Circulating Insulin-Like Growth Factor-1 and Its Binding Protein-3

Lam, Carolyn S.P.; Chen, Ming-Huei; Lacey, Seán; Yang, Qiong; Sullivan, Lisa M.; Xanthakis, Vanessa; Safa, Radwan; Smith, Holly; Peng, Xiao; Sawyer, Douglas B.; Vasan, Ramachandran S.

doi:10.1161/atvbaha.110.203943

Cited by 86 publications

(85 citation statements)

References 48 publications

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“…Specifically, a number of regulators of metabolic and adipocyte homeostasis appeared to predict adverse events in our study: IGF1 is involved in adipocyte proliferation and differentiation, and whereas some studies support a protective role with respect to atherosclerosis, others have not shown any association with coronary artery disease 17, 18. In the FHS, lower IGF1 levels were previously reported to be associated with adverse metabolic risk,19 and we now show an association with mortality in both single‐ and multimarker models. IGF1, in turn, is regulated by insulin‐like growth factor binding protein 1 (IGFBP1), which plays a role in glucose counter‐regulation.…”

Section: Discussionsupporting

confidence: 78%

“…Last, resistin is an adipokine that impairs insulin action and is thought to represent a mechanistic link of obesity with diabetes mellitus 17, 18, 26. In previous FHS analyses, resistin was reported to be associated with incident HF, and it also predicted adverse outcomes among patients with stable coronary disease in the Heart and Soul study 19, 27, 28…”

Section: Discussionmentioning

confidence: 99%

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Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

221

228

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BackgroundThe discovery of novel and highly predictive biomarkers of cardiovascular disease (CVD) has the potential to improve risk‐stratification methods and may be informative regarding biological pathways contributing to disease.Methods and ResultsWe used a discovery proteomic platform that targeted high‐value proteins for CVD to ascertain 85 circulating protein biomarkers in 3523 Framingham Heart Study participants (mean age, 62 years; 53% women). Using multivariable‐adjusted Cox models to account for clinical variables, we found 8 biomarkers associated with incident atherosclerotic CVD, 18 with incident heart failure, 38 with all‐cause mortality, and 35 with CVD death (false discovery rate, q<0.05 for all; P‐value ranges, 9.8×10−34 to 3.6×10−2). Notably, a number of regulators of metabolic and adipocyte homeostasis were associated with cardiovascular events, including insulin‐like growth factor 1 (IGF1), insulin‐like growth factor binding protein 1 (IGFBP1), insulin‐like growth factor binding protein 2 (IGFBP2), leptin, and adipsin. In a multimarker approach that accounted for clinical factors, growth differentiation factor 15 (GDF15) was associated with all outcomes. In addition, N‐terminal pro‐b‐type natriuretic peptide, C‐reactive protein, and leptin were associated with incident heart failure, and C‐type lectin domain family 3 member B (CLEC3B; tetranectin), N‐terminal pro‐b‐type natriuretic peptide, arabinogalactan protein 1 (AGP1), soluble receptor for advanced glycation end products (sRAGE), peripheral myelin protein 2 (PMP2), uncarboxylated matrix Gla protein (UCMGP), kallikrein B1 (KLKB1), IGFBP2, IGF1, leptin receptor, and cystatin‐C were associated with all‐cause mortality in a multimarker model.ConclusionsWe identified numerous protein biomarkers that predicted cardiovascular outcomes and all‐cause mortality, including biomarkers representing regulators of metabolic homeostasis and inflammatory pathways. Further studies are needed to validate our findings and define clinical utility, with the ultimate goal of improving strategies for CVD prevention.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

221

228

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“…In two previous studies on the association of IGF1 with the metabolic syndrome in older populations, U-shaped relationships have been reported (9,10). Others report low IGF1 values to be related to a greater metabolic burden (11,12,13,14). These cohort studies only speculate about the role of this association in the development of CVD over time.…”

Section: Introductionmentioning

confidence: 95%

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

Bunderen

Oosterwerff

Schoor

et al. 2013

European Journal of Endocrinology

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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.

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“…In contrast to these findings, population-based studies (11,12,15,18) mainly revealed conflicting results regarding the associations of IGF1 or IGFBP3 levels with lipid levels. Filipsson Nyström et al (18) detected an inverse relation between IGF1 and cholesterol levels in 202 men and women.…”

Section: Introductionmentioning

confidence: 96%

“…In previous studies, IGF1 levels were linked to cardiovascular risk factors such as insulin resistance (7), metabolic syndrome (8,9), and also single lipid levels (10,11,12,13,14,15,16,17,18,19).…”

Section: Introductionmentioning

confidence: 99%

Cross-sectional and longitudinal relation of IGF1 and IGF-binding protein 3 with lipid metabolism

Eggert

Wallaschofski

Grotevendt

et al. 2014

European Journal of Endocrinology

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Background: Previous intervention studies in patients with GH disorders suggested an impact of IGF1 and IGF-binding protein 3 (IGFBP3) on lipid metabolism, whereas population-based studies revealed conflicting results. Therefore, we aimed to assess the cross-sectional and longitudinal associations between IGF1 or IGFBP3 serum levels and lipids (total, LDL, or HDL cholesterol and triglycerides) in a large-scale study. Methods: Data of 2935 subjects (1356 women) from the population-based Study of Health in Pomerania (SHIP) were used. ANOVA, quantile regression, and logistic regression models adjusted for age, waist circumference, physical activity, and alcohol consumption were performed. Results: In cross-sectional analyses, we detected that IGF1 and IGFBP3 levels were positively related to total and LDL cholesterol and inversely related to HDL cholesterol in both sexes. Furthermore, IGFBP3 levels showed a positive relationship to triglycerides. In total, IGFBP3 levels were more strongly associated to lipids than IGF1. In longitudinal analysis, we found no influence of baseline IGF1 or IGFBP3 serum concentration on incidentally elevated or reduced lipid levels. However, the positive relationship between IGFBP3 and incidentally elevated triglycerides barely missed statistical significance in women. Conclusion: The present study showed strong cross-sectional associations between IGF1 or IGFBP3 and lipids, whereas no longitudinal relationships were revealed. Therefore, our findings suggest IGF1 and IGFBP3 as a risk marker rather than a risk factor for alterations in lipid metabolism. Further studies are needed to elucidate the mechanisms underlying the association between the GH/IGF axis and lipid metabolism.

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Circulating Insulin-Like Growth Factor-1 and Its Binding Protein-3

Cited by 86 publications

References 48 publications

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

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

Cross-sectional and longitudinal relation of IGF1 and IGF-binding protein 3 with lipid metabolism

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