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Metabolomics in Cardiometabolic disease - A population-based perspective

Filip Ottosson, Department of Clinical Sciences Malmö

Background

Type 2 diabetes (T2DM) and coronary artery disease (CAD) are major health concerns worldwide, that are preceded by metabolic alterations occuring years before clinical manifestation. These metabolic alterations could be characterized by shifts in plasma levels of metabolites, small molecules that partake in the chemical reactions collectively known as the metabolism. Recent development in mass spectrometry has enabled simultaneous measurements of hundreds of metabolites from blood plasma samples.

Aims

To characterize metabolite alterations that precede T2DM and CAD, including novel discoveries and replications of earlier associations, between e.g. BCAA related retamolites and T2DM and CAD. The second aim is to identify stratgies to modulate their levels.

Methods

Two liquid chromatography-quadrupole time-of-flight (LC-QTOF)methods were used to measure metabolites in plasma samples from participnts from the Malmö Preventive Project (N=1049), Malmö Diet and Cancer - Cardiovascular Cohort (N=3799), Malmö Offspring Study (MOS) (N=920) and The Crossover Amino Acid Challenge (N=21). Additionally, characterization of the gut microbiota and estimations of dietary intakes were performed in MOS.

Results

Previously shown associations between BCAA-related metabolites and T2DM and cardiometabolic traits were replicated (paper I and III). Additionally, BMI-related metabolites were associated with four gut bacteria (paper III) and postprandial levels of diabetes-associated metabolites were associated with fasting glycaemia (paper II). The levels of two plasma metabolites, dimethylguanidina valerate (paper IV) and asparagine (paperI), were associated with incidence of CAD. In paper V, the purine metabolites (N2, N2-dimethylguanosine and 7-methylguanine) and the camitine biosynthesis intermediate (3-hydroxytrimethyllysine) were, for the first time , shown to be associated with incident T2DM.

Link to the thesis

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00