Researchers from the Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) and the Centre for Omic Sciences of the Universitat Rovira i Virgili, directed by Òscar Yanes, have identified an early blood marker – the oxidized form of the amino acid methionine – the levels of which prevent the high density lipoproteins (known as good cholesterol) from maturing. This prevents the HDL particles from growing and, therefore, from having a protective effect. This effect on the maturation of the HDL lipoproteins can generate metabolic disorders related to type 2 diabetes and cardiovascular diseases.
Metabolites are small molecules in the blood and tissue that reflect the metabolic activity and state of the organism. Using metabolomic techniques based on nuclear magnetic resonance and mass spectrometry – which enable the level of thousands of these metabolites to be recorded – the researchers have identified this marker in a group of 16-year-old girls, all of whom had an excess of androgens and insulin resistance, which are metabolic features connected to the so-called polycystic ovary syndrome, a disorder that affects between 8 and 21% of women of reproductive age. In prepubescent girls and pubescent adolescents, this syndrome initially manifests with an excess of androgens (masculine hormone) and insulin resistance and, in adulthood, they can develop anovulatory infertility, type 2 diabetes, metabolic syndrome and the possibility of cardiovascular diseases.
In this study, which has been done in collaboration with researchers from the Sant Joan de Déu Hospital in Barcelona, directed by the endocrinologist and paediatrician Lourdes Ibáñez, blood samples from all the young participants were examined to find out whether they all coincided in these metabolic prints. These results make it possible to discover metabolic disorders that can lead to a better understanding of the health risks for these girls in the long term because the risks are revealed at a very early stage, even before other signs of diabetes are present. Identifying these markers, then, facilitates early therapeutic intervention.
The study has also shown that the medication given to this group of girls for 18 months – a combination of low doses of pioglitazone, metformin and flutamide, two insulin sensitizers and an antiandrogen – not only reverts the excess of androgens and restores sensitivity to insulin but also normalizes the function of good cholesterol by halting the oxidative stress process of the amino acid methionine and increasing the size of the HDL, a reflection of the improved maturation of the HDL particles. For researchers, the study opens up the possibility of validating and using these early markers in the general population at risk of suffering diabetes. The study also shows that these benefits are not observed after treatment with oral contraceptives, which, to date, has been the treatment of choice for these patients.
Samino, S. et al. Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess. Sci. Rep. 5, 11496; doi: 10.1038/srep11496 (2015).