{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:00Z","timestamp":1785434820251,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["AP22686752"],"award-info":[{"award-number":["AP22686752"]}]},{"award":["AP22686752"],"award-info":[{"award-number":["AP22686752"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Type 2 diabetes (T2D) and prediabetes represent a progressive glycemic continuum associated with multi-pathway metabolic deterioration that often precedes clinical diagnosis. Early identification of molecular alterations underlying this transition is critical for prevention strategies. Untargeted gas chromatography\u2013mass spectrometry (GC\u2013MS) metabolomics combined with multivariate statistical analysis (PCA) was applied to serum samples from 188 participants stratified into Control (n = 48), Prediabetes (n = 113), and Diabetes (n = 27) groups according to ADA\/WHO diagnostic criteria. Progressive metabolic alterations were observed across the glycemic continuum. Several amino acid-, lipid-, and organic acid-related features showed nominal differences between the study groups. However, none of the detected metabolomic features remained statistically significant after false discovery rate (FDR) correction, indicating that these findings should be considered exploratory. Diabetes was associated with widespread downregulation of amino acid-related features, long-chain and complex lipid species, and small organic acids relative to both control and prediabetes groups. PCA (PC1 = 35.9%) showed progressive metabolic stratification primarily driven by hyperglycemia, dyslipidemia, and blood pressure elevation. These exploratory findings suggest that the transition from prediabetes to diabetes may be accompanied by alterations in amino acid, lipid, and energy metabolism. The identified metabolomic features represent candidate metabolites that require validation in larger independent cohorts using targeted metabolomics.<\/jats:p>","DOI":"10.3390\/ijms27156721","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"6721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Progressive Metabolic Dysregulation from Prediabetes to Diabetes Revealed by Untargeted Metabolomics"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6070-4574","authenticated-orcid":false,"given":"Maxat","family":"Toishimanov","sequence":"first","affiliation":[{"name":"Kazakhstan-Japan Innovative Center, Kazakh National Agrarian Research University, Almaty 050010, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-2776","authenticated-orcid":false,"given":"Ivan","family":"Voitsekhovskiy","sequence":"additional","affiliation":[{"name":"Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty 050038, Kazakhstan"},{"name":"Department of Epidemiology and Biostatistics, Semey Medical University, Semey 071400, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aksholpan","family":"Shokan","sequence":"additional","affiliation":[{"name":"Institute of Genetic and Physiology, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakyt","family":"Kanapiyanov","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Semey Medical University, Semey 071400, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurgul","family":"Myrzabayeva","sequence":"additional","affiliation":[{"name":"Kazakhstan-Japan Innovative Center, Kazakh National Agrarian Research University, Almaty 050010, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2904-6083","authenticated-orcid":false,"given":"Alma","family":"Nurtazina","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Semey Medical University, Semey 071400, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, Regional and Country-Level Diabetes Prevalence Estimates for 2021 and Projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. 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