{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T02:19:57Z","timestamp":1768529997023,"version":"3.49.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Min Zhang, Banjun Ruan, Pu Chen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recent studies suggest that high-normal concentrations of free triiodothyronine (FT3) were associated with a lower prevalence of microangiopathy in adult euthyroid people with type 1 diabetes. This study was performed to identify the association between thyroid hormones and lower extremity arterial disease (LEAD) in euthyroid patients with type 2 diabetes mellitus (T2DM). A total of 1052 euthyroid T2DM patients were enrolled, including 704 patients with LEAD as observation group and 348 patients with T2DM alone as control group. The differences in clinical characteristics, biochemical indexes, thyroid hormone between the two groups were compared. At the same time, the association between the incidence of LEAD and thyroid hormone was analyzed. The data demonstrated that FT4 levels were significantly lower in the LEAD patients than in the without LEAD patients (16.1 vs. 16.5 pmol\/L). The logistic regression analysis revealed that free thyroxine (FT4) was significantly associated with the incidence of LEAD in T2DM patients, and the prevalence of LEAD increased gradually from the highest FT4 quartile to the lowest FT4 quartile (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). In conclusion, patients with low-normal FT4 had a higher prevalence of diabetic LEAD, suggesting that adjusting FT4 levels may better regulate metabolism and thus reduce lower extremity arterial injury.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-31396-1","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T01:36:34Z","timestamp":1765244194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low-normal free thyroxine is associated with a higher prevalence of lower extremity arterial disease in euthyroid type 2 diabetes mellitus"],"prefix":"10.1038","volume":"16","author":[{"given":"Min","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenwen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banjun","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"31396_CR1","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.ecl.2021.05.013","volume":"50","author":"MG Tinajero","year":"2021","unstructured":"Tinajero, M. G. & Malik, V. S. An update on the epidemiology of type 2 diabetes: A global perspective. Endocrinol. Metab. Clin. North Am. 50, 337\u2013355. https:\/\/doi.org\/10.1016\/j.ecl.2021.05.013 (2021).","journal-title":"Endocrinol. Metab. Clin. North Am."},{"key":"31396_CR2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/s2213-8587(13)70112-8","volume":"2","author":"PZ Zimmet","year":"2014","unstructured":"Zimmet, P. Z., Magliano, D. J., Herman, W. H. & Shaw, J. E. Diabetes: a 21st century challenge. Lancet Diabets Endocrionol. 2, 56\u201364. https:\/\/doi.org\/10.1016\/s2213-8587(13)70112-8 (2014).","journal-title":"Lancet Diabets Endocrionol."},{"key":"31396_CR3","doi-asserted-by":"publisher","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","volume":"157","author":"P Saeedi","year":"2019","unstructured":"Saeedi, P. et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the international diabetes federation diabetes Atlas, 9(th) edition. Diabetes Res. Clin. Pract. 157, 107843. https:\/\/doi.org\/10.1016\/j.diabres.2019.107843 (2019).","journal-title":"Diabetes Res. Clin. Pract."},{"key":"31396_CR4","doi-asserted-by":"publisher","first-page":"Cd005266","DOI":"10.1002\/14651858.CD005266.pub2","volume":"5","author":"N Peer","year":"2020","unstructured":"Peer, N., Balakrishna, Y. & Durao, S. Screening for type 2 diabetes mellitus. Cochrane Database Syst. Rev. 5, Cd005266. https:\/\/doi.org\/10.1002\/14651858.CD005266.pub2 (2020).","journal-title":"Cochrane Database Syst. Rev."},{"key":"31396_CR5","doi-asserted-by":"publisher","unstructured":"Nativel, M. et al. Lower extremity arterial disease in patients with diabetes: a contemporary narrative review. 17, 138, https:\/\/doi.org\/10.1186\/s12933-018-0781-1 (2018).","DOI":"10.1186\/s12933-018-0781-1"},{"key":"31396_CR6","doi-asserted-by":"publisher","first-page":"109212","DOI":"10.1016\/j.diabres.2022.109212","volume":"184","author":"CW Hicks","year":"2022","unstructured":"Hicks, C. W. et al. Glycated albumin and HbA1c as markers of lower extremity disease inus adults with and without diabetes. Diabetes Res. Clin. Pract. 184, 109212. https:\/\/doi.org\/10.1016\/j.diabres.2022.109212 (2022).","journal-title":"Diabetes Res. Clin. Pract."},{"key":"31396_CR7","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.1161\/circresaha.121.318258","volume":"128","author":"MP Bonaca","year":"2021","unstructured":"Bonaca, M. P., Hamburg, N. M. & Creager, M. A. Contemporary medical management of peripheral artery disease. Circul. Res. 128, 1868\u20131884. https:\/\/doi.org\/10.1161\/circresaha.121.318258 (2021).","journal-title":"Circul. Res."},{"key":"31396_CR8","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1007\/s12020-018-1582-8","volume":"60","author":"B Falkowski","year":"2018","unstructured":"Falkowski, B. et al. Higher free Triiodothyronine concentration is associated with lower prevalence of microangiopathic complications and better metabolic control in adult euthyroid people with type 1 diabetes. Endocrine 60, 458\u2013465. https:\/\/doi.org\/10.1007\/s12020-018-1582-8 (2018).","journal-title":"Endocrine"},{"key":"31396_CR9","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.2337\/diacare.23.8.1108","volume":"23","author":"MM Gabir","year":"2000","unstructured":"Gabir, M. M. et al. The 1997 American diabetes association and 1999 world health organization criteria for hyperglycemia in the diagnosis and prediction of diabetes. Diabetes Care. 23, 1108\u20131112. https:\/\/doi.org\/10.2337\/diacare.23.8.1108 (2000).","journal-title":"Diabetes Care"},{"key":"31396_CR10","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.cmet.2017.06.014","volume":"26","author":"N Mart\u00ednez-S\u00e1nchez","year":"2017","unstructured":"Mart\u00ednez-S\u00e1nchez, N. et al. Hypothalamic AMPK-ER Stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance. Cell Metabol. 26, 212\u2013229e212. https:\/\/doi.org\/10.1016\/j.cmet.2017.06.014 (2017).","journal-title":"Cell Metabol."},{"key":"31396_CR11","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1152\/physrev.00030.2013","volume":"94","author":"R Mullur","year":"2014","unstructured":"Mullur, R., Liu, Y. Y. & Brent, G. A. Thyroid hormone regulation of metabolism. Physiol. Rev. 94, 355\u2013382. https:\/\/doi.org\/10.1152\/physrev.00030.2013 (2014).","journal-title":"Physiol. Rev."},{"key":"31396_CR12","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1093\/eurheartj\/ehx050","volume":"39","author":"C Floriani","year":"2018","unstructured":"Floriani, C., Gencer, B., Collet, T. H. & Rodondi, N. Subclinical thyroid dysfunction and cardiovascular diseases: 2016 update. Eur. Heart J. 39, 503\u2013507. https:\/\/doi.org\/10.1093\/eurheartj\/ehx050 (2018).","journal-title":"Eur. Heart J."},{"key":"31396_CR13","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.cnc.2018.11.003","volume":"31","author":"LM Wiltz-James","year":"2019","unstructured":"Wiltz-James, L. M. & Foley, J. Hospital discharge teaching for patients with peripheral vascular disease. Crit. Care Nurs. Clin. N. Am. 31, 91\u201395. https:\/\/doi.org\/10.1016\/j.cnc.2018.11.003 (2019).","journal-title":"Crit. Care Nurs. Clin. N. Am."},{"key":"31396_CR14","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1016\/j.jacc.2018.02.045","volume":"71","author":"S Razvi","year":"2018","unstructured":"Razvi, S. et al. Thyroid hormones and cardiovascular function and diseases. J. Am. Coll. Cardiol. 71, 1781\u20131796. https:\/\/doi.org\/10.1016\/j.jacc.2018.02.045 (2018).","journal-title":"J. Am. Coll. Cardiol."},{"key":"31396_CR15","doi-asserted-by":"publisher","first-page":"96","DOI":"10.3275\/8190","volume":"35","author":"S La Vignera","year":"2012","unstructured":"La Vignera, S., Condorelli, R., Vicari, E. & Calogero, A. E. Endothelial dysfunction and subclinical hypothyroidism: a brief review. J. Endocrinol. Investig. 35, 96\u2013103. https:\/\/doi.org\/10.3275\/8190 (2012).","journal-title":"J. Endocrinol. Investig."},{"key":"31396_CR16","doi-asserted-by":"publisher","first-page":"275","DOI":"10.3109\/07435800.2015.1135443","volume":"41","author":"A Gungor","year":"2016","unstructured":"Gungor, A. et al. Levels of endothelial cell-specific molecule-1 (ESM-1) in overt hypothyroidisim. Endocr. Res. 41, 275\u2013280. https:\/\/doi.org\/10.3109\/07435800.2015.1135443 (2016).","journal-title":"Endocr. Res."},{"key":"31396_CR17","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/nrendo.2018.10","volume":"14","author":"RA Sinha","year":"2018","unstructured":"Sinha, R. A., Singh, B. K. & Yen, P. M. Direct effects of thyroid hormones on hepatic lipid metabolism. Nat. Rev. Endocrinol. 14, 259\u2013269. https:\/\/doi.org\/10.1038\/nrendo.2018.10 (2018).","journal-title":"Nat. Rev. Endocrinol."},{"key":"31396_CR18","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1089\/thy.2018.0416","volume":"29","author":"AR Cappola","year":"2019","unstructured":"Cappola, A. R. et al. Thyroid and cardiovascular disease: research agenda for enhancing Knowledge, Prevention, and treatment. Thyroid: Official J. Am. Thyroid Association. 29, 760\u2013777. https:\/\/doi.org\/10.1089\/thy.2018.0416 (2019).","journal-title":"Thyroid: Official J. Am. Thyroid Association"},{"key":"31396_CR19","doi-asserted-by":"publisher","first-page":"50","DOI":"10.15420\/ecr.2018.33.1","volume":"14","author":"S Tsalamandris","year":"2019","unstructured":"Tsalamandris, S. et al. The role of inflammation in diabetes: current concepts and future perspectives. Eur. Cardiol. 14, 50\u201359. https:\/\/doi.org\/10.15420\/ecr.2018.33.1 (2019).","journal-title":"Eur. Cardiol."},{"key":"31396_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2015.06.054","volume":"242","author":"F Ag\u00fcero","year":"2015","unstructured":"Ag\u00fcero, F. et al. Prevalence of lower extremity peripheral arterial disease in individuals with chronic immune mediated inflammatory disorders. Atherosclerosis 242, 1\u20137. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2015.06.054 (2015).","journal-title":"Atherosclerosis"},{"key":"31396_CR21","doi-asserted-by":"publisher","first-page":"19689","DOI":"10.1038\/s41598-021-99252-6","volume":"11","author":"J Li","year":"2021","unstructured":"Li, J. et al. Differential lipids in pregnant women with subclinical hypothyroidism and their correlation to the pregnancy outcomes. Sci. Rep. 11, 19689. https:\/\/doi.org\/10.1038\/s41598-021-99252-6 (2021).","journal-title":"Sci. Rep."},{"key":"31396_CR22","doi-asserted-by":"publisher","first-page":"3731","DOI":"10.1210\/jc.2003-030039","volume":"88","author":"S Taddei","year":"2003","unstructured":"Taddei, S. et al. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of Levothyroxine therapy. J. Clin. Endocrinol. Metab. 88, 3731\u20133737. https:\/\/doi.org\/10.1210\/jc.2003-030039 (2003).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"31396_CR23","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1007\/s12020-011-9465-2","volume":"40","author":"F Alibaz Oner","year":"2011","unstructured":"Alibaz Oner, F., Yurdakul, S., Oner, E., Kubat Uzum, A. & Erguney, M. Evaluation of the effect of L-thyroxin therapy on endothelial functions in patients with subclinical hypothyroidism. Endocrine 40, 280\u2013284. https:\/\/doi.org\/10.1007\/s12020-011-9465-2 (2011).","journal-title":"Endocrine"},{"key":"31396_CR24","doi-asserted-by":"publisher","first-page":"e016053","DOI":"10.1136\/bmjopen-2017-016053","volume":"7","author":"T Zhao","year":"2017","unstructured":"Zhao, T. et al. Effect of Levothyroxine on the progression of carotid intima-media thickness in subclinical hypothyroidism patients: a meta-analysis. BMJ open. 7, e016053. https:\/\/doi.org\/10.1136\/bmjopen-2017-016053 (2017).","journal-title":"BMJ open."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-31396-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-31396-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-31396-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:25:36Z","timestamp":1768472736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-31396-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,9]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["31396"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-31396-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,9]]},"assertion":[{"value":"9 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was approved by the Ethics Committee of the First Affiliated Hospital of Xi\u2019an Jiaotong University. All methods in the study were performed in accordance with relevant institutional\/national\/international guidelines. All individuals signed informed consent to participate in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"1709"}}