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The Finnish Vitamin D Trial (FIND) investigated the effects of vitamin D<jats:sub>3<\/jats:sub> supplementation at two different doses on the incidence of type 2 diabetes in a generally healthy older adult population.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>FIND was a 5 year randomised placebo-controlled, parallel-arm trial among 2271 male and female participants aged \u226560 years and \u226565 years, respectively, from a general Finnish population who were free of CVD or cancer and did not use diabetes medications. The study had three arms: placebo, 1600 IU\/day of vitamin D<jats:sub>3<\/jats:sub> or 3200 IU\/day of vitamin D<jats:sub>3<\/jats:sub>. A non-study group statistician carried out sex-stratified simple randomisation in a 1:1:1 ratio, based on computerised random number generation. The participants, investigators and study staff were masked to group assignment. National health registries were used to collect event data. A representative subcohort of 505 participants had more detailed in-person investigations at months 0, 6, 12 and 24.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>During the mean follow-up of 4.2 years, there were 38 (5.0%), 31 (4.2%) and 36 (4.7%) type 2 diabetes events in the placebo (<jats:italic>n<\/jats:italic>=760), 1600 IU\/day vitamin D<jats:sub>3<\/jats:sub> (<jats:italic>n<\/jats:italic>=744; vs placebo: HR 0.81; 95% CI 0.50, 1.30) and 3200 IU\/day vitamin D<jats:sub>3<\/jats:sub> (<jats:italic>n<\/jats:italic>=767; vs placebo: HR 0.92, 95% CI 0.58, 1.45) arms, respectively (<jats:italic>p<\/jats:italic>-trend=0.73). When the two vitamin D<jats:sub>3<\/jats:sub> arms were combined and compared with the placebo arm, the HR was 0.86 (95% CI 0.58, 1.29). In the analyses stratified by BMI (&lt;25 kg\/m<jats:sup>2<\/jats:sup> [<jats:italic>n<\/jats:italic>=813, number of type 2 diabetes events=12], 25\u201330 kg\/m<jats:sup>2<\/jats:sup> [<jats:italic>n<\/jats:italic>=1032, number of events=38], \u226530 kg\/m<jats:sup>2<\/jats:sup> [<jats:italic>n<\/jats:italic>=422, number of events=54]), the HRs in the combined vitamin D<jats:sub>3<\/jats:sub> arms vs the placebo were 0.43 (95% CI 0.14, 1.34), 0.97 (0.50, 1.91) and 1.00 (0.57, 1.75), respectively (<jats:italic>p<\/jats:italic>-interaction &lt;0.001). In the subcohort, the mean (SD) baseline serum 25-hydroxyvitamin D<jats:sub>3<\/jats:sub> (25(OH)D<jats:sub>3<\/jats:sub>) concentration was 74.5 (18.1) nmol\/l. After 12 months, the concentrations were 72.6 (17.7), 99.3 (20.8) and 120.9 (22.1) nmol\/l in the placebo, 1600 IU\/day vitamin D<jats:sub>3<\/jats:sub> and 3200 IU\/day vitamin D<jats:sub>3<\/jats:sub> arms, respectively. In the subcohort, no differences were observed in changes in plasma glucose or insulin concentrations, BMI or waist circumference during the 24 month follow-up (<jats:italic>p<\/jats:italic> values \u22650.19).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\/interpretation<\/jats:title>\n            <jats:p>Among generally healthy older adults who are not at high risk for diabetes and who have serum 25(OH)D<jats:sub>3<\/jats:sub> levels that are sufficient for bone health, vitamin D<jats:sub>3<\/jats:sub> supplementation did not significantly reduce the risk of developing diabetes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration<\/jats:title>\n            <jats:p>ClinicalTrials.gov NCT01463813.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s00125-024-06336-9","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T10:58:07Z","timestamp":1733137087000},"page":"715-726","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The effect of vitamin D3 supplementation on the incidence of type 2 diabetes in healthy older adults not at high risk for diabetes (FIND): a randomised controlled trial"],"prefix":"10.1007","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0648-999X","authenticated-orcid":false,"given":"Jyrki K.","family":"Virtanen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-3847","authenticated-orcid":false,"given":"Sari","family":"Hantunen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niko","family":"Kallio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7326-1904","authenticated-orcid":false,"given":"Christel","family":"Lamberg-Allardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-7595","authenticated-orcid":false,"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarja","family":"Nurmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Pihlajam\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6052-2001","authenticated-orcid":false,"given":"Matti","family":"Uusitupa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0664-2675","authenticated-orcid":false,"given":"Ari","family":"Voutilainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomi-Pekka","family":"Tuomainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"6336_CR1","unstructured":"International Diabetes Federation (2021) IDF diabetes atlas, 10th edn. 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However, the analytical code used for the current study can be made available on reasonable request, and the data are open for potential research collaboration by contacting the corresponding author.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Open access funding provided by University of Eastern Finland (including Kuopio University Hospital). This study was supported by funding from the Academy of Finland (#137826), University of Eastern Finland, Juho Vainio Foundation, Medicinska Underst\u00f6dsf\u00f6reningen Liv och H\u00e4lsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation and Finnish Cultural Foundation. The study funders were not involved in the design of the study, the collection, analysis and interpretation of data or writing of the report, and did not impose any restrictions regarding the publication of the report. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"JKV reports receiving travel support to attend vitamin D research meetings from Abiogen Pharma. CL-A reports involvement in the Nordic Nutrition Recommendations 2023 as a member of the Systematic Review Centre, and in European Food Safety Authority procurement and preparatory work for the 2023 update of the tolerable upper intake levels for vitamin D. JEM reports receiving grants from the National Institutes of Health during the conduct of the study, and grants from the National Institutes of Health and from Mars Edge outside the submitted work. MU reports receiving a grant from Orion outside the submitted work. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"JKV, SH and T-PT designed the research with help from CL-A, JEM, TN and MU. JKV, SH, NK, TN, JP and T-PT conducted the research. JKV and AV carried out the statistical analysis and had full access to all the data and take responsibility for the integrity of the work as a whole and the accuracy of the data analysis. JKV drafted the manuscript. All authors interpreted the study results and provided critical revision of the manuscript for important intellectual content and approved the final manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}