{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:18:55Z","timestamp":1785403135439,"version":"3.56.0"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Graduate Studies and Scientific Research at Jouf University","award":["DSR2023-01-02392"],"award-info":[{"award-number":["DSR2023-01-02392"]}]},{"award":["DSR2023-01-02392"],"award-info":[{"award-number":["DSR2023-01-02392"]}],"id":[{"id":"https:\/\/ror.org\/02zsyt821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Type 2 diabetes mellitus (T2-DM) is a continuing national and global health challenge. Retinoic acid (RA), the major transcription-regulating ligand, plays a critical role in energy metabolism, and pancreatic \u03b2-cell homeostasis. However, human data linking circulating RA levels to T2-DM and its clinical outcomes are sparse and inconsistent. In this ethically approved cross-sectional study of consented hospital-diagnosed adult T2-DM patients (n = 292) and matched healthy controls (n = 64), variation in plasma RA levels and its relationship with disease and patient characteristics were investigated. Methods: RA concentrations assayed via specific ELISA were related to glycemic control indices [fasting blood glucose (FBG) and HbA1c], the triglyceride\u2013glucose ratio for insulin resistance (TyG-IR), treatment modalities, and complications derived from patients\u2019 medical records. Results: RA concentrations were substantially lower in patients with T2-DM (mean \u00b1 SD 2.63 \u00b1 1.54 ng\/mL) than in controls (5.21 \u00b1 4.3 ng\/mL; p &lt; 0.001). Within the diabetic cohort, RA was inversely correlated with indices of glycemic dysregulation and insulin resistance. Plasma RA exhibited strong discriminatory performance for distinguishing diabetic patients from healthy adults. Its AUC is 0.870 (p &lt; 0.0001 and 95% CI = 0.832\u20130.902) with a sensitivity of 79.7% and a specificity of 81.3%, at an optimal cutoff of \u22643.061 ng\/mL. Conclusions: Circulating RA is associated with metabolic perturbations that define T2-DM, and therefore is promising as a clinically useful biomarker. It may reflect pathophysiological processes linking nutrient signaling, energy handling and \u03b2-cell function in T2-DM that merit further evaluation.<\/jats:p>","DOI":"10.3390\/diagnostics16091359","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:32:21Z","timestamp":1777555941000},"page":"1359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Variation in the Circulating Levels of Retinoic Acid and Type 2 Diabetes: Relationships with Glycemic Control Indices, Disease Treatment and Complications"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0220-6160","authenticated-orcid":false,"given":"Aseel A.","family":"Alsaidan","sequence":"first","affiliation":[{"name":"Department of Family and Community Medicine, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1648-0980","authenticated-orcid":false,"given":"Basil M.","family":"Alomair","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9267-2637","authenticated-orcid":false,"given":"Abdulrahman H.","family":"Almaeen","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumanah M. Q.","family":"Aldirbas","sequence":"additional","affiliation":[{"name":"College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bdour R. S.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghad H. S.","family":"Algaed","sequence":"additional","affiliation":[{"name":"College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6479-1671","authenticated-orcid":false,"given":"Alanoud F. B.","family":"Alruwaili","sequence":"additional","affiliation":[{"name":"College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouf M. S.","family":"Alruwaili","sequence":"additional","affiliation":[{"name":"College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duna F. A.","family":"Aljbab","sequence":"additional","affiliation":[{"name":"College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lama A. A.","family":"Alenzi","sequence":"additional","affiliation":[{"name":"College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razan S. S.","family":"Albalawi","sequence":"additional","affiliation":[{"name":"College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8137-970X","authenticated-orcid":false,"given":"Alaa A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"},{"name":"Department of Medical Biochemistry, Faculty of Medicine, Beni-Suef University, Beni-Suef 62521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9040-6642","authenticated-orcid":false,"given":"Tarek H.","family":"EL-Metwally","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"},{"name":"Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut 71526, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.diabres.2016.06.012","article-title":"All-cause mortality and its risk factors among type 1 and type 2 diabetes mellitus in a country facing diabetes epidemic","volume":"118","author":"Youssef","year":"2016","journal-title":"Diabetes Res. 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