{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:01:24Z","timestamp":1791378084490,"version":"4.3.2"},"reference-count":41,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universit\u00e0 Cattolica del Sacro Cuore\u2013Linea D1","award":["R4124500391"],"award-info":[{"award-number":["R4124500391"]}]},{"name":"Universit\u00e0 Cattolica del Sacro Cuore\u2013Linea D1","award":["RF-2018-12367409"],"award-info":[{"award-number":["RF-2018-12367409"]}]},{"name":"Italian ministry of health","award":["R4124500391"],"award-info":[{"award-number":["R4124500391"]}]},{"name":"Italian ministry of health","award":["RF-2018-12367409"],"award-info":[{"award-number":["RF-2018-12367409"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this work, we will investigate if red blood cell (RBC) membrane fluidity, influenced by several hyperglycemia-induced pathways, could provide a complementary index of HbA1c to monitor the development of type 2 diabetes mellitus (T2DM)-related macroangiopathic complications such as Peripheral Artery Disease (PAD). The contextual liquid crystalline (LC) domain spatial organization in the membrane was analysed to investigate the phase dynamics of the transition. Twenty-seven patients with long-duration T2DM were recruited and classified in DM, including 12 non-PAD patients, and DM + PAD, including 15 patients in any stage of PAD. Mean values of RBC generalized polarization (GP), representative of membrane fluidity, together with spatial organization of LC domains were compared between the two groups; p-values &lt; 0.05 were considered statistically significant. Although comparable for anthropometric characteristics, duration of diabetes, and HbA1c, RBC membranes of PAD patients were found to be significantly more fluid (GP: 0.501 \u00b1 0.026) than non-PAD patients (GP: 0.519 \u00b1 0.007). These alterations were shown to be triggered by changes in both LC microdomain composition and distribution. We found a decrease in Feret diameter from 0.245 \u00b1 0.281 \u03bcm in DM to 0.183 \u00b1 0.124 \u03bcm in DM + PAD, and an increase in circularity. Altered RBC membrane fluidity is correlated to a spatial reconfiguration of LC domains, which, by possibly altering metabolic function, are associated with the development of T2DM-related macroangiopathic complications.<\/jats:p>","DOI":"10.3390\/ijms231911126","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T05:33:14Z","timestamp":1663824794000},"page":"11126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Spatial Reorganization of Liquid Crystalline Domains of Red Blood Cells in Type 2 Diabetic Patients with Peripheral Artery Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1257-2295","authenticated-orcid":false,"given":"Giada","family":"Bianchetti","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Biophysics Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5234-8530","authenticated-orcid":false,"given":"Gaetano Emanuele","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Diabetes Care Unit, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Serantoni","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biophysics Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Abeltino","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biophysics Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Diabetes Care Unit, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Tartaglione","sequence":"additional","affiliation":[{"name":"Diabetes Care Unit, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Caputo","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Flex","sequence":"additional","affiliation":[{"name":"Diabetes Care Unit, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4260-5107","authenticated-orcid":false,"given":"Marco","family":"De Spirito","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biophysics Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Pitocco","sequence":"additional","affiliation":[{"name":"Diabetes Care Unit, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2154-319X","authenticated-orcid":false,"given":"Giuseppe","family":"Maulucci","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biophysics Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1177\/1932296813517058","article-title":"Percutaneous Coronary Intervention in Patients with Diabetes: Current Concepts and Future Directions","volume":"8","author":"Armstrong","year":"2014","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and Regional Diabetes Prevalence Estimates for 2019 and Projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th Edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. Clin. 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