{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:58:25Z","timestamp":1791381505556,"version":"4.3.3"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Jiangsu Province Engineering Research Center of Development and Translation of Key Technologies for Chronic Disease Prevention and Control","award":["CDSGK1202502"],"award-info":[{"award-number":["CDSGK1202502"]}]},{"name":"Research on Key Technologies for the Prevention and Control of Major Diseases and Infectious Diseases in Suzhou","award":["GWZX202304"],"award-info":[{"award-number":["GWZX202304"]}]},{"name":"Research on Key Technologies for the Prevention and Control of Major Diseases and Infectious Diseases in Suzhou","award":["GWZX202101"],"award-info":[{"award-number":["GWZX202101"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703316"],"award-info":[{"award-number":["81703316"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"A Project Funded by Priority Academic Program Development of Jiangsu Higher Education Institutions","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]},{"name":"the Youth Science and Technology Talent Support Program of Jiangsu Province","award":["JSTJ-2023-WJ005"],"award-info":[{"award-number":["JSTJ-2023-WJ005"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nutr"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s00394-026-04126-0","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:31:23Z","timestamp":1791379883000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma biomarkers of vitamin B6 homeostasis and the risk of stroke in individuals with type 2 diabetes: a nested case\u2013control study"],"prefix":"10.1007","volume":"65","author":[{"given":"Yi","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xujia","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalong","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Born\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-4307","authenticated-orcid":false,"given":"Chaofu","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"4126_CR1","volume-title":"IDF diabetes atlas","author":"International Diabetes Federation","year":"2025","unstructured":"International Diabetes Federation (2025) IDF diabetes atlas, 11th edn. International Diabetes Federation, Brussels, Belgium","edition":"11th edn"},{"issue":"10440","key":"4126_CR2","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1016\/S0140-6736(24)00757-8","volume":"403","author":"GBD 2021 Diseases and Injuries Collaborators","year":"2024","unstructured":"GBD 2021 Diseases and Injuries Collaborators (2024) Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 403(10440):2133\u20132161. https:\/\/doi.org\/10.1016\/S0140-6736(24)00757-8","journal-title":"Lancet"},{"issue":"4","key":"4126_CR3","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S2213-8587(19)30405-X","volume":"8","author":"TT van Sloten","year":"2020","unstructured":"van Sloten TT, Sedaghat S, Carnethon MR, Launer LJ, Stehouwer CDA (2020) Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression. Lancet Diabetes Endocrinol 8(4):325\u2013336. https:\/\/doi.org\/10.1016\/S2213-8587(19)30405-X","journal-title":"Lancet Diabetes Endocrinol"},{"key":"4126_CR4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1146\/annurev-nutr-071714-034330","volume":"35","author":"PM Ueland","year":"2015","unstructured":"Ueland PM, Ulvik A, Rios-Avila L, Midttun \u00d8, Gregory JF (2015) Direct and functional biomarkers of vitamin B6 status. Annu Rev Nutr 35:33\u201370. https:\/\/doi.org\/10.1146\/annurev-nutr-071714-034330","journal-title":"Annu Rev Nutr"},{"key":"4126_CR5","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1146\/annurev.biochem.73.011303.074021","volume":"73","author":"AC Eliot","year":"2004","unstructured":"Eliot AC, Kirsch JF (2004) Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. Annu Rev Biochem 73:383\u2013415. https:\/\/doi.org\/10.1146\/annurev.biochem.73.011303.074021","journal-title":"Annu Rev Biochem"},{"issue":"1","key":"4126_CR6","doi-asserted-by":"publisher","first-page":"250","DOI":"10.3945\/ajcn.114.083196","volume":"100","author":"A Ulvik","year":"2014","unstructured":"Ulvik A, Midttun \u00d8, Pedersen ER, Eussen SJ, Nyg\u00e5rd O, Ueland PM (2014) Evidence for increased catabolism of vitamin B-6 during systemic inflammation. Am J Clin Nutr 100(1):250\u2013255. https:\/\/doi.org\/10.3945\/ajcn.114.083196","journal-title":"Am J Clin Nutr"},{"key":"4126_CR7","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.mam.2016.08.001","volume":"53","author":"PM Ueland","year":"2017","unstructured":"Ueland PM, McCann A, Midttun \u00d8, Ulvik A (2017) Inflammation, vitamin B6 and related pathways. Mol Aspects Med 53:10\u201327. https:\/\/doi.org\/10.1016\/j.mam.2016.08.001","journal-title":"Mol Aspects Med"},{"issue":"5","key":"4126_CR8","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/S1474-4422(11)70066-7","volume":"10","author":"R Macrez","year":"2011","unstructured":"Macrez R, Ali C, Toutirais O et al (2011) Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol 10(5):471\u2013480. https:\/\/doi.org\/10.1016\/S1474-4422(11)70066-7","journal-title":"Lancet Neurol"},{"issue":"7","key":"4126_CR9","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1038\/s41423-023-01029-6","volume":"20","author":"S Zhu","year":"2023","unstructured":"Zhu S, Zhong S, Cheng K et al (2023) Vitamin B6 regulates IL-33 homeostasis to alleviate type 2 inflammation. Cell Mol Immunol 20(7):794\u2013807. https:\/\/doi.org\/10.1038\/s41423-023-01029-6","journal-title":"Cell Mol Immunol"},{"issue":"1","key":"4126_CR10","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1093\/ajcn\/nqx012","volume":"107","author":"H Zuo","year":"2018","unstructured":"Zuo H, Tell GS, Ueland PM et al (2018) The PAr index, an indicator reflecting altered vitamin B-6 homeostasis, is associated with long-term risk of stroke in the general population: the Hordaland Health Study (HUSK). Am J Clin Nutr 107(1):105\u2013112. https:\/\/doi.org\/10.1093\/ajcn\/nqx012","journal-title":"Am J Clin Nutr"},{"issue":"10","key":"4126_CR11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103669","volume":"21","author":"E Mascolo","year":"2020","unstructured":"Mascolo E, Vern\u00ec F (2020) Vitamin B6 and diabetes: relationship and molecular mechanisms. Int J Mol Sci 21(10):3669. https:\/\/doi.org\/10.3390\/ijms21103669","journal-title":"Int J Mol Sci"},{"issue":"3","key":"4126_CR12","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1093\/jn\/82.3.371","volume":"82","author":"AM Huber","year":"1964","unstructured":"Huber AM, Gershoff SN, Hegsted DM (1964) Carbohydrate and fat metabolism and response to insulin in vitamin B6-deficient rats. J Nutr 82(3):371\u2013378. https:\/\/doi.org\/10.1093\/jn\/82.3.371","journal-title":"J Nutr"},{"issue":"4","key":"4126_CR13","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1007\/s00125-016-3863-1","volume":"59","author":"JM Moreno-Navarrete","year":"2016","unstructured":"Moreno-Navarrete JM, Jove M, Ortega F et al (2016) Metabolomics uncovers the role of adipose tissue PDXK in adipogenesis and systemic insulin sensitivity. Diabetologia 59(4):822\u2013832. https:\/\/doi.org\/10.1007\/s00125-016-3863-1","journal-title":"Diabetologia"},{"issue":"9403","key":"4126_CR14","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0140-6736(03)15268-3","volume":"363","author":"WHO Expert Consultation","year":"2004","unstructured":"WHO Expert Consultation (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363(9403):157\u2013163. https:\/\/doi.org\/10.1016\/S0140-6736(03)15268-3","journal-title":"Lancet"},{"issue":"9","key":"4126_CR15","doi-asserted-by":"publisher","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","volume":"150","author":"AS Levey","year":"2009","unstructured":"Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604\u2013612. https:\/\/doi.org\/10.7326\/0003-4819-150-9-200905050-00006","journal-title":"Ann Intern Med"},{"issue":"5","key":"4126_CR16","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1002\/sim.4780080504","volume":"8","author":"S Durrleman","year":"1989","unstructured":"Durrleman S, Simon R (1989) Flexible regression models with cubic splines. Stat Med 8(5):551\u2013561. https:\/\/doi.org\/10.1002\/sim.4780080504","journal-title":"Stat Med"},{"issue":"1","key":"4126_CR17","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/sim.4085","volume":"30","author":"MJ Pencina","year":"2011","unstructured":"Pencina MJ, D\u2019Agostino RB Sr, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30(1):11\u201321. https:\/\/doi.org\/10.1002\/sim.4085","journal-title":"Stat Med"},{"issue":"6","key":"4126_CR18","doi-asserted-by":"publisher","first-page":"e51","DOI":"10.1161\/01.STR.0000071109.23410.AB","volume":"34","author":"PJ Kelly","year":"2003","unstructured":"Kelly PJ, Shih VE, Kistler JP et al (2003) Low vitamin B6 but not homocyst(e)ine is associated with increased risk of stroke and transient ischemic attack in the era of folic acid grain fortification. Stroke 34(6):e51\u2013e54. https:\/\/doi.org\/10.1161\/01.STR.0000071109.23410.AB","journal-title":"Stroke"},{"issue":"11","key":"4126_CR19","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1161\/STROKEAHA.107.486068","volume":"38","author":"C Weikert","year":"2007","unstructured":"Weikert C, Dierkes J, Hoffmann K et al (2007) B vitamin plasma levels and the risk of ischemic stroke and transient ischemic attack in a German cohort. Stroke 38(11):2912\u20132918. https:\/\/doi.org\/10.1161\/STROKEAHA.107.486068","journal-title":"Stroke"},{"issue":"1","key":"4126_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics9010028","volume":"9","author":"R Obeid","year":"2019","unstructured":"Obeid R, Geisel J, Nix WA (2019) 4-Pyridoxic acid\/pyridoxine ratio in patients with type 2 diabetes is related to global cardiovascular risk scores. Diagnostics (Basel) 9(1):28. https:\/\/doi.org\/10.3390\/diagnostics9010028","journal-title":"Diagnostics (Basel)"},{"issue":"23","key":"4126_CR21","doi-asserted-by":"publisher","first-page":"2788","DOI":"10.1161\/01.cir.103.23.2788","volume":"103","author":"S Friso","year":"2001","unstructured":"Friso S, Jacques PF, Wilson PW, Rosenberg IH, Selhub J (2001) Low circulating vitamin B(6) is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation 103(23):2788\u20132791. https:\/\/doi.org\/10.1161\/01.cir.103.23.2788","journal-title":"Circulation"},{"issue":"7","key":"4126_CR22","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1373\/clinchem.2005.066217","volume":"52","author":"AM Gori","year":"2006","unstructured":"Gori AM, Sofi F, Corsi AM et al (2006) Predictors of vitamin B6 and folate concentrations in older persons: the InCHIANTI study. Clin Chem 52(7):1318\u20131324. https:\/\/doi.org\/10.1373\/clinchem.2005.066217","journal-title":"Clin Chem"},{"issue":"7","key":"4126_CR23","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1017\/S0007114514001858","volume":"112","author":"D Theofylaktopoulou","year":"2014","unstructured":"Theofylaktopoulou D, Ulvik A, Midttun \u00d8 et al (2014) Vitamins B2 and B6 as determinants of kynurenines and related markers of interferon-\u03b3-mediated immune activation in the community-based Hordaland Health Study. Br J Nutr 112(7):1065\u20131072. https:\/\/doi.org\/10.1017\/S0007114514001858","journal-title":"Br J Nutr"},{"issue":"7","key":"4126_CR24","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3390\/cells7070084","volume":"7","author":"M Parra","year":"2018","unstructured":"Parra M, Stahl S, Hellmann H (2018) Vitamin B\u2086 and its role in cell metabolism and physiology. Cells 7(7):84. https:\/\/doi.org\/10.3390\/cells7070084","journal-title":"Cells"},{"issue":"3","key":"4126_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030891","volume":"19","author":"N Shirafuji","year":"2018","unstructured":"Shirafuji N et al (2018) Homocysteine increases tau phosphorylation, truncation and oligomerization. Int J Mol Sci 19(3):891. https:\/\/doi.org\/10.3390\/ijms19030891","journal-title":"Int J Mol Sci"},{"issue":"3","key":"4126_CR26","doi-asserted-by":"publisher","first-page":"7209","DOI":"10.1080\/21655979.2022.2037953","volume":"13","author":"S Shen","year":"2022","unstructured":"Shen S, Hamano T, Yen SH et al (2022) The protective effects of butorphanol tartrate against homocysteine-induced blood-brain barrier dysfunction. Bioengineered 13(3):7209\u20137220. https:\/\/doi.org\/10.1080\/21655979.2022.2037953","journal-title":"Bioengineered"},{"issue":"11","key":"4126_CR27","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1080\/00207454.2020.1860967","volume":"132","author":"M Kumar","year":"2022","unstructured":"Kumar M, Sandhir R (2022) Hydrogen sulfide attenuates hyperhomocysteinemia-induced blood-brain barrier permeability by inhibiting MMP-9. Int J Neurosci 132(11):1061\u20131071. https:\/\/doi.org\/10.1080\/00207454.2020.1860967","journal-title":"Int J Neurosci"},{"issue":"4","key":"4126_CR28","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.1007\/s12035-015-9226-y","volume":"53","author":"W Wu","year":"2016","unstructured":"Wu W, Guan Y, Xu K et al (2016) Plasma homocysteine levels predict the risk of acute cerebral infarction in patients with carotid artery lesions. Mol Neurobiol 53(4):2510\u20132517. https:\/\/doi.org\/10.1007\/s12035-015-9226-y","journal-title":"Mol Neurobiol"},{"issue":"4","key":"4126_CR29","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.freeradbiomed.2003.09.012","volume":"36","author":"K Kannan","year":"2004","unstructured":"Kannan K, Jain SK (2004) Effect of vitamin B6 on oxygen radicals, mitochondrial membrane potential, and lipid peroxidation in H2O2-treated U937 monocytes. Free Radic Biol Med 36(4):423\u2013428. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2003.09.012","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"4126_CR30","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.atherosclerosis.2005.10.035","volume":"188","author":"Y Ji","year":"2006","unstructured":"Ji Y, Diao J, Han Y et al (2006) Pyridoxine prevents dysfunction of endothelial cell nitric oxide production in response to low-density lipoprotein. Atherosclerosis 188(1):84\u201394. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2005.10.035","journal-title":"Atherosclerosis"},{"issue":"2","key":"4126_CR31","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1136\/bmjnph-2020-000088","volume":"3","author":"J Wei","year":"2020","unstructured":"Wei J, Ji JS (2020) Modification of vitamin B6 on the associations of blood lead levels and cardiovascular diseases in the US adults. BMJ Nutr Prev Health 3(2):180\u2013187. https:\/\/doi.org\/10.1136\/bmjnph-2020-000088","journal-title":"BMJ Nutr Prev Health"}],"container-title":["European Journal of Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00394-026-04126-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00394-026-04126-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00394-026-04126-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:31:24Z","timestamp":1791379884000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00394-026-04126-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["4126"],"URL":"https:\/\/doi.org\/10.1007\/s00394-026-04126-0","relation":{},"ISSN":["1436-6207","1436-6215"],"issn-type":[{"value":"1436-6207","type":"print"},{"value":"1436-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"10 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Research Ethics Committee of Jiangsu Provincial Center for Disease Control (REC reference: 2013026).","order":4,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"277"}}