{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:38:05Z","timestamp":1790379485093,"version":"4.1.0"},"reference-count":24,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82405318"],"award-info":[{"award-number":["82405318"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Science and Technology Development Plan Project of Jilin Province","award":["YDZJ202501ZYTS214"],"award-info":[{"award-number":["YDZJ202501ZYTS214"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Type 2 diabetes (T2D) impairs antiviral immunity; however, the causal link between T2D and interferon-\u03b12 (IFN-\u03b12) deficiency remains unclear. This study used genome-wide association study\u2013based Mendelian randomization (MR) to investigate this relationship and validated the findings in an H1N1-infected diabetic mouse model. MR analysis of 26 single nucleotide polymorphisms showed a significant negative association between T2D and IFN-\u03b12 levels (inverse variance weighted odds ratio 0.667; P = 0.000116) without heterogeneity or pleiotropy. In vivo experiments confirmed that db\/db mice exhibited more severe H1N1-induced lung injury, higher viral loads, and lower survival rates compared with nondiabetic controls. However, exogenous IFN-\u03b12 treatment significantly reversed these pathologic outcomes. Inflammatory cytokine profiling showed that IFN-\u03b12 downregulated 21 elevated cytokines and restored Fas ligand levels in lung tissue. Mechanistically, Western blotting demonstrated that IFN-\u03b12 inhibited the phosphorylation of JAK1\/2 and STAT3, thereby suppressing excessive inflammation. In conclusion, our findings indicate that T2D leads to IFN-\u03b12 deficiency, contributing to susceptibility to viral infection. Supplementation with IFN-\u03b12 effectively attenuated virus-induced lung injury by inhibiting JAK\/STAT3 signaling and cytokine storms, positioning IFN-\u03b12 supplementation as a promising therapeutic strategy for managing influenza complications in patients with diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Type 2 diabetes (T2D) is linked to impaired antiviral immunity, but whether it drives interferon-\u03b12 (IFN-\u03b12) deficiency remains unknown. We asked whether T2D causally suppresses IFN-\u03b12 levels and whether exogenous supplementation could rescue host defense mechanisms against influenza infection. By integrating genetic analysis with an H1N1-infected diabetic mouse model, we show that T2D genetically lowers IFN-\u03b12 and that treatment reverses lung injury by inhibiting JAK\/STAT3-mediated hyperinflammation. Our study positions IFN-\u03b12 supplementation as a promising therapeutic strategy to prevent severe viral pneumonia in patients with T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0974","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T14:20:12Z","timestamp":1781274012000},"page":"1450-1459","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":2,"title":["Type 2 Diabetes Reduces IFN-\u03b12 and Compromises Antiviral Defense: Evidence From Mendelian Randomization and H1N1-Infected Diabetic Mice"],"prefix":"10.2337","volume":"75","author":[{"given":"Siye","family":"Lyu","sequence":"first","affiliation":[{"name":"Key Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine 1 , Changchun, China"},{"name":"Changchun University of Chinese Medicine 2 , Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine 1 , Changchun, China"},{"name":"Changchun University of Chinese Medicine 2 , Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihui","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine 1 , Changchun, China"},{"name":"Changchun University of Chinese Medicine 2 , Changchun, 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Medicine, Changchun University of Chinese Medicine 1 , Changchun, China"},{"name":"Changchun University of Chinese Medicine 2 , Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyan","family":"Shao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine 1 , Changchun, China"},{"name":"Jilin Agricultural University 4 , Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingquan","family":"Li","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine 2 , Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine 1 , Changchun, China"},{"name":"Changchun University of Chinese Medicine 2 , Changchun, China"},{"name":"Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University 5 , Yangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5769-8306","authenticated-orcid":false,"given":"Xiaomiao","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Second Medical Center of the People\u2019s Liberation Army General Hospital 6 , Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1126-305X","authenticated-orcid":false,"given":"Jicheng","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Traditional Chinese Medicine 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