{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T10:18:02Z","timestamp":1769854682036,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Metformin is the most widely used drug in type 2 diabetes. Regular metformin use has been associated with changes in concentrations of amino acids. In the present study, we used valid stable-isotope labeled GC-MS methods to measure amino acids and metabolites, including creatinine as well as malondialdehyde (MDA), as an oxidative stress biomarker in plasma, urine, and dialysate samples in a patient at admission to the intensive care unit and during renal replacement treatment because of metformin-associated lactic acidosis (MALA, 21 mM lactate, 175 \u00b5M metformin). GC-MS revealed lower concentrations of amino acids in plasma, normal concentrations of the nitric oxide (NO) metabolites nitrite and nitrate, and normal concentrations of MDA. Renal tubular reabsorption rates were altered on admission. The patient received renal replacement therapy over 50 to 70 h of normalized plasma amino acid concentrations and their tubular reabsorption, as well as the tubular reabsorption of nitrite and nitrate. This study indicates that GC-MS is a versatile analytical tool to measure different classes of physiological inorganic and organic substances in complex biological samples in clinical settings such as MALA.<\/jats:p>","DOI":"10.3390\/jcm13133692","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T12:46:56Z","timestamp":1719319616000},"page":"3692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comprehensive GC-MS Measurement of Amino Acids, Metabolites, and Malondialdehyde in Metformin-Associated Lactic Acidosis at Admission and during Renal Replacement Treatment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7599-1441","authenticated-orcid":false,"given":"Rene A.","family":"Posma","sequence":"first","affiliation":[{"name":"Department of Critical Care, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-6791","authenticated-orcid":false,"given":"Stephan J. L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten W.","family":"Nijsten","sequence":"additional","affiliation":[{"name":"Department of Critical Care, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-4789","authenticated-orcid":false,"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6320-0956","authenticated-orcid":false,"given":"Dimitrios","family":"Tsikas","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, 30623 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.2337\/dci22-0034","article-title":"Management of Hyperglycemia in Type 2 Diabetes, 2022. 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