{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T02:35:18Z","timestamp":1776566118977,"version":"3.51.2"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT","award":["SAICT-POL\/24325\/2016"],"award-info":[{"award-number":["SAICT-POL\/24325\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Type 2 Diabetes Mellitus (T2D) is defined as a chronic condition caused by beta cell loss and\/or dysfunction and insulin resistance (IR). The discovering of novel biomarkers capable of identifying T2D and other metabolic disorders associated with IR in a timely and accurate way is critical. In this review, 2-hydroxybutyric acid (2HB) is presented as that upheaval biomarker with an unexplored potential ahead. Due to the activation of other metabolic pathways during IR, 2HB is synthesized as a coproduct of protein metabolism, being the progression of IR intrinsically related to the increasing of 2HB levels. Hence, the focus of this review will be on the 2HB metabolite and its involvement in glucose homeostasis. A literature review was conducted, which comprised an examination of publications from different databases that had been published over the previous ten years. A total of 19 articles fulfilled the intended set of criteria. The use of 2HB as an early indicator of IR was separated into subjects based on the number of analytes examined simultaneously. In terms of the association between 2HB and IR, it has been established that increasing 2HB levels can predict the development of IR. Thus, 2HB has demonstrated considerable promise as a clinical monitoring molecule, not only as an IR biomarker, but also for disease follow-up throughout IR treatment.<\/jats:p>","DOI":"10.3390\/metabo11120835","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T21:01:45Z","timestamp":1638738105000},"page":"835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Which Role Plays 2-Hydroxybutyric Acid on Insulin Resistance?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1460-5361","authenticated-orcid":false,"given":"Andr\u00e9 P.","family":"Sousa","sequence":"first","affiliation":[{"name":"Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lob\u00e3o Vital 172, 4200-374 Porto, Portugal"},{"name":"School of Health (ESS), Polytechnic Institute of Porto (IPP), R. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine, Porto University (FMUP), Alameda Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Diogo M.","family":"Cunha","sequence":"additional","affiliation":[{"name":"School of Health (ESS), Polytechnic Institute of Porto (IPP), R. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"}]},{"given":"Carolina","family":"Franco","sequence":"additional","affiliation":[{"name":"School of Health (ESS), Polytechnic Institute of Porto (IPP), R. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6934-7641","authenticated-orcid":false,"given":"Catarina","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lob\u00e3o Vital 172, 4200-374 Porto, Portugal"},{"name":"School of Health (ESS), Polytechnic Institute of Porto (IPP), R. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"}]},{"given":"Frantz","family":"Gojon","sequence":"additional","affiliation":[{"name":"Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lob\u00e3o Vital 172, 4200-374 Porto, Portugal"},{"name":"School of Health (ESS), Polytechnic Institute of Porto (IPP), R. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine, Porto University (FMUP), Alameda Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-862X","authenticated-orcid":false,"given":"Pilar","family":"Baylina","sequence":"additional","affiliation":[{"name":"Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lob\u00e3o Vital 172, 4200-374 Porto, Portugal"},{"name":"School of Health (ESS), Polytechnic Institute of Porto (IPP), R. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-3984","authenticated-orcid":false,"given":"Ruben","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lob\u00e3o Vital 172, 4200-374 Porto, Portugal"},{"name":"School of Health (ESS), Polytechnic Institute of Porto (IPP), R. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation Atlas (2019). 463 People Living with Diabetes Million, The International Diabetes Federation."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e000038","DOI":"10.1136\/bmjdrc-2014-000038","article-title":"Serum \u03b1-hydroxybutyrate (\u03b1-HB) predicts elevated 1 h glucose levels and early-phase \u03b2-cell dysfunction during OGTT","volume":"2","author":"Varvel","year":"2014","journal-title":"BMJ Open Diabetes Res. 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