{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:07:44Z","timestamp":1753891664202,"version":"3.41.2"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Several epidemiological studies have suggested an association between low vitamin D status and increased risk for type 2 diabetes (T2D). This study aimed to explore the dose-response relationship of serum 25-hydroxyvitamin D [25(OH)D] concentrations with incident T2D and the interaction between serum 25(OH)D with individual factors on T2D risk. A total of 1,926 adults without diabetes (mean age: 52.08 \u00b1 13.82 years; 42% men) were prospectively followed for 36 months. Cox proportional hazards model and restricted cubic spline analysis were performed to assess the association and dose-response relationship between serum 25(OH)D and T2D incidence. Both additive and multiplicative interactions were calculated between serum 25(OH)D and individual factors. The net reclassification index (NRI) was used to evaluate the improvement of risk prediction of T2D by adding serum 25(OH)D to traditional risk factors. There were 114 new T2D cases over a mean follow-up of 36 months. Serum 25(OH)D was not associated with T2D incidence, and no significant dose-response relationship was found in the total population. However, stratified analyses suggested a non-linear inverse relationship among individuals with baseline fasting plasma glucose (FPG) &amp;lt;5.6 mmol\/L (<jats:italic>P<\/jats:italic><jats:sub>overall<\/jats:sub>= 0.061,<jats:italic>P<\/jats:italic><jats:sub>non\u2013linear<\/jats:sub>= 0.048). And a significant multiplicative interaction was observed between serum 25(OH)D and FPG on T2D risk (<jats:italic>P<\/jats:italic>= 0.005). In addition, we found a significant additive interaction of low serum 25(OH)D with older age (RERI = 0.897, 95% CI: 0.080\u20131.714; AP = 0.468, 95% CI: 0.054\u20130.881), male (AP = 0.441, 95% CI: 0.010\u20130.871), and insufficient physical activity (RERI = 0.875, 95% CI: 0.204\u20131.545; AP = 0.575, 95% CI: 0.039\u20131.111) on T2D risk. Significant additive interactions were also observed between vitamin D deficiency\/insufficiency with male, overweight\/obesity, and insufficient physical activity on T2D risk. Moreover, adding low serum 25(OH)D to a model containing established risk factors yielded significant improvements in the risk reclassification of T2D (NRI = 0.205, 95% CI: 0.019\u20130.391). Our results indicated a non-linear relationship of serum 25(OH)D concentrations with T2D risk among individuals with normal FPG and additive interactions of serum 25(OH)D with gender, overweight\/obesity, and physical activity on T2D risk, suggesting the importance of outdoor exercise.<\/jats:p>","DOI":"10.3389\/fnut.2022.1077734","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T11:38:06Z","timestamp":1672313886000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The modification of individual factors on association between serum 25(OH)D and incident type 2 diabetes: Results from a prospective cohort study"],"prefix":"10.3389","volume":"9","author":[{"given":"Zhiyong","family":"Hu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyuan","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiafu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinxiu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianliang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"journal-title":"Diabetes around the world in 2021.","year":"2021","key":"B1"},{"key":"B2","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41574-021-00593-z","article-title":"The health effects of vitamin D supplementation: evidence from human studies.","volume":"18","author":"Bouillon","year":"2022","journal-title":"Nat Rev Endocrinol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1093\/advances\/nmab142","article-title":"Vitamin D and multiple health outcomes: an umbrella review of observational studies, randomized controlled trials, and mendelian randomization studies.","volume":"13","author":"Liu","year":"2022","journal-title":"Adv Nutr."},{"key":"B4","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.jnutbio.2015.09.013","article-title":"Vitamin D deficiency impairs glucose-stimulated insulin secretion and increases insulin resistance by reducing PPAR-gamma expression in nonobese type 2 diabetic rats.","volume":"27","author":"Park","year":"2016","journal-title":"J Nutr Biochem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1002\/dmrr.873","article-title":"1,25-dihydroxyvitamin D improved the free fatty-acid-induced insulin resistance in cultured C2C12 cells.","volume":"24","author":"Zhou","year":"2008","journal-title":"Diabetes Metab Res Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1210\/en.2004-1322","article-title":"1,25-dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: implications for prevention of diabetes in nonobese diabetic mice.","volume":"146","author":"Gysemans","year":"2005","journal-title":"Endocrinology."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph14020127","article-title":"25-hydroxyvitamin D status and risk for colorectal cancer and type 2 diabetes mellitus: a systematic review and meta-analysis of epidemiological studies.","volume":"14","author":"Ekmekcioglu","year":"2017","journal-title":"Int J Environ Res Public Health."},{"key":"B8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S2213-8587(14)70184-6","article-title":"Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study.","volume":"3","author":"Ye","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.2337\/dc12-0962","article-title":"Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies.","volume":"36","author":"Song","year":"2013","journal-title":"Diabetes Care."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-066222","article-title":"Effect of active vitamin D treatment on development of type 2 diabetes: DPVD randomised controlled trial in Japanese population.","volume":"377","author":"Kawahara","year":"2022","journal-title":"BMJ."},{"key":"B11","article-title":"Effects of long-term vitamin D supplementation on metabolic profile in middle-aged and elderly patients with type 2 diabetes.","volume":"225","author":"Hu","year":"2022","journal-title":"J Steroid Biochem Mol Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"565","DOI":"10.2337\/dc11-1795","article-title":"Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the diabetes prevention program.","volume":"35","author":"Pittas","year":"2012","journal-title":"Diabetes Care."},{"key":"B13","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.2337\/dc10-0790","article-title":"Plasma 25-hydroxyvitamin D concentration and risk of incident type 2 diabetes in women.","volume":"33","author":"Pittas","year":"2010","journal-title":"Diabetes Care."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1038\/ejcn.2012.134","article-title":"Serum 25(OH)D and incident type 2 diabetes: a cohort study.","volume":"66","author":"Husemoen","year":"2012","journal-title":"Eur J Clin Nutr."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157695","article-title":"Low vitamin D levels do not predict hyperglycemia in elderly endurance athletes (but in controls).","volume":"11","author":"Haslacher","year":"2016","journal-title":"PLoS One."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.2337\/dc12-0235","article-title":"Joint effects of obesity and vitamin D insufficiency on insulin resistance and type 2 diabetes: results from the NHANES 2001-2006.","volume":"35","author":"Kabadi","year":"2012","journal-title":"Diabetes Care."},{"key":"B17","doi-asserted-by":"crossref","first-page":"R195","DOI":"10.1530\/EC-20-0274","article-title":"Why do so many trials of vitamin D supplementation fail?","volume":"9","author":"Boucher","year":"2020","journal-title":"Endocr Connect."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/nu14163282","article-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 (=6%) levels.","volume":"14","author":"Zhu","year":"2022","journal-title":"Nutrients."},{"key":"B19","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1111\/dme.12180","article-title":"Non-linear association between 25-hydroxyvitamin D and the incidence of type 2 diabetes: a community-based nested case-control study.","volume":"30","author":"Tohidi","year":"2013","journal-title":"Diabet Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1007\/s10654-013-9844-5","article-title":"Plasma 25-hydroxyvitamin D and its genetic determinants in relation to incident type 2 diabetes: a prospective case-cohort study.","volume":"28","author":"Buijsse","year":"2013","journal-title":"Eur J Epidemiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s10654-013-9769-z","article-title":"Serum 25-hydroxyvitamin D levels and incident diabetes mellitus type 2: a competing risk analysis in a large population-based cohort of older adults.","volume":"28","author":"Schottker","year":"2013","journal-title":"Eur J Epidemiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.ahj.2015.06.017","article-title":"Assessment of serum 25-hydroxy vitamin D improves coronary heart disease risk stratification in patients with type 2 diabetes.","volume":"170","author":"Heidari","year":"2015","journal-title":"Am Heart J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.atherosclerosis.2015.11.020","article-title":"Contribution of vitamin D deficiency to the risk of coronary heart disease in subjects with essential hypertension.","volume":"244","author":"Nargesi","year":"2016","journal-title":"Atherosclerosis."},{"key":"B24","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.2337\/dc17-S005","article-title":"2. classification and diagnosis of diabetes.","volume":"40","year":"2017","journal-title":"Diabetes Care."},{"key":"B25","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.amepre.2011.03.008","article-title":"Physical activity in 22 African countries: results from the world health organization STEPwise approach to chronic disease risk factor surveillance.","volume":"41","author":"Guthold","year":"2011","journal-title":"Am J Prev Med."},{"key":"B26","first-page":"83","article-title":"Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults\u2013study on optimal cut-off points of body mass index and waist circumference in Chinese adults.","volume":"15","author":"Zhou","year":"2002","journal-title":"Biomed Environ Sci."},{"key":"B27","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline.","volume":"96","author":"Holick","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"key":"B28","first-page":"833","article-title":"2016 Chinese guidelines for the management of dyslipidemia in adults.","volume":"44","year":"2016","journal-title":"Zhonghua Xin Xue Guan Bing Za Zhi."},{"key":"B29","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/sim.3841","article-title":"Dose-response analyses using restricted cubic spline functions in public health research.","volume":"29","author":"Desquilbet","year":"2010","journal-title":"Stat Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s10654-005-4410-4","article-title":"Interaction: a word with two meanings creates confusion.","volume":"20","author":"Ahlbom","year":"2005","journal-title":"Eur J Epidemiol."},{"key":"B31","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s10654-005-7835-x","article-title":"Calculating measures of biological interaction.","volume":"20","author":"Andersson","year":"2005","journal-title":"Eur J Epidemiol."},{"key":"B32","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/sim.2929","article-title":"Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond.","volume":"27","author":"Pencina","year":"2008","journal-title":"Stat Med."},{"key":"B33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/sim.4085","article-title":"Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers.","volume":"30","author":"Pencina","year":"2011","journal-title":"Stat Med."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002566","article-title":"Association of vitamin D with risk of type 2 diabetes: a mendelian randomisation study in European and Chinese adults.","volume":"15","author":"Lu","year":"2018","journal-title":"PLoS Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1017\/S1368980019000582","article-title":"25-hydroxyvitamin D and the risk of incident diabetes in Hong Kong Chinese.","volume":"23","author":"Leung","year":"2020","journal-title":"Public Health Nutr."},{"key":"B36","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.nut.2013.01.010","article-title":"A glimpse of vitamin D status in mainland China.","volume":"29","author":"Zhang","year":"2013","journal-title":"Nutrition."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/s12937-016-0224-3","article-title":"Vitamin D status among the elderly Chinese population: a cross-sectional analysis of the 2010-2013 China national nutrition and health survey (CNNHS).","volume":"16","author":"Chen","year":"2017","journal-title":"Nutr J."},{"key":"B38","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJMoa1900906","article-title":"Vitamin D supplementation and prevention of type 2 diabetes.","volume":"381","author":"Pittas","year":"2019","journal-title":"N Engl J Med."},{"key":"B39","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.diabres.2015.01.036","article-title":"Vitamin D and diabetes: where do we stand?","volume":"108","author":"Mathieu","year":"2015","journal-title":"Diabetes Res Clin Pract."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1007\/s00125-012-2529-x","article-title":"Low serum 25-hydroxyvitamin D level predicts progression to type 2 diabetes in individuals with prediabetes but not with normal glucose tolerance.","volume":"55","author":"Deleskog","year":"2012","journal-title":"Diabetologia."},{"key":"B41","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1373\/clinchem.2012.193003","article-title":"Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis.","volume":"59","author":"Afzal","year":"2013","journal-title":"Clin Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/S2213-8587(21)00045-0","article-title":"Epidemiology and determinants of obesity in China.","volume":"9","author":"Pan","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B43","doi-asserted-by":"crossref","DOI":"10.3390\/medicina55090541","article-title":"Deficiency: consequence or cause of obesity?","volume":"55","author":"Vranic","year":"2019","journal-title":"Medicina."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2020-001359","article-title":"Associations between physical activity and trimethylamine N-oxide in those at risk of type 2 diabetes.","volume":"8","author":"Argyridou","year":"2020","journal-title":"BMJ Open Diabetes Res Care."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1093\/ajcn\/nqaa015","article-title":"Associations of plasma trimethylamine N-oxide, choline, carnitine, and betaine with inflammatory and cardiometabolic risk biomarkers and the fecal microbiome in the multiethnic cohort adiposity phenotype study.","volume":"111","author":"Fu","year":"2020","journal-title":"Am J Clin Nutr."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1124\/dmd.116.070615","article-title":"Trimethylamine and trimethylamine N-oxide, a flavin-containing monooxygenase 3 (FMO3)-mediated host-microbiome metabolic axis implicated in health and disease.","volume":"44","author":"Fennema","year":"2016","journal-title":"Drug Metab Dispos."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9896743","article-title":"Vitamin D decreases plasma trimethylamine-N-oxide level in mice by regulating gut microbiota.","volume":"2020","author":"Wang","year":"2020","journal-title":"Biomed Res Int."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/nu11061310","article-title":"A new light on vitamin D in obesity: a novel association with trimethylamine-N-oxide (TMAO).","volume":"11","author":"Barrea","year":"2019","journal-title":"Nutrients."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004289","article-title":"Serum total 25-OH vitamin D adds little prognostic value in patients undergoing coronary catheterization.","volume":"5","author":"Gerling","year":"2016","journal-title":"J Am Heart Assoc."},{"key":"B50","doi-asserted-by":"publisher","first-page":"2916","DOI":"10.2337\/dc20-1765","article-title":"Intratrial exposure to vitamin D and new-onset diabetes among adults with prediabetes: a secondary analysis from the vitamin D and type 2 diabetes (D2d) study.","volume":"43","author":"Dawson-Hughes","year":"2020","journal-title":"Diabetes Care."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.1077734\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T18:03:48Z","timestamp":1701626628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.1077734\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,29]]},"references-count":50,"alternative-id":["10.3389\/fnut.2022.1077734"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.1077734","relation":{},"ISSN":["2296-861X"],"issn-type":[{"type":"electronic","value":"2296-861X"}],"subject":[],"published":{"date-parts":[[2022,12,29]]},"article-number":"1077734"}}