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Breier, M. ; Wahl, S. ; Prehn, C. ; Ferrari, U. ; Sacco, V. ; Weise, M. ; Grallert, H. ; Adamski, J. ; Lechner, A.

Immediate reduction of serum citrulline but no change of steroid profile after initiation of metformin in individuals with type 2 diabetes.

J. Steroid Biochem. Mol. Biol. 174, 114-119 (2017)
Postprint Im Bibliotheksbestand vorhanden DOI PMC
Open Access Green
Metformin is the most important first-line treatment for type 2 diabetes mellitus (T2DM) but its exact mode of action remains unknown. In this study, we used targeted metabolomics to gain new insights into the metabolic effects of metformin in humans with T2DM. We also examined changes in the serum steroid hormone profile. We quantified 167 serum metabolites and 19 steroid hormones using liquid chromatography-tandem mass spectrometry at three time points in individuals with previously untreated T2DM: before the start of metformin therapy (time point A), after the first dose (B) and after short-term therapy for 4-6 weeks (C). For metabolite analysis, we split the study cohort into a discovery and a replication study of 88 and 45 subjects, respectively. The statistical analysis was done using linear mixed-effects models. Among the metabolites quantified, citrulline showed the most pronounced changes. Compared to its baseline serum concentration, citrulline was reduced by 17% after the first dose of metformin (p=1.34E-07) and by 24% after short-term therapy (p=2.84E-08) in the discovery study. These results were confirmed in the replication study. The only other metabolite significantly changed after correction for multiple testing was PC ae C36:4 between baseline and 4-6 weeks. The serum steroid hormone profile showed no significant changes after metformin intake. In summary, we observed an immediate and sustained reduction of serum citrulline by metformin in humans. This may be relevant for some of the wanted or unwanted effects of the drug.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Drug Treatment ; Mode Of Action ; Phosphatidylcholine ; Targeted Metabolomics ; Urea Cycle; Amino-acids; Mellitus Patients; Metabolism; Gluconeogenesis; Association; Therapies; Kinase; Women; Chain; Sex
ISSN (print) / ISBN 0960-0760
e-ISSN 0960-0760
Zeitschrift Journal of Steroid Biochemistry and Molecular Biology, The
Quellenangaben Band: 174, Heft: , Seiten: 114-119 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Oxford
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CCG Biomarker for the subclassification of T2DM (KKG-KDB)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Epidemiology II (EPI2)