{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:40:15Z","timestamp":1760118015802,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Romanian Ministry of Education and Research, CCCDI-UEFISCDI","award":["PN-III-P2-2.1-PED-2019-3313, within PNCDI III"],"award-info":[{"award-number":["PN-III-P2-2.1-PED-2019-3313, within PNCDI III"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Starting from the metabolic profile of type 2 diabetes mellitus (T2DM), we hypothesized that the mechanisms of \u00b9\u00b3\u00b9I-induced cardiotoxicity differ between patients diagnosed with differentiated thyroid cancer (DTC) with\/without T2DM, with metformin potentially acting as a cardioprotective agent by mitigating inflammation in patients with T2DM. To address this hypothesis, we quantified, using ELISA, the serum concentration of several key biomarkers that reflect cardiac injury (NT-proBNP, NT-proANP, ST2\/IL-33R, and cTn I) in 74 female patients with DTC\/\u2212T2DM and 25 with DTC\/+T2DM treated with metformin. All patients received a cumulative oral dose of 131I exceeding 150 mCi (5.55 GBq) over approximately 53 months. Our results showed the following: (i) In DTC\/\u2212T2DM patients, high-cumulative 131I doses promote a pro-inflammatory state that accelerates the development of cardiotoxicity. Monitoring NT-proBNP, ST2\/IL-33R, and cTn I in these patients may help identify those at risk of developing cardiac complications. (ii) In patients with DTC\/+T2DM, high-cumulative 131I doses lead to the release of NT-proANP (r = 0.63), which signals that the atria are under significant stress. (iii) In patients with DTC\/+T2DM, metformin suppresses inflammation, leading to a dose-dependent reduction in cTn I (r = \u22120.59). Monitoring cTn I and NT-proANP, and considering the use of metformin as part of the therapeutic strategy, could help manage cardiotoxicity in T2DM patients undergoing 131I therapy.<\/jats:p>","DOI":"10.3390\/ijms26010037","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T09:00:57Z","timestamp":1735030857000},"page":"37","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Interplay Between High Cumulative Doses of Radioactive Iodine and Type 2 Diabetes Mellitus: A Complex Cardiovascular Challenge"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9494-6686","authenticated-orcid":false,"given":"Adina Elena","family":"Stanciu","sequence":"first","affiliation":[{"name":"Carcinogenesis and Molecular Biology Department, Institute of Oncology Bucharest, 022328 Bucharest, Romania"},{"name":"Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madalina Lucica","family":"Bolovan","sequence":"additional","affiliation":[{"name":"Carcinogenesis and Molecular Biology Department, Institute of Oncology Bucharest, 022328 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6269-9126","authenticated-orcid":false,"given":"Adina","family":"Zamfir-Chiru-Anton","sequence":"additional","affiliation":[{"name":"ENT Department, \u201cGrigore Alexandrescu\u201d Children\u2019s Emergency Hospital, 011743 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catalina","family":"Voiosu","sequence":"additional","affiliation":[{"name":"ENT Department, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest, 050474 Bucharest, Romania"},{"name":"ENT Department, \u201cProf. Dr. Dorin Hociota\u201d Institute of Phonoaudiology and Functional ENT Surgery, 050751 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1409-6771","authenticated-orcid":false,"given":"Pradeep Kumar","family":"Dabla","sequence":"additional","affiliation":[{"name":"G.B. Pant Institute of Postgraduate Medical Education & Research (GIPMER), Delhi 110002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7857-478X","authenticated-orcid":false,"given":"Marcel Marian","family":"Stanciu","sequence":"additional","affiliation":[{"name":"Electrical Engineering Faculty, University \u201cPolitehnica\u201d of Bucharest, 060042 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-9819","authenticated-orcid":false,"given":"Nafija","family":"Serdarevic","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry and Biochemistry, University of Sarajevo Clinics Center, 7100 Sarajevo, Bosnia and Herzegovina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-0428","authenticated-orcid":false,"given":"Mirela","family":"Gherghe","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest, 050474 Bucharest, Romania"},{"name":"Nuclear Medicine Department, Institute of Oncology Bucharest, 022328 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref_1","unstructured":"Magliano, D.J., and Boyko, E.J. 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