Systems-based metabolomics of type 2 diabetes mellitus subtypes

Wei, H. (2012)

Doctoral Thesis

This thesis was to combine metabolomics and Chinese medicine (CM) diagnosis to search for biomakers or metabolic profiles to subtype of type 2 diabetes (T2DM). An explorative study of 50 males with pre-diabetes was designed and two subtypes (A and B) could be identified by urine metabolomics. More metabolic disturbances were indicated in subtype B. The effects of rimonabant and a multi-component preparation (SUB885C), both with reported effects of regulating weight and the improvement on metabolic risks, were assessed by lipidomics on ApoE*3Leiden.CETP Mice. A 4-week rimonabant intervention brought a significant weight reduction, but moderate effects on lipid profile. SUB885C was able to produce multiple anti-atherogenic changes in lipids of the mice to improve metabolic parameters. A combined approach of lipidomics, biochemistry and herbal component profiling was used to evaluate the effects of the ginseng roots of 3__6 years on the regulation of dyslipidemia in diabetic Goto-Kakizaki rats. The more than 4 year ginseng proved to be valuable for drug development to regulate lipids. To conclude, the early metabolomics investigations performed in this thesis converged analytical bioscience, clinical approach and the diagnostic perspectives in other health system to provide the systems biology view on the pre-stage of T2DM.

• Systems biology
• Metabolomics
• Lipoprotein
• Lipidomics
• Ginseng
• Disease subtypes
• Diabetes
• Chinese medicine
• ApoE*3Leiden.CETP mice

• All authors: Wei, H.
• Supervisor: Greef, J. van der
• Co-supervisor: Verheij, E.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Science, Leiden University
• Date: 2012-11-27
• ISBN (print): 9789462032170