{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T08:26:23Z","timestamp":1786782383029,"version":"build-2736575974"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Khoo Teck Puat Health Fund","award":["STAR22103"],"award-info":[{"award-number":["STAR22103"]}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["MOH-001772-01"],"award-info":[{"award-number":["MOH-001772-01"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["MOH-000714-01"],"award-info":[{"award-number":["MOH-000714-01"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010754","name":"National Healthcare Group","doi-asserted-by":"publisher","award":["CSCS-24-01-01"],"award-info":[{"award-number":["CSCS-24-01-01"]}],"id":[{"id":"10.13039\/501100010754","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"DOI":"10.1007\/s12020-026-04749-7","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T07:44:58Z","timestamp":1786779898000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2-hydroxybutyrate as an early predictive biomarker of diabetes remission following intensive dietary intervention"],"prefix":"10.1007","volume":"91","author":[{"given":"Mei Chung","family":"Moh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boon Khim","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuvaneswari","family":"Pandian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalily Binti","family":"Kosnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vi Vien","family":"Seow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Ru","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Mei","family":"Phoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Min","family":"Luah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting Yuan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Binte","family":"Mahadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Chih Chiang","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Low","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wern Ee","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tavintharan","family":"Subramaniam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chee Fang","family":"Sum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Chi","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"4749_CR1","unstructured":"International Diabetes Federation. IDF Diabetes Atlas, 11th edn. Brussels, Belgium: 2025. https:\/\/diabetesatlas.org. Accessed: 20 Nov 2025"},{"issue":"4","key":"4749_CR2","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1007\/s00125-023-06069-1","volume":"67","author":"A Rothberg","year":"2024","unstructured":"A. Rothberg, M. Lean, B. Laferrere, Remission of type 2 diabetes: always more questions, but enough answers for action. Diabetologia 67(4), 602\u2013610 (2024). https:\/\/doi.org\/10.1007\/s00125-023-06069-1","journal-title":"Diabetologia"},{"issue":"10120","key":"4749_CR3","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/S0140-6736(17)33102-1","volume":"391","author":"ME Lean","year":"2018","unstructured":"M.E. Lean, W.S. Leslie, A.C. Barnes, N. Brosnahan, G. Thom, L. McCombie, C. Peters, S. Zhyzhneuskaya, A. Al-Mrabeh, K.G. Hollingsworth, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 391(10120), 541\u2013551 (2018). https:\/\/doi.org\/10.1016\/S0140-6736(17)33102-1","journal-title":"Lancet"},{"issue":"6","key":"4749_CR4","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/S2213-8587(20)30117-0","volume":"8","author":"S Taheri","year":"2020","unstructured":"S. Taheri, H. Zaghloul, O. Chagoury, S. Elhadad, S.H. Ahmed, N. El Khatib, R.A. Amona, K. El Nahas, N. Suleiman, A. Alnaama, A. et al. Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial. Lancet Diabetes Endocrinol. 8(6), 477\u2013489 (2020). https:\/\/doi.org\/10.1016\/S2213-8587(20)30117-0","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"1","key":"4749_CR5","doi-asserted-by":"publisher","first-page":"66","DOI":"10.2337\/dc23-0781","volume":"47","author":"SL Hocking","year":"2024","unstructured":"S.L. Hocking, T.P. Markovic, C.M.Y. Lee, T.J. Picone, K.E. Gudorf, S. Colagiuri, Intensive lifestyle intervention for remission of early type 2 diabetes in primary care in Australia: DiRECT-Aus. Diabetes Care 47(1), 66\u201370 (2024). https:\/\/doi.org\/10.2337\/dc23-0781","journal-title":"Diabetes Care"},{"issue":"10","key":"4749_CR6","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1007\/s00125-008-1116-7","volume":"51","author":"R Taylor","year":"2008","unstructured":"R. Taylor, Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia 51(10), 1781\u20131789 (2008). https:\/\/doi.org\/10.1007\/s00125-008-1116-7","journal-title":"Diabetologia"},{"issue":"12","key":"4749_CR7","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.3390\/ijms17122093","volume":"17","author":"M Grabacka","year":"2016","unstructured":"M. Grabacka, M. Pierzchalska, M. Dean, K. Reiss, Regulation of ketone body metabolism and the role of PPARalpha. Int. J. Mol. Sci. 17(12), 2093 (2016). https:\/\/doi.org\/10.3390\/ijms17122093","journal-title":"Int. J. Mol. Sci."},{"issue":"3","key":"4749_CR8","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s43556-025-00303-5","volume":"2","author":"Y Li","year":"2025","unstructured":"Y. Li, Q. Liu, Z. Jia, B. Guo, Ketone bodies in exercise, health and disease: Metabolic mechanisms, pathophysiology, and therapeutic implications. Adv. Exerc. Health Sci. 2(3), 177\u2013189 (2025). https:\/\/doi.org\/10.1186\/s43556-025-00303-5","journal-title":"Adv. Exerc. Health Sci."},{"issue":"5","key":"4749_CR9","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/osp4.516","volume":"7","author":"JC Anderson","year":"2021","unstructured":"J.C. Anderson, S.G. Mattar, F.L. Greenway, R.J. Lindquist, Measuring ketone bodies for the monitoring of pathologic and therapeutic ketosis. Obes. Sci. Pract. 7(5), 646\u2013656 (2021). https:\/\/doi.org\/10.1002\/osp4.516","journal-title":"Obes. Sci. Pract."},{"issue":"4","key":"4749_CR10","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.cmet.2018.07.003","volume":"28","author":"R Taylor","year":"2018","unstructured":"R. Taylor, A. Al-Mrabeh, S. Zhyzhneuskaya, C. Peters, A.C. Barnes, B.S. Aribisala, K.G. Hollingsworth, J.C. Mathers, N. Sattar, M.E.J. Lean, Remission of human Type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for beta cell recovery. Cell Metab. 28(4), 547\u2013556.e3 (2018). https:\/\/doi.org\/10.1016\/j.cmet.2018.07.003","journal-title":"Cell Metab."},{"issue":"10","key":"4749_CR11","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.2337\/dci21-0034","volume":"44","author":"MC Riddle","year":"2021","unstructured":"M.C. Riddle, W.T. Cefalu, P.H. Evans, H.C. Gerstein, M.A. Nauck, W.K. Oh, A.E. Rothberg, C.W. le Roux, F. Rubino, P. Schauer, et al. Consensus report: definition and interpretation of remission in type 2 diabetes. Diabetes Care 44(10), 2438\u20132444 (2021). https:\/\/doi.org\/10.2337\/dci21-0034","journal-title":"Diabetes Care"},{"issue":"1","key":"4749_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36231-7","volume":"14","author":"H Julkunen","year":"2023","unstructured":"H. Julkunen, A. Cichonska, M. Tiainen, H. Koskela, K. Nybo, V. Makela, J. Nokso-Koivisto, K. Kristiansson, M. Perola, V. Salomaa, et al. Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK Biobank. Nat. Commun. 14(1), 604 (2023). https:\/\/doi.org\/10.1038\/s41467-023-36231-7","journal-title":"Nat. Commun."},{"issue":"12","key":"4749_CR13","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.2337\/diacare.21.12.2191","volume":"21","author":"JC Levy","year":"1998","unstructured":"J.C. Levy, D.R. Matthews, M.P. Hermans, Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 21(12), 2191\u20132192 (1998). https:\/\/doi.org\/10.2337\/diacare.21.12.2191","journal-title":"Diabetes Care"},{"issue":"3","key":"4749_CR14","doi-asserted-by":"publisher","first-page":"446","DOI":"10.14366\/usg.23014","volume":"42","author":"G Ferraioli","year":"2023","unstructured":"G. Ferraioli, A. Raimondi, A. De Silvestri, C. Filice, R.G. Barr, Toward acquisition protocol standardization for estimating liver fat content using ultrasound attenuation coefficient imaging. Ultrasonography 42(3), 446\u2013456 (2023). https:\/\/doi.org\/10.14366\/usg.23014","journal-title":"Ultrasonography"},{"issue":"34","key":"4749_CR15","doi-asserted-by":"publisher","first-page":"3849","DOI":"10.3748\/wjg.v24.i34.3849","volume":"24","author":"JY Jeong","year":"2018","unstructured":"J.Y. Jeong, Y.S. Cho, J.H. Sohn, Role of two-dimensional shear wave elastography in chronic liver diseases: A narrative review. World J. Gastroenterol. 24(34), 3849\u20133860 (2018). https:\/\/doi.org\/10.3748\/wjg.v24.i34.3849","journal-title":"World J. Gastroenterol."},{"issue":"1","key":"4749_CR16","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s00125-022-05815-1","volume":"66","author":"BC Lupsa","year":"2023","unstructured":"B.C. Lupsa, R.G. Kibbey, S.E. Inzucchi, Ketones: the double-edged sword of SGLT2 inhibitors? Diabetologia 66(1), 23\u201332 (2023). https:\/\/doi.org\/10.1007\/s00125-022-05815-1","journal-title":"Diabetologia"},{"key":"4749_CR17","doi-asserted-by":"publisher","unstructured":"S. Cheng, C. Cheng, J. Zhou, Y. Ji, Y. Liu, W. Jiang, C. Liu, H. Wang, Metabolism meets epigenetics: beta-hydroxybutyrate-driven lysine beta-hydroxybutyrylation bridging energy metabolism with transcription and protein functional remodeling. Nutr. Rev. nuaf258 (2025). https:\/\/doi.org\/10.1093\/nutrit\/nuaf258","DOI":"10.1093\/nutrit\/nuaf258"},{"issue":"1","key":"4749_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08055-1","volume":"7","author":"T Yamanashi","year":"2017","unstructured":"T. Yamanashi, M. Iwata, N. Kamiya, K. Tsunetomi, N. Kajitani, N. Wada, T. Iitsuka, T. Yamauchi, A. Miura, S. Pu, Y. Shirayama, et al. Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses. Sci. Rep. 7(1), 7677 (2017). https:\/\/doi.org\/10.1038\/s41598-017-08055-1","journal-title":"Sci. Rep."},{"issue":"1","key":"4749_CR19","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.neuroscience.2006.11.065","volume":"145","author":"M Maalouf","year":"2007","unstructured":"M. Maalouf, P.G. Sullivan, L. Davis, D.Y. Kim, J.M. Rho, Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience 145(1), 256\u2013264 (2007). https:\/\/doi.org\/10.1016\/j.neuroscience.2006.11.065","journal-title":"Neuroscience"},{"key":"4749_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2024.103959","volume":"131","author":"S Shang","year":"2024","unstructured":"S. Shang, L. Wang, X. Lu, beta-Hydroxybutyrate enhances astrocyte glutamate uptake through EAAT1 expression regulation. Mol. Cell Neurosci. 131, 103959 (2024). https:\/\/doi.org\/10.1016\/j.mcn.2024.103959","journal-title":"Mol. Cell Neurosci."},{"issue":"12","key":"4749_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-07268-3","volume":"15","author":"YP Bai","year":"2024","unstructured":"Y.P. Bai, Y.J. Xing, T. Ma, K. Li, T. Zhang, D.G. Wang, S.J. Wan, C.W. Zhang, Y. Sun, M.Y. Wang, et al. beta-Hydroxybutyrate suppresses M1 macrophage polarization through beta-hydroxybutyrylation of the STAT1 protein. Cell Death Dis. 15(12), 874 (2024). https:\/\/doi.org\/10.1038\/s41419-024-07268-3","journal-title":"Cell Death Dis."},{"issue":"2","key":"4749_CR22","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/oby.22051","volume":"26","author":"BJ Stubbs","year":"2018","unstructured":"B.J. Stubbs, P.J. Cox, R.D. Evans, M. Cyranka, K. Clarke, H. de Wet, A ketone ester drink lowers human ghrelin and appetite. Obesity 26(2), 269\u2013273 (2018). https:\/\/doi.org\/10.1002\/oby.22051","journal-title":"Obesity"},{"key":"4749_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.580167","volume":"11","author":"JR Moffett","year":"2020","unstructured":"J.R. Moffett, N. Puthillathu, R. Vengilote, D.M. Jaworski, A.M. Namboodiri, Acetate revisited: a key biomolecule at the nexus of metabolism, epigenetics and oncogenesis-part 1: Acetyl-CoA, acetogenesis and Acyl-CoA short-chain synthetases. Front. Physiol. 11, 580167 (2020). https:\/\/doi.org\/10.3389\/fphys.2020.580167","journal-title":"Front. Physiol."},{"issue":"6","key":"4749_CR24","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/S0022-2275(20)31621-7","volume":"42","author":"W Khovidhunkit","year":"2001","unstructured":"W. Khovidhunkit, J.K. Shigenaga, A.H. Moser, K.R. Feingold, C. Grunfeld, Cholesterol efflux by acute-phase high density lipoprotein: role of lecithin: cholesterol acyltransferase. J. Lipid Res. 42(6), 967\u2013975 (2001)","journal-title":"J. Lipid Res."},{"issue":"3","key":"4749_CR25","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1249\/JES.0000000000000220","volume":"48","author":"NT Broskey","year":"2020","unstructured":"N.T. Broskey, K. Zou, G.L. Dohm, J.A. Houmard, Plasma lactate as a marker for metabolic health. Exerc. Sport. Sci. Rev. 48(3), 119\u2013124 (2020). https:\/\/doi.org\/10.1249\/JES.0000000000000220","journal-title":"Exerc. Sport. Sci. Rev."},{"key":"4749_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.lansea.2022.100111","volume":"9","author":"N Sattar","year":"2023","unstructured":"N. Sattar, P. Welsh, W.S. Leslie, G. Thom, L. McCombie, N. Brosnahan, J. Richardson, J.M.R. Gill, L. Crawford, M.E.J. Lean, Dietary weight-management for type 2 diabetes remissions in South Asians: the South Asian diabetes remission randomised trial for proof-of-concept and feasibility (STANDby). Lancet Reg. Health Southeast. Asia 9, 100111 (2023). https:\/\/doi.org\/10.1016\/j.lansea.2022.100111","journal-title":"Lancet Reg. Health Southeast. Asia"},{"issue":"3","key":"4749_CR27","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s00125-023-06048-6","volume":"67","author":"EW Gregg","year":"2024","unstructured":"E.W. Gregg, H. Chen, M.P. Bancks, R. Manalac, N. Maruthur, M. Munshi, R. Wing, Look ARG. Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study. Diabetologia 67(3), 459\u2013469 (2024). https:\/\/doi.org\/10.1007\/s00125-023-06048-6","journal-title":"Diabetologia"},{"issue":"1","key":"4749_CR28","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s12933-025-02578-y","volume":"24","author":"C Shimayama","year":"2025","unstructured":"C. Shimayama, K. Fujihara, L. Khin, H. Takizawa, C. Horikawa, T. Sato, M. Kitazawa, Y. Matsubayashi, T. Yamada, H. Sone, Impact of diabetes remission or progression on the incidence of cardiovascular disease in Japan: historical cohort study using a nationwide claims database. Cardiovasc. Diabetol. 24(1), 37 (2025). https:\/\/doi.org\/10.1186\/s12933-025-02578-y","journal-title":"Cardiovasc. Diabetol."}],"container-title":["Endocrine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-026-04749-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12020-026-04749-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-026-04749-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T07:45:00Z","timestamp":1786779900000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12020-026-04749-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,15]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4749"],"URL":"https:\/\/doi.org\/10.1007\/s12020-026-04749-7","relation":{},"ISSN":["1559-0100"],"issn-type":[{"value":"1559-0100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,15]]},"assertion":[{"value":"4 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the NHG Health Ethics and Compliance Online System (ECOS Reference: 2022\/00182).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Conflict of interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"274"}}