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However, the metabolic alterations in m.3243A&gt;G carriers, including what differentiates those with and without diabetes, remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate metabolomic profiles in fasting serum and urine samples from m.3243A&gt;G carriers compared to healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Metabolomic profiling of serum and urine samples using nuclear magnetic resonance-based metabolomics in m.3243A&gt;G carriers (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200928) was compared to healthy controls matched for age and sex. Additionally, profiles from m.3243A&gt;G carriers with diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200916) were compared with carriers without diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912) to identify potential metabolites associated with the presence of diabetes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-five metabolites in serum and 16 in urine were identified as metabolites separating m.3243A&gt;G carriers from healthy controls. The m.3243A&gt;G carriers presented with increased triglycerides across lipoprotein particles and altered very-low-density lipoprotein concentrations and composition. In addition, there were alterations in metabolites from a number of metabolic pathways, including glycolysis, the tricarboxylic acid cycle, glutathione, one-carbon, and nucleotide metabolism. A three metabolite-urine signature (uracil, hypoxanthine, and 1-methylnicotinamide) demonstrated discriminating potential between m.3243A&gt;G carriers and controls in exploratory machine learning analyses (area under the curve values 0.94\u20130.99 and cross-validation prediction of 0.81\u20130.93). Among m.3243A&gt;G carriers, branched-chain amino acids were higher in individuals with diabetes compared with carriers without diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dysregulated lipoprotein metabolism represents a significant metabolic fingerprint of m.3243A&gt;G carriers. Furthermore, higher levels of branched-chain amino acids may be associated with the presence of diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11306-026-02503-8","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:22:15Z","timestamp":1783088535000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolomic signature reveals dysregulated lipoprotein profile in m.3243A&gt;G carriers: a case-control study"],"prefix":"10.1007","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5776-0321","authenticated-orcid":false,"given":"Simone Rask","family":"Nielsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4175-0927","authenticated-orcid":false,"given":"Hien Thi Thu","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0213-6528","authenticated-orcid":false,"given":"Malene Pontoppidan","family":"Stoico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3381-1884","authenticated-orcid":false,"given":"Christina","family":"Brock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0891-4224","authenticated-orcid":false,"given":"Kurt","family":"H\u00f8jlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9902-8040","authenticated-orcid":false,"given":"Inge S\u00f8kilde","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-8910","authenticated-orcid":false,"given":"Anja Lisbeth","family":"Frederiksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"2503_CR1","doi-asserted-by":"publisher","first-page":"2298","DOI":"10.1007\/s00125-019-05001-w","volume":"62","author":"AV Ahola-Olli","year":"2019","unstructured":"Ahola-Olli, A. 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