{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:21:35Z","timestamp":1788963695311,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003286","name":"Kuwait Foundation for the Advancement of Sciences","doi-asserted-by":"publisher","award":["RA HM 2019\u2010008"],"award-info":[{"award-number":["RA HM 2019\u2010008"]}],"id":[{"id":"10.13039\/501100003286","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003286","name":"Kuwait Foundation for the Advancement of Sciences","doi-asserted-by":"publisher","award":["PR17\u201013MM\u201007"],"award-info":[{"award-number":["PR17\u201013MM\u201007"]}],"id":[{"id":"10.13039\/501100003286","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003286","name":"Kuwait Foundation for the Advancement of Sciences","doi-asserted-by":"publisher","award":["RA HM\u20102019\u2010030"],"award-info":[{"award-number":["RA HM\u20102019\u2010030"]}],"id":[{"id":"10.13039\/501100003286","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Type 2 diabetes (T2D) is a progressive metabolic disorder characterized by insulin resistance and progressive \u03b2\u2010cell dysfunction. Early detection remains critical to prevent long\u2010term complications. Urinary extracellular vesicle (ECV) microRNAs (miRNAs) have emerged as stable, non\u2010invasive biomarkers with the potential to reflect systemic molecular alterations associated with metabolic disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed previously generated urinary ECV miRNA sequencing data from a well\u2010characterized cohort of 68 adults (40 T2D and 28 healthy controls). Differentially expressed miRNAs were identified and evaluated for diagnostic performance using receiver operating characteristic (ROC) analysis and supervised machine learning models with 10\u2010fold cross\u2010validation. Independent external validation was performed to assess generalizability. Cross\u2010tissue validation was conducted using publicly available datasets from pancreatic islets, blood, liver, and adipose tissue. Predicted target genes were examined across tissues, and miRNA\u2013mRNA interaction networks with pathway enrichment analyses were performed to explore functional relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty\u2010six miRNAs were significantly dysregulated in urinary ECVs from T2D patients compared with controls. Network bottleneck centrality analysis prioritized five key miRNAs (miR\u2010320a, miR\u201016\u20105p, miR\u2010125b\u20105p, miR\u201026a\u20105p, and miR\u201030c\u20105p). Individual miRNAs demonstrated moderate discriminatory capacity (AUC 0.73\u20130.81), while the combined panel improved performance (internal AUC\u2009=\u20090.87; external AUC\u2009=\u20090.86). Dysregulated urinary miRNA patterns partially mirrored expression changes in pancreatic islets and other metabolic tissues. Target gene analysis revealed tissue\u2010specific alterations in key metabolic regulators, including\n                      <jats:italic>PTEN, IGF1R, HMGA1, VEGFA, MCL1, CCND2, BTG2<\/jats:italic>\n                      , and\n                      <jats:italic>SMAD4<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Urinary ECV miRNAs reflect molecular alterations associated with T2D and represent promising complementary, non\u2010invasive biomarkers with mechanistic relevance to disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70309","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:28:14Z","timestamp":1776853694000},"page":"1094-1105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Urinary extracellular vesicle\n                    <scp>miRNA<\/scp>\n                    signature reflects pancreatic islet stress in type 2 diabetes"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6693-0401","authenticated-orcid":false,"given":"Md. Zubbair","family":"Malik","sequence":"first","affiliation":[{"name":"Department of Translational Research Dasman Diabetes Institute  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Dashti","sequence":"additional","affiliation":[{"name":"Department of Translational Research Dasman Diabetes Institute  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6318-8707","authenticated-orcid":false,"given":"Anwar","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Dasman Diabetes Institute  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Al\u2010Sayegh","sequence":"additional","affiliation":[{"name":"Biology Division New York University Abu Dhabi  Abu Dhabi United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3934-4233","authenticated-orcid":false,"given":"Mohammed","family":"Al\u2010Onaizi","sequence":"additional","affiliation":[{"name":"Department of Translational Research Dasman Diabetes Institute  Kuwait City Kuwait"},{"name":"Faculty of Medicine Abdullah Al Salem University (AASU)  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4762-9469","authenticated-orcid":false,"given":"Rasheeba","family":"Nizam","sequence":"additional","affiliation":[{"name":"Department of Translational Research Dasman Diabetes Institute  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija M","family":"Dashti","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center (HSC) Kuwait University  Jabriya Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abu\u2010Farha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Dasman Diabetes Institute  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0681-7305","authenticated-orcid":false,"given":"Jehad","family":"Abubaker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Dasman Diabetes Institute  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahd","family":"Al\u2010Mulla","sequence":"additional","affiliation":[{"name":"Department of Translational Research Dasman Diabetes Institute  Kuwait City Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6623-3374","authenticated-orcid":false,"given":"Hamad","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Translational Research Dasman Diabetes Institute  Kuwait City Kuwait"},{"name":"Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center (HSC) Kuwait University  Jabriya Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Organization WH.Report of the fifth meeting of the WHO Technical Advisory Group on Diabetes: hybrid meeting 7\u20138 June 2023: World Health Organization.2023."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(25)00294-3"},{"key":"e_1_2_8_4_1","unstructured":"MaglianoDJ BoykoEJ.IDF diabetes 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