{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:46:57Z","timestamp":1782902817695,"version":"3.54.5"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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:p>Diabetic foot (DF)\u2013related amputation remains a major cause of morbidity in patients with type 2 diabetes, yet biomarkers associated with amputation risk remain limited. We aimed to assess the independent association between a deep learning (DL)\u2013derived retinal biomarker using coronary artery calcification (Dr. Noon CVD) and DF\u2013related amputation in patients with type 2 diabetes. This retrospective observational study conducted in a university hospital in South Korea included 392 individuals with type 2 diabetes receiving ophthalmic care (79 with DF-related amputation and 313 without). Participants were randomly split into training (70%) and validation (30%) sets. Model performance in relation to DF-related amputation was assessed using area under the receiver operating characteristic curve (AUC), continuous net reclassification index (cNRI), and integrated discrimination improvement (IDI). Prespecified rule-out (sensitivity \u22650.85) and rule-in (specificity \u22650.90) thresholds were also applied. Adding the retinal biomarker to a basic clinical model showed incremental association with DF-related amputation in the validation set (AUC 0.146, 95% CI: 0.046-0.249; cNRI 0.629, 95% CI: 0.184-1.027; IDI 0.062, 95% CI: 0.012-0.110). The full model achieved an AUC of 0.791, and the association remained consistent across sensitivity analyses using DF risk score derived from the external dataset. Under a 27% amputation prevalence (based on the reported prevalence of amputation among patients with diabetic foot), sensitivity was 87.5% with a negative predictive value of 92.6% at the rule-out cutoff; specificity was 90.4% with a positive predictive value of 56.3% at the rule-in cutoff. A DL-derived retinal biomarker shows meaningful association with DF-related amputation beyond conventional diabetes variables.<\/jats:p>","DOI":"10.3389\/fendo.2026.1866694","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:14:28Z","timestamp":1782900868000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Deep learning-derived retinal biomarker associated with diabetes-related amputation in type 2 diabetes"],"prefix":"10.3389","volume":"17","author":[{"given":"Junseok","family":"Park","sequence":"first","affiliation":[{"name":"Seoul National University Hospital","place":["Seoul, Republic of Korea"]},{"name":"Mediwhale Inc.","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Soo","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Myongji Medical Foundation, Myongji Hospital","place":["Ilsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahil","family":"Thakur","sequence":"additional","affiliation":[{"name":"Mediwhale Inc.","place":["Seoul, Republic of Korea"]},{"name":"Singapore Eye Research Institute\/Singapore National Eye Center","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjin","family":"Nam","sequence":"additional","affiliation":[{"name":"Mediwhale Inc.","place":["Seoul, Republic of Korea"]},{"name":"Department of Internal Medicine, Graduate School, College of Medicine, Yonsei University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunjin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hanyang University Guri Hospital","place":["Guri, Republic of 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