IGFBP-2 and aging: a 20-year longitudinal study on IGFBP-2, IGF-I, BMI, insulin sensitivity and mortality in an aging population. Issue 2 (February 2019)

• Record Type: Journal Article
• Authors: van den Beld, Annewieke W; Carlson, Olga D; Doyle, Maire E; Rizopoulos, Dimitris; Ferrucci, Luigi; van der Lely, Aart Jan; Egan, Josephine M
• Is Part Of: European journal of endocrinology. Volume 180:Issue 2(2019)
• Page Start: 109
• Page End: 116
• Publication Date: 2019-02
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/EJE-18-0422
• Languages: English
• ISSNs: 0804-4643

Abstract

Abstract : Objective: Insulin-like growth factor-binding protein-2 (IGFBP-2) concentrations are low in subjects with metabolic syndrome and type 2 diabetes. Intriguingly, recent studies have demonstrated an association between high IGFBP-2 concentrations and increased mortality not only in populations with certain types of cancer, but also in relatively healthy populations. We evaluated the role of IGFBP-2 in relation to BMI and mortality. Design and Participants: BMI, insulin sensitivity, insulin-like growth factor 1 (IGF-I) and IGFBP-2 were assessed repeatedly in 539 participants of the Baltimore Longitudinal Study of Aging around the ages of 55, 65 and 75 years. Results: IGFBP-2 concentrations positively correlated with insulin sensitivity and inversely with BMI, both at baseline and follow-up. Independent of IGF-I, sex, BMI and insulin sensitivity, circulating IGFBP-2 levels positively correlated with age ( P < 0.001). Changes over time in BMI were associated with an inverse correlation in IGFBP-2 concentrations. Furthermore, we found indications of a relationship between low baseline IGFBP-2 levels and mortality. Remarkably, after adjustment for insulin sensitivity, the opposite association was found, as a unit increase of log(IGFBP2) was associated with an increase in the log hazard by 1.43 (95% CI: 0.3–2.6). This accounted for both baseline ( P = 0.02) as well as serial ( P < 0.001) measurements of IGFBP2. Finally, in this longitudinal study, we found that IGF-I concentrations increased with age (0.82 ± 0.2 (µg/L)/year, P < 0.001). Conclusion: This is the first study investigating the relationship between IGFBP-2 levels and age in a longitudinal setting. Serum IGFBP-2 levels increase with age after the age of 50 years and evolve in parallel with insulin sensitivity. IGFBP-2 may therefore be a potential marker for insulin sensitivity. We further show that IGFBP-2 levels can predict mortality in this aging population. However, its predictive value for mortality can only be interpreted in relation to insulin sensitivity. After adjustment for insulin sensitivity, high IGFBP-2 levels are predictive of increased mortality.