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Serum Insulin-Like Growth Factor-1 Binding Proteins 1 and 2 and Mortality in Older Adults: The Health, Aging, and Body Composition Study

Authors

  • Donglei Hu PhD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • ab Ludmila Pawlikowska PhD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • bc Alka Kanaya MD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • a Wen-Chi Hsueh PhD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • ab Lisa Colbert PhD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • f Anne B. Newman MD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • g Suzanne Satterfield MD, DrPH,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • h Clifford Rosen MD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • i Steven R. Cummings MD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • j Tamara B. Harris MD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • k Elad Ziv MD,

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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  • and abde for the Health, Aging, and Body Composition Study

    1. From the aDepartment of Medicine, bInstitute for Human Genetics, cDepartment of Anesthesia, dDepartment of Epidemiology and Biostatistics, eHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CaliforniafDepartment of Kinesiology, University of Wisconsin, Madison, WisconsingDepartment of Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniahDepartment of Preventive Medicine, University of Tennessee, Memphis, TennesseeiJackson Laboratory and St. Joseph Hospital, Bangor, MainejCalifornia Pacific Medical Center Research Institute, San Francisco, California; and kLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
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Address correspondence to Elad Ziv, 1701 Divisadero Street, Suite 554, UCSF Box 1732, San Francisco, CA 94115. E-mail elad.ziv@ucsf.edu

Abstract

OBJECTIVE: To evaluate the relationship between serum insulin-like growth factor 1 (IGF-1), IGF-1 binding protein 1 (IGFBP-1), and IGF-1 binding protein 2 (IGFBP-2) and fasting insulin, fasting glucose, adiposity, and mortality in older adults.

DESIGN: A prospective cohort study with mean follow-up of 6.2 years.

SETTING: Participants were recruited and followed at two centers affiliated with academic medical institutions.

PARTICIPANTS: Six hundred twenty-five men and women aged 70 and older and in good health at the time of enrollment.

MEASUREMENTS: Serum IGF-1, IGFBP-1, and IGFBP-2; fasting serum insulin; fasting serum glucose; visceral fat; and total percent fat.

RESULTS: Higher IGFBP-1 and higher IGFBP-2 were significantly associated with lower fasting insulin, lower fasting glucose, and lower adiposity, but higher IGFBP-1 and IGFBP-2 were associated with greater mortality. In multivariate adjusted models, the hazard ratio for all-cause mortality was 1.48 (95% confidence interval (CI)=1.14–1.92) per standard deviation (SD) increase in IGFBP-2 and 1.34 (95% CI=1.01–1.76) per SD increase in IGFBP-1. No association was found between IGF-1 and all-cause mortality.

CONCLUSIONS: Higher IGFBP-1 and IGFBP-2 are associated with lower adiposity and decreased glucose tolearance but also with greater all-cause mortality. Higher levels of serum IGF-1 binding protein (IGFBP) may indicate greater IGF-1 activity and thus represent an association between higher IGF-1 activity and mortality in humans.

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