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Open AccessArticle

Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients

Steno Diabetes Center Copenhagen, 2820 Gentofte, Denmark
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland
Department of Clinical Medicine, University of Copenhagen, 1165 Copenhagen, Denmark
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, 20520 Turku, Finland
School of Medical Sciences, Örebro University, 702 81 Örebro, Sweden
Department of Chemistry, Örebro University, 702 81 Örebro, Sweden
Author to whom correspondence should be addressed.
Current affiliation: Biosyntia ApS, 2100 Copenhagen, Denmark.
Metabolites 2019, 9(9), 184;
Received: 1 August 2019 / Revised: 30 August 2019 / Accepted: 11 September 2019 / Published: 14 September 2019
(This article belongs to the Special Issue Metabolomics 2019)
Several small molecule biomarkers have been reported in the literature for prediction and diagnosis of (pre)diabetes, its co-morbidities, and complications. Here, we report the development and validation of a novel, quantitative method for the determination of a selected panel of 34 metabolite biomarkers from human plasma. We selected a panel of metabolites indicative of various clinically-relevant pathogenic stages of diabetes. We combined these candidate biomarkers into a single ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method and optimized it, prioritizing simplicity of sample preparation and time needed for analysis, enabling high-throughput analysis in clinical laboratory settings. We validated the method in terms of limits of detection (LOD) and quantitation (LOQ), linearity (R2), and intra- and inter-day repeatability of each metabolite. The method’s performance was demonstrated in the analysis of selected samples from a diabetes cohort study. Metabolite levels were associated with clinical measurements and kidney complications in type 1 diabetes (T1D) patients. Specifically, both amino acids and amino acid-related analytes, as well as specific bile acids, were associated with macro-albuminuria. Additionally, specific bile acids were associated with glycemic control, anti-hypertensive medication, statin medication, and clinical lipid measurements. The developed analytical method is suitable for robust determination of selected plasma metabolites in the diabetes clinic. View Full-Text
Keywords: clinical diagnostics; diabetes; metabolomics; mass spectrometry clinical diagnostics; diabetes; metabolomics; mass spectrometry
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MDPI and ACS Style

Ahonen, L.; Jäntti, S.; Suvitaival, T.; Theilade, S.; Risz, C.; Kostiainen, R.; Rossing, P.; Orešič, M.; Hyötyläinen, T. Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients. Metabolites 2019, 9, 184.

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