Decline in circulating insulin-like growth factors and mortality in older adults: cardiovascular health study all-stars study
Open accessAbstract
BACKGROUND: The association between changes in IGF-I and IGF binding protein (IGFBP) levels and mortality in older adults is unknown. STUDY DESIGN: Participants were 997 persons 77 to 100 yr old enrolled in the Cardiovascular Health Study All Stars Study. Plasma levels of IGF-I, IGFBP-1, and IGFBP-3 were assessed at two study examinations (1996-1997 and 2005-2006). Mortality was assessed between 2006 and 2010. RESULTS: Cumulative mortality (CM) was similar among individuals who had at least 10% decreases over time in IGF-I levels (CM = 29.6%), individuals who had at least 10% increases over time in IGF-I levels (CM = 24.7%), and individuals who had IGF-I levels remaining within ±10% over time (CM = 23.5%). Adjusted for age, sex, race, diabetes, body mass index, creatinine, albumin, and C-reactive protein, decreasing IGF-I level had no significant association with overall cancer mortality or noncancer mortality. Levels of IGFBP-1 increased markedly over time by 38% (median). Individuals with the largest increases in IGFBP-1 level over time had significantly increased risk of mortality. The adjusted hazard ratio per sd of IGFBP-1 change was 1.40 for overall cancer mortality (95% confidence interval = 1.10, 1.77; P = 0.01) and 1.14 for noncancer mortality (95% confidence interval = 1.02, 1.27; P = 0.02). Changes in IGFBP-3 levels were not significantly associated with mortality. CONCLUSION: Among older adults, decreasing IGF-I level over time does not predict subsequent all-cause mortality, whereas increasing IGFBP-1 predicts increased risk of mortality.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Observational studies have reported inconsistent associations between IGF-1 and mortality.
“a series of observational studies have reported inconsistent associations (37-41)”
From Frailty in elderly people (2013) · cites this paper as [37]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Renehan, A. G., Zwahlen, M., Minder, C., O'Dwyer, S. T., Shalet, S. M., & Egger, M. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16044-3 · Cited by 1,697 · see citing works
Le Roith, D. (1997) · New England Journal of Medicine · doi:10.1056/nejm199702273360907 · Cited by 897 · see citing works
Functionally significant insulin-like growth factor I receptor mutations in centenarians
Suh, Y., Atzmon, G., Cho, M.-O., Hwang, D., Liu, B., Leahy, D. J., Barzilai, N., & Cohen, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705467105 · Cited by 703 · see citing works
A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis
Niedernhofer, L. J., Garinis, G. A., Raams, A., Lalai, A. S., Robinson, A. R., Appeldoorn, E., Odijk, H., Oostendorp, R., Ahmad, A., van Leeuwen, W., et al. (2006) · Nature · doi:10.1038/nature05456 · Cited by 669 · see citing works
Growth Hormone Replacement in Healthy Older Men Improves Body Composition but Not Functional Ability
Papadakis, M. A., Grady, D., Black, D., Tierney, M. J., Gooding, G. A. W., Schambelan, M., & Grunfeld, C. (1996) · Annals of Internal Medicine · doi:10.7326/0003-4819-124-8-199604150-00002 · Cited by 474 · see citing works
Blackman, M. R. (2002) · JAMA · doi:10.1001/jama.288.18.2282 · Cited by 455 · see citing works
Laboratory methods and quality assurance in the Cardiovascular Health Study
Cushman, M., Cornell, E. S., Howard, P. R., Bovill, E. G., & Tracy, R. P. (1995) · Clinical Chemistry · doi:10.1093/clinchem/41.2.264 · Cited by 439 · see citing works
Laughlin, G. A., Barrett-Connor, E., Criqui, M. H., & Kritz-Silverstein, D. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030967 · Cited by 374 · see citing works
Systematic review: the safety and efficacy of growth hormone in the healthy elderly
Liu, H., Bravata, D. M., Olkin, I., Nayak, S., Roberts, B., Garber, A. M., & Hoffman, A. R. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-2-200701160-00005 · Cited by 370 · see citing works
Swerdlow, A. J., Higgins, C. D., Adlard, P., & Preece, M. A. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09519-3 · Cited by 289 · see citing works
Vasan, R. S., SULLIVAN, L. M., D’Agostino, R. B., Roubenoff, R., Harris, T. B., Sawyer, D. B., Levy, D. A., & Wilson, P. W. F. (2003) · Annals of Internal Medicine · doi:10.7326/0003-4819-139-8-200310210-00007 · Cited by 279 · see citing works
Nass, R., Pezzoli, S. S., Oliveri, M. C., Patrie, J. T., Harrell, F. E., Clasey, J. L., Heymsfield, S. B., Bach, M. A., Vance, M. L., & Thorner, M. O. (2008) · Annals of Internal Medicine · doi:10.7326/0003-4819-149-9-200811040-00003 · Cited by 255 · see citing works
Domené, H. M., Bengolea, S. V., Martínez, A. S., Ropelato, M. G., Pennisi, P. A., Scaglia, P. A., Heinrich, J. J., & Jasper, H. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa013100 · Cited by 243 · see citing works
Hilding, A., Brismar, K., Degerblad, M., Thoren, M., & Hall, K. E. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.9.7545695 · Cited by 125 · see citing works
Mortality and Serum Insulin-Like Growth Factor (IGF)-I and IGF Binding Protein 3 Concentrations
Friedrich, N., Haring, R., Nauck, M. A., Lüdemann, J., Rosskopf, D., Spilcke-Liss, E., Felix, S. B., Dörr, M., Brabant, G. E., Völzke, H., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2138 · Cited by 116 · see citing works
Leu, J. I.-J., & George, D. L. (2007) · Genes & Development · doi:10.1101/gad.1567107 · Cited by 100 · see citing works
van Bunderen, C. C., van Nieuwpoort, I. C., van Schoor, N. M., Deeg, D. J. H., Lips, P. T. A. M., & Drent, M. L. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0940 · Cited by 95 · see citing works
Brugts, M. P., van den Beld, A. W., Hofland, L. J., van der Wansem, K., van Koetsveld, P. M., Frystyk, J., Lamberts, S. W. J., & Janssen, J. A. M. J. L. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1633 · Cited by 90 · see citing works
Lang, C. H., Vary, T., & Frost, R. (2003) · Endocrinology · doi:10.1210/en.2002-0192 · Cited by 89 · see citing works
Provision or Distribution of Growth Hormone for “Antiaging”
Perls, T. T., Reisman, N. R., & Olshansky, S. J. (2005) · JAMA · doi:10.1001/jama.294.16.2086 · Cited by 87 · see citing works
IL-6 Stimulation of Insulin-like Growth Factor Binding Protein (IGFBP)-1 Production
Samstein, B., Hoimes, M. L., Fan, J., Frost, R. A., Gelato, M. C., & Lang, C. H. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1705 · Cited by 84 · see citing works
Total and Cause-Specific Mortality in the Cardiovascular Health Study
Newman, A. B., Sachs, M. C., Arnold, A. M., Fried, L. P., Kronmal, R. A., Cushman, M., Psaty, B. M., Harris, T. B., Robbins, J. A., Burke, G. L., et al. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/glp127 · Cited by 79 · see citing works
Self-citationHu, D., Pawlikowska, L., Kanaya, A. M., Hsueh, W., Colbert, L. H., Newman, A. B., Satterfield, S., Rosen, C. J., Cummings, S. R., Harris, T. B., et al. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2009.02318.x · Cited by 74 · see citing works
Self-citationKaplan, R. C., McGinn, A. P., Pollak, M., Kuller, L. H., Strickler, H. D., Rohan, T. E., Xue, X., Kritchevsky, S. B., Newman, A. B., & Psaty, B. M. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01637.x · Cited by 53 · see citing works
Self-citationKaplan, R. C., McGinn, A. P., Pollak, M., Kuller, L. H., Strickler, H. D., Rohan, T. E., Cappola, A. R., Xue, X. N., & Psaty, B. M. (2008) · American Heart Journal · doi:10.1016/j.ahj.2007.12.031 · Cited by 33 · see citing works
Self-citation
Flagged first, then by citations
1 of the 26 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Clegg, A., Young, J., Iliffe, S., Rikkert, M. O., & Rockwood, K. (2013) · The Lancet · doi:10.1016/s0140-6736(12)62167-9 · Cited by 9,503 · see citing works
Insulin resistance and cancer: The role of insulin and IGFs
Djiogue, S., Nwabo Kamdje, A. H., Vecchio, L., Kipanyula, M. J., Farahna, M., Aldebasi, Y., & Seke Etet, P. F. (2013) · Endocrine Related Cancer · doi:10.1530/erc-12-0324 · Cited by 263 · see citing works
Low insulin‐like growth factor‐1 level predicts survival in humans with exceptional longevity
Milman, S., Atzmon, G., Huffman, D. M., Wan, J., Crandall, J. P., Cohen, P., & Barzilai, N. (2014) · Aging Cell · doi:10.1111/acel.12213 · Cited by 220 · see citing works
A new link between diabetes and cancer: enhanced WNT/β-catenin signaling by high glucose
García-Jiménez, C., García-Martínez, J. M., Chocarro-Calvo, A., & De la Vieja, A. (2014) · Journal of Molecular Endocrinology · doi:10.1530/jme-13-0152 · Cited by 151 · see citing works
Milman, S., Huffman, D. M., & Barzilai, N. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.014 · Cited by 150 · see citing works
Diabetes-related alterations in the enteric nervous system and its microenvironment
Bagyánszki, M. (2012) · World Journal of Diabetes · doi:10.4239/wjd.v3.i5.80 · Cited by 71 · see citing works
Mukama, T., Srour, B., Johnson, T., Katzke, V. A., & Kaaks, R. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad212 · Cited by 55 · see citing works
van den Beld, A. W., Carlson, O. D., Doyle, M. E., Rizopoulos, D., Ferrucci, L., van der Lely, A. J., & Egan, J. M. (2018) · European Journal of Endocrinology · doi:10.1530/eje-18-0422 · Cited by 51 · see citing works
Kiss, T., Nyúl‐Tóth, Á., Gulej, R., Tarantini, S., Csípő, T., Mukli, P., Ungvari, A., Balasubramanian, P., Yabluchanskiy, A., Benyó, Z., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00519-1 · Cited by 48 · see citing works
Shea, S., Lima, J. A. C., Roux, A. V. D., Jorgensen, N. W., & McClelland, R. L. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165651 · Cited by 47 · see citing works
Specific metabolic biomarkers as risk and prognostic factors in colorectal cancer
Muc‐Wierzgoń, M. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i29.9759 · Cited by 39 · see citing works
Gulej, R., Patai, R., Ungvari, A., Kállai, A., Tarantini, S., Yabluchanskiy, A., Huffman, D. M., Conboy, M. J., Conboy, I. M., Mika Kivimaki, B., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01657-y · Cited by 29 · see citing works
The double trouble of metabolic diseases: the diabetes–cancer link
Tudzarova, S., & Osman, M. A. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-11-1550 · Cited by 26 · see citing works
Trajectories of IGF-I Predict Mortality in Older Adults: The Cardiovascular Health Study
Sanders, J. L., Guo, W., O’Meara, E. S., Kaplan, R. C., Pollak, M., Bartz, T. M., Newman, A. B., Fried, L. P., & Cappola, A. R. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx143 · Cited by 25 · see citing works
Self-citationInsulin-like Growth Factor-Binding Protein-1 (IGFBP-1) as a Biomarker of Cardiovascular Disease
LEWITT, M. S., & Boyd, G. W. (2024) · Biomolecules · doi:10.3390/biom14111475 · Cited by 17 · see citing works
Insulin-Like Growth Factor-1 Bioactivity Plays a Prosurvival Role in Older Participants
Maggio, M. G., Cattabiani, C., Lauretani, F., Bandinelli, S., Vita, F. D., Dall’Aglio, E., Corsonello, A., Lattanzio, F., Paolisso, G., Ferrucci, L., et al. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt045 · Cited by 16 · see citing works
Hormones and Cardiovascular Disease in Older Men
Yeap, B. B., & Flicker, L. A. (2014) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.12.004 · Cited by 14 · see citing works
Aneke-Nash, C. S., Parrinello, C. M., Rajpathak, S. N., Rohan, T. E., Strotmeyer, E. S., Kritchevsky, S. B., Psaty, B. M., Bůžková, P., Kizer, J. R., Newman, A. B., et al. (2015) · Journal of the American Geriatrics Society · doi:10.1111/jgs.13390 · Cited by 13 · see citing works
Self-citationMiyake, H., Kanazawa, I., & Sugimoto, T. (2016) · Endocrine Journal · doi:10.1507/endocrj.ej16-0076 · Cited by 13 · see citing works
Ritsinger, V., Brismar, K., Mellbin, L., Näsman, P., Rydén, L., Söderberg, S., & Norhammar, A. (2018) · Diabetes and Vascular Disease Research · doi:10.1177/1479164118781892 · Cited by 10 · see citing works
Aneke-Nash, C. S., Domínguez‐Islas, C., Bůžková, P., Qi, Q., Xue, X., Pollak, M., Strickler, H. D., & Kaplan, R. C. (2015) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2015.12.007 · Cited by 7 · see citing works
Self-citationAssociation of the IGF1 gene with fasting insulin levels
Willems, S. M., Cornes, B. K., Brody, J. A., Morrison, A. C., Lipovich, L., Dauriz, M., Chen, Y., Liu, C., Rybin, D. V., Gibbs, R. A., et al. (2016) · European Journal of Human Genetics · doi:10.1038/ejhg.2016.4 · Cited by 7 · see citing works
Self-citationÅberg, D., Gadd, G., Jood, K., Redfors, P., Stanne, T. M., Isgaard, J., Blennow, K., Zetterberg, H., Jern, C., Åberg, N. D., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119120 · Cited by 4 · see citing works
Somatotropic Axis’ Role in Ageing and Longevity Could Depend on Life-History Strategies of Species
Bourg, É. L. (2017) · Healthy ageing and longevity · doi:10.1007/978-3-319-63001-4_2 · Cited by 1 · see citing works
- Authors
- Kaplan, R. C., Bùžková, P., Cappola, A. R., Strickler, H. D., McGinn, A. P., Mercer, L. D., Arnold, A. M., Pollak, M. N., & Newman, A. B.
- Affiliations
- Albert Einstein College of Medicine (US)
- Department of Biostatistics (P.B., L.D.M., A.M.A.), University of Washington, Seattle, Washington 98195
- University of Pennsylvania (US)
- University of Washington (US)
- Lady Davis Research Institute of Jewish General Hospital and McGill University (M.N.P.), Montreal, Canada H3T 1E2
- University of Pittsburgh (US)
- Corresponding author
- Kaplan, Robert C.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-06-01
- Volume
- 97
- Issue
- 6
- Pages
- 1970-1976
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3387428
- OpenAlex
- W2100304249
- Cited by
- 24
- References
- 26
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 2
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Jewish General Hospital
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc045133-001, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01hc085085-011, n01hc085083-027, n01hc085080-026, n01hc085086-022, 5r01ag031890-04, n01hc55222-0-0-0, n01hc075150-004, n01hc035129-010)
- National Institute on Aging (R01-AG-031890, AG 20098, 1R01AG031890, R01AG020098, AG023269, AG027058, R56AG020098, R01AG023629, R01AG015928, R01AG027058, P30AG024827)
- National Heart, Lung, and Blood Institute (N01-HC-85081, N01HC85085, N01 HC085086, N01HC-85083, N0-1-HC-85239, HL094555, N01 HC085079, R01HL094555, N01HC85082, N01HC‐75150, N01 HC85086, N01 HC035129, HL-075366, N01HC85080, N01 HC015103, N01 HC55222, R01HL075366, U01HL080295, N01 HC055222, HL080295, R01HL080295, N01 HC075150, N01 HC045133, N01-HC85079, N01-HC85084)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Keywords
- insulin-like growth factor I, IGF-binding protein-1, IGF binding protein-3, mortality, older adults, cancer mortality, non-cancer mortality, all-cause mortality
- MeSH terms
- Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Follow-Up Studies, Humans, Insulin-Like Growth Factor I, Longitudinal Studies, Male, Mortality, Predictive Value of Tests, Risk Factors, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Black People, White People
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
