{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:58:53Z","timestamp":1785427133581,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,16]]},"group-title":"Bioengineering","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1K24HL150476"],"award-info":[{"award-number":["1K24HL150476"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>To characterize subtype-associated heterogeneity in type 2 diabetes mellitus (T2DM), particularly normal-weight diabetes, using extracellular vesicle (EV)-associated molecular features in a clinically stratified cohort.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>EVs were isolated from plasma using ExoTIC and validated by transmission electron microscopy, nanoparticle tracking analysis, flow cytometry, and Western blotting. EVs from Asian normal-weight (A-NWD), Asian overweight (A-OWD), Non-Hispanic White normal-weight (W-NWD), and Non-Hispanic White overweight (W-OWD) T2DM patients were analyzed by multimodal surface-enhanced Raman spectroscopy (SERS; n=65) and EV-RNA sequencing (n=39).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>SERS identified subgroup-associated spectral fingerprints that distinguished the four BMI\u2013 and race\/ethnicity-defined groups in this cohort. EV-RNA sequencing revealed differential microRNA expression across subgroups, with higher miR-208a and miR-132 in A-OWD and higher miR-484 in A-NWD. Unsupervised analyses also showed partially overlapping EV-associated molecular features between A-NWD and W-OWD, suggesting that BMI-based subgrouping alone may not fully capture shared metabolic states.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Multimodal EV profiling identified subgroup-associated spectral and miRNA features in clinically stratified T2DM and provides a framework for studying diabetes heterogeneity, including molecular patterns associated with normal-weight diabetes.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.14.711704","type":"posted-content","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:40:12Z","timestamp":1773657612000},"source":"Crossref","is-referenced-by-count":0,"title":["Analysis of Plasma Extracellular Vesicles in Normal-Weight and Overweight Type 2 Diabetes Mellitus Using Multimodal SERS and RNA-Seq"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7106-5993","authenticated-orcid":false,"given":"Ugur","family":"Parlatan","sequence":"first","affiliation":[{"name":"BioAcoustic MEMS in Medicine BAMM Laboratory, Canary Center, Department of Radiology, Stanford School of Medicine, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6029-8900","authenticated-orcid":false,"given":"Aayan Nilesh","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Stanford School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5939-4006","authenticated-orcid":false,"given":"Hulya","family":"Torun","sequence":"additional","affiliation":[{"name":"BioAcoustic MEMS in Medicine BAMM Laboratory, Canary Center, Department of Radiology, Stanford School of Medicine, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma Humayra","family":"Karim","sequence":"additional","affiliation":[{"name":"BioAcoustic MEMS in Medicine BAMM Laboratory, Canary Center, Department of Radiology, Stanford School of Medicine, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4578-2598","authenticated-orcid":false,"given":"Mehmet Ozgun","family":"Ozen","sequence":"additional","affiliation":[{"name":"BioAcoustic MEMS in Medicine BAMM Laboratory, Canary Center, Department of Radiology, Stanford School of Medicine, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1245-665X","authenticated-orcid":false,"given":"Latha","family":"Palaniappan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Stanford School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2784-1590","authenticated-orcid":false,"given":"Utkan","family":"Demirci","sequence":"additional","affiliation":[{"name":"BioAcoustic MEMS in Medicine BAMM Laboratory, Canary Center, Department of Radiology, Stanford School of Medicine, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026031803451098000_2026.03.14.711704v1.1","unstructured":"Magliano, D. 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