International Diabetes Federation. IDF Diabetes Atlas, 11th edn. Brussels, Belgium: 2025. https://diabetesatlas.org. Accessed: 20 Nov 2025

A. Rothberg, M. Lean, B. Laferrere, Remission of type 2 diabetes: always more questions, but enough answers for action. Diabetologia 67(4), 602–610 (2024). https://doi.org/10.1007/s00125-023-06069-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

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), 541–551 (2018). https://doi.org/10.1016/S0140-6736(17)33102-1

Article  PubMed  Google Scholar 

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), 477–489 (2020). https://doi.org/10.1016/S2213-8587(20)30117-0

Article  PubMed  Google Scholar 

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), 66–70 (2024). https://doi.org/10.2337/dc23-0781

Article  PubMed  PubMed Central  Google Scholar 

R. Taylor, Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia 51(10), 1781–1789 (2008). https://doi.org/10.1007/s00125-008-1116-7

Article  CAS  PubMed  Google Scholar 

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

Article  CAS  PubMed  PubMed Central  Google Scholar 

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), 177–189 (2025). https://doi.org/10.1186/s43556-025-00303-5

Article  Google Scholar 

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), 646–656 (2021). https://doi.org/10.1002/osp4.516

Article  PubMed  PubMed Central  Google Scholar 

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), 547–556.e3 (2018). https://doi.org/10.1016/j.cmet.2018.07.003

Article  CAS  PubMed  Google Scholar 

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), 2438–2444 (2021). https://doi.org/10.2337/dci21-0034

Article  CAS  PubMed  PubMed Central  Google Scholar 

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

Article  CAS  PubMed  PubMed Central  Google Scholar 

J.C. Levy, D.R. Matthews, M.P. Hermans, Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 21(12), 2191–2192 (1998). https://doi.org/10.2337/diacare.21.12.2191

Article  CAS  PubMed  Google Scholar 

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), 446–456 (2023). https://doi.org/10.14366/usg.23014

Article  PubMed  PubMed Central  Google Scholar 

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), 3849–3860 (2018). https://doi.org/10.3748/wjg.v24.i34.3849

Article  PubMed  PubMed Central  Google Scholar 

B.C. Lupsa, R.G. Kibbey, S.E. Inzucchi, Ketones: the double-edged sword of SGLT2 inhibitors? Diabetologia 66(1), 23–32 (2023). https://doi.org/10.1007/s00125-022-05815-1

Article  CAS  PubMed  Google Scholar 

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

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

Article  CAS  PubMed  PubMed Central  Google Scholar 

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), 256–264 (2007). https://doi.org/10.1016/j.neuroscience.2006.11.065

Article  CAS  PubMed  PubMed Central  Google Scholar 

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

Article  CAS  PubMed  Google Scholar 

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

Article  CAS  PubMed  PubMed Central  Google Scholar 

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), 269–273 (2018). https://doi.org/10.1002/oby.22051

Article  CAS  PubMed  Google Scholar 

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

Article  PubMed  PubMed Central  Google Scholar 

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), 967–975 (2001)

Article  CAS  PubMed  Google Scholar 

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), 119–124 (2020). https://doi.org/10.1249/JES.0000000000000220

Article  PubMed  PubMed Central  Google Scholar 

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

Article  PubMed  PubMed Central  Google Scholar 

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), 459–469 (2024). https://doi.org/10.1007/s00125-023-06048-6

Article  CAS  PubMed  PubMed Central  Google Scholar 

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