{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T17:06:35Z","timestamp":1783962395519,"version":"3.55.0"},"reference-count":62,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Apoyo a la Incorporaci\u00f3n de Nuevos PTCs","award":["UDG-PTC-1475"],"award-info":[{"award-number":["UDG-PTC-1475"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"abstract":"<jats:p>\n                    Type 2 diabetes mellitus (T2DM) involves inadequate insulin production and utilization. Osteocalcin (OC) links bone and energy metabolism, existing as carboxylated (cOC) and undercarboxylated (ucOC) isoforms. The ucOC\/cOC ratio is influenced by vitamin K epoxide reductase complex subunit 1 (\n                    <jats:italic toggle=\"yes\">VKORC1<\/jats:italic>\n                    ) gene variants and vitamin intake. This study analyzes the effects of vitamin D3 (VD3) and vitamin K2 (VK2) supplementation on ucOC, insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), and the percentage of functional pancreatic beta cells (%FP\u03b2C) in Mexican Citizens with T2DM carrying the\n                    <jats:italic toggle=\"yes\">VKORC1<\/jats:italic>\n                    rs8050894 variant. The present randomized clinical trial recruited 40 Mexican subjects with T2DM. Participants were assigned to one of three groups receiving VD3, VK2, or a combination of both over a 3-month period. ucOC levels and insulin were measured using an ELISA assay; glucose and lipid profiles were measured by spectrophotometry (ERBA XL200). HOMA-IR and %FP\u03b2C were calculated. The rs8050894 variant was genotyped using allelic discrimination with real-time polymerase chain reaction. All groups exhibited significantly lower levels of glucose and %FP\u03b2C. Significant effects were observed in glucose, insulin, %FP\u03b2C, and HOMA-IR in CG genotype carriers in the VK2 group. On the other hand, CC genotype carriers showed higher ucOC levels compared to other genotypes in the VK2 and VK2\u2009+\u2009D3 intervention groups.\n                  <\/jats:p>\n                  <jats:p>\n                    Trial Registration number: NCT04041492. 2019-07-3.\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/show\/NCT04041492\">https:\/\/clinicaltrials.gov\/show\/NCT04041492<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1177\/10815589261460882","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:06:36Z","timestamp":1780920396000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between the\n                    <i>VKORC1<\/i>\n                    rs8050894 CC genotype and undercarboxylated osteocalcin levels following vitamin K and D supplementation in Mexican Citizens with T2DM: A randomized clinical trial"],"prefix":"10.1177","author":[{"given":"Yahatziri","family":"Salinas-Varela","sequence":"first","affiliation":[{"name":"Instituto de Nutrigen\u00e9tica y Nutrigen\u00f3mica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"},{"name":"Doctorado en Ciencias de la Nutrici\u00f3n Traslacional, Centro Universitario de Ciencias de la Salud, University of Guadalajara, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Antonio","family":"Barajas-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Instituto de Nutrigen\u00e9tica y Nutrigen\u00f3mica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Instituto de Nutrigen\u00e9tica y Nutrigen\u00f3mica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"},{"name":"Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris Monserrat","family":"Llamas-Covarrubias","sequence":"additional","affiliation":[{"name":"Instituto de Nutrigen\u00e9tica y Nutrigen\u00f3mica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"},{"name":"Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5151-041X","authenticated-orcid":false,"given":"Andres","family":"Lopez-Quintero","sequence":"additional","affiliation":[{"name":"Instituto de Nutrigen\u00e9tica y Nutrigen\u00f3mica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"},{"name":"Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"S\u00e1nchez-Enr\u00edquez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitl\u00e1n de Morelos, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar Alfonso","family":"Rivera-Le\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Nutrigen\u00e9tica y Nutrigen\u00f3mica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"},{"name":"Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, M\u00e9xico"},{"name":"Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitl\u00e1n de Morelos, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"issue":"1","key":"e_1_3_3_2_2","article-title":"Introduction and methodology: Standards of Care in Diabetes\u20142023","volume":"46","author":"ElSayed NA","year":"2022","unstructured":"ElSayed NA, Aleppo G, Aroda VR, et al. Introduction and methodology: Standards of Care in Diabetes\u20142023. Diabetes Care 2022; 46(Suppl 1): S1\u2013S4.","journal-title":"Diabetes Care"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcjd.2017.10.003"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2011.07.015"},{"key":"e_1_3_3_5_2","article-title":"Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study","volume":"36","author":"Diniz M de FHS","year":"2020","unstructured":"Diniz M de FHS, Beleigoli AMR, Schmidt MI, et al. Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study. Cad Sa\u00fade P\u00fablica 2020; 36: e00072120.","journal-title":"Cad Sa\u00fade P\u00fablica"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000691"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13020253"},{"key":"e_1_3_3_8_2","volume-title":"Global report on diabetes","author":"Roglic G","year":"2016","unstructured":"Roglic G; World Health Organization (eds). Global report on diabetes. World Health Organization, 2016."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcd.2020.10.001"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.21149\/14832"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194127"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0901-x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gaceta.2017.08.001"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194873"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1412228"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7454376"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu16152420"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189707"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2012.05.013"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01419.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2017.11.020"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.61.471"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1802-7"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-008-0020-y"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-024-02418-8"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.12944\/CRNFSJ.10.3.3"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.05.022"},{"issue":"2","key":"e_1_3_3_28_2","first-page":"602","article-title":"Niveles de referencia de osteocalcina en poblaci\u00f3n sana de M\u00e9xico","volume":"154","author":"Nieto-Flores J","year":"2018","unstructured":"Nieto-Flores J, Villaf\u00e1n-Bernal JR, Rivera-Le\u00f3n EA, et al. Niveles de referencia de osteocalcina en poblaci\u00f3n sana de M\u00e9xico. Gac Med Mex 2018; 154(2): 602.","journal-title":"Gac Med Mex"},{"issue":"1","key":"e_1_3_3_29_2","first-page":"846480","article-title":"Endocrine actions of osteocalcin","volume":"2013","author":"Patti A","year":"2013","unstructured":"Patti A, Gennari L, Merlotti D, et al. Endocrine actions of osteocalcin. Int J Endocrinol 2013; 2013(1): 846480.","journal-title":"Int J Endocrinol"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201409111"},{"issue":"8","key":"e_1_3_3_31_2","first-page":"396","article-title":"Bone as a regulator of glucose metabolism","volume":"71","author":"Veldhuis-Vlug AG","year":"2013","unstructured":"Veldhuis-Vlug AG, Fliers E, Bisschop PH. Bone as a regulator of glucose metabolism. Neth J Med 2013; 71(8): 396\u2013400.","journal-title":"Neth J Med"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.05.046"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-144899"},{"key":"e_1_3_3_34_2","unstructured":"rs8050894\u2014SNP\u2014NCBI [cited 23 January 2026] https:\/\/www.ncbi.nlm.nih.gov\/snp\/?term=rs8050894"},{"key":"e_1_3_3_35_2","unstructured":"rs8050894 (SNP)\u2014Explore this variant\u2014Homo_sapiens\u2014Ensembl genome browser 115 [cited 5 February 2026] https:\/\/www.ensembl.org\/Homo_sapiens\/Variation\/Explore?db=core;r=16:31092688-31093688;v=rs8050894;vdb=variation;vf=923484199"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.55.112"},{"key":"e_1_3_3_37_2","first-page":"47","article-title":"variants as significant predictors of warfarin dose in Emiratis","volume":"12","author":"Al-Mahayri ZN","year":"2019","unstructured":"Al-Mahayri ZN, Jaibeji HSA, Saab Y, et al. VKORC1variants as significant predictors of warfarin dose in Emiratis. Pharmagen Pers Med 2019; 12: 47\u201357.","journal-title":"VKORC1"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044503"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015088"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03672.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes16121396"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu10080970"},{"key":"e_1_3_3_43_2","doi-asserted-by":"crossref","unstructured":"Oldenburg J Watzka M Rost S et al. VKORC1: molecular target of coumarins. J Thromb Haemost 2007; 5 Suppl: 1\u20136.","DOI":"10.1111\/j.1538-7836.2007.02549.x"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-020-00580-w"},{"issue":"1","key":"e_1_3_3_45_2","first-page":"580474","article-title":"The role of vitamin D in diabetes and cardiovascular disease: an updated review of the literature","volume":"2015","author":"Papandreou D","year":"2015","unstructured":"Papandreou D, Hamid ZTN. The role of vitamin D in diabetes and cardiovascular disease: an updated review of the literature. Dis Markers 2015; 2015(1): 580474.","journal-title":"Dis Markers"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-020-02419-6"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu15030480"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-025-01161-0"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu14194082"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2012.201"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.21149\/9028"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.5604\/01.3001.0011.7386"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-0551"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-023-02880-0"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-020-00765-w"},{"issue":"2","key":"e_1_3_3_56_2","first-page":"152","article-title":"Dislipidemia diab\u00e9tica","volume":"27","author":"Cuevas MA","year":"2016","unstructured":"Cuevas MA, Alonso KR. Dislipidemia diab\u00e9tica. Rev Med Clin Condes 2016; 27(2): 152\u2013159.","journal-title":"Rev Med Clin Condes"},{"issue":"3","key":"e_1_3_3_57_2","first-page":"103","article-title":"Gu\u00eda de Tratamiento Farmacol\u00f3gico de Dislipidemias para el primer nivel de atenci\u00f3n","volume":"24","year":"2013","unstructured":"Gu\u00eda de Tratamiento Farmacol\u00f3gico de Dislipidemias para el primer nivel de atenci\u00f3n. Rev Mex Cardiol 2013; 24(3): 103\u2013129.","journal-title":"Rev Mex Cardiol"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2023-003680"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metop.2024.100287"},{"key":"e_1_3_3_60_2","doi-asserted-by":"crossref","unstructured":"Tabesh M Azadbakht L Faghihimani E et al. Effects of calcium\u2013vitamin D co-supplementation on metabolic profiles in vitamin D-insufficient people with type 2 diabetes: a randomised controlled clinical trial. Diabetologia 2014; 57(10): 2038\u20132047. https:\/\/doi.org\/10.1007\/s00125-014-3313-x","DOI":"10.1007\/s00125-014-3313-x"},{"key":"e_1_3_3_61_2","doi-asserted-by":"crossref","unstructured":"Asemi Z Raygan F Bahmani F et al. The effects of vitamin D K and calcium co-supplementation on carotid intima-media thickness and metabolic status in overweight type 2 diabetic patients with CHD. Br J Nutr 2016; 116(2): 286\u2013293. https:\/\/doi.org\/10.1017\/S0007114516001847","DOI":"10.1017\/S0007114516001847"},{"key":"e_1_3_3_62_2","doi-asserted-by":"crossref","unstructured":"Wallace TM Levy JC Matthews DR Use and abuse of HOMA modeling. Diabetes Care 2004; 27(6): 1487\u20131495. https:\/\/doi.org\/10.2337\/diacare.27.6.1487","DOI":"10.2337\/diacare.27.6.1487"},{"key":"e_1_3_3_63_2","doi-asserted-by":"crossref","unstructured":"Cao C Koh H-CE Reeds DN et al. Critical evaluation of indices used to assess \u03b2-cell function. Diabetes 2024; 73(3): 391\u2013400. https:\/\/doi.org\/10.2337\/db23-0613","DOI":"10.2337\/db23-0613"}],"container-title":["Journal of Investigative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10815589261460882","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10815589261460882","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10815589261460882","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:20:19Z","timestamp":1783959619000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10815589261460882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":62,"alternative-id":["10.1177\/10815589261460882"],"URL":"https:\/\/doi.org\/10.1177\/10815589261460882","relation":{},"ISSN":["1081-5589","1708-8267"],"issn-type":[{"value":"1081-5589","type":"print"},{"value":"1708-8267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]},"article-number":"10815589261460882"}}