{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T01:42:58Z","timestamp":1761788578824,"version":"build-2065373602"},"reference-count":42,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The objective of this research was to examine associations between diabetes mellitus (DM) and neurocognitive impairment in survivors of childhood cancer while exploring mechanistic associations with treatment exposures and moderating associations with cardiovascular disease (CVD) and risky lifestyle factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Survivors of the Childhood Cancer Survivor Study (<jats:italic>N<\/jats:italic>\u00a0=\u00a016,196; mean\u00a0\u00b1\u00a0standard deviation age, 32.9\u00a0\u00b1\u00a07.9 years; 50.2% female; <jats:italic>N<\/jats:italic>\u00a0=\u00a0615 with DM) self\u2010reported neurocognitive functioning, risky drinking, physical inactivity, and tobacco use. Medical data were collected from chart review. Multivariable regression determined the association of DM with neurocognitive impairment while adjusting for relevant treatment exposures. Interactions between DM and treatment, risky lifestyle, and cardiovascular predictors on impairment were explored. Path analysis was used to examine the effects of treatment exposures through DM and CVD on impairment. Among survivors with DM, multivariable regressions examined predictors of neurocognitive change over time (mean, 11.21 years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Survivors with DM had an increased risk of impairment relative to survivors without DM (task completion: odds ratio [OR], 1.5; 95% confidence limits [CI], 1.2\u20131.9; emotion regulation: OR, 1.4; 95% CI, 1.1\u20132.0; and organization: OR, 1.5; 95% CI, 1.1\u20132.0). The effects of cranial radiation on neurocognition were mediated by DM, including task completion (\u03b2\u00a0=\u00a00.02), emotion regulation (\u03b2\u00a0=\u00a00.02), memory (\u03b2\u00a0=\u00a00.01), and organization (\u03b2\u00a0=\u00a00.02; all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01). Among survivors with DM, CVD was associated with declines in task completion (estimate\u00a0=\u00a00.44; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01) and organization (estimate\u00a0=\u00a00.27; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.03).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Survivors with DM are at increased risk of neurocognitive impairment. Although CVD did not exacerbate concurrent risk for impairment, it was associated with a decline in neurocognitive functioning over time in survivors with DM. Preventing\/managing CVD in survivors with DM could mitigate additional neurocognitive decline.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.70011","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:00:59Z","timestamp":1754560859000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Diabetes mellitus and neurocognition: A report from the Childhood Cancer Survivor Study"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6216-1502","authenticated-orcid":false,"given":"Rachel T.","family":"Webster","sequence":"first","affiliation":[{"name":"St Jude Children\u2019s Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sedigheh","family":"Mirzaei","sequence":"additional","affiliation":[{"name":"St Jude Children\u2019s Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shalini","family":"Bhatia","sequence":"additional","affiliation":[{"name":"St Jude Children\u2019s Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deo Kumar","family":"Srivastava","sequence":"additional","affiliation":[{"name":"St Jude Children\u2019s Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sogol","family":"Mostoufi\u2010Moab","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-3274","authenticated-orcid":false,"given":"Stephanie B.","family":"Dixon","sequence":"additional","affiliation":[{"name":"St Jude Children\u2019s Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric J.","family":"Chow","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory T.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"St Jude Children\u2019s Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0476-7001","authenticated-orcid":false,"given":"Kevin R.","family":"Krull","sequence":"additional","affiliation":[{"name":"St Jude Children\u2019s Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"van der Plas","sequence":"additional","affiliation":[{"name":"University of Arkansas for Medical Sciences  Little Rock Arkansas USA"},{"name":"Arkansas Children\u2019s Research Institute  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010023\u201000802\u2010w"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.16077"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02533"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.3268"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31975"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(18)30537\u20100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2020.101733"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21643"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592\u2010020\u201001648\u20109"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000035557"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000521653"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010018\u20100728\u20106"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102010\u2010091591"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010018\u20104778\u20109"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33486"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2014.29.2.112"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40200\u2010020\u201000529\u2010w"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2352\u20103026(19)30050\u2010x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000495698"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djx224"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2009.22.3339"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6842"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23809"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1037\/neu0000095"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e3181e0c112"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29609"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.14439"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2009.209"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1206071"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2017.04.006"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2016.10.003"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15112999"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16086"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010020\u201005319\u2010w"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01005"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/348054"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2305\u20105839.2014.08.05"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32510"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12966\u2010017\u20100489\u20108"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2023.102923"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.310961"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.43882"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.70011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:45:01Z","timestamp":1760406301000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.70011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,7]]},"references-count":42,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2025,8,15]]}},"alternative-id":["10.1002\/cncr.70011"],"URL":"https:\/\/doi.org\/10.1002\/cncr.70011","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"type":"print","value":"0008-543X"},{"type":"electronic","value":"1097-0142"}],"subject":[],"published":{"date-parts":[[2025,8,7]]},"assertion":[{"value":"2025-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70011"}}