Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients

: Ahonen L, Jäntti S, Suvitaival T, Theilade S, Risz C, Kostiainen R, Rossing P, Oresic M, Hyötyläinen T

Publisher: MDPI

: 2019

: Metabolites

: METABOLITES

: 184

: 9

: 21

: 2218-1989

DOI: https://doi.org/10.3390/metabo9090184

: https://research.utu.fi/converis/portal/detail/Publication/42619481

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 (R-2), 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.

metabolites-09-00184-v2.pdf