{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:33:21Z","timestamp":1787884401322,"version":"build-2784847793"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"wellcome trust","doi-asserted-by":"publisher","award":["205212\/Z\/16\/Z"],"award-info":[{"award-number":["205212\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"cancer research uk","doi-asserted-by":"publisher","award":["C8221\/A29017"],"award-info":[{"award-number":["C8221\/A29017"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"cancer research uk","doi-asserted-by":"publisher","award":["C60192\/A28516"],"award-info":[{"award-number":["C60192\/A28516"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"medical research council","doi-asserted-by":"publisher","award":["MR\/M012190\/1"],"award-info":[{"award-number":["MR\/M012190\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ndph early career research fellowship"},{"DOI":"10.13039\/501100000321","name":"world cancer research fund","doi-asserted-by":"publisher","award":["2019\/1953"],"award-info":[{"award-number":["2019\/1953"]}],"id":[{"id":"10.13039\/501100000321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Epidemiol"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    While there is strong epidemiological evidence that circulating insulin-like growth factor-I (IGF-I) is associated with a higher risk of several cancers, little is known about its association with non-cancer outcomes. We investigated associations of circulating IGF-I with risk of 25 common conditions, other than cancer, in a large British cohort. Study participants were 318,749 middle-aged adults enrolled in the UK Biobank Study. Serum IGF-I concentration was measured in samples collected at baseline (2006\u20132010), and re-measured in 12,334 participants after an average of 4.3\u00a0years. We followed-up participants over an average of 11.5\u00a0years by linking to hospital admissions and mortality registries. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between circulating IGF-I and 25 common conditions, using the repeated IGF-I measurements to correct for regression dilution bias. After correction for multiple testing (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.002), IGF-I was positively associated with carpal tunnel syndrome (HR per 5\u00a0nmol\/l higher concentration\u2009=\u20091.12, 95% CI 1.08\u20131.16), and inversely associated with varicose veins (0.90, 0.85\u20130.95), cataracts (0.97, 0.95\u20130.99), diabetes (0.92, 0.90\u20130.95), and iron deficiency anaemia (0.90, 0.86\u20130.93). The associations for cataracts and diabetes attenuated when restricted to cases diagnosed after five or more years of follow-up, suggesting that these associations were likely affected by reverse causality. Higher IGF-I concentration might be associated with the risk for several conditions, but genetic studies are needed to clarify which associations may be causal.\n                  <\/jats:p>","DOI":"10.1007\/s10654-021-00811-y","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T19:02:37Z","timestamp":1636311757000},"page":"25-34","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Circulating insulin-like growth factor-I and risk of 25 common conditions: outcome-wide analyses in the UK Biobank study"],"prefix":"10.1007","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4102-6835","authenticated-orcid":false,"given":"Keren","family":"Papier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1049-4836","authenticated-orcid":false,"given":"Anika","family":"Knuppel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Perez-Cornago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9229-2589","authenticated-orcid":false,"given":"Eleanor L.","family":"Watts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy Y. N.","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Key","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth C.","family":"Travis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"issue":"11","key":"811_CR1","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1172\/JCI39375","volume":"119","author":"S Melmed","year":"2009","unstructured":"Melmed S. Acromegaly pathogenesis and treatment. J Clin Investig. 2009;119(11):3189\u2013202.","journal-title":"J Clin Investig"},{"issue":"7","key":"811_CR2","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nrc1387","volume":"4","author":"MN Pollak","year":"2004","unstructured":"Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer. 2004;4(7):505\u201318.","journal-title":"Nat Rev Cancer"},{"issue":"3","key":"811_CR3","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1210\/er.2009-0033","volume":"31","author":"M Sherlock","year":"2010","unstructured":"Sherlock M, Ayuk J, Tomlinson JW, Toogood AA, Aragon-Alonso A, Sheppard MC, et al. Mortality in patients with pituitary disease. Endocr Rev. 2010;31(3):301\u201342.","journal-title":"Endocr Rev"},{"issue":"3","key":"811_CR4","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1002\/ijc.32808","volume":"147","author":"EL Watts","year":"2020","unstructured":"Watts EL, Goldacre R, Key TJ, Allen NE, Travis RC, Perez-Cornago A. Hormone-related diseases and prostate cancer: an English national record linkage study. Int J Cancer. 2020;147(3):803\u201310. https:\/\/doi.org\/10.1002\/ijc.32808.","journal-title":"Int J Cancer"},{"issue":"3","key":"811_CR5","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s40618-019-01111-9","volume":"43","author":"M Parolin","year":"2020","unstructured":"Parolin M, Dassie F, Vettor R, Maffei P. Acromegaly and ultrasound: how, when and why? J Endocrinol Invest. 2020;43(3):279\u201387.","journal-title":"J Endocrinol Invest"},{"issue":"11","key":"811_CR6","doi-asserted-by":"publisher","first-page":"3933","DOI":"10.1210\/jc.2014-2700","volume":"99","author":"L Katznelson","year":"2014","unstructured":"Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933\u201351.","journal-title":"J Clin Endocrinol Metab"},{"issue":"18","key":"811_CR7","doi-asserted-by":"publisher","first-page":"4014","DOI":"10.1158\/0008-5472.CAN-20-1281","volume":"80","author":"A Knuppel","year":"2020","unstructured":"Knuppel A, Fensom GK, Watts EL, Gunter MJ, Murphy N, Papier K, et al. Circulating insulin-like growth factor-I concentrations and risk of 30 cancers: prospective analyses in UK Biobank. Can Res. 2020;80(18):4014\u201321.","journal-title":"Can Res"},{"issue":"9","key":"811_CR8","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.2337\/db11-1488","volume":"61","author":"SN Rajpathak","year":"2012","unstructured":"Rajpathak SN, He M, Sun Q, Kaplan RC, Muzumdar R, Rohan TE, et al. Insulin-like growth factor axis and risk of type 2 diabetes in women. Diabetes. 2012;61(9):2248\u201354. https:\/\/doi.org\/10.2337\/db11-1488.","journal-title":"Diabetes"},{"issue":"9","key":"811_CR9","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1007\/s00125-020-05190-9","volume":"63","author":"SC Larsson","year":"2020","unstructured":"Larsson SC, Micha\u00eblsson K, Burgess S. IGF-1 and cardiometabolic diseases: a Mendelian randomisation study. Diabetologia. 2020;63(9):1775\u201382.","journal-title":"Diabetologia"},{"issue":"11","key":"811_CR10","doi-asserted-by":"publisher","first-page":"E2308","DOI":"10.1210\/jc.2014-1575","volume":"99","author":"D Carlzon","year":"2014","unstructured":"Carlzon D, Svensson J, Petzold M, Karlsson MK, Ljunggren \u00d6, Tivesten \u00c5, et al. Both low and high serum IGF-1 levels associate with increased risk of cardiovascular events in elderly men. J Clin Endocrinol Metab. 2014;99(11):E2308\u201316. https:\/\/doi.org\/10.1210\/jc.2014-1575.","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"811_CR11","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1373\/clinchem.2008.105825","volume":"54","author":"JH Page","year":"2008","unstructured":"Page JH, Ma J, Pollak M, Manson JE, Hankinson SE. Plasma insulinlike growth factor 1 and binding-protein 3 and risk of myocardial infarction in women: a prospective study. Clin Chem. 2008;54(10):1682\u20138. https:\/\/doi.org\/10.1373\/clinchem.2008.105825.","journal-title":"Clin Chem"},{"key":"811_CR12","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa597","author":"A Hartley","year":"2020","unstructured":"Hartley A, Sanderson E, Paternoster L, Teumer A, Kaplan RC, Tobias JH, et al. Mendelian randomization provides evidence for a causal effect of higher serum IGF-1 concentration on risk of hip and knee osteoarthritis. Rheumatology (Oxford). 2020. https:\/\/doi.org\/10.1093\/rheumatology\/keaa597.","journal-title":"Rheumatology (Oxford)"},{"issue":"2","key":"811_CR13","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1002\/pros.10096","volume":"52","author":"AP Chokkalingam","year":"2002","unstructured":"Chokkalingam AP, Gao YT, Deng J, Stanczyk FZ, Sesterhenn IA, Mostofi FK, et al. Insulin-like growth factors and risk of benign prostatic hyperplasia. Prostate. 2002;52(2):98\u2013105. https:\/\/doi.org\/10.1002\/pros.10096.","journal-title":"Prostate"},{"issue":"2","key":"811_CR14","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1002\/ijc.26393","volume":"131","author":"A Soubry","year":"2012","unstructured":"Soubry A, Il\u2019yasova D, Sedjo R, Wang F, Byers T, Rosen C, et al. Increase in circulating levels of IGF-1 and IGF-1\/IGFBP-3 molar ratio over a decade is associated with colorectal adenomatous polyps. Int J Cancer. 2012;131(2):512\u20137. https:\/\/doi.org\/10.1002\/ijc.26393.","journal-title":"Int J Cancer"},{"issue":"4","key":"811_CR15","first-page":"345","volume":"9","author":"E Giovannucci","year":"2000","unstructured":"Giovannucci E, Pollak MN, Platz EA, Willett WC, Stampfer MJ, Majeed N, et al. A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomarkers Prev. 2000;9(4):345\u20139.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"6","key":"811_CR16","doi-asserted-by":"publisher","DOI":"10.1161\/circgen.120.002996","volume":"13","author":"D Zanetti","year":"2020","unstructured":"Zanetti D, Gustafsson S, Assimes TL, Ingelsson E. Comprehensive investigation of circulating biomarkers and their causal role in atherosclerosis-related risk factors and clinical events. Circ Genom Precis Med. 2020;13(6): e002996. https:\/\/doi.org\/10.1161\/circgen.120.002996.","journal-title":"Circ Genom Precis Med"},{"issue":"6","key":"811_CR17","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1093\/aje\/kwv188","volume":"183","author":"D Drogan","year":"2016","unstructured":"Drogan D, Schulze MB, Boeing H, Pischon T. Insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in relation to the risk of type 2 diabetes mellitus: results from the EPIC-Potsdam study. Am J Epidemiol. 2016;183(6):553\u201360. https:\/\/doi.org\/10.1093\/aje\/kwv188.","journal-title":"Am J Epidemiol"},{"issue":"8","key":"811_CR18","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1017\/s0007114519000321","volume":"121","author":"ME Simil\u00e4","year":"2019","unstructured":"Simil\u00e4 ME, Kontto JP, Virtamo J, H\u00e4t\u00f6nen KA, Valsta LM, Sundvall J, et al. Insulin-like growth factor I, binding proteins -1 and -3, risk of type 2 diabetes and macronutrient intakes in men. Br J Nutr. 2019;121(8):938\u201344. https:\/\/doi.org\/10.1017\/s0007114519000321.","journal-title":"Br J Nutr"},{"issue":"3","key":"811_CR19","first-page":"261","volume":"2","author":"SL Ricketts","year":"2011","unstructured":"Ricketts SL, Rensing KL, Holly JM, Chen L, Young EH, Luben R, et al. Prospective study of insulin-like growth factor-I, insulin-like growth factor-binding protein 3, genetic variants in the IGF1 and IGFBP3 genes and risk of coronary artery disease. Int J Mol Epidemiol Genet. 2011;2(3):261\u201385.","journal-title":"Int J Mol Epidemiol Genet"},{"issue":"11","key":"811_CR20","doi-asserted-by":"publisher","first-page":"4258","DOI":"10.1210\/jcem.85.11.6990","volume":"85","author":"SM Harman","year":"2000","unstructured":"Harman SM, Metter EJ, Blackman MR, Landis PK, Carter HB. Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer. J Clin Endocrinol Metab. 2000;85(11):4258\u201365. https:\/\/doi.org\/10.1210\/jcem.85.11.6990.","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"811_CR21","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1038\/bjc.1997.520","volume":"76","author":"CS Mantzoros","year":"1997","unstructured":"Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami HO. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer. 1997;76(9):1115\u20138. https:\/\/doi.org\/10.1038\/bjc.1997.520.","journal-title":"Br J Cancer"},{"issue":"2","key":"811_CR22","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1080\/003655901750170506","volume":"35","author":"P Stattin","year":"2001","unstructured":"Stattin P, Kaaks R, Riboli E, Ferrari P, Dechaud H, Hallmans G. Circulating insulin-like growth factor-I and benign prostatic hyperplasia\u2014a prospective study. Scand J Urol Nephrol. 2001;35(2):122\u20136. https:\/\/doi.org\/10.1080\/003655901750170506.","journal-title":"Scand J Urol Nephrol"},{"issue":"5","key":"811_CR23","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1136\/ard.2003.010751","volume":"63","author":"G Zhai","year":"2004","unstructured":"Zhai G, Rivadeneira F, Houwing-Duistermaat JJ, Meulenbelt I, Bijkerk C, Hofman A, et al. Insulin-like growth factor I gene promoter polymorphism, collagen type II alpha1 (COL2A1) gene, and the prevalence of radiographic osteoarthritis: the Rotterdam Study. Ann Rheum Dis. 2004;63(5):544\u20138. https:\/\/doi.org\/10.1136\/ard.2003.010751.","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"811_CR24","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1053\/joca.1998.0135","volume":"6","author":"L Fraenkel","year":"1998","unstructured":"Fraenkel L, Zhang Y, Trippel SB, McAlindon TE, LaValley MP, Assif A, et al. Longitudinal analysis of the relationship between serum insulin-like growth factor-I and radiographic knee osteoarthritis. Osteoarthritis Cartilage. 1998;6(5):362\u20137. https:\/\/doi.org\/10.1053\/joca.1998.0135.","journal-title":"Osteoarthritis Cartilage"},{"issue":"9319","key":"811_CR25","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1016\/s0140-6736(02)08655-5","volume":"359","author":"MS Sandhu","year":"2002","unstructured":"Sandhu MS, Heald AH, Gibson JM, Cruickshank JK, Dunger DB, Wareham NJ. Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study. Lancet. 2002;359(9319):1740\u20135. https:\/\/doi.org\/10.1016\/s0140-6736(02)08655-5.","journal-title":"Lancet"},{"issue":"9822","key":"811_CR26","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1016\/s0140-6736(12)60404-8","volume":"379","author":"R Collins","year":"2012","unstructured":"Collins R. What makes UK Biobank special? Lancet. 2012;379(9822):1173\u20134. https:\/\/doi.org\/10.1016\/s0140-6736(12)60404-8.","journal-title":"Lancet"},{"issue":"9","key":"811_CR27","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1093\/aje\/kwx246","volume":"186","author":"A Fry","year":"2017","unstructured":"Fry A, Littlejohns TJ, Sudlow C, Doherty N, Adamska L, Sprosen T, et al. Comparison of sociodemographic and health-related characteristics of UK biobank participants with those of the general population. Am J Epidemiol. 2017;186(9):1026\u201334. https:\/\/doi.org\/10.1093\/aje\/kwx246.","journal-title":"Am J Epidemiol"},{"issue":"2","key":"811_CR28","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1093\/ije\/dym276","volume":"37","author":"P Elliott","year":"2008","unstructured":"Elliott P, Peakman TC. The UK Biobank sample handling and storage protocol for the collection, processing and archiving of human blood and urine. Int J Epidemiol. 2008;37(2):234\u201344. https:\/\/doi.org\/10.1093\/ije\/dym276.","journal-title":"Int J Epidemiol"},{"issue":"1","key":"811_CR29","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12916-021-01922-9","volume":"19","author":"K Papier","year":"2021","unstructured":"Papier K, Fensom GK, Knuppel A, Appleby PN, Tong TYN, Schmidt JA, et al. Meat consumption and risk of 25 common conditions: outcome-wide analyses in 475,000 men and women in the UK Biobank study. BMC Med. 2021;19(1):53. https:\/\/doi.org\/10.1186\/s12916-021-01922-9.","journal-title":"BMC Med"},{"issue":"4","key":"811_CR30","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1093\/oxfordjournals.aje.a010013","volume":"150","author":"R Clarke","year":"1999","unstructured":"Clarke R, Shipley M, Lewington S, Youngman L, Collins R, Marmot M, et al. Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Am J Epidemiol. 1999;150(4):341\u201353. https:\/\/doi.org\/10.1093\/oxfordjournals.aje.a010013.","journal-title":"Am J Epidemiol"},{"issue":"8692","key":"811_CR31","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/0140-6736(90)90878-9","volume":"335","author":"S MacMahon","year":"1990","unstructured":"MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al. Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990;335(8692):765\u201374. https:\/\/doi.org\/10.1016\/0140-6736(90)90878-9.","journal-title":"Lancet"},{"issue":"8","key":"811_CR32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050155","volume":"5","author":"EJ Brunner","year":"2008","unstructured":"Brunner EJ, Kivim\u00e4ki M, Witte DR, Lawlor DA, Davey Smith G, Cooper JA, et al. Inflammation, insulin resistance, and diabetes\u2013Mendelian randomization using CRP haplotypes points upstream. PLoS Med. 2008;5(8): e155. https:\/\/doi.org\/10.1371\/journal.pmed.0050155.","journal-title":"PLoS Med"},{"issue":"3","key":"811_CR33","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1210\/jc.2004-0762","volume":"90","author":"T Kalme","year":"2005","unstructured":"Kalme T, Sepp\u00e4l\u00e4 M, Qiao Q, Koistinen R, Nissinen A, Harrela M, et al. Sex hormone-binding globulin and insulin-like growth factor-binding protein-1 as indicators of metabolic syndrome, cardiovascular risk, and mortality in elderly men. J Clin Endocrinol Metab. 2005;90(3):1550\u20136. https:\/\/doi.org\/10.1210\/jc.2004-0762.","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"811_CR34","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1111\/j.1365-2265.2008.03468.x","volume":"71","author":"E Resmini","year":"2009","unstructured":"Resmini E, Tagliafico A, Nizzo R, Bianchi F, Minuto F, Derchi L, et al. Ultrasound of peripheral nerves in acromegaly: changes at 1-year follow-up. Clin Endocrinol (Oxf). 2009;71(2):220\u20135. https:\/\/doi.org\/10.1111\/j.1365-2265.2008.03468.x.","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"2","key":"811_CR35","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1179\/016164104225013851","volume":"26","author":"ED Rabinovsky","year":"2004","unstructured":"Rabinovsky ED. The multifunctional role of IGF-1 in peripheral nerve regeneration. Neurol Res. 2004;26(2):204\u201310. https:\/\/doi.org\/10.1179\/016164104225013851.","journal-title":"Neurol Res"},{"issue":"5","key":"811_CR36","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s11102-015-0642-9","volume":"18","author":"Y Sasagawa","year":"2015","unstructured":"Sasagawa Y, Tachibana O, Doai M, Tonami H, Iizuka H. Median nerve conduction studies and wrist magnetic resonance imaging in acromegalic patients with carpal tunnel syndrome. Pituitary. 2015;18(5):695\u2013700.","journal-title":"Pituitary"},{"issue":"3","key":"811_CR37","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1210\/jc.2007-1719","volume":"93","author":"A Tagliafico","year":"2008","unstructured":"Tagliafico A, Resmini E, Nizzo R, Bianchi F, Minuto F, Ferone D, et al. Ultrasound measurement of median and ulnar nerve cross-sectional area in acromegaly. J Clin Endocrinol Metab. 2008;93(3):905\u20139.","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"811_CR38","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.yexmp.2010.04.002","volume":"89","author":"G Jia","year":"2010","unstructured":"Jia G, Mitra AK, Gangahar DM, Agrawal DK. Insulin-like growth factor-1 induces phosphorylation of PI3K-Akt\/PKB to potentiate proliferation of smooth muscle cells in human saphenous vein. Exp Mol Pathol. 2010;89(1):20\u20136. https:\/\/doi.org\/10.1016\/j.yexmp.2010.04.002.","journal-title":"Exp Mol Pathol"},{"issue":"2","key":"811_CR39","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1160\/th10-06-0379","volume":"105","author":"E Succurro","year":"2011","unstructured":"Succurro E, Arturi F, Caruso V, Rudi S, Sciacqua A, Andreozzi F, et al. Low insulin-like growth factor-1 levels are associated with anaemia in adult non-diabetic subjects. Thromb Haemost. 2011;105(2):365\u201370. https:\/\/doi.org\/10.1160\/th10-06-0379.","journal-title":"Thromb Haemost"},{"issue":"2","key":"811_CR40","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/j.1600-0609.2004.00374.x","volume":"74","author":"H Nilsson-Ehle","year":"2005","unstructured":"Nilsson-Ehle H, Bengtsson BA, Lindstedt G, Mellstr\u00f6m D. Insulin-like growth factor-1 is a predictor of blood haemoglobin concentration in 70-yr-old subjects. Eur J Haematol. 2005;74(2):111\u20136. https:\/\/doi.org\/10.1111\/j.1600-0609.2004.00374.x.","journal-title":"Eur J Haematol"},{"issue":"7","key":"811_CR41","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1093\/gerona\/glu200","volume":"70","author":"E Duron","year":"2015","unstructured":"Duron E, Vidal JS, Funalot B, Brunel N, Viollet C, Rigaud AS, et al. Insulin-like growth factor-i, insulin-like growth factor binding protein-3 and blood hemoglobin concentration in an elderly population. J Gerontol A Biol Sci Med Sci. 2015;70(7):854\u20139. https:\/\/doi.org\/10.1093\/gerona\/glu200.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"11","key":"811_CR42","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.4158\/ep14100.Or","volume":"21","author":"F De Vita","year":"2015","unstructured":"De Vita F, Maggio M, Lauretani F, Crucitti L, Bandinelli S, Mammarella F, et al. Insulin-like growth factor-1 and anemia in older subjects: the inchianti study. Endocr Pract. 2015;21(11):1211\u20138. https:\/\/doi.org\/10.4158\/ep14100.Or.","journal-title":"Endocr Pract"},{"key":"811_CR43","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/292574","volume":"2015","author":"M Maggio","year":"2015","unstructured":"Maggio M, De Vita F, Fisichella A, Lauretani F, Ticinesi A, Ceresini G, et al. The role of the multiple hormonal dysregulation in the onset of \u201canemia of aging\u201d: focus on testosterone, IGF-1, and thyroid hormones. Int J Endocrinol. 2015;2015: 292574. https:\/\/doi.org\/10.1155\/2015\/292574.","journal-title":"Int J Endocrinol"},{"issue":"11","key":"811_CR44","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-032930","volume":"9","author":"A Schop","year":"2019","unstructured":"Schop A, Stouten K, Riedl J, van Houten R, van Rosmalen J, Wolfhagen F, et al. Long-term outcomes in patients newly diagnosed with iron deficiency anaemia in general practice: a retrospective cohort study. BMJ Open. 2019;9(11): e032930. https:\/\/doi.org\/10.1136\/bmjopen-2019-032930.","journal-title":"BMJ Open"},{"issue":"5","key":"811_CR45","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/s10792-013-9733-7","volume":"33","author":"E Kan","year":"2013","unstructured":"Kan E, Kan EK, Atmaca A, Atmaca H, Colak R. Visual field defects in 23 acromegalic patients. Int Ophthalmol. 2013;33(5):521\u20135. https:\/\/doi.org\/10.1007\/s10792-013-9733-7.","journal-title":"Int Ophthalmol"},{"issue":"6","key":"811_CR46","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1006\/exer.2000.0846","volume":"70","author":"A Civil","year":"2000","unstructured":"Civil A, van Genesen ST, Klok EJ, Lubsen NH. Insulin and IGF-I affect the protein composition of the lens fibre cell with possible consequences for cataract. Exp Eye Res. 2000;70(6):785\u201394. https:\/\/doi.org\/10.1006\/exer.2000.0846.","journal-title":"Exp Eye Res"},{"issue":"1","key":"811_CR47","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1007\/s11102-017-0797-7","volume":"20","author":"R Pivonello","year":"2017","unstructured":"Pivonello R, Auriemma RS, Grasso LF, Pivonello C, Simeoli C, Patalano R, et al. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary. 2017;20(1):46\u201362. https:\/\/doi.org\/10.1007\/s11102-017-0797-7.","journal-title":"Pituitary"},{"issue":"9682","key":"811_CR48","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1016\/s0140-6736(09)60619-x","volume":"373","author":"AG Tab\u00e1k","year":"2009","unstructured":"Tab\u00e1k AG, Jokela M, Akbaraly TN, Brunner EJ, Kivim\u00e4ki M, Witte DR. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet. 2009;373(9682):2215\u201321. https:\/\/doi.org\/10.1016\/s0140-6736(09)60619-x.","journal-title":"Lancet"},{"issue":"1","key":"811_CR49","first-page":"9","volume":"6","author":"B Aissani","year":"2015","unstructured":"Aissani B, Zhang K, Wiener H. Genetic determinants of uterine fibroid size in the multiethnic NIEHS uterine fibroid study. Int J Mol Epidemiol Genet. 2015;6(1):9\u201319.","journal-title":"Int J Mol Epidemiol Genet"},{"issue":"1","key":"811_CR50","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1210\/er.2018-00115","volume":"40","author":"MR Gadelha","year":"2019","unstructured":"Gadelha MR, Kasuki L, Lim DST, Fleseriu M. Systemic complications of acromegaly and the impact of the current treatment landscape: an update. Endocr Rev. 2019;40(1):268\u2013332. https:\/\/doi.org\/10.1210\/er.2018-00115.","journal-title":"Endocr Rev"},{"issue":"6","key":"811_CR51","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1210\/er.2001-0033","volume":"23","author":"SM Firth","year":"2002","unstructured":"Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002;23(6):824\u201354. https:\/\/doi.org\/10.1210\/er.2001-0033.","journal-title":"Endocr Rev"}],"container-title":["European Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-021-00811-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10654-021-00811-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-021-00811-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T22:06:51Z","timestamp":1643234811000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10654-021-00811-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,8]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["811"],"URL":"https:\/\/doi.org\/10.1007\/s10654-021-00811-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-666126\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.1101\/2021.05.05.21256665","asserted-by":"object"}]},"ISSN":["0393-2990","1573-7284"],"issn-type":[{"value":"0393-2990","type":"print"},{"value":"1573-7284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,8]]},"assertion":[{"value":"29 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The UK Biobank study was approved by the North West Multi-Centre Research Ethics Committee (Reference Number 16\/NW\/0274).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}