Low Circulating Insulin-Like Growth Factor I Bioactivity in Elderly Men Is Associated with Increased Mortality

Objective: High as well as low levels of IGF1 have been associated with cardiovascular diseases (CVD). The relationship of IGF1 with (components of) the metabolic syndrome could help to clarify this controversy. The aims of this study were: i) to investigate the association of IGF1 concentration with prevalent (components of) the metabolic syndrome; and ii) to examine the role of (components of) the metabolic syndrome in the relationship between IGF1 and incident CVD during 11 years of follow-up. Methods: Data were used from the Longitudinal Aging Study Amsterdam, a cohort study in a representative sample of the Dutch older population (R65 years). Data were available in 1258 subjects. Metabolic syndrome was determined using the definition of the US National Cholesterol Education Program Adult Treatment Panel III. CVD were ascertained by self-reports and mortality data. Results: Levels of IGF1 in the fourth quintile were associated with prevalent metabolic syndrome compared with the lowest quintile (odds ratio: 1.59, 95% confidence interval (CI) 1.09-2.33). The middle up to the highest quintile of IGF1 was positively associated with high triglycerides in women. Metabolic syndrome was not a mediator in the U-shaped relationship of IGF1 with CVD. Both subjects without the metabolic syndrome and low IGF1 levels (hazard ratio (HR) 1.75, 95% CI 1.12-2.71) and subjects with the metabolic syndrome and high IGF1 levels (HR 2.28, 95% CI 1.21-4.28) demonstrated increased risks of CVD. Conclusions: In older people, high-normal IGF1 levels are associated with prevalent metabolic syndrome and high triglycerides. Furthermore, this study suggests the presence of different pathomechanisms for both low and high IGF1 levels and incident CVD.

Section: Discussionmentioning

confidence: 99%

Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study

Bunderen

Oosterwerff

Schoor

et al. 2013

“…bioactive IGF1) (21). Subsequent studies have demonstrated that bioactive IGF1 is inversely correlated with age (22), significantly higher in females compared with males (23), and positively correlated with IGF1 as measured by immunoassay (i.e. total IGF1).…”

Section: Introductionmentioning

confidence: 98%

Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults

Vestergaard

Hansen

Frystyk

et al. 2014

Objective: Senescent changes in body composition and muscle strength are accompanied by reduced production of GH and IGF1, but the causal relationship remains elusive. We speculate that serum bioactive IGF1, measured by the IGF1 kinase receptor activation assay, is closer related to human physiological ageing than total IGF1 measured by immunoassay. Design: We conducted a cross-sectional study in 150 adult males and females, between 20 and 70 years. After an overnight fasting, serum levels of bioactive IGF1, total IGF1 and IGF-binding protein 1 (IGFBP1) and IGFBP3 were assessed. Furthermore, body composition and muscle strength was measured. Results: Total IGF1 levels were higher in females (PZ0.048). Bioactive IGF1 were identical in males and females (PZ0.31), decreasing with age. Total IGF1 tended to decrease more with age compared with bioactive IGF1 (K1.48 vs K0.89 percent/year, PZ0.052). Total body fat (TBF) was lower and BMI was higher in males (P!0.001 and PZ0.005), and both increased with age. Knee extension and elbow flexion force were higher in males (PZ0.001 and PZ0.001), but decreased with age in both genders.Total but not bioactive IGF1 was positively correlated to TBF, knee extension and muscle function in males. In multiple linear regression, only age predicted total IGF1, whereas age and IGFBP1 predicted bioactive IGF1. Conclusions: Bioactive IGF1 tends to decrease to a lesser extent than total IGF1 with age and was not correlated with measures of body composition or muscle strength. Therefore, levels of circulating bioactive IGF1 does not appear to be a better biomarker of physiological ageing than total IGF1.

“…In several studies, lower IGF1 levels have also been associated with all-cause or CVD-related mortality (19,20,21). AAA and atherosclerotic CVD share common risk factors such as smoking and elevated blood pressure or cholesterol levels, and often co-exist.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore a 'healthy survivor' effect is possible which would make our results more conservative and applicable to generally healthier community-dwelling older men, and we cannot comment on associations in women. We did not have the capacity to measure free or unbound IGF1 levels either by immunoassay or ultracentrifugation, nor were we able to measure circulating IGF1 bioactivity (20). Therefore, our assessment was limited to circulating total IGF1, IGFBP1 and IGFBP3.…”

Section: Discussionmentioning

confidence: 99%

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

Yeap

Chubb

McCaul

et al. 2012

Objective: Abdominal 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. Design: A cross-sectional analysis involving 3981 community-dwelling men aged 70-89 years was performed. Methods: Abdominal aortic diameter was measured by ultrasound. Plasma total IGF1, IGFBP1 and IGFBP3 were measured by immunoassays. Results: After 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, PZ0.006), as was the ratio of IGF1/IGFBP3 (ORZ1.22, 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: ORZ1.80, 95% CI 1.20-2.70, PZ0.004) as were IGF1/IGFBP3 ratios (Q5 vs Q1: ORZ2.52, 95% CI 1.59-4.02, P!0.001). IGF1 and IGFBP1 were independently associated with aortic diameter (bZ0.200, 95% CI 0.043-0.357, PZ0.012 and bZ0.274, 95% CI 0.098-0.449, PZ0.002 respectively). Conclusions: In 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.