IGFBP-2 and aging: A 20-year longitudinal study on IGFBP-2, IGF-I, BMI, insulin sensitivity and mortality in an aging population

Annewieke W. Van Den Beld, Olga D. Carlson, Maire E. Doyle, Dimitris Rizopoulos, Luigi Ferrucci, Aart Jan Van Der Lely, Josephine M. Egan

Research output: Contribution to journalArticle

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 St udy 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 inver se 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 st udy, 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 year s 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.

Original languageEnglish (US)
Pages (from-to)109-116
Number of pages8
JournalEuropean Journal of Endocrinology
Volume180
Issue number2
DOIs
StatePublished - Feb 1 2019
Externally publishedYes

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Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor I
Longitudinal Studies
Insulin Resistance
Mortality
Population
Baltimore
Somatomedins
Type 2 Diabetes Mellitus

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

IGFBP-2 and aging : A 20-year longitudinal study on IGFBP-2, IGF-I, BMI, insulin sensitivity and mortality in an aging population. / Van Den Beld, Annewieke W.; Carlson, Olga D.; Doyle, Maire E.; Rizopoulos, Dimitris; Ferrucci, Luigi; Van Der Lely, Aart Jan; Egan, Josephine M.

In: European Journal of Endocrinology, Vol. 180, No. 2, 01.02.2019, p. 109-116.

Research output: Contribution to journalArticle

Van Den Beld, Annewieke W. ; Carlson, Olga D. ; Doyle, Maire E. ; Rizopoulos, Dimitris ; Ferrucci, Luigi ; Van Der Lely, Aart Jan ; Egan, Josephine M. / IGFBP-2 and aging : A 20-year longitudinal study on IGFBP-2, IGF-I, BMI, insulin sensitivity and mortality in an aging population. In: European Journal of Endocrinology. 2019 ; Vol. 180, No. 2. pp. 109-116.
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T2 - A 20-year longitudinal study on IGFBP-2, IGF-I, BMI, insulin sensitivity and mortality in an aging population

AU - Van Den Beld, Annewieke W.

AU - Carlson, Olga D.

AU - Doyle, Maire E.

AU - Rizopoulos, Dimitris

AU - Ferrucci, Luigi

AU - Van Der Lely, Aart Jan

AU - Egan, Josephine M.

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N2 - 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 St udy 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 inver se 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 st udy, 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 year s 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.

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