{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:17:45Z","timestamp":1791278265939,"version":"4.1.0"},"reference-count":34,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":4469,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,8,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress, systemic inflammation, and endothelial dysfunction. We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>The Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 female health professionals aged \u226540 years with a history of cardiovascular disease (CVD) or three or more CVD risk factors, included 4,252 women free of diabetes at baseline. Participants were randomly assigned to either an active treatment group (daily intake of a combination pill of 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12) or to the placebo group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>During a median follow-up of 7.3 years, 504 women had an incident diagnosis of type 2 diabetes. Overall, there was no significant difference between the active treatment group and the placebo group in diabetes risk (relative risk 0.94 [95% CI 0.79\u20131.11]; P = 0.46), despite significant lowering of homocysteine levels. Also, there was no evidence for effect modifications by baseline intakes of dietary folate, vitamin B6, and vitamin B12. In a sensitivity analysis, the null result remained for women compliant with their study pills (0.92 [0.76\u20131.10]; P = 0.36).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Lowering homocysteine levels by daily supplementation with folic acid and vitamins B6 and B12 did not reduce the risk of developing type 2 diabetes among women at high risk for CVD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db09-0087","type":"journal-article","created":{"date-parts":[[2009,6,3]],"date-time":"2009-06-03T00:54:05Z","timestamp":1243990445000},"page":"1921-1928","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":74,"title":["Effect of Homocysteine-Lowering Treatment With Folic Acid and B Vitamins on Risk of Type 2 Diabetes in Women"],"prefix":"10.2337","volume":"58","author":[{"given":"Yiqing","family":"Song","sequence":"first","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy R.","family":"Cook","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Albert","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Division of Cardiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Van Denburgh","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2009,6,2]]},"reference":[{"key":"2022031210520446100_B1","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1056\/NEJM199804093381507","article-title":"Homocysteine and atherothrombosis","volume":"338","author":"Welch","year":"1998","journal-title":"N Engl J Med"},{"key":"2022031210520446100_B2","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1515\/CCLM.2003.223","article-title":"Influence of hyperhomocysteinemia on the cellular redox state: impact on homocysteine-induced endothelial dysfunction","volume":"41","author":"Weiss","year":"2003","journal-title":"Clin Chem Lab Med"},{"key":"2022031210520446100_B3","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1172\/JCI10588","article-title":"Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model","volume":"107","author":"Hofmann","year":"2001","journal-title":"J Clin Invest"},{"key":"2022031210520446100_B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2337\/diabetes.52.1.1","article-title":"Are oxidative stress-activated signaling pathways mediators of insulin resistance and \u03b2-cell dysfunction?","volume":"52","author":"Evans","year":"2003","journal-title":"Diabetes"},{"key":"2022031210520446100_B5","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1161\/01.ATV.0000122852.22604.78","article-title":"Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? 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