{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:54:36Z","timestamp":1789012476716,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"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<\/jats:title>\n                    <jats:p>Growing evidence indicates that thyroid function plays a critical pathophysiological role in diabetic microvascular complications. Nevertheless, the specific association between thyroid hormones, particularly free triiodothyronine (fT3), and diabetic retinopathy (DR) remains controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>After applying the inclusion and exclusion criteria, 3703 patients were included in the baseline analysis. Multivariate logistic regression models were employed to assess the cross-sectional association between baseline fT3 levels and both the prevalence of DR. Subsequently, 1476 patients who underwent follow-up fundus photography were eligible for the retrospective cohort study. This secondary analysis examined the relationship between baseline fT3 quartiles and the risk of DR onset or progression. Additionally, two-sample Mendelian randomization (MR) analysis was performed to analyze the causal effect of circulating fT3 on non-proliferative DR (NPDR) and proliferative DR (PDR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the cross-sectional analysis, higher fT3 levels were inversely associated with DR after multivariable adjustment, including NPDR (OR = 0.61, 95% CI: 0.50-0.74) and PDR (OR = 0.24, 95% CI: 0.13-0.44). In the longitudinal cohort, patients with moderate fT3 levels (Q2\u2013Q3) had a lower risk of DR onset or progression versus the lowest quartile (Q1). This protective association remained significant in those with suboptimal glycemic control (HbA1c \u22657%) or longer diabetes duration (\u2265 10 years), with risk reductions of 43% (Q2) and 37% (Q3) in the former, and 44% (Q2) and 49% (Q3) in the latter. Notably, among older patients (\u2265 55 years), the benefit extended across Q2-Q4. Finally, the MR analysis suggested a potential protective effect of higher fT3 levels on NPDR (MR Egger, OR = 0.131, 95% CI: 0.023-0.755,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.044).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, our study demonstrated an inverse association between fT3 levels and the risk of both NPDR and PDR. Moderate fT3 levels were associated with a lower risk of DR onset or progression, particularly among patients with suboptimal glycemic control (HbA1c \u22657%) or longer diabetes duration (\u2265 10 years). In older patients (\u2265 55years), even relatively higher fT3 levels may be protective. MR analysis suggested a potential protective effect of elevated fT3 levels on the risk of NPDR, which was significant only in the MR Egger model.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1677122","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T05:20:41Z","timestamp":1765948841000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Association between free triiodothyronine and diabetic retinopathy: insights from a longitudinal cohort study and Mendelian randomization"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaotong","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongling","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haodi","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41574-020-00451-4","article-title":"Current 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