{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:05:48Z","timestamp":1790017548858,"version":"4.0.1"},"reference-count":43,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2-SRA-2024-1509-S-B"],"award-info":[{"award-number":["2-SRA-2024-1509-S-B"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["5T32GM8111-35"],"award-info":[{"award-number":["5T32GM8111-35"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMR2208831"],"award-info":[{"award-number":["DMR2208831"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cell, Molecular, and Developmental Biology T32","award":["5T32GM8111-35"],"award-info":[{"award-number":["5T32GM8111-35"]}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["DK126456"],"award-info":[{"award-number":["DK126456"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["DK127497"],"award-info":[{"award-number":["DK127497"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["DK131716"],"award-info":[{"award-number":["DK131716"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["DK138469"],"award-info":[{"award-number":["DK138469"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Proinflammatory T helper 1 (Th1) CD4 T cells orchestrate \u03b2-cell destruction in type 1 diabetes (T1D) by using glycolysis for effector responses. By targeting T-cell metabolism, we may identify novel mechanisms and therapies to effectively delay T cell\u2013mediated autoimmune diseases like T1D. We hypothesized that treatment of prediabetic mice with the glycolysis inhibitor, 2-deoxyglucose (2-DG), during CD4 T-cell activation would diminish proinflammatory Th1 effector responses and delay \u03b2-cell destruction. Treatment of prediabetic nonobese diabetic (NOD) mice with 2-DG significantly delayed spontaneous T1D compared with control mice. In addition to suppressing polyclonal T-cell responses in the pancreatic and mesenteric lymph nodes, diminished Th1 effector responses and an increase in anergy was observed in clonal, autoreactive CD4 T cells stimulated with their cognate autoantigen in the presence of 2-DG. A decrease in CD86 expression in antigen-presenting cells treated with 2-DG may partly explain the induction of CD4 T-cell anergy. Peripheral blood mononuclear cells from patients with or without T1D stimulated with \u03b1-CD3\/\u03b1-CD28\u2013containing microbeads exhibited a decrease in IFNG and TBX21 mRNA with 2-DG treatment. Our studies suggest diminishing glycolysis in autoreactive CD4 T cells can decrease Th1 effector responses and promote anergy as a novel strategy to delay autoimmune diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Our goal: limit glycolysis with 2-deoxyglucose (2-DG) in autoreactive CD4 T cells to delay spontaneous type 1 diabetes in NOD mice. Inhibition of glycolysis with 2-DG during autoreactive CD4 T-cell activation and differentiation decreased effector responses (interferon-\u03b3), increased anergic markers (CD73, folate receptor 4), and delayed spontaneous type 1 diabetes in NOD mice. The effects of 2-DG on antigen-presenting cells resulted in a decrease in CD86 expression that may partly explain the induction of anergy. Inhibiting glycolysis is sufficient to diminish autoreactive CD4 T-cell responses and may be therapeutically applicable to other T cell\u2013mediated inflammatory diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-1152","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:36:57Z","timestamp":1785785817000},"page":"1837-1849","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Blockade of Glycolysis Diminishes Autoreactive CD4 T-Cell Effector Responses in Type 1 Diabetes"],"prefix":"10.2337","volume":"75","author":[{"given":"Miranda D.","family":"Ch\u00e1vez","sequence":"first","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center 1 , Kansas City, KS"},{"name":"Department of Urology, University of Alabama at Birmingham 2 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R.","family":"Mahr","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center 1 , Kansas City, KS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Kansas Medical Center 3 , Kansas City, KS"},{"name":"University of Kansas Alzheimer\u2019s Disease Research Center, University of Kansas Medical Center 4 , Kansas City, KS"},{"name":"Department of Neurology, University of Kansas Medical Center 5 , Kansas City, KS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-7597","authenticated-orcid":false,"given":"Hubert M.","family":"Tse","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center 1 , Kansas City, KS"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"2026092114520046000_B1","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1001\/jama.2024.2103","article-title":"Prevalence of type 1 diabetes among US children and adults by age, sex, race, and ethnicity","volume":"331","author":"Fang","year":"2024","journal-title":"JAMA"},{"key":"2026092114520046000_B2","doi-asserted-by":"crossref","first-page":"17016","DOI":"10.1038\/nrdp.2017.16","article-title":"Type 1 diabetes mellitus","volume":"3","author":"Katsarou","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2026092114520046000_B3","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.2337\/dc22-S002","article-title":"2. 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