinal follow-up of this cohort would be needed to determine whether these distributions of IGF1, IGFBP3 and IGFBP1 predict incidence of cardiovascular events during male ageing.

scholarly journals r-metHuLeptin improves highly active antiretroviral therapy-induced lipoatrophy and the metabolic syndrome, but not through altering circulating IGF and IGF-binding protein levels: observational and interventional studies in humans

2009 ◽  
Vol 160 (2) ◽  
pp. 173-176 ◽  
Author(s):  
Aoife M Brennan ◽  
Jennifer H Lee ◽  
Sotirios Tsiodras ◽  
Jean L Chan ◽  
John Doweiko ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Model Assessment ◽  
Inverse Association ◽  
Igf Binding Proteins ◽  
Cross Sectional ◽  
Highly Active ◽  
The Metabolic Syndrome ◽  
Igf Binding

ObjectiveLeptin is an adipocyte secreted hormone and an important regulator of neuroendocrine, metabolic, and immune function. Both r-metHuLeptin and IGF1 administration result in reduced central adipose tissue in subjects with highly active antiretroviral therapy-induced metabolic syndrome (HAART-MS) but whether the effects of leptin are mediated through increasing IGF levels remains unknown.MethodsTo assess whether r-metHuLeptin improves the HAART-MS by regulating circulating IGF and IGFBPs, we first conducted a cross-sectional study of 118 men and women with HIV infection and >6 months of exposure to antiretroviral medications to examine any association between circulating IGF1 and leptin levels. We also performed a randomized, double-blinded, placebo-controlled, crossover trial of recombinant human leptin (r-metHuLeptin) administration to seven HIV positive men with lipoatrophy and leptin deficiency (leptin <3 ng/ml) related to antiretroviral medication use.ResultsIn the observational study, leptin levels were inversely associated with circulating IGF1 levels after adjusting for age and gender (r=0.27 P=0.002), but this inverse association became non-significant after adjustment for % body fat and exercise. In the interventional leptin study, leptin levels increased significantly during r-metHuLeptin treatment (from 1.34±0.20 ng/ml at baseline to 17±5.05 ng/ml after 8 weeks P=0.046) and metabolic parameters improved including reduced fasting insulin levels and reduced homeostasis model assessment-insulin resistance (HOMA-IR). Despite the increase in circulating leptin levels, there was no change in IGF1, IGF2, free IGF1, or IGF-binding proteins during the 2-month treatment period.ConclusionThe effects of r-metHuLeptin in patients with HAART-MS are not mediated through increasing IGF or IGFBP levels.

scholarly journals Associations of IGF1 and its binding proteins with abdominal aortic aneurysm and aortic diameter in older men

2012 ◽  
Vol 166 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Bu B Yeap ◽  
S A Paul Chubb ◽  
Kieran A McCaul ◽  
Leon Flicker ◽  
Ken K Y Ho ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Binding Proteins ◽  
Older Men ◽  
Community Dwelling ◽  
Aortic Diameter ◽  
Aortic Dilation ◽  
Cross Sectional ◽  
Gh Secretion ◽  
Abdominal Aortic

ObjectiveAbdominal aortic aneurysm (AAA) is most prevalent in older men. GH secretion declines with age resulting in reduced IGF1 levels. IGF1 and its binding proteins (IGFBPs) are expressed in vasculature, and lower IGF1 levels have been associated with cardiovascular risk factors and disease. However, the relationship of the IGF1 system with aortic dilation and AAA is unclear. We tested the hypothesis that circulating IGF1 and IGFBPs are associated with AAA and aortic diameter in older men.DesignA cross-sectional analysis involving 3981 community-dwelling men aged 70–89 years was performed.MethodsAbdominal aortic diameter was measured by ultrasound. Plasma total IGF1, IGFBP1 and IGFBP3 were measured by immunoassays.ResultsAfter adjustment for age, body mass index, waist:hip ratio, smoking, hypertension, dyslipidemia, diabetes, coronary heart disease and serum creatinine, a higher IGF1 level was associated with AAA (odds ratio (OR)/1 s.d. increase 1.18, 95% confidence interval (CI) 1.05–1.33, P=0.006), as was the ratio of IGF1/IGFBP3 (OR=1.22, 95% CI 1.10–1.35, P<0.001). Highest IGF1 concentrations compared with lowest quintile were significantly associated with AAA (quintile (Q) 5 vs Q1: OR=1.80, 95% CI 1.20–2.70, P=0.004) as were IGF1/IGFBP3 ratios (Q5 vs Q1: OR=2.52, 95% CI 1.59–4.02, P<0.001). IGF1 and IGFBP1 were independently associated with aortic diameter (β=0.200, 95% CI 0.043–0.357, P=0.012 and β=0.274, 95% CI 0.098–0.449, P=0.002 respectively).ConclusionsIn older men, higher IGF1 and an increased ratio of IGF1/IGFBP3 are associated with AAA, while IGFBP1 is independently associated with increased aortic diameter. Components of the IGF1 system may contribute to, or be a marker for, aortic dilation in ageing men.

Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone

2002 ◽  
Vol 282 (2) ◽  
pp. E483-E490 ◽  
Author(s):  
Michael I. Lewis ◽  
Gail D. Horvitz ◽  
David R. Clemmons ◽  
Mario Fournier
Keyword(s):  
Binding Proteins ◽  
Muscle Fibers ◽  
Female Rats ◽  
Diaphragm Muscle ◽  
Igf Binding Proteins ◽  
Cross Sectional ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Silastic Implant

Recent studies suggest that the anabolic effects of testosterone in muscle may be mediated, in part, by the insulin-like growth factor (IGF) system. The aim of this study was to examine the effects of nandrolone (NAN) on both IGF-I and IGF-binding proteins (IGFBPs) in the diaphragm muscle of 1-yr-old female rats. NAN (6.6 mg · kg−1 · day−1) was infused continuously for 17 days using a subcutaneous Silastic implant, whereas controls (CTL) received blank capsules. Muscle fibers were classified immunohistochemically, and fiber cross-sectional areas (CSA) were determined quantitatively. IGF-I levels in both serum and muscle were determined by RIA. Immunoreactivity to an IGF-I antibody was used to localize IGF-I expression within individual muscle fibers. Muscle IGFBPs were determined by SDS-PAGE and Western ligand blotting and measured by scanning densitometry. Body weight was higher in the NAN group compared with CTL (9.4 ± 4.5% vs. −0.6 ± 3.1%). There were no changes in the fiber composition of the diaphragm. NAN increased the CSA of type IIa (20%) and type IIx/b (30%) diaphragm fibers. Levels of IGF-I in the diaphragm muscle were significantly higher (50%) in NAN-treated animals. Immunohistochemistry revealed increased localization of IGF-I within type IIx/b diaphragm fibers. In addition, NAN increased IGFBP-3 within the diaphragm (69%), whereas IGFBP-4 decreased (40%). We conclude that NAN-induced diaphragm muscle fiber hypertrophy is mediated, in part, by influences of the IGF system within the muscle, such that coordinated changes in IGFBPs reflect a direction of change that has been associated with an anabolic response in other test systems.

Associations of osteocalcin forms with metabolic syndrome and its individual components in older men: The Health In Men Study

2021 ◽  
Author(s):  
Xiaoying Liu ◽  
Bu B Yeap ◽  
Kaye E Brock ◽  
Itamar Levinger ◽  
Jonathan Golledge ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Animal Studies ◽  
Density Lipoprotein ◽  
Older Men ◽  
Epidemiological Studies ◽  
Metabolic Parameters ◽  
Undercarboxylated Osteocalcin ◽  
Cross Sectional ◽  
Metabolic Outcomes ◽  
Sectional Analysis

Abstract Context The osteoblast-derived polypeptide, osteocalcin (OC), has been associated with lower risk of type 2 diabetes and metabolic syndrome (MetS) in several epidemiological studies. Animal studies indicated the undercarboxylated form of osteocalcin drives its association with metabolic outcomes. We compared associations of undercarboxylated and carboxylated OC with MetS and its components in older men. Design A cross-sectional analysis of 2575 men aged &gt;70 resident in Perth, Western Australia. Undercarboxylated osteocalcin (ucOC) was assayed using a hydroxyapatite binding method and carboxylated OC (cOC) calculated by subtracting ucOC from total OC. Main outcome measures were MetS and its components. Results Both lower serum ucOC and cOC levels, and the proportion of cOC (%cOC) were associated with less favourable metabolic parameters (higher waist circumference, triglyceride, glucose and blood pressure and lower high-density lipoprotein cholesterol), while inverse associations were found with %ucOC. Men in the lowest quintile of ucOC had higher risk of MetS compared to men in the highest quintile (Q1 ≤7.7 vs. Q5 &gt;13.8 ng/ml; OR=2.4, 95% CI 1.8-3.2). Men in the lowest quintile of cOC had higher risk of MetS compared to those in the highest quintile (≤5.8 vs &gt;13.0 ng/ml; OR=2.4, 95%CI 1.8-3.2). Conclusions Lower concentrations of serum ucOC or cOC were associated with less favourable metabolic parameters and a higher risk of MetS. In contrast, a lower proportion of ucOC was associated with better metabolic parameters and lower MetS risk. Further research is warranted to determine whether ucOC and cOC are suitable biomarkers for cardiometabolic risk in men.

scholarly journals Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: the Health in Men Study

2008 ◽  
Vol 158 (6) ◽  
pp. 785-792 ◽  
Author(s):  
S A Paul Chubb ◽  
Zoë Hyde ◽  
Osvaldo P Almeida ◽  
Leon Flicker ◽  
Paul E Norman ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Free Testosterone ◽  
Older Men ◽  
Community Dwelling ◽  
Sex Hormone ◽  
Mass Action ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Hormone Binding ◽  
Cross Sectional

BackgroundReduced circulating testosterone and sex hormone-binding globulin (SHBG) are implicated as risk factors for metabolic syndrome. As SHBG increases with age while testosterone declines, we examined the relative contributions of SHBG and testosterone to the risk of metabolic syndrome in older men.MethodsWe conducted a cross-sectional study of 2502 community-dwelling men aged ≥70 years without known diabetes. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) criteria. Early morning fasting sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations.ResultsThere were 602 men with metabolic syndrome (24.1%). The risk of metabolic syndrome increased for total testosterone <20 nmol/l, SHBG <50 nmol/l and free testosterone <300 pmol/l. In univariate analyses SHBG was associated with all five components of metabolic syndrome, total testosterone was associated with all except hypertension, and free testosterone was associated only with waist circumference and triglycerides. In multivariate analysis, both total testosterone and especially SHBG remained associated with metabolic syndrome, with odds ratios of 1.34 (95% confidence interval (CI): 1.18–1.52) and 1.77 (95% CI: 1.53–2.06) respectively. Men with hypogonadotrophic hypogonadism (total testosterone <8 nmol/l, LH ≤12 IU/l) had the highest prevalence of metabolic syndrome (53%,P<0.001).ConclusionsLower SHBG is more strongly associated with metabolic syndrome than lower total testosterone in community-dwelling older men. SHBG may be the primary driver of these relationships, possibly reflecting its relationship with insulin sensitivity. Further studies should examine whether measures that raise SHBG protect against the development of metabolic syndrome in older men.

scholarly journals Associations of circulating dimethylarginines with the metabolic syndrome in the Framingham Offspring study

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0254577
Author(s):  
Ibrahim Musa Yola ◽  
Carlee Moser ◽  
Meredith S. Duncan ◽  
Edzard Schwedhelm ◽  
Dorothee Atzler ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cox Regression ◽  
Density Lipoprotein ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Sectional Analysis ◽  
Oxide Synthase ◽  
Circulating Levels ◽  
New Onset

Background Circulating levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are positively associated with the prevalence of metabolic syndrome (MetS) in cross-sectional investigations. It is unclear if circulating ADMA and other methylarginines are associated with incident MetS prospectively. Methods We related circulating ADMA, symmetric dimethylarginine (SDMA), L-arginine (ARG) concentrations (measured with a validated tandem mass spectrometry assay) and the ARG/ADMA ratio to MetS and its components in 2914 (cross-sectional analysis, logistic regression; mean age 58 years, 55% women) and 1656 (prospective analysis, Cox regression; mean age 56 years, 59% women) individuals from the Framingham Offspring Study who attended a routine examination. Results Adjusting for age, sex, smoking, and eGFR, we observed significant associations of ADMA (direct) and ARG/ADMA (inverse) with odds of MetS (N = 1461 prevalent cases; Odds Ratio [OR] per SD increment 1.13, 95%CI 1.04–1.22; and 0.89, 95%CI 0.82–0.97 for ADMA and ARG/ADMA, respectively). Upon further adjustment for waist circumference, systolic and diastolic blood pressure, glucose, high-density lipoprotein cholesterol, and triglycerides, we observed a positive relation between SDMA and MetS (OR per SD increment 1.15, 95% CI 1.01–1.30) but the other associations were rendered statistically non-significant. We did not observe statistically significant associations between any of the methylarginines and the risk of new-onset MetS (752 incident events) over a median follow-up of 11 years. Conclusion It is unclear whether dimethylarginines play an important role in the incidence of cardiometabolic risk in the community, notwithstanding cross-sectional associations. Further studies of larger samples are needed to replicate our findings.

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