{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:58:58Z","timestamp":1760230738488,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Saarland state Ministry for Social Affairs, Health, Women and Family Affairs"},{"name":"Baden-W\u00fcrttemberg state Ministry of Science, Research and Arts"},{"name":"Federal Ministry of Education and Research"},{"name":"Federal Ministry of Family Affairs, Senior Citizens, Women and Youth"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Serum 25-hydroxyvitamin (25(OH)D) levels are inversely associated with risk of diabetes. The \u201cfree hormone hypothesis\u201d suggests potential effects to be mainly related to concentrations of \u201cbioavailable\u201d and free rather than total 25(OH)D. We assessed associations of serum concentrations of vitamin D-binding protein (VDBP), as well as total \u201cbioavailable\u201d, complementary \u201cnon-bioavailable\u201d, and free 25(OH)D, with the risk of developing diabetes among non-diabetic older adults in a large population-based cohort study in Germany. Methods: We included 4841 non-diabetic older adults aged 50\u201375 years at the baseline exam from the ESTHER cohort conducted in Saarland, Germany, in 2001\u20132002. Concentrations of \u201cbioavailable\u201d and free 25(OH)D were derived from serum concentrations of VDBP, total 25(OH)D, and albumin. Incidence of diabetes was ascertained during up to 14 years of follow-up. Associations were quantified by multivariable Cox proportional hazards regression models with comprehensive confounder adjustment. Results: During a median follow-up of 10.6 years, 837 non-diabetic participants developed diabetes. We observed similar inverse associations with developing diabetes for VDBP (hazard ratio (HR) for lowest versus highest quintile: 1.37, 95% confidence interval (CI): 1.09, 1.72), total 25(OH)D (HR: 1.31, 95% CI: 1.03, 1.66), and \u201cnon-bioavailable\u201d 25(OH)D (HR: 1.30, 95% CI: 1.02, 1.65). Associations were smaller and statistically insignificant for \u201cbioavailable\u201d and free 25(OH)D. However, associations of total \u201cnon-bioavailable\u201d, \u201cbioavailable\u201d, and free 25(OH)D with incidence of diabetes were much stronger among, and essentially restricted to, participants with lower baseline HbA1c (\u22646%) levels. Conclusions: This large prospective cohort study of older Caucasian adults, in agreement with results from randomized trials and Mendelian randomization studies, supports a protective effect of vitamin D against development of diabetes. The \u201cfree hormone theory\u201d may not be relevant in this context. However, our results underline the importance of adequate vitamin D status among those who have not yet shown any sign of impaired glucose tolerance.<\/jats:p>","DOI":"10.3390\/nu14163282","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T05:43:57Z","timestamp":1660196637000},"page":"3282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Consistent Inverse Associations of Total, \u201cBioavailable\u201d, Free, and \u201cNon-Bioavailable\u201d Vitamin D with Incidence of Diabetes among Older Adults with Lower Baseline HbA1c (\u22646%) Levels"],"prefix":"10.3390","volume":"14","author":[{"given":"Anna","family":"Zhu","sequence":"first","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0200-6743","authenticated-orcid":false,"given":"Sabine","family":"Kuznia","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-3437","authenticated-orcid":false,"given":"Tobias","family":"Niedermaier","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Holleczek","sequence":"additional","affiliation":[{"name":"Saarland Cancer Registry, 66119 Saarbr\u00fccken, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-4521","authenticated-orcid":false,"given":"Ben","family":"Sch\u00f6ttker","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Network Aging Research, Heidelberg University, 69115 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-1572","authenticated-orcid":false,"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Network Aging Research, Heidelberg University, 69115 Heidelberg, Germany"},{"name":"Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2991\/jegh.k.191028.001","article-title":"Epidemiology of Type 2 Diabetes\u2014Global Burden of Disease and Forecasted Trends","volume":"10","author":"Khan","year":"2020","journal-title":"J. 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