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IGF1 and its binding proteins 3 and 1 are differentially associated with metabolic syndrome in older men
Bu B Yeap1, S A Paul Chubb, Ken K Y Ho
1School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia. byeap@cyllene.uwa.edu.au
Insights
In older men, both low and high levels of insulin-like growth factor 1 (IGF1) and IGF-binding protein 3 (IGFBP3) are linked to metabolic syndrome. Insulin-like growth factor 1-binding protein 1 (IGFBP1) shows a protective effect against metabolic syndrome.
Area of Science:
- Endocrinology
- Gerontology
- Metabolic Research
Background:
- Circulating insulin-like growth factor 1 (IGF1) levels decrease with age, with associations to cardiovascular mortality varying across studies.
- The role of IGF-binding proteins 3 (IGFBP3) and 1 (IGFBP1) in cardiovascular disease risk is not well-established.
Purpose of the Study:
- To investigate the associations between IGF1, IGFBP3, and IGFBP1 with metabolic syndrome in elderly men.
- To determine the relationship between these biomarkers and the components of metabolic syndrome.
Main Methods:
- Cross-sectional analysis of 3980 community-dwelling men aged 70 years and older.
- Plasma levels of IGF1, IGFBP3, and IGFBP1 were measured.
- Metabolic syndrome was diagnosed using National Cholesterol Education Program-Adult Treatment Panel III criteria.
Main Results:
- A U-shaped association was observed for IGF1 and IGFBP3 with metabolic syndrome, with middle levels showing the lowest odds.
- Increasing levels of IGFBP1 demonstrated a dose-response reduction in metabolic syndrome risk (P<0.001).
- IGF1 was associated with two, IGFBP1 with four, and IGFBP3 with all five components of metabolic syndrome.
Conclusions:
- Both low and high concentrations of IGF1 and IGFBP3 may be unfavorable for metabolic health in older men.
- IGFBP1 is a significant marker for assessing metabolic syndrome, potentially reflecting insulin sensitivity.
- The IGF1/IGFBP3 ratio is less informative for metabolic syndrome assessment; longitudinal studies are needed to link these factors to cardiovascular events.
Objective:
Circulating 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.
Design:
Cross-sectional analysis of 3980 community-dwelling men aged >or=70 years. Methods Morning 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.
Results:
For 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.
Conclusions:
In 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.
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