High Performance GC- and GCxGC-TOFMS Metabolomics-based Approach for Discovery of Potential Diabetes II Biomarkers in Human Serum
Monday, March 08, 2021: 8:50 AM - 9:10 AM
Over 400 million adults are currently living with diabetes worldwide and this number is expected to rise to 700 million by the year 2045. Type 2 diabetes mellitus (T2D) accounts for approximately 90% of total cases. Diabetes is a major cause of blindness, kidney failure, heart attacks, strokes and lower limb amputations. There is a critical need for the discovery of T2D biomarkers to initiate early medical treatment and avoid the major complications associated with this serious chronic disease. A metabolomics analytical approach is ideal for the investigation of human physiology and discovery of markers for disease diagnosis. The main objective of this study was to implement an untargeted analytical methodology for identification of candidate T2D biomarkers in humans. T2D and control samples were extracted with organic solvents and centrifuged. An aliquot of the supernatant material was placed under vacuum to remove solvents, lyophilized and then derivatized in two-steps: 1) Methoximation and 2) silylation. Mass spectra were collected with an ion source temperature of 250 °C, mass range of 40 to 650 Da and an acquisition rate of 10 spectra per second (200 sps for GCxGC-TOFMS). Data were processed using untargeted Peak Find strategies and compounds were characterized through retention index filtering, and spectral similarity searches. Data processing resulted in contour plots (Detailed compound maps) displaying wide varieties of metabolites including acids, diacids, amino acids, fatty acids, bases, monosaccharides, disaccharides, sugar phosphates, sterols, nucleosides and others. Differentiation of control and disease samples was performed through downstream statistical processing of the data. This work resulted in the identification of several candidate markers for T2D. High-resolution MS experiments were conducted to confirm candidate identifications.
Keywords: Please select up to 4 keywords ONLY:
Chromatography - Other,General Interest,Sample Preparation