{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T03:58:28Z","timestamp":1773115108470,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>SARS-CoV-2 primarily has tissue tropism for the respiratory epithelium; however, it may cause multiple organ dysfunction due to the widespread expression of its entry receptor, ACE2. Specifically, SARS-CoV-2 may enter pancreatic \u03b2-cells by exploiting ACE2, disrupting cellular and hormonal activity, and thereby worsening Cardiovascular-Kidney-Metabolic (CKM) syndrome prognosis in diabetic patients. Furthermore, treatment with renin-angiotensin system inhibitors (RASi) may arguably increase ACE2 expression and facilitate viral entry, making its independent impact highly debated. Accordingly, we sought to elucidate the genuine impact of RASi usage on CKM progression via Propensity Score Matching (PSM) and concurrently investigate the specific contribution of pancreatic \u03b2-cell secretory dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective investigation involving 682 diabetic patients across CKM stages 2 to 4 with confirmed SARS-CoV-2 infection utilizing multivariate logistic regression coupled with 1:1 PSM to rectify selection bias concerning RASi administration and identifying predictors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Post-infection CKM progression was observed in 25.2% of the cohort and while initial multivariate models implicated RASi (OR = 1.56, 95% CI: 1.06\u20132.28; p=0.02) as a risk factor this association lost statistical significance after rigorously balancing baseline characteristics through PSM (OR = 1.56, 95% CI: 0.91\u20132.67; p = 0.156). A paradoxical finding emerged wherein the progression group exhibited low HOMA-IR scores accompanied by reduced fasting C-peptide and elevated glucose thereby indicating severe viral-induced \u03b2-cell secretory dysfunction rather than enhanced insulin sensitivity while High-Density Lipoprotein Cholesterol (HDL-C) persisted as a protective factor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>COVID-19 exacerbates CKM progression in diabetic patients, but this is not driven by RASi therapy itself. RASi use should be interpreted as a \u201cmarker of severity\u201d for baseline comorbidities, rather than a pathogenic factor. Mechanistically, viral infection may cause the failure of compensatory mechanisms in pancreatic \u03b2-cell function (manifested as low C-peptide and spurious low HOMA-IR).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1790281","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:36:09Z","timestamp":1773070569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["COVID-19 associated CKM syndrome progression in diabetic patients is linked to pancreatic beta cell dysfunction, rather than RASi use: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yongcheng","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Health Science and Engineering,University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziqi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizhe","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Health Science and Engineering,University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, 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