{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:51:44Z","timestamp":1791226304852,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1014589","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000}}],"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["856587"],"award-info":[{"award-number":["856587"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["093478"],"award-info":[{"award-number":["093478"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Prediabetes, a subclinical state of high glucose, carries a risk of transitioning to diabetes. One cause of prediabetes is insulin resistance, which impairs the ability of insulin to control blood glucose. However, many individuals with high insulin resistance retain normal glucose due to compensation by enhanced insulin secretion by beta cells. Individuals seem to differ in their maximum compensation level, termed beta cell carrying capacity, such that low carrying capacity is associated with a higher risk of prediabetes and diabetes. Carrying capacity has not been quantified using a mathematical model and at present cannot be estimated from measured glucose and insulin levels in patients, unlike insulin resistance and beta cell function which can be estimated using HOMA-IR and HOMA-B formula. Here we present a mathematical model of beta cell compensation and carrying capacity, and develop a new formula called HOMA-C to estimate it from glucose and insulin measurements. HOMA-C estimates the maximal potential beta cell function of an individual, rather than the current beta cell function. It uses prediabetes as a stress and estimates carrying capacity using the gap between secreted insulin and the needed amount of insulin for homeostasis. We test this approach using longitudinal cohorts of prediabetic people, finding 10-fold variation in carrying capacity. Low HOMA-C associates with higher risk of transitioning to diabetes in a one-year follow up. The interpretation of HOMA-C as a carrying capacity relies on a mathematical model and requires further experimental testing. Quantification of beta cell carrying capacity may help to better understand this understudied risk factor for diabetes.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014589","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:22:12Z","timestamp":1789496532000},"page":"e1014589","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantification of beta-cell carrying capacity in prediabetes"],"prefix":"10.1371","volume":"22","author":[{"given":"Aurore","family":"Woller","sequence":"first","affiliation":[{"name":"Weizmann Institute of Science","place":["Rehovot, Israel"],"department":["Department of Molecular Cell Biology"]},{"name":"Universit\u00e9 Libre de Bruxelles (ULB)","place":["Brussels, Belgium"],"department":["Unit\u00e9 de Chronobiologie th\u00e9orique, Facult\u00e9 des 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Israel"],"department":["Department of Computer Sciences and Applied Mathematics"]},{"name":"Jesse and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children\u2019s Medical Center","place":["Petah Tikva, Israel"]},{"name":"Tel Aviv University","place":["Tel Aviv, Israel"],"department":["Faculty of Medicine and Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Gonze","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Libre de Bruxelles (ULB)","place":["Brussels, Belgium"],"department":["Unit\u00e9 de Chronobiologie th\u00e9orique, Facult\u00e9 des Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Alon","sequence":"additional","affiliation":[{"name":"Weizmann Institute of Science","place":["Rehovot, Israel"],"department":["Department of Molecular Cell 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