{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T09:06:00Z","timestamp":1779959160654,"version":"3.53.1"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetes mellitus (DM) is a frequent and debilitating complication in patients with \u03b2\u2010thalassemia major (\u03b2\u2010TM), driven by chronic iron overload\u2013induced pancreatic and hepatic dysfunction. Validated biomarkers for early diabetes detection in this population remain limited. Follistatin (FST), a secreted glycoprotein modulating TGF\u2010\u03b2\/activin signaling and glucose metabolism, has been associated with Type 2 diabetes (T2D), though its relevance to thalassemia\u2010associated diabetes is unexplored. This cross\u2010sectional study examined plasma FST levels and gene expression relative to diabetic status and glycemic control in 134 participants: 80 \u03b2\u2010TM\/non\u2010diabetic, 34 \u03b2\u2010TM\/diabetic patients, and 20 healthy controls. Iron modulation effects were explored in HepG2 hepatocytes using ferric ammonium citrate (FAC) or deferoxamine (DFO), and metabolic stress effects were assessed in healthy PBMCs exposed to high glucose or insulin. Plasma FST was significantly elevated in \u03b2\u2010TM\/diabetic patients versus \u03b2\u2010TM\/non\u2010diabetic patients or controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). FST correlated positively with glucose and fructosamine (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.23;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.02), but not with serum ferritin. A stepwise increase in plasma FST was observed across glycemic control subgroups, from 2421\u2009pg\/mL in well\u2010controlled to 3831\u2009pg\/mL in poorly controlled diabetics (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). FAC upregulated FST mRNA in HepG2 cells, while DFO suppressed it (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Peripheral Blood Mononuclear Cells (PBMCs) FST mRNA was paradoxically lower in \u03b2\u2010TM\/diabetic patients (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02), a pattern reproduced in PBMCs under high glucose or insulin, indicating tissue\u2010specific metabolic regulation. Collectively, these findings suggest that elevated plasma FST may reflect a convergence of iron\u2010induced hepatic stress and hyperglycemia\u2010related dysregulation and warrant further cross\u2010sectional investigations as a candidate biomarker in this population.\n                  <\/jats:p>","DOI":"10.1002\/cbf.70226","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:24:58Z","timestamp":1778570698000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated Circulating Follistatin Is Associated With Diabetic Status and Glycemic Dysregulation in Patients With \u03b2\u2010Thalassemia Major"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3341-1063","authenticated-orcid":false,"given":"Jalal","family":"Taneera","sequence":"first","affiliation":[{"name":"College of Medicine University of Sharjah Sharjah United Arab Emirates"},{"name":"Research Institute of Medical and Health Sciences University of Sharjah Sharjah United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Khader","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Research Institute of Medical and Health Sciences University of Sharjah Sharjah United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind Mohammed Abed Abu","family":"Shaireh","sequence":"additional","affiliation":[{"name":"College of Medicine University of Sharjah Sharjah United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa Al","family":"Hajji","sequence":"additional","affiliation":[{"name":"College of Medicine University of Sharjah Sharjah United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amani Al","family":"Hajji","sequence":"additional","affiliation":[{"name":"College of Medicine University of Sharjah Sharjah United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutaz Al","family":"Gharaibeh","sequence":"additional","affiliation":[{"name":"College of Medicine University of Sharjah Sharjah United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany","family":"Dewedar","sequence":"additional","affiliation":[{"name":"Dubai Thalassemia Center Dubai Health Authority Dubai United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatheya S.","family":"AlKhaja","sequence":"additional","affiliation":[{"name":"Dubai Thalassemia Center Dubai Health Authority Dubai United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6769-1091","authenticated-orcid":false,"given":"Mawieh","family":"Hamad","sequence":"additional","affiliation":[{"name":"Research Institute of Medical and Health Sciences University of Sharjah Sharjah United Arab 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