{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T22:08:06Z","timestamp":1768946886412,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoglycemia is associated with cardiovascular events reflected by platelet abnormalities. We hypothesized that sequential endothelial changes may occur during hypoglycemia that may enhance cardiovascular risk. In type 2 diabetes (T2D) (n = 23) and controls (n = 23), blood SOMAscan proteomic analysis of endothelial proteins at baseline, insulin-induced hypoglycemia and post hypoglycemia to 24 h were examined using repeated-measures linear mixed modeling with a prospective parallel study design. Most endothelial proteins that changed over time did not differ between groups. Baseline levels of P-selectin, plasminogen activator inhibitor-1 (PAI-1; serpine-1), E-selectin and angiopoietin-1 (ANGPT1) were significantly higher, whilst cadherin-5 was lower in T2D. Several proteins exhibited changes versus baseline in both T2D and controls. Under hypoglycemia, decreases in cadherin-5 and soluble angiopoietin-1 receptor (sTie-2) were observed, with increased P-selectin, intercellular adhesion molecule-3 (ICAM3), ANGPT1 and PAI-1. Post hypoglycemia, decreased cadherin-5 and ICAM5 were observed at 2 h and PAI-1 at 4 h, as well as increases in P-selectin at 30 min, 1 h and 24 h and ICAM3 at 24 h. Post hypoglycemia, E-selectin, P-selectin and ICAM3 were significantly lower in T2D patients at 2 h, while PAI-1 was significantly lower at 4 h and ICAM3 was significantly lower at 24 h. Baseline endothelial proteins differed between T2D and controls, which may suggest local endothelial inflammatory activation leading to a pro-thrombotic, destabilized vascular phenotype characteristic of diabetic vasculopathy. Hypoglycemia may exacerbate this towards a pro-adhesive and pro-thrombotic phenotype, worsening endothelial dysfunction.<\/jats:p>","DOI":"10.3390\/ijms27020822","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:01:14Z","timestamp":1768388474000},"page":"822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Iatrogenic Hypoglycemia in Type 2 Diabetes Affects Endothelial Proteins Involved in Cardiovascular Dysfunction"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0183-4683","authenticated-orcid":false,"given":"Edwina","family":"Brennan","sequence":"first","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5342-2501","authenticated-orcid":false,"given":"Abu Saleh Md","family":"Moin","sequence":"additional","affiliation":[{"name":"School of Postgraduate Studies and Research, Royal College of Surgeons in Ireland Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3544-2231","authenticated-orcid":false,"given":"Thozhukat","family":"Sathyapalan","sequence":"additional","affiliation":[{"name":"Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Dempsey","sequence":"additional","affiliation":[{"name":"Data Science Centre, School of Population Health, Royal College of Surgeons in Ireland, D02 DH60 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5887-7257","authenticated-orcid":false,"given":"Stephen L.","family":"Atkin","sequence":"additional","affiliation":[{"name":"School of Postgraduate Studies and Research, Royal College of Surgeons in Ireland Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-3917","authenticated-orcid":false,"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"School of Postgraduate Studies and Research, Royal College of Surgeons in Ireland Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1001\/jamainternmed.2016.2275","article-title":"Intensive Treatment and Severe Hypoglycemia Among Adults With Type 2 Diabetes","volume":"176","author":"McCoy","year":"2016","journal-title":"JAMA Intern. 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