{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T01:27:06Z","timestamp":1772242026016,"version":"3.50.1"},"reference-count":45,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515010425"],"award-info":[{"award-number":["2023A1515010425"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515013260"],"award-info":[{"award-number":["2024A1515013260"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2301300"],"award-info":[{"award-number":["2021YFC2301300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20220530145210024"],"award-info":[{"award-number":["JCYJ20220530145210024"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["ZDSYS20230626091203007"],"award-info":[{"award-number":["ZDSYS20230626091203007"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:p>Increasing evidence suggests that individuals infected with coronavirus disease 2019 (COVID-19) are at a higher risk of developing type 2 diabetes (T2D) compared with those who are not infected. However, the mechanisms underlying this relationship remain poorly understood. In this study, we aimed to systematically evaluate the mediating roles of 3,283 plasma proteins in the link between COVID-19 susceptibility and T2D by conducting proteome-wide Mendelian randomization (MR) analyses. Reverse MR, validation in independent data sets, and colocalization analyses were conducted to verify the robustness of the MR results. Furthermore, mediation analysis was performed to quantify the mediating effects. MR analyses between protein and T2D-related phenotypes were conducted to enhance the comprehension of potential mechanisms. Finally, the druggability of the identified proteins was evaluated. Four proteins causally associated with susceptibility to COVID-19 (ABO, CD209, CUZD1, and QXOS2) exhibited significant causal links with T2D. The protein CD209, which exhibited significant associations in validation and colocalization analyses, was identified as the causal mediating protein. Mediation analysis indicated that CD209 significantly mediated the total effect from COVID-19 susceptibility to T2D (\u03b2indirect 0.083 [95% CI 0.014, 0.152], P = 0.019). Further MR analyses revealed significant associations between CD209 and hemoglobin A1c, fasting glucose, fasting insulin, and waist-to-hip ratio. Evaluation of druggability demonstrated that CD209 can bind to \u03b1-d-mannose and interact with nine targets of T2D drugs, including dipeptidyl peptidase 4. Our findings highlight CD209 as a potential intervention target in individuals infected with COVID-19 to prevent T2D, providing novel insights into the pathophysiology linking COVID-19 and T2D.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Increasing evidence links coronavirus disease 2019 (COVID-19) infection with heightened type 2 diabetes (T2D) risk; however, the mechanisms underlying this relationship remain poorly understood. We aimed to identify mediating proteins linking COVID-19 infection with T2D, elucidating how COVID-19 might heighten T2D risk. Protein CD209 and central obesity potentially play a crucial role between COVID-19 susceptibility and T2D. Our results highlight CD209 as a potential intervention target for T2D prevention following COVID-19 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db24-0677","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T11:23:41Z","timestamp":1738063421000},"page":"619-629","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Identification of CD209 as an Intervention Target for Type 2 Diabetes After COVID-19 Infection: Insights From Proteome-Wide Mendelian Randomization"],"prefix":"10.2337","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8357-7667","authenticated-orcid":false,"given":"Jiaying","family":"Zhang","sequence":"first","affiliation":[{"name":"1School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China"},{"name":"2School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Jiao","sequence":"additional","affiliation":[{"name":"3Guangzhou Centre for Applied Mathematics, Guangzhou University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenqian","family":"Wang","sequence":"additional","affiliation":[{"name":"1School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China"},{"name":"2School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenfeng","family":"Zou","sequence":"additional","affiliation":[{"name":"1School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China"},{"name":"2School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangjun","family":"Du","sequence":"additional","affiliation":[{"name":"1School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China"},{"name":"2School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"4Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1295-3063","authenticated-orcid":false,"given":"Dewei","family":"Ye","sequence":"additional","affiliation":[{"name":"5Institute of Metabolic Science, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2795-714X","authenticated-orcid":false,"given":"Guozhi","family":"Jiang","sequence":"additional","affiliation":[{"name":"1School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China"},{"name":"2School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"4Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"2025032018521052100_B1","unstructured":"World Health Organization.\n          \n          WHO COVID-19 dashboard. 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